WorldWideScience

Sample records for screening trial design

  1. The utility of screening in the design of trials for symptom management in cancer.

    Science.gov (United States)

    Jeon, Sangchoon; Given, Charles W; Sikorskii, Alla; Given, Barbara

    2009-10-01

    Clinical trials that test interventions for symptom management must target patients whose symptoms are severe and can benefit from participation. Screening symptoms for their severity prior to trial entry may be an important element of trial design. This research describes the utility of screening for severity of symptoms prior to entry into clinical trials for symptom management in cancer. To accomplish this, 601 cancer patients undergoing chemotherapy were assessed at screening and at the initial intervention contact, using the 0-10 rating scale for severity of nine symptoms. Post-test probabilities and likelihood ratios (LRs) were estimated across cut-offs in screening severity scores. Areas under receiver operating characteristic curves for reaching threshold of four at the initial intervention contact were estimated by a nonparametric method. It was found that screening severity scores were good predictors for identifying patients who would not reach threshold but did not always accurately predict patients who would. The cut-offs between 2 and 4 on a 0-10 scale could be used to identify patients that might benefit from receipt of interventions. For all symptoms, the LRs were greater than one across possible screening cut-offs. The findings indicate that decision rules based on screening prior to entry into cancer symptom management trials can provide reasonable discriminative accuracy by differentiating among patients who are likely to reach higher levels of severity later in the trial from those who are not. Optimal severity cut-offs can be established based on LRs and desired sensitivity and specificity.

  2. A randomized controlled trial of Human Papillomavirus (HPV testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial

    Directory of Open Access Journals (Sweden)

    Smith Laurie W

    2010-03-01

    Full Text Available Abstract Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5% were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%. In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%. Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  3. An internal pilot design for prospective cancer screening trials with unknown disease prevalence.

    Science.gov (United States)

    Brinton, John T; Ringham, Brandy M; Glueck, Deborah H

    2015-10-13

    For studies that compare the diagnostic accuracy of two screening tests, the sample size depends on the prevalence of disease in the study population, and on the variance of the outcome. Both parameters may be unknown during the design stage, which makes finding an accurate sample size difficult. To solve this problem, we propose adapting an internal pilot design. In this adapted design, researchers will accrue some percentage of the planned sample size, then estimate both the disease prevalence and the variances of the screening tests. The updated estimates of the disease prevalence and variance are used to conduct a more accurate power and sample size calculation. We demonstrate that in large samples, the adapted internal pilot design produces no Type I inflation. For small samples (N less than 50), we introduce a novel adjustment of the critical value to control the Type I error rate. We apply the method to two proposed prospective cancer screening studies: 1) a small oral cancer screening study in individuals with Fanconi anemia and 2) a large oral cancer screening trial. Conducting an internal pilot study without adjusting the critical value can cause Type I error rate inflation in small samples, but not in large samples. An internal pilot approach usually achieves goal power and, for most studies with sample size greater than 50, requires no Type I error correction. Further, we have provided a flexible and accurate approach to bound Type I error below a goal level for studies with small sample size.

  4. Rationale and design of the HOME trial: A pragmatic randomized controlled trial of home-based human papillomavirus (HPV) self-sampling for increasing cervical cancer screening uptake and effectiveness in a U.S. healthcare system.

    Science.gov (United States)

    Winer, Rachel L; Tiro, Jasmin A; Miglioretti, Diana L; Thayer, Chris; Beatty, Tara; Lin, John; Gao, Hongyuan; Kimbel, Kilian; Buist, Diana S M

    2018-01-01

    Women who delay or do not attend Papanicolaou (Pap) screening are at increased risk for cervical cancer. Trials in countries with organized screening programs have demonstrated that mailing high-risk (hr) human papillomavirus (HPV) self-sampling kits to under-screened women increases participation, but U.S. data are lacking. HOME is a pragmatic randomized controlled trial set within a U.S. integrated healthcare delivery system to compare two programmatic approaches for increasing cervical cancer screening uptake and effectiveness in under-screened women (≥3.4years since last Pap) aged 30-64years: 1) usual care (annual patient reminders and ad hoc outreach by clinics) and 2) usual care plus mailed hrHPV self-screening kits. Over 2.5years, eligible women were identified through electronic medical record (EMR) data and randomized 1:1 to the intervention or control arm. Women in the intervention arm were mailed kits with pre-paid envelopes to return samples to the central clinical laboratory for hrHPV testing. Results were documented in the EMR to notify women's primary care providers of appropriate follow-up. Primary outcomes are detection and treatment of cervical neoplasia. Secondary outcomes are cervical cancer screening uptake, abnormal screening results, and women's experiences and attitudes towards hrHPV self-sampling and follow-up of hrHPV-positive results (measured through surveys and interviews). The trial was designed to evaluate whether a programmatic strategy incorporating hrHPV self-sampling is effective in promoting adherence to the complete screening process (including follow-up of abnormal screening results and treatment). The objective of this report is to describe the rationale and design of this pragmatic trial. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Rationale and design of the iPap trial: a randomized controlled trial of home-based HPV self-sampling for improving participation in cervical screening by never- and under-screened women in Australia

    International Nuclear Information System (INIS)

    Sultana, Farhana; Gertig, Dorota M; English, Dallas R; Simpson, Julie A; Brotherton, Julia ML; Drennan, Kelly; Mullins, Robyn; Heley, Stella; Wrede, C David; Saville, Marion

    2014-01-01

    Organized screening based on Pap tests has substantially reduced deaths from cervical cancer in many countries, including Australia. However, the impact of the program depends upon the degree to which women participate. A new method of screening, testing for human papillomavirus (HPV) DNA to detect the virus that causes cervical cancer, has recently become available. Because women can collect their own samples for this test at home, it has the potential to overcome some of the barriers to Pap tests. The iPap trial will evaluate whether mailing an HPV self-sampling kit increases participation by never- and under-screened women within a cervical screening program. The iPap trial is a parallel randomized controlled, open label, trial. Participants will be Victorian women age 30–69 years, for whom there is either no record on the Victorian Cervical Cytology Registry (VCCR) of a Pap test (never-screened) or the last recorded Pap test was between five to fifteen years ago (under-screened). Enrolment information from the Victorian Electoral Commission will be linked to the VCCR to determine the never-screened women. Variables that will be used for record linkage include full name, address and date of birth. Never- and under-screened women will be randomly allocated to either receive an invitation letter with an HPV self-sampling kit or a reminder letter to attend for a Pap test, which is standard practice for women overdue for a test in Victoria. All resources have been focus group tested. The primary outcome will be the proportion of women who participate, by returning an HPV self-sampling kit for women in the self-sampling arm, and notification of a Pap test result to the Registry for women in the Pap test arm at 3 and 6 months after mailout. The most important secondary outcome is the proportion of test-positive women who undergo further investigations at 6 and 12 months after mailout of results. The iPap trial will provide strong evidence about whether HPV self

  6. A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)

    International Nuclear Information System (INIS)

    Ogilvie, Gina S; Cook, Darrel A; Mei, Wendy; Stuart, Gavin CE; Franco, Eduardo L; Coldman, Andrew J; Niekerk, Dirk J van; Krajden, Mel; Martin, Ruth E; Ehlen, Thomas G; Ceballos, Kathy; Peacock, Stuart J; Smith, Laurie W; Kan, Lisa

    2010-01-01

    In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  7. Case-control Studies on the Effectiveness of Breast Cancer Screening: Insights from the UK Age Trial.

    Science.gov (United States)

    van der Waal, Daniëlle; Broeders, Mireille J M; Verbeek, André L M; Duffy, Stephen W; Moss, Sue M

    2015-07-01

    Ongoing breast cancer screening programs can only be evaluated using observational study designs. Most studies have observed a reduction in breast cancer mortality, but design differences appear to have resulted in different estimates. Direct comparison of case-control and trial analyses gives more insight into this variation. Here, we performed case-control analyses within the randomized UK Age Trial. The Age Trial assessed the effect of screening on breast cancer mortality in women ages 40-49 years. In our approach, case subjects were defined as breast cancer deaths between trial entry (1991-1997) and 2004. Women were ages 39-41 years at entry. For every case subject, five control subjects were selected. All case subjects were included in analyses of screening invitation (356 case subjects, 1,780 controls), whereas analyses of attendance were restricted to women invited to screening (105 case subjects, 525 age-matched controls). Odds ratios (OR) were estimated with conditional logistic regression. We used and compared two methods to correct for self-selection bias. Screening invitation resulted in a breast cancer mortality reduction of 17% (95% confidence interval [CI]: -36%, +6%), similar to trial results. Different exposure definitions and self-selection adjustments influenced the observed breast cancer mortality reduction. Depending on the method, "ever screened" appeared to be associated with a small reduction (OR: 0.86, 95% CI: 0.40, 1.89) or no reduction (OR: 1.02, 95% CI: 0.48, 2.14) using the two methods of correction. Recent attendance resulted in an adjusted mortality reduction of 36% (95% CI: -69%, +31%) or 45% (95% CI: -71%, +5%). Observational studies, and particularly case-control studies, are an important monitoring tool for breast cancer screening programs. The focus should be on diminishing bias in observational studies and gaining a better understanding of the influence of study design on estimates of mortality reduction.

  8. The Danish randomized lung cancer CT screening trial

    DEFF Research Database (Denmark)

    Pedersen, Jesper H; Ashraf, Haseem; Dirksen, Asger

    2009-01-01

    INTRODUCTION: Lung cancer screening with low dose computed tomography (CT) has not yet been evaluated in randomized clinical trials, although several are underway. METHODS: In The Danish Lung Cancer Screening Trial, 4104 smokers and previous smokers from 2004 to 2006 were randomized to either...... lung cancer. Ten of these had stage I disease. Eleven of 17 lung cancers at baseline were treated surgically, eight of these by video assisted thoracic surgery resection. CONCLUSIONS: Screening may facilitate minimal invasive treatment and can be performed with a relatively low rate of false......-positive screen results compared with previous studies on lung cancer screening....

  9. Randomized controlled trial on effectiveness of ultrasonography screening for breast cancer in women aged 40-49 (J-START). Research design

    International Nuclear Information System (INIS)

    Ohuchi, Noriaki; Ishida, Takanori; Kawai, Masaaki; Narikawa, Yoko; Yamamoto, Seiichiro; Sobue, Tomotaka

    2011-01-01

    In cancer screening, it is essential to undertake effective screening with appropriate methodology, which should be supported by evidence of a reduced mortality rate. At present, mammography is the only method for breast cancer screening with such evidence. However, mammography does not achieve sufficient accuracy in breasts with high density at ages below 50. Although ultrasonography achieves better accuracy in Breast Cancer detection even in dense breasts, the effectiveness has not been verified. We have planned a randomized controlled trial to assess the effectiveness of ultrasonography in women aged 40-49, with a design to study 50,000 women with mammography and ultrasonography (intervention group), and 50,000 controls with mammography only (control group). The participants are scheduled to take second round screening with the same modality 2 years on. The primary endpoints are sensitivity and specificity, and the secondary endpoint is the rate of advanced breast cancers. (author)

  10. Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

    2013-07-03

    As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

  11. Systems of support to increase colorectal cancer screening and follow-up rates (SOS): design, challenges, and baseline characteristics of trial participants.

    Science.gov (United States)

    Green, Beverly B; Wang, C Y; Horner, Kathryn; Catz, Sheryl; Meenan, Richard T; Vernon, Sally W; Carrell, David; Chubak, Jessica; Ko, Cynthia; Laing, Sharon; Bogart, Andy

    2010-11-01

    Screening decreases colorectal cancer (CRC) morbidity and mortality, yet remains underutilized. Screening breakdowns arise from lack of uptake and failure to follow-up after a positive screening test. Systems of support to increase colorectal cancer screening and follow-up (SOS) is a randomized trial designed to increase: (1) CRC screening and (2) follow-up of positive screening tests. The Chronic Care Model and the Preventive Health Model inform study design. The setting is a large nonprofit healthcare organization. In part-1 study, patients age 50-75 due for CRC screening are randomized to one of 4 study conditions. Arm 1 receives usual care. Arm 2 receives automated support (mailed information about screening choices and fecal occult blood tests (FOBT)). Arm 3 receives automated and assisted support (a medical assistant telephone call). Arm 4 receives automated, assisted, and care management support (a registered nurse provides behavioral activation and coordination of care). In part-2, study patients with a positive FOBT or adenomas on flexible sigmoidoscopy are randomized to receive either usual care or nurse care management. Primary outcomes are: 1) the proportion with CRC screening, 2) the proportion with a complete diagnostic evaluation after a positive screening test. We sent recruitment letters to 15,414 patients and 4675 were randomized. Randomly assigned treatment groups were similar in age, sex, race, education, self-reported health, and CRC screening history. We will determine the effectiveness and cost effectiveness of stepped increases in systems of support to increase CRC screening and follow-up after a positive screening test over 2years. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

    Science.gov (United States)

    Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

    2016-01-01

    Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in

  13. Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, U.; Aalst, C. van der; Jong, P.A. de; Heuvelmans, M.; Scholten, E.T.; Lammers, J.-W.J.; Ooijen, P. van; Nackaerts, K.; Weenink, C.; Groen, H.; Vliegenthart, R.; Haaf, K. Ten; Oudkerk, M.; Koning, H. de

    2016-01-01

    In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  14. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  15. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A.; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  16. The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.

    Science.gov (United States)

    Field, John K; Duffy, Stephen W; Baldwin, David R; Brain, Kate E; Devaraj, Anand; Eisen, Tim; Green, Beverley A; Holemans, John A; Kavanagh, Terry; Kerr, Keith M; Ledson, Martin; Lifford, Kate J; McRonald, Fiona E; Nair, Arjun; Page, Richard D; Parmar, Mahesh Kb; Rintoul, Robert C; Screaton, Nicholas; Wald, Nicholas J; Weller, David; Whynes, David K; Williamson, Paula R; Yadegarfar, Ghasem; Hansell, David M

    2016-05-01

    consequences were observed in participants who were randomised to the intervention arm and in those who had a major lung abnormality detected, but these differences were modest and temporary. Rollout of screening as a service or design of a full trial would need to address issues of outreach. The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality. The UK Lung Cancer Screening (UKLS) pilot was successfully undertaken with 4055 randomised individuals. The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60-75 years age group, selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocols. The UKLS data will be pooled with the NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek: Dutch-Belgian Randomised Lung Cancer Screening Trial) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data. For now, there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery. Strategies for increasing uptake and providing support for underserved groups will be key to implementation. Current Controlled Trials ISRCTN78513845. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 40. See the NIHR Journals Library website for further project information.

  17. WE-D-207-03: CT Protocols for Screening and the ACR Designated Lung Screening Program

    International Nuclear Information System (INIS)

    McNitt-Gray, M.

    2015-01-01

    In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancer Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in

  18. Increased breast cancer screening and downstaging in Colombian women: A randomized trial of opportunistic breast-screening.

    Science.gov (United States)

    Murillo, Raúl; Díaz, Sandra; Perry, Fernando; Poveda, César; Piñeros, Marion; Sánchez, Oswaldo; Buitrago, Lina; Gamboa, Oscar; Lozano, Teófilo; Yu, Hsiang; Wang, Ching-Yun; Duggan, Catherine; Thomas, David B; Anderson, Benjamin O

    2016-02-01

    The lack of breast cancer screening in low and middle-income countries results in later stage diagnosis and worsened outcomes for women. A cluster randomized trial was performed in Bogotá, Colombia between 2008 and 2012 to evaluate effects of opportunistic breast cancer screening. Thirteen clinics were randomized to an intervention arm and 13 to a control arm. Physicians in intervention clinics were instructed to perform clinical breast examination on all women aged 50-69 years attending clinics for non-breast health issues, and then refer them for mammographic screening. Physicians in control clinics were not explicitly instructed to perform breast screening or mammography referrals, but could do so if they thought it indicated ("usual care"). Women were followed for 2-years postrandomization. 7,436 women were enrolled and 7,419 (99.8%) screened in intervention clinics, versus 8,419 enrolled and 1,108 (13.1%) screened in control clinics. Incidence ratios (IR) of early, advanced and all breast cancers were 2.9 (95% CI 1.1-9.2), 1.0 (0.3-3.5) and 1.9 (0.9-4.1) in the first (screening) year of the trial, and the cumulative IR for all breast cancers converged to 1.4 (0.7-2.8) by the end of follow-up (Year 2). Eighteen (69.2%) of 26 women with early stage disease had breast conservation surgery (BCS) versus 6 (42.5%) of 14 women with late-stage disease (p = 0.02). Fifteen (68.2%) of 22 women with breast cancer in the intervention group had BCS versus nine (50.0%) of 18 women in the control group (p = 0.34). Well-designed opportunistic clinic-based breast cancer screening programs may be useful for early breast cancer detection in LMICs. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  19. Design-corrected variation by centre in mortality reduction in the ERSPC randomised prostate cancer screening trial.

    Science.gov (United States)

    Hakama, Matti; Moss, Sue M; Stenman, Ulf-Hakan; Roobol, Monique J; Zappa, Marco; Carlsson, Sigrid; Randazzo, Marco; Nelen, Vera; Hugosson, Jonas

    2017-06-01

    Objectives To calculate design-corrected estimates of the effect of screening on prostate cancer mortality by centre in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Setting The ERSPC has shown a 21% reduction in prostate cancer mortality in men invited to screening with follow-up truncated at 13 years. Centres either used pre-consent randomisation (effectiveness design) or post-consent randomisation (efficacy design). Methods In six centres (three effectiveness design, three efficacy design) with follow-up until the end of 2010, or maximum 13 years, the effect of screening was estimated as both effectiveness (mortality reduction in the target population) and efficacy (reduction in those actually screened). Results The overall crude prostate cancer mortality risk ratio in the intervention arm vs control arm for the six centres was 0.79 ranging from a 14% increase to a 38% reduction. The risk ratio was 0.85 in centres with effectiveness design and 0.73 in those with efficacy design. After correcting for design, overall efficacy was 27%, 24% in pre-consent and 29% in post-consent centres, ranging between a 12% increase and a 52% reduction. Conclusion The estimated overall effect of screening in attenders (efficacy) was a 27% reduction in prostate cancer mortality at 13 years' follow-up. The variation in efficacy between centres was greater than the range in risk ratio without correction for design. The centre-specific variation in the mortality reduction could not be accounted for by the randomisation method.

  20. Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial.

    Science.gov (United States)

    Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst; Brodersen, John

    2012-01-01

    To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales 'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and 'introvert', with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants-both the participants in the screen group and the control group. This negative impact was greatest for the control group.

  1. European randomized lung cancer screening trials: Post NLST

    DEFF Research Database (Denmark)

    Field, JK; Klaveren, R; Pedersen, JH

    2013-01-01

    Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects...

  2. Screening uptake rates and the clinical and cost effectiveness of screening for gestational diabetes mellitus in primary versus secondary care: study protocol for a randomised controlled trial.

    LENUS (Irish Health Repository)

    O Dea, Angela

    2014-01-17

    The risks associated with gestational diabetes mellitus (GDM) are well recognized, and there is increasing evidence to support treatment of the condition. However, clear guidance on the ideal approach to screening for GDM is lacking. Professional groups continue to debate whether selective screening (based on risk factors) or universal screening is the most appropriate approach. Additionally, there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment. Furthermore, the implications of possible screening options on health care costs are not well established. In response to this uncertainty there have been repeated calls for well-designed, randomised trials to determine the efficacy of screening, diagnosis, and management plans for GDM. We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings. The objective of this study is to assess screening uptake rates, and the clinical and cost effectiveness of screening for GDM in primary versus secondary care.

  3. Recruitment for 'A pilot study of randomized controlled trial to evaluate the efficacy of lung cancer screening by thoracic CT'

    International Nuclear Information System (INIS)

    Sagawa, Motoyasu; Tanaka, Makoto; Mizukami, Satoru

    2011-01-01

    The objective of this study was to evaluate the efficacy of lung cancer screening by thoracic computed tomography (CT), a randomized controlled trial was planned in Japan. The randomized trial was designed as follows: participants were randomly assigned into 2 groups, CT group and XP group; XP group would receive 10 times of lung cancer screening by chest x-ray annually for 10 years; smokers in CT group would receive 10 times of lung cancer screening by thoracic CT annually for 10 years; non-smokers in CT group would receive 3 times of lung cancer screening by thoracic CT and 7 times of chest x-ray during 10 years. A pilot study was performed to evaluate the feasibility of the trial. A letter for recruitment to participate in the above trial was mailed to the citizens in Hakui City, who were 50-64 years old and underwent regular lung cancer screening using chest x-ray this year. In the letter we explained that the efficacy of lung cancer screening by thoracic CT had not been proved yet; only half of the participants could undergo thoracic CT screening; thoracic CT screening might cause unfavorable consequences like radiation exposure, false positives or overdiagnosis. Of 329 persons who received the letter of recruitment, 117 replied. After meeting with us for detailed explanation, 111 persons participated in the above randomized trial. The compliance of recruitment is high (approximately one third) and the above trial may be feasible. (author)

  4. Effect of Fee on Cervical Cancer Screening Attendance—ScreenFee, a Swedish Population-Based Randomised Trial

    Science.gov (United States)

    Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

    2016-01-01

    Background Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Method Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Results Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85–1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Conclusion Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. Trial Registration ClinicalTrials.gov NCT02378324 PMID:26986848

  5. Tracking and tracing of participants in two large cancer screening trials.

    Science.gov (United States)

    Marcus, Pamela M; Childs, Jeffery; Gahagan, Betsy; Gren, Lisa H

    2012-07-01

    Many clinical trials rely on participant report to first learn about study events. It is therefore important to have current contact information and the ability to locate participants should information become outdated. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) and the Lung Screening Study (LSS) component of the National Lung Screening Trial, two large randomized cancer screening trials, enrolled almost 190,000 participants on whom annual contact was necessary. Ten screening centers participated in both trials. Centers developed methods to track participants and trace them when necessary. We describe the methods used to keep track of participants and trace them when lost, and the extent to which each method was used. Screening center coordinators were asked, using a self-administered paper questionnaire, to rate the extent to which specific tracking and tracing methods were used. Many methods were used by the screening centers, including telephone calls, mail, and internet searches. The most extensively used methods involved telephoning the participant on his or her home or cell phone, or telephoning a person identified by the participant as someone who would know about the participant's whereabouts. Internet searches were used extensively as well; these included searches on names, reverse-lookup searches (on addresses or telephone numbers) and searches of the Social Security Death Index. Over time, the percentage of participants requiring tracing decreased. Telephone communication and internet services were useful in keeping track of PLCO and LSS participants and tracing them when contact information was no longer valid. Published by Elsevier Inc.

  6. The ADDITION-Cambridge trial protocol: a cluster – randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients

    Directory of Open Access Journals (Sweden)

    Kinmonth Ann

    2009-05-01

    Full Text Available Abstract Background The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, the benefits of such a strategy remain uncertain. Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of (i a stepwise screening strategy for type 2 diabetes; and (ii intensive multifactorial treatment for people with screen-detected diabetes in primary care. 63 practices in the East Anglia region participated. Three undertook the pilot study, 33 were allocated to three groups: no screening (control, screening followed by intensive treatment (IT and screening plus routine care (RC in an unbalanced (1:3:3 randomisation. The remaining 27 practices were randomly allocated to IT and RC. A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes. In the screening practices, high-risk individuals were invited to take part in a stepwise screening programme. In the IT group, diabetes treatment is optimised through guidelines, target-led multifactorial treatment, audit, feedback, and academic detailing for practice teams, alongside provision of educational materials for newly diagnosed participants. Primary endpoints are modelled cardiovascular risk at one year, and cardiovascular mortality and morbidity at five years after diagnosis of diabetes. Secondary endpoints include all-cause mortality, development of renal and visual impairment, peripheral neuropathy, health service costs, self-reported quality of life, functional status and health utility. Impact of the screening programme at the population level is also assessed through measures of mortality, cardiovascular morbidity, health status and health service use among high-risk individuals. Discussion ADDITION-Cambridge is conducted in a defined high-risk group

  7. Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH: A randomized controlled trial study protocol

    Directory of Open Access Journals (Sweden)

    Tsai Midi

    2011-06-01

    Full Text Available Abstract Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33% do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention or control (no change. At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI and standardized body mass index (zBMI. Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous, Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight

  8. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial.

    Science.gov (United States)

    Patz, Edward F; Greco, Erin; Gatsonis, Constantine; Pinsky, Paul; Kramer, Barnett S; Aberle, Denise R

    2016-05-01

    Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385. Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97-408·26] per 100 000 person-years vs 661·23 [622·07-702·21]) and had lower lung cancer-related mortality (185·82 [95% CI 162·17

  9. Nodule management protocol of the NELSON randomised lung cancer screening trial

    NARCIS (Netherlands)

    Xu, Dong Ming; Gietema, Hester; de Koning, Harry; Vernhout, Rene; Nackaerts, Kristiaan; Prokop, Mathias; Weenink, Carla; Lammers, Jan-Willem; Groen, Harry; Oudkerk, Matthijs; van Klaveren, Rob

    In December 2003, the Dutch-Belgian NELSON trial, a Dutch acronym for "Nederlands-Leuvens Longkanker Screenings ONderzoek", has been launched. Primary objective of the NELSON trial is to investigate whether screening for lung cancer by 16-detector multi-slice CT with 16 mm x 0.75 mm collimation and

  10. Screenings of lung cancer with low dose spiral CT: results of a three year pilot study and design of the randomised controlled trial Italung-CT

    International Nuclear Information System (INIS)

    Picozzi, Giulia; Paci, Enrico; Lopes Pegna, Andrea

    2005-01-01

    Purpose: To report the results of a three-year observational pilot study of lung cancer screening with low dose computed tomography (CT) and to present the study design of a randomised clinical trial named as Italung CT. Materials and methods: Sixty (47 males and 13 females, mean age 64±4.5 years) heavy smokers (at least 20 packs-year) underwent three low-dose spiral CT screening tests one year apart on a single slice or multislice CT scanner. Indeterminate nodules were managed according to the recommendations of the Early Lung Cancer Action Project. Results: Indeterminate nodules were observed in 33 (55%) of the subjects (60% at the baseline screening test, 24% at the first annual test and 16% at the second annual test). The size of the largest indeterminate nodule was [it

  11. Primary HPV screening for cervical cancer prevention: results from European trials

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Rebolj, Matejka

    2009-01-01

    testing increased the detection of cervical intraepithelial neoplasia (CIN) grade 2+. Detection of CIN3+ was significantly increased in two trials (relative risks [RRs] 1.70 and 2.26), but not in three other trials (RRs 1.03, 1.09 and 1.31). In three trials, seven extra women had a false-positive test......Six European, randomized, controlled trials that will compare human papillomavirus (HPV) testing with cytological testing for cervical screening are under way. We reviewed the results published so far to compare the benefits and costs for participating women. At baseline screening, use of HPV...

  12. Design and trial evaluation of the user interface for MusicReader

    NARCIS (Netherlands)

    Leoné, Marco; van Dijk, Elisabeth M.A.G.; van Beijnum, Bernhard J.F.

    2008-01-01

    This paper describes the design and trial results of MusicReader, a networked application realizing sheet music related services for the support of ensemble and orchestra rehearsals and performances. To this end, MusicReader presents sheet music on computer screens and supports annotations, sheet

  13. Effect of Fee on Cervical Cancer Screening Attendance--ScreenFee, a Swedish Population-Based Randomised Trial.

    Science.gov (United States)

    Alfonzo, Emilia; Andersson Ellström, Agneta; Nemes, Szilard; Strander, Björn

    2016-01-01

    Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85-1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. ClinicalTrials.gov NCT02378324.

  14. Interval breast cancers in the 'screening with tomosynthesis or standard mammography' (STORM) population-based trial.

    Science.gov (United States)

    Houssami, Nehmat; Bernardi, Daniela; Caumo, Francesca; Brunelli, Silvia; Fantò, Carmine; Valentini, Marvi; Romanucci, Giovanna; Gentilini, Maria A; Zorzi, Manuel; Macaskill, Petra

    2018-04-01

    The prospective 'screening with tomosynthesis or standard mammography' (STORM) trial recruited women participating in biennial breast screening in Italy (2011-2012), and compared sequential screen-readings based on 2D-mammography alone or based on tomosynthesis (integrated 2D/3D-mammography). The STORM trial showed that tomosynthesis screen-reading significantly increased breast cancer detection compared to 2D-mammography alone. The present study completes reporting of the trial by examining interval breast cancers ascertained at two year follow-up. 9 interval breast cancers were identified; the estimated interval cancer rate was 1.23/1000 screens [9/7292] (95%CI 0.56 to 2.34) or 1.24/1000 negative screens [9/7235] (95%CI 0.57 to 2.36). In concurrently screened women who attended the same screening services and received 2D-mammography, interval cancer rate was 1.60/1000 screens [40/25,058] (95% CI 1.14 to 2.17) or 1.61/1000 negative screens [40/24,922] (95% CI 1.15 to 2.18). Estimated screening sensitivity for the STORM trial was 85.5% [59/69] (95%CI 75.0%-92.8%), and that for 2D-mammography screening was 77.3% [136/176] (95%CI 70.4%-83.2%). Interval breast cancer rate amongst screening participants in the STORM trial was marginally lower (and screening sensitivity higher) than estimates amongst 2D-screened women; these findings should be interpreted with caution given the small number of interval cases and the sample size of the trial. Much larger screening studies, or pooled analyses, are required to examine interval cancer rates arising after breast tomosynthesis screening versus digital mammography screening. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Digital breast tomosynthesis (3D-mammography) screening: A pictorial review of screen-detected cancers and false recalls attributed to tomosynthesis in prospective screening trials.

    Science.gov (United States)

    Houssami, Nehmat; Lång, Kristina; Bernardi, Daniela; Tagliafico, Alberto; Zackrisson, Sophia; Skaane, Per

    2016-04-01

    This pictorial review highlights cancers detected only at tomosynthesis screening and screens falsely recalled in the course of breast tomosynthesis screening, illustrating both true-positive (TP) and false-positive (FP) detection attributed to tomosynthesis. Images and descriptive data were used to characterise cases of screen-detection with tomosynthesis, sourced from prospective screening trials that performed standard (2D) digital mammography (DM) and tomosynthesis (3D-mammography) in the same screening participants. Exemplar cases from four trials highlight common themes of relevance to screening practice including: the type of lesions frequently made more conspicuous or perceptible by tomosynthesis (spiculated masses, and architectural distortions); the histologic findings (both TP and FP) of tomosynthesis-only detection; and the need to extend breast work-up protocols (additional imaging including ultrasound and MRI, and tomosynthesis-guided biopsy) if tomosynthesis is adopted for primary screening. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Why mammography screening has not lived up to expectations from the randomised trials

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Jørgensen, Karsten Juhl; Zahl, Per-Henrik

    2012-01-01

    adjuvant therapy and breast cancer awareness, not screening. We also believe it is more important to reduce the incidence of cancer than to detect it 'early.' Avoiding getting screening mammograms reduces the risk of becoming a breast cancer patient by one-third.......We analysed the relation between tumour sizes and stages and the reported effects on breast cancer mortality with and without screening in trials and observational studies. The average tumour sizes in all the trials suggest only a 12% reduction in breast cancer mortality, which agrees with the 10......% reported in the most reliable trials. Recent studies of tumour sizes and tumour stages show that screening has not lowered the rate of advanced cancers. In agreement with this, recent observational studies of breast cancer mortality have failed to find an effect of screening. In contrast, screening leads...

  17. The impact of radiologists' expertise on screen results decisions in a CT lung cancer screening trial

    International Nuclear Information System (INIS)

    Heuvelmans, Marjolein A.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; Jong, Pim A. de; Mali, Willem P.; Groen, Harry J.M.

    2015-01-01

    To evaluate the impact of radiological expertise on screen result decisions in a CT lung cancer screening trial. In the NELSON lung cancer screening trial, the baseline CT result was based on the largest lung nodule's volume. The protocol allowed radiologists to manually adjust screen results in cases of high suspicion of benign or malignant nodule nature. Participants whose baseline CT result was based on a solid or part-solid nodule were included in this study. Adjustments by radiologists at baseline were evaluated. Histology was the reference for diagnosis or to confirm benignity and stability on subsequent CT examinations. A total of 3,318 participants (2,796 male, median age 58.0 years) were included. In 195 participants (5.9 %) the initial baseline screen result was adjusted by the radiologist. Adjustment was downwards from positive or indeterminate to negative in two and 119 participants, respectively, and from positive to indeterminate in 65 participants. None of these nodules turned out to be malignant. In 9/195 participants (4.6 %) the screen result was adjusted upwards from negative to indeterminate or indeterminate to positive; two nodules were malignant. In one in 20 cases of baseline lung cancer screening, nodules were reclassified by the radiologist, leading to a reduction of false-positive screen results. (orig.)

  18. Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

    Science.gov (United States)

    Autier, Philippe; Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

    2016-01-01

    The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

  19. The Danish Cardiovascular Screening Trial (DANCAVAS)

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Rasmussen, Lars Melholt; Søgaard, Rikke

    2015-01-01

    to cardiovascular seven-faceted screening examinations at one of four locations. The screening will include: (1) low-dose non-contrast CT scan to detect coronary artery calcification and aortic/iliac aneurysms, (2) brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension, (3...... events, and whether the possible health benefits are cost effective. OUTCOME: Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome). RANDOMIZATION: Each of the 45,000 individuals is, by EPIDATA, given a random number from 1-100. Those....../iliac aneurysms) and measurements of the ankle brachial blood pressure index (ABI) as part of a multifocal screening and intervention program for CVD in men aged 65-74. Attendance rate and compliance to initiated preventive actions must be expected to become of major importance. TRIAL REGISTRATION: Current...

  20. Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C

    2011-01-01

    The mammography screening trials have shown varying results. This could be because screening was better in some trials than in others at advancing the time of diagnosis. If so, more cancers would be identified in such trials relative to the control group, and fewer of the cancers would have reach...

  1. Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST)

    DEFF Research Database (Denmark)

    Ashraf, H; Tønnesen, P; Holst Pedersen, J

    2008-01-01

    BACKGROUND: The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. METHODS: This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial...... pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow...... (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20...

  2. The impact of radiologists' expertise on screen results decisions in a CT lung cancer screening trial

    Energy Technology Data Exchange (ETDEWEB)

    Heuvelmans, Marjolein A.; Vliegenthart, Rozemarijn [University of Groningen, University Medical Center Groningen, Center for Medical Imaging - North East Netherlands, Groningen (Netherlands); University of Groningen / University Medical Center Groningen, Department of Radiology, Groningen (Netherlands); Oudkerk, Matthijs [University of Groningen, University Medical Center Groningen, Center for Medical Imaging - North East Netherlands, Groningen (Netherlands); Jong, Pim A. de; Mali, Willem P. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Groen, Harry J.M. [University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen (Netherlands)

    2014-11-04

    To evaluate the impact of radiological expertise on screen result decisions in a CT lung cancer screening trial. In the NELSON lung cancer screening trial, the baseline CT result was based on the largest lung nodule's volume. The protocol allowed radiologists to manually adjust screen results in cases of high suspicion of benign or malignant nodule nature. Participants whose baseline CT result was based on a solid or part-solid nodule were included in this study. Adjustments by radiologists at baseline were evaluated. Histology was the reference for diagnosis or to confirm benignity and stability on subsequent CT examinations. A total of 3,318 participants (2,796 male, median age 58.0 years) were included. In 195 participants (5.9 %) the initial baseline screen result was adjusted by the radiologist. Adjustment was downwards from positive or indeterminate to negative in two and 119 participants, respectively, and from positive to indeterminate in 65 participants. None of these nodules turned out to be malignant. In 9/195 participants (4.6 %) the screen result was adjusted upwards from negative to indeterminate or indeterminate to positive; two nodules were malignant. In one in 20 cases of baseline lung cancer screening, nodules were reclassified by the radiologist, leading to a reduction of false-positive screen results. (orig.)

  3. Methods for the Design of Vasomotor Symptom Trials: The MsFLASH Network

    Science.gov (United States)

    Newton, Katherine M.; Carpenter, Janet S.; Guthrie, Katherine A.; Anderson, Garnet L.; Caan, Bette; Cohen, Lee S.; Ensrud, Kristine E.; Freeman, Ellen W.; Joffe, Hadine; Sternfeld, Barbara; Reed, Susan D.; Sherman, Sheryl; Sammel, Mary D.; Kroenke, Kurt; Larson, Joseph C.; LaCroix, Andrea Z.

    2013-01-01

    Objective This report describes the "Menopausal Strategies: Finding Lasting Answers to Symptoms and Health” (MsFLASH) network and methodological issues addressed in designing and implementing vasomotor symptom trials. Methods Established in response to a National Institute of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented including: 1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; 2) a 2×3 factorial design trial to test three different interventions (yoga, exercise, and omega-3 supplementation) for improvement of vasomotor symptom frequency and bother; and 3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency compared to placebo. The network’s structure and governance are also discussed. Conclusions The methods used and lessons learned in the MsFLASH trials are shared to encourage and support the conduct of similar trials and encourage collaborations with other researchers. PMID:23760428

  4. SPIRIT: A seamless phase I/II randomized design for immunotherapy trials.

    Science.gov (United States)

    Guo, Beibei; Li, Daniel; Yuan, Ying

    2018-06-07

    Immunotherapy-treatments that enlist the immune system to battle tumors-has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression-free survival and the immune response. Progression-free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression-free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design. Copyright © 2018 John Wiley & Sons, Ltd.

  5. Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose CT

    DEFF Research Database (Denmark)

    Ashraf, Haseem; Saghir, Zaigham; Dirksen, Asger

    2014-01-01

    BACKGROUND: We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. METHODS: The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised...... to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening...... round were handled using two different models. RESULTS: There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p

  6. Adaptive Clinical Trials: Advantages and Disadvantages of Various Adaptive Design Elements.

    Science.gov (United States)

    Korn, Edward L; Freidlin, Boris

    2017-06-01

    There is a wide range of adaptive elements of clinical trial design (some old and some new), with differing advantages and disadvantages. Classical interim monitoring, which adapts the design based on early evidence of superiority or futility of a treatment arm, has long been known to be extremely useful. A more recent application of interim monitoring is in the use of phase II/III designs, which can be very effective (especially in the setting of multiple experimental treatments and a reliable intermediate end point) but do have the cost of having to commit earlier to the phase III question than if separate phase II and phase III trials were performed. Outcome-adaptive randomization is an older technique that has recently regained attention; it increases trial complexity and duration without offering substantial benefits to the patients in the trial. The use of adaptive trials with biomarkers is new and has great potential for efficiently identifying patients who will be helped most by specific treatments. Master protocols in which trial arms and treatment questions are added to an ongoing trial can be especially efficient in the biomarker setting, where patients are screened for entry into different subtrials based on evolving knowledge about targeted therapies. A discussion of three recent adaptive clinical trials (BATTLE-2, I-SPY 2, and FOCUS4) highlights the issues. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

  7. The Depression in Visual Impairment Trial (DEPVIT: trial design and protocol

    Directory of Open Access Journals (Sweden)

    Margrain Tom H

    2012-07-01

    Full Text Available Abstract Background The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression. Methods /design The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST, a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D, the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation. Discussion Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment. Trial registration ISRCTN46824140

  8. A clinical trial of a rare earth screen/film system in a periapical cassette

    International Nuclear Information System (INIS)

    Kogon, S.L.; Stephens, R.G.; Reid, J.A.; Lubus, N.J.

    1984-01-01

    In a clinical trial, a slow rare earth screen/film system (Siemens Titan 2D/Kodak XG) was used to obtain intraoral radiographs at conventional monitoring stages in endodontic treatment. The screen film image proved to be an effective substitute for the direct-exposure Ultraspeed periapical film. The intraoral cassettes, designed and fabricated for the study, were an adaptation of the flexible, vacuum-sealed cassettes used in mammography. It is believed that when a practicable periapical cassette is manufactured, many additional indications for the system are probable. Major reductions in patient exposure of at least 85% to 90% per periapical film would be effected

  9. The Performance of Step-Wise Group Screening Designs

    Directory of Open Access Journals (Sweden)

    M.M. Manene

    2005-06-01

    Full Text Available In this paper we evaluate the performance of step-wise group screening designs in which group-factors contain an equal number of factors in the initial step.  A usual assumption in group screening designs is that the directions of possible effects are known a-priori. In practice, however, this assumption is unreasonable. We shall examine step-wise group screening designs without errors in observations when this assumption is relaxed. We shall consider cancellations of effects within group-factors. The performance of step-wise group-screening designs shall then be compared with the performance of multistage group screening designs.

  10. The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

    Science.gov (United States)

    Birnbaum, Jeanette; Gadi, Vijayakrishna K; Markowitz, Elan; Etzioni, Ruth

    2016-02-16

    Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

  11. Psychosocial consequences in the Danish randomised controlled lung cancer screening trial (DLCST).

    Science.gov (United States)

    Rasmussen, Jakob F; Siersma, V; Pedersen, J H; Brodersen, J

    2015-01-01

    To measure the psychosocial consequences in the Danish lung cancer screening trial (DLCST) and compare those between the computed tomography (CT) group and the control group. This study was a single centre randomised controlled trial with five annual screening rounds. Healthy current or former heavy smokers aged 50-70 years (men and women) were randomised 1:1 to a CT group and a control group. Heavy smokers were defined by having smoked ≥20 pack years and former smokers by being abstinent ≤10 years. Both groups were invited annually to the screening clinic to complete the validated lung-cancer-specific questionnaire consequences of screening lung cancer (COS-LC). The CT group was also offered a low dose CT scan of the lungs. The COS-LC measures nine scales with psychosocial properties: Anxiety, Behaviour, Dejection, Negative impact on sleep, Self-blame, Focus on Airway Symptoms, Stigmatisation, Introvert, and Harm of Smoking. 4104 participants were randomised to the DLCST and the COS-LC completion rates for the CT group and the control group were 95.5% and 73.6%, respectively. There was a significant increase in negative psychosocial consequences from baseline through rounds 2-5 for both the CT group and the control group (mean increase >0, p0 and p<.033). Lung cancer CT-screening trials induced more negative psychosocial reactions in both the CT group and the control group compared with the baseline psychosocial profile. The CT group experienced less negative psychosocial consequences compared with the control group, which might be explained by reassurance among those with normal screening results. ClinicalTrials.gov: NCT00496977. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Types of Cancer Clinical Trials

    Science.gov (United States)

    Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

  13. Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial.

    Science.gov (United States)

    Skaane, Per; Sebuødegård, Sofie; Bandos, Andriy I; Gur, David; Østerås, Bjørn Helge; Gullien, Randi; Hofvind, Solveig

    2018-02-10

    Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening. Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50-69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds. 24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers. DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers. ClinicalTrials.gov: NCT01248546.

  14. An intervention to preschool children for reducing screen time: a randomized controlled trial.

    Science.gov (United States)

    Yilmaz, G; Demirli Caylan, N; Karacan, C D

    2015-05-01

    Screen time, defined as time spent watching television, DVDs, or videos or playing computer or video games, has been related to serious health consequences in children, such as impaired language acquisition, violent behaviour, tobacco smoking and obesity. Our aim was to determine if a simple intervention aimed at preschool-aged children, applied at the health maintenance visits, in the primary care setting, would be effective in reducing screen time. We used a two group randomized controlled trial design. Two- to 6-year-old children and their parents were randomly assigned to receive an intervention to reduce their screen time, BMI and parental report of aggressive behaviour. At the end of the intervention we made home visits at 2, 6 and 9 months and the parents completed questionnaire. Parents in the intervention group reported less screen time and less aggressive behaviour than those in the control group but there were no differences in BMI z scores. This study shows that a preschool-based intervention can lead to reductions in young children's television/video viewing. © 2014 John Wiley & Sons Ltd.

  15. Screening for type 2 diabetes in a high-risk population: study design and feasibility of a population-based randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Klijs Bart

    2012-08-01

    Full Text Available Abstract Background We describe the design and present the results of the first year of a population-based study of screening for type 2 diabetes in individuals at high risk of developing the disease. High risk is defined as having abdominal obesity. Methods Between 2006 and 2007, 79,142 inhabitants of two Dutch municipalities aged 40–74 years were approached to participate in screening. Eligible participants had a self-reported waist circumference of ≥80 cm for women and ≥94 cm for men, and no known pre-existing diabetes. Of the respondents (n = 20,578; response rate 26%, 16,135 were abdominally obese. In total, 10,609 individuals gave written informed consent for participation and were randomized into either the screening (n = 5305 or the control arm (n = 5304. Participants in the screening arm were invited to have their fasting plasma glucose (FPG measured and were referred to their general practitioner (GP if it was ≥6.1 mmol/L. In addition, blood lipids were determined in the screening arm, because abdominal obesity is often associated with cardiovascular risk factors. Participants in both arms received written healthy lifestyle information. Between-group differences were analyzed with Chi-square tests and logistic regression (categorical variables and unpaired t-tests (continuous variables. Results The screening attendance rate was 84.1%. Attending screening was associated with age at randomization (OR = 1.03, 95% CI 1.02-1.04, being married (OR = 1.57, 95% CI 1.33-1.83 and not-smoking currently (OR = 0.52, 95% CI 0.44-0.62. Of the individuals screened, 5.6% had hyperglycemia, and a further 11.6% had an estimated absolute cardiovascular disease risk of 5% or higher, according to the Systematic Coronary Risk Evaluation risk model. These participants were referred to their GP. Conclusions Self-reported home-assessed waist circumference could feasibly detect persons at high risk of hyperglycemia or

  16. The Value of Pre-Screening in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease Trial.

    Science.gov (United States)

    Rios-Romenets, S; Giraldo-Chica, M; López, H; Piedrahita, F; Ramos, C; Acosta-Baena, N; Muñoz, C; Ospina, P; Tobón, C; Cho, W; Ward, M; Langbaum, J B; Tariot, P N; Reiman, E M; Lopera, F

    2018-01-01

    The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.

  17. Screening and brief interventions for hazardous alcohol use in accident and emergency departments: a randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Myles Judy

    2009-07-01

    Full Text Available Abstract Background There is a wealth of evidence regarding the detrimental impact of excessive alcohol consumption on the physical, psychological and social health of the population. There also exists a substantial evidence base for the efficacy of brief interventions aimed at reducing alcohol consumption across a range of healthcare settings. Primary research conducted in emergency departments has reinforced the current evidence regarding the potential effectiveness and cost-effectiveness. Within this body of evidence there is marked variation in the intensity of brief intervention delivered, from very minimal interventions to more intensive behavioural or lifestyle counselling approaches. Further the majority of primary research has been conducted in single centre and there is little evidence of the wider issues of generalisability and implementation of brief interventions across emergency departments. Methods/design The study design is a prospective pragmatic factorial cluster randomised controlled trial. Individual Emergency Departments (ED (n = 9 are randomised with equal probability to a combination of screening tool (M-SASQ vs FAST vs SIPS-PAT and an intervention (Minimal intervention vs Brief advice vs Brief lifestyle counselling. The primary hypothesis is that brief lifestyle counselling delivered by an Alcohol Health Worker (AHW is more effective than Brief Advice or a minimal intervention delivered by ED staff. Secondary hypotheses address whether short screening instruments are more acceptable and as efficient as longer screening instruments and the cost-effectiveness of screening and brief interventions in ED. Individual participants will be followed up at 6 and 12 months after consent. The primary outcome measure is performance using a gold-standard screening test (AUDIT. Secondary outcomes include; quantity and frequency of alcohol consumed, alcohol-related problems, motivation to change, health related quality of life and

  18. The accuracy and efficiency of electronic screening for recruitment into a clinical trial on COPD.

    Science.gov (United States)

    Schmickl, Christopher N; Li, Man; Li, Guangxi; Wetzstein, Marnie M; Herasevich, Vitaly; Gajic, Ognjen; Benzo, Roberto P

    2011-10-01

    Participant recruitment is an important process in successful conduct of randomized controlled trials. To facilitate enrollment into a National Institutes of Health-sponsored clinical trial involving patients with chronic obstructive pulmonary disease (COPD), we developed and prospectively validated an automated electronic screening tool based on boolean free-text search of admission notes in electronic medical records. During a 2-week validation period, all patients admitted to prespecified general medical services were screened for eligibility by both the electronic screening tool and a COPD nurse. Group discussion was the gold standard for confirmation of true-positive results. Compared with the gold standard, electronic screening yielded 100% sensitivity, 92% specificity, 100% negative predictive value, and 72% positive predictive value. Compared with traditional manual screening, electronic screening demonstrated time-saving potential of 76%. Thus, the electronic screening tool accurately identifies potential study subjects and improves efficiency of patient accrual for a clinical trial on COPD. This method may be expanded into other institutional and clinical settings. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Design of low cost glaucoma screening

    NARCIS (Netherlands)

    Niessen, A. G.; Langerhorst, C. T.; Geijssen, H. C.; Greve, E. L.

    1997-01-01

    In 1991 the Netherlands Glaucoma Patient Association organized a glaucoma screening survey. This survey was designed to evaluate the effectiveness of a low cost screening setting. During a screening period of 8 days, 1259 subjects over the age of 49 years were examined by a team of

  20. Using simulation to aid trial design: Ring-vaccination trials.

    Directory of Open Access Journals (Sweden)

    Matt David Thomas Hitchings

    2017-03-01

    Full Text Available The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination.We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design.Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the

  1. Using the web for recruitment, screen, tracking, data management, and quality control in a dietary assessment clinical validation trial.

    Science.gov (United States)

    Arab, Lenore; Hahn, Harry; Henry, Judith; Chacko, Sara; Winter, Ashley; Cambou, Mary C

    2010-03-01

    Screening and tracking subjects and data management in clinical trials require significant investments in manpower that can be reduced through the use of web-based systems. To support a validation trial of various dietary assessment tools that required multiple clinic visits and eight repeats of online assessments, we developed an interactive web-based system to automate all levels of management of a biomarker-based clinical trial. The "Energetics System" was developed to support 1) the work of the study coordinator in recruiting, screening and tracking subject flow, 2) the need of the principal investigator to review study progress, and 3) continuous data analysis. The system was designed to automate web-based self-screening into the trial. It supported scheduling tasks and triggered tailored messaging for late and non-responders. For the investigators, it provided real-time status overviews on all subjects, created electronic case reports, supported data queries and prepared analytic data files. Encryption and multi-level password protection were used to insure data privacy. The system was programmed iteratively and required six months of a web programmer's time along with active team engagement. In this study the enhancement in speed and efficiency of recruitment and quality of data collection as a result of this system outweighed the initial investment. Web-based systems have the potential to streamline the process of recruitment and day-to-day management of clinical trials in addition to improving efficiency and quality. Because of their added value they should be considered for trials of moderate size or complexity. Copyright 2009 Elsevier Inc. All rights reserved.

  2. MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

    Science.gov (United States)

    Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

    2016-09-30

    Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Myles Judy

    2009-11-01

    Full Text Available Abstract Background A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Methods and design Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4 and London and the South East Regions (n = 5 will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs; 5-minute simple structured advice (n = 32 OMs and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs. Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ or the Fast Alcohol Screening Test (FAST. There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention. We will also examine the

  4. Maternal and child health nurse screening and care for mothers experiencing domestic violence (MOVE): a cluster randomised trial.

    Science.gov (United States)

    Taft, Angela J; Hooker, Leesa; Humphreys, Cathy; Hegarty, Kelsey; Walter, Ruby; Adams, Catina; Agius, Paul; Small, Rhonda

    2015-06-25

    Mothers are at risk of domestic violence (DV) and its harmful consequences postpartum. There is no evidence to date for sustainability of DV screening in primary care settings. We aimed to test whether a theory-informed, maternal and child health (MCH) nurse-designed model increased and sustained DV screening, disclosure, safety planning and referrals compared with usual care. Cluster randomised controlled trial of 12 month MCH DV screening and care intervention with 24 month follow-up. The study was set in community-based MCH nurse teams (91 centres, 163 nurses) in north-west Melbourne, Australia. Eight eligible teams were recruited. Team randomisation occurred at a public meeting using opaque envelopes. Teams were unable to be blinded. The intervention was informed by Normalisation Process Theory, the nurse-designed good practice model incorporated nurse mentors, strengthened relationships with DV services, nurse safety, a self-completion maternal health screening checklist at three or four month consultations and DV clinical guidelines. Usual care involved government mandated face-to-face DV screening at four weeks postpartum and follow-up as required. Primary outcomes were MCH team screening, disclosure, safety planning and referral rates from routine government data and a postal survey sent to 10,472 women with babies ≤ 12 months in study areas. Secondary outcomes included DV prevalence (Composite Abuse Scale, CAS) and harm measures (postal survey). No significant differences were found in routine screening at four months (IG 2,330/6,381 consultations (36.5 %) versus CG 1,792/7,638 consultations (23.5 %), RR = 1.56 CI 0.96-2.52) but data from maternal health checklists (n = 2,771) at three month IG consultations showed average screening rates of 63.1 %. Two years post-intervention, IG safety planning rates had increased from three (RR 2.95, CI 1.11-7.82) to four times those of CG (RR 4.22 CI 1.64-10.9). Referrals remained low in both intervention groups (IGs

  5. Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23)

    DEFF Research Database (Denmark)

    Thamsborg, Lise Holst; Andersen, Berit; Larsen, Lise Grupe

    2018-01-01

    arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7-8 years. ANALYSES: The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study......INTRODUCTION: The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could...... vaccination as girls. METHODS: Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme...

  6. Adaptive designs in clinical trials

    Directory of Open Access Journals (Sweden)

    Suresh Bowalekar

    2011-01-01

    Full Text Available In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

  7. Adaptive designs in clinical trials.

    Science.gov (United States)

    Bowalekar, Suresh

    2011-01-01

    In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

  8. The optimal design of stepped wedge trials with equal allocation to sequences and a comparison to other trial designs.

    Science.gov (United States)

    Thompson, Jennifer A; Fielding, Katherine; Hargreaves, James; Copas, Andrew

    2017-12-01

    Background/Aims We sought to optimise the design of stepped wedge trials with an equal allocation of clusters to sequences and explored sample size comparisons with alternative trial designs. Methods We developed a new expression for the design effect for a stepped wedge trial, assuming that observations are equally correlated within clusters and an equal number of observations in each period between sequences switching to the intervention. We minimised the design effect with respect to (1) the fraction of observations before the first and after the final sequence switches (the periods with all clusters in the control or intervention condition, respectively) and (2) the number of sequences. We compared the design effect of this optimised stepped wedge trial to the design effects of a parallel cluster-randomised trial, a cluster-randomised trial with baseline observations, and a hybrid trial design (a mixture of cluster-randomised trial and stepped wedge trial) with the same total cluster size for all designs. Results We found that a stepped wedge trial with an equal allocation to sequences is optimised by obtaining all observations after the first sequence switches and before the final sequence switches to the intervention; this means that the first sequence remains in the control condition and the last sequence remains in the intervention condition for the duration of the trial. With this design, the optimal number of sequences is [Formula: see text], where [Formula: see text] is the cluster-mean correlation, [Formula: see text] is the intracluster correlation coefficient, and m is the total cluster size. The optimal number of sequences is small when the intracluster correlation coefficient and cluster size are small and large when the intracluster correlation coefficient or cluster size is large. A cluster-randomised trial remains more efficient than the optimised stepped wedge trial when the intracluster correlation coefficient or cluster size is small. A

  9. Design of Phase II Non-inferiority Trials.

    Science.gov (United States)

    Jung, Sin-Ho

    2017-09-01

    With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

  10. Overview of guidelines on breast screening

    DEFF Research Database (Denmark)

    Juhl Jørgensen, Karsten; Kalager, Mette; Barratt, Alexandra

    2017-01-01

    Updated guidelines on breast cancer screening have been published by several major organisations over the past five years. Recommendations vary regarding both age range, screening interval, and even on whether breast screening should be offered at all. The variation between recommendations reflects....... The estimates vary according to the methodology of the randomised trials, and the design of the observational studies. Guideline recommendations reflect the choice of evidence informing them. While there are well-developed tools to deal with randomised trials in guideline work, these are not always used......, or they may not be followed as recommended. Further, results of trials performed decades ago may no longer be applicable. For observational studies, the framework for inclusion in guidelines is not similarly well-developed and there are methodological concerns specific to screening interventions...

  11. Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lo-Ten-Foe Jerome R

    2010-11-01

    Full Text Available Abstract Background In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. Methods/design We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation or obstetric complication (low birth weight, preterm delivery or fetal death in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. Discussion With this study we aim to provide insight into the balance of risks of undetected and detected Q

  12. Cervical cancer screening and adherence to follow-up among Hispanic women study protocol: a randomized controlled trial to increase the uptake of cervical cancer screening in Hispanic women

    Directory of Open Access Journals (Sweden)

    Duggan Catherine

    2012-05-01

    Full Text Available Abstract Background In the US, Hispanic women have a higher incidence of, and mortality from, cervical cancer than non-Hispanic white women. The reason for this disparity may be attributable to both low rates of screening and poor adherence to recommended diagnostic follow-up after an abnormal Pap test. The 'Cervical Cancer Screening and Adherence to Follow-up Among Hispanic Women' study is a collaboration between a research institution and community partners made up of members from community based organizations, the Yakima Valley Farm Workers Clinic and the Breast, Cervical, and Colon Health Program of the Yakima District . The study will assess the efficacy of two culturally-appropriate, tailored educational programs designed to increase cervical cancer screening among Hispanic women, based in the Yakima Valley, Washington, US. Methods/design A parallel randomized-controlled trial of 600 Hispanic women aged 21–64, who are non-compliant with Papanicolau (Pap test screening guidelines. Participants will be randomized using block randomization to (1 a control arm (usual care; (2 a low-intensity information program, consisting of a Spanish-language video that educates women on the importance of cervical cancer screening; or (3 a high-intensity program consisting of the video plus a ‘promotora’ or lay-community health educator-led, home based intervention to encourage cervical cancer screening. Participants who attend cervical cancer screening, and receive a diagnosis of an abnormal Pap test will be assigned to a patient navigator who will provide support and information to promote adherence to follow-up tests, and any necessary surgery or treatment. Primary endpoint: Participants will be tracked via medical record review at community-based clinics, to identify women who have had a Pap test within 7 months of baseline assessment. Medical record reviewers will be blinded to randomization arm. Secondary endpoint: An evaluation of the patient

  13. Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial.

    Science.gov (United States)

    Denny, Lynette; Kuhn, Louise; De Souza, Michelle; Pollack, Amy E; Dupree, William; Wright, Thomas C

    2005-11-02

    Non-cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women's health clinics in Khayelitsha, South Africa. All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (Pcryotherapy, major complications were rare. Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration http://clinicaltrials.gov Identifier: NCT00233727.

  14. Falls Assessment Clinical Trial (FACT: design, interventions, recruitment strategies and participant characteristics

    Directory of Open Access Journals (Sweden)

    Lawton Beverley

    2007-07-01

    Full Text Available Abstract Background Guidelines recommend multifactorial intervention programmes to prevent falls in older adults but there are few randomised controlled trials in a real life health care setting. We describe the rationale, intervention, study design, recruitment strategies and baseline characteristics of participants in a randomised controlled trial of a multifactorial falls prevention programme in primary health care. Methods Participants are patients from 19 primary care practices in Hutt Valley, New Zealand aged 75 years and over who have fallen in the past year and live independently. Two recruitment strategies were used – waiting room screening and practice mail-out. Intervention participants receive a community based nurse assessment of falls and fracture risk factors, home hazards, referral to appropriate community interventions, and strength and balance exercise programme. Control participants receive usual care and social visits. Outcome measures include number of falls and injuries over 12 months, balance, strength, falls efficacy, activities of daily living, quality of life, and physical activity levels. Results 312 participants were recruited (69% women. Of those who had fallen, 58% of people screened in the practice waiting rooms and 40% when screened by practice letter were willing to participate. Characteristics of participants recruited using the two methods are similar (p > 0.05. Mean age of all participants was 81 years (SD 5. On average participants have 7 medical conditions, take 5.5 medications (29% on psychotropics with a median of 2 falls (interquartile range 1, 3 in the previous year. Conclusion The two recruitment strategies and the community based intervention delivery were feasible and successful, identifying a high risk group with multiple falls. Recruitment in the waiting room gave higher response rates but was less efficient than practice mail-out. Testing the effectiveness of an evidence based intervention in a

  15. Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

    Science.gov (United States)

    Lin, Ja-An; He, Pei

    2015-06-01

    Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Participant recruitment and motivation for participation in optical technology for cervical cancer screening research trials.

