Maximizing scientific knowledge from randomized clinical trials

DEFF Research Database (Denmark)

Gustafsson, Finn; Atar, Dan; Pitt, Bertram

2010-01-01

Trialists have an ethical and financial responsibility to plan and conduct clinical trials in a manner that will maximize the scientific knowledge gained from the trial. However, the amount of scientific information generated by randomized clinical trials in cardiovascular medicine is highly vari...

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

Science.gov (United States)

Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

2012-07-01

Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

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

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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.

Evaluation of internal peer-review to train nurses recruiting to a randomized controlled trial--Internal Peer-review for Recruitment Training in Trials (InterPReTiT).

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Mann, Cindy; Delgado, Debbie; Horwood, Jeremy

2014-04-01

A discussion and qualitative evaluation of the use of peer-review to train nurses and optimize recruitment practice in a randomized controlled trial. Sound recruitment processes are critical to the success of randomized controlled trials. Nurses recruiting to trials must obtain consent for an intervention that is administered for reasons other than anticipated benefit to the patient. This requires not only patients' acquiescence but also evidence that they have weighed the relevant information in reaching their decision. How trial information is explained is vital, but communication and training can be inadequate. A discussion of a new process to train nurses recruiting to a randomized controlled trial. Literature from 1999-2013 about consenting to trials is included. Over 3 months from 2009-2010, recruiting nurses reviewed recruitment interviews recorded during the pilot phase of a single-site randomized controlled trial and noted content, communication style and interactions. They discussed their findings during peer-review meetings, which were audio-recorded and analysed using qualitative methodology. Peer-review can enhance nurses' training in trial recruitment procedures by supporting development of the necessary communication skills, facilitating consistency in information provision and sharing best practice. Nurse-led peer-review can provide a forum to share communication strategies that will elicit and address participant concerns and obtain evidence of participant understanding prior to consent. Comparing practice can improve consistency and accuracy of trial information and facilitate identification of recruitment issues. Internal peer-review was well accepted and promoted team cohesion. Further evaluation is needed. © 2013 John Wiley & Sons Ltd.

A Participatory Health Promotion Mobile App Addressing Alcohol Use Problems (The Daybreak Program): Protocol for a Randomized Controlled Trial.

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Tait, Robert J; Kirkman, Jessica J L; Schaub, Michael P

2018-05-31

), days out of role (Kessler), alcohol consumed (measured with a 7-day drinking diary in standard 10 g drinks), and alcohol-related harms (CORE alcohol and drug survey). We will collect data at baseline and 1, 3, and 6 months and analyze them with random effects models, given the correlated data structure. A randomized trial is required to provide robust evidence of the impact of the online coaching component of the Daybreak program, including over an extended period. Australian New Zealand Clinical Trials Registry ACTRN12618000010291; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373110 (Archived by WebCite at http://www.webcitation.org/6zKRmp0aC). RR1-10.2196/9982. ©Robert J Tait, Jessica J L Kirkman, Michael P Schaub. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 31.05.2018.

RTOG: Updated results of randomized trials

International Nuclear Information System (INIS)

Curran, Walter J.

1997-01-01

Objective: To review the background, rationale and available results for recently completed randomized comparative clinical trials of the Radiation Therapy Oncology Group (RTOG), including inter group trials in which the RTOG has been the managing group or a major participant. When available, laboratory studies will be correlated with clinical results

The Design of Cluster Randomized Trials with Random Cross-Classifications

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Moerbeek, Mirjam; Safarkhani, Maryam

2018-01-01

Data from cluster randomized trials do not always have a pure hierarchical structure. For instance, students are nested within schools that may be crossed by neighborhoods, and soldiers are nested within army units that may be crossed by mental health-care professionals. It is important that the random cross-classification is taken into account…

Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Metaregression Analysis of Randomized Clinical Trials.

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Katsanos, Aristeidis H; Filippatou, Angeliki; Manios, Efstathios; Deftereos, Spyridon; Parissis, John; Frogoudaki, Alexandra; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Pikilidou, Maria; Kargiotis, Odysseas; Voumvourakis, Konstantinos; Alexandrov, Anne W; Alexandrov, Andrei V; Tsivgoulis, Georgios

2017-01-01

Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; Psecondary stroke prevention. © 2016 American Heart Association, Inc.

Guided imagery targeting exercise, food cravings, and stress: a multi-modal randomized feasibility trial.

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Giacobbi, Peter; Long, Dustin; Nolan, Richard; Shawley, Samantha; Johnson, Kelsey; Misra, Ranjita

2018-02-01

The purpose of this randomized wait-list controlled trial was to test the feasibility and preliminary efficacy of a guided imagery based multi-behavior intervention intended to address psychological stress, food cravings, and physical activity. Personalized guided imagery scripts were created and participants were instructed to practice guided imagery every day for 35 consecutive days. Of 48 women who enrolled, we report comparisons between 16 randomized to treatment with 19 who were wait-listed (overall M age  = 45.50; M bodymassindex  = 31.43). Study completers reported 89% compliance with practicing guided imagery during the intervention. A significant time-by-group interaction was observed with reductions in food cravings and increases in physical activity compared with wait-list controls. Telephone-based multi-behavior interventions that utilize guided imagery to address food cravings and exercise behavior appear to be acceptable for overweight and obese women. Future phone-based guided imagery research testing this skill to address multiple health behaviors is justified.

Universal Prevention for Anxiety and Depressive Symptoms in Children: A Meta-analysis of Randomized and Cluster-Randomized Trials.

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Ahlen, Johan; Lenhard, Fabian; Ghaderi, Ata

2015-12-01

Although under-diagnosed, anxiety and depression are among the most prevalent psychiatric disorders in children and adolescents, leading to severe impairment, increased risk of future psychiatric problems, and a high economic burden to society. Universal prevention may be a potent way to address these widespread problems. There are several benefits to universal relative to targeted interventions because there is limited knowledge as to how to screen for anxiety and depression in the general population. Earlier meta-analyses of the prevention of depression and anxiety symptoms among children suffer from methodological inadequacies such as combining universal, selective, and indicated interventions in the same analyses, and comparing cluster-randomized trials with randomized trials without any correction for clustering effects. The present meta-analysis attempted to determine the effectiveness of universal interventions to prevent anxiety and depressive symptoms after correcting for clustering effects. A systematic search of randomized studies in PsychINFO, Cochrane Library, and Google Scholar resulted in 30 eligible studies meeting inclusion criteria, namely peer-reviewed, randomized or cluster-randomized trials of universal interventions for anxiety and depressive symptoms in school-aged children. Sixty-three percent of the studies reported outcome data regarding anxiety and 87 % reported outcome data regarding depression. Seventy percent of the studies used randomization at the cluster level. There were small but significant effects regarding anxiety (.13) and depressive (.11) symptoms as measured at immediate posttest. At follow-up, which ranged from 3 to 48 months, effects were significantly larger than zero regarding depressive (.07) but not anxiety (.11) symptoms. There was no significant moderation effect of the following pre-selected variables: the primary aim of the intervention (anxiety or depression), deliverer of the intervention, gender distribution

Subjective and objective outcomes in randomized clinical trials

DEFF Research Database (Denmark)

Moustgaard, Helene; Bello, Segun; Miller, Franklin G

2014-01-01

explicitly defined the terms. CONCLUSION: The terms "subjective" and "objective" are ambiguous when used to describe outcomes in randomized clinical trials. We suggest that the terms should be defined explicitly when used in connection with the assessment of risk of bias in a clinical trial......OBJECTIVES: The degree of bias in randomized clinical trials varies depending on whether the outcome is subjective or objective. Assessment of the risk of bias in a clinical trial will therefore often involve categorization of the type of outcome. Our primary aim was to examine how the concepts...... "subjective outcome" and "objective outcome" are defined in methodological publications and clinical trial reports. To put this examination into perspective, we also provide an overview of how outcomes are classified more broadly. STUDY DESIGN AND SETTING: A systematic review of methodological publications...

Design of a cluster-randomized trial of electronic health record-based tools to address overweight and obesity in primary care.

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Baer, Heather J; Wee, Christina C; DeVito, Katerina; Orav, E John; Frolkis, Joseph P; Williams, Deborah H; Wright, Adam; Bates, David W

2015-08-01

Primary care providers often fail to identify patients who are overweight or obese or discuss weight management with them. Electronic health record-based tools may help providers with the assessment and management of overweight and obesity. We describe the design of a trial to examine the effectiveness of electronic health record-based tools for the assessment and management of overweight and obesity among adult primary care patients, as well as the challenges we encountered. We developed several new features within the electronic health record used by primary care practices affiliated with Brigham and Women's Hospital in Boston, MA. These features included (1) reminders to measure height and weight, (2) an alert asking providers to add overweight or obesity to the problem list, (3) reminders with tailored management recommendations, and (4) a Weight Management screen. We then conducted a pragmatic, cluster-randomized controlled trial in 12 primary care practices. We randomized 23 clinical teams ("clinics") within the practices to the intervention group (n = 11) or the control group (n = 12). The new features were activated only for clinics in the intervention group. The intervention was implemented in two phases: the height and weight reminders went live on 15 December 2011 (Phase 1), and all of the other features went live on 11 June 2012 (Phase 2). Study enrollment went from December 2011 through December 2012, and follow-up ended in December 2013. The primary outcomes were 6-month and 12-month weight change among adult patients with body mass index ≥25 who had a visit at one of the primary care clinics during Phase 2. Secondary outcome measures included the proportion of patients with a recorded body mass index in the electronic health record, the proportion of patients with body mass index ≥25 who had a diagnosis of overweight or obesity on the electronic health record problem list, and the proportion of patients with body mass index ≥25 who had

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)

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Briel, Matthias; Lane, Melanie; Montori, Victor M; Bassler, Dirk; Glasziou, Paul; Malaga, German; Akl, Elie A; Ferreira-Gonzalez, Ignacio; Alonso-Coello, Pablo; Urrutia, Gerard; Kunz, Regina; Culebro, Carolina Ruiz; da Silva, Suzana Alves; Flynn, David N; Elamin, Mohamed B; Strahm, Brigitte; Murad, M Hassan; Djulbegovic, Benjamin; Adhikari, Neill KJ; Mills, Edward J; Gwadry-Sridhar, Femida; Kirpalani, Haresh; Soares, Heloisa P; Elnour, Nisrin O Abu; You, John J; Karanicolas, Paul J; Bucher, Heiner C; Lampropulos, Julianna F; Nordmann, Alain J; Burns, Karen EA; Mulla, Sohail M; Raatz, Heike; Sood, Amit; Kaur, Jagdeep; Bankhead, Clare R; Mullan, Rebecca J; Nerenberg, Kara A; Vandvik, Per Olav; Coto-Yglesias, Fernando; Schünemann, Holger; Tuche, Fabio; Chrispim, Pedro Paulo M; Cook, Deborah J; Lutz, Kristina; Ribic, Christine M; Vale, Noah; Erwin, Patricia J; Perera, Rafael; Zhou, Qi; Heels-Ansdell, Diane; Ramsay, Tim; Walter, Stephen D; Guyatt, Gordon H

2009-01-01

Background Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation. Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2

Directory of Open Access Journals (Sweden)

Mullan Rebecca J

2009-07-01

Full Text Available Abstract Background Randomized clinical trials (RCTs stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1, which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation. Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic t

Validity of randomized clinical trials in gastroenterology from 1964-2000

DEFF Research Database (Denmark)

Kjaergard, Lise L; Frederiksen, Sarah L; Gluud, Christian

2002-01-01

The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000.......The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000....

Parent Training with High-Risk Immigrant Chinese Families: A Pilot Group Randomized Trial Yielding Practice-Based Evidence

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Lau, Anna S.; Fung, Joey J.; Ho, Lorinda Y.; Liu, Lisa L.; Gudino, Omar G.

2011-01-01

We studied the efficacy and implementation outcomes of a culturally responsive parent training (PT) program. Fifty-four Chinese American parents participated in a wait-list controlled group randomized trial (32 immediate treatment, 22 delayed treatment) of a 14-week intervention designed to address the needs of high-risk immigrant families.…

Weight Gain Prevention among Midlife Women: A Randomized Controlled Trial to Address Needs Related to the Physical and Social Environment

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Courtney D. Perry

2016-05-01

Full Text Available Women tend to gain weight at midlife (40–60 years increasing risk of obesity-related chronic diseases. Within specific eating occasions, needs related to the physical and social environment may result in less healthy eating behavior, which can lead to weight gain over time. The purpose of this study was to determine if a dietitian-delivered nutrition counseling intervention tailored to eating occasion needs could improve diet and prevent weight gain among midlife women over two years. A randomized controlled trial was conducted with healthy midlife women (n = 354 in one U.S. metropolitan area. The intervention group (n = 185 received ten hours of individual nutrition counseling from dietitians over six months, while women in a control group (n = 169 received no counseling. Measured height, weight and waist circumference, and dietary intakes were collected at baseline and every six months over two years. Mixed linear models were used to test for intervention effect on change in outcome variables over time. Dietary intakes of fruit, reduced/low-fat dairy foods and refined grains were significantly improved over time in the intervention compared to control group. However, the intervention had no effect on weight over time (p = 0.48. Nutrition counseling tailored to address eating occasion needs improved self-reported diet but did not significantly affect weight change.

Internet treatment addressing either insomnia or depression, for patients with both diagnoses: a randomized trial.

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Blom, Kerstin; Jernelöv, Susanna; Kraepelien, Martin; Bergdahl, Malin Olséni; Jungmarker, Kristina; Ankartjärn, Linda; Lindefors, Nils; Kaldo, Viktor

2015-02-01

To compare treatment effects when patients with insomnia and depression receive treatment for either insomnia or depression. A 9-w randomized controlled trial with 6- and 12-mo follow-up. Internet Psychiatry Clinic, Stockholm, Sweden. Forty-three adults in whom comorbid insomnia and depression were diagnosed, recruited via media and assessed by psychiatrists. Guided Internet-delivered cognitive behavior therapy (ICBT) for either insomnia or depression. Primary outcome measures were symptom self-rating scales (Insomnia Severity Index [ISI] and the Montgomery Åsberg Depression Rating Scale [MADRS-S]), assessed before and after treatment with follow-up after 6 and 12 mo. The participants' use of sleep medication and need for further treatment after completion of ICBT was also investigated. The insomnia treatment was more effective than the depression treatment in reducing insomnia severity during treatment (P = 0.05), and equally effective in reducing depression severity. Group differences in insomnia severity were maintained during the 12-mo follow-up period. Post treatment, participants receiving treatment for insomnia had significantly less self-rated need for further insomnia treatment (P treatment for depression. The need for depression treatment was similar in both groups. In this study, Internet-delivered treatment with cognitive behavior therapy (ICBT) for insomnia was more effective than ICBT for depression for patients with both diagnoses. This indicates, in line with previous research, that insomnia when comorbid with depression is not merely a symptom of depression, but needs specific treatment. The trial was registered at Clinicaltrials.gov, registration ID: NCT01256099. © 2015 Associated Professional Sleep Societies, LLC.

Effects of psychological therapies in randomized trials and practice-based studies.

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Barkham, Michael; Stiles, William B; Connell, Janice; Twigg, Elspeth; Leach, Chris; Lucock, Mike; Mellor-Clark, John; Bower, Peter; King, Michael; Shapiro, David A; Hardy, Gillian E; Greenberg, Leslie; Angus, Lynne

2008-11-01

Randomized trials of the effects of psychological therapies seek internal validity via homogeneous samples and standardized treatment protocols. In contrast, practice-based studies aim for clinical realism and external validity via heterogeneous samples of clients treated under routine practice conditions. We compared indices of treatment effects in these two types of studies. Using published transformation formulas, the Beck Depression Inventory (BDI) scores from five randomized trials of depression (N = 477 clients) were transformed into Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) scores and compared with CORE-OM data collected in four practice-based studies (N = 4,196 clients). Conversely, the practice-based studies' CORE-OM scores were transformed into BDI scores and compared with randomized trial data. Randomized trials showed a modest advantage over practice-based studies in amount of pre-post improvement. This difference was compressed or exaggerated depending on the direction of the transformation but averaged about 12%. There was a similarly sized advantage to randomized trials in rates of reliable and clinically significant improvement (RCSI). The largest difference was yielded by comparisons of effect sizes which suggested an advantage more than twice as large, reflecting narrower pre-treatment distributions in the randomized trials. Outcomes of completed treatments for depression in randomized trials appeared to be modestly greater than those in routine care settings. The size of the difference may be distorted depending on the method for calculating degree of change. Transforming BDI scores into CORE-OM scores and vice versa may be a preferable alternative to effect sizes for comparisons of studies using these measures.

A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial.

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Morrison, Deborah; Wyke, Sally; Thomson, Neil C; McConnachie, Alex; Agur, Karolina; Saunderson, Kathryn; Chaudhuri, Rekha; Mair, Frances S

2014-05-24

The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes. The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status). Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of

Testing feedback message framing and comparators to address prescribing of high-risk medications in nursing homes: protocol for a pragmatic, factorial, cluster-randomized trial.

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Ivers, Noah M; Desveaux, Laura; Presseau, Justin; Reis, Catherine; Witteman, Holly O; Taljaard, Monica K; McCleary, Nicola; Thavorn, Kednapa; Grimshaw, Jeremy M

2017-07-14

Audit and feedback (AF) interventions that leverage routine administrative data offer a scalable and relatively low-cost method to improve processes of care. AF interventions are usually designed to highlight discrepancies between desired and actual performance and to encourage recipients to act to address such discrepancies. Comparing to a regional average is a common approach, but more recipients would have a discrepancy if compared to a higher-than-average level of performance. In addition, how recipients perceive and respond to discrepancies may depend on how the feedback itself is framed. We aim to evaluate the effectiveness of different comparators and framing in feedback on high-risk prescribing in nursing homes. This is a pragmatic, 2 × 2 factorial, cluster-randomized controlled trial testing variations in the comparator and framing on the effectiveness of quarterly AF in changing high-risk prescribing in nursing homes in Ontario, Canada. We grouped homes that share physicians into clusters and randomized these clusters into the four experimental conditions. Outcomes will be assessed after 6 months; all primary analyses will be by intention-to-treat. The primary outcome (monthly number of high-risk medications received by each patient) will be analysed using a general linear mixed effects regression model. We will present both four-arm and factorial analyses. With 160 clusters and an average of 350 beds per cluster, assuming no interaction and similar effects for each intervention, we anticipate 90% power to detect an absolute mean difference of 0.3 high-risk medications prescribed. A mixed-methods process evaluation will explore potential mechanisms underlying the observed effects, exploring targeted constructs including intention, self-efficacy, outcome expectations, descriptive norms, and goal prioritization. An economic analysis will examine cost-effectiveness analysis from the perspective of the publicly funded health care system. This protocol

A systematic review of the usage of flow diagram in cluster randomized trials

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Kostić M.

2014-01-01

Full Text Available Flow diagram represent an integral part of consolidated standards of reporting trials (CONSORT. Its use in reporting cluster randomization trials is highly recommended. The aim of this article is to present frequency of the use of flow diagram in cluster randomized trials in accordance with standards of reporting. The team has researched Medline database and singled-out 474 studies with cluster randomization for analysis. The studies were reviewed to identify the use of graphic representation, compliance with standards of reporting and the date when study was published. Depending from its duration, studies were divided on completed, and those still ongoing. Usage of CONSORT is recorded in 145 (31% literature units. Frequency of flow diagram was statistically much higher in studies which were in compliance with standards (86,2%, in comparison to those which did not use CONSORT guidelines (71,4%, as well as in completed studies (81,2% in comparison to pilot project studies (54,3%. Number of cluster randomized trials gathered through MEDLINE's search of key words 'cluster randomized trial [ti]' and 'cluster randomised trial [ti]', as well as the use of CONSORT in the reports of cluster randomized trials, are showing linear growth over time (p<0,001. Frequency of flow diagram is higher in the reports of cluster randomized trials that were done in accordance with the standards of reporting.

Health education for microcredit clients in Peru: a randomized controlled trial

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Fernald Lia CH

2011-01-01

Full Text Available Abstract Background Poverty, lack of female empowerment, and lack of education are major risk factors for childhood illness worldwide. Microcredit programs, by offering small loans to poor individuals, attempt to address the first two of these risk factors, poverty and gender disparity. They provide clients, usually women, with a means to invest in their businesses and support their families. This study investigates the health effects of also addressing the remaining risk factor, lack of knowledge about important health issues, through randomization of members of a microcredit organization to receive a health education module based on the World Health Organization's Integrated Management of Childhood Illness (IMCI community intervention. Methods Baseline data were collected in February 2007 from clients of a microcredit organization in Pucallpa, Peru (n = 1,855 and their children (n = 598. Loan groups, consisting of 15 to 20 clients, were then randomly assigned to receive a health education intervention involving eight monthly 30-minute sessions given by the organization's loan officers at monthly loan group meetings. In February 2008, follow-up data were collected, and included assessments of sociodemographic information, knowledge of child health issues, and child health status (including child height, weight, and blood hemoglobin levels. To explore the effects of treatment (i.e., participation in the health education sessions on the key outcome variables, multivariate regressions were implemented using ordinary least squares. Results Individuals in the IMCI treatment arm demonstrated more knowledge about a variety of issues related to child health, but there were no changes in anthropometric measures or reported child health status. Conclusions Microcredit clients randomized to an IMCI educational intervention showed greater knowledge about child health, but no differences in child health outcomes compared to controls. These results imply

Randomized trial of achieving healthy lifestyles in psychiatric rehabilitation: the ACHIEVE trial

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Guallar Eliseo

2010-12-01

Full Text Available Abstract Background Overweight and obesity are highly prevalent among persons with serious mental illness. These conditions likely contribute to premature cardiovascular disease and a 20 to 30 percent shortened life expectancy in this vulnerable population. Persons with serious mental illness need effective, appropriately tailored behavioral interventions to achieve and maintain weight loss. Psychiatric rehabilitation day programs provide logical intervention settings because mental health consumers often attend regularly and exercise can take place on-site. This paper describes the Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation (ACHIEVE. The goal of the study is to determine the effectiveness of a behavioral weight loss intervention among persons with serious mental illness that attend psychiatric rehabilitation programs. Participants randomized to the intervention arm of the study are hypothesized to have greater weight loss than the control group. Methods/Design A targeted 320 men and women with serious mental illness and overweight or obesity (body mass index ≥ 25.0 kg/m2 will be recruited from 10 psychiatric rehabilitation programs across Maryland. The core design is a randomized, two-arm, parallel, multi-site clinical trial to compare the effectiveness of an 18-month behavioral weight loss intervention to usual care. Active intervention participants receive weight management sessions and physical activity classes on-site led by study interventionists. The intervention incorporates cognitive adaptations for persons with serious mental illness attending psychiatric rehabilitation programs. The initial intensive intervention period is six months, followed by a twelve-month maintenance period in which trained rehabilitation program staff assume responsibility for delivering parts of the intervention. Primary outcomes are weight loss at six and 18 months. Discussion Evidence-based approaches to the high burden

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

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Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

Alzheimer's disease - input of vitamin D with mEmantine assay (AD-IDEA trial: study protocol for a randomized controlled trial

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Gautier Jennifer

2011-10-01

Full Text Available Abstract Background Current treatments for Alzheimer's disease and related disorders (ADRD are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine. Methods The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20, hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] Discussion The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD. Trial Registration ClinicalTrials.gov number, NCT01409694

An individually-tailored smoking cessation intervention for rural Veterans: a pilot randomized trial

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Mark W. Vander Weg

2016-08-01

Full Text Available Abstract Background Tobacco use remains prevalent among Veterans of military service and those residing in rural areas. Smokers frequently experience tobacco-related issues including risky alcohol use, post-cessation weight gain, and depressive symptoms that may adversely impact their likelihood of quitting and maintaining abstinence. Telephone-based interventions that simultaneously address these issues may help to increase treatment access and improve outcomes. Methods This study was a two-group randomized controlled pilot trial. Participants were randomly assigned to an individually-tailored telephone tobacco intervention combining counseling for tobacco use and related issues including depressive symptoms, risky alcohol use, and weight concerns or to treatment provided through their state tobacco quitline. Selection of pharmacotherapy was based on medical history and a shared decision interview in both groups. Participants included 63 rural Veteran smokers (mean age = 56.8 years; 87 % male; mean number of cigarettes/day = 24.7. The primary outcome was self-reported 7-day point prevalence abstinence at 12 weeks and 6 months. Results Twelve-week quit rates based on an intention-to-treat analysis did not differ significantly by group (Tailored = 39 %; Quitline Referral = 25 %; odds ratio [OR]; 95 % confidence interval [CI] = 1.90; 0.56, 5.57. Six-month quit rates for the Tailored and Quitline Referral conditions were 29 and 28 %, respectively (OR; 95 % CI = 1.05; 0.35, 3.12. Satisfaction with the Tailored tobacco intervention was high. Conclusions Telephone-based treatment that concomitantly addresses other health-related factors that may adversely affect quitting appears to be a promising strategy. Larger studies are needed to determine whether this approach improves cessation outcomes. Trial registration ClinicalTrials.gov identifier number NCT01592695 registered 11 April 2012.

Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial

NARCIS (Netherlands)

Verberk, W. J.; Kroon, A. A.; Kessels, A. G. H.; Nelemans, P. J.; van Ree, J. W.; Lenders, J. W. M.; Thien, T.; Bakx, J. C.; van Montfrans, G. A.; Smit, A. J.; Beltman, F. W.; de Leeuw, P. W.

2005-01-01

Background. Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in

Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial.

NARCIS (Netherlands)

Verberk, W.J.; Kroon, A.A.; Kessels, A.G.H.; Nelemans, P.J.; Ree, J.W. van; Lenders, J.W.M.; Thien, Th.; Bakx, J.C.; Montfrans, G.A. van; Smit, A.J.; Beltman, F.W.; Leeuw, P.W. de

2005-01-01

BACKGROUND: Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in

Fundamentals of randomized clinical trials in wound care

DEFF Research Database (Denmark)

Eskes, Anne M; Brölmann, Fleur E; Sumpio, Bauer E

2012-01-01

randomization is a necessary feature of a robust comparative study, it is not sufficient to ensure a study at low risk of bias. Randomized clinical trials should also ensure adequate allocation concealment and blinding of outcome assessors, apply intention-to-treat analysis, and use patient-oriented outcomes...

Evaluating the Flipped Classroom: A Randomized Controlled Trial

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Wozny, Nathan; Balser, Cary; Ives, Drew

2018-01-01

Despite recent interest in flipped classrooms, rigorous research evaluating their effectiveness is sparse. In this study, the authors implement a randomized controlled trial to evaluate the effect of a flipped classroom technique relative to a traditional lecture in an introductory undergraduate econometrics course. Random assignment enables the…

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....

The evaluation of subcutaneous proleukin (interleukin-2) in a randomized international trial: rationale, design, and methods of ESPRIT.

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Emery, Sean; Abrams, Donald I; Cooper, David A; Darbyshire, Janet H; Lane, H Clifford; Lundgren, Jens D; Neaton, James D

2002-04-01

The Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) is a large ongoing randomized trial of subcutaneous interleukin-2 (IL-2) plus antiretroviral therapy versus antiretroviral therapy alone in patients with HIV (human immunodeficiency virus) disease and CD4 cell counts of at least 300 cells/mm(3). The primary objective is to determine whether the addition of IL-2 to combination antiretroviral therapy improves morbidity and mortality. The aim is to recruit 4000 participants and follow them for an average of 5 years. Eligible subjects will be recruited at 275 investigational sites in 23 countries around the world. Coupled with broad eligibility criteria this will ensure widely applicable results. A range of secondary objectives will also be addressed in this setting that will include the conduct of observational studies and nested substudies with a public health focus. This article describes the rationale supporting the trial in addition to reviewing the study design, coordination, and governance.

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

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Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

The Chronic Kidney Disease Water Intake Trial: Protocol of a Randomized Controlled Trial

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William F. Clark

2017-08-01

Full Text Available Background: In observational studies, drinking more water associates with a slower rate of kidney function decline; whether the same is true in a randomized controlled trial is unknown. Objective: To examine the 1-year effect of a higher vs usual water intake on estimated glomerular filtration rate (eGFR in patients with chronic kidney disease. Design: Parallel-group randomized controlled trial. Setting: Nine centers in Ontario, Canada. Enrollment and randomization occurred between May 2013 and May 2016; follow-up for the primary outcome will continue until June 2017. Participants: Adults (n = 631 with stage 3 chronic kidney disease (eGFR 30-60 mL/min/1.73 m 2 and microalbuminuria. Intervention: The high water intake group was coached to increase their oral water intake by 1.0 to 1.5 L/day (depending on sex and weight, over and above usual consumed beverages, for a period of 1 year. The control group was coached to maintain their usual water intake during this time. Measures: Participants provided 24-hour urine samples at baseline and at 6 and 12 months after randomization; urine samples were analyzed for volume, creatinine, osmolality, and the albumin-to-creatinine ratio. Blood samples were obtained at baseline and at 3- to 6-month intervals after randomization, and analyzed for creatinine, copeptin, osmolality, and electrolytes. Other measures collected included health-related quality of life, blood pressure, body mass index, and diet. Primary outcome: The between-group change in eGFR from baseline (prerandomization to 12 months after randomization. Secondary outcomes: Change in plasma copeptin concentration, 24-hour urine albumin-to-creatinine ratio, measured creatinine clearance, estimated 5-year risk of kidney failure (using the 4-variable Kidney Failure Risk Equation, and health-related quality of life. Planned analysis: The primary analysis will follow an intention-to-treat approach. The between-group change in eGFR will be compared using

The conflict between randomized clinical trials and the therapeutic obligation.

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Gifford, F

1986-11-01

The central dilemma concerning randomized clinical trials (RCTs) arises out of some simple facts about causal methodology (RCTs are the best way to generate the reliable causal knowledge necessary for optimally-informed action) and a prima facie plausible principle concerning how physicians should treat their patients (always do what it is most reasonable to believe will be best for the patient). A number of arguments related to this in the literature are considered. Attempts to avoid the dilemma fail. Appeals to informed consent and mechanisms for minimizing the resulting harm are important for policy, but informed consent is problematic and mechanisms for minimization of harm do not address the dilemma. Appeals to some sort of contract model of justification are promising and illuminating.

Review of Recent Methodological Developments in Group-Randomized Trials: Part 2-Analysis.

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Turner, Elizabeth L; Prague, Melanie; Gallis, John A; Li, Fan; Murray, David M

2017-07-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have updated that review with developments in analysis of the past 13 years, with a companion article to focus on developments in design. We discuss developments in the topics of the earlier review (e.g., methods for parallel-arm GRTs, individually randomized group-treatment trials, and missing data) and in new topics, including methods to account for multiple-level clustering and alternative estimation methods (e.g., augmented generalized estimating equations, targeted maximum likelihood, and quadratic inference functions). In addition, we describe developments in analysis of alternative group designs (including stepped-wedge GRTs, network-randomized trials, and pseudocluster randomized trials), which require clustering to be accounted for in their design and analysis.

Reducing therapeutic misconception: A randomized intervention trial in hypothetical clinical trials.

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Paul P Christopher

Full Text Available Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials.This prospective randomized trial was conducted from 2015 to 2016 to test the efficacy of an informed consent intervention based on scientific reframing compared to a traditional informed consent procedure (control in reducing therapeutic misconception among patients considering enrollment in hypothetical clinical trials modeled on real-world studies for one of five disease categories. Patients with diabetes mellitus, hypertension, coronary artery disease, head/neck cancer, breast cancer, and major depression were recruited from medical clinics and a clinical research volunteer database. The primary outcomes were therapeutic misconception, as measured by a validated, ten-item Therapeutic Misconception Scale (range = 10-50, and willingness to participate in the clinical trial.154 participants completed the study (age range, 23-87 years; 92.3% white, 56.5% female; 74 (48.1% had been randomized to receive the experimental intervention. Therapeutic misconception was significantly lower (p = 0.004 in the scientific reframing group (26.4, 95% CI [23.7 to 29.1] compared to the control group (30.9, 95% CI [28.4 to 33.5], and remained so after controlling for education (p = 0.017. Willingness to participate in the hypothetical trial was not significantly different (p = 0.603 between intervention (52.1%, 95% CI [40.2% to 62.4%] and control (56.3%, 95% CI [45.3% to 66.6%] groups.An enhanced educational intervention augmenting

Disseminating quality improvement: study protocol for a large cluster-randomized trial

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French Michael T

2011-04-01

with outcome data will be included in the analysis, following the intent-to-treat principle. Organizational covariates in the analysis include program size, management score, and state. Discussion The study offers seven recommendations for conducting a large-scale cluster-randomized trial: provide valuable services, have aims that are clear and important, seek powerful allies, understand the recruiting challenge, cultivate commitment, address turnover, and encourage rigor and flexibility. Trial Registration ClinicalTrials. govNCT00934141

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

NARCIS (Netherlands)

Mohr, J.P.; Overbey, J.R.; Kummer, R. von; Stefani, M.A.; Libman, R.; Stapf, C.; Parides, M.K.; Pile-Spellman, J.; Moquete, E.; Moy, C.S.; Vicaut, E.; Moskowitz, A.J.; Harkness, K.; Cordonnier, C.; Biondi, A.; Houdart, E.; Berkefeld, J.; Klijn, C.J.M.; Barreau, X.; Kim, H.; Hartmann, A.

2017-01-01

OBJECTIVE: To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). METHODS: We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults >/=18

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

NARCIS (Netherlands)

Mohr, J P; Overbey, Jessica R; von Kummer, Ruediger; Stefani, Marco A; Libman, Richard; Stapf, Christian; Parides, Michael K; Pile-Spellman, John; Moquete, Ellen; Moy, Claudia S; Vicaut, Eric; Moskowitz, Alan J; Harkness, Kirsty; Cordonnier, Charlotte; Biondi, Alessandra; Houdart, Emmanuel; Berkefeld, Joachim; Klijn, Karin J M; Barreau, Xavier; Kim, Helen; Hartmann, Andreas; van Dijk, J. Marc C.; Luijckx, Gert Jan

2017-01-01

OBJECTIVE: To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). METHODS: We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18

Cognitive therapy as an early treatment for post-traumatic stress disorder in children and adolescents: a randomized controlled trial addressing preliminary efficacy and mechanisms of action.

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Meiser-Stedman, Richard; Smith, Patrick; McKinnon, Anna; Dixon, Clare; Trickey, David; Ehlers, Anke; Clark, David M; Boyle, Adrian; Watson, Peter; Goodyer, Ian; Dalgleish, Tim

2017-05-01

Few efficacious early treatments for post-traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post-trauma and focused on secondary prevention of later post-traumatic stress; however, considerable natural recovery may still occur up to 6-months post-trauma. No trials have addressed the early treatment of established PTSD (i.e. 2- to 6-months post-trauma). Twenty-nine youth (8-17 years) with PTSD (according to age-appropriate DSM-IV or ICD-10 diagnostic criteria) after a single-event trauma in the previous 2-6 months were randomly allocated to Cognitive Therapy for PTSD (CT-PTSD; n = 14) or waiting list (WL; n = 15) for 10 weeks. Significantly more participants were free of PTSD after CT-PTSD (71%) than WL (27%) at posttreatment (intent-to-treat, 95% CI for difference .04-.71). CT-PTSD yielded greater improvement on child-report questionnaire measures of PTSD, depression and anxiety; clinician-rated functioning; and parent-reported outcomes. Recovery after CT-PTSD was maintained at 6- and 12-month posttreatment. Beneficial effects of CT-PTSD were mediated through changes in appraisals and safety-seeking behaviours, as predicted by cognitive models of PTSD. CT-PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings. This trial provides preliminary support for the efficacy and acceptability of CT-PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of 'watchful waiting' into the 2- to 6-month post-trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required. © 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

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

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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.

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

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Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

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Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

New developments in the conduct and management of multi-center trials

DEFF Research Database (Denmark)

Gluud, C; Sørensen, T I

1995-01-01

There is an urgent need for the performance of more, better designed, and better managed randomized clinical trials. After visits to 43 leading organizations and units involved in clinical trials in Europe and North America during 1993, the way of conducting randomized clinical trials was analyzed...... and data management systems). By employing such developments, randomized clinical trials can run much more efficiently. This facilitates faster and better answers to the questions addressed by randomized clinical trials, thereby also making them more ethical....

Effect of etanercept in polymyalgia rheumatica: a randomized controlled trial

DEFF Research Database (Denmark)

Kreiner, Frederik; Galbo, Henrik

2010-01-01

To elucidate in polymyalgia rheumatica (PMR) the role of tumor necrosis factor (TNF) α and the therapeutic potential of blockade with soluble TNF-α receptor, we carried out the first randomized controlled trial with etanercept in PMR.......To elucidate in polymyalgia rheumatica (PMR) the role of tumor necrosis factor (TNF) α and the therapeutic potential of blockade with soluble TNF-α receptor, we carried out the first randomized controlled trial with etanercept in PMR....

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

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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

Blinding in randomized clinical trials: imposed impartiality

DEFF Research Database (Denmark)

Hróbjartsson, A; Boutron, I

2011-01-01

Blinding, or "masking," is a crucial method for reducing bias in randomized clinical trials. In this paper, we review important methodological aspects of blinding, emphasizing terminology, reporting, bias mechanisms, empirical evidence, and the risk of unblinding. Theoretical considerations...

Assessing Risk of Bias in Randomized Controlled Trials for Autism Spectrum Disorder

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Paola Matiko Martins Okuda

2017-11-01

Full Text Available AimTo determine construct validity and reliability indicators of the Cochrane risk of bias (RoB tool in the context of randomized clinical trials (RCTs for autism spectrum disorder (ASD.MethodsConfirmatory factor analysis was used to evaluate a unidimensional model consisting of 9 RoB categorical indicators evaluated across 94 RCTs addressing interventions for ASD.ResultsOnly five of the nine original RoB items returned good fit indices and so were retained in the analysis. Only one of this five had very high factor loadings. The remaining four indicators had more measurement error than common variance with the RoB latent factor. Together, the five indicators showed poor reliability (ω = 0.687; 95% CI: 0.613–0.761.ConclusionAlthough the Cochrane model of RoB for ASD exhibited good fit indices, the majorities of the items have more residual variance than common variance and, therefore, did not adequately capture the RoB in ASD intervention trials.

Acupuncture for alcohol withdrawal: a randomized controlled trial.

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Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

2003-01-01

Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

Random forests of interaction trees for estimating individualized treatment effects in randomized trials.

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Su, Xiaogang; Peña, Annette T; Liu, Lei; Levine, Richard A

2018-04-29

Assessing heterogeneous treatment effects is a growing interest in advancing precision medicine. Individualized treatment effects (ITEs) play a critical role in such an endeavor. Concerning experimental data collected from randomized trials, we put forward a method, termed random forests of interaction trees (RFIT), for estimating ITE on the basis of interaction trees. To this end, we propose a smooth sigmoid surrogate method, as an alternative to greedy search, to speed up tree construction. The RFIT outperforms the "separate regression" approach in estimating ITE. Furthermore, standard errors for the estimated ITE via RFIT are obtained with the infinitesimal jackknife method. We assess and illustrate the use of RFIT via both simulation and the analysis of data from an acupuncture headache trial. Copyright © 2018 John Wiley & Sons, Ltd.

Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

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Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

2012-06-01

Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

Marketing depression care management to employers: design of a randomized controlled trial

Directory of Open Access Journals (Sweden)

Marshall Donna

2010-03-01

Full Text Available Abstract Background Randomized trials demonstrate that depression care management can improve clinical and work outcomes sufficiently for selected employers to realize a return on investment. Employers can now purchase depression products that provide depression care management, defined as employee screening, education, monitoring, and clinician feedback for all depressed employees. We developed an intervention to encourage employers to purchase a depression product that offers the type, intensity, and duration of care management shown to improve clinical and work outcomes. Methods In a randomized controlled trial conducted with 360 employers of 30 regional business coalitions, the research team proposes to compare the impact of a value-based marketing intervention to usual-care marketing on employer purchase of depression products. The study will also identify mediators and organizational-level moderators of intervention impact. Employers randomized to the value-based condition receive a presentation encouraging them to purchase depression products scientifically shown to benefit the employee and the employer. Employers randomized to the usual-care condition receive a presentation encouraging them to monitor and improve quality indicators for outpatient depression treatment. Because previous research demonstrates that the usual-care intervention will have little to no impact on employer purchasing, depression product purchasing rates in the usual-care condition capture vendor efforts to market depression products to employers in both conditions while the value-based intervention is being conducted. Employers in both conditions are also provided free technical assistance to undertake the actions each presentation encourages. The research team will use intent-to-treat models of all available data to evaluate intervention impact on the purchase of depression products using a cumulative incidence analysis of 12- and 24-month data. Discussion By

Recent randomized controlled trials in otolaryngology.

Science.gov (United States)

Banglawala, Sarfaraz M; Lawrence, Lauren A; Franko-Tobin, Emily; Soler, Zachary M; Schlosser, Rodney J; Ioannidis, John

2015-03-01

To assess recent trends in the prevalence and quality of reporting of randomized controlled trials (RCTs) in 4 otolaryngology journals. Methodology and reporting analysis. Randomized controlled trials in 4 otolaryngology journals. All RCTs published from 2011 to 2013 in 4 major otolaryngology journals were examined for characteristics of study design, quality of design and reporting, and funding. Of 5279 articles published in 4 leading otolaryngology journals from 2011 to 2013, 189 (3.3%) were RCTs. The majority of RCTs were clinical studies (86%), with the largest proportion consisting of sinonasal topics (31%). Most interventions were medical (46%), followed by surgical (38%) and mixed (16%). In terms of quality, randomization method was reported in 54% of RCTs, blinding in 33%, and adverse events in 65%. Intention-to-treat analysis was used in 32%; P values were reported in 87% and confidence intervals in 10%. Research funding was most often absent or not reported (55%), followed by not-for-profit (25%). Based on review of 4 otolaryngology journals, RCTs are still a small proportion of all published studies in the field of otolaryngology. There seem to be trends toward improvement in quality of design and reporting of RCTs, although many quality features remain suboptimal. Practitioners both designing and interpreting RCTs should critically evaluate RCTs for quality. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

[Lower Uterine Segment Trial: A pragmatic open multicenter randomized trial].

Science.gov (United States)

Rozenberg, P; Deruelle, P; Sénat, M-V; Desbrière, R; Winer, N; Simon, E; Ville, Y; Kayem, G; Boutron, I

2018-04-01

The data from literature show that trial of labor and elective repeat cesarean delivery after a prior cesarean delivery both present significant risks and benefits, and these risks and benefits differ for the woman and her fetus. The benefits to the woman can be at the expense of her fetus and vice-versa. This uncertainty is compounded by the scarcity of high-level evidence that preclude accurate quantification of the risks and benefits that could help provide a fair counseling about a trial of labor and elective repeat cesarean delivery. An interesting way of research is to evaluate the potential benefits of a decision rule associated to the ultrasound measurement of the lower uterine segment (LUS). Indeed, ultrasonography may be helpful in determining a specific risk for a given patient by measuring the thickness of the LUS, i,e, the thickness of the cesarean delivery scar area. Although only small and often methodologically biased data have been published, they look promising as their results are concordant: ultrasonographic measurements of the LUS thickness is highly correlated with the intraoperative findings at cesarean delivery. Furthermore, the thinner the LUS becomes on ultrasound, the higher the likelihood of a defect in the LUS. Finally, ultrasound assessment of LUS has an excellent negative predictive value for the risk of uterine defect. Therefore, this exam associated with a rule of decision could help to reduce the rate of elective repeat cesarean delivery and especially to reduce the fetal and maternal mortality and morbidity related to trial of labor after a prior cesarean delivery. This is a pragmatic open multicenter randomized trial with two parallel arms. Randomization will be centralized and computerized. Since blindness is impossible, an adjudication committee will evaluate the components of the primary composite outcome in order to avoid evaluation bias. An interim analysis will be planned mid-strength of the trial. Ultrasound will be

Intention-to-treat analysis and accounting for missing data in orthopaedic randomized clinical trials.