    Science.gov (United States)

    Shuhatovich, Olga M; Sharman, Mathilde P; Mirabal, Yvette N; Earle, Nan R; Follen, Michele; Basen-Engquist, Karen

    2005-12-01

    In order to improve recruitment for cervical cancer screening trials, it is necessary to analyze the effectiveness of recruitment strategies used in current trials. A trial to test optical spectroscopy for the diagnosis of cervical neoplasia recruited 1000 women from the community; the trial evaluated the emerging technology against Pap smears and colposcopically directed biopsies for cervical dysplasia. We have examined women's reasons for participating as well as the effectiveness and efficiency for each recruitment strategy. Reasons for participation were identified and compared between trials. The recruitment method that resulted in the most contacts was newspaper reportorial coverage and advertising, followed by family and friends, then television news coverage. The most cost-effective method for finding eligible women who attend the research appointment is word of mouth from a family member or friend. Recommendations are given for maximizing the efficiency of recruitment for cervical cancer screening trials.

  17. Computer-aided system of evaluation for population-based all-in-one service screening (CASE-PASS): from study design to outcome analysis with bias adjustment.

    Science.gov (United States)

    Chen, Li-Sheng; Yen, Amy Ming-Fang; Duffy, Stephen W; Tabar, Laszlo; Lin, Wen-Chou; Chen, Hsiu-Hsi

    2010-10-01

    Population-based routine service screening has gained popularity following an era of randomized controlled trials. The evaluation of these service screening programs is subject to study design, data availability, and the precise data analysis for adjusting bias. We developed a computer-aided system that allows the evaluation of population-based service screening to unify these aspects and facilitate and guide the program assessor to efficiently perform an evaluation. This system underpins two experimental designs: the posttest-only non-equivalent design and the one-group pretest-posttest design and demonstrates the type of data required at both the population and individual levels. Three major analyses were developed that included a cumulative mortality analysis, survival analysis with lead-time adjustment, and self-selection bias adjustment. We used SAS AF software to develop a graphic interface system with a pull-down menu style. We demonstrate the application of this system with data obtained from a Swedish population-based service screen and a population-based randomized controlled trial for the screening of breast, colorectal, and prostate cancer, and one service screening program for cervical cancer with Pap smears. The system provided automated descriptive results based on the various sources of available data and cumulative mortality curves corresponding to the study designs. The comparison of cumulative survival between clinically and screen-detected cases without a lead-time adjustment are also demonstrated. The intention-to-treat and noncompliance analysis with self-selection bias adjustments are also shown to assess the effectiveness of the population-based service screening program. Model validation was composed of a comparison between our adjusted self-selection bias estimates and the empirical results on effectiveness reported in the literature. We demonstrate a computer-aided system allowing the evaluation of population-based service screening

  18. A screening tool to enhance clinical trial participation at a community center involved in a radiation oncology disparities program.

    Science.gov (United States)

    Proctor, Julian W; Martz, Elaine; Schenken, Larry L; Rainville, Rebecca; Marlowe, Ursula

    2011-05-01

    To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute-funded disparities program but lacking on-site clinical trials personnel. The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials.

  19. A new efficient mixture screening design for optimization of media.

    Science.gov (United States)

    Rispoli, Fred; Shah, Vishal

    2009-01-01

    Screening ingredients for the optimization of media is an important first step to reduce the many potential ingredients down to the vital few components. In this study, we propose a new method of screening for mixture experiments called the centroid screening design. Comparison of the proposed design with Plackett-Burman, fractional factorial, simplex lattice design, and modified mixture design shows that the centroid screening design is the most efficient of all the designs in terms of the small number of experimental runs needed and for detecting high-order interaction among ingredients. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

  20. Barriers to uptake among high-risk individuals declining participation in lung cancer screening: a mixed methods analysis of the UK Lung Cancer Screening (UKLS) trial.

    Science.gov (United States)

    Ali, Noor; Lifford, Kate J; Carter, Ben; McRonald, Fiona; Yadegarfar, Ghasem; Baldwin, David R; Weller, David; Hansell, David M; Duffy, Stephen W; Field, John K; Brain, Kate

    2015-07-14

    The current study aimed to identify the barriers to participation among high-risk individuals in the UK Lung Cancer Screening (UKLS) pilot trial. The UKLS pilot trial is a randomised controlled trial of low-dose CT (LDCT) screening that has recruited high-risk people using a population approach in the Cambridge and Liverpool areas. High-risk individuals aged 50-75 years were invited to participate in UKLS. Individuals were excluded if a LDCT scan was performed within the last year, if they were unable to provide consent, or if LDCT screening was unable to be carried out due to coexisting comorbidities. Statistical associations between individual characteristics and UKLS uptake were examined using multivariable regression modelling. In those who completed a non-participation questionnaire (NPQ), thematic analysis of free-text data was undertaken to identify reasons for not taking part, with subsequent exploratory linkage of key themes to risk factors for non-uptake. Comparative data were available from 4061 high-risk individuals who consented to participate in the trial and 2756 who declined participation. Of those declining participation, 748 (27.1%) completed a NPQ. Factors associated with non-uptake included: female gender (OR=0.64, pemotional barriers. Smokers were more likely to report emotional barriers to participation. A profile of risk factors for non-participation in lung screening has emerged, with underlying reasons largely relating to practical and emotional barriers. Strategies for engaging high-risk, hard-to-reach groups are critical for the equitable uptake of a potential future lung cancer screening programme. The UKLS trial was registered with the International Standard Randomised Controlled Trial Register under the reference 78513845. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial

    Science.gov (United States)

    Bergdahl, Anna Grenabo; Wilderäng, Ulrica; Aus, Gunnar; Carlsson, Sigrid; Damber, Jan-Erik; Frånlund, Maria; Geterud, Kjell; Khatami, Ali; Socratous, Andreas; Stranne, Johan; Hellström, Mikael; Hugosson, Jonas

    2016-01-01

    Background Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer (PC) compared to prostate-specific antigen (PSA) and systematic biopsies (SB). Objective To compare sequential screening (PSA + MRI) with conventional PSA screening. Design, Setting and Participants Of 384 attendees in the 10th screening round of the Göteborg randomised screening trial, 124 men, median age 69.5, had a PSA of ≥1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA ≥3.0 ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in men with tumour-suspicious findings on MRI. Three screening strategies were compared (PSA≥3.0+SB; PSA≥3.0+MRI+TB and PSA≥1.8+MRI+TB). Outcome Measurements and Statistical Analysis Cancer detection rates, sensitivity and specificity were calculated per screening strategy and compared using McNemar´s test. Results and Limitations In total, 28 PC were detected, of which 20 were diagnosed in biopsy-naïve men. Both PSA≥3.0+MRI and PSA≥1.8+MRI significantly increased specificity compared with PSA≥3.0+SB (0.92 and 0.79 vs. 0.52; p=3.0+MRI (0.73 vs. 0.46, p=0.008). The detection rate of significant cancer was higher with PSA≥1.8+MRI compared to PSA≥3.0+SB (5.9 vs. 4.0%), while the detection rate of insignificant cancer was lowered by PSA≥3.0+MRI (0.3 vs. 1.2%). The primary limitation of this study is the small sample of men. Conclusion A screening strategy with a lowered PSA cut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening. Patient Summary Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in

  2. A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

    Science.gov (United States)

    Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

    2012-09-01

    Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

  3. A Randomized Trial of Genetic and Environmental Risk Assessment (GERA) for Colorectal Cancer Risk in Primary Care: Trial Design and Baseline Findings

    Science.gov (United States)

    Myers, Ronald E.; Manne, Sharon L.; Wilfond, Benjamin; Sifri, Randa; Ziring, Barry; Wolf, Thomas A.; Cocroft, James; Ueland, Amy; Petrich, Anett; Swan, Heidi; DiCarlo, Melissa; Weinberg, David S.

    2010-01-01

    Purpose This paper describes an ongoing randomized controlled trial designed to assess the impact of genetic and environmental risk assessment (GERA) on colorectal cancer (CRC) screening. Methods The trial includes asymptomatic patients who are 50-79 years and are not up-to-date with CRC screening guidelines. Patients who responded to a baseline telephone survey are randomized to a GERA or Control group. GERA Group participants meet with a nurse, decide whether to have a GERA blood test (a combination of genetic polymorphism and folate), and, if tested, receive GERA feedback. Follow-up telephone surveys are conducted at one and six months. A chart audit is performed at six months. Results Of 2,223 eligible patients, 562 (25%) have enrolled. Patients who enrolled in the study were significantly younger than those who did not (p<0.001). Participants tended to be 50-59 years (64%), female (58%), white (52%), married (51%), and have more than a high school education (67%). At baseline, most participants had some knowledge of CRC screening and GERA, viewed CRC screening favorably, and reported that they had decided to do screening. Almost half had worries and concerns about CRC. Conclusions One in four eligible primary care patients enrolled in the study. Age was negatively associated with enrollment. Prospective analyses using data for all participants will provide more definitive information on GERA uptake and the impact of GERA feedback. PMID:20828635

  4. Preliminary ten year results from a randomised single centre mass screening trial for abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Juul, Søren; Fasting, H

    2006-01-01

    At present, several regions and countries are considering screening for abdominal aortic aneurysm (AAA). However, The Chichester Aneurysms Screening Trial has reported poor long term benefit of screening for AAA. We therefore supplement previously published data with a preliminary analysis...

  5. Biochemical verification of the self-reported smoking status of screened male smokers of the Dutch-Belgian randomized controlled lung cancer screening trial.

    Science.gov (United States)

    van der Aalst, Carlijn M; de Koning, Harry J

    2016-04-01

    Smoking is the main cause of lung cancer, so data linked to smoking behaviour are important in lung cancer screening trials. However, self-reporting data concerning smoking behaviour are mainly used. The aim of this study was to biochemically determine the validity and reliability of self-reported smoking status among smokers at high risk for developing lung cancer participating in the Dutch-Belgian lung cancer screening (NELSON) trial. For this sub study, a random sample of 475 men was selected who were scheduled for the fourth screening round in the NELSON trial. They were asked to complete a short questionnaire to verify the smoking behaviour for the previous seven days and a blood sample was collected to measure the cotinine level. The validity (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) and reliability (Kappa) of the self-reported smoking status compared to the cotinine level (as golden standard) were determined. Both a completed questionnaire as well as a cotinine level were available for 199 (41.9%) participants. Based on these data, Se and Sp were respectively 98% (95%-Confidence Interval (CI): 91-99) and 98% (95%-CI: 93-100). PPV and NPV were 98% and 96% and Kappa was 0.96. In conclusion, the validity of the self-reported smoking status turned out to be reliable amongst men at high risk for developing lung cancer who participate in the NELSON lung cancer screening trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Screening candidate systems engineers: a research design

    CSIR Research Space (South Africa)

    Goncalves, DP

    2009-07-01

    Full Text Available engineering screening methodology that could be used to screen potential systems engineers. According to their design, this can be achieved by defining a system engineering profile according to specific psychological attributes, and using this profile...

  7. Impact of Prostate-specific Antigen (PSA) Screening Trials and Revised PSA Screening Guidelines on Rates of Prostate Biopsy and Postbiopsy Complications.

    Science.gov (United States)

    Gershman, Boris; Van Houten, Holly K; Herrin, Jeph; Moreira, Daniel M; Kim, Simon P; Shah, Nilay D; Karnes, R Jeffrey

    2017-01-01

    Prostate biopsy and postbiopsy complications represent important risks of prostate-specific antigen (PSA) screening. Although landmark randomized trials and updated guidelines have challenged routine PSA screening, it is unclear whether these publications have affected rates of biopsy or postbiopsy complications. To evaluate whether publication of the 2008 and 2012 US Preventive Services Task Force (USPSTF) recommendations, the 2009 European Randomized Study of Screening for Prostate Cancer and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or the 2013 American Urological Association (AUA) guidelines was associated with changes in rates of biopsy or postbiopsy complications, and to identify predictors of postbiopsy complications. This quasiexperimental study used administrative claims of 5279315 commercially insured US men aged ≥40 yr from 2005 to 2014, of whom 104584 underwent biopsy. Publications on PSA screening. Interrupted time-series analysis was used to evaluate the association of publications with rates of biopsy and 30-d complications. Logistic regression was performed to identify predictors of complications. From 2005 to 2014, biopsy rates fell 33% from 64.1 to 42.8 per 100000 person-months, with immediate reductions following the 2008 USPSTF recommendations (-10.1; 95% confidence interval [CI], -17.1 to -3.0; pprostate-specific antigen screening; however, the relative morbidity of biopsy continues to increase. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  8. Increasing Cervical Cancer Screening Coverage: A Randomised, Community-Based Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Amelia Acera

    Full Text Available Opportunistic cervical cancer screening can lead to suboptimal screening coverage. Coverage could be increased after a personalised invitation to the target population. We present a community randomized intervention study with three strategies aiming to increase screening coverage.The CRICERVA study is a community-based clinical trial to improve coverage of population-based screening in the Cerdanyola SAP area in Barcelona.A total of 32,858 women residing in the study area, aged 30 to 70 years were evaluated. A total of 15,965 women were identified as having no registration of a cervical cytology in the last 3.5 years within the Public Health data base system. Eligible women were assigned to one of four community randomized intervention groups (IGs: (1 (IG1 N = 4197 personalised invitation letter, (2 (IG2 N = 3601 personalised invitation letter + informative leaflet, (3 (IG3 N = 6088 personalised invitation letter + informative leaflet + personalised phone call and (4 (Control N = 2079 based on spontaneous demand of cervical cancer screening as officially recommended. To evaluate screening coverage, we used heterogeneity tests to compare impact of the interventions and mixed logistic regression models to assess the age effect. We refer a "rescue" visit as the screening visit resulting from the study invitation.Among the 13,886 women in the IGs, 2,862 were evaluated as having an adequate screening history after the initial contact; 4,263 were lost to follow-up and 5,341 were identified as having insufficient screening and thus being eligible for a rescue visit. All intervention strategies significantly increased participation to screening compared to the control group. Coverage after the intervention reached 84.1% while the control group reached 64.8%. The final impact of our study was an increase of 20% in the three IGs and of 9% in the control group (p<0.001. Within the intervention arms, age was an important determinant of rescue visits

  9. The use of intermediate endpoints in the design of type 1 diabetes prevention trials.

    Science.gov (United States)

    Krischer, Jeffrey P

    2013-09-01

    This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials.

  10. Screening and brief intervention targeting risky drinkers in Danish general practice - a pragmatic controlled trial

    DEFF Research Database (Denmark)

    Beich, A.; Gannik, D.; Saelan, H.

    2007-01-01

    AIMS: Recommendations for routine alcohol screening and brief counselling intervention in primary health care rest on results from intervention efficacy studies. By conducting a pragmatic controlled trial (PCT), we aimed at evaluating the effectiveness of the WHO recommendations for screening......-14 months. Outcome measures focused on patients' acceptance of screening and intervention and their self-reported alcohol consumption. RESULTS: Patient acceptance of screening and intervention -10.3% (N = 794) of the target population (N = 7, 691) explicitly refused screening. All intervention group...

  11. The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

    Science.gov (United States)

    Quaife, Samantha L; Ruparel, Mamta; Beeken, Rebecca J; McEwen, Andy; Isitt, John; Nolan, Gary; Sennett, Karen; Baldwin, David R; Duffy, Stephen W; Janes, Samuel M; Wardle, Jane

    2016-04-20

    Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. If effective at improving informed uptake of screening and reducing bias in participation, this invitation

  12. Screen-Time Weight-loss Intervention Targeting Children at Home (SWITCH): a randomized controlled trial.

    Science.gov (United States)

    Maddison, Ralph; Marsh, Samantha; Foley, Louise; Epstein, Leonard H; Olds, Timothy; Dewes, Ofa; Heke, Ihirangi; Carter, Karen; Jiang, Yannan; Mhurchu, Cliona Ni

    2014-09-10

    Screen-based activities, such as watching television (TV), playing video games, and using computers, are common sedentary behaviors among young people and have been linked with increased energy intake and overweight. Previous home-based sedentary behaviour interventions have been limited by focusing primarily on the child, small sample sizes, and short follow-up periods. The SWITCH (Screen-Time Weight-loss Intervention Targeting Children at Home) study aimed to determine the effect of a home-based, family-delivered intervention to reduce screen-based sedentary behaviour on body composition, sedentary behaviour, physical activity, and diet over 24 weeks in overweight and obese children. A two-arm, parallel, randomized controlled trial was conducted. Children and their primary caregiver living in Auckland, New Zealand were recruited via schools, community centres, and word of mouth. The intervention, delivered over 20 weeks, consisted of a face-to-face meeting with the parent/caregiver and the child to deliver intervention content, which focused on training and educating them to use a wide range of strategies designed to reduce their child's screen time. Families were given Time Machine TV monitoring devices to assist with allocating screen time, activity packages to promote alternative activities, online support via a website, and monthly newsletters. Control participants were given the intervention material on completion of follow-up. The primary outcome was change in children's BMI z-score from baseline to 24 weeks. Children (n = 251) aged 9-12 years and their primary caregiver were randomized to receive the SWITCH intervention (n = 127) or no intervention (controls; n = 124). There was no significant difference in change of zBMI between the intervention and control groups, although a favorable trend was observed (-0.016; 95% CI: -0.084, 0.051; p = 0.64). There were also no significant differences on secondary outcomes, except for a trend towards

  13. Computer-delivered indirect screening and brief intervention for drug use in the perinatal period: A randomized trial.

    Science.gov (United States)

    Ondersma, Steven J; Svikis, Dace S; Thacker, Casey; Resnicow, Ken; Beatty, Jessica R; Janisse, James; Puder, Karoline

    2018-04-01

    Under-reporting of drug use in the perinatal period is well-documented, and significantly limits the reach of proactive intervention approaches. The Wayne Indirect Drug Use Screener (WIDUS) focuses on correlates of drug use rather than use itself. This trial tested a computer-delivered, brief intervention designed for use with indirect screen-positive cases, seeking to motivate reductions in drug use without presuming its presence. Randomized clinical trial with 500 WIDUS-positive postpartum women recruited between August 14, 2012 and November 19, 2014. Participants were randomly assigned to either a time control condition or a single-session, tailored, indirect brief intervention. The primary outcome was days of drug use over the 6-month follow-up period; secondary outcomes included urine and hair analyses results at 3- and 6-month follow-up. All outcomes were measured by blinded evaluators. Of the 500 participants (252 intervention and 248 control), 36.1% of participants acknowledged drug use in the 3 months prior to pregnancy, but 89% tested positive at the 6-month follow-up. Participants rated the intervention as easy to use (4.9/5) and helpful (4.4/5). Analyses revealed no between-group differences in drug use (52% in the intervention group, vs. 53% among controls; OR 1.03). Exploratory analyses also showed that intervention effects were not moderated by baseline severity, WIDUS score, or readiness to change. The present trial showed no evidence of efficacy for an indirect, single-session, computer-delivered, brief intervention designed as a complement to indirect screening. More direct approaches that still do not presume active drug use may be possible and appropriate. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Spine device clinical trials: design and sponsorship.

    Science.gov (United States)

    Cher, Daniel J; Capobianco, Robyn A

    2015-05-01

    Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (pdevices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Sequential Multiple Assignment Randomized Trials: An Opportunity for Improved Design of Stroke Reperfusion Trials.

    Science.gov (United States)

    Meurer, William J; Seewald, Nicholas J; Kidwell, Kelley

    2017-04-01

    Modern clinical trials in stroke reperfusion fall into 2 categories: alternative systemic pharmacological regimens to alteplase and "rescue" endovascular approaches using targeted thrombectomy devices and/or medications delivered directly for persistently occluded vessels. Clinical trials in stroke have not evaluated how initial pharmacological thrombolytic management might influence subsequent rescue strategy. A sequential multiple assignment randomized trial (SMART) is a novel trial design that can test these dynamic treatment regimens and lead to treatment guidelines that more closely mimic practice. To characterize a SMART design in comparison to traditional approaches for stroke reperfusion trials. We conducted a numerical simulation study that evaluated the performance of contrasting acute stroke clinical trial designs of both initial reperfusion and rescue therapy. We compare a SMART design where the same patients are followed through initial reperfusion and rescue therapy within 1 trial to a standard phase III design comparing 2 reperfusion treatments and a separate phase II futility design of rescue therapy in terms of sample size, power, and ability to address particular research questions. Traditional trial designs can be well powered and have optimal design characteristics for independent treatment effects. When treatments, such as the reperfusion and rescue therapies, may interact, commonly used designs fail to detect this. A SMART design, with similar sample size to standard designs, can detect treatment interactions. The use of SMART designs to investigate effective and realistic dynamic treatment regimens is a promising way to accelerate the discovery of new, effective treatments for stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Lung cancer screening in the NELSON trial: balancing harms and benefits

    NARCIS (Netherlands)

    N. Horeweg (Nanda)

    2014-01-01

    markdownabstract__Abstract__ In this thesis, the harms and benefits of lung cancer screening using low-dose computed tomography were investigated. Data of the Dutch-Belgian NELSON trial were used to quantify its harms and benefits and develop strategies to improve the balance between them. If the

  17. The Screen-ICD trial. Screening for anxiety and cognitive therapy intervention for patients with implanted cardioverter defibrillator (ICD)

    DEFF Research Database (Denmark)

    Berg, Selina Kikkenborg; Herning, Margrethe; Svendsen, Jesper Hastrup

    2016-01-01

    by Structured Clinical Interview for DSM Disorders (SCID). (3) Investigator-initiated randomised clinical superiority trial with blinded outcome assessment, with 1:1 randomisation to cognitive–behavioural therapy (CBT) performed by a cardiac nurse with CBT training, plus usual care or usual care alone...... of starting relevant intervention. Methods and analysis: Screen-ICD consists of 3 parts: (1) screening of all hospitalised and outpatient patients at two university hospitals using the Hospital Anxiety and Depression Scale (HADS), scores ≥8 are invited to participate. (2) Assessment of type of anxiety...

  18. The Viborg vascular (VIVA screening trial of 65-74 year old men in the central region of Denmark: study protocol

    Directory of Open Access Journals (Sweden)

    Henneberg Eskild W

    2010-05-01

    Full Text Available Abstract Background Screening for abdominal aortic aneurysm (AAA of men aged 65-74 years reduces the AAA-related mortality and is generally considered cost effective. Despite of this only a few national health care services have implemented permanent programs. Around 10% of men in this group have peripheral arterial disease (PAD defined by an ankle brachial systolic blood pressure index (ABI below 0.9 resulting in an increased mortality-rate of 25-30%. In addition well-documented health benefits may be achieved through primary prophylaxis by initiating systematic cholesterol-lowering, smoking cessation, low-dose acetylsalicylic acid (aspirins, exercise, a healthy diet and blood-pressure control altogether reducing the increased risks for cardiovascular disease by at least 20-25%. The benefits of combining screening for AAA and PAD seem evident; yet they remain to be established. The objective of this study is to assess the efficacy and the cost-effectiveness of a combined screening program for AAA, PAD and hypertension. Methods The Viborg Vascular (VIVA screening trial is a randomized, clinically controlled study designed to evaluate the benefits of vascular screening and modern vascular prophylaxis in a population of 50,000 men aged 65-74 years. Enrolment started October 2008 and is expected to stop in October 2010. The primary outcome is all-cause mortality. The secondary outcomes are cardiovascular mortality, AAA-related mortality, hospital services related to cardiovascular conditions, prevalence of AAA, PAD and potentially undiagnosed hypertension, health-related quality of life and cost effectiveness. Data analysis by intention to treat. Results Major follow-up will be performed at 3, 5 and 10 years and final study result after 15 years. Trial registration ClinicalTrials.gov NCT00662480

  19. Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc: a multicentre randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Saadatmand Sepideh

    2012-10-01

    Full Text Available Abstract Background To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test. The aim of the Familial MRI Screening Study (FaMRIsc is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density. Methods/Design This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1 has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000, and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000. Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor. Discussion Personalized breast cancer screening

  20. A systematic review of the use of an expertise-based randomised controlled trial design.

    Science.gov (United States)

    Cook, Jonathan A; Elders, Andrew; Boachie, Charles; Bassinga, Ted; Fraser, Cynthia; Altman, Doug G; Boutron, Isabelle; Ramsay, Craig R; MacLennan, Graeme S

    2015-05-30

    Under a conventional two-arm randomised trial design, participants are allocated to an intervention and participating health professionals are expected to deliver both interventions. However, health professionals often have differing levels of expertise in a skill-based interventions such as surgery or psychotherapy. An expertise-based approach to trial design, where health professionals only deliver an intervention in which they have expertise, has been proposed as an alternative. The aim of this project was to systematically review the use of an expertise-based trial design in the medical literature. We carried out a comprehensive search of nine databases--AMED, BIOSIS, CENTRAL, CINAHL, Cochrane Methodology Register, EMBASE, MEDLINE, Science Citation Index, and PsycINFO--from 1966 to 2012 and performed citation searches using the ISI Citation Indexes and Scopus. Studies that used an expertise-based trial design were included. Two review authors independently screened the titles and abstracts and assessed full-text reports. Data were extracted and summarised on the study characteristics, general and expertise-specific study methodology, and conduct. In total, 7476 titles and abstracts were identified, leading to 43 included studies (54 articles). The vast majority (88%) used a pure expertise-based design; three (7%) adopted a hybrid design, and two (5%) used a design that was unclear. Most studies compared substantially different interventions (79%). In many cases, key information relating to the expertise-based design was absent; only 12 (28%) reported criteria for delivering both interventions. Most studies recruited the target sample size or very close to it (median of 101, interquartile range of 94 to 118), although the target was reported for only 40% of studies. The proportion of participants who received the allocated intervention was high (92%, interquartile range of 82 to 99%). While use of an expertise-based trial design is growing, it remains uncommon

  1. Measuring lip force by oral screens Part 2: The importance of screen design, instruction and suction.

    Science.gov (United States)

    Wertsén, Madeleine; Stenberg, Manne

    2017-10-01

    The aim of this study was to find a reliable method for measuring lip force and to find the most important factors that influence the measurements in terms of magnitude and variability. The hypothesis tested was that suction is involved and thus the instruction and the design of the oral screen are of importance when measuring lip force. This is a methodological study in a healthy population. This study was conducted in a general community. The designs of the screens were soft and hard prefabricated screens and 2 semi-individually made with a tube allowing air to pass. The screens and the instructions squeeze or suck were tested on 29 healthy adults, one at a time and on 4 occasions. The test order of the screens was randomized. Data were collected during 4 consecutive days, and the procedure was repeated after 1 month. The participants were 29 healthy adult volunteers. The instruction was an important mean to distinguish between squeezing and sucking. The design of the screen affected the lip force so that it increases in relation to the projected area of the screen. A screen design with a tube allowing air to pass made it possible to avoid suction when squeezing. By measuring with and without allowing air to pass, it was possible to distinguish between suction related and not suction related lip force. The additional screen pressure when sucking was related to the ability to produce a negative intraoral pressure. In conclusion lip force increases in relation to the projected area of the screen, sucking generally increases the measured lip force and the additional screen pressure when sucking is related to the ability to produce a negative intraoral pressure.

  2. Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants

    International Nuclear Information System (INIS)

    Gierada, David S.; Pinsky, Paul F.; Duan, Fenghai; Garg, Kavita; Hart, Eric M.; Kazerooni, Ella A.; Nath, Hrudaya; Watts, Jubal R.; Aberle, Denise R.

    2017-01-01

    This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen. The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer. By retrospective review, 40/44 cases (91%) and 17/44 controls (39%) met the NLST criteria for a positive screen (P < 0.001). Cases had higher estimated likelihood of lung cancer (P < 0.001). Abnormalities included pulmonary nodules ≥4 mm (n = 16), mediastinal (n = 8) and hilar (n = 6) masses, and bronchial lesions (n = 6). Cancers were stage III or IV at diagnosis in 32/44 cases (73%); 37/44 patients (84%) died of lung cancer, compared to 225/649 (35%) for all screen-detected cancers (P < 0.0001). Most cases met the NLST criteria for a positive screen. Awareness of missed abnormalities and interpretation errors may aid lung cancer identification in CT screening. (orig.)

  3. Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants

    Energy Technology Data Exchange (ETDEWEB)

    Gierada, David S. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, Box 8131, St. Louis, MO (United States); Pinsky, Paul F. [National Cancer Institute, Bethesda, MD (United States); Duan, Fenghai [Brown University School of Public Health, Department of Biostatistics and Center for Statistical Sciences, Providence, RI (United States); Garg, Kavita [University of Colorado School of Medicine, Mail Stop F726, Box 6510, Aurora, CO (United States); Hart, Eric M. [Northwestern University, Feinberg School of Medicine, Department of Radiology, Chicago, IL (United States); Kazerooni, Ella A. [University of Michigan Health System, Department of Radiology, Ann Arbor, MI (United States); Nath, Hrudaya; Watts, Jubal R. [University of Alabama at Birmingham School of Medicine, Department of Radiology-JTN370, Birmingham, AL (United States); Aberle, Denise R. [David Geffen School of Medicine at UCLA, Department of Radiological Sciences, Los Angeles, CA (United States)

    2017-08-15

    This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen. The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer. By retrospective review, 40/44 cases (91%) and 17/44 controls (39%) met the NLST criteria for a positive screen (P < 0.001). Cases had higher estimated likelihood of lung cancer (P < 0.001). Abnormalities included pulmonary nodules ≥4 mm (n = 16), mediastinal (n = 8) and hilar (n = 6) masses, and bronchial lesions (n = 6). Cancers were stage III or IV at diagnosis in 32/44 cases (73%); 37/44 patients (84%) died of lung cancer, compared to 225/649 (35%) for all screen-detected cancers (P < 0.0001). Most cases met the NLST criteria for a positive screen. Awareness of missed abnormalities and interpretation errors may aid lung cancer identification in CT screening. (orig.)

  4. Rationale and Design of Khuzestan Vitamin D Deficiency Screening Program in Pregnancy: A Stratified Randomized Vitamin D Supplementation Controlled Trial.

    Science.gov (United States)

    Rostami, Maryam; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Hosseinpanah, Farhad; Alavi Majd, Hamid

    2017-04-07

    Although there have been marked improvements in our understanding of vitamin D functions in different diseases, gaps on its role during pregnancy remain. Due to the lack of consensus on the most accurate marker of vitamin D deficiency during pregnancy and the optimal level of 25-hydroxyvitamin D, 25(OH)D, for its definition, vitamin D deficiency assessment during pregnancy is a complicated process. Besides, the optimal protocol for treatment of hypovitaminosis D and its effect on maternal and neonatal outcomes are still unclear. The aim of our study was to estimate the prevalence of vitamin D deficiency in the first trimester of pregnancy and to compare vitamin D screening strategy with no screening. Also, we intended to compare the effectiveness of various treatment regimens on maternal and neonatal outcomes in Masjed-Soleyman and Shushtar cities of Khuzestan province, Iran. This was a two-phase study. First, a population-based cross-sectional study was conducted; recruiting 1600 and 900 first trimester pregnant women from health centers of Masjed-Soleyman and Shushtar, respectively, using stratified multistage cluster sampling with probability proportional to size (PPS) method. Second, to assess the effect of screening strategy on maternal and neonatal outcomes, Masjed-Soleyman participants were assigned to a screening program versus Shushtar participants who became the nonscreening arm. Within the framework of the screening regimen, an 8-arm blind randomized clinical trial was undertaken to compare the effects of various treatment protocols. A total of 800 pregnant women with vitamin D deficiency were selected using simple random sampling from the 1600 individuals of Masjed-Soleyman as interventional groups. Serum concentrations of 25(OH)D were classified as: (1) severe deficient (20ng/ml). Those with severe and moderate deficiency were randomly divided into 4 subgroups and received vitamin D3 based on protocol and were followed until delivery. Data was analyzed

  5. Developing the clinical components of a complex intervention for a glaucoma screening trial: a mixed methods study

    Directory of Open Access Journals (Sweden)

    2011-04-01

    Full Text Available Abstract Background Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle screening trial that would be feasible and acceptable in a UK eye-care service. Methods A mixed-methods study, based on the Medical Research Council (MRC framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners, and quantitative (economic modelling methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model. Results The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity with or without tonometry (a measure of intraocular pressure. It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty. Conclusions Interventions for screening for open angle

  6. Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol.

    Science.gov (United States)

    Thamsborg, Lise Holst; Andersen, Berit; Larsen, Lise Grupe; Christensen, Jette; Johansen, Tonje; Hariri, Jalil; Christiansen, Sanne; Rygaard, Carsten; Lynge, Elsebeth

    2018-05-26

    The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could therefore be offered less intensive screening. Primary HPV testing is more sensitive than cytology, allowing for a longer screening interval. The aim of Trial23 is to investigate if primary HPV testing with cytology triage of HPV positive samples is a reasonable screening scheme for women offered HPV vaccination as girls. Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7-8 years. The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study including intention-to-treat and per-protocol analyses. The potential effect of primary HPV screening with a 6-year interval will be calculated from the observed data. The study protocol has been submitted to the ethical committee and deemed a method study. All women are screened according to routine guidelines. The study will contribute new evidence on the future screening of HPV vaccinated birth cohorts of women. All results will be published in open-access journal. NCT03049553; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. A Decision Aid to Promote Appropriate Colorectal Cancer Screening among Older Adults: A Randomized Controlled Trial.

    Science.gov (United States)

    Lewis, Carmen L; Kistler, Christine E; Dalton, Alexandra F; Morris, Carolyn; Ferrari, Renée; Barclay, Colleen; Brewer, Noel T; Dolor, Rowena; Harris, Russell; Vu, Maihan; Golin, Carol E

    2018-07-01

    Concerns have been raised about both over- and underutilization of colorectal cancer (CRC) screening in older patients and the need to align screening behavior with likelihood of net benefit. The purpose of this study was to test a novel use of a patient decision aid (PtDA) to promote appropriate CRC screening in older adults. A total of 424 patients ages 70 to 84 y who were not up to date with CRC screening participated in a double-blinded randomized controlled trial of a PtDA targeted to older adults making decisions about whether to undergo CRC screening from March 2012 to February 2015. Patients were randomized to a targeted PtDA or an attention control. The PtDA was designed to facilitate individualized decision making-helping patients understand the potential risks, benefits, and uncertainties of CRC screening given advanced age, health state, preferences, and values. Two composite outcomes, appropriate CRC screening behavior 6 mo after the index visit and appropriate screening intent immediately after the visit, were defined as completed screening or intent for patients in good health, discussion about screening with their provider for patients in intermediate health, and no screening or intent for patients in poor health. Health state was determined by age and Charlson Comorbidity Index. Four hundred twelve (97%) and 421 (99%) patients were analyzed for the primary and secondary outcomes, respectively. Appropriate screening behavior at 6 mo was higher in the intervention group (55% v. 45%, P = 0.023) as was appropriate screening intent following the provider visit (61% v. 47%, P = 0.003). The study took place in a single geographic region. The appropriate CRC screening classification system used in this study has not been formally validated. A PtDA for older adults promoted appropriate CRC screening behavior and intent. Clinicaltrials.gov, registration number NCT01575990. https://clinicaltrials.gov/ct2/show/NCT01575990?term=epic-d&rank=1.

  8. Morphologic abnormalities in 2-year-old children born after in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening : follow-up of a randomized controlled trial

    NARCIS (Netherlands)

    Beukers, Fenny; van der Heide, Maaike; Middelburg, Karin J.; Cobben, Jan Maarten; Mastenbroek, Sebastiaan; Breur, Rinske; van der Lee, Johanna H.; Hadders-Algra, Mijna; Bos, Arend F.; Kok, Joke H.

    Objective: To evaluate the effect of preimplantation genetic screening (PGS) on morphologic outcome in children. Design: Follow-up of a randomized controlled trial (RCT). Setting: University hospital. Patient(s): Two-year-old children born to mothers who participated in an RCT on the efficacy of

  9. Impact of a nurse-led intervention to improve screening for cardiovascular risk factors in people with severe mental illnesses. Phase-two cluster randomised feasibility trial of community mental health teams

    Directory of Open Access Journals (Sweden)

    Nazareth Irwin

    2010-03-01

    Full Text Available Abstract Background People with severe mental illnesses (SMI are at increased risk of cardiovascular disease (CVD. Clinical guidelines recommend regular screening for CVD risk factors. We evaluated a nurse led intervention to improve screening rates across the primary-secondary care interface. Methods Six community mental health teams (CMHTs were randomised to receive either the nurse led intervention plus education pack (n = 3 or education pack only (n = 3. Intervention (6 months: The nurse promoted CVD screening in primary care and then in CMHTs. Patients who remained unscreened were offered screening by the nurse. After the intervention participants with SMI were recruited from each CMHT to collect outcome data. Main outcome: Numbers screened during the six months, confirmed in General Practice notes. Results All six CMHTs approached agreed to randomisation. 121 people with SMI participated in outcome interviews during two waves of recruitment (intervention arm n = 59, control arm n = 62. Participants from both arms of the trial had similar demographic profiles and rates of previous CVD screening in the previous year, with less than 20% having been screened for each risk factor. After the trial, CVD screening had increased in both arms but participants from the intervention arm were significantly more likely to have received screening for blood pressure (96% vs 68%; adjusted Odds Ratio (OR 13.6; 95% CI: 3.5-38.4, cholesterol (66.7% vs 26.9%, OR 6.1; 3.2-11.5, glucose (66.7% vs 36.5% OR 4.4; 2.7-7.1, BMI (92.5% vs 65.2% OR 6.5; 2.1-19.6, and smoking status (88.2% vs 57.8% OR 5.5; 3.2-9.5 and have a 10 year CVD risk score calculated (38.2% vs 10.9% OR 5.2 1.8-15.3. Within the intervention arm approximately half the screening was performed in general practice and half by the trial nurse. Conclusions The nurse-led intervention was superior, resulting in an absolute increase of approximately 30% more people with SMI receiving screening for each

  10. Group sequential designs for stepped-wedge cluster randomised trials.

    Science.gov (United States)

    Grayling, Michael J; Wason, James Ms; Mander, Adrian P

    2017-10-01

    The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into

  11. Practical considerations for adaptive trial design and implementation

    CERN Document Server

    Pinheiro, José; Kuznetsova, Olga

    2014-01-01

    This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers.  In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low.  One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, t...

  12. Active Choice and Financial Incentives to Increase Rates of Screening Colonoscopy-A Randomized Controlled Trial.

    Science.gov (United States)

    Mehta, Shivan J; Feingold, Jordyn; Vandertuyn, Matthew; Niewood, Tess; Cox, Catherine; Doubeni, Chyke A; Volpp, Kevin G; Asch, David A

    2017-11-01

    Behavioral economic approaches could increase uptake for colorectal cancer screening. We performed a randomized controlled trial of 2245 employees to determine whether an email containing a phone number for scheduling (control), an email with the active choice to opt in or opt out (active choice), or the active choice email plus a $100 incentive (financial incentive) increased colonoscopy completion within 3 months. Higher proportions of participants in the financial incentive group underwent screening (3.7%) than in the control (1.6%) or active choice groups (1.5%) (P = .01 and P < .01). We found no difference in uptake of screening between the active choice and control groups (P = .88). The $100 conditional incentive modestly but significantly increased colonoscopy use. ClinicalTrials.gov no: NCT02660671. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Adaptive design methods in clinical trials – a review

    Directory of Open Access Journals (Sweden)

    Chang Mark

    2008-05-01

    Full Text Available Abstract In recent years, the use of adaptive design methods in clinical research and development based on accrued data has become very popular due to its flexibility and efficiency. Based on adaptations applied, adaptive designs can be classified into three categories: prospective, concurrent (ad hoc, and retrospective adaptive designs. An adaptive design allows modifications made to trial and/or statistical procedures of ongoing clinical trials. However, it is a concern that the actual patient population after the adaptations could deviate from the originally target patient population and consequently the overall type I error (to erroneously claim efficacy for an infective drug rate may not be controlled. In addition, major adaptations of trial and/or statistical procedures of on-going trials may result in a totally different trial that is unable to address the scientific/medical questions the trial intends to answer. In this article, several commonly considered adaptive designs in clinical trials are reviewed. Impacts of ad hoc adaptations (protocol amendments, challenges in by design (prospective adaptations, and obstacles of retrospective adaptations are described. Strategies for the use of adaptive design in clinical development of rare diseases are discussed. Some examples concerning the development of Velcade intended for multiple myeloma and non-Hodgkin's lymphoma are given. Practical issues that are commonly encountered when implementing adaptive design methods in clinical trials are also discussed.

  14. Classical and adaptive clinical trial designs using ExpDesign Studio

    National Research Council Canada - National Science Library

    Chang, Mark

    2008-01-01

    ... Relationship 2.2.9 Parallel Design 17 2.2.10 Crossover Design 17 2.2.11 Factorial Design 18 Selection of a Trial Design 18 2.3.1 Balanced Versus Unbalanced Designs 18 2.3.2 Crossover Versus Parallel...

  15. Designing a placebo device: involving service users in clinical trial design.

    Science.gov (United States)

    Gooberman-Hill, Rachael; Jinks, Clare; Bouças, Sofia Barbosa; Hislop, Kelly; Dziedzic, Krysia S; Rhodes, Carol; Burston, Amanda; Adams, Jo

    2013-12-01

    Service users are increasingly involved in the design of clinical trials and in product and device development. Service user involvement in placebo development is crucial to a credible and acceptable placebo for clinical trials, but such involvement has not yet been reported. To enhance the design of a future clinical trial of hand splints for thumb-base osteoarthritis (OA), service users were involved in splint selection and design of a placebo splint. This article describes and reflects on this process. Two fora of service users were convened in 2011. Service users who had been prescribed a thumb splint for thumb-base OA were approached about involvement by Occupational Therapy (OT) practitioners. A total of eight service users took part in the fora. Service users discussed their experience of OA and their own splints and then tried a variety of alternative splints. Through this they identified the active features of splints alongside acceptable and unacceptable design features. Service users focused on wearability and support with or without immobilization. Fora discussed whether a placebo group ('arm') was an acceptable feature of a future trial, and service users developed a potential design for a placebo splint. This is the first project that to involve service users in placebo design. Service users are increasingly involved in product and device design and are ideally placed to identify features to make a placebo credible yet lacking key active ingredients. The future trial will include research into its acceptability. © 2013 John Wiley & Sons Ltd.

  16. Can emergency medicine research benefit from adaptive design clinical trials?

    Science.gov (United States)

    Flight, Laura; Julious, Steven A; Goodacre, Steve

    2017-04-01

    Adaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design. We reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment. Only 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design. Currently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Study Protocol: Screening and Treatment of Alcohol-Related Trauma (START – a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Jayaraj Rama

    2012-10-01

    Full Text Available Abstract Background The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. Methods and design The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP or Treatment as Usual (TAU. The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. Discussion This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma. Trial Registration The trial has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR and Trial Registration: ACTRN12611000135910.

  18. Longitudinal predictors of colorectal cancer screening among participants in a randomized controlled trial.

    Science.gov (United States)

    Murphy, Caitlin C; Vernon, Sally W; Haddock, Nicole M; Anderson, Melissa L; Chubak, Jessica; Green, Beverly B

    2014-09-01

    Few studies use longitudinal data to identify predictors of colorectal cancer screening (CRCS). We examined predictors of (1) initial CRCS during the first year of a randomized trial, and (2) repeat CRCS during the second year of the trial among those that completed FOBT in Year 1. The sample comprised 1247 participants of the Systems of Support to Increase Colorectal Cancer Screening (SOS) Trial (Group Health Cooperative, August 2008 to November 2011). Potential predictors of CRCS were identified with logistic regression and included sociodemographics, health history, and validated scales of psychosocial constructs. Prior CRCS (OR 2.64, 95% CI 1.99-3.52) and intervention group (Automated: OR 2.06 95% CI 1.43-2.95; Assisted: OR 4.03, 95% CI 2.69-6.03; Navigated: OR 5.64, 95% CI 3.74-8.49) were predictors of CRCS completion at Year 1. For repeat CRCS at Year 2, prior CRCS at baseline (OR 1.97, 95% CI 1.25-3.11), intervention group (Automated: OR 9.27, 95% CI 4.56-18.82; Assisted: OR 11.17, 95% CI 5.44-22.94; Navigated: OR 13.10, 95% CI 6.33-27.08), and self-efficacy (OR 1.32, 95% CI 1.00-1.73) were significant predictors. Self-efficacy and prior CRCS are important predictors of future screening behavior. CRCS completion increased when access barriers were removed through interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Multi-type Step-wise group screening designs with unequal A-priori ...

    African Journals Online (AJOL)

    ... design with unequal group sizes and obtain values of the group sizes that minimize the expected number of runs.. Keywords: Group Screening, Group factors, multi-type step-wise group screening, expected number of runs, Optimum group screening designs > East African Journal of Statistics Vol. 1 (1) 2005: pp. 49-67 ...

  20. Breast screening with mammography: Overview of Swedish randomized trials

    International Nuclear Information System (INIS)

    Nystroem, L.; Wall, S.; Lindqvist, M.; Ryden, S.; Andersson, J.; Bjurstam, N.; Fagerberg, G.; Frisell, J.; Tabar, L.; Larson, L.G.

    1993-01-01

    Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, reveals a 24% significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation (breast cancer as underlying cause of death or breast cancer present at death). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomization was estimated at 1.3 per 1,000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1

  1. Shared decision making for prostate cancer screening: the results of a combined analysis of two practice-based randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Sheridan Stacey L

    2012-11-01

    Full Text Available Abstract Background Professional societies recommend shared decision making (SDM for prostate cancer screening, however, most efforts have promoted informed rather than shared decision making. The objective of this study is to 1 examine the effects of a prostate cancer screening intervention to promote SDM and 2 determine whether framing prostate information in the context of other clearly beneficial men’s health services affects decisions. Methods We conducted two separate randomized controlled trials of the same prostate cancer intervention (with or without additional information on more clearly beneficial men’s health services. For each trial, we enrolled a convenience sample of 2 internal medicine practices, and their interested physicians and male patients with no prior history of prostate cancer (for a total of 4 practices, 28 physicians, and 128 men across trials. Within each practice site, we randomized men to either 1 a video-based decision aid and researcher-led coaching session or 2 a highway safety video. Physicians at each site received a 1-hour educational session on prostate cancer and SDM. To assess intervention effects, we measured key components of SDM, intent to be screened, and actual screening. After finding that results did not vary by trial, we combined data across sites, adjusting for the random effects of both practice and physician. Results Compared to an attention control, our prostate cancer screening intervention increased men’s perceptions that screening is a decision (absolute difference +41%; 95% CI 25 to 57% and men’s knowledge about prostate cancer screening (absolute difference +34%; 95% CI 19% to 50%, but had no effect on men’s self-reported participation in shared decisions or their participation at their preferred level. Overall, the intervention decreased screening intent (absolute difference −34%; 95% CI −50% to −18% and actual screening rates (absolute difference −22%; 95% CI −38 to

  2. Data-Driven Decision Support for Radiologists: Re-using the National Lung Screening Trial Dataset for Pulmonary Nodule Management

    OpenAIRE

    Morrison, James J.; Hostetter, Jason; Wang, Kenneth; Siegel, Eliot L.

    2014-01-01

    Real-time mining of large research trial datasets enables development of case-based clinical decision support tools. Several applicable research datasets exist including the National Lung Screening Trial (NLST), a dataset unparalleled in size and scope for studying population-based lung cancer screening. Using these data, a clinical decision support tool was developed which matches patient demographics and lung nodule characteristics to a cohort of similar patients. The NLST dataset was conve...

  3. Efficient pooling designs for library screening

    OpenAIRE

    Bruno, William J.; Knill, Emanuel; Balding, David J.; Bruce, D. C.; Doggett, N. A.; Sawhill, W. W.; Stallings, R. L.; Whittaker, Craig C.; Torney, David C.

    1994-01-01

    We describe efficient methods for screening clone libraries, based on pooling schemes which we call ``random $k$-sets designs''. In these designs, the pools in which any clone occurs are equally likely to be any possible selection of $k$ from the $v$ pools. The values of $k$ and $v$ can be chosen to optimize desirable properties. Random $k$-sets designs have substantial advantages over alternative pooling schemes: they are efficient, flexible, easy to specify, require fewer pools, and have er...

  4. Assessing Cognitive Function in Bipolar Disorder: Challenges and Recommendations for Clinical Trial Design

    Science.gov (United States)

    Burdick, Katherine E.; Ketter, Terence A.; Goldberg, Joseph F.; Calabrese, Joseph R.

    2015-01-01

    provided here as a preliminary guide for future trial design. Recommendations comprise exclusion of certain syndromal level comorbid diagnoses and current affective instability, restrictions on numbers and types of medications, and use of pre-screening assessment to ensure enrollment of subjects with adequate objective evidence of baseline cognitive impairment. CONCLUSIONS Clinical trials to address cognitive deficits in bipolar disorder face distinctive design challenges. As such trials move from proof-of-concept to confirmation of clinical efficacy, it will be important to incorporate distinctive design modifications to adequately address these challenges and increase the likelihood of demonstrating cognitive remediation effects. The field is now primed to address these challenges and a comprehensive effort to formalize best practice guidelines will be a critically important next step. PMID:25830456

  5. Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.

    Science.gov (United States)

    Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B

    2017-02-01

    Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial.

    Science.gov (United States)

    Hersch, Jolyn; McGeechan, Kevin; Barratt, Alexandra; Jansen, Jesse; Irwig, Les; Jacklyn, Gemma; Houssami, Nehmat; Dhillon, Haryana; McCaffery, Kirsten

    2017-10-06

    In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. Serial multiple mediation analysis within a randomised controlled trial. New South Wales, Australia. 811 women aged 48-50 years with no personal history of breast cancer. Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. Intentions to undergo breast cancer screening in the next 2-3 years. Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can

  7. Staying well after depression: trial design and protocol

    Directory of Open Access Journals (Sweden)

    Duggan Danielle S

    2010-03-01

    Full Text Available Abstract Background Depression is often a chronic relapsing condition, with relapse rates of 50-80% in those who have been depressed before. This is particularly problematic for those who become suicidal when depressed since habitual recurrence of suicidal thoughts increases likelihood of further acute suicidal episodes. Therefore the question how to prevent relapse is of particular urgency in this group. Methods/Design This trial compares Mindfulness-Based Cognitive Therapy (MBCT, a novel form of treatment combining mindfulness meditation and cognitive therapy for depression, with both Cognitive Psycho-Education (CPE, an equally plausible cognitive treatment but without meditation, and treatment as usual (TAU. It will test whether MBCT reduces the risk of relapse in recurrently depressed patients and the incidence of suicidal symptoms in those with a history of suicidality who do relapse. It recruits participants, screens them by telephone for main inclusion and exclusion criteria and, if they are eligible, invites them to a pre-treatment session to assess eligibility in more detail. This trial allocates eligible participants at random between MBCT and TAU, CPE and TAU, and TAU alone in a ratio of 2:2:1, stratified by presence of suicidal ideation or behaviour and current anti-depressant use. We aim to recruit sufficient participants to allow for retention of 300 following attrition. We deliver both active treatments in groups meeting for two hours every week for eight weeks. We shall estimate effects on rates of relapse and suicidal symptoms over 12 months following treatment and assess clinical status immediately after treatment, and three, six, nine and twelve months thereafter. Discussion This will be the first trial of MBCT to investigate whether MCBT is effective in preventing relapse to depression when compared with a control psychological treatment of equal plausibility; and to explore the use of MBCT for the most severe recurrent

  8. Shared decision making for prostate cancer screening: the results of a combined analysis of two practice-based randomized controlled trials.

    Science.gov (United States)

    Sheridan, Stacey L; Golin, Carol; Bunton, Audrina; Lykes, John B; Schwartz, Bob; McCormack, Lauren; Driscoll, David; Bangdiwala, Shrikant I; Harris, Russell P

    2012-11-13

    Professional societies recommend shared decision making (SDM) for prostate cancer screening, however, most efforts have promoted informed rather than shared decision making. The objective of this study is to 1) examine the effects of a prostate cancer screening intervention to promote SDM and 2) determine whether framing prostate information in the context of other clearly beneficial men's health services affects decisions. We conducted two separate randomized controlled trials of the same prostate cancer intervention (with or without additional information on more clearly beneficial men's health services). For each trial, we enrolled a convenience sample of 2 internal medicine practices, and their interested physicians and male patients with no prior history of prostate cancer (for a total of 4 practices, 28 physicians, and 128 men across trials). Within each practice site, we randomized men to either 1) a video-based decision aid and researcher-led coaching session or 2) a highway safety video. Physicians at each site received a 1-hour educational session on prostate cancer and SDM. To assess intervention effects, we measured key components of SDM, intent to be screened, and actual screening. After finding that results did not vary by trial, we combined data across sites, adjusting for the random effects of both practice and physician. Compared to an attention control, our prostate cancer screening intervention increased men's perceptions that screening is a decision (absolute difference +41%; 95% CI 25 to 57%) and men's knowledge about prostate cancer screening (absolute difference +34%; 95% CI 19% to 50%), but had no effect on men's self-reported participation in shared decisions or their participation at their preferred level. Overall, the intervention decreased screening intent (absolute difference -34%; 95% CI -50% to -18%) and actual screening rates (absolute difference -22%; 95% CI -38 to -7%) with no difference in effect by frame. SDM interventions can

  9. Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial.

    Science.gov (United States)

    Weigel, Stefanie; Gerss, Joachim; Hense, Hans-Werner; Krischke, Miriam; Sommer, Alexander; Czwoydzinski, Jörg; Lenzen, Horst; Kerschke, Laura; Spieker, Karin; Dickmaenken, Stefanie; Baier, Sonja; Urban, Marc; Hecht, Gerold; Heidinger, Oliver; Kieschke, Joachim; Heindel, Walter

    2018-05-14

    Development of digital breast tomosynthesis (DBT) provides a technology that generates three-dimensional data sets, thus reducing the pitfalls of overlapping breast tissue. Observational studies suggest that the combination of two-dimensional (2D) digital mammography and DBT increases diagnostic accuracy. However, because of duplicate exposure, this comes at the cost of an augmented radiation dose. This undesired adverse impact can be avoided by using synthesised 2D images reconstructed from the DBT data (s2D).We designed a diagnostic superiority trial on a high level of evidence with the aim of providing a comparison of screening efficacy parameters resulting from DBT+s2D versus the current screening standard 2D full-field digital mammography (FFDM) in a multicentre and multivendor setting on the basis of the quality-controlled, population-based, biennial mammography screening programme in Germany. 80 000 women in the eligible age 50-69 years attending the routine mammography screening programme and willing to participate in the TOSYMA trial will be assigned by 1:1 randomisation to either the intervention arm (DBT+s2D) or the control arm (FFDM) during a 12-month recruitment period in screening units of North Rhine-Westphalia and Lower Saxony. State cancer registries will provide the follow-up of interval cancers.Primary endpoints are the detection rate of invasive breast cancers at screening examination and the cumulative incidence of interval cancers in the 2 years after a negative examination. Secondary endpoints are the detection rate of ductal carcinoma in situ and of tumour size T1, the recall rate for assessment, the positive predictive value of recall and the cumulative 12-month incidence of interval cancers. An adaptive statistical design with one interim analysis provides the option to modify the design. This protocol has been approved by the local medical ethical committee (2016-132-f-S). Results will be submitted to international peer

  10. Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing

    OpenAIRE

    Kauffman, Tia L.; Wilfond, Benjamin S.; Jarvik, Gail P.; Leo, Michael C.; Lynch, Frances L.; Reiss, Jacob A.; Richards, C. Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O.; Goddard, Katrina A.B.

    2016-01-01

    Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results...

  11. WE-B-207-01: CT Lung Cancer Screening and the Medical Physicist: Background, Findings and Participant Dosimetry Summary of the National Lung Screening Trial (NLST)

    International Nuclear Information System (INIS)

    Kruger, R.

    2015-01-01

    The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Under the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan

  12. WE-B-207-01: CT Lung Cancer Screening and the Medical Physicist: Background, Findings and Participant Dosimetry Summary of the National Lung Screening Trial (NLST)

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, R. [Marshfield Clinic, Marshfield, WI (United States)

    2015-06-15

    The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Under the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan

  13. The design of light pipe with microstructures for touch screen

    Science.gov (United States)

    Yang, Bo; Lu, Kan; Liu, Pengfei; Wei, Xiaona

    2010-11-01

    Touch screen has a very wide range of applications. Most of them are used in public information inquiries, for instance, service inquiries in telecommunication bureau, tax bureau, bank system, electric department, etc...Touch screen can also be used for entertainment and virtual reality applications too. Traditionally, touch screen was composed of pairs of infrared LED and correspondent receivers which were all installed in the screen frame. Arrays of LED were set in the adjacent sides of the frame of an infrared touch screen while arrays of the infrared receivers were fixed in each opposite side, so that the infrared detecting network was formed. While the infrared touch screen has some technical limitations nowadays such as the low resolution, limitations of touching methods and fault response due to environmental disturbances. The plastic material has a relatively high absorption rate for infrared light, which greatly limits the size of the touch screen. Our design uses laser diode as source and change the traditional inner structure of touch screen by using a light pipe with microstructures. The geometric parameters of the light pipe and the microstructures were obtained through equation solving. Simulation results prove that the design method for touch screen proposed in this paper could achieve high resolution and large size of touch screen.

  14. Resolution V fractional factorial Design for Screening of factors affecting weakly basic drugs liposomal systems.

    Science.gov (United States)

    El-Helaly, Sara Nageeb; Habib, Basant A; Abd El-Rahman, Mohamed K

    2018-04-21

    This study aims to investigate factors affecting weakly basic drugs liposomal systems. Resolution V fractional factorial design (2 V 5-1 ) is used as an example of screening designs that would better be used as a wise step before proceeding with detailed factors effects or optimization studies. Five factors probable to affect liposomal systems of weakly basic drugs were investigated using Amisulpride as a model drug. Factors studied were; A: Preparation technique B: Phosphatidyl choline (PhC) amount (mg) C: Cholesterol: PhC molar ratio, D: Hydration volume (ml) and E: Sonication type. Levels investigated were; Ammonium sulphate-pH gradient technique or Transmembrane zinc chelation-pH gradient technique, 200 or 400 mg, 0 or 0.5, 10 or 20 ml and bath or probe sonication for A, B, C, D and E respectively. Responses measured were Particle size (PS) (nm), Zeta potential (ZP) (mV) and Entrapment efficiency percent (EE%). Ion selective electrode was used as a novel method for measuring unentrapped drug concentration and calculating entrapment efficiency without the need for liposomal separation. Factors mainly affecting the studied responses were Cholesterol: PhC ratio and hydration volume for PS, preparation technique for ZP and preparation technique and hydration volume for EE%. The applied 2 V 5-1 design enabled the use of only 16 trial combinations for screening the influence of five factors on weakly basic drugs liposomal systems. This clarifies the value of the use of screening experiments before extensive investigation of certain factors in detailed optimization studies. Copyright © 2017. Published by Elsevier B.V.

  15. Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial.