Science.gov (United States)

Herman, Amir; Botser, Itamar Busheri; Tenenbaum, Shay; Chechick, Ahron

2009-09-01

The intention-to-treat principle implies that all patients who are randomized in a clinical trial should be analyzed according to their original allocation. This means that patients crossing over to another treatment group and patients lost to follow-up should be included in the analysis as a part of their original group. This principle is important for preserving the randomization scheme, which is the basis for correct inference in any randomized trial. In this study, we examined the use of the intention-to-treat principle in recently published orthopaedic clinical trials. We surveyed eight leading orthopaedic journals for randomized clinical trials published between January 2005 and August 2008. We determined whether the intention-to-treat principle was implemented and, if so, how it was used in each trial. Specifically, we ascertained which methods were used to account for missing data. Our search yielded 274 randomized clinical trials, and the intention-to-treat principle was used in ninety-six (35%) of them. There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; this practice was most notable in studies of surgical interventions. The most popular method of adjusting for missing data was the "last observation carried forward" technique. In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission might introduce bias to

Rain dance: the role of randomization in clinical trials

Directory of Open Access Journals (Sweden)

Diniz JB

2016-07-01

Full Text Available Juliana Belo Diniz,1 Victor Fossaluza,2 Carlos Alberto de Bragança Pereira,1,2 Sergio Wechsler2 1Institute of Psychiatry, Clinics Hospital University of São Paulo Medical School, 2Department of Statistics, Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil Abstract: Randomized clinical trials are the gold standard for testing efficacy of treatment interventions. However, although randomization protects against deliberately biased samples, it does not guarantee random imbalances will not occur. Methods of intentional allocation that can overcome such deficiency of randomization have been developed, but are less frequently applied than randomization. Initially, we introduce a fictitious case example to revise and discuss the reasons of researchers' resistance to intentionally allocate instead of simply randomizing. We then introduce a real case example to evaluate the performance of an intentional protocol for allocation based on compositional data balance. A real case of allocation of 50 patients in two arms was compared with an optimal allocation of global instead of sequential arrivals. Performance was measured by a weighted average of Aitchison distances, between arms, of prognostic factors. To compare the intentional allocation with simple random allocation, 50,000 arrival orderings of 50 patients were simulated. To each one of the orders, both kinds of allocations into two arms were considered. Intentional allocation performed as well as optimal allocation in the case considered. In addition, out of the 50,000 simulated orders, 61% of them performed better with intentional allocation than random allocation. Hence, we conclude that intentional allocation should be encouraged in the design of future interventional clinical trials as a way to prevent unbalanced samples. Our sequential method is a viable alternative to overcome technical difficulties for study designs that require sequential inclusion of

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

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Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement

Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials

International Nuclear Information System (INIS)

Vernon, Clare C.; Hand, Jeffrey W.; Field, Stanley B.; Machin, David; Whaley, Jill B.; Zee, Jacoba van der; Putten, Wim L.J. van; Rhoon, Gerard C. van; Dijk, Jan D.P. van; Gonzalez, Dionisio Gonzalez; Liu, F.-F.; Goodman, Phyllis; Sherar, Michael

1996-01-01

Purpose: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. Methods and Materials: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. Results: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. Conclusion: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that

Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding

DEFF Research Database (Denmark)

Hróbjartsson, A; Forfang, E; Haahr, M T

2007-01-01

Blinding can reduce bias in randomized clinical trials, but blinding procedures may be unsuccessful. Our aim was to assess how often randomized clinical trials test the success of blinding, the methods involved and how often blinding is reported as being successful....

Use acupuncture to treat functional constipation: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Li Ying

2012-07-01

Full Text Available Abstract Background Whether acupuncture is effective for patients with functional constipation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using acupuncture to treat functional constipation. Design A randomized, controlled, four-arm design, large-scale trial is currently undergoing in China. Seven hundred participants are randomly assigned to three acupuncture treatment groups and Mosapride Citrate control group in a 1:1:1:1 ratio. Participants in acupuncture groups receive 16 sessions of acupuncture treatment, and are followed up for a period of 9 weeks after randomization. The acupuncture groups are: (1 Back-Shu and Front-Mu acupoints of Large Intestine meridians (Shu-Mu points group; (2 He-Sea and Lower He-Sea acupoints of Large Intestine meridians (He points group; (3 Combining used Back-Shu, Front-Mu, He-Sea, and Lower He-Sea acupoints of Large Intestine meridians (Shu-Mu-He points group. The control group is Mosapride Citrate group. The primary outcome is frequency of defecation per week at the fourth week after randomization. The secondary outcomes include Bristol stool scale, the extent of difficulty during defecating, MOS 36-item Short Form health survey (SF-36, Self-Rating Anxiety Scale (SAS, and Self-rating Depression Scale (SDS. The first two of second outcomes are measured 1 week before randomization and 2, 4, and 8 weeks after randomization. Other second outcomes are measured 1 week before randomization and 2 and 4 weeks after randomization, but SF-36 is measured at randomization and 4 weeks after randomization. Discussion The result of this trial (which will be available in 2012 will confirm whether acupuncture is effective to treat functional constipation and whether traditional acupuncture theories play an important role in it. Trials registration Clinical Trials.gov NCT01411501

Telegerontology as a Novel Approach to Address Health and Safety by Supporting Community-Based Rural Dementia Care Triads: Randomized Controlled Trial Protocol.

Science.gov (United States)

Wallack, Elizabeth M; Harris, Chelsea; Ploughman, Michelle; Butler, Roger

2018-02-22

Telegerontology is an approach using videoconferencing to connect an interdisciplinary team in a regional specialty center to patients in rural communities, which is becoming increasingly practical for addressing current limitations in rural community-based dementia care. Using the remotely-delivered expertise of the Telegerontology dementia care team, we aim to enhance the caregiver/patient/physician triad and thereby provide the necessary support for the person with dementia to "age in place." This is a cluster randomized feasibility trial with four rural regions in the province of Newfoundland and Labrador, Canada (2 regions randomly assigned to "intervention" and 2 to "control"). The study population includes 22 "dementia triads" that consist of a community-dwelling older Canadian with moderate to late dementia, their family caregivers, and their Primary Care Physician (PCP). Over the 6-month active study period, all participants will be provided an iPad. The intervention is intended as an adjunct to existing PCP care, consisting of weekly Skype-based videoconferencing calls with the Telegerontology physician, and other team members as needed (occupational therapist, physical therapist etc). Control participants receive usual community-based dementia care with their PCP. A baseline (pre-) assessment will be performed during a home visit with the study team. Post intervention, 6- and 12-month follow-up assessments will be collected remotely using specialized dementia monitoring applications and Skype calls. Primary outcomes include admission to long-term care, falls, emergency room visits, hospital stays, and caregiver burden. Results will be available in March of 2018. Results from this study will demonstrate a novel approach to dementia care that has the potential to impact both rural PCPs, family caregivers, and people with dementia, as well as provide evidence for the utility of Telegerontology in models of eHealth-based care. ©Elizabeth M. Wallack, Chelsea

Feasibility study of a clinically-integrated randomized trial of modifications to radical prostatectomy

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Vickers Andrew J

2012-02-01

Full Text Available Abstract Background Numerous technical modifications to radical prostatectomy have been proposed. Such modifications are likely to lead to only slight improvements in outcomes. Although small differences would be worthwhile, an appropriately powered randomized trial would need to be very large, and thus of doubtful feasibility given the expense, complexity and regulatory burden of contemporary clinical trials. We have proposed a novel methodology, the clinically-integrated randomized trial, which dramatically streamlines trial procedures in order to reduce the marginal cost of an additional patient towards zero. We aimed to determine the feasibility of implementing such a trial for radical prostatectomy. Methods Patients undergoing radical prostatectomy as initial treatment for prostate cancer were randomized in a factorial design to involvement of the fascia during placement of the anastomotic sutures, urethral irrigation, both or neither. Endpoint data were obtained from routine clinical documentation. Accrual and compliance rates were monitored to determine the feasibility of the trial. Results From a total of 260 eligible patients, 154 (59% consented; 56 patients declined to participate, 20 were not approached on recommendation of the treating surgeon, and 30 were not approached for logistical reasons. Although recording by surgeons of the procedure used was incomplete (~80%, compliance with randomization was excellent when it was recorded, with only 6% of procedures inconsistent with allocation. Outcomes data was received from 71% of patients at one year. This improved to 83% as the trial progressed. Conclusions A clinically-integrated randomized trial was conducted at low cost, with excellent accrual, and acceptable compliance with treatment allocation and outcomes reporting. This demonstrates the feasibility of the methodology. Improved methods to ensure documentation of surgical procedures would be required before wider implementation

The SafeBoosC II randomized trial

DEFF Research Database (Denmark)

Plomgaard, Anne M; van Oeveren, Wim; Petersen, Tue Hvass

2016-01-01

BACKGROUND: The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group...

The psychosocial effects of a companion robot: a randomized controlled trial.

Science.gov (United States)

Robinson, Hayley; Macdonald, Bruce; Kerse, Ngaire; Broadbent, Elizabeth

2013-09-01

To investigate the psychosocial effects of the companion robot, Paro, in a rest home/hospital setting in comparison to a control group. Randomized controlled trial. Residents were randomized to the robot intervention group or a control group that attended normal activities instead of Paro sessions. Sessions took place twice a week for an hour over 12 weeks. Over the trial period, observations were conducted of residents' social behavior when interacting as a group with the robot. As a comparison, observations were also conducted of all the residents during general activities when the resident dog was or was not present. A residential care facility in Auckland, New Zealand. Forty residents in hospital and rest home care. Residents completed a baseline measure assessing cognitive status, loneliness, depression, and quality of life. At follow-up, residents completed a questionnaire assessing loneliness, depression, and quality of life. During observations, behavior was noted and collated for instances of talking and stroking the dog/robot. In comparison with the control group, residents who interacted with the robot had significant decreases in loneliness over the period of the trial. Both the resident dog and the seal robot made an impact on the social environment in comparison to when neither was present. Residents talked to and touched the robot significantly more than the resident dog. A greater number of residents were involved in discussion about the robot in comparison with the resident dog and conversation about the robot occurred more. Paro is a positive addition to this environment and has benefits for older people in nursing home care. Paro may be able to address some of the unmet needs of older people that a resident animal may not, particularly relating to loneliness. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

The Effectiveness of Music in Pediatric Healthcare: A Systematic Review of Randomized Controlled Trials

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Karline Treurnicht Naylor

2011-01-01

Full Text Available The aim of this study was to systematically review the effectiveness of music on pediatric health-related outcomes. Five electronic databases were searched for randomized controlled/crossover trial designs published between 1984 and 2009. Eligible studies used music as a therapy or intervention, included participants 1 to 18 years, and focused on at least one health-related outcome (with the exclusion of procedural pain. Seventeen studies met the inclusion criteria. Quantitative synthesis was hampered by an inability to aggregate data arising from heterogeneity of interventions, outcomes and measurement tools. Qualitative synthesis revealed significant improvements in one or more health outcomes within four of seven trials involving children with learning and developmental disorders; two of three trials involving children experiencing stressful life events; and four of five trials involving children with acute and/or chronic physical illness. No significant effects were found for two trials involving children with mood disorders and related psychopathology. These findings offer limited qualitative evidence to support the effectiveness of music on health-related outcomes for children and adolescents with clinical diagnoses. Recommendations for establishing a consensus on research priorities and addressing methodological limitations are put forth to support the continued advancement of this popular intervention.

The Effectiveness of Music in Pediatric Healthcare: A Systematic Review of Randomized Controlled Trials

Science.gov (United States)

Treurnicht Naylor, Karline; Kingsnorth, Shauna; Lamont, Andrea; McKeever, Patricia; Macarthur, Colin

2011-01-01

The aim of this study was to systematically review the effectiveness of music on pediatric health-related outcomes. Five electronic databases were searched for randomized controlled/crossover trial designs published between 1984 and 2009. Eligible studies used music as a therapy or intervention, included participants 1 to 18 years, and focused on at least one health-related outcome (with the exclusion of procedural pain). Seventeen studies met the inclusion criteria. Quantitative synthesis was hampered by an inability to aggregate data arising from heterogeneity of interventions, outcomes and measurement tools. Qualitative synthesis revealed significant improvements in one or more health outcomes within four of seven trials involving children with learning and developmental disorders; two of three trials involving children experiencing stressful life events; and four of five trials involving children with acute and/or chronic physical illness. No significant effects were found for two trials involving children with mood disorders and related psychopathology. These findings offer limited qualitative evidence to support the effectiveness of music on health-related outcomes for children and adolescents with clinical diagnoses. Recommendations for establishing a consensus on research priorities and addressing methodological limitations are put forth to support the continued advancement of this popular intervention. PMID:20976017

Effective Recruitment of Schools for Randomized Clinical Trials: Role of School Nurses.

Science.gov (United States)

Petosa, R L; Smith, L

2017-01-01

In school settings, nurses lead efforts to improve the student health and well-being to support academic success. Nurses are guided by evidenced-based practice and data to inform care decisions. The randomized controlled trial (RCT) is considered the gold standard of scientific rigor for clinical trials. RCTs are critical to the development of evidence-based health promotion programs in schools. The purpose of this article is to present practical solutions to implementing principles of randomization to RCT trials conducted in school settings. Randomization is a powerful sampling method used to build internal and external validity. The school's daily organization and educational mission provide several barriers to randomization. Based on the authors' experience in conducting school-based RCTs, they offer a host of practical solutions to working with schools to successfully implement randomization procedures. Nurses play a critical role in implementing RCTs in schools to promote rigorous science in support of evidence-based practice.

Experiences of randomization: interviews with patients and clinicians in the SPCG-IV trial.

Science.gov (United States)

Bill-Axelson, Anna; Christensson, Anna; Carlsson, Marianne; Norlén, Bo Johan; Holmberg, Lars

2008-01-01

Recruitment of both patients and clinicians to randomized trials is difficult. Low participation carries the risk of terminating studies early and making them invalid owing to insufficient statistical power. This study investigated patients' and clinicians' experiences of randomization with the aim of facilitating trial participation in the future. This was a qualitative study using content analysis. Patients offered to participate in a randomized trial and randomizing clinicians were interviewed. Five participants, four non-participants and five randomizing clinicians were interviewed, 2-8 years from randomization. Clinicians used strategies in interaction with the patients to facilitate decision making. Patients' attitudes differed and experiences of relatives or friends were often stated as reasons for treatment preferences. Patients described that letting chance decide treatment was a difficult barrier to overcome for randomization. The clinicians used a number of different strategies perceived to make randomization more acceptable to their patients. The clinicians' own motivation for randomizing patients for trials depended on the medical relevance of the study question and the clinicians' major obstacle was to maintain equipoise over time. Regular meetings with the study group helped to maintain equipoise and motivation. To establish a good platform for randomization the clinician needs to know about the patient's treatment preferences and the patient's attitude concerning the role of the clinician to facilitate decision making. The strategies used by the clinicians were perceived as helpful and could be tested in an intervention study.

Randomized trials, generalizability, and meta-analysis: Graphical insights for binary outcomes

Directory of Open Access Journals (Sweden)

Kramer Barnett S

2003-06-01

Full Text Available Abstract Background Randomized trials stochastically answer the question. "What would be the effect of treatment on outcome if one turned back the clock and switched treatments in the given population?" Generalizations to other subjects are reliable only if the particular trial is performed on a random sample of the target population. By considering an unobserved binary variable, we graphically investigate how randomized trials can also stochastically answer the question, "What would be the effect of treatment on outcome in a population with a possibly different distribution of an unobserved binary baseline variable that does not interact with treatment in its effect on outcome?" Method For three different outcome measures, absolute difference (DIF, relative risk (RR, and odds ratio (OR, we constructed a modified BK-Plot under the assumption that treatment has the same effect on outcome if either all or no subjects had a given level of the unobserved binary variable. (A BK-Plot shows the effect of an unobserved binary covariate on a binary outcome in two treatment groups; it was originally developed to explain Simpsons's paradox. Results For DIF and RR, but not OR, the BK-Plot shows that the estimated treatment effect is invariant to the fraction of subjects with an unobserved binary variable at a given level. Conclusion The BK-Plot provides a simple method to understand generalizability in randomized trials. Meta-analyses of randomized trials with a binary outcome that are based on DIF or RR, but not OR, will avoid bias from an unobserved covariate that does not interact with treatment in its effect on outcome.

Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors

DEFF Research Database (Denmark)

Artang, Ramin; Rome, Eric; Nielsen, Jørn Dalsgaard

2013-01-01

. To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization. We furthermore performed a secondary meta-analysis on atrial fibrillation stroke prevention...... to experience an MI than their counterparts treated with warfarin (285 of 23,333 vs 133 of 16,024, odds ratio 1.35, 95% confidence interval 1.10 to 1.66, p = 0.005). For secondary analysis, 8 studies (69,615 patients) were identified that compared warfarin with alternative anticoagulant including factor Xa...

Randomized Controlled Trials: The Most Powerful Tool In Modern ...

African Journals Online (AJOL)

Randomized controlled trial (RCT) can be said to be one of the simplest but most powerful tool of research. It is the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost effectiveness of a treatment. Through the randomization, bias will be avoided ...

Can ginger ameliorate chemotherapy-induced nausea? Protocol of a randomized double blind, placebo-controlled trial.

Science.gov (United States)

Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; Vitetta, Luis; McKavanagh, Daniel; Thomson, Damien; Sali, Avni; Isenring, Liz

2014-04-09

Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. In a double-blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

Science.gov (United States)

Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

2017-07-01

Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Randomized Trial of a Lifestyle Program in Obese Infertile Women

NARCIS (Netherlands)

Mutsaerts, Meike A. Q.; van Oers, Anne M.; Groen, Henk; Burggraaff, Jan M.; Kuchenbecker, Walter K. H.; Perquin, Denise A. M.; Koks, Carolien A. M.; van Golde, Ron; Kaaijk, Eugenie M.; Schierbeek, Jaap M.; Oosterhuis, Gerrit J. E.; Broekmans, Frank J.; Bemelmans, Wanda J. E.; Lambalk, Cornelis B.; Verberg, Marieke F. G.; van der Veen, Fulco; Klijn, Nicole F.; Mercelina, Patricia E. A. M.; van Kasteren, Yvonne M.; Nap, Annemiek W.; Brinkhuis, Egbert A.; Vogel, Niels E. A.; Mulder, Robert J. A. B.; Gondrie, Ed T. C. M.; de Bruin, Jan P.; Sikkema, J. Marko; de Greef, Mathieu H. G.; ter Bogt, Nancy C. W.; Land, Jolande A.; Mol, Ben W. J.; Hoek, Annemieke

2016-01-01

BACKGROUND Small lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. METHODS We randomly assigned infertile women with a body-mass index (the weight in kilograms

A randomized, controlled trial of oral propranolol in infantile hemangioma.

Science.gov (United States)

Léauté-Labrèze, Christine; Hoeger, Peter; Mazereeuw-Hautier, Juliette; Guibaud, Laurent; Baselga, Eulalia; Posiunas, Gintas; Phillips, Roderic J; Caceres, Hector; Lopez Gutierrez, Juan Carlos; Ballona, Rosalia; Friedlander, Sheila Fallon; Powell, Julie; Perek, Danuta; Metz, Brandie; Barbarot, Sebastien; Maruani, Annabel; Szalai, Zsuzsanna Zsofia; Krol, Alfons; Boccara, Olivia; Foelster-Holst, Regina; Febrer Bosch, Maria Isabel; Su, John; Buckova, Hana; Torrelo, Antonio; Cambazard, Frederic; Grantzow, Rainer; Wargon, Orli; Wyrzykowski, Dariusz; Roessler, Jochen; Bernabeu-Wittel, Jose; Valencia, Adriana M; Przewratil, Przemyslaw; Glick, Sharon; Pope, Elena; Birchall, Nicholas; Benjamin, Latanya; Mancini, Anthony J; Vabres, Pierre; Souteyrand, Pierre; Frieden, Ilona J; Berul, Charles I; Mehta, Cyrus R; Prey, Sorilla; Boralevi, Franck; Morgan, Caroline C; Heritier, Stephane; Delarue, Alain; Voisard, Jean-Jacques

2015-02-19

Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by

Improving Language Comprehension in Preschool Children with Language Difficulties: A Cluster Randomized Trial

Science.gov (United States)

Hagen, Åste M.; Melby-Lervåg, Monica; Lervåg, Arne

2017-01-01

Background: Children with language comprehension difficulties are at risk of educational and social problems, which in turn impede employment prospects in adulthood. However, few randomized trials have examined how such problems can be ameliorated during the preschool years. Methods: We conducted a cluster randomized trial in 148 preschool…

Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2 Years of a Randomized Controlled Trial

OpenAIRE

Tirosh, Amir; Golan, Rachel; Harman-Boehm, Ilana; Henkin, Yaakov; Schwarzfuchs, Dan; Rudich, Assaf; Kovsan, Julia; Fiedler, Georg M.; Blüher, Matthias; Stumvoll, Michael; Thiery, Joachim; Stampfer, Meir J.; Shai, Iris

2013-01-01

OBJECTIVE This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m2; mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine 0.05) across...

Perception of young adults with sickle cell disease or sickle cell trait about participation in the CHOICES randomized controlled trial.

Science.gov (United States)

Hershberger, Patricia E; Gallo, Agatha M; Molokie, Robert; Thompson, Alexis A; Suarez, Marie L; Yao, Yingwei; Wilkie, Diana J

2016-06-01

To gain an in-depth understanding of the perceptions of young adults with sickle cell disease and sickle cell trait about parenthood and participating in the CHOICES randomized controlled trial that used computer-based, educational programmes. In the USA, there is insufficient education to assure that all young adults with sickle cell disease or sickle cell trait understand genetic inheritance risks and reproductive options to make informed reproductive decisions. To address this educational need, we developed a computer-based, multimedia program (CHOICES) and reformatted usual care into a computer-based (e-Book) program. We then conducted a two-year randomized controlled trial that included a qualitative component that would deepen understanding of young adults' perceptions of parenthood and use of computer-based, educational programmes. A qualitative descriptive approach completed after a randomized controlled trial. Sixty-eight men and women of childbearing age participated in semi-structured interviews at the completion of the randomized controlled trial from 2012-2013. Thematic content analysis guided the qualitative description. Three main themes were identified: (1) increasing knowledge and new ways of thinking and behaving; (2) rethinking parenting plans; and (3) appraising the program design and delivery. Most participants reported increased knowledge and rethinking of their parenting plans and were supportive of computer-based learning. Some participants expressed difficulty in determining individual transmission risks. Participants perceived the computer programs as beneficial to their learning. Future development of an Internet-based educational programme is warranted, with emphasis on providing tailored education or memory boosters about individual transmission risks. © 2015 John Wiley & Sons Ltd.

The QUIT-PRIMO provider-patient Internet-delivered smoking cessation referral intervention: a cluster-randomized comparative effectiveness trial: study protocol

Directory of Open Access Journals (Sweden)

Ford Daniel E

2010-11-01

Full Text Available Abstract Background Although screening for tobacco use is increasing with electronic health records and standard protocols, other tobacco-control activities, such as referral of patients to cessation resources, is quite low. In the QUIT-PRIMO study, an online referral portal will allow providers to enter smokers' email addresses into the system. Upon returning home, the smokers will receive automated emails providing education about tobacco cessation and encouragement to use the patient smoking cessation website (with interactive tools, educational resources, motivational email messages, secure messaging with a tobacco treatment specialist, and online support group. Methods The informatics system will be evaluated in a comparative effectiveness trial of 160 community-based primary care practices, cluster-randomized at the practice level. In the QUIT-PRIMO intervention, patients will be provided a paper information-prescription referral and then "e-referred" to the system. In the comparison group, patients will receive only the paper-based information-prescription referral with the website address. Once patients go to the website, they are subsequently randomized within practices to either a standard patient smoking cessation website or an augmented version with access to a tobacco treatment specialist online, motivational emails, and an online support group. We will compare intervention and control practice participation (referral rates and patient participation (proportion referred who go to the website. We will then compare the effectiveness of the standard and augmented patient websites. Discussion Our goal is to evaluate an integrated informatics solution to increase access to web-delivered smoking cessation support. We will analyze the impact of this integrated system in terms of process (provider e-referral and patient login and patient outcomes (six-month smoking cessation. Trial Registration Web-delivered Provider Intervention for

Use of 'sham' radiotherapy in randomized clinical trials

International Nuclear Information System (INIS)

Schwarz, F.; Christie, D.