    Science.gov (United States)

    Löwe, Bernd; Blankenberg, Stefan; Wegscheider, Karl; König, Hans-Helmut; Walter, Dirk; Murray, Alexandra M; Gierk, Benjamin; Kohlmann, Sebastian

    2017-02-01

    International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking. To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening. Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening. The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group. Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression. © The Royal College of Psychiatrists 2017.

  16. Applying Probabilistic Decision Models to Clinical Trial Design

    Science.gov (United States)

    Smith, Wade P; Phillips, Mark H

    2018-01-01

    Clinical trial design most often focuses on a single or several related outcomes with corresponding calculations of statistical power. We consider a clinical trial to be a decision problem, often with competing outcomes. Using a current controversy in the treatment of HPV-positive head and neck cancer, we apply several different probabilistic methods to help define the range of outcomes given different possible trial designs. Our model incorporates the uncertainties in the disease process and treatment response and the inhomogeneities in the patient population. Instead of expected utility, we have used a Markov model to calculate quality adjusted life expectancy as a maximization objective. Monte Carlo simulations over realistic ranges of parameters are used to explore different trial scenarios given the possible ranges of parameters. This modeling approach can be used to better inform the initial trial design so that it will more likely achieve clinical relevance.

  17. The design and development of a complex multifactorial falls assessment intervention for falls prevention: The Prevention of Falls Injury Trial (PreFIT).

    Science.gov (United States)

    Bruce, Julie; Ralhan, Shvaita; Sheridan, Ray; Westacott, Katharine; Withers, Emma; Finnegan, Susanne; Davison, John; Martin, Finbarr C; Lamb, Sarah E

    2017-06-01

    This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). A complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of 'red flags'; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and

  18. Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

    Science.gov (United States)

    Kurbel, Sven; Mihaljević, Slobodan

    2017-10-01

    Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

  19. Human factors engineering review for CRT screen design

    International Nuclear Information System (INIS)

    Yi, S. M.; Joo, C. Y.; Ra, J. C.

    1999-01-01

    The information interface between man and machine may be more important than hardware and workplace layout considerations. Transmitting and receiving data through this information interface can be characterized as a communication or interface problem. Management of man-machine interface is essential for the enhancement of the information processing and decision-making capability of computer users working in real time, demanding task. The design of human-computer interface is not a rigid and static procedure. The content and context of each interface varies according to the specific application. So, the purpose of this study is to review the human factor design process for interfaces, to make human factor guidelines for CRT screen and to apply these to CRT screen design. (author)

  20. Enhanced maternal and child health nurse care for women experiencing intimate partner/family violence: protocol for MOVE, a cluster randomised trial of screening and referral in primary health care.

    Science.gov (United States)

    Taft, Angela J; Small, Rhonda; Humphreys, Cathy; Hegarty, Kelsey; Walter, Ruby; Adams, Catina; Agius, Paul

    2012-09-20

    Intimate partner violence (IPV) can result in significant harm to women and families and is especially prevalent when women are pregnant or recent mothers. Maternal and child health nurses (MCHN) in Victoria, Australia are community-based nurse/midwives who see over 95% of all mothers with newborns. MCHN are in an ideal position to identify and support women experiencing IPV, or refer them to specialist family violence services. Evidence for IPV screening in primary health care is inconclusive to date. The Victorian government recently required nurses to screen all mothers when babies are four weeks old, offering an opportunity to examine the effectiveness of MCHN IPV screening practices. This protocol describes the development and design of MOVE, a study to examine IPV screening effectiveness and the sustainability of screening practice. MOVE is a cluster randomised trial of a good practice model of MCHN IPV screening involving eight maternal and child health nurse teams in Melbourne, Victoria. Normalisation Process Theory (NPT) was incorporated into the design, implementation and evaluation of the MOVE trial to enhance and evaluate sustainability. Using NPT, the development stage combined participatory action research with intervention nurse teams and a systematic review of nurse IPV studies to develop an intervention model incorporating consensus guidelines, clinical pathway and strategies for individual nurses, their teams and family violence services. Following twelve months' implementation, primary outcomes assessed include IPV inquiry, IPV disclosure by women and referral using data from MCHN routine data collection and a survey to all women giving birth in the previous eight months. IPV will be measured using the Composite Abuse Scale. Process and impact evaluation data (online surveys and key stakeholders interviews) will highlight NPT concepts to enhance sustainability of IPV identification and referral. Data will be collected again in two years. MOVE

  1. Healthcare costs in the Danish randomised controlled lung cancer CT-screening trial

    DEFF Research Database (Denmark)

    Rasmussen, J.F.; Siersma, V.; Pedersen, Jesper H.

    2014-01-01

    : This registry study was nested in a randomised controlled trial (DLCST). 4104 participants, current or former heavy smokers, aged 50-70 years were randomised to five annual low dose CT scans or usual care during 2004-2010. Total healthcare costs and healthcare utilisation data for both the primary...... and the secondary healthcare sector were retrieved from public registries from randomisation - September 2011 and compared between (1) the CT-screening group and the control group and, (2) the control group and each of the true-positive, false-positive and true-negative groups. RESULTS: The median annual costs per...... participant were significantly higher in the CT-screening group (Euros [EUR] 1342, interquartile range [IQR] 750-2980) compared with the control group (EUR 1190, IQR 590-2692) (pcost of the CT-screening programme was excluded, there was no longer a statistically significant difference...

  2. Pragmatic trial design elements showed a different impact on trial interpretation and feasibility than explanatory elements

    NARCIS (Netherlands)

    Nieuwenhuis, Joost B.; Irving, Elaine; Oude Rengerink, Katrien; Lloyd, Emily; Goetz, Iris; Grobbee, Diederick E.; Stolk, Pieter; Groenwold, Rolf H H; Zuidgeest, Mira G P

    2016-01-01

    OBJECTIVE: To illustrate how pragmatic trial design elements, or inserting explanatory trial elements in pragmatic trials affect validity, generalizability, precision and operational feasibility. STUDY DESIGN AND SETTING: From illustrative examples identified through the IMI Get Real Consortium, we

  3. WE-B-207-02: CT Lung Cancer Screening and the Medical Physicist: A Dosimetry Summary of CT Participants in the National Lung Cancer Screening Trial (NLST)

    International Nuclear Information System (INIS)

    Lee, C.

    2015-01-01

    The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Under the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan

  4. WE-B-207-02: CT Lung Cancer Screening and the Medical Physicist: A Dosimetry Summary of CT Participants in the National Lung Cancer Screening Trial (NLST)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C. [National Cancer Institute (United States)

    2015-06-15

    The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Under the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan

  5. Design, analysis and presentation of factorial randomised controlled trials

    Directory of Open Access Journals (Sweden)

    Little Paul

    2003-11-01

    Full Text Available Abstract Background The evaluation of more than one intervention in the same randomised controlled trial can be achieved using a parallel group design. However this requires increased sample size and can be inefficient, especially if there is also interest in considering combinations of the interventions. An alternative may be a factorial trial, where for two interventions participants are allocated to receive neither intervention, one or the other, or both. Factorial trials require special considerations, however, particularly at the design and analysis stages. Discussion Using a 2 × 2 factorial trial as an example, we present a number of issues that should be considered when planning a factorial trial. The main design issue is that of sample size. Factorial trials are most often powered to detect the main effects of interventions, since adequate power to detect plausible interactions requires greatly increased sample sizes. The main analytical issues relate to the investigation of main effects and the interaction between the interventions in appropriate regression models. Presentation of results should reflect the analytical strategy with an emphasis on the principal research questions. We also give an example of how baseline and follow-up data should be presented. Lastly, we discuss the implications of the design, analytical and presentational issues covered. Summary Difficulties in interpreting the results of factorial trials if an influential interaction is observed is the cost of the potential for efficient, simultaneous consideration of two or more interventions. Factorial trials can in principle be designed to have adequate power to detect realistic interactions, and in any case they are the only design that allows such effects to be investigated.

  6. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

    Science.gov (United States)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  7. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

    Science.gov (United States)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  8. Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications.

    Science.gov (United States)

    Larkey, Linda; Szalacha, Laura; Herman, Patricia; Gonzalez, Julie; Menon, Usha

    2017-02-01

    Regular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations). This group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results. The novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial. Copyright © 2016. Published by Elsevier Inc.

  9. Design of Screens for Sand Control of Wells

    Directory of Open Access Journals (Sweden)

    Ján Pinka

    2006-04-01

    Full Text Available Drilling, completion, production, and reservoir engineers, supervisors, foremen, superintendents, service company personnel, technologists and anyone involved with recommending, selecting, designing or on-site performance of well completions or workovers where sand production is, or may become, a serious problem will benefit from this course. Less sand influx can be expected in a horizontal well than in a vertical well. If horizontal holes in weak formation sands can be successfully gravel packed, the result could be significantly higher well productivity than with a liner, screen or pre-packed screen alone. The article covers innovative screens for sand control used in oil and gas industry from the world leaders in total completion. The type of screen (wire wrapped, reinforced, pre-packed, ect. should also be chosen with due consideration to running-in condition (curve radius, compression when the screens are pushed along the drain hole, etc..

  10. Using community engagement to inform and implement a community-randomized controlled trial in the Anishinaabek Cervical Cancer Screening Study (ACCSS

    Directory of Open Access Journals (Sweden)

    Brianne eWood

    2014-02-01

    Full Text Available Social, political, and economic factors are directly and indirectly associated with the quality and distribution of health resources across Canada. First Nations (FN women in particular endure a disproportionate burden of ill health in contrast to the mainstream population. The complex relationship of health, social, and historical determinants are inherent to increased cervical cancer in FN women. This can be traced back to the colonial oppression suffered by Canadian FN and the social inequalities they have since faced. Screening - the Papinacolaou (Pap test – and early immunization have rendered cervical cancer almost entirely preventable but despite these options, FN women endure notably higher rates of diagnosis and mortality due to cervical cancer. The Anishinaabek Cervical Cancer Screening Study (ACCSS is a participatory action research project investigating the factors underlying the cervical cancer burden in FN women. ACCSS is a collaboration with 11 FN communities in Northwest Ontario, Canada and a multidisciplinary research team from across Canada with expertise in cancer biology, epidemiology, medical anthropology, public health, virology, women’s health, and pathology. Interviews with healthcare providers and community members revealed that prior to any formal data collection education must be offered. Consequently, an educational component was integrated into the existing quantitative design of the study: a two-armed, community-randomized trial that compares the uptake of two different cervical screening modalities. In ACCSS, the Research Team integrates community engagement and the flexible nature of participatory research with the scientific rigor of a randomized controlled trial. ACCSS findings will inform culturally appropriate screening strategies, aiming to reduce the disproportionate burden of cervical disease in concert with priorities of the partner FN communities.

  11. A Community-Based Randomized Trial of Hepatitis B Screening Among High-Risk Vietnamese Americans.

    Science.gov (United States)

    Ma, Grace X; Fang, Carolyn Y; Seals, Brenda; Feng, Ziding; Tan, Yin; Siu, Philip; Yeh, Ming Chin; Golub, Sarit A; Nguyen, Minhhuyen T; Tran, Tam; Wang, Minqi

    2017-03-01

    To evaluate the effectiveness of a community-based liver cancer prevention program on hepatitis B virus (HBV) screening among low-income, underserved Vietnamese Americans at high risk. We conducted a cluster randomized trial involving 36 Vietnamese community-based organizations and 2337 participants in Pennsylvania, New Jersey, and New York City between 2009 and 2014. We randomly assigned 18 community-based organizations to a community-based multilevel HBV screening intervention (n = 1131). We randomly assigned the remaining 18 community-based organizations to a general cancer education program (n = 1206), which included information about HBV-related liver cancer prevention. We assessed HBV screening rates at 6-month follow-up. Intervention participants were significantly more likely to have undergone HBV screening (88.1%) than were control group participants (4.6%). In a Cochran-Mantel-Haenszel analysis, the intervention effect on screening outcomes remained statistically significant after adjustment for demographic and health care access variables, including income, having health insurance, having a regular health provider, and English proficiency. A community-based, culturally appropriate, multilevel HBV screening intervention effectively increases screening rates in a high-risk, hard-to-reach Vietnamese American population.

  12. 77 FR 41791 - Proposed Collection; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening...

    Science.gov (United States)

    2012-07-16

    ... Collection: This trial was designed to determine if cancer screening for prostate, lung, colorectal, and... annually in the U.S. The design is a two-armed randomized trial of men and women aged 55 to 74 at entry... submission is that the Supplemental Questionnaire is being replaced with the Medication Use Questionnaire. As...

  13. Commentary: considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product.

    Science.gov (United States)

    Bibby, Anna C; Torgerson, David J; Leach, Samantha; Lewis-White, Helen; Maskell, Nick A

    2018-01-08

    The 'trials within cohorts' (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort. To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations. We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule. We have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future.

  14. SARCOPENIA: DESIGNING PHASE IIB TRIALS

    Science.gov (United States)

    CHUMLEA, WM.C.; CESARI, M.; EVANS, W.J.; FERRUCCI, L.; FIELDING, R.A.; PAHOR, M.; STUDENSKI, S.; VELLAS, B.

    2012-01-01

    Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. PMID:21623466

  15. Design and Polarization Characteristics Analysis of Dihedral Based on Salisbury Screen

    Directory of Open Access Journals (Sweden)

    Zhang Ran

    2016-12-01

    Full Text Available Salisbury screens have a number of unique electromagnetic scattering characteristics. When appropriately designed, the Salisbury screen can reach the radar target signature transform. Based on the electromagnetic scattering characteristics of the Salisbury screen, we designed a novel dihedral corner, and theoretically analyzed and simulated its electromagnetic scattering characteristics in this study. The results reveal the monostatic radar cross section curves of the 90°and 60° Salisbury screen dihedral and metal dihedral, respectively. Taking an orthogonal dihedral corner as an example, we obtained the polarization scattering matrixes for different incident degrees. In addition, we investigated the influence of illumination frequency, target gestures, and other key factors on the polarization characteristics of the Salisbury screen dihedral corner. The theoretical and simulation analysis results show that compared with the conventional metal dihedral corner, the Salisbury screen dihedral corner significantly influences the scattering characteristics and will have potential application in electronic warfare.

  16. Computer tomography colonography participation and yield in patients under surveillance for 6-9 mm polyps in a population-based screening trial

    NARCIS (Netherlands)

    Tutein Nolthenius, Charlotte J.; Boellaard, Thierry N.; de Haan, Margriet C.; Nio, C. Yung; Thomeer, Maarten G. J.; Bipat, Shandra; Montauban van Swijndregt, Alexander D.; van de Vijver, Marc J.; Biermann, Katharina; Kuipers, Ernst J.; Dekker, Evelien; Stoker, Jaap

    2016-01-01

    Surveillance CT colonography (CTC) is a viable option for 6-9 mm polyps at CTC screening for colorectal cancer. We established participation and diagnostic yield of surveillance and determined overall yield of CTC screening. In an invitational CTC screening trial 82 of 982 participants harboured 6-9

  17. A literature review of applied adaptive design methodology within the field of oncology in randomised controlled trials and a proposed extension to the CONSORT guidelines.

    Science.gov (United States)

    Mistry, Pankaj; Dunn, Janet A; Marshall, Andrea

    2017-07-18

    The application of adaptive design methodology within a clinical trial setting is becoming increasingly popular. However the application of these methods within trials is not being reported as adaptive designs hence making it more difficult to capture the emerging use of these designs. Within this review, we aim to understand how adaptive design methodology is being reported, whether these methods are explicitly stated as an 'adaptive design' or if it has to be inferred and to identify whether these methods are applied prospectively or concurrently. Three databases; Embase, Ovid and PubMed were chosen to conduct the literature search. The inclusion criteria for the review were phase II, phase III and phase II/III randomised controlled trials within the field of Oncology that published trial results in 2015. A variety of search terms related to adaptive designs were used. A total of 734 results were identified, after screening 54 were eligible. Adaptive designs were more commonly applied in phase III confirmatory trials. The majority of the papers performed an interim analysis, which included some sort of stopping criteria. Additionally only two papers explicitly stated the term 'adaptive design' and therefore for most of the papers, it had to be inferred that adaptive methods was applied. Sixty-five applications of adaptive design methods were applied, from which the most common method was an adaptation using group sequential methods. This review indicated that the reporting of adaptive design methodology within clinical trials needs improving. The proposed extension to the current CONSORT 2010 guidelines could help capture adaptive design methods. Furthermore provide an essential aid to those involved with clinical trials.

  18. A qualitative study exploring the acceptability of the McNulty-Zelen design for randomised controlled trials evaluating educational interventions.

    Science.gov (United States)

    McNulty, Cliodna; Ricketts, Ellie J; Rugman, Claire; Hogan, Angela; Charlett, Andre; Campbell, Rona

    2015-11-17

    Traditional randomised controlled trials evaluating the effect of educational interventions in general practice may produce biased results as participants know they are being evaluated. We aimed to explore the acceptability of a McNulty-Zelen Cluster Randomised Control Trial (CRT) design which conceals from educational participants that they are in a RCT. Consent is obtained from a trusted third party considered appropriate to give consent on participants' behalf, intervention practice staff then choose whether to attend the offered education as would occur with normal continuing professional development. We undertook semi structured telephone interviews in England with 16 general practice (GP) staff involved in a RCT evaluating an educational intervention aimed at increasing chlamydia screening tests in general practice using the McNulty-Zelen design, 4 Primary Care (PC) Research Network officers, 5 Primary Care Trust leads in Public or sexual health, and one Research Ethics committee Chair. Interviews were undertaken by members of the original intervention evaluation McNulty-Zelen design RCT study team. These experienced qualitative interviewers used an agreed semi-structured interview schedule and were careful not to lead the participants. To further mitigate against bias, the data analysis was undertaken by a researcher (CR) not involved in the original RCT. We reached data saturation and found five main themes; Support for the design: All found the McNulty-Zelen design acceptable because they considered that it generated more reliable evidence of the value of new educational interventions in real life GP settings. Lack of familiarity with study design: The design was novel to all. GP staff likened the evaluation using the McNulty-Zelen design to audit of their activities with feedback, which were to them a daily experience and therefore acceptable. Ethical considerations: Research stakeholders considered the consent procedure should be very clear and that

  19. Embracing model-based designs for dose-finding trials.

    Science.gov (United States)

    Love, Sharon B; Brown, Sarah; Weir, Christopher J; Harbron, Chris; Yap, Christina; Gaschler-Markefski, Birgit; Matcham, James; Caffrey, Louise; McKevitt, Christopher; Clive, Sally; Craddock, Charlie; Spicer, James; Cornelius, Victoria

    2017-07-25

    Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators' preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.

  20. Mortality results from the Göteborg Randomised Prostate Cancer Screening Trial

    Science.gov (United States)

    Hugosson, Jonas; Carlsson, Sigrid; Aus, Gunnar; Bergdahl, Svante; Khatami, Ali; Lodding, Pär; Pihl, Carl-Gustaf; Stranne, Johan; Holmberg, Erik; Lilja, Hans

    2013-01-01

    Summary Background Prostate cancer is one of the leading causes of death from malignant disease among men in the Western world. One strategy to decrease the risk of dying from this disease is screening with Prostate-Specific Antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. Methods In December 1994, 20 000 men born 1930 to 1944, randomly sampled from the Population Register, were computer randomised in a 1:1 ratio to a screening group invited for biennial PSA testing or to a control group not invited. In each arm, 48 men were excluded from analysis due to either death or emigration before randomization date or prevalent prostate cancer. The primary endpoint was prostate cancer specific mortality analyzed according to the intention-to-screen principle. Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with elevated PSA were offered additional tests such as digital rectal examination and prostate biopsies. The study is still ongoing inviting men who have not yet reached the upper age limit. This is the first planned report on cumulative prostate cancer incidence and mortality calculated up to Dec 31 2008. This study is registered [as an International Standard Randomised Controlled Trial], number [ISRCTN49127736]. Findings Among men randomised to screening 7578/9952 (76%) attended at least once (attendees). During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer resulting in a cumulative incidence of prostate cancer of 12.7% in the screening arm and 8.2% in the control arm (hazard ratio 1.64; 95% confidence interval [CI] 1.50–1.80; pattendees compared to the control group was 0.44 (95% CI 0.28–0.68; p=0.0002). Overall, 293 men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. Interpretation The benefit of prostate cancer

  1. Screening and brief interventions for hazardous and harmful alcohol use in probation services: a cluster randomised controlled trial protocol.

    Science.gov (United States)

    Newbury-Birch, Dorothy; Bland, Martin; Cassidy, Paul; Coulton, Simon; Deluca, Paolo; Drummond, Colin; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; Kaner, Eileen; Myles, Judy; Oyefeso, Adenekan; Parrott, Steve; Perryman, Katherine; Phillips, Tom; Shenker, Don; Shepherd, Jonathan

    2009-11-18

    A large number of randomised controlled trials in health settings have consistently reported positive effects of brief intervention in terms of reductions in alcohol use. However, although alcohol misuse is common amongst offenders, there is limited evidence of alcohol brief interventions in the criminal justice field. This factorial pragmatic cluster randomised controlled trial with Offender Managers (OMs) as the unit of randomisation will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in probation and different intensities of brief intervention to reduce excessive drinking in probation clients. Ninety-six OMs from 9 probation areas across 3 English regions (the North East Region (n = 4) and London and the South East Regions (n = 5)) will be recruited. OMs will be randomly allocated to one of three intervention conditions: a client information leaflet control condition (n = 32 OMs); 5-minute simple structured advice (n = 32 OMs) and 20-minute brief lifestyle counselling delivered by an Alcohol Health Worker (n = 32 OMs). Randomisation will be stratified by probation area. To test the relative effectiveness of different screening methods all OMs will be randomised to either the Modified Single Item Screening Questionnaire (M-SASQ) or the Fast Alcohol Screening Test (FAST). There will be a minimum of 480 clients recruited into the trial. There will be an intention to treat analysis of study outcomes at 6 and 12 months post intervention. Analysis will include client measures (screening result, weekly alcohol consumption, alcohol-related problems, re-offending, public service use and quality of life) and implementation measures from OMs (the extent of screening and brief intervention beyond the minimum recruitment threshold will provide data on acceptability and feasibility of different models of brief intervention). We will also examine the practitioner and organisational factors

  2. Breast Cancer Screening, Mammography, and Other Modalities.

    Science.gov (United States)

    Fiorica, James V

    2016-12-01

    This article is an overview of the modalities available for breast cancer screening. The modalities discussed include digital mammography, digital breast tomosynthesis, breast ultrasonography, magnetic resonance imaging, and clinical breast examination. There is a review of pertinent randomized controlled trials, studies and meta-analyses which contributed to the evolution of screening guidelines. Ultimately, 5 major medical organizations formulated the current screening guidelines in the United States. The lack of consensus in these guidelines represents an ongoing controversy about the optimal timing and method for breast cancer screening in women. For mammography screening, the Breast Imaging Reporting and Data System lexicon is explained which corresponds with recommended clinical management. The presentation and discussion of the data in this article are designed to help the clinician individualize breast cancer screening for each patient.

  3. Patient education for colon cancer screening: a randomized trial of a video mailed before a physical examination.

    Science.gov (United States)

    Zapka, Jane G; Lemon, Stephenie C; Puleo, Elaine; Estabrook, Barbara; Luckmann, Roger; Erban, Stephen

    2004-11-02

    Colorectal cancer screening is underused, and primary care clinicians are challenged to provide patient education within the constraints of busy practices. To test the effect of an educational video, mailed to patients' homes before a physical examination, on performance of colorectal cancer screening, particularly sigmoidoscopy. Randomized, controlled trial. 5 primary care practices in central Massachusetts. 938 patients age 50 to 74 years who were scheduled for an upcoming physical examination, had no personal history of colorectal cancer, and were eligible for lower-endoscopy screening according to current guidelines. Participants were randomly assigned to receive usual care (n = 488) or a video about colorectal cancer, the importance of early detection, and screening options (n = 450). Baseline and 6-month follow-up telephone assessments were conducted. A dependent variable classified screening since baseline as 1) sigmoidoscopy with or without other tests, 2) another test or test combination, or 3) no tests. Overall screening rates were the same in the intervention and control groups (55%). In regression modeling, intervention participants were nonsignificantly more likely to complete sigmoidoscopy alone or in combination with another test (odds ratio, 1.22 [95% CI, 0.88 to 1.70]). Intervention dose (viewing at least half of the video) was significantly related to receiving sigmoidoscopy with or without another test (odds ratio, 2.81 [CI, 1.85 to 4.26]). Recruitment records showed that at least 23% of people coming for periodic health assessments were currently screened by a lower-endoscopy procedure and therefore were not eligible. The primary care sample studied consisted primarily of middle-class white persons who had high screening rates at baseline. The results may not be generalizable to other populations. The trial was conducted during a period of increased health insurance coverage for lower-endoscopy procedures and public media attention to colon

  4. Results of a Community-Based Randomized Trial to Increase Colorectal Cancer Screening Among Filipino Americans

    Science.gov (United States)

    Bastani, Roshan; Danao, Leda L.; Antonio, Cynthia; Garcia, Gabriel M.; Crespi, Catherine M.

    2010-01-01

    Objectives. We conducted 1 of the first community-based trials to develop a multicomponent intervention that would increase colorectal cancer screening among an Asian American population. Methods. Filipino Americans (n = 548) nonadherent to colorectal cancer (CRC) screening guidelines were randomized into an intervention group that received an education session on CRC screening and free fecal occult blood test (FOBT) kits; a second intervention group that received an education session but no free FOBT kits; and a control group that received an education session on the health benefits of physical activity. Results. Self-reported CRC screening rates during the 6-month follow-up period were 30%, 25%, and 9% for participants assigned to intervention with FOBT kit, intervention without the kit, and control group, respectively. Participants in either of the 2 intervention groups were significantly more likely to report screening at follow-up than were participants in the control group. Conclusions. A multicomponent intervention that includes an educational group session in a community setting can significantly increase CRC screening among Filipino Americans, even when no free FOBT kits are distributed. PMID:20864724

  5. The impact of nurse-driven targeted HIV screening in 8 emergency departments: study protocol for the DICI-VIH cluster-randomized two-period crossover trial.

    Science.gov (United States)

    Leblanc, Judith; Rousseau, Alexandra; Hejblum, Gilles; Durand-Zaleski, Isabelle; de Truchis, Pierre; Lert, France; Costagliola, Dominique; Simon, Tabassome; Crémieux, Anne-Claude

    2016-02-01

    the control and targeted groups respectively, a sample size of 140,000 patients was estimated corresponding to 8,750 patients per ED and per period. Inclusions started in June 2014. Results are expected by mid-2016. The DICI-VIH study is the first large randomized controlled trial designed to assess nurse-driven targeted HIV screening. This study can provide valuable information on HIV screening in health care settings. ClinicalTrials.gov: NCT02127424 (29 April 2014).

  6. Screening for type 2 diabetes in a high-risk population: Study design and feasibility of a population-based randomized controlled trial

    NARCIS (Netherlands)

    B. Klijs (Bart); S.J. Otto (Suzie); R.J. Heine (Robert); Y. van der Graaf (Yolanda); J.J. Lous (Jan); H.J. de Koning (Harry)

    2012-01-01

    textabstractBackground: We describe the design and present the results of the first year of a population-based study of screening for type 2 diabetes in individuals at high risk of developing the disease. High risk is defined as having abdominal obesity. Methods. Between 2006 and 2007, 79,142

  7. Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework.

    Science.gov (United States)

    Wilson, Caroline; Rooshenas, Leila; Paramasivan, Sangeetha; Elliott, Daisy; Jepson, Marcus; Strong, Sean; Birtle, Alison; Beard, David J; Halliday, Alison; Hamdy, Freddie C; Lewis, Rebecca; Metcalfe, Chris; Rogers, Chris A; Stein, Robert C; Blazeby, Jane M; Donovan, Jenny L

    2018-01-19

    Research has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment. Eight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs. The eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR - Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received. The SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work

  8. Big Data in Designing Clinical Trials: Opportunities and Challenges.

    Science.gov (United States)

    Mayo, Charles S; Matuszak, Martha M; Schipper, Matthew J; Jolly, Shruti; Hayman, James A; Ten Haken, Randall K

    2017-01-01

    Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  9. Big Data in Designing Clinical Trials: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Charles S. Mayo

    2017-08-01

    Full Text Available Emergence of big data analytics resource systems (BDARSs as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  10. The role of GPs in increasing compliance to colorectal cancer screening: a randomised controlled trial (Italy).

    Science.gov (United States)

    Federici, Antonio; Giorgi Rossi, Paolo; Bartolozzi, Francesco; Farchi, Sara; Borgia, Piero; Guastcchi, Gabriella

    2006-02-01

    To assess the effect of the provider (GPs versus hospital) on the compliance in returning the faecal occult blood test. To analyse the characteristics of the GP associated with high compliance among his beneficiaries. A questionnaire about screening attitudes was mailed to the 1192 GPs working in 13 districts of the Lazio region. We asked the GPs to participate in a randomised trial, we sampled 130 GPs and about 1/10 of the GPs' 50-75 year old beneficiaries (n = 3657) were invited to be screened at the GP office and 1/10 (3675) at the nearest gastroenterology centre. 58.5% of the GPs completed the questionnaire and 22.7% agreed to participate in the trial. The compliance in the GP arm was 50%, in the hospital arm 16% (RR 3.4; 95% CI: 3.13-3.70). There was a high variability in the compliance obtained by the GPs. GPs with more than 25 patients visited/day and those incorrectly recommended screening of colorectal cancer obtained a lower compliance (OR 0.74, 95% CI: 0.57-0.95 and OR 0.76, 95% CI: 0.59-0.97, respectively). The involvement of GPs in colorectal cancer screening can be very effective to enhance the compliance, but the effectiveness is dependent on their willingness to be involved.

  11. Screening for type 2 diabetes in a high-risk population: study design and feasibility of a population-based randomized controlled trial

    NARCIS (Netherlands)

    Klijs, B.; Otto, S.J.; Heine, R.J.; van der Graaf, Y.; Lous, J.J.; Koning, H.J.

    2012-01-01

    Background: We describe the design and present the results of the first year of a population-based study of screening for type 2 diabetes in individuals at high risk of developing the disease. High risk is defined as having abdominal obesity. Methods. Between 2006 and 2007, 79,142 inhabitants of two

  12. The Role and Design of Screen Images in Software Documentation.

    Science.gov (United States)

    van der Meij, Hans

    2000-01-01

    Discussion of learning a new computer software program focuses on how to support the joint handling of a manual, input devices, and screen display. Describes a study that examined three design styles for manuals that included screen images to reduce split-attention problems and discusses theory versus practice and cognitive load theory.…

  13. Optimizing adherence in HIV prevention product trials: Development and psychometric evaluation of simple tools for screening and adherence counseling.

    Science.gov (United States)

    Tolley, Elizabeth E; Guthrie, Kate Morrow; Zissette, Seth; Fava, Joseph L; Gill, Katherine; Louw, Cheryl E; Kotze, Philip; Reddy, Krishnaveni; MacQueen, Kathleen

    2018-01-01

    Low adherence in recent HIV prevention clinical trials highlights the need to better understand, measure, and support product use within clinical trials. Conventional self-reported adherence instruments within HIV prevention trials, often relying on single-item questions, have proven ineffective. While objective adherence measures are desirable, none currently exist that apply to both active and placebo arms. Scales are composed of multiple items in the form of questions or statements that, when combined, measure a more complex construct that may not be directly observable. When psychometrically validated, such measures may better assess the multiple factors contributing to adherence/non-adherence. This study aimed to develop and psychometrically evaluate tools to screen and monitor trial participants' adherence to HIV prevention products within the context of clinical trial research. Based on an extensive literature review and conceptual framework, we identified and refined 86 items assessing potential predictors of adherence and 48 items assessing adherence experience. A structured survey, including adherence items and other variables, was administered to former ASPIRE and Ring Study participants and similar non-trial participants (n = 709). We conducted exploratory factor analyses (EFA) to identify a reduced set of constructs and items that could be used at screening to predict potential adherence, and at follow-up to monitor and intervene on adherence. We examined associations with other variables to assess content and construct validity. The EFA of screener items resulted in a 6-factor solution with acceptable to very good internal reliability (α: .62-.84). Similar to our conceptual framework, factors represent trial-related commitment (Distrust of Research and Commitment to Research); alignment with trial requirements (Visit Adherence and Trial Incompatibility); Belief in Trial Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4

  14. Preimplantation genetic screening.

    Science.gov (United States)

    Harper, Joyce C

    2018-03-01

    Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

  15. Research design considerations for single-dose analgesic clinical trials in acute pain

    DEFF Research Database (Denmark)

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C

    2016-01-01

    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials......, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay...... sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable...

  16. CRISPR-FOCUS: A web server for designing focused CRISPR screening experiments

    OpenAIRE

    Cao, Qingyi; Ma, Jian; Chen, Chen-Hao; Xu, Han; Chen, Zhi; Li, Wei; Liu, X. Shirley

    2017-01-01

    The recently developed CRISPR screen technology, based on the CRISPR/Cas9 genome editing system, enables genome-wide interrogation of gene functions in an efficient and cost-effective manner. Although many computational algorithms and web servers have been developed to design single-guide RNAs (sgRNAs) with high specificity and efficiency, algorithms specifically designed for conducting CRISPR screens are still lacking. Here we present CRISPR-FOCUS, a web-based platform to search and prioriti...

  17. Designing an idea screening framework for employee-driven innovation

    OpenAIRE

    Ciriello, Raffaele Fabio; Richter, Alexander; Schwabe, Gerhard

    2016-01-01

    As ever more companies encourage their employees to realize innovations, a surplus of ideas that exceeds the available resources to implement them has become reality in many organizations. With this paper, we follow recent calls for designing IT-supported, comprehensive, multi-attributive idea screening throughout the whole innovation cycle. Our Idea Screening Framework is grounded in literature and empirical data we collected from a two-year field study in a multinational European banking so...

  18. Incentives in Diabetic Eye Assessment by Screening (IDEAS): study protocol of a three-arm randomized controlled trial using financial incentives to increase screening uptake in London.

    Science.gov (United States)

    Judah, Gaby; Vlaev, Ivo; Gunn, Laura; King, Dominic; King, Derek; Valabhji, Jonathan; Darzi, Ara; Bicknell, Colin

    2016-03-18

    Diabetes is an increasing public health problem in the UK and globally. Diabetic retinopathy is a microvascular complication of diabetes, and is one of the leading causes of blindness in the UK working age population. The diabetic eye screening programme in England aims to invite all people with diabetes aged 12 or over for retinal photography to screen for the presence of diabetic retinopathy. However, attendance rates are only 81 %, leaving many people at risk of preventable sight loss. This is a three arm randomized controlled trial to investigate the impact of different types of financial incentives (based on principles from behavioral economics) on increasing attendance at diabetic eye screening appointments in London. Eligible participants will be aged 16 or over, and are those who have been invited to screening appointments annually, but who have not attended, or telephoned to rearrange an appointment, within the last 24 months. Eligible participants will be randomized to one of three conditions: 1. Control condition (usual invitation letter) 2. Fixed incentive condition (usual invitation letter, including a voucher for £10 if they attend their appointment) 3. Probabilistic incentive condition (invitation letter, including a voucher for a 1 in 100 chance of winning £1000 if they attend their appointment). Participants will be sent invitation letters, and the primary outcome will be whether or not they attend their appointment. One thousand participants will be included in total, randomized with a ratio of 1.4:1:1. In order to test whether the incentive scheme has a differential impact on patients from different demographic or socio-economic groups, information will be recorded on age, gender, distance from screening center, socio-economic status and length of time since they were last screened. A cost-effectiveness analysis will also be performed. This study will be the first trial of financial incentives for improving uptake of diabetic eye screening. If

  19. A randomized controlled Alzheimer's disease prevention trial's evolution into an exposure trial: the PREADViSE Trial.

    Science.gov (United States)

    Kryscio, R J; Abner, E L; Schmitt, F A; Goodman, P J; Mendiondo, M; Caban-Holt, A; Dennis, B C; Mathews, M; Klein, E A; Crowley, J J

    2013-01-01

    To summarize the ongoing prevention of Alzheimer's disease (AD) by vitamin E and selenium (PREADViSE) trial as an ancillary study to SELECT (a large prostate cancer prevention trial) and to present the blinded results of the first year as an exposure study. PREADViSE was designed as a double blind randomized controlled trial (RCT). SELECT terminated after median of 5.5 years of exposure to supplements due to a futility analysis. Both trials then converted into an exposure study. In the randomized component PREADViSE enrolled 7,547 men age 62 or older (60 if African American). Once the trial terminated 4,246 of these men volunteered for the exposure study. Demographics were similar for both groups with exposure volunteers having baseline mean age 67.3 ± 5.2 years, 15.3 ± 2.4 years of education, 9.8% African Americans, and 22.0% reporting a family history of dementia. In the RCT men were randomly assigned to either daily doses of 400 IU of vitamin E or placebo and 200 µg of selenium or placebo using a 2x2 factorial structure. In the RCT, participants completed the memory impairment screen (MIS), and if they failed, underwent a longer screening (based on an expanded Consortium to Establish a Registry in AD [CERAD] battery). CERAD failure resulted in visits to their clinician for medical examination with records of these examinations forwarded to the PREADViSE center for further review. In the exposure study, men are contacted by telephone and complete the telephone version of the memory impairment screen (MIS-T) screen. If they fail the MIS-T, a modified telephone interview of cognitive status (TICS-M) exam is given. A failed TICS-M exam also leads to a visit to their clinician for an in-depth examination and forwarding of records for a centralized consensus diagnosis by expert clinicians. A subgroup of the men who pass the MIS-T also take the TICS-M exam for validation purposes. While this ancillary trial was open to all 427 SELECT clinical sites, only 130 (30

  20. Community-led trials: Intervention co-design in a cluster randomised controlled trial.

    Science.gov (United States)

    Andersson, Neil

    2017-05-30

    In conventional randomised controlled trials (RCTs), researchers design the interventions. In the Camino Verde trial, each intervention community designed its own programmes to prevent dengue. Instead of fixed actions or menus of activities to choose from, the trial randomised clusters to a participatory research protocol that began with sharing and discussing evidence from a local survey, going on to local authorship of the action plan for vector control.Adding equitable stakeholder engagement to RCT infrastructure anchors the research culturally, making it more meaningful to stakeholders. Replicability in other conditions is straightforward, since all intervention clusters used the same engagement protocol to discuss and to mobilize for dengue prevention. The ethical codes associated with RCTs play out differently in community-led pragmatic trials, where communities essentially choose what they want to do. Several discussion groups in each intervention community produced multiple plans for prevention, recognising different time lines. Some chose fast turnarounds, like elimination of breeding sites, and some chose longer term actions like garbage disposal and improving water supplies.A big part of the skill set for community-led trials is being able to stand back and simply support communities in what they want to do and how they want to do it, something that does not come naturally to many vector control programs or to RCT researchers. Unexpected negative outcomes can come from the turbulence implicit in participatory research. One example was the gender dynamic in the Mexican arm of the Camino Verde trial. Strong involvement of women in dengue control activities seems to have discouraged men in settings where activity in public spaces or outside of the home would ordinarily be considered a "male competence".Community-led trials address the tension between one-size-fits-all programme interventions and local needs. Whatever the conventional wisdom about how

  1. Community-led trials: Intervention co-design in a cluster randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Neil Andersson

    2017-05-01

    Full Text Available Abstract In conventional randomised controlled trials (RCTs, researchers design the interventions. In the Camino Verde trial, each intervention community designed its own programmes to prevent dengue. Instead of fixed actions or menus of activities to choose from, the trial randomised clusters to a participatory research protocol that began with sharing and discussing evidence from a local survey, going on to local authorship of the action plan for vector control. Adding equitable stakeholder engagement to RCT infrastructure anchors the research culturally, making it more meaningful to stakeholders. Replicability in other conditions is straightforward, since all intervention clusters used the same engagement protocol to discuss and to mobilize for dengue prevention. The ethical codes associated with RCTs play out differently in community-led pragmatic trials, where communities essentially choose what they want to do. Several discussion groups in each intervention community produced multiple plans for prevention, recognising different time lines. Some chose fast turnarounds, like elimination of breeding sites, and some chose longer term actions like garbage disposal and improving water supplies. A big part of the skill set for community-led trials is being able to stand back and simply support communities in what they want to do and how they want to do it, something that does not come naturally to many vector control programs or to RCT researchers. Unexpected negative outcomes can come from the turbulence implicit in participatory research. One example was the gender dynamic in the Mexican arm of the Camino Verde trial. Strong involvement of women in dengue control activities seems to have discouraged men in settings where activity in public spaces or outside of the home would ordinarily be considered a “male competence”. Community-led trials address the tension between one-size-fits-all programme interventions and local needs. Whatever the

  2. More ethical and more efficient clinical research: multiplex trial design.

    Science.gov (United States)

    Keus, Frederik; van der Horst, Iwan C C; Nijsten, Maarten W

    2014-08-14

    Today's clinical research faces challenges such as a lack of clinical equipoise between treatment arms, reluctance in randomizing for multiple treatments simultaneously, inability to address interactions and increasingly restricted resources. Furthermore, many trials are biased by extensive exclusion criteria, relatively small sample size and less appropriate outcome measures. We propose a 'Multiplex' trial design that preserves clinical equipoise with a continuous and factorial trial design that will also result in more efficient use of resources. This multiplex design accommodates subtrials with appropriate choice of treatment arms within each subtrial. Clinical equipoise should increase consent rates while the factorial design is the best way to identify interactions. The multiplex design may evolve naturally from today's research limitations and challenges, while principal objections seem absent. However this new design poses important infrastructural, organisational and psychological challenges that need in depth consideration.

  3. Evaluating the design and reporting of pragmatic trials in osteoarthritis research.

    Science.gov (United States)

    Ali, Shabana Amanda; Kloseck, Marita; Lee, Karen; Walsh, Kathleen Ellen; MacDermid, Joy C; Fitzsimmons, Deborah

    2018-01-01

    Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  4. Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools

    Directory of Open Access Journals (Sweden)

    Pressler Taylor R

    2012-05-01

    Full Text Available Abstract Background Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. Methods The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Results Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV of 54.12% and 0.7%, respectively, and a negative predictive value (NPV of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. Conclusions This software is intended to provide an initial list of eligible patients to a

  5. Increasing chlamydia screening tests in general practice: a modified Zelen prospective Cluster Randomised Controlled Trial evaluating a complex intervention based on the Theory of Planned Behaviour.

    Science.gov (United States)

    McNulty, Cliodna A M; Hogan, Angela H; Ricketts, Ellie J; Wallace, Louise; Oliver, Isabel; Campbell, Rona; Kalwij, Sebastian; O'Connell, Elaine; Charlett, Andre

    2014-05-01

    To determine if a structured complex intervention increases opportunistic chlamydia screening testing of patients aged 15-24 years attending English general practitioner (GP) practices. A prospective, Cluster Randomised Controlled Trial with a modified Zelen design involving 160 practices in South West England in 2010. The intervention was based on the Theory of Planned Behaviour (TPB). It comprised of practice-based education with up to two additional contacts to increase the importance of screening to GP staff and their confidence to offer tests through skill development (including videos). Practical resources (targets, posters, invitation cards, computer reminders, newsletters including feedback) aimed to actively influence social cognitions of staff, increasing their testing intention. Data from 76 intervention and 81 control practices were analysed. In intervention practices, chlamydia screening test rates were 2.43/100 15-24-year-olds registered preintervention, 4.34 during intervention and 3.46 postintervention; controls testing rates were 2.61/100 registered patients prior intervention, 3.0 during intervention and 2.82 postintervention. During the intervention period, testing in intervention practices was 1.76 times as great (CI 1.24 to 2.48) as controls; this persisted for 9 months postintervention (1.57 times as great, CI 1.27 to 2.30). Chlamydia infections detected increased in intervention practices from 2.1/1000 registered 15-24-year-olds prior intervention to 2.5 during the intervention compared with 2.0 and 2.3/1000 in controls (Estimated Rate Ratio intervention versus controls 1.4 (CI 1.01 to 1.93). This complex intervention doubled chlamydia screening tests in fully engaged practices. The modified Zelen design gave realistic measures of practice full engagement (63%) and efficacy of this educational intervention in general practice; it should be used more often. The trial was registered on the UK Clinical Research Network Study Portfolio database

  6. A multicentre randomised controlled trial of day hospital-based falls prevention programme for a screened population of community-dwelling older people at high risk of falls

    OpenAIRE

    Conroy, Simon; Kendrick, Denise; Harwood, Rowan; Gladman, John; Coupland, Carol; Sach, Tracey; Drummond, Avril; Youde, Jane; Edmans, Judi; Masud, Tahir

    2010-01-01

    Objective: to determine the clinical effectiveness of a day hospital-delivered multifactorial falls prevention programme, for community-dwelling older people at high risk of future falls identified through a screening process. Design: multicentre randomised controlled trial. Setting: eight general practices and three day hospitals based in the East Midlands, UK. Participants: three hundred and sixty-four participants, mean age 79 years, with a median of three falls risk factors per person at ...

  7. A P300-based Brain-Computer Interface with Stimuli on Moving Objects: Four-Session Single-Trial and Triple-Trial Tests with a Game-Like Task Design

    Science.gov (United States)

    Ganin, Ilya P.; Shishkin, Sergei L.; Kaplan, Alexander Y.

    2013-01-01

    Brain-computer interfaces (BCIs) are tools for controlling computers and other devices without using muscular activity, employing user-controlled variations in signals recorded from the user’s brain. One of the most efficient noninvasive BCIs is based on the P300 wave of the brain’s response to stimuli and is therefore referred to as the P300 BCI. Many modifications of this BCI have been proposed to further improve the BCI’s characteristics or to better adapt the BCI to various applications. However, in the original P300 BCI and in all of its modifications, the spatial positions of stimuli were fixed relative to each other, which can impose constraints on designing applications controlled by this BCI. We designed and tested a P300 BCI with stimuli presented on objects that were freely moving on a screen at a speed of 5.4°/s. Healthy participants practiced a game-like task with this BCI in either single-trial or triple-trial mode within four sessions. At each step, the participants were required to select one of nine moving objects. The mean online accuracy of BCI-based selection was 81% in the triple-trial mode and 65% in the single-trial mode. A relatively high P300 amplitude was observed in response to targets in most participants. Self-rated interest in the task was high and stable over the four sessions (the medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing in the single-trial and triple-trial modes, respectively). We conclude that the movement of stimulus positions relative to each other may not prevent the efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic devices and in video games. PMID:24302977

  8. Lessons learned from recruiting young female students to a randomised controlled trial of chlamydia screening.

    Science.gov (United States)

    Ivaz, Stella; Brennan, Sarah; Dean, Sally; Hay, Sima; Hay, Phillip; Kerry, Sally; Oakeshott, Pippa

    2006-04-01

    Recruitment is a problem in many trials. Two female medical students offered to help with recruiting problems in a community-based trial of chlamydia screening to prevent pelvic inflammatory disease. We need to recruit 2500 sexually active female students and ask them to provide a self-taken low vaginal swab and complete a questionnaire with follow-up after a year. To identify recruitment difficulties in a community-based trial of chlamydia screening and to investigate how they might be overcome. Descriptive study. London South Bank and Kingston Universities. The students observed the recruitment methods used for the first 4 months of the trial. This comprised single researchers recruiting individual women in student bars and common rooms. With the researchers they piloted a new method of group recruitment with pairs of researchers making announcements at the end of lectures after first sending out all male students and those aged>25 years. This involved extra time planning and liaising with the lecturers in advance of recruitment sessions. The recruitment rate had been averaging only 25 participants per week. Many students were ineligible: never been sexually active, too old, recently been tested for chlamydia. Many eligible students were reluctant to take part because of embarrassment or anxiety about providing a swab. Using a new method of group recruitment after lectures we recruited 192 participants in 2 weeks. For a study on a sensitive topic, two researchers recruiting women in groups after lectures may be a more effective and cost-effective way than individual recruitment by researchers working alone.

  9. Informing men about prostate cancer screening: a randomized controlled trial of patient education materials.

    Science.gov (United States)

    Ilic, Dragan; Egberts, Kristine; McKenzie, Joanne E; Risbridger, Gail; Green, Sally

    2008-04-01

    Patient education materials can assist patient decision making on prostate cancer screening. To explore the effectiveness of presenting health information on prostate cancer screening using video, internet, and written interventions on patient decision making, attitudes, knowledge, and screening interest. Randomized controlled trial. A total of 161 men aged over 45, who had never been screened for prostate cancer, were randomized to receive information on prostate cancer screening. Participants were assessed at baseline and 1-week postintervention for decisional conflict, screening interest, knowledge, anxiety, and decision-making preference. A total of 156 men were followed-up at 1-week postintervention. There was no statistical, or clinical, difference in mean change in decisional conflict scores between the 3 intervention groups (video vs internet -0.06 [95% CI -0.24 to 0.12]; video vs pamphlet 0.04 [95%CI -0.15 to 0.22]; internet vs pamphlet 0.10 [95%CI -0.09 to 0.28]). There was also no statistically significant difference in mean knowledge, anxiety, decision-making preference, and screening interest between the 3 intervention groups. Results from this study indicate that there are no clinically significant differences in decisional conflict when men are presented health information on prostate cancer screening via video, written materials, or the internet. Given the equivalence of the 3 methods, other factors need to be considered in deciding which method to use. Health professionals should provide patient health education materials via a method that is most convenient to the patient and their preferred learning style.

  10. Automated recycling of chemistry for virtual screening and library design.

    Science.gov (United States)

    Vainio, Mikko J; Kogej, Thierry; Raubacher, Florian

    2012-07-23

    An early stage drug discovery project needs to identify a number of chemically diverse and attractive compounds. These hit compounds are typically found through high-throughput screening campaigns. The diversity of the chemical libraries used in screening is therefore important. In this study, we describe a virtual high-throughput screening system called Virtual Library. The system automatically "recycles" validated synthetic protocols and available starting materials to generate a large number of virtual compound libraries, and allows for fast searches in the generated libraries using a 2D fingerprint based screening method. Virtual Library links the returned virtual hit compounds back to experimental protocols to quickly assess the synthetic accessibility of the hits. The system can be used as an idea generator for library design to enrich the screening collection and to explore the structure-activity landscape around a specific active compound.

  11. Smoking cessation and lung cancer screening

    DEFF Research Database (Denmark)

    Pedersen, Jesper Johannes Holst; Tønnesen, Philip; Ashraf, Haseem

    2016-01-01

    Smoking behavior may have a substantial influence on the overall effect of lung cancer screening. Non-randomized studies of smoking behavior during screening have indicated that computer tomography (CT) screening induces smoking cessation. Randomized studies have further elaborated that this effect...... and decrease smoking relapse rate. Also low smoking dependency and high motivation to quit smoking at baseline predicted smoking abstinence in screening trials. Lung cancer screening therefore seems to be a teachable moment for smoking cessation. Targeted smoking cessation counselling should be an integrated...... part of future lung cancer screening trials....

  12. Deep brain stimulation targeting the fornix for mild Alzheimer dementia: design of the ADvance randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Holroyd KB

    2015-07-01

    stimulation (DBS of memory circuits may improve symptoms and possibly slow disease progression. The ADvance trial was designed to examine DBS of the fornix as a treatment for mild AD. Methods: ADvance is a randomized, double-blind, placebo-controlled, delayed-start, multicenter clinical trial conducted at six sites in the US and one site in Canada. Eighty-five subjects initially consented to be screened for the trial. Of these, 42 subjects who met inclusion and exclusion criteria were implanted with DBS leads anterior to the columns of the fornix bilaterally. They were randomized 1:1 to DBS “off” or DBS “on” groups for the initial 12 months of follow-up. After 1 year, all subjects will have their devices turned “on” for the remainder of the study. Postimplantation, subjects will return for 13 follow-up visits over 48 months for cognitive and psychiatric assessments, brain imaging (up to 12 months, and safety monitoring. The primary outcome measures include Alzheimer's Disease Assessment Scale – cognitive component (ADAS-cog-13, Clinical Dementia Rating sum of boxes (CDR-SB, and cerebral glucose metabolism measured with positron emission tomography. This report details the study methods, baseline subject characteristics of screened and implanted participants, and screen-to-baseline test–retest reliability of the cognitive outcomes. Results: Implanted subjects had a mean age of 68.2 years, were mostly male (55%, and had baseline mean ADAS-cog-13 and CDR-SB scores of 28.9 (SD, 5.2 and 3.9 (SD, 1.6, respectively. There were no significant differences between screened and implanted or nonimplanted subjects on most demographic or clinical assessments. Implanted subjects had significantly lower (better ADAS-cog-11 (17.5 vs 21.1 scores, but did not differ on CDR-SB. Scores on the major outcome measures for the trial were consistent at screening and baseline. Conclusion: ADvance was successful in enrolling a substantial group of patients for this novel application of

  13. Design of Phase I Combination Trials: Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee

    Science.gov (United States)

    Paller, Channing J.; Bradbury, Penelope A.; Ivy, S. Percy; Seymour, Lesley; LoRusso, Patricia M.; Baker, Laurence; Rubinstein, Larry; Huang, Erich; Collyar, Deborah; Groshen, Susan; Reeves, Steven; Ellis, Lee M.; Sargent, Daniel J.; Rosner, Gary L.; LeBlanc, Michael L.; Ratain, Mark J.

    2014-01-01

    Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistical and regulatory challenges. The phase 1 trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee developed a set of recommendations for the phase 1 development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biological or pharmacological rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase 1 clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamic (i.e., biomarker). PMID:25125258

  14. Design of a projection display screen with vanishing color shift for rear-projection HDTV

    Science.gov (United States)

    Liu, Xiu; Zhu, Jin-lin

    1996-09-01

    Using bi-convex cylinder lens with matrix structure, the transmissive projection display screen with high contrast and wider viewing angle has been widely used in large rear projection TV and video projectors, it obtained a inhere color shift and puzzled the designer of display screen for RGB projection tube in-line adjustment. Based on the method of light beam racing, the general software of designing projection display screen has been developed and the computer model of vanishing color shift for rear projection HDTV has bee completed. This paper discussed the practical designing method to vanish the defect of color shift and mentioned the relations between the primary optical parameters of display screen and relative geometry sizes of lens' surface. The distributions of optical gain to viewing angle and the influences on engineering design are briefly analyzed.

  15. Effectiveness of school dental screening on dental visits and untreated caries among primary schoolchildren: study protocol for a cluster randomised controlled trial.

    Science.gov (United States)

    Alayadi, Haya; Sabbah, Wael; Bernabé, Eduardo

    2018-04-13

    Dental caries is one of the most common diseases affecting children in Saudi Arabia despite the availability of free dental services. School-based dental screening could be a potential intervention that impacts uptake of dental services, and subsequently, dental caries' levels. The purpose of this study is to evaluate the effectiveness of two alternative approaches for school-based dental screening in promoting dental attendance and reducing untreated dental caries among primary schoolchildren. This is a cluster randomised controlled trial comparing referral of screened-positive children to a specific treatment facility (King Saud University Dental College) against conventional referral (information letter advising parents to take their child to a dentist). A thousand and ten children in 16 schools in Riyadh, Saudi Arabia, will be recruited for the trial. Schools (clusters) will be randomly selected and allocated to either group. Clinical assessment for dental caries will be conducted at baseline and after 12 months by dentists using the World Health Organisation (WHO) criteria. Data on sociodemographic, behavioural factors and children's dental visits will be collected through structured questionnaires at baseline and follow-up. The primary outcome is the change in number of teeth with untreated dental caries 12 months after referral. Secondary outcomes are the changes in the proportions of children having untreated caries and of those who visited the dentist over the trial period. This project should provide high level of evidence on the clinical benefits of school dental screening. The findings should potentially inform policies related to the continuation/implementation of school-based dental screening in Saudi Arabia. ClinicalTrials.gov , ID: NCT03345680 . Registered on 17 November 2017.

  16. Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial

    Science.gov (United States)

    2014-01-01

    Background Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens. However, it is not clear how best to treat patients with antibodies. This trial will test a combined screening and treatment protocol in renal transplant recipients. Methods/Design Recipients >1 year post-transplantation, aged 18 to 70 with an estimated glomerular filtration rate >30 mL/min will be randomly allocated to blinded or unblinded screening arms, before being screened for the presence of antibodies. In the unblinded arm, test results will be revealed. Those with antibodies will have biomarker-led care, consisting of a change in their anti-rejection drugs to prednisone, tacrolimus and mycophenolate mofetil. In the blinded arm, screening results will be double blinded and all recruits will remain on current therapy (standard care). In both arms, those without antibodies will be retested every 8 months for 3 years. The primary outcome is the 3-year kidney failure rate for the antibody-positive recruits, as measured by initiation of long-term dialysis or re-transplantation, predicted to be approximately 20% in the standard care group but transplant dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of adherence with medication and a health economic analysis of the combined screening and treatment protocol. Blood samples will be collected and stored every 4 months and will form the basis of separately funded studies to identify new biomarkers associated with the outcomes. Discussion We have evidence that the biomarker-led care regime will be effective at preventing graft dysfunction and expect this to

  17. Simulations for designing and interpreting intervention trials in infectious diseases.

    Science.gov (United States)

    Halloran, M Elizabeth; Auranen, Kari; Baird, Sarah; Basta, Nicole E; Bellan, Steven E; Brookmeyer, Ron; Cooper, Ben S; DeGruttola, Victor; Hughes, James P; Lessler, Justin; Lofgren, Eric T; Longini, Ira M; Onnela, Jukka-Pekka; Özler, Berk; Seage, George R; Smith, Thomas A; Vespignani, Alessandro; Vynnycky, Emilia; Lipsitch, Marc

    2017-12-29

    Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods. Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, which are critical for proper trial design and interpretation. Certain ethical aspects of a trial can also be quantified using simulations. Further, after a trial has been conducted, simulations can be used to explore the possible explanations for the observed effects. Much is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods, and the conduct of clinical trials.

  18. Data-driven decision support for radiologists: re-using the National Lung Screening Trial dataset for pulmonary nodule management.

    Science.gov (United States)

    Morrison, James J; Hostetter, Jason; Wang, Kenneth; Siegel, Eliot L

    2015-02-01

    Real-time mining of large research trial datasets enables development of case-based clinical decision support tools. Several applicable research datasets exist including the National Lung Screening Trial (NLST), a dataset unparalleled in size and scope for studying population-based lung cancer screening. Using these data, a clinical decision support tool was developed which matches patient demographics and lung nodule characteristics to a cohort of similar patients. The NLST dataset was converted into Structured Query Language (SQL) tables hosted on a web server, and a web-based JavaScript application was developed which performs real-time queries. JavaScript is used for both the server-side and client-side language, allowing for rapid development of a robust client interface and server-side data layer. Real-time data mining of user-specified patient cohorts achieved a rapid return of cohort cancer statistics and lung nodule distribution information. This system demonstrates the potential of individualized real-time data mining using large high-quality clinical trial datasets to drive evidence-based clinical decision-making.

  19. Design of extended length submerged traveling screen and submerged bar screen fish guidance equipment

    International Nuclear Information System (INIS)

    Bardy, D.; Lindstrom, M.; Fechner, D.