2008-01-01

The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used.

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...

Randomized clinical trial of laparoscopic versus open appendicectomy

DEFF Research Database (Denmark)

Pedersen, A G; Petersen, O B; Wara, P

2001-01-01

BACKGROUND: Laparoscopy in patients with a clinical suspicion of acute appendicitis has not gained wide acceptance, and its use remains controversial. METHODS: In a randomized controlled trial of laparoscopic versus open appendicectomy, 583 of 828 consecutive patients consented to participate...

Short and long-term safety and efficacy of polymer-free vs. durable polymer drug-eluting stents. A comprehensive meta-analysis of randomized trials including 6178 patients

NARCIS (Netherlands)

Navarese, E.P.; Kowalewski, M.; Cortese, B.; Kandzari, D.; Dias, S.; Wojakowski, W.; Buffon, A.; Lansky, A.; Angelini, P.; Torguson, R.; Kubica, J.; Kelm, M.; Boer, M.J. de; Waksman, R.; Suryapranata, H.

2014-01-01

BACKGROUND: The efficacy and safety of polymer-free drug-eluting stents (DESs) in clinical practice is currently subject of debate; randomized trials (RCTs) conducted so far provided conflicting results or were underpowered to definitively address this question; we aimed to investigate the efficacy

Integrated Optical Content Addressable Memories (CAM and Optical Random Access Memories (RAM for Ultra-Fast Address Look-Up Operations

Directory of Open Access Journals (Sweden)

Christos Vagionas

2017-07-01

Full Text Available Electronic Content Addressable Memories (CAM implement Address Look-Up (AL table functionalities of network routers; however, they typically operate in the MHz regime, turning AL into a critical network bottleneck. In this communication, we demonstrate the first steps towards developing optical CAM alternatives to enable a re-engineering of AL memories. Firstly, we report on the photonic integration of Semiconductor Optical Amplifier-Mach Zehnder Interferometer (SOA-MZI-based optical Flip-Flop and Random Access Memories on a monolithic InP platform, capable of storing the binary prefix-address data-bits and the outgoing port information for next hop routing, respectively. Subsequently the first optical Binary CAM cell (B-CAM is experimentally demonstrated, comprising an InP Flip-Flop and a SOA-MZI Exclusive OR (XOR gate for fast search operations through an XOR-based bit comparison, yielding an error-free 10 Gb/s operation. This is later extended via physical layer simulations in an optical Ternary-CAM (T-CAM cell and a 4-bit Matchline (ML configuration, supporting a third state of the “logical X” value towards wildcard bits of network subnet masks. The proposed functional CAM and Random Access Memories (RAM sub-circuits may facilitate light-based Address Look-Up tables supporting search operations at 10 Gb/s and beyond, paving the way towards minimizing the disparity with the frantic optical transmission linerates, and fast re-configurability through multiple simultaneous Wavelength Division Multiplexed (WDM memory access requests.

Asthma Self-Management Model: Randomized Controlled Trial

Science.gov (United States)

Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

2016-01-01

Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

The steps to health employee weight management randomized control trial: rationale, design and baseline characteristics.

Science.gov (United States)

Østbye, Truls; Stroo, Marissa; Brouwer, Rebecca J N; Peterson, Bercedis L; Eisenstein, Eric L; Fuemmeler, Bernard F; Joyner, Julie; Gulley, Libby; Dement, John M

2013-07-01

The workplace can be an important setting for addressing obesity. An increasing number of employers offer weight management programs. Present the design, rationale and baseline characteristics of the Steps to Health study (STH), a randomized trial to evaluate the effectiveness of two preexisting employee weight management programs offered at Duke University and Medical Center. 550 obese (BMI ≥30) employee volunteers were randomized 1:1 to two programs. Baseline data, collected between January 2011 and July 2012, included height/weight, accelerometry, workplace injuries, health care utilization, and questionnaires querying socio-cognitive factors, perceptions of health climate, physical activity, and dietary intake. In secondary analyses participants in the two programs will also be compared to a non-randomized observational control group of obese employees. At baseline, the mean age was 45 years, 83% were female, 41% white, and 53% black. Mean BMI was 37.2. Participants consumed a mean of 2.37 servings of fruits and vegetables per day (in the past week), participated in 11.5 min of moderate-to-vigorous physical activity, and spent 620 min being sedentary. STH addresses the need for evaluation of worksite interventions to promote healthy weight. In addition to having direct positive effects on workers' health, worksite programs have the potential to increase productivity and reduce health care costs. Copyright © 2013 Elsevier Inc. All rights reserved.

Baseline and follow-up characteristics of participants and nonparticipants in a randomized clinical trial of multifactorial fall prevention in Denmark

DEFF Research Database (Denmark)

Vind, Ane B; Andersen, Hanne E; Pedersen, Kirsten D

2009-01-01

outpatient department. PARTICIPANTS: One thousand one hundred five community-dwelling adults aged 65 and older who had sustained at least one injurious fall. MEASUREMENTS: Marital status, housing tenure, income, comorbidity, hospitalization, fractures, and drug use before invitation to participate......OBJECTIVES: To address the external validity of a trial of multifactorial fall prevention through an analysis of differences between participants and nonparticipants regarding socioeconomic and morbidity variables. DESIGN: Analysis of nonresponse in a randomized clinical trial. SETTING: Geriatric...... nonparticipants of a trial of multifactorial fall prevention differed significantly from participants in terms of socioeconomic and morbidity variables and were more likely to be hospitalized or die during 6 months of follow-up. Because of the differences between the two populations, it is questionable whether...

A random walk model for evaluating clinical trials involving serial observations.

Science.gov (United States)

Hopper, J L; Young, G P

1988-05-01

For clinical trials where the variable of interest is ordered and categorical (for example, disease severity, symptom scale), and where measurements are taken at intervals, it might be possible to achieve a greater discrimination between the efficacy of treatments by modelling each patient's progress as a stochastic process. The random walk is a simple, easily interpreted model that can be fitted by maximum likelihood using a maximization routine with inference based on standard likelihood theory. In general the model can allow for randomly censored data, incorporates measured prognostic factors, and inference is conditional on the (possibly non-random) allocation of patients. Tests of fit and of model assumptions are proposed, and application to two therapeutic trials of gastroenterological disorders are presented. The model gave measures of the rate of, and variability in, improvement for patients under different treatments. A small simulation study suggested that the model is more powerful than considering the difference between initial and final scores, even when applied to data generated by a mechanism other than the random walk model assumed in the analysis. It thus provides a useful additional statistical method for evaluating clinical trials.

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0268 TITLE: Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Eric Winer CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: OCTOBER 2017 TYPE OF REPORT: ANNUAL PREPARED FOR...CONTRACT NUMBER Randomized Trial of Asprin as Adjuvant Therapy for Node- Positive Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

A Data Management System Integrating Web-based Training and Randomized Trials: Requirements, Experiences and Recommendations.

Science.gov (United States)

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance of web-course-trained participants (intervention group) and printed-manual-trained participants (comparison group) to determine the effectiveness of the web-course in teaching CBT skills. A single DMS was needed to support all aspects of the study: web-course delivery and management, as well as randomized trial management. The authors briefly reviewed several other systems that were described as built either to handle randomized trials or to deliver and evaluate web-based training. However it was clear that these systems fell short of meeting our needs for simultaneous, coordinated management of the web-course and the randomized trial. New England Research Institute's (NERI) proprietary Advanced Data Entry and Protocol Tracking (ADEPT) system was coupled with the web-programmed course and customized for our purposes. This article highlights the requirements for a DMS that operates at the intersection of web-based course management systems and randomized clinical trial systems, and the extent to which the coupled, customized ADEPT satisfied those requirements. Recommendations are included for institutions and individuals considering conducting randomized trials and web-based training programs, and seeking a DMS that can meet similar requirements.

Evaluation of cluster-randomized trials on maternal and child health research in developing countries

DEFF Research Database (Denmark)

Handlos, Line Neerup; Chakraborty, Hrishikesh; Sen, Pranab Kumar

2009-01-01

To summarize and evaluate all publications including cluster-randomized trials used for maternal and child health research in developing countries during the last 10 years. METHODS: All cluster-randomized trials published between 1998 and 2008 were reviewed, and those that met our criteria...... for inclusion were evaluated further. The criteria for inclusion were that the trial should have been conducted in maternal and child health care in a developing country and that the conclusions should have been made on an individual level. Methods of accounting for clustering in design and analysis were......, and the trials generally improved in quality. CONCLUSIONS: Shortcomings exist in the sample-size calculations and in the analysis of cluster-randomized trials conducted during maternal and child health research in developing countries. Even though there has been improvement over time, further progress in the way...

Cost-effectiveness of peer-delivered interventions for cocaine and alcohol abuse among women: a randomized controlled trial.

Directory of Open Access Journals (Sweden)

Jennifer Prah Ruger

Full Text Available To determine whether the additional interventions to standard care are cost-effective in addressing cocaine and alcohol abuse at 4 months (4 M and 12 months (12 M from baseline.We conducted a cost-effectiveness analysis of a randomized controlled trial with three arms: (1 NIDA's Standard intervention (SI; (2 SI plus a Well Woman Exam (WWE; and, (3 SI, WWE, plus four Educational Sessions (4ES.To obtain an additional cocaine abstainer, WWE compared to SI cost $7,223 at 4 M and $3,611 at 12 M. Per additional alcohol abstainer, WWE compared to SI cost $3,611 and $7,223 at 4 M and 12 M, respectively. At 12 M, 4ES was dominated (more costly and less effective by WWE for abstinence outcomes.To our knowledge, this is the first cost-effectiveness analysis simultaneously examining cocaine and alcohol abuse in women. Depending on primary outcomes sought and priorities of policy makers, peer-delivered interventions can be a cost-effective way to address the needs of this growing, underserved population.ClinicalTrials.gov NCT01235091.

Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

Science.gov (United States)

NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

2017-08-01

Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

Objective and Subjective Measures of Simultaneous vs Sequential Bilateral Cochlear Implants in Adults A Randomized Clinical Trial : A Randomized Clinical Trial

NARCIS (Netherlands)

Kraaijenga, Véronique J C; Ramakers, Geerte G J; Smulders, Yvette E; van Zon, Alice; Stegeman, Inge; Smit, Adriana L; Stokroos, Robert J; Hendrice, Nadia; Free, Rolien H; Maat, Bert; Frijns, Johan H M; Briaire, Jeroen J; Mylanus, E A M; Huinck, Wendy J; Van Zanten, Gijsbert A; Grolman, Wilko

IMPORTANCE To date, no randomized clinical trial on the comparison between simultaneous and sequential bilateral cochlear implants (BiCIs) has been performed. OBJECTIVE To investigate the hearing capabilities and the self-reported benefits of simultaneous BiCIs compared with those of sequential

Saving and Empowering Young Lives in Europe (SEYLE: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Nemes Bogdan

2010-04-01

Full Text Available Abstract Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior, and, in most of those studies, the target populations were primarily adults, whereas few focused on adolescents. Essentially, there have been no randomized controlled studies comparing the efficacy, cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools. There is also a lack of information on whether suicide-preventive interventions can, in addition to preventing suicide, reduce risk behaviors and promote healthier ones as well as improve young people's mental health. The aim of the SEYLE project, which is funded by the European Union under the Seventh Framework Health Program, is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological database; testing, in a randomized controlled trial, three different suicide-preventive interventions; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors. Methods and design The study comprises 11,000 adolescents emitted from randomized schools in 11 European countries: Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the scientific coordinating center. Each country performs three active interventions and one minimal intervention as a control group. The active interventions include gatekeeper training (QPR, awareness training on mental health promotion for adolescents, and screening for at-risk adolescents by health professionals. Structured questionnaires are utilized at baseline, 3- and 12-month follow-ups in order to assess changes. Discussion Although it has been reported that

Saving and Empowering Young Lives in Europe (SEYLE): a randomized controlled trial

LENUS (Irish Health Repository)

Wasserman, Danuta

2010-04-13

Abstract Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior, and, in most of those studies, the target populations were primarily adults, whereas few focused on adolescents. Essentially, there have been no randomized controlled studies comparing the efficacy, cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools. There is also a lack of information on whether suicide-preventive interventions can, in addition to preventing suicide, reduce risk behaviors and promote healthier ones as well as improve young people\\'s mental health. The aim of the SEYLE project, which is funded by the European Union under the Seventh Framework Health Program, is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological database; testing, in a randomized controlled trial, three different suicide-preventive interventions; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors. Methods and design The study comprises 11,000 adolescents emitted from randomized schools in 11 European countries: Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the scientific coordinating center. Each country performs three active interventions and one minimal intervention as a control group. The active interventions include gatekeeper training (QPR), awareness training on mental health promotion for adolescents, and screening for at-risk adolescents by health professionals. Structured questionnaires are utilized at baseline, 3- and 12-month follow-ups in order to assess changes. Discussion Although it has been reported that suicide

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

Energy Technology Data Exchange (ETDEWEB)

Yamoah, Kosj [Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2015-11-15

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: In primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.

Trial sequential analyses of meta-analyses of complications in laparoscopic vs. small-incision cholecystectomy: more randomized patients are needed

DEFF Research Database (Denmark)

Keus, Frederik; Wetterslev, Jørn; Gluud, Christian

2010-01-01

Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small-incision ......Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small...

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.

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.

Effect of Providing Ankle-Foot Orthoses in Patients with Acute and Subacute Stroke: a Randomized Controlled Trial : A randomized controlled trial

NARCIS (Netherlands)

Nikamp-Simons, Corien D.M.; Buurke, Jaap H.; Van Der Palen, Job; Hermens, Hermie J.; Rietman, Johan S.; Ibánez, Jaime; Azorín, José María; Akay, Metin; Pons, José Luis

2017-01-01

Despite frequent application of ankle-foot orthoses (AFOs), little scientific evidence is available to guide AFO-provision early after stroke. A randomized controlled trial was conducted to study the effects of AFO-provision in (sub-) acute stroke patients. Primary aim: to study effects of the

A systematic review of randomized controlled trials using music therapy for children.

Science.gov (United States)

Mrázová, Marcela; Celec, Peter

2010-10-01

Music therapy is a promising approach widening the potential applications of psychotherapy. Music influences both, psychologic and physiologic parameters, and children are especially responsive to this form of therapy. Many aspects of its action mechanisms remain to be elucidated, underscoring the need for evidence-based medicine (EBM) for clinical use of music therapy. This review seeks to highlight some of the issues of music therapy research and to initiate a discussion about the need for international multicenter cooperation to bring scientifically sound evidence of the benefits of music therapy in pediatric patients. Scientific bibliographic databases were searched for randomized controlled trials on use of music therapy for children. Identified articles were evaluated according to criteria for scientific quality. Twenty-eight studies were identified. Most of the trials were biased by the number of participants, and some trials showed the need to improve design of control groups. Indeed, the novelty of this area of study has produced a large number of different studies (with variability in diagnoses, interventions, control groups, duration, and/or outcome parameters), and there is a need for a more homogeneous and systematic approach. Available studies highlight the need to address reproducibility issues. This analysis identifies the need for a subsequent series of clinical studies on the efficacy of music in the pediatric population, with more focus on eligibility criteria with respect to EBM and reproducibility.

Protocol for the Osteoporosis Choice trial. A pilot randomized trial of a decision aid in primary care practice

Directory of Open Access Journals (Sweden)

Tulledge-Scheitel Sidna M

2009-12-01

Full Text Available Abstract Background Bisphosphonates can reduce fracture risk in patients with osteoporosis, but many at-risk patients do not start or adhere to these medications. The aims of this study are to: (1 preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid (OSTEOPOROSIS CHOICE for postmenopausal women at risk for osteoporotic fractures; and (2 assess the feasibility and validity (i.e., absence of contamination of patient-level randomization (vs. cluster randomization in pilot trials of decision aid efficacy. Methods/Design This is a protocol for a parallel, 2-arm, randomized trial to compare an intervention group receiving OSTEOPOROSIS CHOICE to a control group receiving usual primary care. Postmenopausal women with bone mineral density T-scores of STEOPOROSIS CHOICE on five outcomes: (a patient knowledge regarding osteoporosis risk factors and treatment; (b quality of the decision-making process for both the patient and clinician; (c patient and clinician acceptability and satisfaction with the decision aid; (d rate of bisphosphonate use and adherence, and (e trial processes (e.g., ability to recruit participants, collect patient outcomes. To capture these outcomes, we will use patient and clinician surveys following each visit and video recordings of the clinical encounters. These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients (i.e., contamination. Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months. Discussion This pilot trial will provide evidence of feasibility, validity of patient randomization, and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures. The results will inform

Randomized controlled trials in evidence-based mental health care: getting the right answer to the right question.

Science.gov (United States)

Essock, Susan M; Drake, Robert E; Frank, Richard G; McGuire, Thomas G

2003-01-01

The purpose of clinical research is to answer this question: Would a new treatment, when added to the existing range of treatment options available in practice, help patients? Randomized controlled trials (RCTs)--in particular, double-blind RCTs--have important methodological advantages over observational studies for addressing this question. These advantages, however, come at a price. RCTs compare treatments using a particular allocation rule for assigning patients to treatments (random assignment) that does not mimic real-world practice. "Favorable" results from an RCT indicating that a new treatment is superior to existing treatments are neither necessary nor sufficient for establishing a "yes" answer to the question posed above. Modeled on an experimental design, RCTs are expensive in time and money and must compare simple differences in treatments. Findings have a high internal validity but may not address the needs of the field, particularly where treatment is complex and rapidly evolving. Design of clinical research needs to take account of the way treatments are allocated in actual practice and include flexible designs to answer important questions most effectively.

Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Bouwense Stefan A

2012-11-01

Full Text Available Abstract Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy, and uncomplicated biliary colics occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early

[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

Science.gov (United States)

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles

Cluster Randomized Controlled Trial: Clinical and Cost-Effectiveness of a System of Longer-Term Stroke Care.

Science.gov (United States)

Forster, Anne; Young, John; Chapman, Katie; Nixon, Jane; Patel, Anita; Holloway, Ivana; Mellish, Kirste; Anwar, Shamaila; Breen, Rachel; Knapp, Martin; Murray, Jenni; Farrin, Amanda

2015-08-01

We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was -0.6 points (95% confidence interval, -1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. © 2015 Bradford Teaching Hospitals NHS Foundation Trust.

Cognitive-Behavioral Family Treatment for Suicide Attempt Prevention: A Randomized Controlled Trial.

Science.gov (United States)

Asarnow, Joan Rosenbaum; Hughes, Jennifer L; Babeva, Kalina N; Sugar, Catherine A

2017-06-01

Suicide is a leading cause of death. New data indicate alarming increases in suicide death rates, yet no treatments with replicated efficacy or effectiveness exist for youths with self-harm presentations, a high-risk group for both fatal and nonfatal suicide attempts. We addressed this gap by evaluating Safe Alternatives for Teens and Youths (SAFETY), a cognitive-behavioral, dialectical behavior therapy-informed family treatment designed to promote safety. Randomized controlled trial for adolescents (12-18 years of age) with recent (past 3 months) suicide attempts or other self-harm. Youth were randomized either to SAFETY or to treatment as usual enhanced by parent education and support accessing community treatment (E-TAU). Outcomes were evaluated at baseline, 3 months, or end of treatment period, and were followed up through 6 to 12 months. The primary outcome was youth-reported incident suicide attempts through the 3-month follow-up. Survival analyses indicated a significantly higher probability of survival without a suicide attempt by the 3-month follow-up point among SAFETY youths (cumulative estimated probability of survival without suicide attempt = 1.00, standard error = 0), compared to E-TAU youths (cumulative estimated probability of survival without suicide attempt = 0.67, standard error = 0.14; z = 2.45, p = .02, number needed to treat = 3) and for the overall survival curves (Wilcoxon χ 2 1  = 5.81, p = .02). Sensitivity analyses using parent report when youth report was unavailable and conservative assumptions regarding missing data yielded similar results for 3-month outcomes. Results support the efficacy of SAFETY for preventing suicide attempts in adolescents presenting with recent self-harm. This is the second randomized trial to demonstrate that treatment including cognitive-behavioral and family components can provide some protection from suicide attempt risk in these high-risk youths. Clinical trial registration information

The effect of ginseng (the genus panax on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials.

Directory of Open Access Journals (Sweden)

Esra' Shishtar

Full Text Available Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.MEDLINE, EMBASE, CINAHL and the Cochrane Library (through July 3, 2013.Randomized controlled trials ≥30 days assessing the glycemic effects of ginseng in people with and without diabetes.Relevant data were extracted by 2 independent reviewers. Discrepancies were resolved by consensus. The Heyland Methodological Quality Score and the Cochrane risk of bias tool were used to assess study quality and risk of bias respectively.Sixteen trials were included, in which 16 fasting blood glucose (n = 770, 10 fasting plasma insulin (n = 349, 9 glycated hemoglobin (n = 264, and 7 homeostasis model assessment of insulin resistance (n = 305 comparisons were reported. Ginseng significantly reduced fasting blood glucose compared to control (MD =  -0.31 mmol/L [95% CI: -0.59 to -0.03], P = 0.03. Although there was no significant effect on fasting plasma insulin, glycated hemoglobin, or homeostasis model assessment of insulin resistance, a priori subgroup analyses did show significant reductions in glycated hemoglobin in parallel compared to crossover trials (MD = 0.22% [95%CI: 0.06 to 0.37], P = 0.01.Most trials were of short duration (67% trials<12wks, and included participants with a relatively good glycemic control (median HbA1c non-diabetes = 5.4% [2 trials]; median HbA1c diabetes = 7.1% [7 trials].Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. In order to address the uncertainty in our effect estimates and provide better assessments of ginseng's anti

Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial.

Science.gov (United States)

Maruani, Annabel; Boutron, Isabelle; Baron, Gabriel; Ravaud, Philippe

2014-09-19

To evaluate the impact of sending an email to responsible parties of completed trials that do not comply with the Food and Drug Administration Amendments Act 801 legislation, to remind them of the legal requirement to post results. Cohort embedded pragmatic randomized controlled trial. Trials registered on ClinicalTrials.gov. 190 out of 379 trials randomly selected by computer generated randomization list to receive the intervention (personalized emails structured as a survey and sent by one of us to responsible parties of the trials, indirectly reminding them of the legal requirement and potential penalties for non-compliance). The primary outcome was the proportion of results posted on ClinicalTrials.gov at three months. The secondary outcome was the proportion posted at six months. In a second step, two assessors blinded to the intervention group collected the date of the first results being received on ClinicalTrials.gov. A post hoc sensitivity analysis excluding trials wrongly included was performed. Among 379 trials included, 190 were randomized to receive the email intervention. The rate of posting of results did not differ at three months between trials with or without the intervention: 36/190 (19%) v 24/189 (13%), respectively (relative risk 1.5, 95% confidence interval 0.9 to 2.4, P=0.096) but did at six months: 46/190 (24%) v 27/189 (14%), 1.7, 1.1 to 2.6, P=0.014. In the sensitivity analysis, which excluded 48/379 trials (13%), 26/190 (14%) and 22/189 (12%), respectively, results were significant at three months (relative risk 5.1, 1.1 to 22.9, P=0.02) and at six months (4.1, 1.3 to 10.6, P=0.001). Sending email reminders about the FDA's legal requirement to post results at ClinicalTrials.gov improved significantly the posting rate at six months but not at three months.Trial registration ClinicalTrials.gov NCT01658254. © Maruani et al 2014.