    1991-01-01

    The hydropower projects on the Snake and lower Columbia Rivers in the Pacific Northwest are unique because these rivers are also the spawning grounds for migratory salmon. The salmon swim upstream from the ocean, lay their eggs, and die. The newly hatched fingerlings must then make their way past the hydroelectric dams to the ocean. Two separate bypass systems are needed, one to pass the adult fish going upstream, and one to pass the fingerlings going downstream. This paper addresses the design considerations for two of the components of the downstream migrant fish passage facilities, the extended Submerged Traveling Screen and Submerged Bar Screen

  20. Mammography screening: A major issue in medicine.

    Science.gov (United States)

    Autier, Philippe; Boniol, Mathieu

    2018-02-01

    -detected cancers. Overdiagnosis leads to overtreatment and inflicts considerable physical, psychological and economic harm on many women. Overdiagnosis has also exerted considerable disruptive effects on the interpretation of clinical outcomes expressed in percentages (instead of rates) or as overall survival (instead of mortality rates or stage-specific survival). Rates of radical mastectomies have not decreased following the introduction of screening and keep rising in some countries (e.g. the United States of America (USA)). Hence, the epidemiological picture of mammography screening closely resembles that of screening for neuroblastoma. Reappraisals of Swedish mammography trials demonstrate that the design and statistical analysis of these trials were different from those of all trials on screening for cancers other than breast cancer. We found compelling indications that these trials overestimated reductions in breast cancer mortality associated with screening, in part because of the statistical analyses themselves, in part because of improved therapies and underreporting of breast cancer as the underlying cause of death in screening groups. In this regard, Swedish trials should publish the stage-specific breast cancer mortality rates for the screening and control groups separately. Results of the Greater New York Health Insurance Plan trial are biased because of the underreporting of breast cancer cases and deaths that occurred in women who did not participate in screening. After 17 years of follow-up, the United Kingdom (UK) Age Trial showed no benefit from mammography screening starting at age 39-41. Until around 2005, most proponents of breast screening backed the monitoring of changes in advanced cancer incidence and comparative studies on breast cancer mortality for the evaluation of breast screening effectiveness. However, in an attempt to mitigate the contradictions between results of mammography trials and population data, breast-screening proponents have elected to

  1. Results of a lay health education intervention to increase colorectal cancer screening among Filipino Americans: A cluster randomized controlled trial.

    Science.gov (United States)

    Cuaresma, Charlene F; Sy, Angela U; Nguyen, Tung T; Ho, Reginald C S; Gildengorin, Ginny L; Tsoh, Janice Y; Jo, Angela M; Tong, Elisa K; Kagawa-Singer, Marjorie; Stewart, Susan L

    2018-04-01

    Filipino colorectal cancer (CRC) screening rates fall below Healthy People 2020 goals. In this study, the authors explore whether a lay health educator (LHE) approach can increase CRC screening among Filipino Americans ages 50 to 75 years in Hawai'i. A cluster randomized controlled trial from 2012 through 2015 compared an intervention, which consisted of LHEs delivering 2 education sessions and 2 telephone follow-up calls on CRC screening plus a CRC brochure versus an attention control, in which 2 lectures and 2 follow-up calls on nutrition and physical activity plus a CRC brochure were provided. The primary outcome was change in self-reported ever receipt of CRC screening at 6 months. Among 304 participants (77% women, 86% had > 10 years of residence in the United States), the proportion of participants who reported ever having received CRC screening increased significantly in the intervention group (from 80% to 89%; P = .0003), but not in the control group (from 73% to 74%; P = .60). After covariate adjustment, there was a significant intervention effect (odds ratio, 1.9; 95% confidence interval, 1.0-3.5). There was no intervention effect on up-to-date screening. This first randomized controlled trial for CRC screening among Hawai'i's Filipinos used an LHE intervention with mixed, but promising, results. Cancer 2018;124:1535-42. © 2018 American Cancer Society. © 2018 American Cancer Society.

  2. Screen Design Guidelines for Motivation in Interactive Multimedia Instruction: A Survey and Framework for Designers.

    Science.gov (United States)

    Lee, Sung Heum; Boling, Elizabeth

    1999-01-01

    Identifies guidelines from the literature relating to screen design and design of interactive instructional materials. Describes two types of guidelines--those aimed at enhancing motivation and those aimed at preventing loss of motivation--for typography, graphics, color, and animation and audio. Proposes a framework for considering motivation in…

  3. The design of the run Clever randomized trial

    DEFF Research Database (Denmark)

    Ramskov, Daniel; Nielsen, Rasmus Oestergaard; Sørensen, Henrik

    2016-01-01

    BACKGROUND: Injury incidence and prevalence in running populations have been investigated and documented in several studies. However, knowledge about injury etiology and prevention is needed. Training errors in running are modifiable risk factors and people engaged in recreational running need...... evidence-based running schedules to minimize the risk of injury. The existing literature on running volume and running intensity and the development of injuries show conflicting results. This may be related to previously applied study designs, methods used to quantify the performed running...... and the statistical analysis of the collected data. The aim of the Run Clever trial is to investigate if a focus on running intensity compared with a focus on running volume in a running schedule influences the overall injury risk differently. METHODS/DESIGN: The Run Clever trial is a randomized trial with a 24-week...

  4. Web-based alcohol screening and brief intervention for university students: a randomized trial.

    Science.gov (United States)

    Kypri, Kypros; Vater, Tina; Bowe, Steven J; Saunders, John B; Cunningham, John A; Horton, Nicholas J; McCambridge, Jim

    2014-03-26

    Unhealthy alcohol use is a leading contributor to the global burden of disease, particularly among young people. Systematic reviews suggest efficacy of web-based alcohol screening and brief intervention and call for effectiveness trials in settings where it could be sustainably delivered. To evaluate a national web-based alcohol screening and brief intervention program. A multisite, double-blind, parallel-group, individually randomized trial was conducted at 7 New Zealand universities. In April and May of 2010, invitations containing hyperlinks to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening test were e-mailed to 14,991 students aged 17 to 24 years. Participants who screened positive (AUDIT-C score ≥4) were randomized to undergo screening alone or to 10 minutes of assessment and feedback (including comparisons with medical guidelines and peer norms) on alcohol expenditure, peak blood alcohol concentration, alcohol dependence, and access to help and information. A fully automated 5-month follow-up assessment was conducted that measured 6 primary outcomes: consumption per typical occasion, drinking frequency, volume of alcohol consumed, an academic problems score, and whether participants exceeded medical guidelines for acute harm (binge drinking) and chronic harm (heavy drinking). A Bonferroni-corrected significance threshold of .0083 was used to account for the 6 comparisons and a sensitivity analysis was used to assess possible attrition bias. Of 5135 students screened, 3422 scored 4 or greater and were randomized, and 83% were followed up. There was a significant effect on 1 of the 6 prespecified outcomes. Relative to control participants, those who received intervention consumed less alcohol per typical drinking occasion (median 4 drinks [interquartile range {IQR}, 2-8] vs 5 drinks [IQR 2-8]; rate ratio [RR], 0.93 [99.17% CI, 0.86-1.00]; P = .005) but not less often (RR, 0.95 [99.17% CI, 0.88-1.03]; P = .08) or less

  5. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers.

    Science.gov (United States)

    Horeweg, Nanda; Scholten, Ernst Th; de Jong, Pim A; van der Aalst, Carlijn M; Weenink, Carla; Lammers, Jan-Willem J; Nackaerts, Kristiaan; Vliegenthart, Rozemarijn; ten Haaf, Kevin; Yousaf-Khan, Uraujh A; Heuvelmans, Marjolein A; Thunnissen, Erik; Oudkerk, Matthijs; Mali, Willem; de Koning, Harry J

    2014-11-01

    Low-dose CT screening is recommended for individuals at high risk of developing lung cancer. However, CT screening does not detect all lung cancers: some might be missed at screening, and others can develop in the interval between screens. The NELSON trial is a randomised trial to assess the effect of screening with increasing screening intervals on lung cancer mortality. In this prespecified analysis, we aimed to assess screening test performance, and the epidemiological, radiological, and clinical characteristics of interval cancers in NELSON trial participants assigned to the screening group. Eligible participants in the NELSON trial were those aged 50-75 years, who had smoked 15 or more cigarettes per day for more than 25 years or ten or more cigarettes for more than 30 years, and were still smoking or had quit less than 10 years ago. We included all participants assigned to the screening group who had attended at least one round of screening. Screening test results were based on volumetry using a two-step approach. Initially, screening test results were classified as negative, indeterminate, or positive based on nodule presence and volume. Subsequently, participants with an initial indeterminate result underwent follow-up screening to classify their final screening test result as negative or positive, based on nodule volume doubling time. We obtained information about all lung cancer diagnoses made during the first three rounds of screening, plus an additional 2 years of follow-up from the national cancer registry. We determined epidemiological, radiological, participant, and tumour characteristics by reassessing medical files, screening CTs, and clinical CTs. The NELSON trial is registered at www.trialregister.nl, number ISRCTN63545820. 15,822 participants were enrolled in the NELSON trial, of whom 7915 were assigned to low-dose CT screening with increasing interval between screens, and 7907 to no screening. We included 7155 participants in our study, with

  6. Prostate Cancer Screening Results from PLCO

    Science.gov (United States)

    Learn the results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a large-scale clinical trial to determine whether certain cancer screening tests can help reduce deaths from prostate, lung, colorectal, and ovarian cancer.

  7. A Randomized Trial to Compare Alternative Educational Interventions to Increase Colorectal Cancer Screening in a Hard-to-Reach Urban Minority Population with Health Insurance.

    Science.gov (United States)

    Basch, Charles E; Zybert, Patricia; Wolf, Randi L; Basch, Corey H; Ullman, Ralph; Shmukler, Celia; King, Fionnuala; Neugut, Alfred I; Shea, Steven

    2015-10-01

    This randomized controlled trial assessed different educational approaches for increasing colorectal cancer screening uptake in a sample of primarily non-US born urban minority individuals, over aged 50, with health insurance, and out of compliance with screening guidelines. In one group, participants were mailed printed educational material (n = 180); in a second, participants' primary care physicians received academic detailing to improve screening referral and follow-up practices (n = 185); in a third, physicians received academic detailing and participants received tailored telephone education (n = 199). Overall, 21.5% of participants (n = 121) received appropriate screening within one year of randomization. There were no statistically significant pairwise differences between groups in screening rate. Among those 60 years of age or older, however, the detailing plus telephone education group had a higher screening rate than the print group (27.3 vs. 7.7%, p = .02). Different kinds of interventions will be required to increase colorectal cancer screening among the increasingly small population segment that remains unscreened. ClinicalTrials.gov Identifier: NCT02392143.

  8. Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial.

    Science.gov (United States)

    Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

    2016-06-01

    The Systolic Blood Pressure Intervention Trial is a multicenter, randomized clinical trial of 9361 participants with hypertension who are ≥50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal recruitment strategies and lessons learned during recruitment of the Systolic Blood Pressure Intervention Trial cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥75 years, women, and minorities. In collaboration with the National Institutes of Health Project Office and Systolic Blood Pressure Intervention Trial Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began on 8 November 2010 and ended on 15 March 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Recruitment was scheduled to last 24 months to enroll a target of 9250 participants; in just over 28 months, the trial enrolled 9361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by Systolic Blood Pressure Intervention Trial staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, Internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized/number screened) was 64% (9361 randomized/14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those aged ≥75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional

  9. Mobile Phone Multilevel and Multimedia Messaging Intervention for Breast Cancer Screening: Pilot Randomized Controlled Trial.

    Science.gov (United States)

    Lee, Hee; Ghebre, Rahel; Le, Chap; Jang, Yoo Jeong; Sharratt, Monica; Yee, Douglas

    2017-11-07

    Despite the increasing breast cancer incidence and mortality rates, Korean American immigrant women have one of the lowest rates of breast cancer screening across racial groups in the United States. Mobile health (mHealth), defined as the delivery of health care information or services through mobile communication devices, has been utilized to successfully improve a variety of health outcomes. This study adapted the principles of mHealth to advance breast cancer prevention efforts among Korean American immigrant women, an underserved community. Using a randomized controlled trial design, 120 Korean American women aged 40 to 77 years were recruited and randomly assigned to either the mMammogram intervention group (n=60) to receive culturally and personally tailored multilevel and multimedia messages through a mobile phone app along with health navigator services or the usual care control group (n=60) to receive a printed brochure. Outcome measures included knowledge, attitudes, and beliefs about breast cancer screening, readiness for mammography, and mammogram receipt. The feasibility and acceptability of the mMammogram intervention was also assessed. The intervention group showed significantly greater change on scores of knowledge of breast cancer and screening guidelines (P=.01). The intervention group also showed significantly greater readiness for mammography use after the intervention compared with the control group. A significantly higher proportion of women who received the mMammogram intervention (75%, 45/60) completed mammograms by the 6-month follow-up compared with the control group (30%, 18/60; Pservice was a feasible, acceptable, and effective intervention mechanism to promote breast cancer screening in Korean American immigrant women. A flexible, easily tailored approach that relies on recent technological advancements can reach underserved and hard-to-recruit populations that bear disproportionate cancer burdens. Clinicaltrials.gov NCT01972048;

  10. Screening Children for Family Violence: A Review of the Evidence for the US Preventive Services Task Force

    Science.gov (United States)

    Nygren, Peggy; Nelson, Heidi D.; Klein, Jonathan

    2004-01-01

    BACKGROUND We wanted to evaluate the benefits and harms of screening children in primary health care settings for abuse and neglect resulting from family violence by examining the evidence on the performance of screening instruments and the effectiveness of interventions. METHODS We searched for relevant studies in MEDLINE, PsycINFO, CINAHL, ERIC, Cochrane Controlled Trials Register, and reference lists. English language abstracts with original data about family violence against children focusing on screening and interventions initiated or based in health care settings were included. We extracted selected information about study design, patient populations and settings, methods of assessment or intervention, and outcome measures, and applied a set of criteria to evaluate study quality. RESULTS All instruments designed to screen for child abuse and neglect were directed to parents, particularly pregnant women. These instruments had fairly high sensitivity but low specificity when administered in high-risk study populations and have not been widely tested in other populations. Randomized controlled trials of frequent nurse home visitation programs beginning during pregnancy that address behavioral and psychological factors indicated improved abuse measures and outcomes. No studies were identified about interventions in older children or harms associated with screening and intervention. CONCLUSIONS No trials of the effectiveness of screening in a health care setting have been published. Clinician referrals to nurse home visitation during pregnancy and in early childhood may reduce abuse in selected populations. There are no studies about harms of screening and interventions. PMID:15083858

  11. The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds.

    Science.gov (United States)

    C Kitchener, Henry; Canfell, Karen; Gilham, Clare; Sargent, Alexandra; Roberts, Chris; Desai, Mina; Peto, Julian

    2014-04-01

    The ARTISTIC (A Randomised Trial In Screening To Improve Cytology) trial originally reported after two rounds of primary cervical screening with human papillomavirus (HPV). Extended follow-up of the randomised trial cohort through a third round could provide valuable insight into the duration of protection of a negative HPV test, which could allow extended screening intervals. If HPV primary screening is to be considered in the national programme, then determining its cost-effectiveness is key, and a detailed economic analysis using ARTISTIC data is needed. (1) To determine the round 3 and cumulative rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (2+) and CIN grade 3 or worse (CIN3+) between the revealed and concealed arms of ARTISTIC after three screening rounds over 6 years. (2) To compare the cumulative incidence of CIN2+ over three screening rounds following negative screening cytology with that following negative baseline HPV. (3) To determine whether or not HPV screening could safely extend the screening interval from 3 to 6 years. (4) To study the potential clinical utility of an increased cut-off of 2 relative light unit/mean control (RLU/Co) for Hybrid Capture 2 (HC2) and HPV genotyping in primary cervical screening. (5) To determine the potential impact of HPV vaccination with Cervarix™ in terms of preventing abnormal cytology and CIN2+. (6) To determine the cost-effectiveness of HPV primary screening compared with current practice using cervical cytology in England. The ARTISTIC study cohort was recalled for a third round of screening 3 years after round 2 and 6 years following their enrolment to the study. Both arms of the original trial used a single protocol during round 3. ARTISTIC study cohort undergoing cervical screening in primary care in Greater Manchester, UK. Between July 2007 and September 2009, 8873 women participated in round 3; 6337 had been screened in round 2 and 2536 had not been screened since round 1. All women

  12. Group sequential and confirmatory adaptive designs in clinical trials

    CERN Document Server

    Wassmer, Gernot

    2016-01-01

    This book provides an up-to-date review of the general principles of and techniques for confirmatory adaptive designs. Confirmatory adaptive designs are a generalization of group sequential designs. With these designs, interim analyses are performed in order to stop the trial prematurely under control of the Type I error rate. In adaptive designs, it is also permissible to perform a data-driven change of relevant aspects of the study design at interim stages. This includes, for example, a sample-size reassessment, a treatment-arm selection or a selection of a pre-specified sub-population. Essentially, this adaptive methodology was introduced in the 1990s. Since then, it has become popular and the object of intense discussion and still represents a rapidly growing field of statistical research. This book describes adaptive design methodology at an elementary level, while also considering designing and planning issues as well as methods for analyzing an adaptively planned trial. This includes estimation methods...

  13. Clinical Trial Design for HIV Prevention Research: Determining Standards of Prevention.

    Science.gov (United States)

    Dawson, Liza; Zwerski, Sheryl

    2015-06-01

    This article seeks to advance ethical dialogue on choosing standards of prevention in clinical trials testing improved biomedical prevention methods for HIV. The stakes in this area of research are high, given the continued high rates of infection in many countries and the budget limitations that have constrained efforts to expand treatment for all who are currently HIV-infected. New prevention methods are still needed; at the same time, some existing prevention and treatment interventions have been proven effective but are not yet widely available in the countries where they most urgently needed. The ethical tensions in this field of clinical research are well known and have been the subject of extensive debate. There is no single clinical trial design that can optimize all the ethically important goals and commitments involved in research. Several recent articles have described the current ethical difficulties in designing HIV prevention trials, especially in resource limited settings; however, there is no consensus on how to handle clinical trial design decisions, and existing international ethical guidelines offer conflicting advice. This article acknowledges these deep ethical dilemmas and moves beyond a simple descriptive approach to advance an organized method for considering what clinical trial designs will be ethically acceptable for HIV prevention trials, balancing the relevant criteria and providing justification for specific design decisions. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  14. Investigating Effects of Screen Layout Elements on Interface and Screen Design Aesthetics

    OpenAIRE

    Altaboli, Ahamed; Lin, Yingzi

    2011-01-01

    A recent study suggested the use of the screen layout elements of balance, unity, and sequence as a part of a computational model of interface aesthetics. It is argued that these three elements are the most contributed terms in the model. In the current study, a controlled experiment was designed and conducted to systematically investigate effects of these three elements (balance, unity, and sequence) on the perceived interface aesthetics. Results showed that the three elements have signific...

  15. Gestalt Theory in Visual Screen Design — A New Look at an old subject

    OpenAIRE

    Chang, D.; Dooley, L.; Tuovinen, J. E

    2002-01-01

    Although often presented as a single basis for educational visual screen design, Gestalt theory is not a single small set of visual principles uniformly applied by all designers. In fact, it appears that instructional visual design literature often deals with only a small set of Gestalt laws. In this project Gestalt literature was consulted to distil the most relevant Gestalt laws for educational visual screen design. Eleven laws were identified. They deal with balance/symmetry, continuation,...

  16. Induced Polarization Surveying for Acid Rock Screening in Highway Design

    Science.gov (United States)

    Butler, K. E.; Al, T.; Bishop, T.

    2004-05-01

    Highway and pipeline construction agencies have become increasingly vigilant in their efforts to avoid cutting through sulphide-bearing bedrock that has potential to produce acid rock drainage. Blasting and fragmentation of such rock increases the surface area available for sulphide oxidation and hence increases the risk of acid rock drainage unless the rock contains enough natural buffering capacity to neutralize the pH. In December, 2001, the New Brunswick Department of Transportation (NBOT) sponsored a field trial of geophysical surveying in order to assess its suitability as a screening tool for locating near-surface sulphides along proposed highway alignments. The goal was to develop a protocol that would allow existing programs of drilling and geochemical testing to be targeted more effectively, and provide design engineers with the information needed to reduce rock cuts where necessary and dispose of blasted material in a responsible fashion. Induced polarization (IP) was chosen as the primary geophysical method given its ability to detect low-grade disseminated mineralization. The survey was conducted in dipole-dipole mode using an exploration-style time domain IP system, dipoles 8 to 25 m in length, and six potential dipoles for each current dipole location (i.e. n = 1 - 6). Supplementary information was provided by resistivity and VLF-EM surveys sensitive to lateral changes in electrical conductivity, and by magnetic field surveying chosen for its sensitivity to the magnetic susceptibility of pyrrhotite. Geological and geochemical analyses of samples taken from several IP anomalies located along 4.3 line-km of proposed highway confirmed the effectiveness of the screening technique. IP pseudosections from a region of metamorphosed shales and volcaniclastic rocks identified discrete, well-defined mineralized zones. Stronger, overlapping, and more laterally extensive IP anomalies were observed over a section of graphitic and sulphide-bearing metasedimentary

  17. Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

    Science.gov (United States)

    Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

    2016-12-01

    This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical

  18. Design of clinical trials involving multiple hypothesis tests with a common control.

    Science.gov (United States)

    Schou, I Manjula; Marschner, Ian C

    2017-07-01

    Randomized clinical trials comparing several treatments to a common control are often reported in the medical literature. For example, multiple experimental treatments may be compared with placebo, or in combination therapy trials, a combination therapy may be compared with each of its constituent monotherapies. Such trials are typically designed using a balanced approach in which equal numbers of individuals are randomized to each arm, however, this can result in an inefficient use of resources. We provide a unified framework and new theoretical results for optimal design of such single-control multiple-comparator studies. We consider variance optimal designs based on D-, A-, and E-optimality criteria, using a general model that allows for heteroscedasticity and a range of effect measures that include both continuous and binary outcomes. We demonstrate the sensitivity of these designs to the type of optimality criterion by showing that the optimal allocation ratios are systematically ordered according to the optimality criterion. Given this sensitivity to the optimality criterion, we argue that power optimality is a more suitable approach when designing clinical trials where testing is the objective. Weighted variance optimal designs are also discussed, which, like power optimal designs, allow the treatment difference to play a major role in determining allocation ratios. We illustrate our methods using two real clinical trial examples taken from the medical literature. Some recommendations on the use of optimal designs in single-control multiple-comparator trials are also provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The Relations Between False Positive and Negative Screens and Smoking Cessation and Relapse in the National Lung Screening Trial: Implications for Public Health.

    Science.gov (United States)

    Clark, Melissa A; Gorelick, Jeremy J; Sicks, JoRean D; Park, Elyse R; Graham, Amanda L; Abrams, David B; Gareen, Ilana F

    2016-01-01

    Lung screening is an opportunity for smoking cessation and relapse prevention, but smoking behaviors may differ across screening results. Changes in smoking were evaluated among 18 840 current and former smokers aged 55-74 scheduled to receive three annual lung screenings. Participants were randomized to low-dose computed tomography or single-view chest radiography in the American College of Radiology/National Lung Screening Trial. Outcome measures included point and sustained (6-month) abstinence and motivation to quit among smokers; and relapse among smokers who quit during follow-up, recent quitters (quit < 6 months), and long-term former smokers (quit ≥ 6 months). During five years of follow-up, annual point prevalence quit rates ranged from 11.6%-13.4%; 48% of current smokers reported a quit attempt and 7% of long-term former smokers relapsed. Any false positive screening result was associated with subsequent increased point (multivariable hazard ratio HR = 1.23, 95% CI = 1.13, 1.35) and sustained (HR = 1.28, 95% CI = 1.15, 1.43) abstinence among smokers. Recent quitters with ≥1 false positive screen were less likely to relapse (HR = 0.72, 95% CI = 0.54, 0.96). Screening result was not associated with relapse among long-term former smokers or among baseline smokers who quit during follow-up. A false positive screen was associated with increased smoking cessation and less relapse among recent quitters. Consistently negative screens were not associated with greater relapse among long-term former smokers. Given the Affordable Care Act requires most health plans to cover smoking cessation and lung screening, the impact and cost-effectiveness of lung screening could be further enhanced with the addition of smoking cessation interventions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial.

    Science.gov (United States)

    Simmons, Rebecca K; Echouffo-Tcheugui, Justin B; Sharp, Stephen J; Sargeant, Lincoln A; Williams, Kate M; Prevost, A Toby; Kinmonth, Ann Louise; Wareham, Nicholas J; Griffin, Simon J

    2012-11-17

    The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, uncertainty persists around the benefits of screening for type 2 diabetes. We assessed the effect of a population-based stepwise screening programme on mortality. In a pragmatic parallel group, cluster-randomised trial, 33 general practices in eastern England were randomly assigned by the method of minimisation in an unbalanced design to: screening followed by intensive multifactorial treatment for people diagnosed with diabetes (n=15); screening plus routine care of diabetes according to national guidelines (n=13); and a no-screening control group (n=5). The study population consisted of 20,184 individuals aged 40-69 years (mean 58 years), at high risk of prevalent undiagnosed diabetes, on the basis of a previously validated risk score. In screening practices, individuals were invited to a stepwise programme including random capillary blood glucose and glycated haemoglobin (HbA(1c)) tests, a fasting capillary blood glucose test, and a confirmatory oral glucose tolerance test. The primary outcome was all-cause mortality. All participants were flagged for mortality surveillance by the England and Wales Office of National Statistics. Analysis was by intention-to-screen and compared all-cause mortality rates between screening and control groups. This study is registered, number ISRCTN86769081. Of 16,047 high-risk individuals in screening practices, 15,089 (94%) were invited for screening during 2001-06, 11,737 (73%) attended, and 466 (3%) were diagnosed with diabetes. 4137 control individuals were followed up. During 184,057 person-years of follow up (median duration 9·6 years [IQR 8·9-9·9]), there were 1532 deaths in the screening practices and 377 in control practices (mortality hazard ratio [HR] 1·06, 95% CI 0·90-1·25). We noted no significant reduction in

  1. Mobile applications for handheld devices to screen and randomize acute stroke patients in clinical trials.

    Science.gov (United States)

    Qureshi, Ai; Connelly, B; Abbott, Ei; Maland, E; Kim, J; Blake, J

    2012-08-01

    The availability of internet connectivity and mobile application software used by low-power handheld devices makes smart phones of unique value in time-sensitive clinical trials. Trial-specific applications can be downloaded by investigators from various mobile software distribution platforms or web applications delivered over HTTP. The Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) II investigators in collaboration with MentorMate released the ATACH-II Patient Recruitment mobile application available on iPhone, Android, and Blackberry in 2011. The mobile application provides tools for pre-screening, assessment of eligibility, and randomization of patients. Since the release of ATACH-II mobile application, the CLEAR-IVH (Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage) trial investigators have also adopted such a mobile application. The video-conferencing capabilities of the most recent mobile devices open up additional opportunities to involve central coordinating centers in the recruitment process in real time.

  2. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials

    DEFF Research Database (Denmark)

    Savović, Jelena; Jones, Hayley E; Altman, Douglas G

    2012-01-01

    bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design...... characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes....

  3. Incremental Costs and Cost Effectiveness of Intensive Treatment in Individuals with Type 2 Diabetes Detected by Screening in the ADDITION-UK Trial: An Update with Empirical Trial-Based Cost Data.

    Science.gov (United States)

    Laxy, Michael; Wilson, Edward C F; Boothby, Clare E; Griffin, Simon J

    2017-12-01

    There is uncertainty about the cost effectiveness of early intensive treatment versus routine care in individuals with type 2 diabetes detected by screening. To derive a trial-informed estimate of the incremental costs of intensive treatment as delivered in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Europe (ADDITION) trial and to revisit the long-term cost-effectiveness analysis from the perspective of the UK National Health Service. We analyzed the electronic primary care records of a subsample of the ADDITION-Cambridge trial cohort (n = 173). Unit costs of used primary care services were taken from the published literature. Incremental annual costs of intensive treatment versus routine care in years 1 to 5 after diagnosis were calculated using multilevel generalized linear models. We revisited the long-term cost-utility analyses for the ADDITION-UK trial cohort and reported results for ADDITION-Cambridge using the UK Prospective Diabetes Study Outcomes Model and the trial-informed cost estimates according to a previously developed evaluation framework. Incremental annual costs of intensive treatment over years 1 to 5 averaged £29.10 (standard error = £33.00) for consultations with general practitioners and nurses and £54.60 (standard error = £28.50) for metabolic and cardioprotective medication. For ADDITION-UK, over the 10-, 20-, and 30-year time horizon, adjusted incremental quality-adjusted life-years (QALYs) were 0.014, 0.043, and 0.048, and adjusted incremental costs were £1,021, £1,217, and £1,311, resulting in incremental cost-effectiveness ratios of £71,232/QALY, £28,444/QALY, and £27,549/QALY, respectively. Respective incremental cost-effectiveness ratios for ADDITION-Cambridge were slightly higher. The incremental costs of intensive treatment as delivered in the ADDITION-Cambridge trial were lower than expected. Given UK willingness-to-pay thresholds in patients with screen

  4. Design and protocol of a randomized multiple behavior change trial: Make Better Choices 2 (MBC2).

    Science.gov (United States)

    Pellegrini, Christine A; Steglitz, Jeremy; Johnston, Winter; Warnick, Jennifer; Adams, Tiara; McFadden, H G; Siddique, Juned; Hedeker, Donald; Spring, Bonnie

    2015-03-01

    Suboptimal diet and inactive lifestyle are among the most prevalent preventable causes of premature death. Interventions that target multiple behaviors are potentially efficient; however the optimal way to initiate and maintain multiple health behavior changes is unknown. The Make Better Choices 2 (MBC2) trial aims to examine whether sustained healthful diet and activity change are best achieved by targeting diet and activity behaviors simultaneously or sequentially. Study design approximately 250 inactive adults with poor quality diet will be randomized to 3 conditions examining the best way to prescribe healthy diet and activity change. The 3 intervention conditions prescribe: 1) an increase in fruit and vegetable consumption (F/V+), decrease in sedentary leisure screen time (Sed-), and increase in physical activity (PA+) simultaneously (Simultaneous); 2) F/V+ and Sed- first, and then sequentially add PA+ (Sequential); or 3) Stress Management Control that addresses stress, relaxation, and sleep. All participants will receive a smartphone application to self-monitor behaviors and regular coaching calls to help facilitate behavior change during the 9 month intervention. Healthy lifestyle change in fruit/vegetable and saturated fat intakes, sedentary leisure screen time, and physical activity will be assessed at 3, 6, and 9 months. MBC2 is a randomized m-Health intervention examining methods to maximize initiation and maintenance of multiple healthful behavior changes. Results from this trial will provide insight about an optimal technology supported approach to promote improvement in diet and physical activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial.

    Science.gov (United States)

    Hugosson, Jonas; Carlsson, Sigrid; Aus, Gunnar; Bergdahl, Svante; Khatami, Ali; Lodding, Pär; Pihl, Carl-Gustaf; Stranne, Johan; Holmberg, Erik; Lilja, Hans

    2010-08-01

    Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. In December, 1994, 20,000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10,000) or to a control group not invited (n=10,000). Men in the screening group were invited up to the upper age limit (median 69, range 67-71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243. In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12.7% in the screening group and 8.2% in the control group (hazard ratio 1.64; 95% CI 1.50-1.80; pattendees compared with the control group was 0.44 (95% CI 0.28-0.68; p=0.0002). Overall, 293 (95% CI 177-799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. This study shows that prostate

  6. A Comparison Study of Second-Order Screening Designs and Their Extension

    Science.gov (United States)

    2013-12-01

    H2 97 V. Nonlinear Screening Designs for Defense Testing: An Overview and Case Study 5.1 Introduction “Necessity is the Mother of Invention.” Plato is...involved concepts like design resolution, minimum aber- ration , power, the number of clear (non-confounded) effects, concepts like rotatability

  7. Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts: Interim Report of a Prospective Comparative Trial.

    Science.gov (United States)

    Tagliafico, Alberto S; Calabrese, Massimo; Mariscotti, Giovanna; Durando, Manuela; Tosto, Simona; Monetti, Francesco; Airaldi, Sonia; Bignotti, Bianca; Nori, Jacopo; Bagni, Antonella; Signori, Alessio; Sormani, Maria Pia; Houssami, Nehmat

    2016-03-09

    Debate on adjunct screening in women with dense breasts has followed legislation requiring that women be informed about their mammographic density and related adjunct imaging. Ultrasound or tomosynthesis can detect breast cancer (BC) in mammography-negative dense breasts, but these modalities have not been directly compared in prospective trials. We conducted a trial of adjunct screening to compare, within the same participants, incremental BC detection by tomosynthesis and ultrasound in mammography-negative dense breasts. Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts is a prospective multicenter study recruiting asymptomatic women with mammography-negative screens and dense breasts. Eligible women had tomosynthesis and physician-performed ultrasound with independent interpretation of adjunct imaging. Outcome measures included cancer detection rate (CDR), number of false-positive (FP) recalls, and incremental CDR for each modality; these were compared using McNemar's test for paired binary data in a preplanned interim analysis. Among 3,231 mammography-negative screening participants (median age, 51 years; interquartile range, 44 to 78 years) with dense breasts, 24 additional BCs were detected (23 invasive): 13 tomosynthesis-detected BCs (incremental CDR, 4.0 per 1,000 screens; 95% CI, 1.8 to 6.2) versus 23 ultrasound-detected BCs (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.2 to 10.0), P = .006. Incremental FP recall occurred in 107 participants (3.33%; 95% CI, 2.72% to 3.96%). FP recall (any testing) did not differ between tomosynthesis (FP = 53) and ultrasound (FP = 65), P = .26; FP recall (biopsy) also did not differ between tomosynthesis (FP = 22) and ultrasound (FP = 24), P = .86. The Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts' interim analysis shows that ultrasound has better incremental BC detection than tomosynthesis in mammography

  8. Informed choice about Down syndrome screening

    DEFF Research Database (Denmark)

    Skjøth, Mette Maria; Draborg, Eva; Lamont, Ronald Francis

    2015-01-01

    INTRODUCTION: The aim of this study was to evaluate the effect of an eHealth intervention (interactive website) on pregnant women's ability to make an informed choice about Down syndrome screening. MATERIAL AND METHODS: The study was designed as a randomized controlled trial with allocation...... to an intervention group and a control group in a ratio of 1:1. Subsequent subgroup analysis was conducted. Participants were recruited from 5 August 2013 to 25 April 2014 at Odense University Hospital, Denmark. Inclusion criteria were: pregnant women aged ≥18 years who were invited to participate in Down syndrome...... screening. Exclusion criteria were: high risk of abortion, psycho-socially vulnerable women, late referral, inability to speak Danish and women declining to participate. The primary outcome was informed choice about Down syndrome screening. The Multidimensional Measure of Informed Choice was used to assess...

  9. When ethics constrains clinical research: trial design of control arms in "greater than minimal risk" pediatric trials.

    Science.gov (United States)

    de Melo-Martín, Inmaculada; Sondhi, Dolan; Crystal, Ronald G

    2011-09-01

    For more than three decades clinical research in the United States has been explicitly guided by the idea that ethical considerations must be central to research design and practice. In spite of the centrality of this idea, attempting to balance the sometimes conflicting values of advancing scientific knowledge and protecting human subjects continues to pose challenges. Possible conflicts between the standards of scientific research and those of ethics are particularly salient in relation to trial design. Specifically, the choice of a control arm is an aspect of trial design in which ethical and scientific issues are deeply entwined. Although ethical quandaries related to the choice of control arms may arise when conducting any type of clinical trials, they are conspicuous in early phase gene transfer trials that involve highly novel approaches and surgical procedures and have children as the research subjects. Because of children's and their parents' vulnerabilities, in trials that investigate therapies for fatal, rare diseases affecting minors, the scientific and ethical concerns related to choosing appropriate controls are particularly significant. In this paper we use direct gene transfer to the central nervous system to treat late infantile neuronal ceroid lipofuscinosis to illustrate some of these ethical issues and explore possible solutions to real and apparent conflicts between scientific and ethical considerations.

  10. Ethical considerations of neuro-oncology trial design in the era of precision medicine.

    Science.gov (United States)

    Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

    2017-08-01

    The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

  11. Sequential, Multiple Assignment, Randomized Trial Designs in Immuno-oncology Research.

    Science.gov (United States)

    Kidwell, Kelley M; Postow, Michael A; Panageas, Katherine S

    2018-02-15

    Clinical trials investigating immune checkpoint inhibitors have led to the approval of anti-CTLA-4 (cytotoxic T-lymphocyte antigen-4), anti-PD-1 (programmed death-1), and anti-PD-L1 (PD-ligand 1) drugs by the FDA for numerous tumor types. In the treatment of metastatic melanoma, combinations of checkpoint inhibitors are more effective than single-agent inhibitors, but combination immunotherapy is associated with increased frequency and severity of toxicity. There are questions about the use of combination immunotherapy or single-agent anti-PD-1 as initial therapy and the number of doses of either approach required to sustain a response. In this article, we describe a novel use of sequential, multiple assignment, randomized trial (SMART) design to evaluate immune checkpoint inhibitors to find treatment regimens that adapt within an individual based on intermediate response and lead to the longest overall survival. We provide a hypothetical example SMART design for BRAF wild-type metastatic melanoma as a framework for investigating immunotherapy treatment regimens. We compare implementing a SMART design to implementing multiple traditional randomized clinical trials. We illustrate the benefits of a SMART over traditional trial designs and acknowledge the complexity of a SMART. SMART designs may be an optimal way to find treatment strategies that yield durable response, longer survival, and lower toxicity. Clin Cancer Res; 24(4); 730-6. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Design and evaluation of new overview screens for the LABIHS simulator

    International Nuclear Information System (INIS)

    Oliveira, Mauro V.; Almeida, Jose C.S.; Jaime, Guilherme D.G.; Augusto, Silas C.

    2015-01-01

    The development and evaluation of Human-System Interfaces (HSIs) for control rooms is a research area at the Human-System Interface Laboratory (LABIHS). The main objective of this laboratory is to develop and evaluate projects of HSIs for industrial plants using different methodology construction. The evaluation of the interfaces is carried out in the LABIHS simulator at the Nuclear Engineering Institute (IEN). Previous evaluation of the overview screen of the nuclear power plant (NPP) simulator of the LABIHS showed the necessity of additional information to reduce the operator workload. To overcome this issue, a set of three 52-inch LCD TV was acquired to replace the projector in the task of showing the overview screen to the simulator operators. A new set of screens was developed to gather information in the three LCD screens. The approach used on the development of the new screens was based on human factors guidelines and recommendations. The objective of this work is present the design of these new overview screens and to evaluate their contribution to reduce the operators mental workload in this new scenario. (author)

  13. Placebo effect in clinical trial design for irritable bowel syndrome.

    Science.gov (United States)

    Shah, Eric; Pimentel, Mark

    2014-04-30

    Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various ap-proaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.

  14. Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial (SPRINT)

    Science.gov (United States)

    Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

    2016-01-01

    Background The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter, randomized clinical trial of 9,361 participants with hypertension who are ≥ 50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal recruitment strategies and lessons learned during recruitment of the SPRINT cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥ 75 years, women, and minorities. Methods In collaboration with the National Institutes of Health Project Office and SPRINT Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began November 8, 2010 and ended March 15, 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Results Recruitment was scheduled to last 24 months to enroll a target of 9,250 participants; in just over 28 months, the trial enrolled 9,361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by SPRINT staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized /number screened) was 64% (9,361 randomized /14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those age ≥ 75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional clinics were included and inclusion criteria were broadened, keeping event rates

  15. Direct mailing was a successful recruitment strategy for a lung-cancer screening trial.

    Science.gov (United States)

    Hinshaw, Lisa B; Jackson, Sharon A; Chen, Michael Y

    2007-08-01

    To analyze advertising, recruitment methods, and study participant demographics for the National Lung Screening Trial (NLST) site at Wake Forest University School of Medicine to define efficient ways to recruit participants for general clinical trials. Recruitment method data, demographics, geographic location, and date of enrollment were collected from all 1,112 NLST participants. Marketing data and financial records were analyzed to determine the effectiveness of each recruitment method. The total amount spent on advertising was $144,668, with the cost of enrollment per participant averaging $130. For black participants, the recruitment cost per person was $406, whereas for white and other race participants, the cost was $122 (PTV ads cost $382 per participant. Direct mailing to a targeted group was the most efficient way to recruit participants. Printed advertising methods, that is, newspaper ads and brochures, were quite effective, whereas television ads were expensive. Appropriate minority recruitment needs sufficient attention and resources to ensure census groups are adequately represented.

  16. Screening and Brief Interventions for Hazardous and Harmful Alcohol Use among University Students in South Africa: Results from a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hendry van der Heever

    2013-05-01

    Full Text Available The aim of this study was to assess the effectiveness of Screening and Brief Intervention (SBI for alcohol problems among university students in South Africa. The study design for this efficacy study is a randomized controlled trial with 6- and 12-month follow-ups to examine the effects of a brief alcohol intervention to reduce alcohol use by hazardous and harmful drinkers in a university setting. The unit of randomization is the individual university student identified as a hazardous or harmful drinker attending public recruitment venues in a university campus. University students were screened for alcohol problems, and those identified as hazardous or harmful drinkers were randomized into an experimental or control group. The experimental group received one brief counseling session on alcohol risk reduction, while the control group received a health education leaflet. Results indicate that of the 722 screened for alcohol and who agreed to participate in the trial 152 (21.1% tested positive for the Alcohol Use Disorder Identification Test (AUDIT (score 8 or more. Among the 147 (96.7% university students who also attended the 12-month follow-up session, the intervention effect on the AUDIT score was −1.5, which was statistically significant (P = 0.009. Further, the depression scores marginally significantly decreased over time across treatment groups, while other substance use (tobacco and cannabis use, self-rated health status and Posttraumatic Stress Disorder (PTSD scores did not change over time across treatment groups. The study provides evidence of effective brief intervention by assistant nurses with hazardous and harmful drinkers in a university setting in South Africa. The short duration of the brief intervention makes it a realistic candidate for use in a university setting.

  17. A cluster randomized trial of strategies to increase uptake amongst young women invited for their first cervical screen: The STRATEGIC trial.

    Science.gov (United States)

    Kitchener, H; Gittins, M; Cruickshank, M; Moseley, C; Fletcher, S; Albrow, R; Gray, A; Brabin, L; Torgerson, D; Crosbie, E J; Sargent, A; Roberts, C

    2018-06-01

    Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation. Results Phase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69-2.53, p < 0.001). Phase 2 randomized 10,126 non-attenders, with 32-34 clusters for each intervention and 100 clusters as controls. Sending self-sample kits increased uptake at 12 months (OR 1.51, 95% CI 1.20-1.91, p = 0.001), as did timed appointments (OR 1.41, 95% CI 1.14-1.74, p = 0.001). The offer of a nurse navigator, a self-sample kits on request, and choice between timed appointments and nurse navigator were ineffective. Conclusions Amongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake.

  18. Is the screening of product ideas supported by the NPD process design?

    DEFF Research Database (Denmark)

    Jespersen, Kristina Risom

    2007-01-01

    literature will benefit from knowledge of the process of implementing "best practices" of NPD. Companies follow guidelines, but how is the NPD process followed through? This paper supports the need for improved insight into the complexity of screening decisions as well as knowledge of the screening...... determinants. Practical implications - The implementation of cross-functional teams and interacting phases demands more attention by management in order to reduce costs of NPD relative to the ROI of new products. Originality/value - By showing that the screening is detached from the NPD process design...

  19. Explanatory Versus Pragmatic Trials: An Essential Concept in Study Design and Interpretation.

    Science.gov (United States)

    Merali, Zamir; Wilson, Jefferson R

    2017-11-01

    Randomized clinical trials often represent the highest level of clinical evidence available to evaluate the efficacy of an intervention in clinical medicine. Although the process of randomization serves to maximize internal validity, the external validity, or generalizability, of such studies depends on several factors determined at the design phase of the trial including eligibility criteria, study setting, and outcomes of interest. In general, explanatory trials are optimized to demonstrate the efficacy of an intervention in a highly selected patient group; however, findings from these studies may not be generalizable to the larger clinical problem. In contrast, pragmatic trials attempt to understand the real-world benefit of an intervention by incorporating design elements that allow for greater generalizability and clinical applicability of study results. In this article we describe the explanatory-pragmatic continuum for clinical trials in greater detail. Further, a well-accepted tool for grading trials on this continuum is described, and applied, to 2 recently published trials pertaining to the surgical management of lumbar degenerative spondylolisthesis.

  20. Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial.

    Science.gov (United States)

    Maldonado, Fabien; Duan, Fenghai; Raghunath, Sushravya M; Rajagopalan, Srinivasan; Karwoski, Ronald A; Garg, Kavita; Greco, Erin; Nath, Hrudaya; Robb, Richard A; Bartholmai, Brian J; Peikert, Tobias

    2015-09-15

    Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

  1. Real-Time Enrollment Dashboard For Multisite Clinical Trials.

    Science.gov (United States)

    Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio

    2015-10-30

    Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system.

  2. poolHiTS: A Shifted Transversal Design based pooling strategy for high-throughput drug screening

    Directory of Open Access Journals (Sweden)

    Woolf Peter J

    2008-05-01

    Full Text Available Abstract Background A key goal of drug discovery is to increase the throughput of small molecule screens without sacrificing screening accuracy. High-throughput screening (HTS in drug discovery involves testing a large number of compounds in a biological assay to identify active compounds. Normally, molecules from a large compound library are tested individually to identify the activity of each molecule. Usually a small number of compounds are found to be active, however the presence of false positive and negative testing errors suggests that this one-drug one-assay screening strategy can be significantly improved. Pooling designs are testing schemes that test mixtures of compounds in each assay, thereby generating a screen of the whole compound library in fewer tests. By repeatedly testing compounds in different combinations, pooling designs also allow for error-correction. These pooled designs, for specific experiment parameters, can be simply and efficiently created using the Shifted Transversal Design (STD pooling algorithm. However, drug screening contains a number of key constraints that require specific modifications if this pooling approach is to be useful for practical screen designs. Results In this paper, we introduce a pooling strategy called poolHiTS (Pooled High-Throughput Screening which is based on the STD algorithm. In poolHiTS, we implement a limit on the number of compounds that can be mixed in a single assay. In addition, we show that the STD-based pooling strategy is limited in the error-correction that it can achieve. Due to the mixing constraint, we show that it is more efficient to split a large library into smaller blocks of compounds, which are then tested using an optimized strategy repeated for each block. We package the optimal block selection algorithm into poolHiTS. The MATLAB codes for the poolHiTS algorithm and the corresponding decoding strategy are also provided. Conclusion We have produced a practical version

  3. Randomized Controlled Trials in Music Therapy: Guidelines for Design and Implementation.

    Science.gov (United States)

    Bradt, Joke

    2012-01-01

    Evidence from randomized controlled trials (RCTs) plays a powerful role in today's healthcare industry. At the same time, it is important that multiple types of evidence contribute to music therapy's knowledge base and that the dialogue of clinical effectiveness in music therapy is not dominated by the biomedical hierarchical model of evidence-based practice. Whether or not one agrees with the hierarchical model of evidence in the current healthcare climate, RCTs can contribute important knowledge to our field. Therefore, it is important that music therapists are prepared to design trials that meet current methodological standards and, equally important, are able to respond appropriately to those design aspects that may not be feasible in music therapy research. To provide practical guidelines to music therapy researchers for the design and implementation of RCTs as well as to enable music therapists to be well-informed consumers of RCT evidence. This article reviews key design aspects of RCTs and discusses how to best implement these standards in music therapy trials. A systematic presentation of basic randomization methods, allocation concealment strategies, issues related to blinding in music therapy trials and strategies for implementation, the use of treatment manuals, types of control groups, outcome selection, and sample size computation is provided. Despite the challenges of meeting all key design demands typical of an RCT, it is possible to design rigorous music therapy RCTs that accurately estimate music therapy treatment benefits.

  4. Risk Stratification and Shared Decision Making for Colorectal Cancer Screening: A Randomized Controlled Trial.

    Science.gov (United States)

    Schroy, Paul C; Duhovic, Emir; Chen, Clara A; Heeren, Timothy C; Lopez, William; Apodaca, Danielle L; Wong, John B

    2016-05-01

    Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer (CRC) screening, yet providers often fail to comply with patient preferences that differ from their own. To determine whether risk stratification for advanced colorectal neoplasia (ACN) influences provider willingness to comply with patient preferences when selecting a desired CRC screening option. Randomized controlled trial. Asymptomatic, average-risk patients due for CRC screening in an urban safety net health care setting. Patients were randomized 1:1 to a decision aid alone (n= 168) or decision aid plus risk assessment (n= 173) arm between September 2012 and September 2014. The primary outcome was concordance between patient preference and test ordered; secondary outcomes included patient satisfaction with the decision-making process, screening intentions, test completion rates, and provider satisfaction. Although providers perceived risk stratification to be useful in selecting an appropriate screening test for their average-risk patients, no significant differences in concordance were observed between the decision aid alone and decision aid plus risk assessment groups (88.1% v. 85.0%,P= 0.40) or high- and low-risk groups (84.5% v. 87.1%,P= 0.51). Concordance was highest for colonoscopy and relatively low for tests other than colonoscopy, regardless of study arm or risk group. Failure to comply with patient preferences was negatively associated with satisfaction with the decision-making process, screening intentions, and test completion rates. Single-institution setting; lack of provider education about the utility of risk stratification into their decision making. Providers perceived risk stratification to be useful in their decision making but often failed to comply with patient preferences for tests other than colonoscopy, even among those deemed to be at low risk of ACN. © The Author(s) 2016.

  5. Tribulations of a prostate cancer trial - lessons learned from TOAD, a cancer council Victoria and Transtasman Radiation Oncology Group Trial

    International Nuclear Information System (INIS)

    Duchesne, Gillian M.

    2010-01-01

    Full text: From 2004-2009 a total of 226 out of a target of 750 prostate cancer patients have been randomised into the Timing of Androgen Deprivation trial between immediate and delayed androgen deprivation. A screening log was kept by participating centres for the first 928 patients, which documented the reasons for non-entry into the trial; 42.7% of screened patients were ineligible and a further 33.0% were not entered for other reasons. Fewer than 10% of patients cited not wanting to be part of a clinical trial as a reason for non-entry. Strategies to improve recruitment included broadening the eligibility criteria, encouraging international collaboration, the use and support of research nurses in the private health care environment, and the use of phone follow-up. Recruitment will be completed at the number originally intended to inform the interim analysis designed to test the validity of the statistical assumptions, and a combined survival analysis with the Canadian study is planned.

  6. Universal Screening for Intimate Partner and Sexual Violence in Trauma Patients - What About the Men? An EAST Multicenter Trial.

    Science.gov (United States)

    Zakrison, Tanya L; Rattan, Rishi; Milian Valdés, Davel; Ruiz, Xiomara; Gelbard, Rondi; Cline, John; Turay, David; Luo-Owen, Xian; Namias, Nicholas; George, Jessica; Yeh, Dante; Pust, Daniel; Williams, Brian H

    2018-02-14

    A recent EAST-supported, multicenter trial demonstrated a similar rate of intimate partner and sexual violence (IPSV) between male and female trauma patients, regardless of mechanism. Our objective was to perform a subgroup analysis of our affected male cohort as this remains an understudied group in the trauma literature. We conducted a recent EAST-supported, cross-sectional, multicenter trial over one year (03/15-04/16) involving four Level I trauma centers throughout the United States. We performed universal screening of adult trauma patients using the validated HITS (Hurt, Insult, Threaten, Scream) and SAVE (sexual violence) screening surveys. Risk factors for male patients were identified. Chi-squared test compared categorical variables with significance at p<0.05. Parametric data is presented as mean +/-standard deviation. A total of 2,034 trauma patients were screened, of which 1,281 (63%) were men. Of this cohort, 119 men (9.3%) screened positive for intimate partner violence, 14.1% for IPSV and 6.5% for sexual violence. On categorical analysis of the HITS screen, the proportion of men that were physically hurt was 4.8% compared to 4.3% for women (p = 0.896). A total of 4.8% of men screened positive for both intimate partner and sexual violence. The total proportion of men who presented with any history of intimate partner violence, sexual violence or both (IPSV) was 15.8%. More men affected by penetrating trauma screened positive for IPSV (p < 0.00001). IPSV positivity in men was associated with mental illness, substance abuse, and trauma recidivism. One out of every twenty men that present to trauma centers is a survivor of both intimate partner and sexual violence, with one out of every six men experiencing some form of violence. Men are at similar risk for physical abuse as women when this intimate partner violence occurs. IPSV is associated with penetrating trauma in men. Support programs for this population may potentially impact associated mental

  7. Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

    Science.gov (United States)

    Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C; Farrar, John T; Fillingim, Roger B; Gilron, Ian; Markman, John D; Oaklander, Anne Louise; Polydefkis, Michael J; Raja, Srinivasa N; Robinson, James P; Woolf, Clifford J; Ziegler, Dan; Ashburn, Michael A; Burke, Laurie B; Cowan, Penney; George, Steven Z; Goli, Veeraindar; Graff, Ole X; Iyengar, Smriti; Jay, Gary W; Katz, Joel; Kehlet, Henrik; Kitt, Rachel A; Kopecky, Ernest A; Malamut, Richard; McDermott, Michael P; Palmer, Pamela; Rappaport, Bob A; Rauschkolb, Christine; Steigerwald, Ilona; Tobias, Jeffrey; Walco, Gary A

    2015-07-01

    Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

  8. Innovative approaches to clinical development and trial design

    Directory of Open Access Journals (Sweden)

    John J Orloff

    2011-01-01

    Full Text Available Pharmaceutical innovation is increasingly risky, costly and at times inefficient, which has led to a decline in industry productivity. Despite the increased investment in R&D by the industry, the number of new molecular entities achieving marketing authorization is not increasing. Novel approaches to clinical development and trial design could have a key role in overcoming some of these challenges by improving efficiency and reducing attrition rates. The effectiveness of clinical development can be improved by adopting a more integrated model that increases flexibility and maximizes the use of accumulated knowledge. Central to this model of drug development are novel tools, including modelling and simulation, Bayesian methodologies, and adaptive designs, such as seamless adaptive designs and sample-size re-estimation methods. Applications of these methodologies to early- and late-stage drug development are described with some specific examples, along with advantages, challenges, and barriers to implementation. Because they are so flexible, these new trial designs require significant statistical analyses, simulations and logistical considerations to verify their operating characteristics, and therefore tend to require more time for the planning and protocol development phase. Greater awareness of the distinct advantages of innovative designs by regulators and sponsors are crucial to increasing the adoption of these modern tools.

  9. Community screening for visual impairment in older people.

    Science.gov (United States)

    Clarke, Emily L; Evans, Jennifer R; Smeeth, Liam

    2018-02-20

    Visual problems in older people are common and frequently under-reported. The effects of poor vision in older people are wide reaching and include falls, confusion and reduced quality of life. Much of the visual impairment in older ages can be treated (e.g. cataract surgery, correction of refractive error). Vision screening may therefore reduce the number of older people living with sight loss. The objective of this review was to assess the effects on vision of community vision screening of older people for visual impairment. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 23 November 2017. We included randomised controlled trials (RCTs) that compared vision screening alone or as part of a multi-component screening package as compared to no vision screening or standard care, on the vision of people aged 65 years or over in a community setting. We included trials that used self-reported visual problems or visual acuity testing as the screening tool. We used standard methods expected by Cochrane. We graded the certainty of the evidence using GRADE. Visual outcome data were available for 10,608 people in 10 trials. Four trials took place in the UK, two in Australia, two in the United States and two in the Netherlands. Length of follow-up ranged from one to five years. Three of these studies were cluster-randomised trials whereby general practitioners or family physicians were randomly allocated to undertake vision screening or no vision screening. All studies were funded by government agencies. Overall we judged the studies to be at low risk of bias and only downgraded the certainty of the evidence (GRADE) for imprecision.Seven trials compared vision screening as part of a multi-component screening versus no screening. Six of these studies used self

  10. Pediatric-based intervention to motivate mothers to seek follow-up for depression screens: The Motivating Our Mothers (MOM) trial.

    Science.gov (United States)

    Fernandez y Garcia, Erik; Joseph, Jill; Wilson, Machelle D; Hinton, Ladson; Simon, Gregory; Ludman, Evette; Scott, Fiona; Kravitz, Richard L

    2015-01-01

    To determine the initial effectiveness of a novel, pediatric office-based intervention in motivating mothers to seek further assessment of positive depression screens. In this pilot randomized controlled trial, English-speaking mothers (n = 104) with positive 2-question depression screens and presenting with children 0 to 12 years old for well-child care to a general pediatric training clinic received interventions from a trained research assistant. The Motivating Our Mothers (MOM) intervention included office-based written and verbal targeted depression education and motivational messages encouraging further depression assessment and a semistructured telephone booster delivered 2 days later. The control intervention included nontargeted written and verbal messages and 2 days later, an attention control telephone survey. Both groups received a list of depression care resources. The primary outcome was the proportion of mothers in each group who reported trying to contact any of 6 types of resources to discuss the positive screen at 2 weeks after intervention (ClinicalTrials.gov NCT01453790). Despite 6 contact attempts, 10 MOM and 9 control mothers were lost to follow-up. More mothers in the MOM intervention tried to contact a resource compared to control (73.8% vs 53.5%, difference 20.3%, 95% confidence interval for difference -0.1 to 38.5, P = .052). Mothers receiving the MOM intervention made more attempts to contact a resource for follow-up of positive depression screens. If found effective in larger studies, MOM may prove a promising approach for motivating depression screen-positive mothers identified in general pediatric settings within and beyond the postpartum period to seek further depression assessment and support. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  11. Microrandomized trials: An experimental design for developing just-in-time adaptive interventions.

    Science.gov (United States)

    Klasnja, Predrag; Hekler, Eric B; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A

    2015-12-01

    This article presents an experimental design, the microrandomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals' health behaviors. Microrandomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. The article describes the microrandomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Microrandomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Microrandomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions' effects, enabling creation of more effective JITAIs. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  12. Clinical Trials

    Medline Plus

    Full Text Available ... more screening tests to see which test produces the best results. Some companies and groups sponsor clinical trials that test the ... and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...

  13. Fractal apertures in waveguides, conducting screens and cavities analysis and design

    CERN Document Server

    Ghosh, Basudeb; Kartikeyan, M V

    2014-01-01

    This book deals with the design and analysis of fractal apertures in waveguides, conducting screens and cavities using numerical electromagnetics and field-solvers. The aim is to obtain design solutions with improved accuracy for a wide range of applications. To achieve this goal, a few diverse problems are considered. The book is organized with adequate space dedicated for the design and analysis of fractal apertures in waveguides, conducting screens, and cavities, microwave/millimeter wave applications followed by detailed case-study problems to infuse better insight and understanding of the subject. Finally, summaries and suggestions are given for future work. Fractal geometries were widely used in electromagnetics, specifically for antennas and frequency selective surfaces (FSS). The self-similarity of fractal geometry gives rise to a multiband response, whereas the  space-filling nature of the fractal geometries makes it an efficient element in antenna and FSS unit cell miniaturization. Until now, no e...

  14. Virtual high screening throughput and design of 14α-lanosterol ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... Virtual high screening throughput and design of. 14α-lanosterol demethylase inhibitors against. Mycobacterium tuberculosis. Hildebert B. Maurice1*, Esther Tuarira1 and Kennedy Mwambete2. 1School of Pharmaceutical Sciences, Institute of Allied Health Sciences, Muhimbili University of Health and.

  15. The Correction of Myopia Evaluation Trial: lessons from the study design.

    Science.gov (United States)

    Hyman, L; Gwiazda, J

    2004-01-01

    The Correction of Myopia Evaluation Trial (COMET), a multicentre clinical trial based in 4 schools of optometry in the United States, evaluated the effect of progressive addition lenses versus single vision lenses on myopia progression in an ethnically diverse group of 469 myopic children aged 6 to 11 years. Completion of the clinical trial phase of the study provides an opportunity to evaluate aspects of the study design that contribute to its success. This article describes aspects of the study design that were influential in ensuring the smooth conduct of COMET. These include a dedicated team of investigators, an organisational structure with strong leadership and an independent Co-ordinating Centre, regular communication among investigators, flexible and creative approaches to recruitment and retention, sensitivity to concerns for child safety and child participation, and methods for enhancing and monitoring data reliability. The experience with COMET has provided a number of valuable lessons for all aspects of the study design that should benefit the development and implementation of future clinical trials, particularly those done in similar populations of children. The use of a carefully designed protocol using standard methods by dedicated members of the study team is essential in ensuring achievement of the study aims.

  16. Improving Clinical Trial Efficiency: Thinking outside the Box.

    Science.gov (United States)

    Mandrekar, Sumithra J; Dahlberg, Suzanne E; Simon, Richard

    2015-01-01

    Clinical trial design strategies have evolved over the past few years as a means to accelerate the drug development process so that the right therapies can be delivered to the right patients. Basket, umbrella, and adaptive enrichment strategies represent a class of novel designs for testing targeted therapeutics in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple subtrials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. Adaptive enrichment designs offer the potential to enrich for patients with a particular molecular feature that is predictive of benefit for the test treatment based on accumulating evidence from the trial. This review will aim to discuss the fundamentals of these design strategies, the underlying statistical framework, the logistical barriers of implementation, and, ultimately, the interpretation of the trial results. New statistical approaches, extensive multidisciplinary collaboration, and state of the art data capture technologies are needed to implement these strategies in practice. Logistical challenges to implementation arising from centralized assay testing, requirement of multiple specimens, multidisciplinary collaboration, and infrastructure requirements will also be discussed. This review will present these concepts in the context of the National Cancer Institute's precision medicine initiative trials: MATCH, ALCHEMIST, Lung MAP, as well as other trials such as FOCUS4.

  17. Overcoming obstacles in the design of cancer anorexia/weight loss trials.

    Science.gov (United States)

    Le-Rademacher, Jennifer G; Crawford, Jeffrey; Evans, William J; Jatoi, Aminah

    2017-09-01

    Most advanced cancer patients suffer loss of appetite (anorexia) and loss of weight. Despite the fact that cancer anorexia and weight loss are associated with a poor prognosis and detract from quality of life, no interventions have been demonstrated to palliate this syndrome in its entirety, particularly in patients with treatment-refractory malignancies. Recently, two registration trials - one with anamorelin and another with enobosarm - failed to reach their primary endpoints, thus raising questions. Were both these agents ineffective? Alternatively, did study design issues compromise the ability of these trials to identify effective agents? Thus, this review is timely insofar it serves as an introduction to study design, offers guidance on how to test promising agents for cancer anorexia/weight loss, and provides advice for overcoming trial design obstacles. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Potential of adaptive clinical trial designs in pharmacogenetic research, A simulation based on the IPASS trial

    NARCIS (Netherlands)

    Van Der Baan, Frederieke H.; Knol, Mirjam J.|info:eu-repo/dai/nl/304820350; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; Egberts, Toine C.G.|info:eu-repo/dai/nl/162850050; Grobbee, Diederick E.; Roes, Kit C.B.

    2011-01-01

    Background: An adaptive clinical trial design that allows population enrichment after interim analysis can be advantageous in pharmacogenetic research if previous evidence is not strong enough to exclude part of the patient population beforehand.With this design, underpowered studies or unnecessary

  19. The Data Gap in the EHR for Clinical Research Eligibility Screening.

    Science.gov (United States)

    Butler, Alex; Wei, Wei; Yuan, Chi; Kang, Tian; Si, Yuqi; Weng, Chunhua

    2018-01-01

    Much effort has been devoted to leverage EHR data for matching patients into clinical trials. However, EHRs may not contain all important data elements for clinical research eligibility screening. To better design research-friendly EHRs, an important step is to identify data elements frequently used for eligibility screening but not yet available in EHRs. This study fills this knowledge gap. Using the Alzheimer's disease domain as an example, we performed text mining on the eligibility criteria text in Clinicaltrials.gov to identify frequently used eligibility criteria concepts. We compared them to the EHR data elements of a cohort of Alzheimer's Disease patients to assess the data gap by usingthe OMOP Common Data Model to standardize the representations for both criteria concepts and EHR data elements. We identified the most common SNOMED CT concepts used in Alzheimer 's Disease trials, andfound 40% of common eligibility criteria concepts were not even defined in the concept space in the EHR dataset for a cohort of Alzheimer 'sDisease patients, indicating a significant data gap may impede EHR-based eligibility screening. The results of this study can be useful for designing targeted research data collection forms to help fill the data gap in the EHR.

  20. Newborn screening for galactosaemia.

    Science.gov (United States)

    Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

    2017-12-23

    Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the

  1. Incorporating alternative design clinical trials in network meta-analyses

    Directory of Open Access Journals (Sweden)

    Thorlund K

    2014-12-01

    Full Text Available Kristian Thorlund,1–3 Eric Druyts,1,4 Kabirraaj Toor,1,5 Jeroen P Jansen,1,6 Edward J Mills1,3 1Redwood Outcomes, Vancouver, BC, 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Stanford Prevention Research Center, Stanford University, Stanford, CA, USA; 4Department of Medicine, Faculty of Medicine, 5School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; 6Department of Public Health and Community Medicine, Tufts University, Boston, MA, USA Introduction: Network meta-analysis (NMA is an extension of conventional pairwise meta-analysis that allows for simultaneous comparison of multiple interventions. Well-established drug class efficacies have become commonplace in many disease areas. Thus, for reasons of ethics and equipoise, it is not practical to randomize patients to placebo or older drug classes. Unique randomized clinical trial designs are an attempt to navigate these obstacles. These alternative designs, however, pose challenges when attempting to incorporate data into NMAs. Using ulcerative colitis as an example, we illustrate an example of a method where data provided by these trials are used to populate treatment networks. Methods: We present the methods used to convert data from the PURSUIT trial into a typical parallel design for inclusion in our NMA. Data were required for three arms: golimumab 100 mg; golimumab 50 mg; and placebo. Golimumab 100 mg induction data were available; however, data regarding those individuals who were nonresponders at induction and those who were responders at maintenance were not reported, and as such, had to be imputed using data from the rerandomization phase. Golimumab 50 mg data regarding responses at week 6 were not available. Existing relationships between the available components were used to impute the expected proportions in this missing subpopulation. Data for placebo maintenance

  2. School-based intervention on healthy behaviour among Ecuadorian adolescents: effect of a cluster-randomized controlled trial on screen-time.

    Science.gov (United States)

    Andrade, Susana; Verloigne, Maïté; Cardon, Greet; Kolsteren, Patrick; Ochoa-Avilés, Angelica; Verstraeten, Roosmarijn; Donoso, Silvana; Lachat, Carl

    2015-09-22

    Effective interventions on screen-time behaviours (television, video games and computer time) are needed to prevent non-communicable diseases in low- and middle-income countries. The present manuscript investigates the effect of a school-based health promotion intervention on screen-time behaviour among 12- to 15-year-old adolescents. We report the effect of the trial on screen-time after two stages of implementation. We performed a cluster-randomised pair matched trial in urban schools in Cuenca-Ecuador. Participants were adolescents of grade eight and nine (mean age 12.8 ± 0.8 years, n = 1370, control group n = 684) from 20 schools (control group n = 10). The intervention included an individual and environmental component tailored to the local context and resources. The first intervention stage focused on diet, physical activity and screen-time behaviour, while the second stage focused only on diet and physical activity. Screen-time behaviours, primary outcome, were assessed at baseline, after the first (18 months) and second stage (28 months). Mixed linear models were used to analyse the data. After the first stage (data from n = 1224 adolescents; control group n = 608), the intervention group had a lower increase in TV-time on a week day (β = -15.7 min; P = 0.003) and weekend day (β = -18.9 min; P = 0.005), in total screen-time on a weekday (β = -25.9 min; P = 0.03) and in the proportion of adolescents that did not meet the screen-time recommendation (β = -4 percentage point; P = 0.01), compared to the control group. After the second stage (data from n = 1078 adolescents; control group n = 531), the TV-time on a weekday (β = 13.1 min; P = 0.02), and total screen-time on a weekday (β = 21.4 min; P = 0.03) increased more in adolescents from the intervention group. No adverse effects were reported. A multicomponent school-based intervention was only able to mitigate the increase

  3. Information Engineering and Workflow Design in a Clinical Decision Support System for Colorectal Cancer Screening in Iran.

    Science.gov (United States)

    Maserat, Elham; Seied Farajollah, Seiede Sedigheh; Safdari, Reza; Ghazisaeedi, Marjan; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

    2015-01-01

    Colorectal cancer is a major cause of morbidity and mortality throughout the world. Colorectal cancer screening is an optimal way for reducing of morbidity and mortality and a clinical decision support system (CDSS) plays an important role in predicting success of screening processes. DSS is a computer-based information system that improves the delivery of preventive care services. The aim of this article was to detail engineering of information requirements and work flow design of CDSS for a colorectal cancer screening program. In the first stage a screening minimum data set was determined. Developed and developing countries were analyzed for identifying this data set. Then information deficiencies and gaps were determined by check list. The second stage was a qualitative survey with a semi-structured interview as the study tool. A total of 15 users and stakeholders' perspectives about workflow of CDSS were studied. Finally workflow of DSS of control program was designed by standard clinical practice guidelines and perspectives. Screening minimum data set of national colorectal cancer screening program was defined in five sections, including colonoscopy data set, surgery, pathology, genetics and pedigree data set. Deficiencies and information gaps were analyzed. Then we designed a work process standard of screening. Finally workflow of DSS and entry stage were determined. A CDSS facilitates complex decision making for screening and has key roles in designing optimal interactions between colonoscopy, pathology and laboratory departments. Also workflow analysis is useful to identify data reconciliation strategies to address documentation gaps. Following recommendations of CDSS should improve quality of colorectal cancer screening.

  4. A qualitative study of lung cancer risk perceptions and smoking beliefs among national lung screening trial participants.

    Science.gov (United States)

    Park, Elyse R; Streck, Joanna M; Gareen, Ilana F; Ostroff, Jamie S; Hyland, Kelly A; Rigotti, Nancy A; Pajolek, Hannah; Nichter, Mark

    2014-02-01

    The National Comprehensive Cancer Network and the American Cancer Society recently released lung screening guidelines that include smoking cessation counseling for smokers undergoing screening. Previous work indicates that smoking behaviors and risk perceptions of the National Lung Screening Trial (NLST) participants were relatively unchanged. We explored American College of Radiology Imaging Network (ACRIN)/NLST former and current smokers' risk perceptions specifically to (a) determine whether lung screening is a cue for behavior change, (b) elucidate risk perceptions for lung cancer and smoking-related diseases, and (c) explore postscreening behavioral intentions and changes. A random sample of 35 participants from 4 ACRIN sites were qualitatively interviewed 1-2 years postscreen. We used a structured interview guide based on Health Belief Model and Self-Regulation Model constructs. Content analyses were conducted with NVivo 8. Most participants endorsed high-risk perceptions for lung cancer and smoking-related diseases, but heightened concern about these risks did not appear to motivate participants to seek screening. Risk perceptions were mostly attributed to participants' heavy smoking histories; former smokers expressed greatly reduced risk. Lung cancer and smoking-related diseases were perceived as very severe although participants endorsed low worry. Current smokers had low confidence in their ability to quit, and none reported quitting following their initial screen. Lung screening did not appear to be a behavior change cue to action, and high-risk perceptions did not translate into quitting behaviors. Cognitive and emotional dissonance and avoidance strategies may deter engagement in smoking behavior change. Smoking cessation and prevention interventions during lung screening should explore risk perceptions, emotions, and quit confidence.

  5. Noninvasive Computed Tomography–based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial

    Science.gov (United States)

    Maldonado, Fabien; Duan, Fenghai; Raghunath, Sushravya M.; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Garg, Kavita; Greco, Erin; Nath, Hrudaya; Robb, Richard A.; Bartholmai, Brian J.

    2015-01-01

    Rationale: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. Objectives: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. Methods: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. Measurements and Main Results: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. Conclusions: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas. PMID:26052977

  6. Risks of Cervical Cancer Screening

    Science.gov (United States)

    ... women. Human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Although most women with ... clinical trials is available from the NCI website . Risks of Cervical Cancer Screening Key Points Screening tests ...

  7. Screening for breast cancer with mammography

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Nielsen, Margrethe

    2009-01-01

    BACKGROUND: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. OBJECTIVES: To assess the effect of screening for breast cancer with mammography on mortality and morbidity. SEARCH STRATEGY: We searched Pub...... excluded a biased trial and included 600,000 women in the analyses. Three trials with adequate randomisation did not show a significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomisation showed...... a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of differential...

  8. Pregnant Women's Perceptions of the Risks and Benefits of Disclosure During Web-Based Mental Health E-Screening Versus Paper-Based Screening: Randomized Controlled Trial.

    Science.gov (United States)

    Kingston, Dawn; Biringer, Anne; Veldhuyzen van Zanten, Sander; Giallo, Rebecca; McDonald, Sarah; MacQueen, Glenda; Vermeyden, Lydia; Austin, Marie-Paule

    2017-10-20

    Pregnant women's perceptions of the risks and benefits during mental health screening impact their willingness to disclose concerns. Early research in violence screening suggests that such perceptions may vary by mode of screening, whereby women view the anonymity of e-screening as less risky than other approaches. Understanding whether mode of screening influences perceptions of risk and benefit of disclosure is important in screening implementation. The objective of this randomized controlled trial was to compare the perceptions of pregnant women randomized to a Web-based screening intervention group and a paper-based screening control group on the level of risk and benefit they perceive in disclosing mental health concerns to their prenatal care provider. A secondary objective was to identify factors associated with women's perceptions of risk and benefit of disclosure. Pregnant women recruited from maternity clinics, hospitals, and prenatal classes were computer-randomized to a fully automated Web-based e-screening intervention group or a paper-based control. The intervention group completed the Antenatal Psychosocial Health Assessment and the Edinburgh Postnatal Depression Scale on a computer tablet, whereas the control group completed them on paper. The primary outcome was women's perceptions of the risk and benefits of mental health screening using the Disclosure Expectations Scale (DES). A completer analysis was conducted. Statistical significance was set at Pcontrol (n=331) groups. There were no significant baseline differences between groups. The mode of screening was not associated with either perceived risk or benefit of screening. There were no differences in groups in the mean scores of the risk and benefit of disclosure subscales. Over three-quarters of women in both intervention and control groups perceived that mental health screening was beneficial. However, 43.1% (272/631) of women in both groups reported feeling very, moderately, or somewhat

  9. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

    Science.gov (United States)

    Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

    2015-05-01

    The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Population newborn screening for inherited metabolic disease: current UK perspectives.

    Science.gov (United States)

    Green, A; Pollitt, R J

    1999-06-01

    Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

  11. Sensitivity study of the monogroove with screen heat pipe design

    Science.gov (United States)

    Evans, Austin L.; Joyce, Martin

    1988-01-01

    The present sensitivity study of design variable effects on the performance of a monogroove-with-screen heat pipe obtains performance curves for maximum heat-transfer rates vs. operating temperatures by means of a computer code; performance projections for both 1-g and zero-g conditions are obtainable. The variables in question were liquid and vapor channel design, wall groove design, and the number of feed lines in the evaporator and condenser. The effect on performance of three different working fluids, namely ammonia, methanol, and water, were also determined. Greatest sensitivity was to changes in liquid and vapor channel diameters.

  12. Does routine psychosocial screening improve referral to psychosocial care providers and patient-radiotherapist communication? A cluster randomized controlled trial.

    Science.gov (United States)

    Braeken, Anna P B M; Lechner, Lilian; Eekers, Daniëlle B P; Houben, Ruud M A; van Gils, Francis C J M; Ambergen, Ton; Kempen, Gertrudis I J M

    2013-11-01

    This study tests whether using a screening instrument improves referral to psychosocial care providers (e.g. psychologist) and facilitates patient-radiotherapist communication. A cluster randomized controlled trial was used. Fourteen radiotherapists were randomly allocated to the experimental or control group and 568 of their patients received care in accordance with the group to which their radiotherapist was allocated. Patients in the experimental group were asked to complete a screening instrument before and at the end of the radiation treatment period. All patients were requested to complete questionnaires concerning patient-physician communication after the first consultation and concerning psychosocial care 3 and 12 months post-intervention. Patients who completed the screening instrument were referred to social workers at an earlier stage than patients who did not (Pcommunication. Our results suggest that a simple screening procedure can be valuable for the timely treatment of psychosocial problems in patients. Future efforts should be directed at appropriate timing of screening and enhancing physicians' awareness regarding the importance of identifying, discussing and treating psychosocial problems in cancer patients. Psychosocial screening can be enhanced by effective radiotherapist-patient communication. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Clinical Trials

    Medline Plus

    Full Text Available ... sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and Veterans Affairs; ... age and frequency for doing screening tests, such as mammography; and compare two or more screening tests ...

  14. Clinical Trials

    Medline Plus

    Full Text Available ... healthy people to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial participants ... DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH requires DSMBs ...

  15. Framing the conversation: use of PRECIS-2 ratings to advance understanding of pragmatic trial design domains.

    Science.gov (United States)

    Lipman, Paula Darby; Loudon, Kirsty; Dluzak, Leanora; Moloney, Rachael; Messner, Donna; Stoney, Catherine M

    2017-11-10

    There continues to be debate about what constitutes a pragmatic trial and how it is distinguished from more traditional explanatory trials. The NIH Pragmatic Trials Collaborative Project, which includes five trials and a coordinating unit, has adopted the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) instrument. The purpose of the study was to collect PRECIS-2 ratings at two points in time to assess whether the tool was sensitive to change in trial design, and to explore with investigators the rationale for rating shifts. A mixed-methods design included sequential collection and analysis of quantitative data (PRECIS-2 ratings) and qualitative data. Ratings were collected at two annual, in-person project meetings, and subsequent interviews conducted with investigators were recorded, transcribed, and coded using NVivo 11 Pro for Windows. Rating shifts were coded as either (1) actual change (reflects a change in procedure or protocol), (2) primarily a rating shift reflecting rater variability, or (3) themes that reflect important concepts about the tool and/or pragmatic trial design. Based on PRECIS-2 ratings, each trial was highly pragmatic at the planning phase and remained so 1 year later in the early phases of trial implementation. Over half of the 45 paired ratings for the nine PRECIS-2 domains indicated a rating change from Time 1 to Time 2 (N = 24, 53%). Of the 24 rating changes, only three represented a true change in the design of the trial. Analysis of rationales for rating shifts identified critical themes associated with the tool or pragmatic trial design more generally. Each trial contributed one or more relevant comments, with Eligibility, Flexibility of Adherence, and Follow-up each accounting for more than one. PRECIS-2 has proved useful for "framing the conversation" about trial design among members of the Pragmatic Trials Collaborative Project. Our findings suggest that design elements assessed by the PRECIS-2 tool may represent

  16. The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

    Science.gov (United States)

    Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

    2015-07-01

    The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

  17. Rethinking non-inferiority: a practical trial design for optimising treatment duration.

    Science.gov (United States)

    Quartagno, Matteo; Walker, A Sarah; Carpenter, James R; Phillips, Patrick Pj; Parmar, Mahesh Kb

    2018-06-01

    Background Trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, tuberculosis and hepatitis C. However, standard non-inferiority designs have several limitations, including arbitrariness of non-inferiority margins, choice of research arms and very large sample sizes. Methods We recast the problem of finding an appropriate non-inferior treatment duration in terms of modelling the entire duration-response curve within a pre-specified range. We propose a multi-arm randomised trial design, allocating patients to different treatment durations. We use fractional polynomials and spline-based methods to flexibly model the duration-response curve. We call this a 'Durations design'. We compare different methods in terms of a scaled version of the area between true and estimated prediction curves. We evaluate sensitivity to key design parameters, including sample size, number and position of arms. Results A total sample size of ~ 500 patients divided into a moderate number of equidistant arms (5-7) is sufficient to estimate the duration-response curve within a 5% error margin in 95% of the simulations. Fractional polynomials provide similar or better results than spline-based methods in most scenarios. Conclusion Our proposed practical randomised trial 'Durations design' shows promising performance in the estimation of the duration-response curve; subject to a pending careful investigation of its inferential properties, it provides a potential alternative to standard non-inferiority designs, avoiding many of their limitations, and yet being fairly robust to different possible duration-response curves. The trial outcome is the whole duration-response curve, which may be used by clinicians and policymakers to make informed decisions, facilitating a move away from a forced binary hypothesis testing paradigm.

  18. Effect of second timed appointments for non-attenders of breast cancer screening in England: a randomised controlled trial.

    Science.gov (United States)

    Allgood, Prue C; Maroni, Roberta; Hudson, Sue; Offman, Judith; Turnbull, Anne E; Peacock, Lesley; Steel, Jim; Kirby, Geraldine; Ingram, Christine E; Somers, Julie; Fuller, Clare; Threlfall, Anthony G; Gabe, Rhian; Maxwell, Anthony J; Patnick, Julietta; Duffy, Stephen W

    2017-07-01

    In England, participation in breast cancer screening has been decreasing in the past 10 years, approaching the national minimum standard of 70%. Interventions aimed at improving participation need to be investigated and put into practice to stop this downward trend. We assessed the effect on participation of sending invitations for breast screening with a timed appointment to women who did not attend their first offered appointment within the NHS Breast Screening Programme (NHSBSP). In this open, randomised controlled trial, women in six centres in the NHSBSP in England who were invited for routine breast cancer screening were randomly assigned (1:1) to receive an invitation to a second appointment with fixed date and time (intervention) or an invitation letter with a telephone number to call to book their new screening appointment (control) in the event of non-attendance at the first offered appointment. Randomisation was by SX number, a sequential unique identifier of each woman within the NHSBSP, and at the beginning of the study a coin toss decided whether women with odd or even SX numbers would be allocated to the intervention group. Women aged 50-70 years who did not attend their first offered appointment were eligible for the analysis. The primary endpoint was participation (ie, attendance at breast cancer screening) within 90 days of the date of the first offered appointment; we used Poisson regression to compare the proportion of women who participated in screening in the study groups. All analyses were by intention to treat. This trial is registered with Barts Health, number 009304QM. We obtained 33 146 records of women invited for breast cancer screening at the six centres between June 2, 2014, and Sept 30, 2015, who did not attend their first offered appointment. 26 054 women were eligible for this analysis (12 807 in the intervention group and 13 247 in the control group). Participation within 90 days of the first offered appointment was

  19. A Multimedia Child Developmental Screening Checklist: Design and Validation.

    Science.gov (United States)

    Cheng, Hsin-Yi Kathy; Chen, Li-Ying; Cheng, Chih-Hsiu; Ju, Yan-Ying; Chen, Chia-Ling; Tseng, Kevin C

    2016-10-24

    Identifying disability early in life confers long-term benefits for children. The Taipei City Child Development Screening tool, second version (Taipei II) provides checklists for 13 child age groups from 4 months to 6 years. However, the usability of a text-based screening tool largely depends on the literacy level and logical reasoning ability of the caregivers, as well as language barriers caused by increasing numbers of immigrants. The objectives of this study were to (1) design and develop a Web-based multimedia version of the current Taipei II developmental screening tool, and (2) investigate the measurement equivalence of this multimedia version to the original paper-based version. To develop the multimedia version of Taipei II, a team of experts created illustrations, translations, and dubbing of the original checklists. The developmental screening test was administered to a total of 390 primary caregivers of children aged between 4 months and 6 years. Psychometric testing revealed excellent agreement between the paper and multimedia versions of Taipei II. Good to excellent reliabilities were demonstrated for all age groups for both the cross-mode similarity (mode intraclass correlation range 0.85-0.96) and the test-retest reliability (r=.93). Regarding the usability, the mean score was 4.80 (SD 0.03), indicating that users were satisfied with their multimedia website experience. The multimedia tool produced essentially equivalent results to the paper-based tool. In addition, it had numerous advantages, such as it can facilitate active participation and promote early screening of target populations. Clinicaltrials.gov NCT02359591; https://clinicaltrials.gov/ct2/show/NCT02359591 (Archived by WebCite at http://www.webcitation.org/6l21mmdNn).

  20. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

    Science.gov (United States)

    Kloppenburg, M; Maheu, E; Kraus, V B; Cicuttini, F; Doherty, M; Dreiser, R-L; Henrotin, Y; Jiang, G-L; Mandl, L; Martel-Pelletier, J; Nelson, A E; Neogi, T; Pelletier, J-P; Punzi, L; Ramonda, R; Simon, L S; Wang, S

    2015-05-01

    Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH): A randomized controlled trial study protocol

    OpenAIRE

    Tsai Midi; Jiang Yannan; Epstein Leonard; Foley Louise; Mhurchu Cliona; Maddison Ralph; Dewes Ofa; Heke Ihirangi

    2011-01-01

    Abstract Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33%) do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family orie...

  2. Idea Screening in Engineering Design Using Employee-driven Wisdom of the Crowds

    OpenAIRE

    Onarheim, Balder; Christensen, Bo T.

    2011-01-01

    The paper investigates the question of screening ideas in the ‘fuzzy front end’ of engineering design, examining the validity of employee voting schemes and related biases. After an employee-driven innovation project at {Company Name removed for review}, 99 ideas were to be screened for further development. Based on the concept of ‘wisdom of the crowds’, all ideas were individually rated by a broad selection of employees, and their choices of ideas and idea categories compared ...

  3. Effects of a health education and telephone counseling program on patients with a positive fecal occult blood test result for colorectal cancer screening: A randomized controlled trial.

    Science.gov (United States)

    Chiu, Hui-Chuan; Hung, Hsin-Yuan; Lin, Hsiu-Chen; Chen, Shu-Ching

    2017-10-01

    Our purpose was to evaluate the effects of a health education and telephone counseling program on knowledge and attitudes about colorectal cancer and screening and the psychological impact of positive screening results. A randomized controlled trial was conducted with 2 groups using a pretest and posttest measures design. Patients with positive colorectal cancer screening results were selected and randomly assigned to an experimental (n = 51) or control (n = 51) group. Subjects in the experimental group received a health education and telephone counseling program, while the control group received routine care only. Patients were assessed pretest before intervention (first visit to the outpatient) and posttest at 4 weeks after intervention (4 weeks after first visit to the outpatient). Patients in the experimental group had a significantly better level of knowledge about colorectal cancer and the psychological impact of a positive screening result than did the control group. Analysis of covariance revealed that the health education and telephone counseling program had a significant main effect on colorectal cancer knowledge. A health education and telephone counseling program can improve knowledge about colorectal cancer and about the psychological impact in patients with positive colorectal cancer screening results. The health education and telephone counseling program is an easy, simple, and convenient method of improving knowledge, improving attitudes, and alleviating psychological distress in patients with positive colorectal cancer screening results, and this program can be expanded to other types of cancer screening. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Screening for type 2 diabetes: a short report for the National Screening Committee.

    Science.gov (United States)

    Waugh, N R; Shyangdan, D; Taylor-Phillips, S; Suri, G; Hall, B

    2013-08-01

    The prevalence of type 2 diabetes mellitus (T2DM) has been increasing, owing to increases in overweight and obesity, decreasing physical activity and the changing demographic structure of the population. People can develop T2DM without symptoms and up to 20% may be undiagnosed. They may have diabetic complications, such as retinopathy, by the time they are diagnosed, or may suffer a heart attack, without warning. Undiagnosed diabetes can be detected by raised blood glucose levels. The aim of this review was to provide an update for the UK National Screening Committee (NSC) on screening for T2DM. As this review was undertaken to update a previous Health Technology Assessment review published in 2007, and a more recent Scottish Public Health Network review, searches for evidence were restricted from 2009 to end of January 2012, with selected later studies added. The databases searched were MEDLINE, EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index and Conference Proceedings Citation Index. The case for screening was considered against the criteria used by the NSC to assess proposed population screening programmes. Population screening for T2DM does not meet all of the NSC criteria. Criterion 12, on optimisation of existing management, has not been met. A report by the National Audit Office (NAO) gives details of shortcomings. Criterion 13 requires evidence from high-quality randomised controlled trials that screening is beneficial. This has not been met. The Ely trial of screening showed no benefit. The ADDITION trial was not a trial of screening, but showed no benefit in cardiovascular outcomes from intensive management in people with screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to have been met, according to the NAO report. Criterion 19 requires that all other options, including prevention, should have been considered. A large proportion of cases of T2DM could be prevented if people avoided becoming

  5. Manufacturing the truth: From designing clinical trials to publishing trial data.

    Science.gov (United States)

    Whitstock, Margaret

    2018-01-01

    This paper expands on some of the points made by Deepak Natarajan on techniques used in designing clinical trials of new drugs to ensure favourable outcomes. It also considers the nexus between the manufacturers of new drugs and the publishers of medical journals in which edited versions of these favourable outcomes are presented to the medical fraternity. The argument will be illustrated by referring to the clinical trials of rofecoxib (Vioxx®) and etoricoxib (Arcoxia®). Both these drugs are COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) manufactured by Merck and Co. Because of the unparalleled access to Merck's internal confidential documents, due to the subpoenaing of these documents by government and private individuals in civil and criminal actions, we are still learning about the company's unconscionable acts. What we learn can inform our judgement concerning published reports of both new and old drugs.

  6. Effect of transient liquid flow on retention characteristics of screen acquisition systems. [design of Space Shuttle feed system

    Science.gov (United States)

    Cady, E. C.

    1977-01-01

    A design analysis, is developed based on experimental data, to predict the effects of transient flow and pressure surges (caused either by valve or pump operation, or by boiling of liquids in warm lines) on the retention performance of screen acquisition systems. A survey of screen liquid acquisition system applications was performed to determine appropriate system environment and classification. A screen model was developed which assumed that the screen device was a uniformly distributed composite orthotropic structure, and which accounted for liquid inflow/outflow, gas ingestion quality, screen stress, and liquid spill. A series of 177 tests using 13 specimens (5 screen meshes, 4 screen device construction/backup methods, and 2 orientations) with three test fluids (isopropyl alcohol, Freon 114, and LH2) provided data which verified important features of the screen model and resulted in a design tool which could accurately predict the transient startup performance acquisition devices.

  7. Effectiveness of an annular closure device in a "real-world" population: stratification of registry data using screening criteria from a randomized controlled trial.

    Science.gov (United States)

    Kuršumović, Adisa; Rath, Stefan A

    2018-01-01

    Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.

  8. Efficient design of clinical trials and epidemiological research: is it possible?

    Science.gov (United States)

    Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

    2017-08-01

    Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

  9. Design of High-Precision Infrared Multi-Touch Screen Based on the EFM32

    Directory of Open Access Journals (Sweden)

    Zhong XIAOLING

    2014-07-01

    Full Text Available Due to the low accuracy of traditional infrared multi-touch screen, it’s difficult to ascertain the touch point. Putting forward a design scheme based on ARM Cortex-M3 kernel EFM32 processor of high precision infrared multi-touch screen. Using tracking scanning area algorithm after accessed electricity for the first time to scan, it greatly improved the scanning efficiency and response speed. Based on the infrared characteristic difference, putting forward a data fitting algorithm, employing the subtraction relationship between the covering area and sampling value to curve fitting, concluding the infrared sampling value of subtraction characteristic curve, establishing a sampling value differential data tables, at last ensuring the precise location of touch point. Besides, practices have proved that the accuracy of the infrared touch screen can up to 0.5 mm. The design uses standard USB port which connected to the PC can also be widely used in various terminals.

  10. Tai Chi for osteopenic women: design and rationale of a pragmatic randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Fischer Mary

    2010-03-01

    Full Text Available Abstract Background Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks. Methods/Design A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen, bone formation (osteocalcin, and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry. Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16 to explore the feasibility of modeling skeletal

  11. Risk stratification and rapid geriatric screening in an emergency department - a quasi-randomised controlled trial.

    Science.gov (United States)

    Foo, Chik Loon; Siu, Vivan Wing Yin; Ang, Hou; Phuah, Madeline Wei Ling; Ooi, Chee Kheong

    2014-08-30

    To determine if risk stratification followed by rapid geriatric screening in an emergency department (ED) reduced functional decline, ED reattendance and hospitalisation. This was a quasi-randomised controlled trial. Patients were randomised by the last digit of their national registration identity card (NRIC). Odd number controls received standard ED care; even number patients received geriatric screening, followed by intervention and/or onward referrals. Patients were followed up for 12 months. There were 500 and 280 patients in the control and intervention groups. The intervention group had higher Triage Risk Screening Tool (TRST) scores (34.3% vs 25.4% TRST ≥3, p = 0.01) and lower baseline Instrumental Activity of Daily Living (IADL) scores (22.84 vs 24.18, p fall risk (65.0%), vision (61.4%), and footwear (58.2%). 28.2% were referred to a geriatric clinic and 11.8% were admitted. 425 (85.0%) controls and 234 (83.6%) in the intervention group completed their follow-up. After adjusting for TRST and baseline IADL, the intervention group had significant preservation in function (Basic ADL -0.99 vs -0.24, p geriatric screening at the request of the ED doctor. A major limitation was that a large proportion of patients who were randomized to the intervention group either refused (18.8%) or left the ED before being approached (32.0%). These two groups were not followed up, and hence were excluded in our analysis. Risk stratification and focused geriatric screening in ED resulted in significant preservation of patients' function at 12 months. National Healthcare Group (NHG) Domain Specific Review Board (DSRB) C/09/023. Registered 5th March 2009.

  12. Hawthorne effect with transient behavioral and biochemical changes in a randomized controlled sleep extension trial of chronically short-sleeping obese adults: implications for the design and interpretation of clinical studies.

    Science.gov (United States)

    Cizza, Giovanni; Piaggi, Paolo; Rother, Kristina I; Csako, Gyorgy

    2014-01-01

    To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit. Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later. Outpatient. Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, sleep/night. Non-pharmacological sleep extension. Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids. Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 vs. 388.1±48.6 min/night; mean±SD; Psleep quality improved (9.1±3.2 vs. 8.2±3.0 PSQI score; Pattention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research. ClinicalTrials.gov NCT00261898.

  13. Directions for new developments on statistical design and analysis of small population group trials.

    Science.gov (United States)

    Hilgers, Ralf-Dieter; Roes, Kit; Stallard, Nigel

    2016-06-14

    Most statistical design and analysis methods for clinical trials have been developed and evaluated where at least several hundreds of patients could be recruited. These methods may not be suitable to evaluate therapies if the sample size is unavoidably small, which is usually termed by small populations. The specific sample size cut off, where the standard methods fail, needs to be investigated. In this paper, the authors present their view on new developments for design and analysis of clinical trials in small population groups, where conventional statistical methods may be inappropriate, e.g., because of lack of power or poor adherence to asymptotic approximations due to sample size restrictions. Following the EMA/CHMP guideline on clinical trials in small populations, we consider directions for new developments in the area of statistical methodology for design and analysis of small population clinical trials. We relate the findings to the research activities of three projects, Asterix, IDeAl, and InSPiRe, which have received funding since 2013 within the FP7-HEALTH-2013-INNOVATION-1 framework of the EU. As not all aspects of the wide research area of small population clinical trials can be addressed, we focus on areas where we feel advances are needed and feasible. The general framework of the EMA/CHMP guideline on small population clinical trials stimulates a number of research areas. These serve as the basis for the three projects, Asterix, IDeAl, and InSPiRe, which use various approaches to develop new statistical methodology for design and analysis of small population clinical trials. Small population clinical trials refer to trials with a limited number of patients. Small populations may result form rare diseases or specific subtypes of more common diseases. New statistical methodology needs to be tailored to these specific situations. The main results from the three projects will constitute a useful toolbox for improved design and analysis of small

  14. The effectiveness of the Screening Inventory of Psychosocial Problems (SIPP) in cancer patients treated with radiotherapy: design of a cluster randomised controlled trial

    International Nuclear Information System (INIS)

    Braeken, Anna PBM; Lechner, Lilian; Gils, Francis CJM van; Houben, Ruud MA; Eekers, Daniëlle; Ambergen, Ton; Kempen, Gertrudis IJM

    2009-01-01

    The Screening Inventory of Psychosocial Problems (SIPP) is a short, validated self-reported questionnaire to identify psychosocial problems in Dutch cancer patients. The one-page 24-item questionnaire assesses physical complaints, psychological complaints and social and sexual problems. Very little is known about the effects of using the SIPP in consultation settings. Our study aims are to test the hypotheses that using the SIPP (a) may contribute to adequate referral to relevant psychosocial caregivers, (b) should facilitate communication between radiotherapists and cancer patients about psychosocial distress and (c) may prevent underdiagnosis of early symptoms reflecting psychosocial problems. This paper presents the design of a cluster randomised controlled trial (CRCT) evaluating the effectiveness of using the SIPP in cancer patients treated with radiotherapy. A CRCT is developed using a Solomon four-group design (two intervention and two control groups) to evaluate the effects of using the SIPP. Radiotherapists, instead of cancer patients, are randomly allocated to the experimental or control groups. Within these groups, all included cancer patients are randomised into two subgroups: with and without pre-measurement. Self-reported assessments are conducted at four times: a pre-test at baseline before the first consultation and a post-test directly following the first consultation, and three and 12 months after baseline measurement. The primary outcome measures are the number and types of referrals of cancer patients with psychosocial problems to relevant (psychosocial) caregivers. The secondary outcome measures are patients' satisfaction with the radiotherapist-patient communication, psychosocial distress and quality of life. Furthermore, a process evaluation will be carried out. Data of the effect-evaluation will be analysed according to the intention-to-treat principle and data regarding the types of referrals to health care providers and patient

  15. Age Nutrition Chirugie (ANC) study: impact of a geriatric intervention on the screening and management of undernutrition in elderly patients operated on for colon cancer, a stepped wedge controlled trial.

    Science.gov (United States)

    Dupuis, Marine; Kuczewski, Elisabetta; Villeneuve, Laurent; Bin-Dorel, Sylvie; Haine, Max; Falandry, Claire; Gilbert, Thomas; Passot, Guillaume; Glehen, Olivier; Bonnefoy, Marc

    2017-01-07

    Undernutrition prior to major abdominal surgery is frequent and increases morbidity and mortality, especially in older patients. The management of undernutrition reduces postoperative complications. Nutritional management should be a priority in patient care during the preoperative period. However undernutrition is rarely detected and the guidelines are infrequently followed. Preoperative undernutrition screening should allow a better implementation of the guidelines. The ANC ("Age Nutrition Chirurgie") study is an interventional, comparative, prospective, multicenter, randomized protocol based on the stepped wedge trial design. For the intervention, the surgeon will inform the patient of the establishment of a systematic preoperative geriatric assessment that will allow the preoperative diagnosis of the nutritional status and the implementation of an adjusted nutritional support in accordance with the nutritional guidelines. The primary outcome measure is to determine the impact of the geriatric intervention on the level of perioperative nutritional management, in accordance with the current European guidelines. The implementation of the intervention in the five participating centers will be rolled-out sequentially over six time periods (every six months). Investigators must recommend that all patients aged 70 years or over and who are consulting for a surgery for a colorectal cancer should consider participating in this study. The ANC study is based on an original methodology, the stepped wedge trial design, which is appropriate for evaluating the implementation of a geriatric and nutritional assessment during the perioperative period. We describe the purpose of this geriatric intervention, which is expected to apply the ESPEN and SFNEP recommendations through the establishment of an undernutrition screening and a management program for patients with cancer. This intervention should allow a decrease in patient morbidity and mortality due to undernutrition. This

  16. Risks of Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... cancer. Having hepatitis or cirrhosis can increase the risk of developing liver cancer. Anything that increases the ... clinical trials is available from the NCI website . Risks of Liver (Hepatocellular) Cancer Screening Key Points Screening ...

  17. Designing "Real-World" trials to meet the needs of health policy makers at marketing authorization.

    Science.gov (United States)

    Calvert, Melanie; Wood, John; Freemantle, Nick

    2011-07-01

    There is increasing interest in conducting "Real-World" trials that go beyond traditional assessment of efficacy and safety to examine market access and value for money questions before marketing authorization of a new pharmaceutical product or health technology. This commentary uses practical examples to demonstrate how high-quality evidence of the cost-effectiveness of an intervention may be gained earlier in the development process. Issues surrounding the design and analysis of "Real-World" trials to demonstrate relative cost-effectiveness early in the life of new technologies are discussed. The modification of traditional phase III trial designs, de novo trial designs, the combination of trial-based and epidemiological data, and the use of simulation model-based approaches to address reimbursement questions are described. Modest changes to a phase III trial protocol and case report form may be undertaken at the design stage to provide valid estimates of health care use and the benefits accrued; however, phase III designs often preclude "real-life" practice. Relatively small de novo trials may be used to address adherence to therapy or patient preference, although simply designed studies with active comparators enrolling large numbers of patients may provide evidence on long-term safety and rare adverse events. Practical examples demonstrate that it is possible to provide high-quality evidence of the cost-effectiveness of an intervention earlier in the development process. Payers and decision makers should preferentially adopt treatments with such evidence than treatments for which evidence is lacking or of lower quality. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. 3D mosquito screens to create window double screen traps for mosquito control.

    Science.gov (United States)

    Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo

    2017-08-29

    Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and

  19. The antidepressant debate and the balanced placebo trial design: an ethical analysis.

    Science.gov (United States)

    Waring, Duff R

    2008-12-01

    There is ongoing debate about whether randomized, placebo-controlled trials under a double-blind have reliably established the pharmacological efficacy of antidepressants. Numerous meta-analyses of antidepressant efficacy trials, e.g., Kirsch et al. [Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. food and drug administration. Prevention and Treatment, 5, Article 23. (Retrieved July 19, 2007 from http://journals.apa.org/prevention/volume5)], have shown a modest drug-placebo difference but methodological problems with standard trial design preclude a definitive conclusion that this difference results from specific biological effects of antidepressants or the nonspecific factors that have not been adequately excluded. Standard trial design assumes the additivity thesis of pharmacological efficacy, being the assumption that the specific or "true" magnitude of the pharmacological effect is limited to the difference between the drug and placebo responses in a standard trial. If the drug effects are as small as these meta-analyses suggest, then their clinical effectiveness is questionable. If the drug effects are actually larger but masked by placebo effects, then the additivity thesis is not valid and we risk false negative results with standard trial design. Kirsch et al. propose an alternative, four arm balanced placebo trial design (BPTD) that can accurately test the additivity thesis. The BPTD uses antidepressants, active placebos and the intentional deception of research subjects. My focal question is whether the BPTD is ethically defensible. I will explore two objections that can be raised against it: 1) lying to BPTD research subjects violates their autonomy and exploits their illness and 2) the BPTD may not enable us to test the additivity thesis with accuracy, i.e., it may contribute to the masking of drug effects that it aims to avoid. I argue that these

  20. Screening, intervention and outcome in autism and other developmental disorders: the role of randomized controlled trials.

    Science.gov (United States)

    Fernell, Elisabeth; Wilson, Philip; Hadjikhani, Nouchine; Bourgeron, Thomas; Neville, Brian; Taylor, David; Minnis, Helen; Gillberg, Christopher

    2014-08-01

    We draw attention to a number of important considerations in the arguments about screening and outcome of intervention in children with autism and other developmental disorders. Autism screening in itself never provides a final clinical diagnosis, but may well identify developmental deviations indicative of autism-or of other developmental disorders-that should lead to referral for further clinical assessment. Decisions regarding population or clinic screening cannot be allowed to be based on the fact that prospective longitudinal RCT designs over decades could never be performed in complex developmental disorders. We propose an alternative approach. Early screening for autism and other developmental disorders is likely to be of high societal importance and should be promoted and rigorously evaluated.

  1. WE-D-207-01: Background and Clinical Implementation of a Screening Program

    International Nuclear Information System (INIS)

    Aberle, D.

    2015-01-01

    In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancer Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in

  2. Prospects for population screening and diagnosis of lung cancer

    DEFF Research Database (Denmark)

    Field, John K; Oudkerk, Matthijs; Pedersen, Jesper Holst

    2013-01-01

    Deaths from lung cancer exceed those from any other type of malignancy, with 1·5 million deaths in 2010. Prevention and smoking cessation are still the main methods to reduce the death toll. The US National Lung Screening Trial, which compared CT screening with chest radiograph, yielded a mortality......, and pooled analysis of European CT screening trials, we discuss the main topics that will need consideration. These unresolved issues are risk prediction models to identify patients for CT screening; radiological protocols that use volumetric analysis for indeterminate nodules; options for surgical resection...

  3. Micro-Randomized Trials: An Experimental Design for Developing Just-in-Time Adaptive Interventions

    Science.gov (United States)

    Klasnja, Predrag; Hekler, Eric B.; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A.

    2015-01-01

    Objective This paper presents an experimental design, the micro-randomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals’ health behaviors. Micro-randomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. Methods The paper describes the micro-randomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Results Micro-randomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Conclusions Micro-randomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions’ effects, enabling creation of more effective JITAIs. PMID:26651463

  4. A randomized controlled trial of a multilevel intervention to increase colorectal cancer screening among Latino immigrants in a primary care facility.

    Science.gov (United States)

    Aragones, Abraham; Schwartz, Mark D; Shah, Nirav R; Gany, Francesca M

    2010-06-01

    Latino immigrants face a higher burden of colorectal cancer (CRC) and screening rates are low. To assess the effectiveness of a multilevel intervention in increasing the rate of CRC screening among Latino immigrants. A randomized controlled trial, with randomization at the physician level. Pairs of 65 primary care physicians and 65 Latino immigrant patients participated, 31 in the intervention and 34 in the control group. CRC educational video in Spanish on a portable personal digital video display device accompanied by a brochure with key information for the patient, and a patient-delivered paper-based reminder for their physician. Completed CRC screening, physician recommendation for CRC screening, and patient adherence to physician recommended CRC screening. The overall rate of completed screening for CRC was 55% for the intervention and 18% for the control group (p = 0.002). Physicians recommended CRC screening for 61% of patients in the intervention group versus 41% in the control group (p = 0.08). Of those that received a recommendation, 90% in the intervention group adhered to it versus 26% in the control group (p = 0.007). The intervention was successful in increasing rates of completed CRC screening primarily through increasing adherence after screening was recommended. Additional efforts should focus on developing new strategies to increase physician recommendation for CRC screening, while employing effective patient adherence interventions.

  5. Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial.

    Science.gov (United States)

    Kerrigan, Deanna; Tudor, Carrie; Motlhaoleng, Katlego; Lebina, Limakatso; Qomfu, Cokiswa; Variava, Ebrahim; Chon, Sandy; Martinson, Neil; Golub, Jonathan E

    2018-04-16

    Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa. Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted. Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts. Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics. The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

  6. Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

    Energy Technology Data Exchange (ETDEWEB)

    Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Zhang, Jianjun [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2017-03-15

    Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.

  7. Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

    International Nuclear Information System (INIS)

    Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

    2017-01-01

    Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.

  8. A studentized permutation test for three-arm trials in the 'gold standard' design.

    Science.gov (United States)

    Mütze, Tobias; Konietschke, Frank; Munk, Axel; Friede, Tim

    2017-03-15

    The 'gold standard' design for three-arm trials refers to trials with an active control and a placebo control in addition to the experimental treatment group. This trial design is recommended when being ethically justifiable and it allows the simultaneous comparison of experimental treatment, active control, and placebo. Parametric testing methods have been studied plentifully over the past years. However, these methods often tend to be liberal or conservative when distributional assumptions are not met particularly with small sample sizes. In this article, we introduce a studentized permutation test for testing non-inferiority and superiority of the experimental treatment compared with the active control in three-arm trials in the 'gold standard' design. The performance of the studentized permutation test for finite sample sizes is assessed in a Monte Carlo simulation study under various parameter constellations. Emphasis is put on whether the studentized permutation test meets the target significance level. For comparison purposes, commonly used Wald-type tests, which do not make any distributional assumptions, are included in the simulation study. The simulation study shows that the presented studentized permutation test for assessing non-inferiority in three-arm trials in the 'gold standard' design outperforms its competitors, for instance the test based on a quasi-Poisson model, for count data. The methods discussed in this paper are implemented in the R package ThreeArmedTrials which is available on the comprehensive R archive network (CRAN). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. The transitive fallacy for randomized trials: If A bests B and B bests C in separate trials, is A better than C?

    Directory of Open Access Journals (Sweden)

    Kramer Barnett S

    2002-11-01

    Full Text Available Abstract Background If intervention A bests B in one randomized trial, and B bests C in another randomized trial, can one conclude that A is better than C? The problem was motivated by the planning of a randomized trial, where A is spiral-CT screening, B is x-ray screening, and C is no screening. On its surface, this would appear to be a straightforward application of the transitive principle of logic. Methods We extended the graphical approach for omitted binary variables that was originally developed to illustrate Simpson's paradox, applying it to hypothetical, but plausible scenarios involving lung cancer screening, treatment for gastric cancer, and antibiotic therapy for clinical pneumonia. Results Graphical illustrations of the three examples show different ways the transitive fallacy for randomized trials can arise due to changes in an unobserved or unadjusted binary variable. In the most dramatic scenario, B bests C in the first trial, A bests B in the second trial, but C bests A at the time of the second trial. Conclusion Even with large sample sizes, combining results from a previous randomized trial of B versus C with results from a new randomized trial of A versus B will not guarantee correct inference about A versus C. A three-arm trial of A, B, and C would protect against this problem and should be considered when the sequential trials are performed in the context of changing secular trends in important omitted variables such as therapy in cancer screening trials.

  10. Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Tamarelle, Jeanne; Thiébaut, Anne C M; Sabin, Bénédicte; Bébéar, Cécile; Judlin, Philippe; Fauconnier, Arnaud; Rahib, Delphine; Méaude-Roufai, Layidé; Ravel, Jacques; Morré, Servaas A; de Barbeyrac, Bertille; Delarocque-Astagneau, Elisabeth

    2017-11-13

    Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months. This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status. This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to

  11. Improving clinical trial design for hepatocellular carcinoma treatments

    Directory of Open Access Journals (Sweden)

    Robert G. Gish

    2011-12-01

    Full Text Available Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.

  12. Understanding sustained domestic violence identification in maternal and child health nurse care: process evaluation from a 2-year follow-up of the MOVE trial.

    Science.gov (United States)

    Hooker, Leesa; Small, Rhonda; Taft, Angela

    2016-03-01

    To investigate factors contributing to the sustained domestic violence screening and support practices of Maternal and Child Health nurses 2 years after a randomized controlled trial. Domestic violence screening by healthcare professionals has been implemented in many primary care settings. Barriers to screening exist and screening rates remain low. Evidence for longer term integration of nurse screening is minimal. Trial outcomes showed sustained safety planning behaviours by intervention group nurses. Process evaluation in 2-year follow-up of a cluster randomized controlled trial. Evaluation included a repeat online nurse survey and 14 interviews (July-September 2013). Survey analysis included comparison of proportionate group difference between arms and between trial baseline and 2 year follow-up surveys. Framework analysis was used to assess qualitative data. Normalization Process Theory informed evaluation design and interpretation of results. Survey response was 77% (n = 123/160). Sustainability of nurse identification of domestic violence appeared to be due to greater nurse discussion and domestic violence disclosure by women, facilitated by use of a maternal health and well-being checklist. Over time, intervention group nurses used the maternal checklist more at specific maternal health visits and found the checklist the most helpful resource assisting their domestic violence work. Nurses' spoke of a degree of 'normalization' to domestic violence screening that will need constant investment to maintain. Sustainable domestic violence screening and support outcomes can be achieved in an environment of comprehensive, nurse designed and theory driven implementation. Continuing training, discussion and monitoring of domestic violence work is needed to retain sustainable practices. © 2015 John Wiley & Sons Ltd.

  13. Using Electronic Health Records Data for Substance Use Screening, Brief Intervention, and Referral to Treatment among Adults with Type 2 Diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network Study

    Science.gov (United States)

    Wu, Li-Tzy; Brady, Kathleen T.; Spratt, Susan E.; Dunham, Ashley A.; Heidenfelder, Brooke; Batch, Bryan C.; Lindblad, Robert; VanVeldhuisen, Paul; Rusincovitch, Shelley A.; Killeen, Therese K.; Ghitza, Udi E.

    2015-01-01

    Background The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. Methods We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. Discussion By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions. PMID:26563446

  14. Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

    Science.gov (United States)

    Viksveen, Petter; Relton, Clare; Nicholl, Jon

    2017-07-06

    Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

  15. Designing a Visual Factors-Based Screen Display Interface: The New Role of the Graphic Technologist.

    Science.gov (United States)

    Faiola, Tony; DeBloois, Michael L.

    1988-01-01

    Discusses the role of the graphic technologist in preparing computer screen displays for interactive videodisc systems, and suggests screen design guidelines. Topics discussed include the grid system; typography; visual factors research; color; course mobility through branching and software menus; and a model of course integration. (22 references)…

  16. A Population-Level Data Analytics Portal for Self-Administered Lifestyle and Mental Health Screening.

    Science.gov (United States)

    Zhang, Xindi; Warren, Jim; Corter, Arden; Goodyear-Smith, Felicity

    2016-01-01

    This paper describes development of a prototype data analytics portal for analysis of accumulated screening results from eCHAT (electronic Case-finding and Help Assessment Tool). eCHAT allows individuals to conduct a self-administered lifestyle and mental health screening assessment, with usage to date chiefly in the context of primary care waiting rooms. The intention is for wide roll-out to primary care clinics, including secondary school based clinics, resulting in the accumulation of population-level data. Data from a field trial of eCHAT with sexual health questions tailored to youth were used to support design of a data analytics portal for population-level data. The design process included user personas and scenarios, screen prototyping and a simulator for generating large-scale data sets. The prototype demonstrates the promise of wide-scale self-administered screening data to support a range of users including practice managers, clinical directors and health policy analysts.

  17. Computer Enabled Neuroplasticity Treatment: a Clinical Trial of a Novel Design for Neurofeedback Therapy in Adult ADHD

    Directory of Open Access Journals (Sweden)

    Benjamin eCowley

    2016-05-01

    Full Text Available BackgroundWe report a randomised controlled clinical trial of neurofeedback therapy intervention for ADHD/ADD in adults. We focus on internal mechanics of neurofeedback learning, to elucidate the primary role of cortical self-regulation in neurofeedback. We report initial results; more extensive analysis will follow.MethodsTrial has two phases: intervention and follow-up. The intervention consisted of neurofeedback treatment, including intake and outtake measurements, using a waiting-list control group. Treatment involved $sim$40 hour-long sessions 2-5 times per week. Training involved either theta/beta or sensorimotor-rhythm regimes, adapted by adding a novel 'inverse-training' condition to promote self-regulation. Follow-up (ongoing will consist of self-report and executive function tests.SettingIntake and outtake measurements were conducted at University of Helsinki. Treatment was administered at partner clinic Mental Capital Care, Helsinki.RandomisationWe randomly allocated half the sample then adaptively allocated the remainder to minimise baseline differences in prognostic variables.BlindingWaiting-list control design meant trial was not blinded.Participants54 adult Finnish participants (mean age 36 years; 29 females were recruited after screening by psychiatric review. 44 had ADHD diagnoses, 10 had ADD.MeasurementsSymptoms were assessed by computerised attention test (T.O.V.A. and self-report scales, at intake and outtake. Performance during neurofeedback trials was recorded.ResultsParticipants were recruited and completed intake measurements during summer 2012, before assignment to treatment and control, September 2012. Outtake measurements ran April-August 2013. After dropouts, 23 treatment and 21 waiting-list participants remained for analysis.Initial analysis showed that, compared to waiting-list control, neurofeedback promoted improvement of self-reported ADHD symptoms, but did not show transfer of learning to T.O.V.A. Comprehensive

  18. A Review of Different Behavior Modification Strategies Designed to Reduce Sedentary Screen Behaviors in Children

    Directory of Open Access Journals (Sweden)

    Jeremy A. Steeves

    2012-01-01

    Full Text Available Previous research suggests that reducing sedentary screen behaviors may be a strategy for preventing and treating obesity in children. This systematic review describes strategies used in interventions designed to either solely target sedentary screen behaviors or multiple health behaviors, including sedentary screen behaviors. Eighteen studies were included in this paper; eight targeting sedentary screen behaviors only, and ten targeting multiple health behaviors. All studies used behavior modification strategies for reducing sedentary screen behaviors in children (aged 1–12 years. Nine studies only used behavior modification strategies, and nine studies supplemented behavior modification strategies with an electronic device to enhance sedentary screen behaviors reductions. Many interventions (50% significantly reduced sedentary screen behaviors; however the magnitude of the significant reductions varied greatly (−0.44 to −3.1 h/day and may have been influenced by the primary focus of the intervention, number of behavior modification strategies used, and other tools used to limit sedentary screen behaviors.

  19. A review of different behavior modification strategies designed to reduce sedentary screen behaviors in children.

    Science.gov (United States)

    Steeves, Jeremy A; Thompson, Dixie L; Bassett, David R; Fitzhugh, Eugene C; Raynor, Hollie A

    2012-01-01

    Previous research suggests that reducing sedentary screen behaviors may be a strategy for preventing and treating obesity in children. This systematic review describes strategies used in interventions designed to either solely target sedentary screen behaviors or multiple health behaviors, including sedentary screen behaviors. Eighteen studies were included in this paper; eight targeting sedentary screen behaviors only, and ten targeting multiple health behaviors. All studies used behavior modification strategies for reducing sedentary screen behaviors in children (aged 1-12 years). Nine studies only used behavior modification strategies, and nine studies supplemented behavior modification strategies with an electronic device to enhance sedentary screen behaviors reductions. Many interventions (50%) significantly reduced sedentary screen behaviors; however the magnitude of the significant reductions varied greatly (-0.44 to -3.1 h/day) and may have been influenced by the primary focus of the intervention, number of behavior modification strategies used, and other tools used to limit sedentary screen behaviors.

  20. Summary of trial design of improved marine nuclear reactors

    International Nuclear Information System (INIS)

    1984-01-01

    In order to carry out the research and development of improved marine nuclear reactors, the Japan Nuclear Ship Research and Development Agency decided the project for the purpose in accordance with the procedure of research and development shown by the Nuclear Ship Research and Development Committee of Atomic Energy Commission in December, 1979, and along the basic plan regarding the development of nuclear ships of the Agency decided in February, 1981. As the first step, the Agency has been advancing the research on the design evaluation comprising the trial design and conceptual design to establish the concept of the marine reactor plant with excellent economical efficiency and reliability, which will be developed as the practical plant for future nuclear ships. The trial design started as a three-year project from 1983 is related to a 100 MWt marine reactor, and it is to obtain the concept of improved marine reactors which can be realized after adequate development period based on the pressurized water reactors of separate type, one-body type and semi-one-body type. In this summary, the works carried out in fiscal year 1983 are reported, that is, the design and calculation of the reactor core and the equipment of primary cooling system, and the selection of the required items of research and development. (Kako, I.)

  1. Primary Care Provider-Delivered Smoking Cessation Interventions and Smoking Cessation Among Participants in the National Lung Screening Trial.