Implementation of the Participatory Approach for Supervisors to Increase Self-Efficacy in Addressing Risk of Sick Leave of Employees : Results of a Cluster-Randomized Controlled Trial

NARCIS (Netherlands)

Ketelaar, S. M.; Schaafsma, F. G.; Geldof, M. F.; Kraaijeveld, R. A.; Boot, C. R. L.; Shaw, W. S.; Bultmann, U.; Anema, J. R.

Purpose To study the effectiveness of a multifaceted strategy to implement the participatory approach (PA) for supervisors to increase their self-efficacy in addressing risk of sick leave of employees. Methods Supervisors from three organizations were invited to participate. Randomization was

Pancreatic enzyme supplementation after gastrectomy for gastric cancer: a randomized controlled trial.

Science.gov (United States)

Catarci, Marco; Berlanda, Manuele; Grassi, Giovanni Battista; Masedu, Francesco; Guadagni, Stefano

2018-05-01

Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out. After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI). BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy. PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.

Review of Randomized Controlled Trials of Massage in Preterm Infants

Directory of Open Access Journals (Sweden)

Anna-Kaisa Niemi

2017-04-01

Full Text Available Preterm birth affects about 10% of infants born in the United States. Massage therapy is being used in some neonatal intensive care units for its potential beneficial effects on preterm infants. This article reviews published randomized controlled trials on the effects of massage in preterm infants. Most studies evaluating the effect of massage in weight gain in premature infants suggest a positive effect on weight gain. Increase in vagal tone has been reported in infants who receive massage and has been suggested as a possible mechanism for improved weight gain. More studies are needed on the underlying mechanisms of the effects of massage therapy on weight gain in preterm infants. While some trials suggest improvements in developmental scores, decreased stress behavior, positive effects on immune system, improved pain tolerance and earlier discharge from the hospital, the number of such studies is small and further evidence is needed. Further studies, including randomized controlled trials, are needed on the effects of massage in preterm infants.

Automatic generation of randomized trial sequences for priming experiments.

Science.gov (United States)

Ihrke, Matthias; Behrendt, Jörg

2011-01-01

In most psychological experiments, a randomized presentation of successive displays is crucial for the validity of the results. For some paradigms, this is not a trivial issue because trials are interdependent, e.g., priming paradigms. We present a software that automatically generates optimized trial sequences for (negative-) priming experiments. Our implementation is based on an optimization heuristic known as genetic algorithms that allows for an intuitive interpretation due to its similarity to natural evolution. The program features a graphical user interface that allows the user to generate trial sequences and to interactively improve them. The software is based on freely available software and is released under the GNU General Public License.

A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety ...

African Journals Online (AJOL)

A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of Lornoxicam with Diclofenac Sodium in Patients of Osteoarthritis Knee. ... All patients were assessed with visual analogue scale and 100 meter walking test before starting of therapy, at 15 days and at 1, 2 and 3 months of therapy.

Randomized trial of BCG vaccination at birth to low-birth-weight children

DEFF Research Database (Denmark)

Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik

2011-01-01

Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.......Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

Alzheimer’s disease multiple intervention trial (ADMIT: study protocol for a randomized controlled clinical trial

Directory of Open Access Journals (Sweden)

Callahan Christopher M

2012-06-01

Full Text Available Abstract Background Given the current lack of disease-modifying therapies, it is important to explore new models of longitudinal care for older adults with dementia that focus on improving quality of life and delaying functional decline. In a previous clinical trial, we demonstrated that collaborative care for Alzheimer’s disease reduces patients’ neuropsychiatric symptoms as well as caregiver stress. However, these improvements in quality of life were not associated with delays in subjects’ functional decline. Trial design Parallel randomized controlled clinical trial with 1:1 allocation. Participants A total of 180 community-dwelling patients aged ≥45 years who are diagnosed with possible or probable Alzheimer’s disease; subjects must also have a caregiver willing to participate in the study and be willing to accept home visits. Subjects and their caregivers are enrolled from the primary care and geriatric medicine practices of an urban public health system serving Indianapolis, Indiana, USA. Interventions All patients receive best practices primary care including collaborative care by a dementia care manager over two years; this best practices primary care program represents the local adaptation and implementation of our prior collaborative care intervention in the urban public health system. Intervention patients also receive in-home occupational therapy delivered in twenty-four sessions over two years in addition to best practices primary care. The focus of the occupational therapy intervention is delaying functional decline and helping both subjects and caregivers adapt to functional impairments. The in-home sessions are tailored to the specific needs and goals of each patient-caregiver dyad; these needs are expected to change over the course of the study. Objective To determine whether best practices primary care plus home-based occupational therapy delays functional decline among patients with Alzheimer’s disease compared

Financial management of a large multisite randomized clinical trial.

Science.gov (United States)

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants

Directory of Open Access Journals (Sweden)

Dunkley David

2008-09-01

Full Text Available Abstract Background Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants. Methods and design Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals, and are randomly assigned to the experimental (Cues intervention or to an attention control (Care condition. The Cues intervention teaches mothers to attend to their own physiological, cognitive, and emotional cues that signal anxiety and worry, and to use cognitive-behavioural strategies to reduce distress. Mothers are also taught to understand infant cues and to respond sensitively to those cues. Mothers in the Care group receive general information about infant care. Both groups have 6 contacts with a trained intervener; 5 of the 6 sessions take place during the infant's hospitalization, and the sixth contact occurs after discharge, in the participant mother's home. The primary outcome is maternal symptoms of anxiety, assessed via self-report questionnaire immediately post-intervention. Secondary outcomes include maternal sensitive behaviour, maternal symptoms of posttraumatic stress, and infant development at 6 months corrected age. Discussion The Cues and Care trial will

The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants

Science.gov (United States)

Zelkowitz, Phyllis; Feeley, Nancy; Shrier, Ian; Stremler, Robyn; Westreich, Ruta; Dunkley, David; Steele, Russell; Rosberger, Zeev; Lefebvre, Francine; Papageorgiou, Apostolos

2008-01-01

Background Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues) in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants. Methods and design Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals, and are randomly assigned to the experimental (Cues) intervention or to an attention control (Care) condition. The Cues intervention teaches mothers to attend to their own physiological, cognitive, and emotional cues that signal anxiety and worry, and to use cognitive-behavioural strategies to reduce distress. Mothers are also taught to understand infant cues and to respond sensitively to those cues. Mothers in the Care group receive general information about infant care. Both groups have 6 contacts with a trained intervener; 5 of the 6 sessions take place during the infant's hospitalization, and the sixth contact occurs after discharge, in the participant mother's home. The primary outcome is maternal symptoms of anxiety, assessed via self-report questionnaire immediately post-intervention. Secondary outcomes include maternal sensitive behaviour, maternal symptoms of posttraumatic stress, and infant development at 6 months corrected age. Discussion The Cues and Care trial will provide important information

Did you get any help? A post-hoc secondary analysis of a randomized controlled trial of psychoeducation for patients with antisocial personality disorder in outpatient substance abuse treatment programs

OpenAIRE

Thylstrup, Birgitte; Schr?der, Sidsel; Fridell, Mats; Hesse, Morten

2017-01-01

Background People in treatment for substance use disorder commonly have comorbid personality disorders, including antisocial personality disorder. Little is known about treatments that specifically address comorbid antisocial personality disorder. Methods Self-rated help received for antisocial personality disorder was assessed during follow-ups at 3, 9 and 15 months post-randomization of a randomized trial of psychoeducation for people with comorbid substance use and antisocial personality d...

Randomized, Controlled Trial of CBT Training for PTSD Providers

Science.gov (United States)

2015-10-01

PI, program manager, and two research assistants will guide the mixed-method coding, analysis, and synthesis of the three consultation data sources...A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine , and pill placebo in the treatment of

Randomized controlled trials in dentistry: common pitfalls and how to avoid them.

Science.gov (United States)

Fleming, Padhraig S; Lynch, Christopher D; Pandis, Nikolaos

2014-08-01

Clinical trials are used to appraise the effectiveness of clinical interventions throughout medicine and dentistry. Randomized controlled trials (RCTs) are established as the optimal primary design and are published with increasing frequency within the biomedical sciences, including dentistry. This review outlines common pitfalls associated with the conduct of randomized controlled trials in dentistry. Common failings in RCT design leading to various types of bias including selection, performance, detection and attrition bias are discussed in this review. Moreover, methods of minimizing and eliminating bias are presented to ensure that maximal benefit is derived from RCTs within dentistry. Well-designed RCTs have both upstream and downstream uses acting as a template for development and populating systematic reviews to permit more precise estimates of treatment efficacy and effectiveness. However, there is increasing awareness of waste in clinical research, whereby resource-intensive studies fail to provide a commensurate level of scientific evidence. Waste may stem either from inappropriate design or from inadequate reporting of RCTs; the importance of robust conduct of RCTs within dentistry is clear. Optimal reporting of randomized controlled trials within dentistry is necessary to ensure that trials are reliable and valid. Common shortcomings leading to important forms or bias are discussed and approaches to minimizing these issues are outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Health education for microcredit clients in Peru: a randomized controlled trial.

Science.gov (United States)

Hamad, Rita; Fernald, Lia Ch; Karlan, Dean S

2011-01-24

Poverty, lack of female empowerment, and lack of education are major risk factors for childhood illness worldwide. Microcredit programs, by offering small loans to poor individuals, attempt to address the first two of these risk factors, poverty and gender disparity. They provide clients, usually women, with a means to invest in their businesses and support their families. This study investigates the health effects of also addressing the remaining risk factor, lack of knowledge about important health issues, through randomization of members of a microcredit organization to receive a health education module based on the World Health Organization's Integrated Management of Childhood Illness (IMCI) community intervention. Baseline data were collected in February 2007 from clients of a microcredit organization in Pucallpa, Peru (n = 1,855) and their children (n = 598). Loan groups, consisting of 15 to 20 clients, were then randomly assigned to receive a health education intervention involving eight monthly 30-minute sessions given by the organization's loan officers at monthly loan group meetings. In February 2008, follow-up data were collected, and included assessments of sociodemographic information, knowledge of child health issues, and child health status (including child height, weight, and blood hemoglobin levels). To explore the effects of treatment (i.e., participation in the health education sessions) on the key outcome variables, multivariate regressions were implemented using ordinary least squares. Individuals in the IMCI treatment arm demonstrated more knowledge about a variety of issues related to child health, but there were no changes in anthropometric measures or reported child health status. Microcredit clients randomized to an IMCI educational intervention showed greater knowledge about child health, but no differences in child health outcomes compared to controls. These results imply that the intervention did not have sufficient intensity to change

Music intervention during daily weaning trials-A 6 day prospective randomized crossover trial.

Science.gov (United States)

Liang, Zhan; Ren, Dianxu; Choi, JiYeon; Happ, Mary Beth; Hravnak, Marylyn; Hoffman, Leslie A

2016-12-01

To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation. Using a crossover repeated measures design, patients were randomized to music vs no music on the first intervention day. Provision of music was alternated for 6 days, resulting in 3 music and 3 no music days. During weaning trials on music days, data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music (total 90min). On no music days, data were collected for 90min. Outcome measures were heart rate (HR), respiratory rate (RR), oxygen saturation (SpO 2 ), blood pressure (BP), dyspnea and anxiety assessed with a visual analog scale (VAS-D, VAS-A) and weaning duration (meanh per day on music and non-music days). Of 31 patients randomized, 23 completed the 6-day intervention. When comparisons were made between the 3 music and 3 no music days, there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days (pmusic days (pmusic during daily weaning trials is a simple, low-cost, potentially beneficial intervention for patients on prolonged mechanical ventilation. Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomized Clinical Trial of Interceptive and Comprehensive Orthodontics

Science.gov (United States)

King, G.J.; Spiekerman, C.F.; Greenlee, G.M.; Huang, G.J.

2012-01-01

Focusing public insurance programs on interceptive orthodontics (IO) may increase access for low-income children. This report presents outcomes from a randomized clinical trial (RCT) comparing IO with comprehensive orthodontics (CO) in Medicaid patients. One hundred seventy pre-adolescents with Medicaid-eligible malocclusions were randomized to IO (n = 86) followed by observation (OBS) or OBS followed by CO (n = 84). One hundred thirty-four completed the trial. Models at pre-treatment (baseline) and following ≤ 2 years of intervention and 2 years of OBS (48 mos) were scored by calibrated examiners using the Peer Assessment Rating (PAR) and Index of Complexity, Outcome and Need (ICON). Overall outcomes and clinically meaningful categorical ICON data on need/acceptability, complexity, and improvement were compared. At baseline, groups were balanced by age, gender, ethnicity, and PAR/ICON scores. Most were minorities. Most (77%) were rated as difficult-to-very difficult. Scores improved significantly for both groups, but CO more than IO (PAR, 18.6 [95%CI 15.1, 22.1] vs.10.1 [95%CI 6.7, 13.4]; ICON, 44.8 [95% CI 39.7, 49.9] vs. 35.2 [95%CI 29.7, 40.6], respectively). On average, IO is effective at reducing malocclusions in Medicaid patients, but less than CO. (ClinicalTrials.gov number CT00067379) PMID:22699670

External validity of randomized controlled trials in older adults, a systematic review.

Directory of Open Access Journals (Sweden)

Floor J van Deudekom

Full Text Available To critically assess the external validity of randomized controlled trials (RCTs it is important to know what older adults have been enrolled in the trials. The aim of this systematic review is to study what proportion of trials specifically designed for older patients report on somatic status, physical and mental functioning, social environment and frailty in the patient characteristics.PubMed was searched for articles published in 2012 and only RCTs were included. Articles were further excluded if not conducted with humans or only secondary analyses were reported. A random sample of 10% was drawn. The current review analyzed this random sample and further selected trials when the reported mean age was ≥ 60 years. We extracted geriatric assessments from the population descriptives or the in- and exclusion criteria.In total 1396 trials were analyzed and 300 trials included. The median of the reported mean age was 66 (IQR 63-70 and the median percentage of men in the trials was 60 (IQR 45-72. In 34% of the RCTs specifically designed for older patients somatic status, physical and mental functioning, social environment or frailty were reported in the population descriptives or the in- and exclusion criteria. Physical and mental functioning was reported most frequently (22% and 14%. When selecting RCTs on a mean age of 70 or 80 years the report of geriatric assessments in the patient characteristics was 46% and 85% respectively but represent only 5% and 1% of the trials.Somatic status, physical and mental functioning, social environment and frailty are underreported even in RCTs specifically designed for older patients published in 2012. Therefore, it is unclear for clinicians to which older patients the results can be applied. We recommend systematic to transparently report these relevant characteristics of older participants included in RCTs.

Canadian Optically-guided approach for Oral Lesions Surgical (COOLS) trial: study protocol for a randomized controlled trial

International Nuclear Information System (INIS)

Poh, Catherine F; Durham, J Scott; Brasher, Penelope M; Anderson, Donald W; Berean, Kenneth W; MacAulay, Calum E; Lee, J Jack; Rosin, Miriam P

2011-01-01

Oral cancer is a major health problem worldwide. The 5-year survival rate ranges from 30-60%, and has remained unchanged in the past few decades. This is mainly due to late diagnosis and high recurrence of the disease. Of the patients who receive treatment, up to one third suffer from a recurrence or a second primary tumor. It is apparent that one major cause of disease recurrence is clinically unrecognized field changes which extend beyond the visible tumor boundary. We have previously developed an approach using fluorescence visualization (FV) technology to improve the recognition of the field at risk surrounding a visible oral cancer that needs to be removed and preliminary results have shown a significant reduction in recurrence rates. This paper describes the study design of a randomized, multi-centre, double blind, controlled surgical trial, the COOLS trial. Nine institutions across Canada will recruit a total of 400 patients with oral severe dysplasia or carcinoma in situ (N = 160) and invasive squamous cell carcinoma (N = 240). Patients will be stratified by participating institution and histology grade and randomized equally into FV-guided surgery (experimental arm) or white light-guided surgery (control arm). The primary endpoint is a composite of recurrence at or 1 cm within the previous surgery site with 1) the same or higher grade histology compared to the initial diagnosis (i.e., the diagnosis used for randomization); or 2) further treatment due to the presence of severe dysplasia or higher degree of change at follow-up. This is the first randomized, multi-centre trial to validate the effectiveness of the FV-guided surgery. In this paper we described the strategies, novelty, and challenges of this unique trial involving a surgical approach guided by the FV technology. The success of the trial requires training, coordination, and quality assurance across multiple sites within Canada. The COOLS trial, an example of translational research, may result in

A Data Management System Integrating Web-Based Training and Randomized Trials

Science.gov (United States)

Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D.

2011-01-01

This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance…

Mobile electronic versus paper case report forms in clinical trials: a randomized controlled trial.

Science.gov (United States)

Fleischmann, Robert; Decker, Anne-Marie; Kraft, Antje; Mai, Knut; Schmidt, Sein

2017-12-01

Regulations, study design complexity and amounts of collected and shared data in clinical trials render efficient data handling procedures inevitable. Recent research suggests that electronic data capture can be key in this context but evidence is insufficient. This randomized controlled parallel group study tested the hypothesis that time efficiency is superior when electronic (eCRF) instead of paper case report forms (pCRF) are used for data collection. We additionally investigated predictors of time saving effects and data integrity. This study was conducted on top of a clinical weight loss trial performed at a clinical research facility over six months. All study nurses and patients participating in the clinical trial were eligible to participate and randomly allocated to enter cross-sectional data obtained during routine visits either through pCRF or eCRF. A balanced randomization list was generated before enrolment commenced. 90 and 30 records were gathered for the time that 27 patients and 2 study nurses required to report 2025 and 2037 field values, respectively. The primary hypothesis, that eCRF use is faster than pCRF use, was tested by a two-tailed t-test. Analysis of variance and covariance were used to evaluate predictors of entry performance. Data integrity was evaluated by descriptive statistics. All randomized patients were included in the study (eCRF group n = 13, pCRF group n = 14). eCRF, as compared to pCRF, data collection was associated with significant time savings  across all conditions (8.29 ± 5.15 min vs. 10.54 ± 6.98 min, p = .047). This effect was not defined by participant type, i.e. patients or study nurses (F (1,112)  = .15, p = .699), CRF length (F (2,112)  = .49, p = .609) or patient age (Beta = .09, p = .534). Additional 5.16 ± 2.83 min per CRF were saved with eCRFs due to data transcription redundancy when patients answered questionnaires directly in eCRFs. Data integrity was

OARSI Clinical Trials Recommendations

DEFF Research Database (Denmark)

Katz, J N; Losina, E; Lohmander, L S

2015-01-01

To highlight methodological challenges in the design and conduct of randomized trials of surgical interventions and to propose strategies for addressing these challenges. This paper focuses on three broad areas: enrollment; intervention; and assessment including implications for analysis. For eac...

Behavioral insights and business taxation: Evidence from two randomized controlled trials

OpenAIRE

Biddle, Nicholas; Fels, Katja; Sinning, Mathias

2017-01-01

This paper presents the findings of two Randomized Controlled Trials (RCTs) that were conducted in collaboration with the Australian Taxation Office (ATO). The first trial tests the effect of changes to letters (timing, social norms, color, and provision of information about charitable donations) on response rates of businesses, the timing of payments and the amount of tax debt payments. The second trial consists of two parts. The first part aims to raise awareness of the relevance of tax deb...

Promoting healthful family meals to prevent obesity: HOME Plus, a randomized controlled trial

OpenAIRE

Fulkerson, Jayne A.; Friend, Sarah; Flattum, Colleen; Horning, Melissa; Draxten, Michelle; Neumark-Sztainer, Dianne; Gurvich, Olga; Story, Mary; Garwick, Ann; Kubik, Martha Y.

2015-01-01

Background Family meal frequency has been shown to be strongly associated with better dietary intake; however, associations with weight status have been mixed. Family meals-focused randomized controlled trials with weight outcomes have not been previously conducted. Therefore, this study purpose was to describe weight-related outcomes of the HOME Plus study, the first family meals-focused randomized controlled trial to prevent excess weight gain among youth. Methods Families (n?=?160 8-12-yea...

Considerations for preparing a randomized population health intervention trial: lessons from a South African–Canadian partnership to improve the health of health workers

Directory of Open Access Journals (Sweden)

Annalee Yassi

2014-05-01

Full Text Available Background: Community-based cluster-randomized controlled trials (RCTs are increasingly being conducted to address pressing global health concerns. Preparations for clinical trials are well-described, as are the steps for multi-component health service trials. However, guidance is lacking for addressing the ethical and logistic challenges in (cluster RCTs of population health interventions in low- and middle-income countries. Objective: We aimed to identify the factors that population health researchers must explicitly consider when planning RCTs within North–South partnerships. Design: We reviewed our experiences and identified key ethical and logistic issues encountered during the pre-trial phase of a recently implemented RCT. This trial aimed to improve tuberculosis (TB and Human Immunodeficiency Virus (HIV prevention and care for health workers by enhancing workplace assessment capability, addressing concerns about confidentiality and stigma, and providing onsite counseling, testing, and treatment. An iterative framework was used to synthesize this analysis with lessons taken from other studies. Results: The checklist of critical factors was grouped into eight categories: 1 Building trust and shared ownership; 2 Conducting feasibility studies throughout the process; 3 Building capacity; 4 Creating an appropriate information system; 5 Conducting pilot studies; 6 Securing stakeholder support, with a view to scale-up; 7 Continuously refining methodological rigor; and 8 Explicitly addressing all ethical issues both at the start and continuously as they arise. Conclusion: Researchers should allow for the significant investment of time and resources required for successful implementation of population health RCTs within North–South collaborations, recognize the iterative nature of the process, and be prepared to revise protocols as challenges emerge.

Circle of Security–Parenting: A randomized controlled trial in Head Start

Science.gov (United States)

CASSIDY, JUDE; BRETT, BONNIE E.; GROSS, JACQUELYN T.; STERN, JESSICA A.; MARTIN, DAVID R.; MOHR, JONATHAN J.; WOODHOUSE, SUSAN S.