    Science.gov (United States)

    Park, Elyse R; Gareen, Ilana F; Japuntich, Sandra; Lennes, Inga; Hyland, Kelly; DeMello, Sarah; Sicks, JoRean D; Rigotti, Nancy A

    2015-09-01

    The National Lung Screening Trial (NLST) found a reduction in lung cancer mortality among participants screened with low-dose computed tomography vs chest radiography. In February 2015, Medicare announced its decision to cover annual lung screening for patients with a significant smoking history. These guidelines promote smoking cessation treatment as an adjunct to screening, but the frequency and effectiveness of clinician-delivered smoking cessation interventions delivered after lung screening are unknown. To determine the association between the reported clinician-delivered 5As (ask, advise, assess, assist [talk about quitting or recommend stop-smoking medications or recommend counseling], and arrange follow-up) after lung screening and smoking behavior changes. A matched case-control study (cases were quitters and controls were continued smokers) of 3336 NLST participants who were smokers at enrollment examined participants' rates and patterns of 5A delivery after a lung screen and reported smoking cessation behaviors. Prevalence of the clinician-delivered 5As and associated smoking cessation after lung screening. Delivery of the 5As 1 year after screening were as follows: ask, 77.2%; advise, 75.6%; assess, 63.4%; assist, 56.4%; and arrange follow-up, 10.4%. Receipt of ask, advise, and assess was not significantly associated with quitting in multivariate models that adjusted for sociodemographic characteristics, medical history, screening results, nicotine dependence, and motivation to quit. Assist was associated with a 40% increase in the odds of quitting (odds ratio, 1.40; 95% CI, 1.21-1.63), and arrange was associated with a 46% increase in the odds of quitting (odds ratio, 1.46; 95% CI, 1.19-1.79). Assist and arrange follow-up delivered by primary care providers to smokers who were participating in the NLST were associated with increased quitting; less intensive interventions (ask, advise, and assess) were not. However, rates of assist and arrange

  2. Clinical Trials

    Medline Plus

    Full Text Available ... treatments produce better results for certain illnesses or groups of people; look at the best age and frequency for doing screening tests, such as mammography; and compare two or more screening tests to see which test ... Some companies and groups sponsor clinical trials that test the safety of ...

  3. Systematic Review of Guidelines on Peripheral Artery Disease Screening

    NARCIS (Netherlands)

    Ferket, Bart S.; Spronk, Sandra; Colkesen, Ersen B.; Hunink, M. G. Myriam

    2012-01-01

    BACKGROUND: Peripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed.

  4. Design of an off-axis visual display based on a free-form projection screen to realize stereo vision

    Science.gov (United States)

    Zhao, Yuanming; Cui, Qingfeng; Piao, Mingxu; Zhao, Lidong

    2017-10-01

    A free-form projection screen is designed for an off-axis visual display, which shows great potential in applications such as flight training for providing both accommodation and convergence cues for pilots. The method based on point cloud is proposed for the design of the free-form surface, and the design of the point cloud is controlled by a program written in the macro-language. In the visual display based on the free-form projection screen, when the error of the screen along Z-axis is 1 mm, the error of visual distance at each filed is less than 1%. And the resolution of the design for full field is better than 1‧, which meet the requirement of resolution for human eyes.

  5. Assessment and model guided cancer screening promotion by village doctors in China: a randomized controlled trial protocol.

    Science.gov (United States)

    Feng, Rui; Shen, Xingrong; Chai, Jing; Chen, Penglai; Cheng, Jing; Liang, Han; Zhao, Ting; Sha, Rui; Li, Kaichun; Wang, Debin

    2015-10-12

    Proven cost-effectiveness contrasted by low uptake of cancer screening (CS) calls for new methodologies promoting the service. Contemporary interventions in this regard relies primarily on strategies targeting general or specific groups with limited attention being paid to individualized approaches. This trial tests a novel package promoting CS utilization via continuous and tailored counseling delivered by primary caregivers. It aims at demonstrating that high risk individuals in the intervention arm will, compared to those in the delayed intervention condition, show increased use of CS service. The trial adopts a quasi-randomized controlled trial design and involves 2160 high risk individuals selected, via rapid and detailed risk assessments, from about 72,000 farmers aged 35+ in 36 administrative villages randomized into equal intervention and delayed intervention arms. The CS intervention package uses: a) village doctors and village clinics to deliver personalized and thus relatively sophisticated CS counseling; b) two-stage risk assessment models in identifying high risk individuals to focus the intervention on the most needed; c) standardized operation procedures to guide conduct of counseling; d) real-time effectiveness and quality monitoring to leverage continuous improvement; e) web-based electronic system to enable prioritizing complex determinants of CS uptake and tailoring counseling sessions to the changing needs of individual farmers. The intervention arm receives baseline and semiannual follow up evaluations plus CS counseling for 5 years; while the delayed intervention arm, only the same baseline and follow-up evaluations for the first 5 years and CS counseling starting from the 6th year if the intervention proved effective. Evaluation measures include: CS uptake by high risk farmers and changes in their knowledge, perceptions and self-efficacy about CS. Given the complexity and heterogeneity in the determinant system of individual CS service

  6. NMR screening in fragment-based drug design: a practical guide.

    Science.gov (United States)

    Kim, Hai-Young; Wyss, Daniel F

    2015-01-01

    Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

  7. Recruitment, screening, and baseline participant characteristics in the WALK 2.0 study: A randomized controlled trial using web 2.0 applications to promote physical activity

    Directory of Open Access Journals (Sweden)

    Cristina M. Caperchione

    2016-04-01

    Conclusion: The results of this recruitment process demonstrate the successful use of multiple strategies to obtain a diverse sample of adults eligible to take part in a web-based physical activity promotion intervention. The use of dual screening processes ensured safe participation in the intervention. This approach to recruitment and physical activity screening can be used as a model for further trials in this area.

  8. Sensitivity of adaptive enrichment trial designs to accrual rates, time to outcome measurement, and prognostic variables

    Directory of Open Access Journals (Sweden)

    Tianchen Qian

    2017-12-01

    Full Text Available Adaptive enrichment designs involve rules for restricting enrollment to a subset of the population during the course of an ongoing trial. This can be used to target those who benefit from the experimental treatment. Trial characteristics such as the accrual rate and the prognostic value of baseline variables are typically unknown when a trial is being planned; these values are typically assumed based on information available before the trial starts. Because of the added complexity in adaptive enrichment designs compared to standard designs, it may be of special concern how sensitive the trial performance is to deviations from assumptions. Through simulation studies, we evaluate the sensitivity of Type I error, power, expected sample size, and trial duration to different design characteristics. Our simulation distributions mimic features of data from the Alzheimer's Disease Neuroimaging Initiative cohort study, and involve two subpopulations based on a genetic marker. We investigate the impact of the following design characteristics: the accrual rate, the time from enrollment to measurement of a short-term outcome and the primary outcome, and the prognostic value of baseline variables and short-term outcomes. To leverage prognostic information in baseline variables and short-term outcomes, we use a semiparametric, locally efficient estimator, and investigate its strengths and limitations compared to standard estimators. We apply information-based monitoring, and evaluate how accurately information can be estimated in an ongoing trial.

  9. Randomized controlled trial of storytelling compared to a personal risk tool intervention on colorectal cancer screening in low-income patients.

    Science.gov (United States)

    Larkey, Linda K; McClain, Darya; Roe, Denise J; Hector, Richard D; Lopez, Ana Maria; Sillanpaa, Brian; Gonzalez, Julie

    2015-01-01

    Screening rates for colorectal cancer (CRC) lag for low-income, minority populations, contributing to poorer survival rates. A model of storytelling as culture-centric health promotion was tested for promoting CRC screening. A two-group parallel randomized controlled trial. Primary care, safety-net clinics. Low-income patients due for CRC screening, ages 50 to 75 years, speaking English or Spanish. Patients were exposed to either a video created from personal stories composited into a drama about "Papa" receiving CRC screening, or an instrument estimating level of personal cancer risk. Patients received a health care provider referral for CRC screening and were followed up for 3 months to document adherence. Behavioral factors related to the narrative model (identification and engagement) and theory of planned behavior. Main effects of the interventions on screening were tested, controlling for attrition factors, and demographic factor associations were assessed. Path analysis with model variables was used to test the direct effects and multiple mediator models. Main effects on CRC screening (roughly half stool-based tests, half colonoscopy) did not indicate significant differences (37% and 42% screened for storytelling and risk-based messages, respectively; n = 539; 33.6% male; 62% Hispanic). Factors positively associated with CRC screening included being female, Hispanic, married or living with a partner, speaking Spanish, having a primary care provider, lower income, and no health insurance. Engagement, working through positive attitudes toward the behavior, predicted CRC screening. A storytelling and a personalized risk-tool intervention achieved similar levels of screening among unscreened/underscreened, low-income patients. Factors usually associated with lower rates of screening (e.g., no insurance, being Hispanic) were related to more adherence. Both interventions' engagement factor facilitated positive attitudes about CRC screening associated with behavior

  10. Generalisability of the results of the Dutch-Belgian randomised controlled lung cancer CT screening trial (NELSON) : Does self-selection play a role?

    NARCIS (Netherlands)

    van der Aalst, C. M.; van Iersel, C. A.; van Klaveren, R. J.; Frenken, F. J. M.; Fracheboud, J.; Otto, S. J.; de Jong, P. A.; Oudkerk, M.; de Koning, H. J.

    The degree of self-selection in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON) was determined to assess the generalisability of the study results. 335,441 (mainly) men born in 1928-1953 received a questionnaire. Of the respondents (32%), eligible subjects were invited

  11. Low adherence to cervical cancer screening after subtotal hysterectomy

    DEFF Research Database (Denmark)

    Andersen, Lea Laird; Møller, Lars Mikael Alling; Gimbel, Helga Margrethe

    2015-01-01

    INTRODUCTION: A reason for not recommending subtotal hysterectomy is the risk of cervical pathology. We aimed to evaluate cervical cancer screening and to describe cervical pathology after subtotal and total hysterectomy for benign indications. METHODS: Data regarding adherence to screening...... Hospital, Rigs-hospitalet and Roskilde Hospital, Denmark. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01880710....

  12. Implications of Clinical Trial Design on Sample Size Requirements

    OpenAIRE

    Leon, Andrew C.

    2008-01-01

    The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two par...

  13. Baseline prevalence of abdominal aortic aneurysm, peripheral arterial disease and hypertension in men aged 65-74 years from a population screening study (VIVA trial)

    DEFF Research Database (Denmark)

    Grøndal, N; Søgaard, R; Lindholt, J S

    2015-01-01

    (PAD) and possible hypertension (HT), and detection rates. METHODS: This observational study was based on the intervention arm of a screening trial in 25 083 Danish men aged 65-74 years. A combined screening programme for AAA, PAD and HT was offered at local hospitals. Participants with positive test...... results were offered secondary prophylaxis and/or referred to their general practitioner. The programme set-up included decentralized screening by three mobile teams at 14 venues. Diagnostic criteria were: aortic diameter at least 30 mm for AAA, ankle : brachial pressure index below 0·9 or above 1...

  14. Does access to a colorectal cancer screening website and/or a nurse-managed telephone help line provided to patients by their family physician increase fecal occult blood test uptake?: A pragmatic cluster randomized controlled trial study protocol

    Directory of Open Access Journals (Sweden)

    Clouston Kathleen

    2012-05-01

    Full Text Available Abstract Background Fecal occult blood test screening in Canada is sub-optimal. Family physicians play a central role in screening and are limited by the time constraints of clinical practice. Patients face multiple barriers that further reduce completion rates. Tools that support family physicians in providing their patients with colorectal cancer information and that support uptake may prove useful. The primary objective of the study is to evaluate the efficacy of a patient decision aid (nurse-managed telephone support line and/or colorectal cancer screening website distributed by community-based family physicians, in improving colorectal cancer screening rates. Secondary objectives include evaluation of (disincentives to patient FOBT uptake and internet use among 50 to 74 year old males and females for health-related questions. Challenges faced by family physicians in engaging in collaborative partnerships with primary healthcare researchers will be documented. Methods/design A pragmatic, two-arm, randomized cluster controlled trial conducted in 22 community-based family practice clinics (36 clusters with 76 fee-for-service family physicians in Winnipeg, Manitoba, Canada. Each physician will enroll 30 patients attending their periodic health examination and at average risk for colorectal cancer. All physicians will follow their standard clinical practice for screening. Intervention group physicians will provide a fridge magnet to each patient that contains information facilitating access to the study-specific colorectal cancer screening decision aids (telephone help-line and website. The primary endpoint is patient fecal occult blood test completion rate after four months (intention to treat model. Multi-level analysis will include clinic, physician and patient level variables. Patient Personal Health Identification Numbers will be collected from those providing consent to facilitate analysis of repeat screening behavior. Secondary outcome

  15. Staying well after depression: trial design and protocol.

    Science.gov (United States)

    Williams, J Mark G; Russell, Ian T; Crane, Catherine; Russell, Daphne; Whitaker, Chris J; Duggan, Danielle S; Barnhofer, Thorsten; Fennell, Melanie J V; Crane, Rebecca; Silverton, Sarah

    2010-03-19

    Depression is often a chronic relapsing condition, with relapse rates of 50-80% in those who have been depressed before. This is particularly problematic for those who become suicidal when depressed since habitual recurrence of suicidal thoughts increases likelihood of further acute suicidal episodes. Therefore the question how to prevent relapse is of particular urgency in this group. This trial compares Mindfulness-Based Cognitive Therapy (MBCT), a novel form of treatment combining mindfulness meditation and cognitive therapy for depression, with both Cognitive Psycho-Education (CPE), an equally plausible cognitive treatment but without meditation, and treatment as usual (TAU). It will test whether MBCT reduces the risk of relapse in recurrently depressed patients and the incidence of suicidal symptoms in those with a history of suicidality who do relapse. It recruits participants, screens them by telephone for main inclusion and exclusion criteria and, if they are eligible, invites them to a pre-treatment session to assess eligibility in more detail. This trial allocates eligible participants at random between MBCT and TAU, CPE and TAU, and TAU alone in a ratio of 2:2:1, stratified by presence of suicidal ideation or behaviour and current anti-depressant use. We aim to recruit sufficient participants to allow for retention of 300 following attrition. We deliver both active treatments in groups meeting for two hours every week for eight weeks. We shall estimate effects on rates of relapse and suicidal symptoms over 12 months following treatment and assess clinical status immediately after treatment, and three, six, nine and twelve months thereafter. This will be the first trial of MBCT to investigate whether MCBT is effective in preventing relapse to depression when compared with a control psychological treatment of equal plausibility; and to explore the use of MBCT for the most severe recurrent depression--that in people who become suicidal when depressed.

  16. Evaluation of the mammography screening studies conducted in Europe and North America

    International Nuclear Information System (INIS)

    Schreer, I.

    2001-01-01

    The ancient randomized-controlled trials of breast cancer screening have offered clear evidence that invitation to participate in mammography screening with/without clinical examination is effective in breast cancer mortality reduction and underline the detection sensitivity of mammography. Recently published criticism of both the effect and fundamental data handling could be shown to be untenable. Randomized studies underestimate the effect while well-designed observational studies do not systematically overestimate the magnitude of the effect. To transform high-quality study results in all-day's practice is a huge challenge, but affordable as has been demonstrated in Great Britain, the Netherlands and Sweden. (orig.) [de

  17. Financial disincentives? A three-armed randomised controlled trial of the effect of financial Incentives  in Diabetic Eye Assessment  by Screening (IDEAS) trial.

    Science.gov (United States)

    Judah, Gaby; Darzi, Ara; Vlaev, Ivo; Gunn, Laura; King, Derek; King, Dominic; Valabhji, Jonathan; Bicknell, Colin

    2018-05-23

    Conflicting evidence exists regarding the impact of financial incentives on encouraging attendance at medical screening appointments. The primary aim was to determine whether financial incentives increase attendance at diabetic eye screening in persistent non-attenders. A three-armed randomised controlled trial was conducted in London in 2015. 1051 participants aged over 16 years, who had not attended eye screening appointments for 2 years or more, were randomised (1.4:1:1 randomisation ratio) to receive the usual invitation letter (control), an offer of £10 cash for attending screening (fixed incentive) or a 1 in 100 chance of winning £1000 (lottery incentive) if they attend. The primary outcome was the proportion of invitees attending screening, and a comparative analysis was performed to assess group differences. Pairwise comparisons of attendance rates were performed, using a conservative Bonferroni correction for independent comparisons. 34/435 (7.8%) of control, 17/312 (5.5%) of fixed incentive and 10/304 (3.3%) of lottery incentive groups attended. Participants who received any incentive were significantly less likely to attend their appointment compared with controls (risk ratio (RR)=0.56; 95% CI 0.34 to 0.92). Those in the probabilistic incentive group (RR=0.42; 95% CI 0.18 to 0.98), but not the fixed incentive group (RR=1.66; 95% CI 0.65 to 4.21), were significantly less likely to attend than those in the control group. Financial incentives, particularly lottery-based incentives, attract fewer patients to diabetic eye screening than standard invites in this population. Financial incentives should not be used to promote screening unless tested in context, as they may negatively affect attendance rates. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

    Science.gov (United States)

    Paoletti, X; Ezzalfani, M; Le Tourneau, C

    2015-09-01

    More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection.

    Science.gov (United States)

    Huang, David T; Angus, Derek C; Chang, Chung-Chou H; Doi, Yohei; Fine, Michael J; Kellum, John A; Peck-Palmer, Octavia M; Pike, Francis; Weissfeld, Lisa A; Yabes, Jonathan; Yealy, Donald M

    2017-08-29

    Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns. The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection. We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation. ClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

  20. Iterative design and field trial of an aphasia-friendly email tool

    NARCIS (Netherlands)

    Al Mahmud, A.; Martens, J.B.O.S.

    2015-01-01

    In this article, we describe the iterative design and field trial of Amail, an email client specifically designed for people with aphasia who have problems expressing themselves verbally. We conducted a 3-month study with eight persons with aphasia to better understand how people with aphasia could

  1. Neighborhood Effects in a Behavioral Randomized Controlled Trial

    OpenAIRE

    Pruitt, Sandi L.; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

    2014-01-01

    Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5,628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially import...

  2. Design of a general-purpose European compound screening library for EU-OPENSCREEN.

    Science.gov (United States)

    Horvath, Dragos; Lisurek, Michael; Rupp, Bernd; Kühne, Ronald; Specker, Edgar; von Kries, Jens; Rognan, Didier; Andersson, C David; Almqvist, Fredrik; Elofsson, Mikael; Enqvist, Per-Anders; Gustavsson, Anna-Lena; Remez, Nikita; Mestres, Jordi; Marcou, Gilles; Varnek, Alexander; Hibert, Marcel; Quintana, Jordi; Frank, Ronald

    2014-10-01

    This work describes a collaborative effort to define and apply a protocol for the rational selection of a general-purpose screening library, to be used by the screening platforms affiliated with the EU-OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening-compliant physicochemical properties, loose compliance to drug-likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre-filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in-house methodology and expertise. An in-depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics-driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general-purpose self-organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU-OPENSCREEN library could

  3. Breast cancer screening

    International Nuclear Information System (INIS)

    Vandenbroucke, A.

    1987-01-01

    Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

  4. Screening for abdominalt aortaaneurisme

    DEFF Research Database (Denmark)

    Lindholt, J S; Juul, Svend; Henneberg, E W

    1997-01-01

    rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...... on uncertain assumptions concerning prevalence, incidence and risk of rupture. Therefore a randomized trial screening of 65-73 year old males is taking place in the County of Viborg in Denmark. Udgivelsesdato: 1997-Mar-24...

  5. Design of clinical trials Phase I and II with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Giannone, C.A.; Soroa, V.E.

    2015-01-01

    We presented some usual designs for clinical studies in Phase I and Phase II. For Phase I we considered the 3 + 3 Classic design, designs with accelerated titration and those with dose escalation schemes with overdose control (EWOC). For Phase II designs with efficacy outcomes are presented. The design proposed by Fleming is discussed as well as those with inclusion of patients in two stages: Gehan’s design and the Optimal two–stage Simon’s design. We also discussed the design of combined endpoints of efficacy and safety of Bryant and Day with an application example of therapeutically Lu-177. Finally some proposals for phase II trials with control group are considered. (authors) [es

  6. Valuing Trial Designs from a Pharmaceutical Perspective Using Value-Based Pricing.

    Science.gov (United States)

    Breeze, Penny; Brennan, Alan

    2015-11-01

    Our aim was to adapt the traditional framework for expected net benefit of sampling (ENBS) to be more compatible with drug development trials from the pharmaceutical perspective. We modify the traditional framework for conducting ENBS and assume that the price of the drug is conditional on the trial outcomes. We use a value-based pricing (VBP) criterion to determine price conditional on trial data using Bayesian updating of cost-effectiveness (CE) model parameters. We assume that there is a threshold price below which the company would not market the new intervention. We present a case study in which a phase III trial sample size and trial duration are varied. For each trial design, we sampled 10,000 trial outcomes and estimated VBP using a CE model. The expected commercial net benefit is calculated as the expected profits minus the trial costs. A clinical trial with shorter follow-up, and larger sample size, generated the greatest expected commercial net benefit. Increasing the duration of follow-up had a modest impact on profit forecasts. Expected net benefit of sampling can be adapted to value clinical trials in the pharmaceutical industry to optimise the expected commercial net benefit. However, the analyses can be very time consuming for complex CE models. © 2014 The Authors. Health Economics published by John Wiley & Sons Ltd.

  7. Large screen mimic display design research for advanced main control room in nuclear power plant

    International Nuclear Information System (INIS)

    Zheng Mingguang; Yang Yanhua; Xu Jijun; Zhang Qinshun; Ning Zhonghe

    2002-01-01

    Firstly the evolution of mimic diagrams or displays used in the main control room of nuclear power plant was introduced. The active functions of mimic diagrams were analyzed on the release of operator psychological burden and pressure, the assistance of operator for the information searching, status understanding, manual actuation, correct decision making as well as the safe and reliable operation of the nuclear power plant. The importance and necessity to use the (large screen) mimic diagrams in advanced main control room of nuclear power plant, the design principle, design details and verification measures of large screen mimic display are also described

  8. Study design issues in trials among children with MAM

    International Nuclear Information System (INIS)

    Friis, Henrik

    2014-01-01

    There is a need for acceptable and affordable food aid products for children with moderate acute malnutrition (MAM), which effectively restore body tissues and functions. The effects of potential products need to be assessed through randomised controlled trials (RCT). However, nutritional RCTs pose ethical and scientific challenges. Control groups are usually given “standard of care”, but recommendations for treatment do not exist in all settings or supplements are not always available. In places where treatment is nonexistent, not giving any food to children in the control group is not without ethical concerns. However, from public health and scientific perspectives, it is problematic to compare with supplements which are not recommended or the effect of which is unknown. Firstly, it is of questionable value for a low-income country that a trial is conducted to compare an experimental supplement to a supplement that is not already standard of care, and national ethics committees may not grant permission for such a trial. Secondly, it is difficult to interpret findings from a trial comparing an experimental supplement to one that has not been properly tested. Hence, where supplementation is not standard of care, it may be ethically justifiable to have an unsupplemented control group. In such cases, mothers should receive health education and the children should receive medical attention, be monitored closely, and referred for further medical examination and treatment if not recovering. Delayed supplementation may also be considered. Food interventions are complex, since supplements with the same energy content may be based on different ingredients, and nutrients in different forms and amounts. Consequently, there are an infinite number of potential food supplements, yet only a few can be tested in trials. Some components may be potentially important, but costly. If several factors are of interest, then a factorial design may be needed. E.g. the treatFOOD trial

  9. Using electronic health record data for substance use Screening, Brief Intervention, and Referral to Treatment among adults with type 2 diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network study.

    Science.gov (United States)

    Wu, Li-Tzy; Brady, Kathleen T; Spratt, Susan E; Dunham, Ashley A; Heidenfelder, Brooke; Batch, Bryan C; Lindblad, Robert; VanVeldhuisen, Paul; Rusincovitch, Shelley A; Killeen, Therese K; Ghitza, Udi E

    2016-01-01

    The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Rates of Delirium Diagnosis Do Not Improve with Emergency Risk Screening: Results of the Emergency Department Delirium Initiative Trial.

    Science.gov (United States)

    Arendts, Glenn; Love, Jennefer; Nagree, Yusuf; Bruce, David; Hare, Malcolm; Dey, Ian

    2017-08-01

    To determine whether a bundled risk screening and warning or action card system improves formal delirium diagnosis and person-centered outcomes in hospitalized older adults. Prospective trial with sequential introduction of screening and interventional processes. Two tertiary referral hospitals in Australia. Individuals aged 65 and older presenting to the emergency department (ED) and not requiring immediate resuscitation (N = 3,905). Formal ED delirium screening algorithm and use of a risk warning card with a recommended series of actions for the prevention and management of delirium during the subsequent admission MEASUREMENTS: Delirium diagnosis at hospital discharge, proportion discharged to new assisted living arrangements, in-hospital complications (use of sedation, falls, aspiration pneumonia, death), hospital length of stay. Participants with a positive risk screen were significantly more likely (relative risk = 6.0, 95% confidence interval = 4.9-7.3) to develop delirium, and the proportion of at-risk participants with a positive screen was constant across three study phases. Delirium detection rate in participants undergoing the final intervention (Phase 3) was 12.1% (a 2% absolute and 17% relative increase from the baseline rate) but this was not statistically significant (P = .29), and a similar relative increase was seen over time in participants not receiving the intervention CONCLUSION: A risk screening and warning or action card intervention in the ED did not significantly improve rates of delirium detection or other important outcomes. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  11. Factors influencing the decline in lung density in a Danish lung cancer screening cohort

    NARCIS (Netherlands)

    S.B. Shaker (Saher); A. Dirksen (Asger); P. Lo (Pechin); L.T. Skovgaard (Lene); M. de Bruijne (Marleen); J.H. Pedersen (Jerry)

    2012-01-01

    textabstractLung cancer screening trials provide an opportunity to study the natural history of emphysema by using computed tomography (CT) lung density as a surrogate parameter. In the Danish Lung Cancer Screening Trial, 2,052 participants were included. At screening rounds, smoking habits were

  12. The DIAN-TU Next Generation Alzheimer’s prevention trial: adaptive design and disease progression model

    Science.gov (United States)

    Bateman, Randall J.; Benzinger, Tammie L.; Berry, Scott; Clifford, David B.; Duggan, Cynthia; Fagan, Anne M.; Fanning, Kathleen; Farlow, Martin R.; Hassenstab, Jason; McDade, Eric M.; Mills, Susan; Paumier, Katrina; Quintana, Melanie; Salloway, Stephen P.; Santacruz, Anna; Schneider, Lon S.; Wang, Guoqiao; Xiong, Chengjie

    2016-01-01

    INTRODUCTION The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer’s disease in autosomal dominant Alzheimer’s disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation Prevention Trial (NexGen). METHODS In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the NIH, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen trial. RESULTS Our expanded trials toolbox consists of a Disease Progression Model for ADAD, primary endpoint DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. CONCLUSION These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD. PMID:27583651

  13. WE-D-207-00: CT Lung Cancer Screening and the Medical Physicist: Moving Forward

    International Nuclear Information System (INIS)

    2015-01-01

    In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancer Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in

  14. Screenings of lung cancer with low dose spiral CT: results of a three year pilot study and design of the randomised controlled trial Italung-CT; Screening della neoplasia polmonare con TC spirale a bassa dose: risultati di uno studio pilota triennale e disegno dello studio clinico randomizzato Italung-CT

    Energy Technology Data Exchange (ETDEWEB)

    Picozzi, Giulia [Firenze Univ., Firenze (Italy). Radiodiagnostica I-Dipartimento di Fisiopatologia Clinica; Paci, Enrico [Azienda Ospedaliera Universitaria di Careggi, Firenze (Italy). Unita' di Epidemiologia Clinica e Descrittiva Centro per lo Studio e la Prevenzione Oncologica; Lopes Pegna, Andrea [Azienda Ospedaliera Universitaria di Careggi, Firenze (Italy). U.O. Pneumologia] [and others

    2005-02-01

    Purpose: To report the results of a three-year observational pilot study of lung cancer screening with low dose computed tomography (CT) and to present the study design of a randomised clinical trial named as Italung CT. Materials and methods: Sixty (47 males and 13 females, mean age 64{+-}4.5 years) heavy smokers (at least 20 packs-year) underwent three low-dose spiral CT screening tests one year apart on a single slice or multislice CT scanner. Indeterminate nodules were managed according to the recommendations of the Early Lung Cancer Action Project. Results: Indeterminate nodules were observed in 33 (55%) of the subjects (60% at the baseline screening test, 24% at the first annual test and 16% at the second annual test). The size of the largest indeterminate nodule was <5mm in diameter in 20 subjects. 10 of whom showed the nodule at the baseline test. Forty-five subjects (75%) completed the first annual test and 42 (70%) the second annual test. One (1.6%) prevalent lung cancer (adenosquamous carcinoma) and one (2.2%) incident lung cancer (small cell cancer at the first annual examination) were observed, as well as pulmonary localisation of Hodgkin's lymphoma (at the second annual test). In addition, one subject underwent lung surgery for a chondromatous hamartoma. Conclusions: The results of the pilot study are substantially in line with those of other observational studies of greater sample size. This justifies optimism about the reliability of the results in the screened arm of the Italung Ct trial which hast just began. [Italian] Scopo: Riportare i risultati di uno studio pilota osservazionale di screening della neoplasia polmonare con TC a bassa dose della durata di tre anni e presentare il disegno dello studio clinico randomizzato Italung-CT. Materiale e metodi: Sessanta (47 uomini e 13 donne, eta' media 64{+-}4,5 anni) forti fumatori (almeno 20 pacchetti/anno) sono stati sottoposti ad un esame basale e a due controlli annuali con TC single o

  15. Optimal cost-effective designs of Phase II proof of concept trials and associated go-no go decisions.

    Science.gov (United States)

    Chen, Cong; Beckman, Robert A

    2009-01-01

    This manuscript discusses optimal cost-effective designs for Phase II proof of concept (PoC) trials. Unlike a confirmatory registration trial, a PoC trial is exploratory in nature, and sponsors of such trials have the liberty to choose the type I error rate and the power. The decision is largely driven by the perceived probability of having a truly active treatment per patient exposure (a surrogate measure to development cost), which is naturally captured in an efficiency score to be defined in this manuscript. Optimization of the score function leads to type I error rate and power (and therefore sample size) for the trial that is most cost-effective. This in turn leads to cost-effective go-no go criteria for development decisions. The idea is applied to derive optimal trial-level, program-level, and franchise-level design strategies. The study is not meant to provide any general conclusion because the settings used are largely simplified for illustrative purposes. However, through the examples provided herein, a reader should be able to gain useful insight into these design problems and apply them to the design of their own PoC trials.

  16. Recruitment, screening, and baseline participant characteristics in the WALK 2.0 study: A randomized controlled trial using web 2.0 applications to promote physical activity.

    Science.gov (United States)

    Caperchione, Cristina M; Duncan, Mitch J; Rosenkranz, Richard R; Vandelanotte, Corneel; Van Itallie, Anetta K; Savage, Trevor N; Hooker, Cindy; Maeder, Anthony J; Mummery, W Kerry; Kolt, Gregory S

    2016-04-15

    To describe in detail the recruitment methods and enrollment rates, the screening methods, and the baseline characteristics of a sample of adults participating in the Walk 2.0 Study, an 18 month, 3-arm randomized controlled trial of a Web 2.0 based physical activity intervention. A two-fold recruitment plan was developed and implemented, including a direct mail-out to an extract from the Australian Electoral Commission electoral roll, and other supplementary methods including email and telephone. Physical activity screening involved two steps: a validated single-item self-report instrument and the follow-up Active Australia Questionnaire. Readiness for physical activity participation was also based on a two-step process of administering the Physical Activity Readiness Questionnaire and, where needed, further clearance from a medical practitioner. Across all recruitment methods, a total of 1244 participants expressed interest in participating, of which 656 were deemed eligible. Of these, 504 were later enrolled in the Walk 2.0 trial (77% enrollment rate) and randomized to the Walk 1.0 group (n = 165), the Walk 2.0 group (n = 168), or the Logbook group (n = 171). Mean age of the total sample was 50.8 years, with 65.2% female and 79.1% born in Australia. The results of this recruitment process demonstrate the successful use of multiple strategies to obtain a diverse sample of adults eligible to take part in a web-based physical activity promotion intervention. The use of dual screening processes ensured safe participation in the intervention. This approach to recruitment and physical activity screening can be used as a model for further trials in this area.

  17. Quality control for digital mammography: Part II recommendations from the ACRIN DMIST trial

    International Nuclear Information System (INIS)

    Yaffe, Martin J.; Bloomquist, Aili K.; Mawdsley, Gordon E.

    2006-01-01

    The Digital Mammography Imaging Screening Trial (DMIST), conducted under the auspices of the American College of Radiology Imaging Network (ACRIN), is a clinical trial designed to compare the accuracy of digital versus screen-film mammography in a screening population [E. Pisano et al., ACRIN 6652--Digital vs. Screen-Film Mammography, ACRIN (2001)]. Part I of this work described the Quality Control program developed to ensure consistency and optimal operation of the digital equipment. For many of the tests, there were no failures during the 24 months imaging was performed in DMIST. When systems failed, they generally did so suddenly rather than through gradual deterioration of performance. In this part, the utility and effectiveness of those tests are considered. This suggests that after verification of proper operation, routine extensive testing would be of minimal value. A recommended set of tests is presented including additional and improved tests, which we believe meet the intent and spirit of the Mammography Quality Standards Act regulations to ensure that full-field digital mammography systems are functioning correctly, and consistently producing mammograms of excellent image quality

  18. Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

    NARCIS (Netherlands)

    Wille, M.M.W.; Riel, S.J. van; Saghir, Z.; Dirksen, A.; Pedersen, J.H.; Jacobs, C.; Thomsen, L.H.u.; Scholten, E.T.; Skovgaard, L.T.; Ginneken, B. van

    2015-01-01

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models.From the DLCST database, 1,152

  19. Sweeten, soother and swaddle for retinopathy of prematurity screening: a randomised placebo controlled trial.

    LENUS (Irish Health Repository)

    O'Sullivan, A

    2012-02-01

    OBJECTIVE: To assess the efficacy of oral sucrose combined with swaddling and non-nutritive suck (NNS) as a method for reducing pain associated with retinopathy of prematurity (ROP) screening. DESIGN: Randomised placebo controlled study. SETTING: Tertiary level neonatal intensive care unit. SAMPLE: 40 infants undergoing primary eye examination for ROP screening. INTERVENTION: The control group were swaddled, and received 0.2 ml of sterile water given by mouth using a syringe and a soother. The intervention group were swaddled, and received 0.2 ml of sucrose 24% given by mouth using a syringe and a soother. RESULTS: 40 infants were included in the study. There was no difference in mean gestational age at birth, mean birth weight or corrected gestational age at first examination between both groups. The sucrose group had a significantly lower median Neonatal Pain, Agitation and Sedation Scale (N-PASS) score during ROP screening, initially following insertion of the speculum (6.5 vs 5, p=0.02) and subsequently during scleral indentation (9.5 vs 7.5, p=0.03). Fewer infants experienced episodes of desaturations or bradycardia in the intervention group (1 vs 4, p=0.18). CONCLUSION: ROP screening is a necessary but recognised painful procedure. Sucrose combined with NNS and swaddling reduced the behavioural and physiological pain responses. However, pain scores remained consistently high and appropriate pain relief for ROP screening remains a challenge.

  20. Associations of maternal influences with outdoor play and screen time of two-year-olds: Findings from the Healthy Beginnings Trial.

    Science.gov (United States)

    Xu, Huilan; Wen, Li Ming; Rissel, Chris

    2014-09-01

    This study aims to investigate if maternal influences are associated with children's outdoor playtime and screen time at the age of 2 years. A cross-sectional study with 497 first-time mothers and their children was conducted using the data from the Healthy Beginnings Trial undertaken in Sydney, Australia during 2007-2010. Maternal influences included their own physical activity and screen time, television rules for their child, perceived neighbourhood environment, parental self-efficacy and parenting style (warmth and hostility). Children's outdoor playtime, screen time and maternal influences were collected through face-to-face interviews with participating mothers when the children were 2 years old. Logistic regression analysis was conducted to examine the associations between maternal influences and children's outdoor play and screen time. Mothers with low levels of parental hostility and high perceived safe outdoor play environment were more likely to have children playing outdoor for ≥ 2 h/day with adjusted odds ratio (AOR) 2.65 (95% confidence interval (CI) 1.68-4.20, P maternal influences were independently associated with children's outdoor play or screen time at an early stage of life. Therefore, different intervention strategies are needed to increase children's outdoor playtime and decrease their screen time. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  1. Recruitment of patients into head and neck clinical trials: acceptability of studies to patients from perspective of the research team.

    Science.gov (United States)

    Ho, M W; Pick, A S; Sutton, D N; Dyker, K; Cardale, K; Gilbert, K; Johnson, J; Quantrill, J; McCaul, J A

    2018-05-01

    We reviewed longitudinal recruitment data to assess recruitment into head and neck cancer trials, and to identify factors that could influence this and affect their acceptability to patients. We retrieved data from the prospective computerised database (2009-2016) to measure acceptability to patients using the recruitment:screening ratio, and compared observational with interventional studies, single specialty (or site) with multispecialty (or site) studies, and "step-up" randomisation with "non-inferiority" randomisation designs. A total of 1283 patients were screened and 583 recruited. The recruitment:screening ratio for all National Institute for Health Research (NIHR) portfolio studies combined was 0.47 (486/1133). Studies that involved treatment by several specialties or at several sites had a significantly adverse impact on acceptability (p=0.01). Recruitment into non-inferiority randomised controlled studies was lower than that into step-up randomised studies (p=0.06). The complexity of a study's design did not compromise recruitment. Treatment across several specialties or several sites and perceived non-inferiority designs, reduced the acceptability of some trials. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  2. Topical anesthesia or oral dextrose for the relief of pain in screening for retinopathy of prematurity: a randomized controlled double-blinded trial.

    Science.gov (United States)

    Nesargi, Saudamini V; Nithyanandam, Suneetha; Rao, Suman; Nimbalkar, Somashekhar; Bhat, Swarnarekha

    2015-02-01

    Compare efficacy of 0.5% proparacaine eye drops and oral 25% dextrose in reducing pain during screening for retinopathy of prematurity (ROP). Double-blinded randomized controlled trial. Twenty eligible babies were randomized. Group I received 0.5% proparacaine eye drops at first ROP screening, while Group II received 25% dextrose orally. At second examination, babies received no intervention. Pain was assessed using Premature Infant Pain Profile (PIPP) score. The mean ( ± SD) PIPP during procedure in Group I were 15.5 ± 2.06 and 14 ± 2.4 at first and second screening (p = 0.259). The mean ( ± SD) PIPP in Group II were 14.2 ± 1. 8 and 14.9 ± 2.5 at the first and second screening (p = 0.428). Differences were not statistically significant. The PIPP scores of Group I and Group II at the first screening were also not significantly different (p = 0.165). ROP screening causes moderate to severe pain and neither proparacaine nor dextrose is an effective analgesic. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. The effect of screening doors and windows on indoor density of Anopheles arabiensis in south-west Ethiopia: a randomized trial.

    Science.gov (United States)

    Massebo, Fekadu; Lindtjørn, Bernt

    2013-09-12

    Screening of houses might have impact on density of indoor host-seeking Anopheles mosquitoes. A randomized trial of screening windows and doors with metal mesh, and closing openings on eves and walls by mud was conducted to assess if reduce indoor densities of biting mosquitoes. Mosquitoes were collected in forty houses using Centers for Diseases Control and Prevention (CDC) light traps biweekly in March and April 2011. A randomization of houses into control and intervention groups was done based on the baseline data. Windows and doors of 20 houses were screened by metal mesh, and openings on the walls and eves closed by mud and the rest 20 houses were used as control group. Mosquitoes were collected biweekly in October and November 2011 from both control and intervention houses. A Generalized Estimating Equations (GEE) with a negative binomial error distribution was used to account for over dispersion of Anopheles arabiensis and culicine counts and repeated catches made in the same house. Screening doors and windows, and closing openings on eves and wall by mud reduced the overall indoor densities of An. arabiensis by 40%. The effect of screenings pronounced on unfed An. arabiensis by resulting 42% reduction in houses with interventions. The total costs for screening windows and doors, and to close openings on the eves and walls by mud was 7.34 USD per house. Screening houses reduced indoor density of An. arabiensis, and it was cheap and can easily incorporated into malaria vector strategies by local communities, but improving doors and windows fitness for screening should be considered during house construction to increase the efficacy of screenings.

  4. Shared decision-making for prostate cancer screening and treatment: a systematic review of randomised controlled trials.

    Science.gov (United States)

    Martínez-González, Nahara Anani; Plate, Andreas; Senn, Oliver; Markun, Stefan; Rosemann, Thomas; Neuner-Jehle, Stefan

    2018-02-23

    Men facing prostate cancer screening and treatment need to make critical and highly preference-sensitive decisions that involve a variety of potential benefits and risks. Shared decision-making (SDM) is considered fundamental for "preference-sensitive" medical decisions and it is guideline-recommended. There is no single definition of SDM however. We systematically reviewed the extent of SDM implementation in interventions to facilitate SDM for prostate cancer screening and treatment. We searched Medline Ovid, Embase (Elsevier), CINHAL (EBSCOHost), The Cochrane Library (Wiley), PsychINFO (EBSCOHost), Scopus, clinicaltrials.gov, ISRCTN registry, the WHO search portal, ohri.ca, opengrey.eu, Google Scholar, and the reference lists of included studies, clinical guidelines and relevant reviews. We also contacted the authors of relevant abstracts without available full text. We included primary peer-reviewed and grey literature of randomised controlled trials (RCTs) reported in English, conducted in primary and specialised care, addressing interventions aiming to facilitate SDM for prostate cancer screening and treatment. Two reviewers independently selected studies, appraised interventions and assessed the extent of SDM implementation based on the key features of SDM, namely information exchange, deliberation and implementation. We considered bi-directional deliberation as a central and mandatory component of SDM. We performed a narrative synthesis. Thirty-six RCTs including 19 196 randomised patients met the eligibility criteria; they were mainly conducted in North America (n = 28). The median year of publication was 2008 (1997-2015). Twenty-three RCTs addressed decision-making for screening, twelve for treatment and one for both screening and treatment for prostate cancer. Bi-directional interactions between healthcare providers and patients were verified in 31 RCTs, but only 14 fulfilled the three key SDM features, 14 had at least "deliberation", one had "unclear

  5. Web-based screening and brief intervention for poly-drug use among teenagers: study protocol of a multicentre two-arm randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Arnaud Nicolas

    2012-09-01

    Full Text Available Abstract Background Mid to late adolescence is characterised by a vulnerability to problematic substance use since the consumption of alcohol and illicit drugs is frequently initiated and increased in this life period. While the detrimental long- and short-term effects of problematic consumption patterns in adolescence pose a major public health concern, current prevention programs targeting alcohol- and other substance-using adolescents are scarce. The study described in this protocol will test the effectiveness of a web-based brief intervention aimed at reducing problematic alcohol use and promoting abstinence from illegal drugs in adolescents with risky substance use aged 16 to 18 years old in four EU-countries. Methods/design To determine the effectiveness of our web-BI, we apply a two-arm randomized controlled trial (RCT study design, with baseline assessment at study entry and a three month follow-up assessment. Adolescents aged 16 to 18 years from Belgium, the Czech Republic, Germany, and Sweden will be randomly assigned to either the fully electronically delivered brief intervention group (N = 400 or an assessment only control group (N = 400 depending on their screening for risky substance use (using the CRAFFT. Recruitment, informed consent, randomization, intervention and follow-up will be implemented online. Primary outcomes are reductions in frequency and quantity of use of alcohol and drugs other than alcohol over a 30 day period, as well as consumption per typical occasion. Secondary outcomes concern changes in substance use related cognitions including the constructs of the Theory of Planned Behaviour, implementation intentions, and stages of change. Moreover the study addresses a number of moderator variables, including age of first use, general psychopathology and quality of parent–child relationship. Discussion The trial is expected to contribute to the growing literature on theory- and web-based brief interventions

  6. The Pap smear screening as an occasion for smoking cessation and physical activity counselling: baseline characteristics of women involved in the SPRINT randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Chellini Elisabetta

    2011-12-01

    Full Text Available Abstract Background Gender-specific smoking cessation strategies have rarely been developed. Evidence of effectiveness of physical activity (PA promotion and intervention in adjunct to smoking cessation programs is not strong. SPRINT study is a randomized controlled trial (RCT designed to evaluate a counselling intervention on smoking cessation and PA delivered to women attending the Italian National Health System Cervical Cancer Screening Program. This paper presents study design and baseline characteristics of the study population. Methods/Design Among women undergoing the Pap examination in three study centres (Florence, Turin, Mantua, participants were randomized to the smoking cessation counselling [S], the smoking cessation + PA counselling [S + PA], or the control [C] groups. The program under evaluation is a standard brief counselling on smoking cessation combined with a brief counselling on increasing PA, and was delivered in 2010. A questionnaire, administered before, after 6 months and 1 year from the intervention, was used to track behavioural changes in tobacco use and PA, and to record cessation rates in participants. Discussion Out of the 5,657 women undergoing the Pap examination, 1,100 participants (55% of smokers were randomized in 1 of the 3 study groups (363 in the S, 366 in the S + PA and 371 in the C groups. The three arms did not differ on any demographic, PA, or tobacco-use characteristics. Recruited smokers were older, less educated than non-participant women, more motivated to quit (33% vs.9% in the Preparation stage, p p p Trial registration number ISRCTN: ISRCTN52660565

  7. DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Keeling Sally

    2008-05-01

    Full Text Available Abstract Background Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. Methods/design The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL. Secondary outcomes include depressive symptoms (Geriatric Depression Scale, quality of life (SF-36, physical activity (AHS Physical Activity Questionnaire and falls (self report. Discussion Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12605000475640

  8. [Cervical screening: toward a new paradigm?].

    Science.gov (United States)

    Lavoué, V; Bergeron, C; Riethmuller, D; Daraï, E; Mergui, J-L; Baldauf, J-J; Gondry, J; Douvier, S; Lopès, P; de Reilhac, P; Quéreux, C; Letombe, B; Marchetta, J; Boulanger, J-C; Levêque, J

    2010-04-01

    Analysis of the trials which compare the virologic testing (HPV testing) and the cytology in the cervical screening. The MedLine database was consulted using the Keywords: "cervical screening", "pap smear", "liquid based cytology", "HPV testing", "adults", "adolescents", "cervical intraepithelial neoplasia (CIN)", "uterine cervix cancer". Articles were selected according their concern about the debate of the uterine cervix cancer screening in France. The HPV testing seems interesting allowing a decreasing delay in the diagnosis of CIN (more diagnosis of CIN2+ in the first round and less during the second one). But, when the two rounds are added, the number of CIN2+ are identical in the two arms (cytology and HPV testing) in all the trials (except the Italian NTCC trial). A negative HPV testing protects the women much longer than cytology can do: a delay of five years between two rounds seems ideal. The HPV testing alone increases the detection rate of cervical lesions, which could regress spontaneously and may induce an overtreatment, especially in the youngest population: a triage is necessary and the cytology appears to be the best way to select the candidates for colposcopy in case of positive HPV testing and cytology. The HPV infection presents some particularities in adolescent females: for this reason, the HPV testing should not be used in this special population. In vaccinated women, a consensus for the screening is necessary. The health care providers in France have to understand the characteristics of the HPV testing: its advantages compared to the cytologic screening are only evident in case of an organization of the screening in France and even in Europe. (c) 2010 Elsevier Masson SAS. All rights reserved.

  9. Engineering aspects of Passavant screening

    International Nuclear Information System (INIS)

    Siddle, K.R.; Sharma, R.K.

    1978-01-01

    The Passavant screen was developed in Europe almost 30 years ago. The Passavant screen is a vertical traveling screen; however, the basic difference between the conventional vertical traveling screen and the Passavant screen is that in the conventional screen water passes through the front screen belt and then the back screen belt, whereas in the Passavant screen the water enters in between the two belts and passes laterally through either of the belts. Thus, theoretically, the screening surface of the Passavant screen is doubled as compared to the same size conventional vertical traveling screen. Various design and operational modifications of the Passavant screen are possible to yield optimum design and performance characteristics which make it amenable to installation at power plants for safe removal of not only fish but also smaller organisms such as fish eggs and larvae. In this paper, details of the screen design and operational characteristics are discussed with notes on how these features can be modified to suit site- and organism-specific requirements

  10. Outcomes following vaginal prolapse repair and mid urethral sling (OPUS) trial--design and methods.

    Science.gov (United States)

    Wei, John; Nygaard, Ingrid; Richter, Holly; Brown, Morton; Barber, Matthew; Xiao Xu; Kenton, Kimberly; Nager, Charles; Schaffer, Joseph; Visco, Anthony; Weber, Anne

    2009-04-01

    The primary aims of this trial are to determine whether the use of a concomitant prophylactic anti-incontinence procedure may prevent stress urinary incontinence symptom development in women undergoing vaginal prolapse surgery and to evaluate the cost-effectiveness of this prophylactic approach. To present the rationale and design of a randomized controlled surgical trial (RCT), the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) Trial highlighting the challenges in the design and implementation. The challenges of implementing this surgical trial combined with a cost-effectiveness study and patient preference group are discussed including the study design, ethical issues regarding use of sham incision, maintaining the masking of study staff, and pragmatic difficulties encountered in the collection of cost data. The trial is conducted by the NICHD-funded Pelvic Floor Disorders Network. The ongoing OPUS trial started enrollment in May 2007 with a planned accrual of 350. The use of sham incision was generally well accepted but the collection of cost data using conventional billing forms was found to potentially unmask key study personnel. This necessitated changes in the study forms and planned timing for collection of cost data. To date, the enrollment to the patient preference group has been lower than the limit established by the protocol suggesting a willingness on the part of women to participate in the randomization. Given the invasive nature of surgical intervention trials, potential participants may be reluctant to accept random assignment, potentially impacting generalizability. Findings from the OPUS trial will provide important information that will help surgeons to better counsel women on the benefits and risks of concomitant prophylactic anti-incontinence procedure at the time of vaginal surgery for prolapse. The implementation of the OPUS trial has necessitated that investigators consider ethical issues up front, remain flexible

  11. RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes.

    Science.gov (United States)

    Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

    2015-08-01

    Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool , a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature.

  12. The prevention access and risk taking in young people (PARTY project protocol: A cluster randomised controlled trial of health risk screening and motivational interviewing for young people presenting to general practice

    Directory of Open Access Journals (Sweden)

    Sanci Lena

    2012-06-01

    Full Text Available Abstract Background There are growing worldwide concerns about the ability of primary health care systems to manage the major burden of illness in young people. Over two thirds of premature adult deaths result from risks that manifest in adolescence, including injury, neuropsychiatric problems and consequences of risky behaviours. One policy response is to better reorientate primary health services towards prevention and early intervention. Currently, however, there is insufficient evidence to support this recommendation for young people. This paper describes the design and implementation of a trial testing an intervention to promote psychosocial risk screening of all young people attending general practice and to respond to identified risks using motivational interviewing. Main outcomes: clinicians’ detection of risk-taking and emotional distress, young people’s intention to change and reduction of risk taking. Secondary outcomes: pathways to care, trust in the clinician and likelihood of returning for future visits. The design of the economic and process evaluation are not detailed in this protocol. Methods PARTY is a cluster randomised trial recruiting 42 general practices in Victoria, Australia. Baseline measures include: youth friendly practice characteristics; practice staff’s self-perceived competency in young people’s care and clinicians’ detection and response to risk taking behaviours and emotional distress in 14–24 year olds, attending the practice. Practices are then stratified by a social disadvantage index and billing methods and randomised. Intervention practices receive: nine hours of training and tools; feedback of their baseline data and two practice visits over six weeks. Comparison practices receive a three hour seminar in youth friendly practice only. Six weeks post-intervention, 30 consecutive young people are interviewed post-consultation from each practice and followed-up for self-reported risk taking

  13. The development of a web- and a print-based decision aid for prostate cancer screening

    Directory of Open Access Journals (Sweden)

    Schwartz Marc D

    2010-03-01

    Full Text Available Abstract Background Whether early detection and treatment of prostate cancer (PCa will reduce disease-related mortality remains uncertain. As a result, tools are needed to facilitate informed decision making. While there have been several decision aids (DAs developed and tested, very few have included an exercise to help men clarify their values and preferences about PCa screening. Further, only one DA has utilized an interactive web-based format, which allows for an expansion and customization of the material. We describe the development of two DAs, a booklet and an interactive website, each with a values clarification component and designed for use in diverse settings. Methods We conducted two feasibility studies to assess men's (45-70 years Internet access and their willingness to use a web- vs. a print-based tool. The booklet was adapted from two previous versions evaluated in randomized controlled trials (RCTs and the website was created to closely match the content of the revised booklet. Usability testing was conducted to obtain feedback regarding draft versions of the materials. The tools were also reviewed by a plain language expert and the interdisciplinary research team. Feedback on the content and presentation led to iterative modifications of the tools. Results The feasibility studies confirmed that the Internet was a viable medium, as the majority of men used a computer, had access to the Internet, and Internet use increased over time. Feedback from the usability testing on the length, presentation, and content of the materials was incorporated into the final versions of the booklet and website. Both the feasibility studies and the usability testing highlighted the need to address men's informed decision making regarding screening. Conclusions Informed decision making for PCa screening is crucial at present and may be important for some time, particularly if a definitive recommendation either for or against screening does not

  14. Challenges and opportunities in designing clinical trials for neuromyelitis optica

    Science.gov (United States)

    Barron, Gerard; Behne, Jacinta M.; Bennett, Jeffery L.; Chin, Peter S.; Cree, Bruce A.C.; de Seze, Jerome; Flor, Armando; Fujihara, Kazuo; Greenberg, Benjamin; Higashi, Sayumi; Holt, William; Khan, Omar; Knappertz, Volker; Levy, Michael; Melia, Angela T.; Palace, Jacqueline; Smith, Terry J.; Sormani, Maria Pia; Van Herle, Katja; VanMeter, Susan; Villoslada, Pablo; Walton, Marc K.; Wasiewski, Warren; Wingerchuk, Dean M.; Yeaman, Michael R.

    2015-01-01

    Current management of neuromyelitis optica (NMO) is noncurative and only partially effective. Immunosuppressive or immunomodulatory agents are the mainstays of maintenance treatment. Safer, better-tolerated, and proven effective treatments are needed. The perceived rarity of NMO has impeded clinical trials for this disease. However, a diagnostic biomarker and recognition of a wider spectrum of NMO presentations has expanded the patient population from which study candidates might be recruited. Emerging insights into the pathogenesis of NMO have provided rationale for exploring new therapeutic targets. Academic, pharmaceutical, and regulatory communities are increasingly interested in meeting the unmet needs of patients with NMO. Clinical trials powered to yield unambiguous outcomes and designed to facilitate rapid evaluation of an expanding pipeline of experimental agents are needed. NMO-related disability occurs incrementally as a result of attacks; thus, limiting attack frequency and severity are critical treatment goals. Yet, the severity of NMO and perception that currently available agents are effective pose challenges to study design. We propose strategies for NMO clinical trials to evaluate agents targeting recovery from acute attacks and prevention of relapses, the 2 primary goals of NMO treatment. Aligning the interests of all stakeholders is an essential step to this end. PMID:25841026

  15. Uptake of community-based, self-collected HPV testing vs. visual inspection with acetic acid for cervical cancer screening in Kampala, Uganda: preliminary results of a randomised controlled trial.

    Science.gov (United States)

    Moses, Erin; Pedersen, Heather N; Mitchell, Sheona M; Sekikubo, Musa; Mwesigwa, David; Singer, Joel; Biryabarema, Christine; Byamugisha, Josaphat K; Money, Deborah M; Ogilvie, Gina S

    2015-10-01

    To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA). Pilot randomised controlled trial of 500 women aged 30-65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates. In the HR-HPV arm, 248 of 250 (p < 0.01) women provided samples, while in the VIA arm, 121 of 250 (48.4%) women attended screening. Among the 73 of 248 HR-HPV-positive women, 45.2% (N = 33) attended VIA screening for follow-up, 21.2% (N = 7) of whom screened positive; five received treatment and two were missing clinical follow-up records. Of the 121 women in the VIA arm who attended screening, 13.2% (N = 16) screened positive; seven received cryotherapy, three refused treatment, five were referred to colposcopy; and one woman had suspected cervical cancer and received treatment after confirmatory testing. This pilot study demonstrated trial feasibility and willingness of the women to participate and be randomised successfully into the two arms. Self-collection-based cervical cancer screening had a higher uptake than VIA. © 2015 John Wiley & Sons Ltd.

  16. Design of the Xylitol for Adult Caries Trial (X-ACT

    Directory of Open Access Journals (Sweden)

    Amaechi Bennett T

    2010-09-01

    Full Text Available Abstract Background Dental caries incidence in adults is similar to that in children and adolescents, but few caries preventive agents have been evaluated for effectiveness in adults populations. In addition, dentists direct fewer preventive services to their adult patients. Xylitol, an over-the-counter sweetener, has shown some potential as a caries preventive agent, but the evidence for its effectiveness is not yet conclusive and is based largely on studies in child populations. Methods/Design X-ACT is a three-year, multi-center, placebo controlled, double-blind, randomized clinical trial that tests the effects of daily use of xylitol lozenges versus placebo lozenges on the prevention of adult caries. The trial has randomized 691 participants (ages 21-80 to the two arms. The primary outcome is the increment of cavitated lesions. Discussion This trial should help resolve the overall issue of the effectiveness of xylitol in preventing caries by contributing evidence with a low risk of bias. Just as importantly, the trial will provide much-needed information about the effectiveness of a promising caries prevention agent in adults. An effective xylitol-based caries prevention intervention would represent an easily disseminated method to extend caries prevention to individuals not receiving caries preventive treatment in the dental office. Trial Registration ClinicalTrials.Gov NCT00393055

  17. Rationale, design, and results of the first screening round of a comprehensive, register-based, Chlamydia screening implementation programme in the Netherlands

    Directory of Open Access Journals (Sweden)

    Koekenbier Rik H

    2010-10-01

    Full Text Available Abstract Background Implementing Chlamydia trachomatis screening in the Netherlands has been a point of debate for several years. The National Health Council advised against implementing nationwide screening until additional data collected from a pilot project in 2003 suggested that screening by risk profiles could be effective. A continuous increase in infections recorded in the national surveillance database affirmed the need for a more active approach. Here, we describe the rationale, design, and implementation of a Chlamydia screening demonstration programme. Methods A systematic, selective, internet-based Chlamydia screening programme started in April 2008. Letters are sent annually to all 16 to 29-year-old residents of Amsterdam, Rotterdam, and selected municipalities of South Limburg. The letters invite sexually active persons to login to http://www.chlamydiatest.nl with a personal code and to request a test kit. In the lower prevalence area of South Limburg, test kits can only be requested if the internet-based risk assessment exceeds a predefined value. Results We sent invitations to 261,025 people in the first round. One-fifth of the invitees requested a test kit, of whom 80% sent in a sample for testing. The overall positivity rate was 4.2%. Conclusions This programme advances Chlamydia control activities in the Netherlands. Insight into the feasibility, effectiveness, cost-effectiveness, and impact of this large-scale screening programme will determine whether the programme will be implemented nationally.

  18. Evaluating biomarkers for prognostic enrichment of clinical trials.

    Science.gov (United States)

    Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

    2017-12-01

    A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

  19. Colorectal cancer screening

    OpenAIRE

    McLoughlin, Monica Ramona

    2008-01-01

    Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...

  20. Comparison of mailed invitation strategies to improve fecal occult blood test participation in men: protocol for a randomized controlled trial.