2017-01-01

Although evidence shows that attachment insecurity and disorganization increase risk for the development of psychopathology (Fearon, Bakermans-Kranenburg, van IJzendoorn, Lapsley, & Roisman, 2010; Groh, Roisman, van IJzendoorn, Bakermans-Kranenburg, & Fearon, 2012), implementation challenges have precluded dissemination of attachment interventions on the broad scale at which they are needed. The Circle of Security–Parenting Intervention (COS-P; Cooper, Hoffman, & Powell, 2009), designed with broad implementation in mind, addresses this gap by training community service providers to use a manualized, video-based program to help caregivers provide a secure base and a safe haven for their children. The present study is a randomized controlled trial of COS-P in a low-income sample of Head Start enrolled children and their mothers. Mothers (N = 141; 75 intervention, 66 waitlist control) completed a baseline assessment and returned with their children after the 10-week intervention for the outcome assessment, which included the Strange Situation. Intent to treat analyses revealed a main effect for maternal response to child distress, with mothers assigned to COS-P reporting fewer unsupportive (but not more supportive) responses to distress than control group mothers, and a main effect for one dimension of child executive functioning (inhibitory control but not cognitive flexibility when maternal age and marital status were controlled), with intervention group children showing greater control. There were, however, no main effects of intervention for child attachment or behavior problems. Exploratory follow-up analyses suggested intervention effects were moderated by maternal attachment style or depressive symptoms, with moderated intervention effects emerging for child attachment security and disorganization, but not avoidance; for inhibitory control but not cognitive flexibility; and for child internalizing but not externalizing behavior problems. This initial

Circle of Security-Parenting: A randomized controlled trial in Head Start.

Science.gov (United States)

Cassidy, Jude; Brett, Bonnie E; Gross, Jacquelyn T; Stern, Jessica A; Martin, David R; Mohr, Jonathan J; Woodhouse, Susan S

2017-05-01

Although evidence shows that attachment insecurity and disorganization increase risk for the development of psychopathology (Fearon, Bakermans-Kranenburg, van IJzendoorn, Lapsley, & Roisman, 2010; Groh, Roisman, van IJzendoorn, Bakermans-Kranenburg, & Fearon, 2012), implementation challenges have precluded dissemination of attachment interventions on the broad scale at which they are needed. The Circle of Security-Parenting Intervention (COS-P; Cooper, Hoffman, & Powell, 2009), designed with broad implementation in mind, addresses this gap by training community service providers to use a manualized, video-based program to help caregivers provide a secure base and a safe haven for their children. The present study is a randomized controlled trial of COS-P in a low-income sample of Head Start enrolled children and their mothers. Mothers (N = 141; 75 intervention, 66 waitlist control) completed a baseline assessment and returned with their children after the 10-week intervention for the outcome assessment, which included the Strange Situation. Intent to treat analyses revealed a main effect for maternal response to child distress, with mothers assigned to COS-P reporting fewer unsupportive (but not more supportive) responses to distress than control group mothers, and a main effect for one dimension of child executive functioning (inhibitory control but not cognitive flexibility when maternal age and marital status were controlled), with intervention group children showing greater control. There were, however, no main effects of intervention for child attachment or behavior problems. Exploratory follow-up analyses suggested intervention effects were moderated by maternal attachment style or depressive symptoms, with moderated intervention effects emerging for child attachment security and disorganization, but not avoidance; for inhibitory control but not cognitive flexibility; and for child internalizing but not externalizing behavior problems. This initial randomized

Rehabilitation for improved cognition in patients with stress-related exhaustion disorder: RECO - a randomized clinical trial.

Science.gov (United States)

Malmberg Gavelin, Hanna; Eskilsson, Therese; Boraxbekk, Carl-Johan; Josefsson, Maria; Stigsdotter Neely, Anna; Slunga Järvholm, Lisbeth

2018-04-25

Stress-related exhaustion has been associated with selective and enduring cognitive impairments. However, little is known about how to address cognitive deficits in stress rehabilitation and how this influences stress recovery over time. The aim of this open-label, parallel randomized controlled trial (ClinicalTrials.gov: NCT03073772) was to investigate the long-term effects of 12 weeks cognitive or aerobic training on cognitive function, psychological health, and work ability for patients diagnosed with exhaustion disorder (ED). One-hundred-and-thirty-two patients (111 women) participating in multimodal stress rehabilitation were randomized to receive additional cognitive training (n = 44), additional aerobic training (n = 47), or no additional training (n = 41). Treatment effects were assessed before, immediately after and one-year post intervention. The primary outcome was global cognitive function. Secondary outcomes included domain-specific cognition, self-reported burnout, depression, anxiety, fatigue and work ability, aerobic capacity, and sick-leave levels. Intention-to-treat analysis revealed a small but lasting improvement in global cognitive functioning for the cognitive training group, paralleled by a large improvement on a trained updating task. The aerobic training group showed improvements in aerobic capacity and episodic memory immediately after training, but no long-term benefits. General improvements in psychological health and work ability were observed, with no difference between interventional groups. Our findings suggest that cognitive training may be a viable method to address cognitive impairments for patients with ED, whereas the effects of aerobic exercise on cognition may be more limited when performed during a restricted time period. The implications for clinical practice in supporting patients with ED to adhere to treatment are discussed.

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...

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

Science.gov (United States)

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

Complementary feeding: a Global Network cluster randomized controlled trial

Directory of Open Access Journals (Sweden)

Pasha Omrana

2011-01-01

Full Text Available Abstract Background Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated. Methods/Design A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months; neurocognitive development (12 and 18 months; and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial. Discussion Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

Science.gov (United States)

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

The pursuit of balance in sequential randomized trials

Directory of Open Access Journals (Sweden)

Raymond P. Guiteras

2016-06-01

Full Text Available In many randomized trials, subjects enter the sample sequentially. Because the covariates for all units are not known in advance, standard methods of stratification do not apply. We describe and assess the method of DA-optimal sequential allocation (Atkinson, 1982 for balancing stratification covariates across treatment arms. We provide simulation evidence that the method can provide substantial improvements in precision over commonly employed alternatives. We also describe our experience implementing the method in a field trial of a clean water and handwashing intervention in Dhaka, Bangladesh, the first time the method has been used. We provide advice and software for future researchers.

The blind leading the blind: use and misuse of blinding in randomized controlled trials.

Science.gov (United States)

Miller, Larry E; Stewart, Morgan E

2011-03-01

The use of blinding strengthens the credibility of randomized controlled trials (RCTs) by minimizing bias. However, there is confusion surrounding the definition of blinding as well as the terms single, double, and triple blind. It has been suggested that these terms should be discontinued due to their broad misinterpretation. We recommend that, instead of abandoning the use of these terms, explicit definitions of blinding should be adopted. We address herein the concept of blinding, propose standard definitions for the consistent use of these terms, and detail when different types of blinding should be utilized. Standardizing the definition of blinding and utilizing proper blinding methods will improve the quality and clarity of reporting in RCTs. Copyright © 2010 Elsevier Inc. All rights reserved.

Marketing depression care management to employers: design of a randomized controlled trial.

Science.gov (United States)

Rost, Kathryn M; Marshall, Donna

2010-03-16

Randomized trials demonstrate that depression care management can improve clinical and work outcomes sufficiently for selected employers to realize a return on investment. Employers can now purchase depression products that provide depression care management, defined as employee screening, education, monitoring, and clinician feedback for all depressed employees. We developed an intervention to encourage employers to purchase a depression product that offers the type, intensity, and duration of care management shown to improve clinical and work outcomes. In a randomized controlled trial conducted with 360 employers of 30 regional business coalitions, the research team proposes to compare the impact of a value-based marketing intervention to usual-care marketing on employer purchase of depression products. The study will also identify mediators and organizational-level moderators of intervention impact. Employers randomized to the value-based condition receive a presentation encouraging them to purchase depression products scientifically shown to benefit the employee and the employer. Employers randomized to the usual-care condition receive a presentation encouraging them to monitor and improve quality indicators for outpatient depression treatment. Because previous research demonstrates that the usual-care intervention will have little to no impact on employer purchasing, depression product purchasing rates in the usual-care condition capture vendor efforts to market depression products to employers in both conditions while the value-based intervention is being conducted. Employers in both conditions are also provided free technical assistance to undertake the actions each presentation encourages. The research team will use intent-to-treat models of all available data to evaluate intervention impact on the purchase of depression products using a cumulative incidence analysis of 12- and 24-month data. By addressing the 'value to whom?' question, the study advances

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

Science.gov (United States)

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple

Two controlled trials to increase participant retention in a randomized controlled trial of mobile phone-based smoking cessation support in the United Kingdom.

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Severi, Ettore; Free, Caroline; Knight, Rosemary; Robertson, Steven; Edwards, Philip; Hoile, Elizabeth

2011-10-01

Loss to follow-up of trial participants represents a threat to research validity. To date, interventions designed to increase participants' awareness of benefits to society of completing follow-up, and the impact of a telephone call from a senior female clinician and researcher requesting follow-up have not been evaluated robustly. Trial 1 aimed to evaluate the effect on trial follow-up of written information regarding the benefits of participation to society. Trial 2 aimed to evaluate the effect on trial follow-up of a telephone call from a senior female clinician and researcher. Two single-blind randomized controlled trials were nested within a larger trial, Txt2stop. In Trial 1, participants were allocated using minimization to receive a refrigerator magnet and a text message emphasizing the benefits to society of completing follow-up, or to a control group receiving a simple reminder regarding follow-up. In Trial 2, participants were randomly allocated to receive a telephone call from a senior female clinician and researcher, or to a control group receiving standard Txt2stop follow-up procedures. Trial 1: 33.5% (327 of 976) of the intervention group and 33.8% (329 of 974) of the control group returned the questionnaire within 26 weeks of randomization, risk ratio (RR) 0.99; 95% confidence interval (CI) 0.88-1.12. In all, 83.3% (813 of 976) of the intervention group and 82.2% (801 of/974) of the control group sent back the questionnaire within 30 weeks of randomization, RR 1.01; 95% CI 0.97, 1.05. Trial 2: 31% (20 of 65) of the intervention group and 32% (20 of 62) of the control group completed trial follow-up, RR 0.93; 95%CI 0.44, 1.98. In presence of other methods to increase follow-up neither experimental method (refrigerator magnet and text message emphasizing participation's benefits to society nor a telephone call from study's principal investigator) increased participant follow-up in the Txt2stop trial.

Design considerations of a randomized controlled trial of sedation level during hip fracture repair surgery: a strategy to reduce the incidence of postoperative delirium in elderly patients.

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Li, Tianjing; Wieland, L Susan; Oh, Esther; Neufeld, Karin J; Wang, Nae-Yuh; Dickersin, Kay; Sieber, Frederick E

2017-06-01

Background Delirium is an acute change in mental status characterized by sudden onset, fluctuating course, inattention, disorganized thinking, and abnormal level of consciousness. The objective of the randomized controlled trial "A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" (STRIDE) is to assess the effectiveness of light versus heavy sedation on delirium and other outcomes in elderly patients undergoing hip fracture repair surgery. Our goal is to describe the design considerations and lessons learned in planning and implementing the STRIDE trial. Methods Discussed are challenges encountered including (1) how to ensure that we quickly identify, assess the eligibility of, and randomize traumatic hip fracture patients; (2) how to implement interventions that involve continuous monitoring and adjustment during the surgery; and (3) how to measure and ascertain the primary outcome, delirium. Results To address the first challenge, we monitored the operating room schedule more actively than anticipated. We constructed and organized eligibility assessment data collection forms by purpose and by source of information needed to complete them. We decided that randomization needs to take place in the operating room. To address the second challenge, we designed and implemented a treatment protocol and covered the bispectral index monitor to prevent the Anesthesiologist/Anesthetist from being influenced by the bispectral index reading while administering the intervention. Finally, clinical assessment of delirium consisted of standardized interviews of the patient using validated instruments, interviews of those caring for the patient, and review of the medical record. A consensus panel made the final determination of a delirium diagnosis. We note that STRIDE is a single-center trial. The decisions we took may have different implications for multi-center trials. Conclusions Lessons learned are likely to provide useful information to others

Financial Management of a Large Multi-site Randomized Clinical Trial

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Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

2014-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

Acupuncture, Counseling, and Usual care for Depression (ACUDep: study protocol for a randomized controlled trial

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MacPherson Hugh

2012-11-01

Full Text Available Abstract Background The evidence on the effect of acupuncture or counseling for depression is not conclusive yet is sufficient to warrant further research. Our aim is to conduct a full-scale RCT to determine the clinical and cost effectiveness of acupuncture and counseling compared to usual care alone. We will explore the experiences and perspectives of patients and practitioners. Methods/Design Randomized controlled trial with three parallel arms: acupuncture plus usual care, counseling plus usual care, and usual care alone, in conjunction with a nested qualitative study using in-depth interviews with purposive samples of trial participants. Participants: Patients aged over 18 years diagnosed with depression or mood disorder by their GP and with a score of 20 or above on the Beck Depression Inventory (BDI-II. Randomization: Computer randomization by York Trials Unit to acupuncture, counseling, and usual care alone in proportions of 2:2:1, respectively, with secure allocation concealment. Interventions: Patients allocated to acupuncture and counseling groups receive the offer of up to 12 weekly sessions. Both interventions allow flexibility to address patient variation, yet are constrained within defined protocols. Acupuncture is based on traditional Chinese medicine and counseling is non-directive within the humanistic tradition. Outcome: The PHQ-9 is the primary outcome measure, collected at baseline, 3, 6, 9, and 12 months. Also measured is BDI-II, SF-36 Bodily pain subscale, and EQ-5D. Texted mood scores are collected weekly over the first 15 weeks. Health-related resource use is collected over 12 months. Analysis: The sample size target was for 640 participants, calculated for an effect size of 0.32 on the PHQ-9 when comparing acupuncture with counseling given 90% power, 5% significance, and 20% loss to follow-up. Analysis of covariance will be used on an intention-to-treat basis. Thematic analysis will be used for qualitative data. We will

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

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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

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology.

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Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C; Hobbs, Brian P; Berry, Donald A; Pentz, Rebecca D; Tam, Alda; Hong, Waun K; Ellis, Lee M; Abbruzzese, James; Overman, Michael J

2015-11-01

The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P medicine, additional initiatives are needed to minimize selective reporting. © 2015 by American Society of Clinical Oncology.

Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol.

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Naidoo, Kogieleum; Gengiah, Santhanalakshmi; Yende-Zuma, Nonhlanhla; Padayatchi, Nesri; Barker, Pierre; Nunn, Andrew; Subrayen, Priashni; Abdool Karim, Salim S

2017-11-13

A large and compelling clinical evidence base has shown that integrated TB and HIV services leads to reduction in human immunodeficiency virus (HIV)- and tuberculosis (TB)-associated mortality and morbidity. Despite official policies and guidelines recommending TB and HIV care integration, its poor implementation has resulted in TB and HIV remaining the commonest causes of death in several countries in sub-Saharan Africa, including South Africa. This study aims to reduce mortality due to TB-HIV co-infection through a quality improvement strategy for scaling up of TB and HIV treatment integration in rural primary healthcare clinics in South Africa. The study is designed as an open-label cluster randomized controlled trial. Sixteen clinic supervisors who oversee 40 primary health care (PHC) clinics in two rural districts of KwaZulu-Natal, South Africa will be randomized to either the control group (provision of standard government guidance for TB-HIV integration) or the intervention group (provision of standard government guidance with active enhancement of TB-HIV care integration through a quality improvement approach). The primary outcome is all-cause mortality among TB-HIV patients. Secondary outcomes include time to antiretroviral therapy (ART) initiation among TB-HIV co-infected patients, as well as TB and HIV treatment outcomes at 12 months. In addition, factors that may affect the intervention, such as conditions in the clinic and staff availability, will be closely monitored and documented. This study has the potential to address the gap between the establishment of TB-HIV care integration policies and guidelines and their implementation in the provision of integrated care in PHC clinics. If successful, an evidence-based intervention comprising change ideas, tools, and approaches for quality improvement could inform the future rapid scale up, implementation, and sustainability of improved TB-HIV integration across sub-Sahara Africa and other resource

Inadequate description of educational interventions in ongoing randomized controlled trials

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Pino Cécile

2012-05-01

Full Text Available Abstract Background The registration of clinical trials has been promoted to prevent publication bias and increase research transparency. Despite general agreement about the minimum amount of information needed for trial registration, we lack clear guidance on descriptions of non-pharmacologic interventions in trial registries. We aimed to evaluate the quality of registry descriptions of non-pharmacologic interventions assessed in ongoing randomized controlled trials (RCTs of patient education. Methods On 6 May 2009, we searched for all ongoing RCTs registered in the 10 trial registries accessible through the World Health Organization International Clinical Trials Registry Platform. We included trials evaluating an educational intervention (that is, designed to teach or train patients about their own health and dedicated to participants, their family members or home caregivers. We used a standardized data extraction form to collect data related to the description of the experimental intervention, the centers, and the caregivers. Results We selected 268 of 642 potentially eligible studies and appraised a random sample of 150 records. All selected trials were registered in 4 registers, mainly ClinicalTrials.gov (61%. The median [interquartile range] target sample size was 205 [100 to 400] patients. The comparator was mainly usual care (47% or active treatment (47%. A minority of records (17%, 95% CI 11 to 23% reported an overall adequate description of the intervention (that is, description that reported the content, mode of delivery, number, frequency, duration of sessions and overall duration of the intervention. Further, for most reports (59%, important information about the content of the intervention was missing. The description of the mode of delivery of the intervention was reported for 52% of studies, the number of sessions for 74%, the frequency of sessions for 58%, the duration of each session for 45% and the overall duration for 63

Methods for synthesizing findings on moderation effects across multiple randomized trials.

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Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2013-04-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design.

Pregnant womens' concerns when invited to a randomized trial: a qualitative case control study

NARCIS (Netherlands)

Oude Rengerink, Katrien; Logtenberg, Sabine; Hooft, Lotty; Bossuyt, Patrick M.; Mol, Ben Willem

2015-01-01

Pregnant women were excluded from clinical trials until the 1990s, but the Food and Drug Administration nowadays allows--and even encourages--responsible inclusion of pregnant women in trials with adequate safety monitoring. Still, randomized trials in pregnant women face specific enrolment

Pregnant womens' concerns when invited to a randomized trial : a qualitative case control study

NARCIS (Netherlands)

Oude Rengerink, Katrien; Logtenberg, Sabine; Hooft, Lotty; Bossuyt, Patrick M; Mol, Ben Willem; Oude Rengerink, K

2015-01-01

BACKGROUND: Pregnant women were excluded from clinical trials until the 1990s, but the Food and Drug Administration nowadays allows--and even encourages--responsible inclusion of pregnant women in trials with adequate safety monitoring. Still, randomized trials in pregnant women face specific

The handsearching of 2 medical journals of Bahrain for reports of randomized controlled trials.

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Al-Hajeri, Amani A; Fedorowicz, Zbigniew; Amin, Fawzi A; Eisinga, Anne

2006-04-01

To identify reports of randomized trials by handsearching 2 Bahrain medical journals, which are indexed in the biomedical database EMBASE and to determine any added value of the handsearching by comparing the reports found by handsearching with what would have been found by searching EMBASE to examine (i) the precision and sensitivity of the EMBASE index term Randomized Controlled Trial (RCT) and (ii) The Cochrane Collaboration's systematic electronic search of EMBASE (which uses 4 index terms and 9 free-text terms). All issues of the Bahrain Medical Bulletin (BMB) (1979-2004) and the Journal of the Bahrain Medical Society (JBMS) (1989-2004) were handsearched in February 2005 for reports of RCTs or Controlled Clinical Trials (CCTs), according to Cochrane eligibility criteria. Out of 395 articles in BMB we found reports of 12 RCTs and 4 CCTs. Distribution by country of corresponding author: Jordan (4 RCTs, one CCT), Bahrain (one RCT, one CCT), India (3 RCTs, one CCT), Kuwait (one CCT), Saudi Arabia (2 RCTs), USA/Bahrain (one RCT), and Oman (one RCT); and by specialty: Anesthesia (8), Surgery (1) Pediatrics (1), Radiotherapy (1), Community Medicine (1), Sports Medicine (1), Obstetrics/Gynecology (3). The Journal of the Bahrain Medical Society included reports of 14 RCTs and 3 CCTs, out of 97 articles. Distribution by country of corresponding author: Jordan (9 RCTs, 2 CCTs), Bahrain (3 RCTs), Egypt (one RCT), Kuwait (one RCT), and Saudi Arabia (one RCT); and by specialty: Anesthesia (7), General Surgery (3), Obstetrics/Gynecology (1), Radiotherapy (1), Pediatrics (1), Orthopaedic Surgery (1), Education (1) Ear Nose and Throat (1) Ophthalmology (1). Overall, of the 33 reports of trials found by handsearching both journals, only 23 were included in EMBASE of which only 6 had been indexed with the term RCT. Of the 23 reports of trials included in EMBASE, 16 had been identified in the Collaboration s systematic search of EMBASE. Two reports of trials could have been

Reporting funding source or conflict of interest in abstracts of randomized controlled trials, no evidence of a large impact on general practitioners' confidence in conclusions, a three-arm randomized controlled trial.

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Buffel du Vaure, Céline; Boutron, Isabelle; Perrodeau, Elodie; Ravaud, Philippe

2014-04-28

Systematic reporting of funding sources is recommended in the CONSORT Statement for abstracts. However, no specific recommendation is related to the reporting of conflicts of interest (CoI). The objective was to compare physicians' confidence in the conclusions of abstracts of randomized controlled trials of pharmaceutical treatment indexed in PubMed. We planned a three-arm parallel-group randomized trial. French general practitioners (GPs) were invited to participate and were blinded to the study's aim. We used a representative sample of 75 abstracts of pharmaceutical industry-funded randomized controlled trials published in 2010 and indexed in PubMed. Each abstract was standardized and reported in three formats: 1) no mention of the funding source or CoI; 2) reporting the funding source only; and 3) reporting the funding source and CoI. GPs were randomized according to a computerized randomization on a secure Internet system at a 1:1:1 ratio to assess one abstract among the three formats. The primary outcome was GPs' confidence in the abstract conclusions (0, not at all, to 10, completely confident). The study was planned to detect a large difference with an effect size of 0.5. Between October 2012 and June 2013, among 605 GPs contacted, 354 were randomized, 118 for each type of abstract. The mean difference (95% confidence interval) in GPs' confidence in abstract findings was 0.2 (-0.6; 1.0) (P = 0.84) for abstracts reporting the funding source only versus no funding source or CoI; -0.4 (-1.3; 0.4) (P = 0.39) for abstracts reporting the funding source and CoI versus no funding source and CoI; and -0.6 (-1.5; 0.2) (P = 0.15) for abstracts reporting the funding source and CoI versus the funding source only. We found no evidence of a large impact of trial report abstracts mentioning funding sources or CoI on GPs' confidence in the conclusions of the abstracts. ClinicalTrials.gov identifier: NCT01679873.