    Science.gov (United States)

    Duncan, Amy; Zajac, Ian; Flight, Ingrid; Stewart, Benjamin J R; Wilson, Carlene; Turnbull, Deborah

    2013-07-31

    Men have a significantly increased risk of being diagnosed with, and dying from, colorectal cancer (CRC) than women. Men also participate in fecal occult blood test (FOBT) screening at a lower rate than women. This study will determine whether strategies that target men's attitudes toward screening, and matched to stage of readiness to screen, increase men's FOBT participation compared to a standard approach. Eligible trial participants will be a national sample of 9,200 men aged 50 to 74 years, living in urban Australia and randomly selected from the Australian electoral roll. Trial participants will be mailed an advance notification letter, followed 2 weeks later by an invitation letter and a free fecal immunochemical test (FIT) kit. The intervention is a factorial design, randomized controlled trial (RCT) with four trial arms, including a control. The content of the advance notification and invitation letters will differ by trial arm as follows: 1) standard advance notification and standard invitation (control arm); 2) targeted advance notification and standard invitation; 3) standard advance notification and targeted invitation; and 4) targeted advance notification and targeted invitation. The standard letters will replicate as closely as possible the letters included in the Australian National Bowel Cancer Screening Program (NBCSP). Modified advance notification and invitation letters will incorporate additional messages to target men in the precontemplation (advance notification) and contemplation stages (invitation). The primary outcome is return of the completed FIT within 12 weeks of invitation. Analysts will be blinded to trial assignment and participants will be blinded to the use of varying invitational materials. Subsamples from each trial arm will complete baseline and endpoint surveys to measure the psychological impact of the intervention, and qualitative interviews will be conducted to evaluate attitudes toward the intervention. The outcomes of

  1. Role of resistant starch on diabetes risk factors in people with prediabetes: Design, conduct, and baseline results of the STARCH trial.

    Science.gov (United States)

    Marlatt, Kara L; White, Ursula A; Beyl, Robbie A; Peterson, Courtney M; Martin, Corby K; Marco, Maria L; Keenan, Michael J; Martin, Roy J; Aryana, Kayanush J; Ravussin, Eric

    2018-02-01

    Dietary resistant starch (RS) might alter gastrointestinal tract function in a manner that improves human health, particularly among adults at risk for diabetes. Here, we report the design and baseline results (with emphasis on race differences) from the STARCH trial, the first comprehensive metabolic phenotyping of people with prediabetes enrolled in a randomized clinical trial testing the effect of RS on risk factors for diabetes. Overweight/obese participants (BMI≥27kg/m 2 and weight≤143kg), age 35-75y, with confirmed prediabetes were eligible. Participants were randomized to consume 45g/day of RS (RS=amylose) or amylopectin (Control) for 12weeks. The study was designed to evaluate the effect of RS on insulin sensitivity and secretion, ectopic fat, and inflammatory markers. Secondary outcomes included energy expenditure, substrate oxidation, appetite, food intake, colonic microbial composition, fecal and plasma levels of short-chain fatty acids, fecal RS excretion, and gut permeability. Out of 280 individuals screened, 68 were randomized, 65 started the intervention, and 63 were analyzed at baseline (mean age 55y, BMI 35.6kg/m 2 ); 2 were excluded from baseline analyses due to abnormal insulin and diabetes. Sex and race comparisons at baseline were reported. African-Americans had higher baseline acute insulin response to glucose (AIRg measured by frequently sampled intravenous glucose tolerance test) compared to Caucasians, despite having less visceral adipose tissue mass and intrahepatic lipid; all other glycemic variables were similar between races. Sleep energy expenditure was ~90-100kcal/day lower in African-Americans after adjusting for insulin sensitivity and secretion. This manuscript provides an overview of the strategy used to enroll people with prediabetes into the STARCH trial and describes methodologies used in the assessment of risk factors for diabetes. Clinicaltrials.gov identifier: STARCH (NCT01708694). The present study reference can be

  2. Breast cancer screening with digital breast tomosynthesis.

    Science.gov (United States)

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  3. Microclimate evaluation of a new design of insect-proof screens in a Mediterranean greenhouse

    Directory of Open Access Journals (Sweden)

    Alejandro Lopez-Martinez

    2014-05-01

    Full Text Available This work studies natural ventilation in a Mediterranean greenhouse, comparing a new experimental screen of 13×30 threads cm-2 (porosity 39.0% with a commercial control screen of 10×20 threads cm-2 (porosity 33.5%. In addition, both screens were tested in a wind tunnel to determine the discharge coefficients Cd of the greenhouse side and roof vents, which proved to be 0.16 for the commercial control screen and 0.18 for the experimental screen at both vents. These values represent a theoretical increase of 11% (Cd,φ-10×20 /Cd,φ-13×30 = 0.89 in the natural ventilation capacity of the greenhouse when the experimental screen is used. The greenhouse was divided into two separate sections allowing us to analyze natural ventilation in both sectors simultaneously. Air velocity was measured in the lateral and roof vents with two 3D and six 2D sonic anemometers. Using the commercial control screen there was an average reduction of 16% in ventilation rate, and an average increase of 0.5ºC in the average indoor air temperature, compared to the experimental screen. In addition, the ventilation efficiency ηT was higher with the experimental screen (mean value of 0.9 than with the control (mean value 0.6. We have designed an experimental insect-proof screen (13×30 threads cm-2 with smaller thread diameter, higher thread density, smaller pore size and higher porosity than are used in most commercial meshes. All of these factors promote natural ventilation and improve the greenhouse microclimate.

  4. Generalizability of results from the National Lung Screening Trial

    International Nuclear Information System (INIS)

    Heuvers, Marlies E.; Wisnivesky, Juan; Stricker, Bruno H.; Aerts, Joachim G.

    2012-01-01

    Lung cancer is the major cause of cancer-related death worldwide, with a 5-year survival of only 16 %. Most lung cancer cases are diagnosed at an advanced incurable stage. As earlier stages have a better prognosis, the key to reducing mortality could be early diagnosis of the disease. At present, low-dose computed tomographic (CT) screening has shown promising data. Lung cancer death rates were reduced by 20 % when CT screening is compared to chest radiography in a high-risk group. There are many advantages of CT screening in lung cancer, however there are also some important issues that should be taken into account. Therefore, the applicability of the results to clinical practice is not clear yet. In this Commentary we discuss different aspects that play important roles in the balance between harms and benefits of screening, including overdiagnosis, availability of treatment options worldwide, ethical considerations, costs, and prolonged life expectancy. We conclude that clinicians should be cautious in generalizing findings to the total population of smokers and take into account that the use of lung cancer screening in clinical practice may have limitations.

  5. Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

    Science.gov (United States)

    Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

    2013-01-01

    Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

  6. Rationale and design of Mi-CARE: The mile square colorectal cancer screening, awareness and referral and education project.

    Science.gov (United States)

    Buscemi, Joanna; Miguel, Yazmin San; Tussing-Humphreys, Lisa; Watts, Elizabeth A; Fitzgibbon, Marian L; Watson, Karriem; Winn, Robert A; Matthews, Kameron L; Molina, Yamile

    2017-01-01

    Although colorectal cancer (CRC) is largely preventable through identification of pre-cancerous polyps through various screening modalities, morbidity and mortality rates remain a challenge, especially in African-American, Latino, low-income and uninsured/underinsured patients. Barriers to screening include cost, access to health care facilities, lack of recommendation to screen, and psychosocial factors such as embarrassment, fear of the test, anxiety about testing preparation and fear of a cancer diagnosis. Various intervention approaches to improve CRC screening rates have been developed. However, comparative effectiveness research (CER) to investigate the relative performance of different approaches has been understudied, especially across different real-life practice settings. Assessment of differential efficacy across diverse vulnerable populations is also lacking. The current paper describes the rationale and design for the Mile Square Colorectal Cancer Screening, Awareness and Referral and Education Project (Mi-CARE), which aims to increase CRC screening rates in 3 clinics of a large Federally Qualified Health Center (FQHC) by reducing prominent barriers to screening for low-income, minority and underserved patients. Patients attending these clinics will receive one of three interventions to increase screening uptake: lay patient navigator (LPN)-based navigation, provider level navigation, or mailed birthday CRC screening reminders. The design of our program allows for comparison of the effectiveness of the tailored interventions across sites and patient populations. Data from Mi-CARE may help to inform the dissemination of tailored interventions across FQHCs to reduce health disparities in CRC. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. What Value Can Qualitative Research Add to Quantitative Research Design? An Example From an Adolescent Idiopathic Scoliosis Trial Feasibility Study.

    Science.gov (United States)

    Toye, Francine; Williamson, Esther; Williams, Mark A; Fairbank, Jeremy; Lamb, Sarah E

    2016-08-09

    Using an example of qualitative research embedded in a non-surgical feasibility trial, we explore the benefits of including qualitative research in trial design and reflect on epistemological challenges. We interviewed 18 trial participants and used methods of Interpretive Phenomenological Analysis. Our findings demonstrate that qualitative research can make a valuable contribution by allowing trial stakeholders to see things from alternative perspectives. Specifically, it can help to make specific recommendations for improved trial design, generate questions which contextualize findings, and also explore disease experience beyond the trial. To make the most out of qualitative research embedded in quantitative design it would be useful to (a) agree specific qualitative study aims that underpin research design, (b) understand the impact of differences in epistemological truth claims, (c) provide clear thematic interpretations for trial researchers to utilize, and (d) include qualitative findings that explore experience beyond the trial setting within the impact plan. © The Author(s) 2016.

  8. Likelihood of myocardial infarction during stroke rehabilitation preceded by cardiovascular screening and an exercise tolerance test: the Locomotor Experience Applied Post-Stroke (LEAPS) trial.

    Science.gov (United States)

    Nadeau, Stephen E; Rose, Dorian Kay; Dobkin, Bruce; Wu, Samuel S; Dai, Yufeng E; Schofield, Richard; Duncan, Pamela W

    2014-12-01

    Coronary artery disease is highly prevalent in patients with stroke, but because revascularization does not improve major clinical outcomes in patients with stable coronary artery disease relative to intensive medical therapy, routine evaluation for this disease is not warranted in stroke patients. However, it might be warranted in patients destined to undergo vigorous physical therapy. The Locomotor Experience Applied Post-Stroke study, a randomized controlled trial of 408 participants that tested the relative efficacy of two rehabilitation techniques on functional walking level, provided the opportunity to address this question. The study aims to test the efficacy of screening for cardiovascular disease and an exercise tolerance test in assuring safety among patients undergoing vigorous rehabilitation for gait impairment. All participants were screened for serious cardiovascular and pulmonary conditions. At six-weeks poststroke, they also completed a cardiovascular screening inventory and underwent an exercise tolerance test involving bicycle ergometry. Participants received 36, 90-min sessions of a prescribed physical therapy (three per week), initiated at either two-months or six-months poststroke. Twenty-nine participants were excluded on the basis of the cardiac screening questionnaire, and 15 failed the exercise tolerance test for cardiovascular reasons. No participant experienced a cardiac event during a treatment session. Two participants experienced myocardial infarctions, but continued in the trial. In three additional participants, myocardial infarctions caused or contributed to death. The combination of a negative cardiac screen and the absence of exercise tolerance test failure appeared to have a high negative predictive value for cardiac events during treatment, despite the likelihood of a high prevalence of coronary artery disease in our population. © 2014 World Stroke Organization.

  9. Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features

    OpenAIRE

    Rabinowitz, Jonathan; Levine, Stephen Z.; Barkai, Orna; Davidov, Ori

    2008-01-01

    Dropout is often used as an outcome measure in clinical trials of antipsychotic medication. Previous research is inconclusive regarding (a) differences in dropout rates between first- and second-generation antipsychotic medications and (b) how trial design features reduce dropout. Meta-analysis of randomized controlled trials (RCTs) of antipsychotic medication was conducted to compare dropout rates for first- and second-generation antipsychotic drugs and to examine how a broad range of design...

  10. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  11. There are calls for a national screening programme for prostate cancer: what is the evidence to justify such a national screening programme?

    Science.gov (United States)

    Green, A; Tait, C; Aboumarzouk, O; Somani, B K; Cohen, N P

    2013-05-01

    Prostate cancer is the commonest cancer in men and a major health issue worldwide. Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. To assess the latest evidence regarding prostate cancer screening and whether it meets the necessary requirements to be established as a national programme for all men. Electronic databases and library catalogues were searched electronically and manual retrieval was performed. Only primary research results were used for the analysis. In recent years, several important randomised controlled trials have produced varied outcomes. In Europe the largest study thus far concluded that screening reduced prostate cancer mortality by 20%. On the contrary, a large American trial found no reduction in mortality after 7-10 years follow-up. Most studies comment on the adverse effects of screening - principally those of overdiagnosis and subsequent overtreatment. Further information about the natural history of prostate cancer and accuracy of screening is needed before a screening programme can be truly justified. In the interim, doctors and patients should discuss the risks, benefits and sequelae of taking part in voluntary screening for prostate cancer.

  12. Investigating Effects of Screen Layout Elements on Interface and Screen Design Aesthetics

    Directory of Open Access Journals (Sweden)

    Ahamed Altaboli

    2011-01-01

    Full Text Available A recent study suggested the use of the screen layout elements of balance, unity, and sequence as a part of a computational model of interface aesthetics. It is argued that these three elements are the most contributed terms in the model. In the current study, a controlled experiment was designed and conducted to systematically investigate effects of these three elements (balance, unity, and sequence on the perceived interface aesthetics. Results showed that the three elements have significant effects on the perceived interface aesthetics. Significant interactions were also found among the three elements. A regression model relating the perceived visual aesthetics to the three elements was constructed. When validating the model using standard questionnaire scores of real web pages, high correlations were found between the values computed by the model and scores of questionnaire items related to visual layout of the web pages, indicating that layout-based measures are good at assessing the classical dimension of website aesthetics.

  13. Psychological distress associated with cancer screening: A systematic review.

    Science.gov (United States)

    Chad-Friedman, Emma; Coleman, Sarah; Traeger, Lara N; Pirl, William F; Goldman, Roberta; Atlas, Steven J; Park, Elyse R

    2017-10-15

    Current national cancer screening recommendations include the potential risk of psychological harm related to screening. However, data on the relation of psychological distress to cancer screening is limited. The authors conducted a systematic review to assess psychological distress associated with cancer screening procedures. Studies that administered measures of psychological distress between 2 weeks before and 1 month after the screening procedure were included. In total, 22 eligible studies met criteria for review, including 13 observational trials and 9 randomized controlled trials. Eligible studies used a broad range of validated and unvalidated measures. Anxiety was the most commonly assessed construct and was measured using the State Trait Anxiety Inventory. Studies included breast, colorectal, prostate, lung, and cervical screening procedures. Distress was low across procedures, with the exception of colorectal screening. Distress did not vary according to the time at which distress was measured. None of the studies were conducted exclusively with the intention of assessing distress at the time of screening. Evidence of low distress during the time of cancer screening suggests that distress might not be a widespread barrier to screening among adults who undergo screening. However, more studies are needed using validated measures of distress to further understand the extent to which screening may elicit psychological distress and impede adherence to national screening recommendations. Cancer 2017;123:3882-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

  14. Screening for diabetic retinopathy with or without a copayment in a randomized controlled trial: influence of the inverse care law.

    Science.gov (United States)

    Lian, Jin Xiao; McGhee, Sarah M; Gangwani, Rita A; Hedley, Anthony J; Lam, Cindy Lo Kuen; Yap, Maurice Keng Hung; Lai, Wico W; Chu, Daniel Wai Sing; Wong, David S H

    2013-06-01

    To examine whether the inverse care law operates in a screening program for diabetic retinopathy (DR) based on fee for service in Hong Kong. Randomized controlled trial. All those with type 1 or 2 diabetes from 2 clinics were recruited. Diabetic retinopathy screening with a small copayment versus free access in a publicly funded family medicine service. Uptake of screening and severity of DR detected. Association between these outcome variables and independent variables were determined using multivariate logistic regression models and reported as odds ratios (ORs). After randomization, 1387 subjects in the free group and 1379 subjects in the pay group were eligible for screening, and 94.9% (1316/1387) and 92.6% (1277/1379), respectively, agreed to participate in the study. The offer of screening was accepted by 94.8% (1247/1316) in the free group and 91.2% (1164/1277) in the pay group, and the final uptake ratios were 88.5% (1165/1316) and 82.4% (1052/1277), respectively (Pearson chi = 19.74, Plaw seems to operate in a preventive intervention when a relatively small copayment is applied. There is a case for making effective preventive services free of charge. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  15. Screening, diagnosis, and management of intrauterine growth restriction.

    Science.gov (United States)

    Lausman, Andrea; McCarthy, Fergus P; Walker, Melissa; Kingdom, John

    2012-01-01

    To provide comprehensive background knowledge relevant to the SOGC Maternal-Fetal Medicine Committee-approved guideline entitled "Intrauterine Growth Restriction: Screening, Diagnosis, and Management." Publications in English were retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and any key words (fetal growth, restriction, growth retardation, intrauterine growth restriction [IUGR], low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and high-quality prospective and retrospective observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Evidence obtained from at least one properly randomized controlled trial, Cochrane Reviews, and high quality cohort data have been combined to provide clinicians with evidence to optimize their practice for screening, diagnosis, and management of intrauterine growth restriction. Considerable advances have been made to improve clinicians' ability to screen, diagnose, and manage pregnancies with suspected IUGR more effectively, including several properly randomized controlled trials. Pregnancies with late-onset IUGR may be managed equally effectively by early delivery or delayed delivery (with increased surveillance) anticipating favourable outcomes. By contrast, many aspects of the management of early-onset IUGR require further clinical trials.

  16. What implementation interventions increase cancer screening rates? a systematic review

    Directory of Open Access Journals (Sweden)

    Lent Barbara

    2011-09-01

    Full Text Available Abstract Background Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC screening. The interventions considered were: client reminders, client incentives, mass media, small media, group education, one-on-one education, reduction in structural barriers, reduction in out-of-pocket costs, provider assessment and feedback interventions, and provider incentives. Our primary outcome, screening completion, was calculated as the overall median post-intervention absolute percentage point (PP change in completed screening tests. Methods Our first step was to conduct an iterative scoping review in the research area. This yielded three relevant high-quality systematic reviews. Serving as our evidentiary foundation, we conducted a formal update. Randomized controlled trials and cluster randomized controlled trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and PSYCHinfo. Results The update yielded 66 studies new eligible studies with 74 comparisons. The new studies ranged considerably in quality. Client reminders, small media, and provider audit and feedback appear to be effective interventions to increase the uptake of screening for three cancers. One-on-one education and reduction of structural barriers also appears effective, but their roles with CRC and cervical screening, respectively, are less established. More study is required to assess client incentives, mass media, group education, reduction of out-of-pocket costs, and provider incentive interventions. Conclusion The new evidence generally aligns with the evidence and conclusions from the original systematic

  17. Multifaceted intervention to enhance the screening and care of hospitalised malnourished children: study protocol for the PREDIRE cluster randomized controlled trial

    Science.gov (United States)

    2013-01-01

    Background Hospital malnutrition is an underestimated problem and as many as half of malnourished patients do not receive appropriate treatment. In order to extend the management of malnutrition in health care facilities, multidisciplinary teams focusing on clinical nutrition were established in France. The establishment of such teams within hospital facilities remains nonetheless difficult. We have consequently developed a multifaceted intervention coordinated by a Nutritional Support Team (NST). Our study aims to evaluate the impact of this multifaceted intervention coordinated by a NST, in adherence to recommended practices for the care of malnourished children, among health care workers of a paediatric university hospital. Methods/design We carried out 1) a six-month observational phase focusing on the medical care procedures relative to malnourished children followed by 2) a cluster randomised controlled trial phase to evaluate the impact of a multidisciplinary nutrition team over an 18 month time frame. Based on power analyses and assuming a conservative intracluster correlation coefficient, 1289 children were needed to detect a 25% difference in rates between the two groups of the cluster trial. The implementation of our intervention was coordinated by the NST and had three major components: a) access to a computerised malnutrition screening system associated with an automatic alert system, b) an awareness campaign directed toward the health care workers and c) a leadership based strategy. Main outcomes included the number of daily weighings during hospitalisation, the investigation of malnutrition etiology and the management of malnutrition by a dietician and/or the NST. Due to the clustered nature of the data with children nested in departments, a generalized estimated equations approach will be used to analyse the impact of the multifaceted intervention on primary and secondary outcomes. Discussion Our results will provide an overall response regarding

  18. Design of a multi-arm randomized clinical trial with no control arm.

    Science.gov (United States)

    Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

    2016-01-01

    Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Increasingly strong reduction in breast cancer mortality due to screening

    Science.gov (United States)

    van Schoor, G; Moss, S M; Otten, J D M; Donders, R; Paap, E; den Heeten, G J; Holland, R; Broeders, M J M; Verbeek, A L M

    2011-01-01

    Background: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. Methods: In Nijmegen, the Netherlands, 55 529 women received an invitation for screening between 1975 and 2008. We designed a case–referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50–69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. Results: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49–0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975–1991 (OR=0.72; 95% CI=0.47–1.09) to 65% in the period 1992–2008 (OR=0.35; 95% CI=0.19–0.64). Conclusion: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening. PMID:21343930

  20. Effectiveness of school dental screening on stimulating dental attendance rates in Vikarabad town: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Gadde Praveen

    2014-01-01

    Full Text Available Background: The school dental screening program has been in existence from the beginning of 20 th century. Its value in encouraging attendance among school children is not fully established. Aim: The aim was to determine the effectiveness of school dental screening on stimulating dental attendance rates among school children in Vikarabad town. Objectives: (a To compare the dental attendance rates between 6-9 and 10-13 years old age groups, among male and female school children in Vikarabad town. (b To identify the type of dental treatment received by the school children. Materials and Methods: A randomized controlled trial was conducted among school children aged 6-13 years old from 16 schools that were randomly selected and divided into two groups. Eight schools had a dental screening program (study group = 300 children and had blanket referral cards and 8 schools that did not have the intervention (control group = 300. The dental attendance rates were determined after 3 months of follow-up period by evaluating the blanket referral cards for the study group and by an oral questionnaire for the control group. Results: The dental attendance rate was 27% for the study group and 18% for the control group which is statistically significant. The attendance rate was higher among 10-13 years of children both in test group and control groups. Among the children who visited the dentist, 53% in the control group and 69% from the test group got simple amalgam and glass ionomer cement restorations. Conclusion: The dental attendance rates were improved following school dental screening.

  1. Efficient high-throughput biological process characterization: Definitive screening design with the ambr250 bioreactor system.

    Science.gov (United States)

    Tai, Mitchell; Ly, Amanda; Leung, Inne; Nayar, Gautam

    2015-01-01

    The burgeoning pipeline for new biologic drugs has increased the need for high-throughput process characterization to efficiently use process development resources. Breakthroughs in highly automated and parallelized upstream process development have led to technologies such as the 250-mL automated mini bioreactor (ambr250™) system. Furthermore, developments in modern design of experiments (DoE) have promoted the use of definitive screening design (DSD) as an efficient method to combine factor screening and characterization. Here we utilize the 24-bioreactor ambr250™ system with 10-factor DSD to demonstrate a systematic experimental workflow to efficiently characterize an Escherichia coli (E. coli) fermentation process for recombinant protein production. The generated process model is further validated by laboratory-scale experiments and shows how the strategy is useful for quality by design (QbD) approaches to control strategies for late-stage characterization. © 2015 American Institute of Chemical Engineers.

  2. Impact of intermittent screening and treatment for malaria among school children in Kenya: a cluster randomised trial.

    Directory of Open Access Journals (Sweden)

    Katherine E Halliday

    2014-01-01

    Full Text Available Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence of the benefits of alternative school-based malaria interventions or how the impacts of interventions vary according to intensity of malaria transmission. We investigated the effect of intermittent screening and treatment (IST for malaria on the health and education of school children in an area of low to moderate malaria transmission.A cluster randomised trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010-2012. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up for 24 months. Once a school term, children were screened by public health workers using malaria rapid diagnostic tests (RDTs, and children (with or without malaria symptoms found to be RDT-positive were treated with a six dose regimen of artemether-lumefantrine (AL. Given the nature of the intervention, the trial was not blinded. The primary outcomes were anaemia and sustained attention. Secondary outcomes were malaria parasitaemia and educational achievement. Data were analysed on an intention-to-treat basis. During the intervention period, an average of 88.3% children in intervention schools were screened at each round, of whom 17.5% were RDT-positive. 80.3% of children in the control and 80.2% in the intervention group were followed-up at 24 months. No impact of the malaria IST intervention was observed for prevalence of anaemia at either 12 or 24 months (adjusted risk ratio [Adj.RR]: 1.03, 95% CI 0.93-1.13, p = 0.621 and Adj.RR: 1.00, 95% CI 0.90-1.11, p = 0.953 respectively, or on prevalence of P. falciparum infection or scores of classroom attention. No effect of IST was observed on educational achievement in the older class, but an apparent negative effect was seen on spelling scores in

  3. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  4. Randomized controlled trials and neuro-oncology: should alternative designs be considered?

    Science.gov (United States)

    Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

    2015-09-01

    Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the

  5. Experimental burn plot trial in the Kruger National Park: history, experimental design and suggestions for data analysis

    Directory of Open Access Journals (Sweden)

    R. Biggs

    2003-12-01

    Full Text Available The experimental burn plot (EBP trial initiated in 1954 is one of few ongoing long-termfire ecology research projects in Africa. The trial aims to assess the impacts of differentfire regimes in the Kruger National Park. Recent studies on the EBPs have raised questions as to the experimental design of the trial, and the appropriate model specificationwhen analysing data. Archival documentation reveals that the original design was modified on several occasions, related to changes in the park's fire policy. These modifications include the addition of extra plots, subdivision of plots and changes in treatmentsover time, and have resulted in a design which is only partially randomised. The representativity of the trial plots has been questioned on account of their relatively small size,the concentration of herbivores on especially the frequently burnt plots, and soil variation between plots. It is suggested that these factors be included as covariates inexplanatory models or that certain plots be excluded from data analysis based on resultsof independent studies of these factors. Suggestions are provided for the specificationof the experimental design when analysing data using Analysis of Variance. It is concluded that there is no practical alternative to treating the trial as a fully randomisedcomplete block design.

  6. The effect of offering different numbers of colorectal cancer screening test options in a decision aid: a pilot randomized trial

    Directory of Open Access Journals (Sweden)

    Brenner Alison RT

    2008-01-01

    Full Text Available Abstract Background Decision aids can improve decision making processes, but the amount and type of information that they should attempt to communicate is controversial. We sought to compare, in a pilot randomized trial, two colorectal cancer (CRC screening decision aids that differed in the number of screening options presented. Methods Adults ages 48–75 not currently up to date with screening were recruited from the community and randomized to view one of two versions of our previously tested CRC screening decision aid. The first version included five screening options: fecal occult blood test (FOBT, sigmoidoscopy, a combination of FOBT and sigmoidoscopy, colonoscopy, and barium enema. The second discussed only the two most frequently selected screening options, FOBT and colonoscopy. Main outcomes were differences in screening interest and test preferences between groups after decision aid viewing. Patient test preference was elicited first without any associated out-of-pocket costs (OPC, and then with the following costs: FOBT-$10, sigmoidoscopy-$50, barium enema-$50, and colonoscopy-$200. Results 62 adults participated: 25 viewed the 5-option decision aid, and 37 viewed the 2-option version. Mean age was 54 (range 48–72, 58% were women, 71% were White, 24% African-American; 58% had completed at least a 4-year college degree. Comparing participants that viewed the 5-option version with participants who viewed the 2-option version, there were no differences in screening interest after viewing (1.8 vs. 1.9, t-test p = 0.76. Those viewing the 2-option version were somewhat more likely to choose colonoscopy than those viewing the 5-option version when no out of pocket costs were assumed (68% vs. 46%, p = 0.11, but not when such costs were imposed (41% vs. 42%, p = 1.00. Conclusion The number of screening options available does not appear to have a large effect on interest in colorectal cancer screening. The effect of offering differing

  7. Challenges in the design of a Home Telemanagement trial for patients with ulcerative colitis.

    Science.gov (United States)

    Cross, Raymond K; Finkelstein, Joseph

    2009-12-01

    Nonadherence, inadequate monitoring, and side-effects result in suboptimal outcomes in ulcerative colitis (UC). We hypothesize that telemanagement for UC will improve symptoms, quality of life, adherence, and decrease costs. This article describes the challenges encountered in the design of the home telemanagement in patients with UC trial. In a randomized trial to assess the effectiveness of telemanagement for UC compared to best available care, 100 patients will be enrolled. Subjects in the intervention arm will complete self-testing with telemanagement weekly; best available care subjects will receive scheduled follow up, educational fact sheets, and written action plans. Telemanagement consists of a home-unit, decision support server, and web-based clinician portal. The home-unit includes a scale and laptop. Subjects will respond to questions about symptoms, side-effects, adherence, and knowledge weekly; subjects will receive action plans after self-testing. Outcome variables to be assessed every 4 months include: disease activity, using the Seo index; quality of life, using the Inflammatory Bowel Disease Questionnaire; adherence, using pharmacy refill data and the Morisky Medication Adherence Scale; utilization of healthcare resources, using urgent care visits and hospitalizations. We encountered several challenges during design and implementation of our trial. First, we selected a randomized controlled trial design. We could have selected a quasiexperimental design to decrease the sample size needed and costs. Second, identification of a control group was challenging. Telemanagement patients received self-care plans and an educational curriculum. Since controls would not receive these interventions, we thought our results would be biased in favor of telemanagement. In addition, we wanted to evaluate the mode of delivery of these components of care. Therefore, we included written action plans and educational materials for patients in the control group ('best

  8. Partially nested designs in psychotherapy trials: A review of modeling developments.

    Science.gov (United States)

    Sterba, Sonya K

    2017-07-01

    Individually-randomized psychotherapy trials are often partially nested. For instance, individuals assigned to a treatment arm may be clustered into therapy groups for purposes of treatment administration, whereas individuals assigned to a wait-list control are unclustered. The past several years have seen rapid expansion and investigation of methods for analyzing partially nested data. Yet partial nesting often remains ignored in psychotherapy trials. This review integrates and disseminates developments in the analysis of partially nested data that are particularly relevant for psychotherapy researchers. First, we differentiate among alternative partially nested designs. Then, we present adaptations of multilevel model specifications that accommodate each design. Next, we address how moderation by treatment as well as mediation of the treatment effect can be investigated in partially nested designs. Model fitting results, annotated software syntax, and illustrative data sets are provided and key methodological issues are discussed. We emphasize that cluster-level variability in the treatment arm need not be considered a nuisance; it can be modeled to yield insights about the treatment process.

  9. Innovating cystic fibrosis clinical trial designs in an era of successful standard of care therapies.

    Science.gov (United States)

    VanDevanter, Donald R; Mayer-Hamblett, Nicole

    2017-11-01

    Evolving cystic fibrosis 'standards of care' have influenced recent cystic fibrosis clinical trial designs for new therapies; care additions/improvements will require innovative trial designs to maximize feasibility and efficacy detection. Three cystic fibrosis therapeutic areas (pulmonary exacerbations, Pseudomonas aeruginosa airway infections, and reduced cystic fibrosis transmembrane conductance regulator [CFTR] protein function) differ with respect to the duration for which recognized 'standards of care' have been available. However, developers of new therapies in all the three areas are affected by similar challenges: standards of care have become so strongly entrenched that traditional placebo-controlled studies in cystic fibrosis populations likely to benefit from newer therapies have become less and less feasible. Today, patients/clinicians are more likely to entertain participation in active-comparator trial designs, that have substantial challenges of their own. Foremost among these are the selection of 'valid' active comparator(s), estimation of a comparator's current clinical efficacy (required for testing noninferiority hypotheses), and effective blinding of commercially available comparators. Recent and future cystic fibrosis clinical trial designs will have to creatively address this collateral result of successful past development of effective cystic fibrosis therapies: patients and clinicians are much less likely to accept simple, placebo-controlled studies to evaluate future therapies.

  10. Material characterisation and preliminary mechanical design for the HL-LHC shielded beam screens operating at cryogenic temperatures

    CERN Document Server

    Garion, C; Koettig, T; Machiocha, W; Morrone, M

    2015-01-01

    The High Luminosity LHC project (HL-LHC) aims at increasing the luminosity (rate of collisions) in the Large Hadron Collider (LHC) experiments by a factor of 10 beyond the original design value (from 300 to 3000 fb-1). It relies on new superconducting magnets, installed close to the interaction points, equipped with new beam screen. This component has to ensure the vacuum performance together with shielding the cold mass from physics debris and screening the cold bore cryogenic system from beam induced heating. The beam screen operates in the range 40-60 K whereas the magnet cold bore temperature is 1.9 K. A tungsten-based material is used to absorb the energy of particles. In this paper, measurements of the mechanical and physical properties of such tungsten material are shown at room and cryogenic temperature. In addition, the design and the thermal mechanical behaviour of the beam screen assembly are presented also. They include the heat transfer from the tungsten absorbers to the cooling pipes and the sup...

  11. Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

    Science.gov (United States)

    Perucca, Emilio

    2008-01-01

    Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

  12. The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) framework: protocol to determine a core outcome set for efficacy and effectiveness trials of alcohol screening and brief intervention.

    Science.gov (United States)

    Shorter, G W; Heather, N; Bray, Jeremy W; Giles, E L; Holloway, A; Barbosa, C; Berman, A H; O'Donnell, A J; Clarke, M; Stockdale, K J; Newbury-Birch, D

    2017-12-22

    The evidence base to assess the efficacy and effectiveness of alcohol brief interventions (ABI) is weakened by variation in the outcomes measured and by inconsistent reporting. The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) project aims to develop a core outcome set (COS) and reporting guidance for its use in future trials of ABI in a range of settings. An international Special Interest Group was convened through INEBRIA (International Network on Brief Interventions for Alcohol and Other Drugs) to inform the development of a COS for trials of ABI. ORBITAL will incorporate a systematic review to map outcomes used in efficacy and effectiveness trials of ABI and their measurement properties, using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. This will support a multi-round Delphi study to prioritise outcomes. Delphi panellists will be drawn from a range of settings and stakeholder groups, and the Delphi study will also be used to determine if a single COS is relevant for all settings. A consensus meeting with key stakeholder representation will determine the final COS and associated guidance for its use in trials of ABI. ORBITAL will develop a COS for alcohol screening and brief intervention trials, with outcomes stratified into domains and guidance on outcome measurement instruments. The standardisation of ABI outcomes and their measurement will support the ongoing development of ABI studies and a systematic synthesis of emerging research findings. We will track the extent to which the COS delivers on this promise through an exploration of the use of the guidance in the decade following COS publication.

  13. Design and Methodology of the Trial to Assess Chelation Therapy (TACT)

    Science.gov (United States)

    Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Drisko, Jeanne A.; Lee, Kerry L.

    2011-01-01

    The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010. PMID:22172430

  14. Cervical cancer screening at crossroads

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada

    2014-01-01

    Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark......, screening decreased the incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented...... cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT...

  15. A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

    Science.gov (United States)

    Palma, Anton; Lounsbury, David W; Schlecht, Nicolas F; Agalliu, Ilir

    2016-02-01

    Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Screening asymptomatic patients with diabetes for unknown coronary artery disease: Does it reduce risk? An open-label randomized trial comparing a strategy based on exercise testing aimed at revascularization with management based on pharmacological/behavioural treatment of traditional risk factors. DADDY-D Trial (Does coronary Atherosclerosis Deserve to be Diagnosed and treated early in Diabetics?

    Directory of Open Access Journals (Sweden)

    Romano Stefania

    2009-12-01

    Full Text Available Abstract Background Coronary artery disease is the leading cause of morbidity and mortality in patients with type 2 diabetes. Screening for asymptomatic coronary artery disease with treatment by means of revascularization seems to be an appealing option for prevention. The utility of such a strategy has never been challenged in a randomized trial. Methods/Design In the present study a cohort of diabetic patients without any symptoms and without known coronary artery disease will be screened at two diabetes outpatients services. Those with intermediate or high risk (equal or greater than 10% according to the Italian risk chart will be asked to participate and enrolled. They will be seen and followed in order to provide the best adherence to medical therapy. Half of the patients will be randomized to undergo an exercise tolerance testing while the other group will continue to be regularly seen at diabetes outpatients services. Best medical/behavioral therapy will be offered to both groups. Those patients with a positive exercise tolerance testing will be studied by coronary angiography and treated according to the severity of coronary lesions by percutaneous stenting or surgery. The objective of the study is to evaluate the efficacy of the screening strategy aimed at revascularization. A cost-effectiveness analysis will be performed at the end of the follow up. Discussion The study will provide useful information about prevention and treatment of diabetic patients at high risk of coronary events. It will be made clearer if detection of silent coronary artery disease has to be recommended and followed by treatment. Given the simplicity of the study protocol, it will be easily transferable to the real world. Trial registration (ClinicalTrials.gov: NCT00547872

  17. Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

    International Nuclear Information System (INIS)

    Scholten, Ernst T.; Horeweg, Nanda; Koning, Harry J. de; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; Mali, Willem P.T.M.; Jong, Pim A. de

    2015-01-01

    To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

  18. Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

    Energy Technology Data Exchange (ETDEWEB)

    Scholten, Ernst T. [University Medical Centre, Department of Radiology, Utrecht (Netherlands); Kennemer Gasthuis, Department of Radiology, Haarlem (Netherlands); Horeweg, Nanda [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Erasmus University Medical Centre, Department of Pulmonary Medicine, Rotterdam (Netherlands); Koning, Harry J. de [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Vliegenthart, Rozemarijn [University of Groningen, University Medical Centre Groningen, Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Oudkerk, Matthijs [University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Mali, Willem P.T.M.; Jong, Pim A. de [University Medical Centre, Department of Radiology, Utrecht (Netherlands)

    2015-01-15

    To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

  19. Learning From Past Failures of Oral Insulin Trials.

    Science.gov (United States)

    Michels, Aaron W; Gottlieb, Peter A

    2018-07-01

    Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical type 1 diabetes, which was the primary end point. The unfortunate outcome follows the previous large-scale trial, the Diabetes Prevention Trial-Type 1 (DPT-1), which again failed to delay diabetes onset with oral insulin or low-dose subcutaneous insulin injections in a randomized controlled trial with relatives at risk for type 1 diabetes. These sobering results raise the important question, "Where does the type 1 diabetes prevention field move next?" In this Perspective, we advocate for a paradigm shift in which smaller mechanistic trials are conducted to define immune mechanisms and potentially identify treatment responders. The stage is set for these interventions in individuals at risk for type 1 diabetes as Type 1 Diabetes TrialNet has identified thousands of relatives with islet autoantibodies and general population screening for type 1 diabetes risk is under way. Mechanistic trials will allow for better trial design and patient selection based upon molecular markers prior to large randomized controlled trials, moving toward a personalized medicine approach for the prevention of type 1 diabetes. © 2018 by the American Diabetes Association.

  20. Screening for Speech and Language Delay in Children 5 Years Old and Younger: A Systematic Review.

    Science.gov (United States)

    Wallace, Ina F; Berkman, Nancy D; Watson, Linda R; Coyne-Beasley, Tamera; Wood, Charles T; Cullen, Katherine; Lohr, Kathleen N

    2015-08-01

    No recommendation exists for or against routine use of brief, formal screening instruments in primary care to detect speech and language delay in children through 5 years of age. This review aimed to update the evidence on screening and treating children for speech and language since the 2006 US Preventive Services Task Force systematic review. Medline, the Cochrane Library, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and reference lists. We included studies reporting diagnostic accuracy of screening tools and randomized controlled trials reporting benefits and harms of treatment of speech and language. Two independent reviewers extracted data, checked accuracy, and assigned quality ratings using predefined criteria. We found no evidence for the impact of screening on speech and language outcomes. In 23 studies evaluating the accuracy of screening tools, sensitivity ranged between 50% and 94%, and specificity ranged between 45% and 96%. Twelve treatment studies improved various outcomes in language, articulation, and stuttering; little evidence emerged for interventions improving other outcomes or for adverse effects of treatment. Risk factors associated with speech and language delay were male gender, family history, and low parental education. A limitation of this review is the lack of well-designed, well-conducted studies addressing whether screening for speech and language delay or disorders improves outcomes. Several screening tools can accurately identify children for diagnostic evaluations and interventions, but evidence is inadequate regarding applicability in primary care settings. Some treatments for young children identified with speech and language delays and disorders may be effective. Copyright © 2015 by the American Academy of Pediatrics.

  1. Hot Topic: Preimplantation aneuploidy screening

    Directory of Open Access Journals (Sweden)

    Kayhan Yakın

    2009-03-01

    Full Text Available Preimplantation Genetic Screening (PGS is a technique that has been introduced into clinical practice to screen and eliminate aneuploid embryos form transfer with the intention to improve implantation rates and decrease pregnancy wastage. Although practiced widely throughout the world the PGS unfortunately has been adopted without being subjected to rigorous scientific validation. Data from recent prospective randomized trials have shed doubt on the efficacy of the procedure when used in women with advanced age, one of the target populations for PGS. Other purported indications for the application of this complicated technique such as recurrent implantation failure and recurrent spontaneous abortion have not been subjected to randomized controlled trials. For the best interest of patients, we feel it is timely for a debate regarding the efficacy and safety of PGS.

  2. Lessons learned from IDeAl - 33 recommendations from the IDeAl-net about design and analysis of small population clinical trials.

    Science.gov (United States)

    Hilgers, Ralf-Dieter; Bogdan, Malgorzata; Burman, Carl-Fredrik; Dette, Holger; Karlsson, Mats; König, Franz; Male, Christoph; Mentré, France; Molenberghs, Geert; Senn, Stephen

    2018-05-11

    IDeAl (Integrated designs and analysis of small population clinical trials) is an EU funded project developing new statistical design and analysis methodologies for clinical trials in small population groups. Here we provide an overview of IDeAl findings and give recommendations to applied researchers. The description of the findings is broken down by the nine scientific IDeAl work packages and summarizes results from the project's more than 60 publications to date in peer reviewed journals. In addition, we applied text mining to evaluate the publications and the IDeAl work packages' output in relation to the design and analysis terms derived from in the IRDiRC task force report on small population clinical trials. The results are summarized, describing the developments from an applied viewpoint. The main result presented here are 33 practical recommendations drawn from the work, giving researchers a comprehensive guidance to the improved methodology. In particular, the findings will help design and analyse efficient clinical trials in rare diseases with limited number of patients available. We developed a network representation relating the hot topics developed by the IRDiRC task force on small population clinical trials to IDeAl's work as well as relating important methodologies by IDeAl's definition necessary to consider in design and analysis of small-population clinical trials. These network representation establish a new perspective on design and analysis of small-population clinical trials. IDeAl has provided a huge number of options to refine the statistical methodology for small-population clinical trials from various perspectives. A total of 33 recommendations developed and related to the work packages help the researcher to design small population clinical trial. The route to improvements is displayed in IDeAl-network representing important statistical methodological skills necessary to design and analysis of small-population clinical trials. The methods

  3. A Multi-Center Diabetes Eye Screening Study in Community Settings: Study Design and Methodology.

    Science.gov (United States)

    Murchison, Ann P; Friedman, David S; Gower, Emily W; Haller, Julia A; Lam, Byron L; Lee, David J; McGwin, Gerald; Owsley, Cynthia; Saaddine, Jinan; Insight Study Group

    2016-01-01

    Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings. Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process. Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal. The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings.

  4. Clinical inquiries: which women should we screen for gestational diabetes mellitus?

    Science.gov (United States)

    Namak, Shahla; Lord, Richard W; Zolotor, Adam J; Kramer, Rochelle

    2010-08-01

    It's unclear which women we should screen. No randomized controlled trials (RCTs) demonstrate that either universal screening or risk factor screening for gestational diabetes mellitus (GDM) prevents maternal and fetal adverse outcomes. That said, the common practice of universal screening is more sensitive than screening based on risk factors. Historic risk factors are poor predictors of GDM in a current pregnancy.

  5. The Diabetes Telephone Study: Design and challenges of a pragmatic cluster randomized trial to improve diabetic peripheral neuropathy treatment.

    Science.gov (United States)

    Adams, Alyce S; Bayliss, Elizabeth A; Schmittdiel, Julie A; Altschuler, Andrea; Dyer, Wendy; Neugebauer, Romain; Jaffe, Marc; Young, Joseph D; Kim, Eileen; Grant, Richard W

    2016-06-01

    Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration, and quality of life among patients with symptomatic diabetic peripheral neuropathy. We implemented a pragmatic cluster randomized controlled trial to test the effectiveness of an automated interactive voice response tool designed to provide physicians with real-time patient-reported data about responses to newly prescribed diabetic peripheral neuropathy medicines. A total of 1834 primary care physicians treating patients in the diabetes registry at Kaiser Permanente Northern California were randomized into the intervention or control arm. In September 2014, we began identification and recruitment of patients assigned to physicians in the intervention group who receive three brief interactive calls every 2 months after a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms. These calls provide patients with the opportunity to report on symptoms, side effects, self-titration of medication dose and overall satisfaction with treatment. We plan to compare changes in self-reported quality of life between the intervention group and patients in the control group who receive three non-interactive automated educational phone calls. Successful implementation of this clinical trial required robust stakeholder engagement to help tailor the intervention and to address pragmatic concerns such as provider time constraints. As of 27 October 2015, we had screened 2078 patients, 1447 of whom were eligible for participation. We consented and enrolled 1206 or 83% of those eligible. Among those enrolled, 53% are women and the mean age

  6. Prevention of Contrast-Induced AKI: A Review of Published Trials and the Design of the Prevention of Serious Adverse Events following Angiography (PRESERVE) Trial

    Science.gov (United States)

    Gallagher, Martin; Kaufman, James; Cass, Alan; Parikh, Chirag R.; Chertow, Glenn M.; Shunk, Kendrick A.; McCullough, Peter A.; Fine, Michael J.; Mor, Maria K.; Lew, Robert A.; Huang, Grant D.; Conner, Todd A.; Brophy, Mary T.; Lee, Joanne; Soliva, Susan; Palevsky, Paul M.

    2013-01-01

    Summary Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial. PMID:23660180

  7. Can an alert in primary care electronic medical records increase participation in a population-based screening programme for colorectal cancer? COLO-ALERT, a randomised clinical trial

    International Nuclear Information System (INIS)

    Guiriguet-Capdevila, Carolina; Fuentes-Peláez, Antonio; Reina-Rodríguez, Dolores; De León-Gallo, Rosa; Mendez-Boo, Leonardo; Torán-Monserrat, Pere; Muñoz-Ortiz, Laura; Rivero-Franco, Irene; Vela-Vallespín, Carme; Vilarrubí-Estrella, Mercedes; Torres-Salinas, Miquel; Grau-Cano, Jaume; Burón-Pust, Andrea; Hernández-Rodríguez, Cristina

    2014-01-01

    Colorectal cancer is an important public health problem in Spain. Over the last decade, several regions have carried out screening programmes, but population participation rates remain below recommended European goals. Reminders on electronic medical records have been identified as a low-cost and high-reach strategy to increase participation. Further knowledge is needed about their effect in a population-based screening programme. The main aim of this study is to evaluate the effectiveness of an electronic reminder to promote the participation in a population-based colorectal cancer screening programme. Secondary aims are to learn population’s reasons for refusing to take part in the screening programme and to find out the health professionals’ opinion about the official programme implementation and on the new computerised tool. This is a parallel randomised trial with a cross-sectional second stage. Participants: all the invited subjects to participate in the public colorectal cancer screening programme that includes men and women aged between 50–69, allocated to the eleven primary care centres of the study and all their health professionals. The randomisation unit will be the primary care physician. The intervention will consist of activating an electronic reminder, in the patient’s electronic medical record, in order to promote colorectal cancer screening, during a synchronous medical appointment, throughout the year that the intervention takes place. A comparison of the screening rates will then take place, using the faecal occult blood test of the patients from the control and the intervention groups. We will also take a questionnaire to know the opinions of the health professionals. The main outcome is the screening status at the end of the study. Data will be analysed with an intention-to-treat approach. We expect that the introduction of specific reminders in electronic medical records, as a tool to facilitate and encourage direct referral by

  8. Technology-facilitated depression care management among predominantly Latino diabetes patients within a public safety net care system: comparative effectiveness trial design.

    Science.gov (United States)

    Wu, Shinyi; Ell, Kathleen; Gross-Schulman, Sandra G; Sklaroff, Laura Myerchin; Katon, Wayne J; Nezu, Art M; Lee, Pey-Jiuan; Vidyanti, Irene; Chou, Chih-Ping; Guterman, Jeffrey J

    2014-03-01

    Health disparities in minority populations are well recognized. Hispanics and Latinos constitute the largest ethnic minority group in the United States; a significant proportion receives their care via a safety net. The prevalence of diabetes mellitus and comorbid depression is high among this group, but the uptake of evidence-based collaborative depression care management has been suboptimal. The study design and baseline characteristics of the enrolled sample in the Diabetes-Depression Care-management Adoption Trial (DCAT) establishes a quasi-experimental comparative effectiveness research clinical trial aimed at accelerating the adoption of collaborative depression care in safety net clinics. The study was conducted in collaboration with the Los Angeles County Department of Health Services at eight county-operated clinics. DCAT has enrolled 1406 low-income, predominantly Hispanic/Latino patients with diabetes to test a translational model of depression care management. This three-group study compares usual care with a collaborative care team support model and a technology-facilitated depression care model that provides automated telephonic depression screening and monitoring tailored to patient conditions and preferences. Call results are integrated into a diabetes disease management registry that delivers provider notifications, generates tasks, and issues critical alerts. All subjects receive comprehensive assessments at baseline, 6, 12, and 18 months by independent English-Spanish bilingual interviewers. Study outcomes include depression outcomes, treatment adherence, satisfaction, acceptance of assessment and monitoring technology, social and economic stress reduction, diabetes self-care management, health care utilization, and care management model cost and cost-effectiveness comparisons. DCAT's goal is to optimize depression screening, treatment, follow-up, outcomes, and cost savings to reduce health disparities. Copyright © 2013 Elsevier Inc. All rights

  9. Design and analysis of group-randomized trials in cancer: A review of current practices.

    Science.gov (United States)

    Murray, David M; Pals, Sherri L; George, Stephanie M; Kuzmichev, Andrey; Lai, Gabriel Y; Lee, Jocelyn A; Myles, Ranell L; Nelson, Shakira M

    2018-06-01

    The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues. Published by Elsevier Inc.

  10. Family in Focus: On Design and Field Trial of the Dynamic Collage [DC

    NARCIS (Netherlands)

    René Bakker; Koen van Turnhout; Jasper Jeurens

    2014-01-01

    In this paper we present the design and field trial of the Dynamic Collage. The Dynamic Collage was designed to facilitate and to stimulate participation of family members in the informal care of an elderly person. The Dynamic Collage enabled relatives to update their current activity by sending a

  11. Screening for and subsequent participation in a trial for depression and anxiety in people with type 2 diabetes treated in primary care: Who do we reach?

    NARCIS (Netherlands)

    Stoop, C.H.; Nefs, G.M.; Pop, V.J.M.; Pouwer, F.

    2017-01-01

    AIMS: This study investigated (factors related to) (a) the response to a screening procedure for depression and anxiety in people with type 2 diabetes in primary care, and (b) participation in a subsequent randomised controlled trial targeting depressive or anxiety symptoms. METHODS: People with

  12. Screening for and subsequent participation in a trial for depression and anxiety in people with type 2 diabetes treated in primary care : Who do we reach?

    NARCIS (Netherlands)

    Stoop, C.H.; Nefs, G.M.; Pop, V.J.M.; Pouwer, François

    2017-01-01

    Aims: This study investigated (factors related to) (a) the response to a screening procedure for depression and anxiety in people with type 2 diabetes in primary care, and (b) participation in a subsequent randomised controlled trial targeting depressive or anxiety symptoms. Methods: People with

  13. Cost effectiveness analysis of screening in the early diagnosis of prostate cancer (PCA)

    International Nuclear Information System (INIS)

    Mueller-Lisse, U.G.; Mueller-Lisse, U.L.

    2002-01-01

    Purpose. The authors attempted to provide an overview of current concepts and the status of research in the field of cost effectiveness analysis (CEA) of screening for prostate cancer (PCA).Material and methods. Basic concepts and methods of CEA were reviewed. Examples of CEA-related studies of PCA were obtained from pertinent literature through medical databases.Results. Screening for PCA has so far been restricted to limited groups of health care recipients, usually within the framework of clinical trials. In those trials, screening for PCA usually results in higher numbers of PCAs being detected at lower average stages in a given population. As a consequence of screening, the rate of potentially curable PCAs increases. However, it has not yet been demonstrated that screening for PCA decreases PCA-related mortality or morbidity from metastatic PCA. On the other hand, additional costs are associated with the screening measure and with increased use of resources for diagnosis and treatment of the additional PCAs detected through screening.Conclusions. Throughout the European Union and North America, mass screening for PCA has not been implemented. This may chiefly be due to the current lack of information on long term benefits of PCA screening, particularly disease-specific survival. Currently, major studies are underway to assess the effects of PCA screening and its cost effectiveness. These studies include the US-American prostate, lung, colon and ovary trials (PLCO) and the European randomised study of Screening for Prostate Cancer (ERSPC). (orig.) [de

  14. High-throughput bioaffinity mass spectrometry for screening and identification of designer anabolic steroids in dietary supplements.

    Science.gov (United States)

    Aqai, Payam; Cevik, Ebru; Gerssen, Arjen; Haasnoot, Willem; Nielen, Michel W F

    2013-03-19

    A generic high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of known and unknown recombinant human sex hormone-binding globulin (rhSHBG)-binding designer steroids in dietary supplements. For screening, a semi-automated competitive inhibition binding assay was combined with fast ultrahigh-performance-LC-electrospray ionization-triple-quadrupole-MS (UPLC-QqQ-MS). 17β-Testosterone-D3 was used as the stable isotope label of which the binding to rhSHBG-coated paramagnetic microbeads was inhibited by any other binding (designer) steroid. The assay was performed in a 96-well plate and combined with the fast LC-MS, 96 measurements could be performed within 4 h. The concentration-dependent inhibition of the label by steroids in buffer and dietary supplements was demonstrated. Following an adjusted bioaffinity isolation procedure, suspect extracts were injected into a chip-UPLC(NanoTile)-Q-time-of-flight-MS system for full-scan accurate mass identification. Next to known steroids, 1-testosterone was identified in three of the supplements studied and the designer steroid tetrahydrogestrinone was identified in a spiked supplement. The generic steroid-binding assay can be used for high-throughput screening of androgens, estrogens, and gestagens in dietary supplements to fight doping. When combined with chip-UPLC-MS, it is a powerful tool for early warning of unknown emerging rhSHBG bioactive designer steroids in dietary supplements.

  15. Clinical Trials

    Medline Plus

    Full Text Available ... combination of estrogen and progestin, the risk of breast cancer also increased. As a result, the U.S. Food ... to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial participants often were ...

  16. Correlates of women’s intentions to be screened for human papillomavirus for cervical cancer screening with an extended interval

    Directory of Open Access Journals (Sweden)

    Gina S. Ogilvie

    2016-03-01

    Full Text Available Abstract Background High-risk HPV DNA testing has been proposed as a primary tool for cervical cancer screening (HPV-CCS as an alternative to the Papanicolaou cytology- method. This study describes factors associated with women’s intentions to attend cervical cancer screening if high-risk HPV DNA testing (HPV-CCS was implemented as a primary screening tool, and if screening were conducted every 4 years starting after age 25. Methods This online survey was designed using the Theory of Planned Behaviour to assess factors that impact women’s intentions to attend HPV-CCS among women aged 25–69 upon exit of the HPV FOCAL trial. Univariate and regression analyses were performed to compare the demographic, sexual history, and smoking characteristics between women willing and unwilling to screen, and scales for intention to attend HPV-CCS. A qualitative analysis was performed by compiling and coding the comments section of the survey. Results Of the 981 women who completed the survey in full, only 51.4 % responded that they intended to attend HPV-CCS with a delayed start age and extended screening interval. Women who intended to screen were more likely to have higher education (AOR 0.59, 95 % CI [0.37, 0.93], while both positive attitudes (AOR 1.26, 95 % CI [1.23, 1.30] and perceived behavior control (AOR 1.06, 95 % CI [1.02, 1.10] were significant predictors of intention to screen. Among women who provided comments in the survey, a large number of women expressed fears about not being checked more than every 4 years, but 12 % stated that these fears may be alleviated by having more information. Conclusions Acceptability of increased screening intervals and starting age could be improved through enhanced education of benefits. Program planners should consider measures to assess and improve women’s knowledge, attitudes and beliefs prior to the implementation of new screening programs to avoid unintended consequences.

  17. Material characterisation and preliminary mechanical design for the HL-LHC shielded beam screens operating at cryogenic temperatures.

    Science.gov (United States)

    Garion, C.; Dufay-Chanat, L.; Koettig, T.; Machiocha, W.; Morrone, M.

    2015-12-01

    The High Luminosity LHC project (HL-LHC) aims at increasing the luminosity (rate of collisions) in the Large Hadron Collider (LHC) experiments by a factor of 10 beyond the original design value (from 300 to 3000 fb-1). It relies on new superconducting magnets, installed close to the interaction points, equipped with new beam screen. This component has to ensure the vacuum performance together with shielding the cold mass from physics debris and screening the cold bore cryogenic system from beam induced heating. The beam screen operates in the range 40-60 K whereas the magnet cold bore temperature is 1.9 K. A tungsten-based material is used to absorb the energy of particles. In this paper, measurements of the mechanical and physical properties of such tungsten material are shown at room and cryogenic temperature. In addition, the design and the thermal mechanical behaviour of the beam screen assembly are presented also. They include the heat transfer from the tungsten absorbers to the cooling pipes and the supporting system that has to minimise the heat inleak into the cold mass. The behaviour during a magnet quench is also presented.

  18. Material characterisation and preliminary mechanical design for the HL-LHC shielded beam screens operating at cryogenic temperatures

    International Nuclear Information System (INIS)

    Garion, C; Dufay-Chanat, L; Koettig, T; Machiocha, W; Morrone, M

    2015-01-01

    The High Luminosity LHC project (HL-LHC) aims at increasing the luminosity (rate of collisions) in the Large Hadron Collider (LHC) experiments by a factor of 10 beyond the original design value (from 300 to 3000 fb -1 ). It relies on new superconducting magnets, installed close to the interaction points, equipped with new beam screen. This component has to ensure the vacuum performance together with shielding the cold mass from physics debris and screening the cold bore cryogenic system from beam induced heating. The beam screen operates in the range 40-60 K whereas the magnet cold bore temperature is 1.9 K. A tungsten-based material is used to absorb the energy of particles. In this paper, measurements of the mechanical and physical properties of such tungsten material are shown at room and cryogenic temperature. In addition, the design and the thermal mechanical behaviour of the beam screen assembly are presented also. They include the heat transfer from the tungsten absorbers to the cooling pipes and the supporting system that has to minimise the heat inleak into the cold mass. The behaviour during a magnet quench is also presented. (paper)

  19. Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Jacobsen, Rikke Kart; Toft, Ulla

    2014-01-01

    of Copenhagen, Denmark. PARTICIPANTS: 59,616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n = 11,629) and a control group (n = 47,987). INTERVENTION: The intervention group was invited for screening, risk assessment, and lifestyle counselling up...... sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening......OBJECTIVE: To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. DESIGN: Randomised controlled community based trial. SETTING: Suburbs...

  20. [Therapeutic impact of screening for myocardial ischemia among asymptomatic type 2 diabetic subjects].

    Science.gov (United States)

    Wallemacq, Caroline M; Scheen, André J

    2008-08-27

    Coronary artery disease is the major cause of mortality of type 2 diabetic subjects. Its early diagnosis to prevent progression and clinical events has intuitive appeal. Somehow, rationale for screening has not been clearly established. Screening should not modify the medical therapy because diabetic subjects have to be treated in a secondary prevention strategy. We have no data from randomized trials concerning a better outcome after revascularization in this specific population. The question how to select the high risk population to be screened has no response by now. SPECT and stress echocardiography seem valuable for screening but not for risk stratification. A large randomized clinical trial is required to confirm the cost-utility ratio of such a screening.

  1. False-positive Human Papillomavirus DNA tests in cervical screening

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Pribac, Igor; Lynge, Elsebeth

    2011-01-01

    Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus (HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated...

  2. iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2017-11-01

    Full Text Available In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD. Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ, a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.

  3. Factors influencing the decline in lung density in a Danish lung cancer screening cohort

    DEFF Research Database (Denmark)

    Shaker, Saher B.; Dirksen, Asger; Lo, Pechin Chien Pau

    2012-01-01

    Lung cancer screening trials provide an opportunity to study the natural history of emphysema by using CT lung density as a surrogate parameter.In the Danish Lung Cancer Screening Trial, 2,052 participants were included. At screening rounds, smoking habits were recorded and spirometry was performed....... CT lung density was measured as the volume-adjusted 15th percentile density (PD15). A mixed effects model was used with former smoking males with...

  4. Morphologic abnormalities in 2-year-old children born after in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening: follow-up of a randomized controlled trial

    NARCIS (Netherlands)

    Beukers, Fenny; van der Heide, Maaike; Middelburg, Karin J.; Cobben, Jan Maarten; Mastenbroek, Sebastiaan; Breur, Rinske; van der Lee, Johanna H.; Hadders-Algra, Mijna; Bos, Arend F.; Kok, Joke H.; Houtzager, Bregje A.; Repping, Sjoerd; Twisk, Moniek; van der Veen, Fulco; Haadsma, Maaike; Heineman, Maas Jan; van Hoften, Jacorina; Jongbloed-Pereboom, Marjolein; Keating, Paul; Seggers, Jorien

    2013-01-01

    To evaluate the effect of preimplantation genetic screening (PGS) on morphologic outcome in children. Follow-up of a randomized controlled trial (RCT). University hospital. Two-year-old children born to mothers who participated in an RCT on the efficacy of PGS: 50 children born after in vitro

  5. Bayesian methods for the design and interpretation of clinical trials in very rare diseases

    Science.gov (United States)

    Hampson, Lisa V; Whitehead, John; Eleftheriou, Despina; Brogan, Paul

    2014-01-01

    This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is clearly infeasible. Rather, the expectation of any such trial has to be limited to the generation of an improved understanding of treatment options. We propose a Bayesian approach for the conduct of rare-disease trials comparing an experimental treatment with a control where patient responses are classified as a success or failure. A systematic elicitation from clinicians of their beliefs concerning treatment efficacy is used to establish Bayesian priors for unknown model parameters. The process of determining the prior is described, including the possibility of formally considering results from related trials. As sample sizes are small, it is possible to compute all possible posterior distributions of the two success rates. A number of allocation ratios between the two treatment groups can be considered with a view to maximising the prior probability that the trial concludes recommending the new treatment when in fact it is non-inferior to control. Consideration of the extent to which opinion can be changed, even by data from the best feasible design, can help to determine whether such a trial is worthwhile. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:24957522

  6. Applying normalization process theory to understand implementation of a family violence screening and care model in maternal and child health nursing practice: a mixed method process evaluation of a randomised controlled trial.

    Science.gov (United States)

    Hooker, Leesa; Small, Rhonda; Humphreys, Cathy; Hegarty, Kelsey; Taft, Angela

    2015-03-28

    In Victoria, Australia, Maternal and Child Health (MCH) services deliver primary health care to families with children 0-6 years, focusing on health promotion, parenting support and early intervention. Family violence (FV) has been identified as a major public health concern, with increased prevalence in the child-bearing years. Victorian Government policy recommends routine FV screening of all women attending MCH services. Using Normalization Process Theory (NPT), we aimed to understand the barriers and facilitators of implementing an enhanced screening model into MCH nurse clinical practice. NPT informed the process evaluation of a pragmatic, cluster randomised controlled trial in eight MCH nurse teams in metropolitan Melbourne, Victoria, Australia. Using mixed methods (surveys and interviews), we explored the views of MCH nurses, MCH nurse team leaders, FV liaison workers and FV managers on implementation of the model. Quantitative data were analysed by comparing proportionate group differences and change within trial arm over time between interim and impact nurse surveys. Qualitative data were inductively coded, thematically analysed and mapped to NPT constructs (coherence, cognitive participation, collective action and reflexive monitoring) to enhance our understanding of the outcome evaluation. MCH nurse participation rates for interim and impact surveys were 79% (127/160) and 71% (114/160), respectively. Twenty-three key stakeholder interviews were completed. FV screening work was meaningful and valued by participants; however, the implementation coincided with a significant (government directed) change in clinical practice which impacted on full engagement with the model (coherence and cognitive participation). The use of MCH nurse-designed FV screening/management tools in focussed women's health consultations and links with FV services enhanced the participants' work (collective action). Monitoring of FV work (reflexive monitoring) was limited. The use of

  7. Prostate cancer screening: and yet it moves!

    Directory of Open Access Journals (Sweden)

    Maciej Kwiatkowski

    2015-06-01

    Full Text Available The debate of prostate cancer (PCa screening has been shaped over decades. There is a plethora of articles in the literature supporting as well as declining prostate-specific antigen (PSA screening. Does screening decrease PCa mortality? With the long-term results of the European Randomized Study of Screening for Prostate (ERSPC the answer is clearly YES. It moves! However, in medicine there are no benefits without any harm and thus, screening has to be performed in targeted and smart way-or in other words-in a risk-adapted fashion when compared with the way it was done in the past. Here, we discuss the main findings of the ERSPC trials and provide insights on how the future screening strategies should be implemented.

  8. 'Away Days' in multi-centre randomised controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment.

    Science.gov (United States)

    Jefferson, Laura; Cook, Liz; Keding, Ada; Brealey, Stephen; Handoll, Helen; Rangan, Amar

    2015-11-06

    'Away Days' (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multi-centre randomised controlled trials (RCTs). We explored the use of Away Days in multi-centre RCTs and analysed the effect on patient recruitment in a case study. Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multi-centre pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. A total of 94 people responded to the survey. The majority (78%), who confirmed had organised an Away Day previously, found them to be useful. This is despite their costs.. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multi-centre surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. A novel hypothesis on the sensitivity of the fecal occult blood test: Results of a joint analysis of 3 randomized controlled trials.

    Science.gov (United States)

    Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Boer, Rob; Zauber, Ann; Habbema, J Dik F

    2009-06-01

    Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening. We used the MISCAN-Colon microsimulation model to estimate sensitivity and duration, accounting for differences between the trials in demography, background incidence, and trial design. We tested 3 hypotheses for FOBT sensitivity: sensitivity is the same for all preclinical CRC stages, sensitivity increases with each stage, and sensitivity is higher for the stage in which the cancer would have been diagnosed in the absence of screening than for earlier stages. Goodness-of-fit was evaluated by comparing expected and observed rates of screen-detected and interval CRC. The hypothesis with a higher sensitivity in the stage of clinical diagnosis gave the best fit. Under this hypothesis, sensitivity of FOBT was 51% in the stage of clinical diagnosis and 19% in earlier stages. The average duration of preclinical CRC was estimated at 6.7 years. Our analysis corroborated a long duration of preclinical CRC, with FOBT most sensitive in the stage of clinical diagnosis. (c) 2009 American Cancer Society.

  10. The effect of changing stool collection processes on compliance in nationwide organized screening using a fecal occult blood test (FOBT) in Korea: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Shin, Hye Young; Suh, Mina; Baik, Hyung Won; Choi, Kui Son; Park, Boyoung; Jun, Jae Kwan; Lee, Chan Wha; Oh, Jae Hwan; Lee, You Kyoung; Han, Dong Soo; Lee, Do-Hoon

    2014-11-26

    Colorectal cancer (CRC) screening by fecal occult blood test (FOBT) significantly reduces CRC mortality, and compliance rates directly influence the efficacy of this screening method. The aim of this study is to investigate whether stool collection strategies affect compliance with the FOBT. In total, 3,596 study participants aged between 50 and 74 years will be recruited. The study will be conducted using a randomized controlled trial, with a 2 × 2 factorial design resulting in four groups. The first factor is the method of stool-collection device distribution (mailing vs. visiting the clinic) and the second is the type of stool-collection device (sampling kit vs. conventional container). Participants will be randomly assigned to one of four groups: (1) sampling kit received by mail; (2) conventional container received by mail; (3) sampling kit received at the clinic; (4) conventional container received at the clinic (control group). The primary outcome will be the FOBT compliance rate; satisfaction and intention to be rescreened in the next screening round will also be evaluated. The rates of positive FOBT results and detection of advanced adenomas or cancers through colonoscopies will also be compared between the two collection containers. Identifying a method of FOBT that yields high compliance rates will be a key determinant of the success of CRC screening. The findings of this study will provide reliable information for health policy makers to develop evidence-based strategies for a high compliance rate. KCT0000803 Date of registration in primary registry: 9 January, 2013.

  11. Imaging and screening in lung cancer

    Directory of Open Access Journals (Sweden)

    Matteo Giaj Levra

    2008-12-01

    Full Text Available Lung cancer is the main cause of death for neoplasia in the world. Hence it’s growing the necessity to investigate screening tests to detect tumoral lesions at the early stages: several trials have been performed to establish the best method, target and frequence of the screening to offer. CT, X-ray, PET, sputum citology and CAD software are here analyzed, together with the associated statistics and bias.

  12. Decision-theoretic designs for a series of trials with correlated treatment effects using the Sarmanov multivariate beta-binomial distribution.

    Science.gov (United States)

    Hee, Siew Wan; Parsons, Nicholas; Stallard, Nigel

    2018-03-01

    The motivation for the work in this article is the setting in which a number of treatments are available for evaluation in phase II clinical trials and where it may be infeasible to try them concurrently because the intended population is small. This paper introduces an extension of previous work on decision-theoretic designs for a series of phase II trials. The program encompasses a series of sequential phase II trials with interim decision making and a single two-arm phase III trial. The design is based on a hybrid approach where the final analysis of the phase III data is based on a classical frequentist hypothesis test, whereas the trials are designed using a Bayesian decision-theoretic approach in which the unknown treatment effect is assumed to follow a known prior distribution. In addition, as treatments are intended for the same population it is not unrealistic to consider treatment effects to be correlated. Thus, the prior distribution will reflect this. Data from a randomized trial of severe arthritis of the hip are used to test the application of the design. We show that the design on average requires fewer patients in phase II than when the correlation is ignored. Correspondingly, the time required to recommend an efficacious treatment for phase III is quicker. © 2017 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Non-participation in systematic screening for osteoporosis-the ROSE trial

    DEFF Research Database (Denmark)

    Rothmann, M J; Möller, S; Holmberg, T

    2017-01-01

    Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65-81 years. Although participation rate was high, non-participation was associated with comorbidity, aging other risk facto...

  14. Transactional sex and prevalence of STIs: a cross-sectional study of MSM and transwomen screened for an HIV prevention trial.

    Science.gov (United States)

    Solomon, Marc M; Nureña, César R; Tanur, Judith M; Montoya, Orlando; Grant, Robert M; McConnell, J Jeff

    2015-10-01

    Few studies have characterised the degree of engagement in transactional sex among men and transgender women who have sex with men and explored its association with sexually transmitted infections and human immunodeficiency virus in Ecuador. We screened 642 men who have sex with men and transgender women for a pre-exposure prophylaxis clinical trial (iPrEx) in Guayaquil, Ecuador, 2007-2009. We analysed the association of degree of engagement in transactional sex and prevalence of sexually transmitted infections including human immunodeficiency virus using chi-square and analysis of variance tests. Although just 6.2% of those who screened self-identified as sex workers, 52.1% reported having engaged in transactional sex. Compared to those who had never been paid for sex, those who had been paid were more likely to have a sexually transmitted infection (56.6% vs. 45.0%, p = 0.007) and trended towards a higher human immunodeficiency virus prevalence (16.6% vs. 10.4%, p = 0.082) at screening. Transgender women compared to other men who have sex with men were more likely to have sexually transmitted infections diagnosed at screening (75.6% vs. 50.0%, p = 0.001). Transactional sex is practiced widely but occasionally among the men who have sex with men and transgender women in Guayaquil who screened for the iPrEx study; however, engaging in transactional sex may not lead to a sex worker self-identification. Both transactional sex and being a transgender woman are associated with sexually transmitted infections prevalence. © The Author(s) 2015.

  15. Adaptive intervention design in mobile health: Intervention design and development in the Cell Phone Intervention for You trial.

    Science.gov (United States)

    Lin, Pao-Hwa; Intille, Stephen; Bennett, Gary; Bosworth, Hayden B; Corsino, Leonor; Voils, Corrine; Grambow, Steven; Lazenka, Tony; Batch, Bryan C; Tyson, Crystal; Svetkey, Laura P

    2015-12-01

    The obesity epidemic has spread to young adults, and obesity is a significant risk factor for cardiovascular disease. The prominence and increasing functionality of mobile phones may provide an opportunity to deliver longitudinal and scalable weight management interventions in young adults. The aim of this article is to describe the design and development of the intervention tested in the Cell Phone Intervention for You study and to highlight the importance of adaptive intervention design that made it possible. The Cell Phone Intervention for You study was a National Heart, Lung, and Blood Institute-sponsored, controlled, 24-month randomized clinical trial comparing two active interventions to a usual-care control group. Participants were 365 overweight or obese (body mass index≥25 kg/m2) young adults. Both active interventions were designed based on social cognitive theory and incorporated techniques for behavioral self-management and motivational enhancement. Initial intervention development occurred during a 1-year formative phase utilizing focus groups and iterative, participatory design. During the intervention testing, adaptive intervention design, where an intervention is updated or extended throughout a trial while assuring the delivery of exactly the same intervention to each cohort, was employed. The adaptive intervention design strategy distributed technical work and allowed introduction of novel components in phases intended to help promote and sustain participant engagement. Adaptive intervention design was made possible by exploiting the mobile phone's remote data capabilities so that adoption of particular application components could be continuously monitored and components subsequently added or updated remotely. The cell phone intervention was delivered almost entirely via cell phone and was always-present, proactive, and interactive-providing passive and active reminders, frequent opportunities for knowledge dissemination, and multiple tools

  16. Protocol for population testing of an Internet-based Personalised Decision Support system for colorectal cancer screening

    Directory of Open Access Journals (Sweden)

    Wilson Carlene J

    2010-09-01

    Full Text Available Abstract Background Australia has a comparatively high incidence of colorectal (bowel cancer; however, population screening uptake using faecal occult blood test (FOBT remains low. This study will determine the impact on screening participation of a novel, Internet-based Personalised Decision Support (PDS package. The PDS is designed to measure attitudes and cognitive concerns and provide people with individually tailored information, in real time, that will assist them with making a decision to screen. The hypothesis is that exposure to (tailored PDS will result in greater participation in screening than participation following exposure to non-tailored PDS or resulting from the current non-tailored, paper-based approach. Methods/design A randomised parallel trial comprising three arms will be conducted. Men and women aged 50-74 years (N = 3240 will be recruited. They must have access to the Internet; have not had an FOBT within the previous 12 months, or sigmoidoscopy or colonoscopy within the previous 5 years; have had no clinical diagnosis of bowel cancer. Groups 1 and 2 (PDS arms will access a website and complete a baseline survey measuring decision-to-screen stage, attitudes and cognitive concerns and will receive immediate feedback; Group 1 will receive information 'tailored' to their responses in the baseline survey and group 2 will received 'non-tailored' bowel cancer information. Respondents in both groups will subsequently receive an FOBT kit. Group 3 (usual practice arm will complete a paper-based version of the baseline survey and respondents will subsequently receive 'non-tailored' paper-based bowel cancer information with accompanying FOBT kit. Following despatch of FOBTs, all respondents will be requested to complete an endpoint survey. Main outcome measures are (1 completion of FOBT and (2 change in decision-to-screen stage. Secondary outcomes include satisfaction with decision and change in attitudinal scores from baseline to

  17. The prevention access and risk taking in young people (PARTY) project protocol: a cluster randomised controlled trial of health risk screening and motivational interviewing for young people presenting to general practice.

    Science.gov (United States)

    Sanci, Lena; Grabsch, Brenda; Chondros, Patty; Shiell, Alan; Pirkis, Jane; Sawyer, Susan; Hegarty, Kelsey; Patterson, Elizabeth; Cahill, Helen; Ozer, Elizabeth; Seymour, Janelle; Patton, George

    2012-06-06

    There are growing worldwide concerns about the ability of primary health care systems to manage the major burden of illness in young people. Over two thirds of premature adult deaths result from risks that manifest in adolescence, including injury, neuropsychiatric problems and consequences of risky behaviours. One policy response is to better reorientate primary health services towards prevention and early intervention. Currently, however, there is insufficient evidence to support this recommendation for young people. This paper describes the design and implementation of a trial testing an intervention to promote psychosocial risk screening of all young people attending general practice and to respond to identified risks using motivational interviewing. clinicians' detection of risk-taking and emotional distress, young people's intention to change and reduction of risk taking. pathways to care, trust in the clinician and likelihood of returning for future visits. The design of the economic and process evaluation are not detailed in this protocol. PARTY is a cluster randomised trial recruiting 42 general practices in Victoria, Australia. Baseline measures include: youth friendly practice characteristics; practice staff's self-perceived competency in young people's care and clinicians' detection and response to risk taking behaviours and emotional distress in 14-24 year olds, attending the practice. Practices are then stratified by a social disadvantage index and billing methods and randomised. Intervention practices receive: nine hours of training and tools; feedback of their baseline data and two practice visits over six weeks. Comparison practices receive a three hour seminar in youth friendly practice only. Six weeks post-intervention, 30 consecutive young people are interviewed post-consultation from each practice and followed-up for self-reported risk taking behaviour and emotional distress three and 12 months post consultation. The PARTY trial is the

  18. Preliminary Design of the HiLumi-LHC Triplet Area Beam Screen

    CERN Document Server

    Kersevan, R; Kos, N

    2014-01-01

    The so-called beam screen (BS) is a proven solution for intercepting the thermal loads caused by the circulating beams in the cryogenically-cooled sections of the LHC and minimizing dynamic vacuum effects [1]. The new triplet area foreseen for the HiLumi-LHC (HL-LHC) machine upgrade [2] has the additional feature of needing internal tungsten shields to reduce the amount of collision debris which is deflected by the high-gradient triplet magnets towards the superconducting magnets' cold masses and coils. The very aggressive optics design, based on large beam separations, calls for a maximum of physical space to remain available to the counter rotating beams in the common BS. This places severe constraints to the fabrication and installation tolerances of the BS itself, in addition to affecting the design and routing of the cryogenic lines in the area. The latest version of the BS design will be shown and discussed, together with future plans for testing materials, fabrication procedures, and installation.

  19. A Study of Trial and Error Learning in Technology, Engineering, and Design Education

    Science.gov (United States)

    Franzen, Marissa Marie Sloan

    2016-01-01

    The purpose of this research study was to determine if trial and error learning was an effective, practical, and efficient learning method for Technology, Engineering, and Design Education students at the post-secondary level. A mixed methods explanatory research design was used to measure the viability of the learning source. The study sample was…

  20. Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

    Science.gov (United States)

    Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

    2015-05-01

    Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

  1. A fast, simple method for screening radiation susceptibility genes by RNA interference

    International Nuclear Information System (INIS)

    Tsuji, Atsushi B.; Sudo, Hitomi; Sugyo, Aya; Otsuki, Marika; Miyagishi, Makoto; Taira, Kazunari; Imai, Takashi; Harada, Yoshi-nobu

    2005-01-01

    Radiotherapy can cause unacceptable levels of damage to normal tissues in some cancer patients. To understand the molecular mechanisms underlying radiation-induced physiological responses, and to be able to predict the radiation susceptibility of normal tissues in individual patients, it is important to identify a comprehensive set of genes responsible for radiation susceptibility. We have developed a simple and rapid 96-well screening protocol using cell proliferation assays and RNA interference to identify genes associated with radiation susceptibility. We evaluated the performance of alamarBlue-, BrdU-, and sulforhodamine B-based cell proliferation assays using the 96-well format. Each proliferation assay detected the known radiation susceptibility gene, PRKDC. In a trial screen using 28 shRNA vectors, another known gene, CDKN1A, and one new radiation susceptibility gene, ATP5G3, were identified. Our results indicate that this method may be useful for large-scale screens designed to identify novel radiation susceptibility genes

  2. Hospital costs and benefits of screening for abdominal aortic aneurysms. Results from a randomised population screening trial

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Juul, Søren; Fasting, H

    2002-01-01

    to analyse the hospital costs and benefits of screening older males for abdominal aortic aneurysm (AAA). MATERIALS and......to analyse the hospital costs and benefits of screening older males for abdominal aortic aneurysm (AAA). MATERIALS and...

  3. A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION: Rationale and design

    Directory of Open Access Journals (Sweden)

    Clarke Simon D

    2011-03-01

    Full Text Available Abstract Background The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD. The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study. Methods Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment, Session 2 (six weeks, atomoxetine or placebo, and Session 3 (13 weeks, cross-over after one-week washout period. The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo. Results The methodology for the ACTION study has been detailed. Conclusions The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD

  4. Cost-effectiveness of intensive multifactorial treatment compared with routine care for individuals with screen-detected Type 2 diabetes : analysis of the ADDITION-UK cluster-randomized controlled trial

    NARCIS (Netherlands)

    Tao, L.; Wilson, E. C. F.; Wareham, N. J.; Sandbaek, A.; Rutten, G. E. H. M.; Lauritzen, T.; Khunti, K.; Davies, M. J.; Borch-Johnsen, K.; Griffin, S. J.; Simmons, R. K.

    Aims To examine the short- and long-term cost-effectiveness of intensive multifactorial treatment compared with routine care among people with screen-detected Type 2 diabetes. Methods Cost-utility analysis in ADDITION-UK, a cluster-randomized controlled trial of early intensive treatment in people

  5. Health on the web: randomised controlled trial of online screening and brief alcohol intervention delivered in a workplace setting.

    Directory of Open Access Journals (Sweden)

    Zarnie Khadjesari

    Full Text Available BACKGROUND: Alcohol misuse in England costs around £7.3 billion (US$12.2 billion annually from lost productivity and absenteeism. Delivering brief alcohol interventions to employees as part of a health check may be acceptable, particularly with online delivery which can provide privacy for this stigmatised behaviour. Research to support this approach is limited and methodologically weak. The aim was to determine the effectiveness of online screening and personalised feedback on alcohol consumption, delivered in a workplace as part of a health check. METHODS AND FINDINGS: This two-group online individually randomised controlled trial recruited employees from a UK-based private sector organisation (approx. 100,000 employees. 3,375 employees completed the online health check in the three week recruitment period. Of these, 1,330 (39% scored five or more on the AUDIT-C (indicating alcohol misuse and were randomised to receive personalised feedback on their alcohol intake, alongside feedback on other health behaviours (n = 659, or to receive feedback on all health behaviours except alcohol intake (n = 671. Participants were mostly male (75%, with a median age of 48 years and half were in managerial positions (55%. Median Body Mass Index was 26, 12% were smokers, median time undertaking moderate/vigorous physical activity a week was 173 minutes and median fruit and vegetable consumption was three portions a day. Eighty percent (n = 1,066 of participants completed follow-up questionnaires at three months. An intention to treat analysis found no difference between experimental groups for past week drinking (primary outcome (5.6% increase associated with the intervention (95% CI -4.7% to 16.9%; p = .30, AUDIT (measure of alcohol-related harm and health utility (EQ-5D. CONCLUSIONS: There was no evidence to support the use of personalised feedback within an online health check for reducing alcohol consumption among employees in this

  6. Health on the Web: Randomised Controlled Trial of Online Screening and Brief Alcohol Intervention Delivered in a Workplace Setting

    Science.gov (United States)

    Khadjesari, Zarnie; Freemantle, Nick; Linke, Stuart; Hunter, Rachael; Murray, Elizabeth

    2014-01-01

    Background Alcohol misuse in England costs around £7.3 billion (US$12.2 billion) annually from lost productivity and absenteeism. Delivering brief alcohol interventions to employees as part of a health check may be acceptable, particularly with online delivery which can provide privacy for this stigmatised behaviour. Research to support this approach is limited and methodologically weak. The aim was to determine the effectiveness of online screening and personalised feedback on alcohol consumption, delivered in a workplace as part of a health check. Methods and Findings This two-group online individually randomised controlled trial recruited employees from a UK-based private sector organisation (approx. 100,000 employees). 3,375 employees completed the online health check in the three week recruitment period. Of these, 1,330 (39%) scored five or more on the AUDIT-C (indicating alcohol misuse) and were randomised to receive personalised feedback on their alcohol intake, alongside feedback on other health behaviours (n = 659), or to receive feedback on all health behaviours except alcohol intake (n = 671). Participants were mostly male (75%), with a median age of 48 years and half were in managerial positions (55%). Median Body Mass Index was 26, 12% were smokers, median time undertaking moderate/vigorous physical activity a week was 173 minutes and median fruit and vegetable consumption was three portions a day. Eighty percent (n = 1,066) of participants completed follow-up questionnaires at three months. An intention to treat analysis found no difference between experimental groups for past week drinking (primary outcome) (5.6% increase associated with the intervention (95% CI −4.7% to 16.9%; p = .30)), AUDIT (measure of alcohol-related harm) and health utility (EQ-5D). Conclusions There was no evidence to support the use of personalised feedback within an online health check for reducing alcohol consumption among employees in this organisation

  7. Idea Screening in Engineering Design Using Employee-Driven Wisdom of the Crowds

    DEFF Research Database (Denmark)

    Onarheim, Balder; Christensen, Bo Thomas

    /ownership of ideas. The study shows that the crowd wisdom of employees significantly correlates with the preferences of the marketing team: overall, in top 12 selected ideas and in choice of idea categories. This match increases when including only the ratings of the most experienced employees. The experienced......The paper investigates the question of screening ideas in the ‘fuzzy front end’ of engineering design, examining the validity of employee voting schemes and related biases. After an employee-driven innovation project at {Company Name removed for review}, 99 ideas were to be screened for further...... development. Based on the concept of ‘wisdom of the crowds’, all ideas were individually rated by a broad selection of employees, and their choices of ideas and idea categories compared to those of a small team of senior marketers. The study also tested for two biases: visual complexity and endowment effect...

  8. Hip-Hop to Health Jr. Randomized Effectiveness Trial

    Science.gov (United States)

    Kong, Angela; Buscemi, Joanna; Stolley, Melinda R.; Schiffer, Linda A.; Kim, Yoonsang; Braunschweig, Carol L.; Gomez-Perez, Sandra L.; Blumstein, Lara B.; Van Horn, Linda; Dyer, Alan R.; Fitzgibbon, Marian L.

    2015-01-01

    Introduction The preschool years provide a unique window of opportunity to intervene on obesity-related lifestyle risk factors during the formative years of a child’s life. The purpose of this study was to assess the impact of a preschool-based obesity prevention effectiveness trial at 1-year follow-up. Design RCT. Settings/participants Primarily African American children (aged 3–5 years, N=618) attending Head Start preschool programs administered by Chicago Public Schools. Methods Eighteen preschools were randomly assigned in 2007–2008 to receive either: (1) a 14-week teacher-delivered intervention focused on healthy lifestyle behaviors; or (2) a 14-week teacher-delivered general health curriculum (control group). Main outcome measures The primary outcome, BMI, was measured at baseline, post-intervention, and 1-year follow-up. Diet and screen time behaviors were also assessed at these time points. Multilevel mixed effects models were used to test for between-group differences. Data were analyzed in 2014. Results Significant between-group differences were observed in diet, but not in BMI z-score or screen time at 1-year follow-up. Diet differences favored the intervention arm over controls in overall diet quality (p=0.02) and in subcomponents of diet quality, as measured by the Healthy Eating Index-2005, and in fruit intake (servings/day, excludes juice) (p=0.02). Diet quality worsened more among controls than the intervention group at 1-year follow-up. Conclusions The adaptation of Hip-Hop to Health Jr. produced modest benefits in diet quality, but did not significantly impact weight gain trajectory. Not unlike other effectiveness trials, this real-world version delivered by Head Start teachers produced fewer benefits than the more rigorous efficacy trial. It is important to understand and build upon the lessons learned from these types of trials so that we can design, implement, and disseminate successful evidence-based programs more widely and effectively

  9. Implications of clinical trial design on sample size requirements.

    Science.gov (United States)

    Leon, Andrew C

    2008-07-01

    The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly relevant aspects of such a design often receive insufficient attention in an RCT. Multiple outcomes inflate type I error, and an unreliable assessment process introduces bias and reduces statistical power. Here we describe how both unreliability and multiple outcomes can increase the study costs and duration and reduce the feasibility of the study. The objective of this article is to consider strategies that overcome the problems of unreliability and multiplicity.

  10. Effectiveness of a theory-based intervention to increase colorectal cancer screening among Iranian health club members: a randomized trial.

    Science.gov (United States)

    Salimzadeh, Hamideh; Eftekhar, Hassan; Majdzadeh, Reza; Montazeri, Ali; Delavari, Alireza

    2014-10-01

    Colorectal cancer is the third most commonly diagnosed cancer and the fourth leading cause of death in the world. There are few published studies that have used theory-based interventions designed to increase colorectal cancer screening in community lay health organizations. The present study was guided by the theoretical concepts of the preventive health model. Twelve health clubs of a municipal district in Tehran were randomized to two study groups with equal ratio. The control group received usual services throughout the study while the intervention group also received a theory-based educational program on colorectal cancer screening plus a reminder call. Screening behavior, the main outcome, was assessed 4 months after randomization. A total of 360 members aged 50 and older from 12 health clubs completed a baseline survey. Participants in the intervention group reported increased knowledge of colorectal cancer and screening tests at 4 months follow-up (p's theory-based intervention significantly improved self-efficacy, perceived susceptibility, efficacy of screening, social support, and intention to be screened for colorectal cancer, from baseline to 4 months follow-up (p's theory-based intervention was found to have a significant effect on colorectal cancer screening use as measured by self-report. The findings could have implications for colorectal cancer screening program development and implementation in primary health care settings and through other community organizations.

  11. The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results.

    Science.gov (United States)

    Mahon, Jeffrey L; Sosenko, Jay M; Rafkin-Mervis, Lisa; Krause-Steinrauf, Heidi; Lachin, John M; Thompson, Clinton; Bingley, Polly J; Bonifacio, Ezio; Palmer, Jerry P; Eisenbarth, George S; Wolfsdorf, Joseph; Skyler, Jay S

    2009-04-01

    TrialNet's goal to test preventions for type 1 diabetes has created an opportunity to gain new insights into the natural history of pre-type 1 diabetes. The TrialNet Natural History Study (NHS) will assess the predictive value of existing and novel risk markers for type 1 diabetes and will find subjects for prevention trials. The NHS is a three-phase, prospective cohort study. In phase 1 (screening), pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell antibodies) are measured. Phase 2 (baseline risk assessment) includes oral glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5-yr diabetes risks according to the OGTT and number of confirmed positive antibody tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6 months. In phases 2 and 3, samples are collected for future tests of T-lymphocyte function, autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome is diabetes onset. Of 12 636 relatives screened between March 2004 and December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of these, 322 were confirmed antibody positive and completed phase 2, of whom 296 subjects were given preliminary 5-yr diabetes risks of or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =50%). The NHS is identifying potential prevention trial subjects and is assembling a large cohort that will provide new natural history information about pre-type 1 diabetes. Follow-up to diabetes will help establish the biological significance and clinical value of novel type 1 diabetes risk markers.

  12. Responding to Young People's Health Risks in Primary Care: A Cluster Randomised Trial of Training Clinicians in Screening and Motivational Interviewing.

    Directory of Open Access Journals (Sweden)

    Lena Sanci

    Full Text Available To evaluate the effectiveness of a complex intervention implementing best practice guidelines recommending clinicians screen and counsel young people across multiple psychosocial risk factors, on clinicians' detection of health risks and patients' risk taking behaviour, compared to a didactic seminar on young people's health.Pragmatic cluster randomised trial where volunteer general practices were stratified by postcode advantage or disadvantage score and billing type (private, free national health, community health centre, then randomised into either intervention or comparison arms using a computer generated random sequence. Three months post-intervention, patients were recruited from all practices post-consultation for a Computer Assisted Telephone Interview and followed up three and 12 months later. Researchers recruiting, consenting and interviewing patients and patients themselves were masked to allocation status; clinicians were not.General practices in metropolitan and rural Victoria, Australia.General practices with at least one interested clinician (general practitioner or nurse and their 14-24 year old patients.This complex intervention was designed using evidence based practice in learning and change in clinician behaviour and general practice systems, and included best practice approaches to motivating change in adolescent risk taking behaviours. The intervention involved training clinicians (nine hours in health risk screening, use of a screening tool and motivational interviewing; training all practice staff (receptionists and clinicians in engaging youth; provision of feedback to clinicians of patients' risk data; and two practice visits to support new screening and referral resources. Comparison clinicians received one didactic educational seminar (three hours on engaging youth and health risk screening.Primary outcomes were patient report of (1 clinician detection of at least one of six health risk behaviours (tobacco, alcohol

  13. Responding to Young People's Health Risks in Primary Care: A Cluster Randomised Trial of Training Clinicians in Screening and Motivational Interviewing.

    Science.gov (United States)

    Sanci, Lena; Chondros, Patty; Sawyer, Susan; Pirkis, Jane; Ozer, Elizabeth; Hegarty, Kelsey; Yang, Fan; Grabsch, Brenda; Shiell, Alan; Cahill, Helen; Ambresin, Anne-Emmanuelle; Patterson, Elizabeth; Patton, George

    2015-01-01

    To evaluate the effectiveness of a complex intervention implementing best practice guidelines recommending clinicians screen and counsel young people across multiple psychosocial risk factors, on clinicians' detection of health risks and patients' risk taking behaviour, compared to a didactic seminar on young people's health. Pragmatic cluster randomised trial where volunteer general practices were stratified by postcode advantage or disadvantage score and billing type (private, free national health, community health centre), then randomised into either intervention or comparison arms using a computer generated random sequence. Three months post-intervention, patients were recruited from all practices post-consultation for a Computer Assisted Telephone Interview and followed up three and 12 months later. Researchers recruiting, consenting and interviewing patients and patients themselves were masked to allocation status; clinicians were not. General practices in metropolitan and rural Victoria, Australia. General practices with at least one interested clinician (general practitioner or nurse) and their 14-24 year old patients. This complex intervention was designed using evidence based practice in learning and change in clinician behaviour and general practice systems, and included best practice approaches to motivating change in adolescent risk taking behaviours. The intervention involved training clinicians (nine hours) in health risk screening, use of a screening tool and motivational interviewing; training all practice staff (receptionists and clinicians) in engaging youth; provision of feedback to clinicians of patients' risk data; and two practice visits to support new screening and referral resources. Comparison clinicians received one didactic educational seminar (three hours) on engaging youth and health risk screening. Primary outcomes were patient report of (1) clinician detection of at least one of six health risk behaviours (tobacco, alcohol and

  14. Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

    Science.gov (United States)

    Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

    2011-07-01

    Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

  15. Preliminary design of the beam screen cooling for the Future Circular Collider of hadron beams

    CERN Document Server

    Kotnig, C

    2015-01-01

    Following recommendations of the recent update of the European strategy in particle physics, CERN has undertaken an international study of possible future circular colliders beyond the LHC. This study considers an option for a very high energy (100 TeV) hadron-hadron collider located in a quasi-circular underground tunnel having a circumference of 80 to 100 km. The synchrotron radiation emitted by the high-energy hadron beam increases by more than two orders of magnitude compared to the LHC. To reduce the entropic load on the superconducting magnets' refrigeration system, beam screens are indispensable to extract the heat load at a higher temperature level. After illustrating the decisive constraints of the beam screen's refrigeration design, this paper presents a preliminary design of the length of a continuous cooling loop comparing helium and neon, for different cooling channel geometries with emphasis on the cooling length limitations and the exergetic efficiency.

  16. Preliminary design of the beam screen cooling for the Future Circular Collider of hadron beams

    Science.gov (United States)

    Kotnig, C.; Tavian, L.

    2015-12-01

    Following recommendations of the recent update of the European strategy in particle physics, CERN has undertaken an international study of possible future circular colliders beyond the LHC. This study considers an option for a very high energy (100 TeV) hadron-hadron collider located in a quasi-circular underground tunnel having a circumference of 80 to 100 km. The synchrotron radiation emitted by the high-energy hadron beam increases by more than two orders of magnitude compared to the LHC. To reduce the entropic load on the superconducting magnets’ refrigeration system, beam screens are indispensable to extract the heat load at a higher temperature level. After illustrating the decisive constraints of the beam screen's refrigeration design, this paper presents a preliminary design of the length of a continuous cooling loop comparing helium and neon, for different cooling channel geometries with emphasis on the cooling length limitations and the exergetic efficiency.

  17. Prevalence of Neuropathy and Peripheral Arterial Disease and the Impact of Treatment in People With Screen-Detected Type 2 Diabetes: The ADDITION-Denmark study

    DEFF Research Database (Denmark)

    Charles, Morten; Ejskjær, Niels; Witte, Daniel R

    2011-01-01

    in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial. RESEARCH DESIGN AND METHODS-A stepwise screening program in 1.90 general practices in Denmark was used to identify 1...

  18. Control system design of the CERN/CMS tracker thermal screen

    CERN Document Server

    Carrone, E

    2003-01-01

    The Tracker is one of the CMS (Compact Muon Solenoid experiment) subdetectors to be installed at the LHC (Large Hadron Collider) accelerator, scheduled to start data taking in 2007 at CERN (European Organization for Nuclear Research). The tracker will be operated at a temperature of -10 degree C in order to reduce the radiation damage on the silicon detectors; hence, an insulated environment has to be provided by means of a screen that introduces a thermal separation between the Tracker and the neighboring detection systems. The control system design includes a formal description of the process by means of a thermodynamic model; then, the electrical equivalence is derived. The transfer function is inferred by the ratio of the voltage on the outer skin and the voltage input, i.e. the ratio of the temperature outside the tracker and the heat generated (which is the controlled variable). A PID (Proportional Integral Derivative) controller has been designed using MatLab. The results achieved so far prove that thi...

  19. Personalized medicine enrichment design for DHA supplementation clinical trial

    Directory of Open Access Journals (Sweden)

    Yang Lei

    2017-03-01

    Full Text Available Personalized medicine aims to match patient subpopulation to the most beneficial treatment. The purpose of this study is to design a prospective clinical trial in which we hope to achieve the highest level of confirmation in identifying and making treatment recommendations for subgroups, when the risk levels in the control arm can be ordered. This study was motivated by our goal to identify subgroups in a DHA (docosahexaenoic acid supplementation trial to reduce preterm birth (gestational age<37 weeks rate. We performed a meta-analysis to obtain informative prior distributions and simulated operating characteristics to ensure that overall Type I error rate was close to 0.05 in designs with three different models: independent, hierarchical, and dynamic linear models. We performed simulations and sensitivity analysis to examine the subgroup power of models and compared results to a chi-square test. We performed simulations under two hypotheses: a large overall treatment effect and a small overall treatment effect. Within each hypothesis, we designed three different subgroup effects scenarios where resulting subgroup rates are linear, flat, or nonlinear. When the resulting subgroup rates are linear or flat, dynamic linear model appeared to be the most powerful method to identify the subgroups with a treatment effect. It also outperformed other methods when resulting subgroup rates are nonlinear and the overall treatment effect is big. When the resulting subgroup rates are nonlinear and the overall treatment effect is small, hierarchical model and chi-square test did better. Compared to independent and hierarchical models, dynamic linear model tends to be relatively robust and powerful when the control arm has ordinal risk subgroups.

  20. Personalized Medicine Enrichment Design for DHA Supplementation Clinical Trial.

    Science.gov (United States)

    Lei, Yang; Mayo, Matthew S; Carlson, Susan E; Gajewski, Byron J

    2017-03-01

    Personalized medicine aims to match patient subpopulation to the most beneficial treatment. The purpose of this study is to design a prospective clinical trial in which we hope to achieve the highest level of confirmation in identifying and making treatment recommendations for subgroups, when the risk levels in the control arm can be ordered. This study was motivated by our goal to identify subgroups in a DHA (docosahexaenoic acid) supplementation trial to reduce preterm birth (gestational agerate. We performed a meta-analysis to obtain informative prior distributions and simulated operating characteristics to ensure that overall Type I error rate was close to 0.05 in designs with three different models: independent, hierarchical, and dynamic linear models. We performed simulations and sensitivity analysis to examine the subgroup power of models and compared results to a chi-square test. We performed simulations under two hypotheses: a large overall treatment effect and a small overall treatment effect. Within each hypothesis, we designed three different subgroup effects scenarios where resulting subgroup rates are linear, flat, or nonlinear. When the resulting subgroup rates are linear or flat, dynamic linear model appeared to be the most powerful method to identify the subgroups with a treatment effect. It also outperformed other methods when resulting subgroup rates are nonlinear and the overall treatment effect is big. When the resulting subgroup rates are nonlinear and the overall treatment effect is small, hierarchical model and chi-square test did better. Compared to independent and hierarchical models, dynamic linear model tends to be relatively robust and powerful when the control arm has ordinal risk subgroups.

  1. The Japanese Guidelines for Breast Cancer Screening.

    Science.gov (United States)

    Hamashima, Chisato; Hamashima C, Chisato; Hattori, Masakazu; Honjo, Satoshi; Kasahara, Yoshio; Katayama, Takafumi; Nakai, Masahiro; Nakayama, Tomio; Morita, Takako; Ohta, Koji; Ohnuki, Koji; Sagawa, Motoyasu; Saito, Hiroshi; Sasaki, Seiju; Shimada, Tomoyuki; Sobue, Tomotaka; Suto, Akihiko

    2016-05-01

    The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Design, synthesis, and validation of an in vitro platform peptide-whole cell screening assay using MTT reagent

    Directory of Open Access Journals (Sweden)

    Sahar Ahmed

    2017-05-01

    Full Text Available An in vitro platform to perform peptide screening against different cancer cell lines was designed. The strategy for this screening relied on the design and detection of high-affinity cancer-targeting peptides based on the sequences of NGR and P160. Evaluation of the best binding peptides was performed via incubation of the peptide array-bounded cells with MTT reagent, which is reduced to purple formazan in living cells and further quantified using an Elispot and Kodak imager. For proof of concept, a peptide library (132 spots, and 66 different peptides was designed, synthesized, and screened against different cancer cell lines. The current strategy assists in the identification of positive and negative peptides as well as the relative binding between positive ones. Better binding peptide sequences of the NGR motif were demonstrated to show up to a 2.6-fold increase in CD13+ cell lines with insignificant binding to CD13− ones. Comparable results were observed for P160 peptide sequences, to which different peptides had increased binding, with an up to 3-fold increase relative to the native P160 peptide. Based on our results, new peptide sequences for cancer targeting were identified, and the developed strategy was applied to two different peptide libraries.

  3. Design paper: The CapOpus trial: a randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis

    DEFF Research Database (Denmark)

    Hjorthøj, Carsten; Fohlmann, Allan; Larsen, Anne-Mette

    2008-01-01

    : The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. DESIGN: The trial is designed as a randomized, parallel-group, observer-blinded clinical...

  4. Evaluation of the trial design studies for an advanced marine reactor, (1)

    International Nuclear Information System (INIS)

    1988-03-01

    The trial design of three type reactors, semi-integrated, integrated and integrated (self-pressurized) type, was carried out in order to clarify the reactor type for the advanced marine reactor that would be developed for its realization in future and in order to extract its research and development theme. The trial design was carried and finished as for the three type reactors in same specifications in order to improve the following characteristics, small in size, light in weight, high in safety and reliability, and economic. In this report, a comparison and review of the following items are described as for the above three type reactors, (1) specifications, (2) shielding, (3) refueling, (4) in-service inspection, (5) analysis of the transients and accidents, (6) piping systems, (7) control systems, (8) dynamic analysis, (9) overall comparison, (10) research and development theme and theme for study in future. (author)

  5. Motivational interviewing and colorectal cancer screening: a peek from the inside out.

    Science.gov (United States)

    Wahab, Stéphanie; Menon, Usha; Szalacha, Laura

    2008-08-01

    This article focuses on design, training, and delivery of motivational interview (MI) in a longitudinal randomized controlled trial intended to assess the efficacy of two separate interventions designed to increase colorectal screening when compared to a usual care, control group. One intervention was a single-session, telephone-based MI, created to increase colorectal cancer screening within primary care populations. The other was tailored health counseling. We present the rationale, design, and process discussions of the one-time motivational interviewing telephone intervention. We discuss in this paper the training and supervision of study interventionists, in order to enhance practice and research knowledge concerned with fidelity issues in motivational interview interventions. To improve motivational interviewing proficiency and effectiveness, we developed a prescribed training program adapting MI to a telephone counseling session. The three interventionists trained in MI demonstrate some MI proficiency assessed by the motivational interviewing treatment integrity scale. In the post-intervention interview, 20.5% of the MI participants reported having had a CRC screening test, and another 19.75% (n=16) had scheduled a screening test. Almost half of the participants (43%) indicated that the phone conversation helped them to overcome the reasons why they had not had a screening test. Ongoing supervision and training (post-MI workshop) are crucial to supporting MI fidelity. The trajectory of learning MI demonstrated by the interventionists is consistent with the eight stages of learning MI. The MI road map created for the interventionists has shown to be more of a distraction than a facilitator in the delivery of the telephone intervention. MI can, however, be considered a useful tool for health education and warrants further study. MI training should include consistent training and process evaluation. MI can, however, be considered a useful tool for health

  6. Conducting a randomized trial in rural and urban safety-net health centers: Added value of community-based participatory research

    Directory of Open Access Journals (Sweden)

    Meera Muthukrishnan

    2018-06-01

    Full Text Available Background: Colorectal cancer (CRC is the second most common cancer in the US. Despite evidence that screening reduces CRC incidence and mortality, screening rates are sub-optimal with disparities by race/ethnicity, income, and geography. Rural-urban differences in CRC screening are understudied even though approximately one-fifth of the US population lives in rural areas. This focus on urban populations limits the generalizability and dissemination potential of screening interventions. Methods: Using community-based participatory research (CBPR principles, we designed a cluster-randomized trial, adaptable to a range of settings, including rural and urban health centers. We enrolled 483 participants across 11 health centers representing 2 separate networks. Both networks serve medically-underserved communities; however one is primarily rural and one primarily urban. Results: Our goal in this analysis is to describe baseline characteristics of participants and examine setting-level differences. CBPR was a critical for recruiting networks to the trial. Patient respondents were predominately female (61.3%, African-American (66.5%, and earned <$1200 per month (87.1%. The rural network sample was older; more likely to be female, white, disabled or retired, and have a higher income, but fewer years of education. Conclusions: Variation in the samples partly reflects the CBPR process and partly reflects inherent differences in the communities. This confirmed the importance of using CBPR when planning for eventual dissemination, as it enhanced our ability to work within diverse settings. These baseline findings indicate that using a uniform approach to implementing a trial or intervention across diverse settings might not be effective or efficient. Keywords: Colorectal cancer screening, Community-based participatory research, Health disparities, Medically underserved populations, Dissemination and implementation, Randomized trial

  7. Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Jacobsen, Rikke Kart; Toft, Ulla

    2014-01-01

    of Copenhagen, Denmark PARTICIPANTS: 59 616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n=11 629) and a control group (n=47 987). INTERVENTION: The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four...... of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. MAIN......OBJECTIVE: To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. DESIGN: Randomised controlled community based trial. SETTING: Suburbs...

  8. Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

    Directory of Open Access Journals (Sweden)

    Kazemier Brenda M

    2012-06-01

    Full Text Available Abstract Background The prevalence of asymptomatic bacteriuria (ASB in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. Methods/Design We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind. Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. Discussion This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment. Trial registration Dutch trial registry: NTR-3068

  9. Modern dose-finding designs for cancer phase I trials drug combinations and molecularly targeted agents

    CERN Document Server

    Hirakawa, Akihiro; Daimon, Takashi; Matsui, Shigeyuki

    2018-01-01

    This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of tw...

  10. Discovery of potent inhibitors of soluble epoxide hydrolase by combinatorial library design and structure-based virtual screening.

    Science.gov (United States)

    Xing, Li; McDonald, Joseph J; Kolodziej, Steve A; Kurumbail, Ravi G; Williams, Jennifer M; Warren, Chad J; O'Neal, Janet M; Skepner, Jill E; Roberds, Steven L

    2011-03-10

    Structure-based virtual screening was applied to design combinatorial libraries to discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition to the conserved hydrogen bonds with the catalytic machinery of sEH. By exploitation of the favorable binding elements, two iterations of library design based on amide coupling were employed, guided principally by the docking results of the enumerated virtual products. Biological screening of the libraries demonstrated as high as 90% hit rate, of which over two dozen compounds were single digit nanomolar sEH inhibitors by IC(50) determination. In total the library design and synthesis produced more than 300 submicromolar sEH inhibitors. In cellular systems consistent activities were demonstrated with biochemical measurements. The SAR understanding of the benzoxazole template provides valuable insights into discovery of novel sEH inhibitors as therapeutic agents.

  11. Human papillomavirus-based cervical cancer prevention: long-term results of a randomized screening trial.

    Science.gov (United States)

    Denny, Lynette; Kuhn, Louise; Hu, Chih-Chi; Tsai, Wei-Yann; Wright, Thomas C

    2010-10-20

    Screen-and-treat approaches to cervical cancer prevention are an attractive option for low-resource settings, but data on their long-term efficacy are lacking. We evaluated the efficacy of two screen-and-treat approaches through 36 months of follow-up in a randomized trial. A total of 6637 unscreened South African women aged 35-65 years who were tested for the presence of high-risk human papillomavirus (HPV) DNA in cervical samples underwent visual inspection of the cervix using acetic acid staining and HIV serotesting. Of these, 6555 were randomly assigned to three study arms: 1) HPV-and-treat, in which all women with a positive HPV DNA test result underwent cryotherapy; 2) visual inspection-and-treat, in which all women with a positive visual inspection test result underwent cryotherapy; or 3) control, in which further evaluation or treatment was delayed for 6 months. All women underwent colposcopy with biopsy at 6 months. All women who were HPV DNA- or visual inspection-positive at enrollment, and a subset of all other women had extended follow-up to 36 months (n = 3639) with yearly colposcopy. The endpoint-cervical intraepithelial neoplasia grade 2 or worse (CIN2+)-was analyzed using actuarial life-table methods. All statistical tests were two-sided. After 36 months, there was a sustained statistically significant decrease in the cumulative detection of CIN2+ in the HPV-and-treat arm compared with the control arm (1.5% vs 5.6%, difference = 4.1%, 95% confidence interval [CI] = 2.8% to 5.3%, P cryotherapy.

  12. Design and preliminary analysis of a vaginal inserter for speculum-free cervical cancer screening.

    Directory of Open Access Journals (Sweden)

    Mercy Nyamewaa Asiedu

    Full Text Available Cervical cancer screening usually requires use of a speculum to provide a clear view of the cervix. The speculum is one potential barrier to screening due to fear of pain, discomfort and embarrassment. The aim of this paper is to present and demonstrate the feasibility of a tampon-sized inserter and the POCkeT Colposcope, a miniature pen sized-colposcope, for comfortable, speculum-free and potentially self-colposcopy.We explored different designs using 3D computer-aided design (CAD software and performed mechanical testing simulations on each. Designs were rapid prototyped and tested using a custom vaginal phantom across a range of vaginal pressures and uterine tilts to select an optimal design. Two final designs were tested with fifteen volunteers to assess cervix visualization, comfort and usability compared to the speculum and the optimal design, the curved-tip inserter, was selected for testing in volunteers.We present a vaginal inserter as an alternative to the standard speculum for use with the POCkeT Colposcope. The device has a slim tubular body with a funnel-like curved tip measuring approximately 2.5 cm in diameter. The inserter has a channel through which a 2 megapixel (MP mini camera with LED illumination fits to enable image capture. Mechanical finite element testing simulations with an applied pressure of 15 cm H2O indicated a high factor of safety (90.9 for the inserter. Testing of the device with a custom vaginal phantom, across a range of supine vaginal pressures and uterine tilts (retroverted, anteverted and sideverted, demonstrated image capture with a visual area comparable to the speculum for a normal/axial positioned uteri and significantly better than the speculum for anteverted and sideverted uteri (p<0.00001. Volunteer studies with self-insertion and physician-assisted cervix image capture showed adequate cervix visualization for 83% of patients. In addition, questionnaire responses from volunteers indicated a 92

  13. Innovative design for a phase 1 trial with intra-patient dose escalation: The Crotoxin study

    Directory of Open Access Journals (Sweden)

    Jacques Medioni

    2017-09-01

    Full Text Available Introduction: Crotoxin has a broad antitumor activity but has shown frequent neurotoxic toxicity. To induce tolerance and limit this toxicity, we propose a new design with intra-patient dose escalation. Methods: A new Dose Limiting Toxicity definition was used. The concept of Target Ceiling Dose was introduced. Results: Dose Limiting Toxicity was the inability to dose escalate twice. Target Ceiling Dose was the highest planned dose to be administered to a patient and could change for patients along time. Recommended Dose was defined similarly as in a (3 + 3 conventional design. Conclusion: This innovant design was used and the clinical trial is now closed for inclusions. Results will be presented later. Keywords: Clinical trial, Phase 1, Intra-patient dose escalation, Cancer

  14. Psychotherapy with traumatised refugees – the design of a randomised clinical trial

    DEFF Research Database (Denmark)

    Vindbjerg, Erik; Carlsson, Jessica Mariana; Klimpke, Christoph Axel

    2014-01-01

    There is little evidence as to which kind of psychotherapy is the most effective in the treatment of traumatised refugees. At the Competence Center for  Transcultural Psychiatry, a series of clinical trials have been conducted since 2008. The first results are pending publication. The aim...... of this paper is to discuss some of the challenges in adapting Cognitive Behavioural Therapy (CBT) to the treatment of traumatised refugees, as well as describe a randomised clinical trial designed to test two such adaptations. In the described trial one group receives CBT with a focus on cognitive...... restructuring while the other group receives CBT focusing on Stress Management. A main goal of this setup is to test whether some, perhaps even most, of the traumatised refugees referred to treatment, may benefit from a more direct focus on current stress, and its alleviation through simple, repetitive...

  15. A clinical trial design using the concept of proportional time using the generalized gamma ratio distribution.

    Science.gov (United States)

    Phadnis, Milind A; Wetmore, James B; Mayo, Matthew S

    2017-11-20

    Traditional methods of sample size and power calculations in clinical trials with a time-to-event end point are based on the logrank test (and its variations), Cox proportional hazards (PH) assumption, or comparison of means of 2 exponential distributions. Of these, sample size calculation based on PH assumption is likely the most common and allows adjusting for the effect of one or more covariates. However, when designing a trial, there are situations when the assumption of PH may not be appropriate. Additionally, when it is known that there is a rapid decline in the survival curve for a control group, such as from previously conducted observational studies, a design based on the PH assumption may confer only a minor statistical improvement for the treatment group that is neither clinically nor practically meaningful. For such scenarios, a clinical trial design that focuses on improvement in patient longevity is proposed, based on the concept of proportional time using the generalized gamma ratio distribution. Simulations are conducted to evaluate the performance of the proportional time method and to identify the situations in which such a design will be beneficial as compared to the standard design using a PH assumption, piecewise exponential hazards assumption, and specific cases of a cure rate model. A practical example in which hemorrhagic stroke patients are randomized to 1 of 2 arms in a putative clinical trial demonstrates the usefulness of this approach by drastically reducing the number of patients needed for study enrollment. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial.

    Science.gov (United States)

    Rahbar, Mohammad H; Dickerson, Aisha S; Cai, Chunyan; Pedroza, Claudia; Hessabi, Manouchehr; Shen, Loren; Pandurengan, Renganayaki; Jacobs, Amber Nicole M; Indupuru, Hari; Sline, Melvin R; Delgado, Rigoberto I; Macdonald, Claire; Ford, Gary A; Grotta, James C; Barreto, Andrew D

    2015-09-01

    We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality. Copyright © 2015. Published by Elsevier Inc.

  17. Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

    Science.gov (United States)

    Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

    2016-08-01

    Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

  18. CMOST: an open-source framework for the microsimulation of colorectal cancer screening strategies.

    Science.gov (United States)

    Prakash, Meher K; Lang, Brian; Heinrich, Henriette; Valli, Piero V; Bauerfeind, Peter; Sonnenberg, Amnon; Beerenwinkel, Niko; Misselwitz, Benjamin

    2017-06-05

    Colorectal cancer (CRC) is a leading cause of cancer-related mortality. CRC incidence and mortality can be reduced by several screening strategies, including colonoscopy, but randomized CRC prevention trials face significant obstacles such as the need for large study populations with long follow-up. Therefore, CRC screening strategies will likely be designed and optimized based on computer simulations. Several computational microsimulation tools have been reported for estimating efficiency and cost-effectiveness of CRC prevention. However, none of these tools is publicly available. There is a need for an open source framework to answer practical questions including testing of new screening interventions and adapting findings to local conditions. We developed and implemented a new microsimulation model, Colon Modeling Open Source Tool (CMOST), for modeling the natural history of CRC, simulating the effects of CRC screening interventions, and calculating the resulting costs. CMOST facilitates automated parameter calibration against epidemiological adenoma prevalence and CRC incidence data. Predictions of CMOST were highly similar compared to a large endoscopic CRC prevention study as well as predictions of existing microsimulation models. We applied CMOST to calculate the optimal timing of a screening colonoscopy. CRC incidence and mortality are reduced most efficiently by a colonoscopy between the ages of 56 and 59; while discounted life years gained (LYG) is maximal at 49-50 years. With a dwell time of 13 years, the most cost-effective screening is at 59 years, at $17,211 discounted USD per LYG. While cost-efficiency varied according to dwell time it did not influence the optimal time point of screening interventions within the tested range. Predictions of CMOST are highly similar compared to a randomized CRC prevention trial as well as those of other microsimulation tools. This open source tool will enable health-economics analyses in for various countries

  19. ACR Appropriateness Criteria® Ovarian Cancer Screening.

    Science.gov (United States)

    Pandharipande, Pari V; Lowry, Kathryn P; Reinhold, Caroline; Atri, Mostafa; Benson, Carol B; Bhosale, Priyadarshani R; Green, Edward D; Kang, Stella K; Lakhman, Yulia; Maturen, Katherine E; Nicola, Refky; Salazar, Gloria M; Shipp, Thomas D; Simpson, Lynn; Sussman, Betsy L; Uyeda, Jennifer; Wall, Darci J; Whitcomb, Bradford; Zelop, Carolyn M; Glanc, Phyllis

    2017-11-01

    There has been much interest in the identification of a successful ovarian cancer screening test, in particular, one that can detect ovarian cancer at an early stage and improve survival. We reviewed the currently available data from randomized and observational trials that examine the role of imaging for ovarian cancer screening in average-risk and high-risk women. We found insufficient evidence to recommend ovarian cancer screening, when considering the imaging modality (pelvic ultrasound) and population (average-risk postmenopausal women) for which there is the greatest available published evidence; randomized controlled trials have not demonstrated a mortality benefit in this setting. Screening high-risk women using pelvic ultrasound may be appropriate in some clinical situations; however, related data are limited because large, randomized trials have not been performed in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  20. Evaluation of a new website design for iwantthekit for chlamydia, gonorrhea, and trichomonas screening.

    Science.gov (United States)

    Kuder, Margaret; Goheen, Mary Jett; Dize, Laura; Barnes, Mathilda; Gaydos, Charlotte A

    2015-05-01

    The www.iwantthekit.org provides Internet-based, at-home sexually transmitted infection screening. The Web site implemented an automated test result access system. To evaluate potential deleterious effects of the new system, we analyzed demographics, Web site usage, and treatment. The post-Web site design captured more participant information and no decrease in requests, kit return, or treatment adherence.