Individual Placement and Support supplemented with cognitive remediation and work-related social skills training in Denmark: study protocol for a randomized controlled trial.

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Christensen, Thomas Nordahl; Nielsen, Iben Gammelgaard; Stenager, Elsebeth; Morthorst, Britt Reuter; Lindschou, Jane; Nordentoft, Merete; Eplov, Lene Falgaard

2015-06-21

Individual Placement and Support (IPS) appears to be an effective vocational intervention for obtaining competitive employment for people with severe mental illness. However, no IPS studies or trials have been conducted in Denmark, a country characterized by a specialized labor market with a higher minimum wage and fewer entry-level jobs in comparison with other countries such as the US. Furthermore, long-term job retention and economic self-sufficiency have not been clearly demonstrated. Integrating methods such as cognitive remediation and work-related social skills training may be ways to address these issues. The trial design is an investigator-initiated, randomized, assessor-blinded, multi-center trial. A total of 750 patients with severe mental illness will be randomly assigned into three groups: (1) IPS, (2) IPS enhanced with cognitive remediation and work-related social skills training, and (3) service as usual. The primary outcome is number of hours in competitive employment or education at 18-month follow-up. Secondary and exploratory outcomes are money earned, days to first employment, symptoms, functional level, self-esteem, and self-efficacy at 18-month follow-up. Thirty- and 60-month follow-ups will be register-based. This will be one of the largest randomized trials investigating IPS to date. The trial will be conducted with high methodological quality in order to reduce the risk of bias. If the results of this trial show that IPS, or IPS enhanced with cognitive remediation and work-related social skills training, is superior to service as usual, this will support preliminary evidence. Furthermore, it will show that the method is generalizable to a variety of labor markets and welfare systems and provide important knowledge about the effect of adding cognitive remediation and social skills training to the IPS intervention. ClinicalTrials registration number: NCT01722344 (registered 2 Nov. 2012).

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

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Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.

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Nottage, Kerri A; Hankins, Jane S; Faughnan, Lane G; James, Dustin M; Richardson, Julie; Christensen, Robbin; Kang, Guolian; Smeltzer, Matthew; Cancio, Maria I; Wang, Winfred C; Anghelescu, Doralina L

2016-08-01

Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical. In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff. Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures

Reporting methods of blinding in randomized trials assessing nonpharmacological treatments.

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Isabelle Boutron

2007-02-01

Full Text Available BACKGROUND: Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on "creative" (nonstandard methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. METHODS AND FINDINGS: We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment, or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography, or adjudications of clinical events. CONCLUSIONS: This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials.

Research staff training in a multisite randomized clinical trial: Methods and recommendations from the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial.

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Walker, Robrina; Morris, David W; Greer, Tracy L; Trivedi, Madhukar H

2014-01-01

Descriptions of and recommendations for meeting the challenges of training research staff for multisite studies are limited despite the recognized importance of training on trial outcomes. The STRIDE (STimulant Reduction Intervention using Dosed Exercise) study is a multisite randomized clinical trial that was conducted at nine addiction treatment programs across the United States within the National Drug Abuse Treatment Clinical Trials Network (CTN) and evaluated the addition of exercise to addiction treatment as usual (TAU), compared to health education added to TAU, for individuals with stimulant abuse or dependence. Research staff administered a variety of measures that required a range of interviewing, technical, and clinical skills. In order to address the absence of information on how research staff are trained for multisite clinical studies, the current manuscript describes the conceptual process of training and certifying research assistants for STRIDE. Training was conducted using a three-stage process to allow staff sufficient time for distributive learning, practice, and calibration leading up to implementation of this complex study. Training was successfully implemented with staff across nine sites. Staff demonstrated evidence of study and procedural knowledge via quizzes and skill demonstration on six measures requiring certification. Overall, while the majority of staff had little to no experience in the six measures, all research assistants demonstrated ability to correctly and reliably administer the measures throughout the study. Practical recommendations are provided for training research staff and are particularly applicable to the challenges encountered with large, multisite trials.

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

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Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

Behavioral activation for smoking cessation and mood management following a cardiac event: results of a pilot randomized controlled trial

Directory of Open Access Journals (Sweden)

Andrew M. Busch

2017-04-01

Full Text Available Abstract Background Smoking cessation following hospitalization for Acute Coronary Syndrome (ACS significantly reduces subsequent mortality. Depressed mood is a major barrier to cessation post-ACS. Although existing counseling treatments address smoking and depression independently in ACS patients, no integrated treatment addresses both. We developed an integrated treatment combining gold standard cessation counseling with behavioral activation-based mood management; Behavioral Activation Treatment for Cardiac Smokers (BAT-CS. The purpose of this pilot randomized controlled trial was to test feasibility, acceptability, and preliminary efficacy of BAT-CS vs. Standard of Care (SC. Methods Participants were recruited during hospitalization for ACS and were randomly assigned to BAT-CS or SC. The nicotine patch was offered in both conditions. Smoking, mood, and stress outcomes were collected at end-of-treatment and 24-week follow-up. Results Fifty-nine participants (28 BAT-CS, 31 SC were recruited over 42 weeks, and assessment completion was above 80% in both conditions. Treatment acceptability and fidelity were high. At 24 week follow-up adjusted odds ratios favoring BAT-CS were 1.27 (95% CI: 0.41–3.93 for 7-day point prevalence abstinence and 1.27 (95% CI: 0.42–3.82 for continuous abstinence. Time to first smoking lapse was significantly longer in BAT-CS (62.4 vs. 31.8 days, p = 0.03. At 24-weeks, effect sizes for mood and stress outcomes ranged from η2 partial of.07–.11, with significant between treatment effects for positive affect, negative affect, and stress. Conclusions The design of this study proved feasible and acceptable. Results provide preliminary evidence that combining behavioral activation with standard smoking cessation counseling could be efficacious for this high risk population. A larger trial with longer follow-up is warranted. Trial registration NCT01964898 . First received by clinicaltrials.gov October 15, 2013.

Global randomized trials: the promise of India and China.

Science.gov (United States)

Perkovic, Vlado; Patil, Vinodvenkatesh; Wei, Liu; Lv, Jicheng; Petersen, Marisa; Patel, Anushka

2012-07-18

Although modern clinical trials are traditionally conducted in Western countries, currently there is a shift to involve developing countries, particularly China and India. For these trials, the large population size of India and China means that substantial numbers of individuals affected by rare diseases may be found, increasing the likelihood of successfully completing enrollment in a clinical trial. Furthermore, the increasing involvement of Asian countries in global clinical trials is likely to lead to greater appreciation of the value of evidence-based treatment decisions in the region. These sites are more cost-effective, although this advantage is being eroded over time. Asian participants in clinical trials are also typically more likely to complete study follow-up and procedures, and to adhere to their randomized treatment allocation than individuals from Western countries. Challenges include relevance of the proposed trial to the region, capacity limitations because of undeveloped training, and ensuring research implementation quality and different intellectual property practices. There are specific challenges to conducting clinical trials in India, such as the status of ethics committees, health insurance and coverage for participants, and variability in languages and record-keeping. Challenges in both countries are substantial but are able to be managed with appropriate planning.

Implementation, recruitment and baseline characteristics: A randomized trial of combined treatments for smoking cessation and weight control

Directory of Open Access Journals (Sweden)

Terry Bush

2017-09-01

Full Text Available Background: Two-thirds of treatment-seeking smokers are obese or overweight. Most smokers are concerned about gaining weight after quitting. The average smoker experiences modest post-quit weight gain which discourages many smokers from quitting. Although evidence suggests that combined interventions to help smokers quit smoking and prevent weight gain can be helpful, studies have not been replicated in real world settings. Methods: This paper describes recruitment and participant characteristics of the Best Quit Study, a 3-arm randomized controlled trial testing tobacco cessation treatment alone or combined with simultaneous or sequential weight management. Study participants were recruited via tobacco quitlines from August 5, 2013 to December 15, 2014. Results: Statistical analysis on baseline data was conducted in 2015/2016. Among 5082 potentially eligible callers to a tobacco quitline, 2540 were randomized (50% of eligible. Compared with individuals eligible but not randomized, those randomized were significantly more likely to be female (65.7% vs 54.5%, p < 0.01, overweight or obese (76.3% vs 62.5%, p < 0.01, more confident in quitting (p < 0.01, more addicted (first cigarette within 5 min: 50.0% vs 44.4%, p < 0.01, and have a chronic disease (28.6% vs. 24.4%, p < 0.01. Randomized groups were not statistically significantly different on demographics, tobacco or weight variables. Two-thirds of participants were female and white with a mean age of 43. Conclusions: Adding weight management interventions to tobacco cessation quitlines was feasible and acceptable to smokers. If successful for cessation and weight outcomes, a combined intervention may provide a treatment approach for addressing weight gain with smoking cessation through tobacco quitlines. Trial registration: Clinicaltrials.gov NCT01867983. Keywords: Smoking, Weight gain, Quitlines, Simultaneous, Sequential

The NKF-NUS hemodialysis trial protocol - a randomized controlled trial to determine the effectiveness of a self management intervention for hemodialysis patients

Directory of Open Access Journals (Sweden)

Krishnan Deby

2011-01-01

Full Text Available Abstract Background Poor adherence to treatment is common in patients on hemodialysis which may increase risk for poor clinical outcomes and mortality. Self management interventions have been shown to be effective in improving compliance in other chronic populations. The aim of this trial is to evaluate the effectiveness of a recently developed group based self management intervention for hemodialysis patients compared to standard care. Methods/Design This is a multicentre parallel arm block randomized controlled trial (RCT of a four session group self management intervention for hemodialysis patients delivered by health care professionals compared to standard care. A total of 176 consenting adults maintained on hemodialysis for a minimum of 6 months will be randomized to receive the self management intervention or standard care. Primary outcomes are biochemical markers of clinical status and adherence. Secondary outcomes include general health related quality of life, disease-specific quality of life, mood, self efficacy and self-reported adherence. Outcomes will be measured at baseline, immediately post-intervention and at 3 and 9 months post-intervention by an independent assessor and analysed on intention to treat principles with linear mixed-effects models across all time points. A qualitative component will examine which aspects of program participants found particularly useful and any barriers to change. Discussion The NKF-NUS intervention builds upon previous research emphasizing the importance of empowering patients in taking control of their treatment management. The trial design addresses weaknesses of previous research by use of an adequate sample size to detect clinically significant changes in biochemical markers, recruitment of a sufficiently large representative sample, a theory based intervention and careful assessment of both clinical and psychological endpoints at various follow up points. Inclusion of multiple dependent

Cluster randomized trial in the general practice research database: 2. Secondary prevention after first stroke (eCRT study: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Dregan Alex

2012-10-01

Full Text Available Abstract Background The purpose of this research is to develop and evaluate methods for conducting pragmatic cluster randomized trials in a primary care electronic database. The proposal describes one application, in a less frequent chronic condition of public health importance, secondary prevention of stroke. A related protocol in antibiotic prescribing was reported previously. Methods/Design The study aims to implement a cluster randomized trial (CRT using the electronic patient records of the General Practice Research Database (GPRD as a sampling frame and data source. The specific objective of the trial is to evaluate the effectiveness of a computer-delivered intervention at enhancing the delivery of stroke secondary prevention in primary care. GPRD family practices will be allocated to the intervention or usual care. The intervention promotes the use of electronic prompts to support adherence with the recommendations of the UK Intercollegiate Stroke Working Party and NICE guidelines for the secondary prevention of stroke in primary care. Primary outcome measure will be the difference in systolic blood pressure between intervention and control trial arms at 12-month follow-up. Secondary outcomes will be differences in serum cholesterol, prescribing of antihypertensive drugs, statins, and antiplatelet therapy. The intervention will continue for 12 months. Information on the utilization of the decision-support tools will also be analyzed. Discussion The CRT will investigate the effectiveness of using a computer-delivered intervention to reduce the risk of stroke recurrence following a first stroke event. The study will provide methodological guidance on the implementation of CRTs in electronic databases in primary care. Trial registration Current Controlled Trials ISRCTN35701810

Methods for Synthesizing Findings on Moderation Effects Across Multiple Randomized Trials

Science.gov (United States)

Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2011-01-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis, and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design. PMID:21360061

Mental skills training with basic combat training soldiers: A group-randomized trial.

Science.gov (United States)

Adler, Amy B; Bliese, Paul D; Pickering, Michael A; Hammermeister, Jon; Williams, Jason; Harada, Coreen; Csoka, Louis; Holliday, Bernie; Ohlson, Carl

2015-11-01

Cognitive skills training has been linked to greater skills, self-efficacy, and performance. Although research in a variety of organizational settings has demonstrated training efficacy, few studies have assessed cognitive skills training using rigorous, longitudinal, randomized trials with active controls. The present study examined cognitive skills training in a high-risk occupation by randomizing 48 platoons (N = 2,432 soldiers) in basic combat training to either (a) mental skills training or (b) an active comparison condition (military history). Surveys were conducted at baseline and 3 times across the 10-week course. Multilevel mixed-effects models revealed that soldiers in the mental skills training condition reported greater use of a range of cognitive skills and increased confidence relative to those in the control condition. Soldiers in the mental skills training condition also performed better on obstacle course events, rappelling, physical fitness, and initial weapons qualification scores, although effects were generally moderated by gender and previous experience. Overall, effects were small; however, given the rigor of the design, the findings clearly contribute to the broader literature by providing supporting evidence that cognitive training skills can enhance performance in occupational and sports settings. Future research should address gender and experience to determine the need for targeting such training appropriately. (c) 2015 APA, all rights reserved).

Mixed methods evaluation of a randomized control pilot trial targeting sugar-sweetened beverage behaviors.

Science.gov (United States)

Zoellner, Jamie; Cook, Emily; Chen, Yvonnes; You, Wen; Davy, Brenda; Estabrooks, Paul

2013-02-01

This Excessive sugar-sweetened beverage (SSB) consumption and low health literacy skills have emerged as two public health concerns in the United States (US); however, there is limited research on how to effectively address these issues among adults. As guided by health literacy concepts and the Theory of Planned Behavior (TPB), this randomized controlled pilot trial applied the RE-AIM framework and a mixed methods approach to examine a sugar-sweetened beverage (SSB) intervention (SipSmartER), as compared to a matched-contact control intervention targeting physical activity (MoveMore). Both 5-week interventions included two interactive group sessions and three support telephone calls. Executing a patient-centered developmental process, the primary aim of this paper was to evaluate patient feedback on intervention content and structure. The secondary aim was to understand the potential reach (i.e., proportion enrolled, representativeness) and effectiveness (i.e. health behaviors, theorized mediating variables, quality of life) of SipSmartER. Twenty-five participants were randomized to SipSmartER (n=14) or MoveMore (n=11). Participants' intervention feedback was positive, ranging from 4.2-5.0 on a 5-point scale. Qualitative assessments reavealed several opportunties to improve clarity of learning materials, enhance instructions and communication, and refine research protocols. Although SSB consumption decreased more among the SipSmartER participants (-256.9 ± 622.6 kcals), there were no significant group differences when compared to control participants (-199.7 ± 404.6 kcals). Across both groups, there were significant improvements for SSB attitudes, SSB behavioral intentions, and two media literacy constructs. The value of using a patient-centered approach in the developmental phases of this intervention was apparent, and pilot findings suggest decreased SSB may be achieved through targeted health literacy and TPB strategies. Future efforts are needed to examine

Randomized Trial of Thymectomy in Myasthenia Gravis.

Science.gov (United States)

Wolfe, Gil I; Kaminski, Henry J; Aban, Inmaculada B; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J Gabriel; Heckmann, Jeannine M; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O; Beydoun, Said R; Chalk, Colin H; Barboi, Alexandru C; Amato, Anthony A; Shaibani, Aziz I; Katirji, Bashar; Lecky, Bryan R F; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T; Rivner, Michael H; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M; Jackson, Carlayne E; Garcia Ramos, Guillermo S; Verschuuren, Jan J G M; Massey, Janice M; Kissel, John T; Werneck, Lineu C; Benatar, Michael; Barohn, Richard J; Tandan, Rup; Mozaffar, Tahseen; Conwit, Robin; Odenkirchen, Joanne; Sonett, Joshua R; Jaretzki, Alfred; Newsom-Davis, John; Cutter, Gary R

2016-08-11

Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, Pmyasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

A Prospective, Randomized, Double-blind Clinical Trial of One Nano ...

African Journals Online (AJOL)

2015-12-16

Dec 16, 2015 ... prospective randomized clinical trial that evaluated the clinical performance of one high‑viscosity bulk‑fill composite resin in Class II cavities of posterior teeth. .... amount of glass ionomer needed was used to cover the calcium ...

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

Science.gov (United States)

Krebs, Teri S; Johansen, Pål-Ørjan

2012-07-01

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

The combined effect of Parathyroid hormone (1-34) and whole-body Vibration exercise in the treatment of OSteoporosis (PaVOS)- study protocol for a randomized controlled trial

DEFF Research Database (Denmark)

Jepsen, Ditte Beck; Ryg, Jesper; Jørgensen, Niklas Rye

2018-01-01

Background: PaVOS is a randomized controlled trial (RCT) which aims to address the use of whole-body vibration exercise (WBV) in combination with parathyroid hormone 1-34 fragment teriparatide (PTH 1-34) treatment in patients with osteoporosis. PTH 1-34 is an effective but expensive anabolic...... fracture risk. Methods/design: PaVOS is a multicenter, assessor-blinded, superiority, two-armed randomized controlled trial (RCT). Postmenopausal women (n = 40, aged 50 years and older) starting taking PTH 1-34 from outpatient clinics will be randomized and assigned to a PTH 1-34 + WBV-exercise group...... (intervention group), or a PTH 1-34-alone group (control group). The intervention group will undergo WBV three sessions a week (12 min each, including 1:1 ratio of exercise: rest, 30 Hz, 1 mm amplitude) for a 12-month intervention period. Both the intervention and the control group will receive PTH 1...

Seated T'ai Chi in Older Taiwanese People Using Wheelchairs: A Randomized Controlled Trial Investigating Mood States and Self-Efficacy.

Science.gov (United States)

Hsu, Chen-Yuan; Moyle, Wendy; Cooke, Marie; Jones, Cindy

2016-12-01

There is growing interest in t'ai chi, but little research has addressed whether t'ai chi is effective in older people using wheelchairs for mobilization. The aim of this study was to compare the effects of seated t'ai chi exercise and usual standard activities on mood states and self-efficacy in older people living in a long-term care facility and using wheelchairs for mobilization. Randomized controlled trial (trial registration no. ACTRN12613000029796). One long-term-care facility in Taiwan. Sixty participants were randomly assigned by a computer-generated random sequence to a t'ai chi group (n = 30) or a usual exercise and entertainment activities group (n = 30). Seated t'ai chi exercise for 40 minutes three times a week for 26 weeks was provided. Mood states (Profile of Mood States Short Form [POMS-SF]) and self-efficacy (Self-Efficacy for Exercise [SEE]). At week 26, participants in the t'ai chi group reported significantly lower mood states on the fatigue-inertia dimension of the POMS-SF (mean score ± standard deviation, 3.56 ± 3.71) than did the control group (mean score, 7.16 ± 6.36) (F [1, 58] = 7.15; p self-efficacy for older people using wheelchairs.

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...

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

Science.gov (United States)

Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

2015-01-01

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

Platelet-rich fibrin versus albumin in surgical wound repair: a randomized trial with paired design

DEFF Research Database (Denmark)

Danielsen, Patricia L; Ågren, Sven Per Magnus; Jørgensen, Lars Nannestad

2010-01-01

To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial.......To study the effects of autologous platelet-rich fibrin (PRF) versus human albumin on incisional wound breaking strength and subcutaneous collagen deposition in patients undergoing laparoscopic cholecystectomy in a randomized trial....

Mindfulness-based stress reduction for residents: A randomized controlled trial

NARCIS (Netherlands)

Verweij, H.; Ravesteijn, H.J. van; Hooff, M.L.M. van; Lagro-Janssen, A.L.M.; Speckens, A.E.M.

2018-01-01

Background: Burnout is highly prevalent in residents. No randomized controlled trials have been conducted measuring the effects of Mindfulness-Based Stress Reduction (MBSR) on burnout in residents. Objective: To determine the effectiveness of MBSR in reducing burnout in residents. Design: A

Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials

DEFF Research Database (Denmark)

Keus, F; Wetterslev, J; Gluud, C

2009-01-01

of statistical method on inference. RESULTS: In seven meta-analyses of seven outcomes from 15 trials, there were zero-event trials in 0 to 71.4% of the trials. We found inconsistency in significance in one of seven outcomes (14%; 95% confidence limit 0.4%-57.9%). There was also considerable variability......OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical...... methods are identified for meta-analysis with zero-event trials, leading to numerous data analyses. We used the binary outcomes from our Cochrane review of randomized trials of laparoscopic vs. small-incision cholecystectomy for patients with symptomatic cholecystolithiasis to illustrate the influence...

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation

Science.gov (United States)

Acosta, Joie D.; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S.

2016-01-01

Restorative practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this article describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI)…

A Systematic Review of Surgical Randomized Controlled Trials: Part 2. Funding Source, Conflict of Interest, and Sample Size in Plastic Surgery.

Science.gov (United States)

Voineskos, Sophocles H; Coroneos, Christopher J; Ziolkowski, Natalia I; Kaur, Manraj N; Banfield, Laura; Meade, Maureen O; Chung, Kevin C; Thoma, Achilleas; Bhandari, Mohit

2016-02-01

The authors examined industry support, conflict of interest, and sample size in plastic surgery randomized controlled trials that compared surgical interventions. They hypothesized that industry-funded trials demonstrate statistically significant outcomes more often, and randomized controlled trials with small sample sizes report statistically significant results more frequently. An electronic search identified randomized controlled trials published between 2000 and 2013. Independent reviewers assessed manuscripts and performed data extraction. Funding source, conflict of interest, primary outcome direction, and sample size were examined. Chi-squared and independent-samples t tests were used in the analysis. The search identified 173 randomized controlled trials, of which 100 (58 percent) did not acknowledge funding status. A relationship between funding source and trial outcome direction was not observed. Both funding status and conflict of interest reporting improved over time. Only 24 percent (six of 25) of industry-funded randomized controlled trials reported authors to have independent control of data and manuscript contents. The mean number of patients randomized was 73 per trial (median, 43, minimum, 3, maximum, 936). Small trials were not found to be positive more often than large trials (p = 0.87). Randomized controlled trials with small sample size were common; however, this provides great opportunity for the field to engage in further collaboration and produce larger, more definitive trials. Reporting of trial funding and conflict of interest is historically poor, but it greatly improved over the study period. Underreporting at author and journal levels remains a limitation when assessing the relationship between funding source and trial outcomes. Improved reporting and manuscript control should be goals that both authors and journals can actively achieve.

Selection bias and subject refusal in a cluster-randomized controlled trial

Directory of Open Access Journals (Sweden)

Rochelle Yang

2017-07-01

Full Text Available Abstract Background Selection bias and non-participation bias are major methodological concerns which impact external validity. Cluster-randomized controlled trials are especially prone to selection bias as it is impractical to blind clusters to their allocation into intervention or control. This study assessed the impact of selection bias in a large cluster-randomized controlled trial. Methods The Improved Cardiovascular Risk Reduction to Enhance Rural Primary Care (ICARE study examined the impact of a remote pharmacist-led intervention in twelve medical offices. To assess eligibility, a standardized form containing patient demographics and medical information was completed for each screened patient. Eligible patients were approached by the study coordinator for recruitment. Both the study coordinator and the patient were aware of the site’s allocation prior to consent. Patients who consented or declined to participate were compared across control and intervention arms for differing characteristics. Statistical significance was determined using a two-tailed, equal variance t-test and a chi-square test with adjusted Bonferroni p-values. Results were adjusted for random cluster variation. Results There were 2749 completed screening forms returned to research staff with 461 subjects who had either consented or declined participation. Patients with poorly controlled diabetes were found to be significantly more likely to decline participation in intervention sites compared to those in control sites. A higher mean diastolic blood pressure was seen in patients with uncontrolled hypertension who declined in the control sites compared to those who declined in the intervention sites. However, these findings were no longer significant after adjustment for random variation among the sites. After this adjustment, females were now found to be significantly more likely to consent than males (odds ratio = 1.41; 95% confidence interval = 1.03, 1

Effects of unstratified and centre-stratified randomization in multi-centre clinical trials.

Science.gov (United States)

Anisimov, Vladimir V

2011-01-01

This paper deals with the analysis of randomization effects in multi-centre clinical trials. The two randomization schemes most often used in clinical trials are considered: unstratified and centre-stratified block-permuted randomization. The prediction of the number of patients randomized to different treatment arms in different regions during the recruitment period accounting for the stochastic nature of the recruitment and effects of multiple centres is investigated. A new analytic approach using a Poisson-gamma patient recruitment model (patients arrive at different centres according to Poisson processes with rates sampled from a gamma distributed population) and its further extensions is proposed. Closed-form expressions for corresponding distributions of the predicted number of the patients randomized in different regions are derived. In the case of two treatments, the properties of the total imbalance in the number of patients on treatment arms caused by using centre-stratified randomization are investigated and for a large number of centres a normal approximation of imbalance is proved. The impact of imbalance on the power of the study is considered. It is shown that the loss of statistical power is practically negligible and can be compensated by a minor increase in sample size. The influence of patient dropout is also investigated. The impact of randomization on predicted drug supply overage is discussed. Copyright © 2010 John Wiley & Sons, Ltd.

Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Stéphanie J.E. Becker

2014-09-01

 Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial. 

Many multicenter trials had few events per center, requiring analysis via random-effects models or GEEs.

Science.gov (United States)

Kahan, Brennan C; Harhay, Michael O

2015-12-01

Adjustment for center in multicenter trials is recommended when there are between-center differences or when randomization has been stratified by center. However, common methods of analysis (such as fixed-effects, Mantel-Haenszel, or stratified Cox models) often require a large number of patients or events per center to perform well. We reviewed 206 multicenter randomized trials published in four general medical journals to assess the average number of patients and events per center and determine whether appropriate methods of analysis were used in trials with few patients or events per center. The median number of events per center/treatment arm combination for trials using a binary or survival outcome was 3 (interquartile range, 1-10). Sixteen percent of trials had less than 1 event per center/treatment combination, 50% fewer than 3, and 63% fewer than 5. Of the trials which adjusted for center using a method of analysis which requires a large number of events per center, 6% had less than 1 event per center-treatment combination, 25% fewer than 3, and 50% fewer than 5. Methods of analysis that allow for few events per center, such as random-effects models or generalized estimating equations (GEEs), were rarely used. Many multicenter trials contain few events per center. Adjustment for center using random-effects models or GEE with model-based (non-robust) standard errors may be beneficial in these scenarios. Copyright © 2015 Elsevier Inc. All rights reserved.

Inference in randomized trials with death and missingness.

Science.gov (United States)

Wang, Chenguang; Scharfstein, Daniel O; Colantuoni, Elizabeth; Girard, Timothy D; Yan, Ying

2017-06-01

In randomized studies involving severely ill patients, functional outcomes are often unobserved due to missed clinic visits, premature withdrawal, or death. It is well known that if these unobserved functional outcomes are not handled properly, biased treatment comparisons can be produced. In this article, we propose a procedure for comparing treatments that is based on a composite endpoint that combines information on both the functional outcome and survival. We further propose a missing data imputation scheme and sensitivity analysis strategy to handle the unobserved functional outcomes not due to death. Illustrations of the proposed method are given by analyzing data from a recent non-small cell lung cancer clinical trial and a recent trial of sedation interruption among mechanically ventilated patients. © 2016, The International Biometric Society.

Encouraging GPs to undertake screening and a brief intervention in order to reduce problem drinking: a randomized controlled trial

DEFF Research Database (Denmark)

Hansen, Lars Jørgen; Olivarius, Niels de Fine; Beich, Anders

1999-01-01

intervention, problem drinking, randomized controlled trial, family practice, marketing of health services......intervention, problem drinking, randomized controlled trial, family practice, marketing of health services...

The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women : a randomized controlled trial

NARCIS (Netherlands)

Hak, AE; Bak, AAA; Lindemans, J; Planellas, J; Bennink, HJTC; Hofman, A; Grobbee, DE; Witteman, JCM

2001-01-01

Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine

Interventions to address deficits of pharmacological pain management in nursing home residents--A cluster-randomized trial.

Science.gov (United States)

Könner, F; Budnick, A; Kuhnert, R; Wulff, I; Kalinowski, S; Martus, P; Dräger, D; Kreutz, R

2015-10-01

To evaluate the effect of interventions for general practitioners and nursing home staff to improve pain severity and appropriateness of pain medication in nursing home residents (NHR). This cluster-randomized controlled trial was conducted in six nursing homes in the intervention and control group, respectively. Pain management was analysed before (T0) and after (T1, T2) an educational intervention in 239 NHR, aged ≥65 years, without moderate or severe cognitive impairment. Primary and secondary outcomes were average pain severity and appropriateness of pain medication as determined with the Numeric Rating Scale and Pain Medication Appropriateness Scale (PMASD ), respectively. At T0, 72.2% and 73.7% of NHR (mean age 83 years) reported pain (average pain severity 2.4) in the intervention and control group, respectively. The PMASD at T0 was 53.9 in the intervention group and 60.8 in the control group (p = 0.12), while 20.6% compared to 6.9% (p = 0.009) received no pain medication in the two groups. At T2, non-significant improvements in the average pain severity (1.59) and PMASD (61.07) were observed in the intervention group. Moreover, the mean individual PMASD increased by 8.09 (p = 0.03) and the proportion of NHR without pain medication decreased by 50% (p = 0.03) in the intervention group. No appreciable changes were found in the control group at T2. NHR exhibited a high prevalence of pain with overall low severity, while a high proportion of individuals received inappropriate pain medications. Both findings were not significantly improved by the intervention, although some aspects of drug treatment were meaningful improved. © 2015 European Pain Federation - EFIC®

Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial

NARCIS (Netherlands)

Beishuizen, Cathrien R. L.; Coley, Nicola; Moll van Charante, Eric P.; van Gool, Willem A.; Richard, Edo; Andrieu, Sandrine

2017-01-01

To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. Secondary analysis.

Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial

NARCIS (Netherlands)

Beishuizen, C.R.; Coley, N.; Charante, E.P.M. van; Gool, W.A. van; Richard, E.; Andrieu, S.

2017-01-01

OBJECTIVES: To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. DESIGN:

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review

OpenAIRE

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-01-01

Luke Perraton, Zuzana Machotka, Saravana KumarInternational Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia, AustraliaAim: Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS). The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials.Method: A systematic review of randomized controlled trials was conducted. Onl...

Aerobic training for improved memory in patients with stress-related exhaustion: a randomized controlled trial.

Science.gov (United States)

Eskilsson, Therese; Slunga Järvholm, Lisbeth; Malmberg Gavelin, Hanna; Stigsdotter Neely, Anna; Boraxbekk, Carl-Johan

2017-09-02

Patients with stress-related exhaustion suffer from cognitive impairments, which often remain after psychological treatment or work place interventions. It is important to find effective treatments that can address this problem. Therefore, the aim of this study was to investigate the effects on cognitive performance and psychological variables of a 12-week aerobic training program performed at a moderate-vigorous intensity for patients with exhaustion disorder who participated in a multimodal rehabilitation program. In this open-label, parallel, randomized and controlled trial, 88 patients diagnosed with exhaustion disorder participated in a 24-week multimodal rehabilitation program. After 12 weeks in the program the patients were randomized to either a 12-week aerobic training intervention or to a control group with no additional training. Primary outcome measure was cognitive function, and secondary outcome measures were psychological health variables and aerobic capacity. In total, 51% patients in the aerobic training group and 78% patients in the control group completed the intervention period. The aerobic training group significantly improved in maximal oxygen uptake and episodic memory performance. No additional improvement in burnout, depression or anxiety was observed in the aerobic group compared with controls. Aerobic training at a moderate-vigorous intensity within a multimodal rehabilitation program for patients with exhaustion disorder facilitated episodic memory. A future challenge would be the clinical implementation of aerobic training and methods to increase feasibility in this patient group. ClinicalTrials.gov: NCT03073772 . Retrospectively registered 21 February 2017.

Targeting functional fitness, hearing and health-related quality of life in older adults with hearing loss: Walk, Talk 'n' Listen, study protocol for a pilot randomized controlled trial.

Science.gov (United States)

Lambert, Justin; Ghadry-Tavi, Rouzbeh; Knuff, Kate; Jutras, Marc; Siever, Jodi; Mick, Paul; Roque, Carolyn; Jones, Gareth; Little, Jonathan; Miller, Harry; Van Bergen, Colin; Kurtz, Donna; Murphy, Mary Ann; Jones, Charlotte Ann

2017-01-28

Hearing loss (HL) is a disability associated with poorer health-related quality of life including an increased risk for loneliness, isolation, functional fitness declines, falls, hospitalization and premature mortality. The purpose of this pilot trial is to determine the feasibility and acceptability of a novel intervention to reduce loneliness, improve functional fitness, social connectedness, hearing and health-related quality of life in older adults with HL. This 10-week, single-blind, pilot randomized control trial (RCT) will include a convenience sample of ambulatory adults aged 65 years or older with self-reported HL. Following baseline assessments, participants will be randomized to either intervention (exercise, health education, socialization and group auditory rehabilitation (GAR)) or control (GAR only) groups. The intervention group will attend a local YMCA twice a week and the control group once a week. Intervention sessions will include 45 min of strengthening, balance and resistance exercises, 30 min of group walking at a self-selected pace and 60 min of interactive health education or GAR. The control group will attend 60-min GAR sessions. GAR sessions will include education about hearing, hearing technologies, enhancing communication skills, and psychosocial support. Pre-post trial data collection and measures will include: functional fitness (gait speed, 30-s Sit to Stand Test), hearing and health-related quality of life, loneliness, depression, social participation and social support. At trial end, feasibility (recruitment, randomization, retention, acceptability) and GAR will be evaluated. Despite evidence suggesting that HL is associated with declines in functional fitness, there are no studies aimed at addressing functional fitness declines associated with the disability of HL. This pilot trial will provide knowledge about the physical, mental and social impacts on health related to HL as a disability. This will inform the feasibility of a

A Randomized Controlled Trial of Mindfulness Meditation for Chronic Insomnia

Science.gov (United States)

Ong, Jason C.; Manber, Rachel; Segal, Zindel; Xia, Yinglin; Shapiro, Shauna; Wyatt, James K.

2014-01-01

Study Objectives: To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. Design: Three-arm, single-site, randomized controlled trial. Setting: Academic medical center. Participants: Fifty-four adults with chronic insomnia. Interventions: Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. Measurements and Results: Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P insomnia and could provide an alternative to traditional treatments for insomnia. Trial Registration: Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781 Citation: Ong JC, Manber R, Segal Z, Xia Y, Shapiro S, Wyatt JK. A randomized controlled trial of mindfulness meditation for chronic insomnia. SLEEP 2014;37(9):1553-1563. PMID:25142566

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review.

Science.gov (United States)

Perraton, Luke; Machotka, Zuzana; Kumar, Saravana

2009-11-30

Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS). The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials. A systematic review of randomized controlled trials was conducted. Only trials that have reported significant FMS-related outcomes were included. Data relating to the components of hydrotherapy programs (exercise type, duration, frequency and intensity, environmental factors, and service delivery) were analyzed. Eleven randomized controlled trials were included in this review. Overall, the quality of trials was good. Aerobic exercise featured in all 11 trials and the majority of hydrotherapy programs included either a strengthening or flexibility component. Great variability was noted in both the environmental components of hydrotherapy programs and service delivery. Aerobic exercise, warm up and cool-down periods and relaxation exercises are common features of hydrotherapy programs that report significant FMS-related outcomes. Treatment duration of 60 minutes, frequency of three sessions per week and an intensity equivalent to 60%-80% maximum heart rate were the most commonly reported exercise components. Exercise appears to be the most important component of an effective hydrotherapy program for FMS, particularly when considering mental health-related outcomes.

Recruitment of black and Latina women to a randomized controlled trial.

Science.gov (United States)

Martin, Anika; Negron, Rennie; Balbierz, Amy; Bickell, Nina; Howell, Elizabeth A

2013-08-01

Minority women are often not adequately represented in randomized controlled trials, limiting the generalizability of research trial results. We implemented a recruitment strategy for a postpartum depression prevention trial that utilized patient feedback to identify and understand the recruitment barriers of black and Latina postpartum women. Feedback on patients' reasons for trial refusal informed adaptations to the recruitment process. We calculated weekly recruitment rates and analyzed qualitative and quantitative data from patient refusals. Of the 668 women who were approached and completed the consent process, 540 enrolled in the trial and 128 declined participation. Over 52-weeks of recruitment, refusal rates decreased from 40% to 19%. A taxonomy of eight reasons for refusal derived from patient responses identified barriers to recruitment and generated targeted revisions to the recruitment message. A recruitment strategy designed to incorporate and respond to patient feedback improved recruitment of Black and Latina women to a clinical trial.

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.

Quality of reporting of randomized controlled trials of pharmacologic treatment of bipolar disorders: a systematic review.

Science.gov (United States)

Strech, Daniel; Soltmann, Bettina; Weikert, Beate; Bauer, Michael; Pfennig, Andrea

2011-09-01

This study aimed to assess (1) the quality of reporting of randomized controlled trials of pharmacologic treatment of bipolar disorder, (2) the potential improvement in quality of reporting over time, and (3) differences in quality of reporting between journals that endorse or do not endorse the Uniform Requirements for Manuscripts Submitted to Biomedical Journals developed by the International Committee of Medical Journal Editors. A systematic literature search was done to identify all randomized controlled trials published between 2000 and 2008 relevant to the pharmacologic treatment of bipolar disorder. The search strategy of the published National Institute for Health and Clinical Excellence guideline for management of bipolar disorders was used and adapted. All included and excluded clinical trials mentioned in the guideline and published from 2000 onward were reviewed for eligibility. For an update search from July 2004 through December 2008, an adapted search strategy was used in MEDLINE, EMBASE, PsycINFO, CINAHL, Ovid, and Cochrane Central Register of Controlled Trials. Titles and abstracts were scanned for relevance, and full texts were ordered in case of uncertainty to maximize sensitivity. Reference lists of retrieved systematic reviews were checked. All full texts were checked for eligibility. Only relevant randomized controlled trials published between 2000 and 2008 were included. Abstracts, randomized controlled trials published before 2000, nonrandomized clinical studies, pooled analyses, editorials, reviews, case reports, observational studies, and unpublished reports were excluded. A checklist based on the Consolidated Standards of Reporting Trials (CONSORT) statement was used to assess quality of reporting of all included studies. A total of 105 randomized controlled trials were included in the analysis. Of the 72 applicable checklist items, 42% were generally reported adequately and 25% inadequately. Reporting was especially poor for

Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial

Science.gov (United States)

Sung, Vivian W.; Borello-France, Diane; Dunivan, Gena; Gantz, Marie; Lukacz, Emily S.; Moalli, Pamela; Newman, Diane K.; Richter, Holly E.; Ridgeway, Beri; Smith, Ariana L.; Weidner, Alison C.; Meikle, Susan

2016-01-01

Introduction Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months. Methods ESTEEM is a multi-site, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient-centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure and need for additional treatment. Results The final study design was implemented in November 2013 across 8 clinical sites in the Pelvic Floor Disorders Network. As of February 27, 2016, 433 total /472 targeted participants have been randomized. Conclusions We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision-making. PMID:27287818

Quantity and quality assessment of randomized controlled trials on orthodontic practice in PubMed.

Science.gov (United States)

Shimada, Tatsuo; Takayama, Hisako; Nakamura, Yoshiki

2010-07-01

To find current high-quality evidence for orthodontic practice within a reasonable time, we tested the performance of a PubMed search. PubMed was searched using publication type randomized controlled trial and medical subject heading term "orthodontics" for articles published between 2003 and 2007. The PubMed search results were compared with those from a hand search of four orthodontic journals to determine the sensitivity of PubMed search. We evaluated the precision of the PubMed search result and assessed the quality of individual randomized controlled trials using the Jadad scale. Sensitivity and precision were 97.46% and 58.12%, respectively. In PubMed, of the 277 articles retrieved, 161 (58.12%) were randomized controlled trials on orthodontic practice, and 115 of the 161 articles (71.42%) were published in four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics. Assessment by the Jadad scale revealed 60 high-quality randomized controlled trials on orthodontic practice, of which 45 (75%) were published in these four journals. PubMed is a highly desirable search engine for evidence-based orthodontic practice. To stay current and get high-quality evidence, it is reasonable to look through four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics.

Eligibility audits for the randomized neuropathic bone pain trial (TROG 96.05)

International Nuclear Information System (INIS)

Roos, D.E.; Turner, S.L.

2000-01-01

In February 1996 the Trans-Tasman Radiation Oncology Group (TROG) initiated a two-arm, multicentre, prospective randomized trial on radiotherapy for neuropathic pain due to bone metastases (TROG 96.05). This trial compares the response to a single 8-Gy fraction with 20 Gy in five fractions. The accrual target is 270 patients. In order to evaluate compliance with eligibility criteria after approximately 1 year of accrual, an independent audit of the first 42 randomized patients was commissioned. This found that only one of these patients did not have genuine neuropathic pain, but that this patient and seven others (19%) had infringements of other eligibility/exclusion criteria for the trial. Accordingly it was decided to continue the full audit up to 90 patients. This detected no further patients without genuine neuropathic pain, and found only one other eligibility infringement (1/48; 2%). It is concluded that this quality assurance (QA) measure undertaken early in the trial led to significantly improved clinician awareness of, and compliance with, eligibility/exclusion criteria. It also enabled an accurate comparison of outcome data for all randomized versus all eligible patients at the time of the preplanned first interim analysis at 90 patients. In view of the excellent compliance demonstrated in the second audit, a one-in-five sampling is proposed for future audits from centres that have already accrued at least five consecutive eligible patients. This is consistent with TROG QA guidelines now operational. Copyright (2000) Blackwell Science Pty Ltd

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.

A prospective randomized trial of Kotase ® (Bromelain + Trypsin) in ...

African Journals Online (AJOL)

International Journal of Medicine and Health Development. Journal Home · ABOUT THIS ... A prospective randomized trial of Kotase® (Bromelain + Trypsin) in the management of post-operative abdominal wounds at the University of Nigeria Teaching Hospital Enugu, Nigeria. Emmanuel R Ezeome, Aloy E Aghaji ...

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

NARCIS (Netherlands)

Scheltens, P.; Kamphuis, P.J.; Verhey, F.R.J.; Olde Rikkert, M.G.M.; Wurtman, R.J.; Wilkinson, D.; Twisk, J.W.R.; Kurz, A.

2010-01-01

OBJECTIVE: To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). METHODS: A total of 225 drug-naive AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a

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.

Yoga for High‑Risk Pregnancy: A Randomized Controlled Trial ...

African Journals Online (AJOL)

The study was a single‑blind randomized controlled clinical trial. Perceived stress scale (PSS) was measured during the 12th, 20th, and 28th weeks of pregnancy. SPSS version 16.0 (Chicago, IL, USA) was used for all data analysis. When the data were found to be normally distributed,the RMANOVA were used to assess ...

Personalized Genetic Risk Counseling to Motivate Diabetes Prevention: A randomized trial

OpenAIRE

Grant, Richard W.; O’Brien, Kelsey E.; Waxler, Jessica L.; Vassy, Jason L.; Delahanty, Linda M.; Bissett, Laurie G.; Green, Robert C.; Stember, Katherine G.; Guiducci, Candace; Park, Elyse R.; Florez, Jose C.; Meigs, James B.

2013-01-01

OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top an...

Survival after relapse in patients with endometrial cancer : results from a randomized trial

NARCIS (Netherlands)

Creutzberg, CL; van Putten, WLJ; Koper, PC; Lybeert, MLM; Jobsen, JJ; Warlam-Rodenhuis, CC; De Winter, KAJ; Lutgens, LCHW; van den Bergh, ACM; van der Steen-Banasik, E; Beerman, H; van Lent, M

Objective. The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. Methods, The PORTEC trial included 715 patients with stage I endometrial cancer, either grade I or 2

Fractional Nonablative 1540 nm Laser Resurfacing for Thermal Burn Scars: A Randomized Controlled Trial

DEFF Research Database (Denmark)

Haedersdal, M.; Moreau, K.E.R.; Beyer, D.M.

2009-01-01

Background and Objective: Burn scars cause permanent and disfiguring problems for many patients and limited treatments are available. Nonablative fractional lasers induce a wound healing response, which may lead to remodeling of burn sear texture. This randomized trial evaluates efficacy and adve......Background and Objective: Burn scars cause permanent and disfiguring problems for many patients and limited treatments are available. Nonablative fractional lasers induce a wound healing response, which may lead to remodeling of burn sear texture. This randomized trial evaluates efficacy...

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial

DEFF Research Database (Denmark)

Gullestad, Lars; Iversen, Martin; Mortensen, Svend-Aage

2010-01-01

The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking.......The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking....

Telerehabilitation Versus Traditional Care Following Total Hip Replacement: A Randomized Controlled Trial Protocol.

Science.gov (United States)

Nelson, Mark; Bourke, Michael; Crossley, Kay; Russell, Trevor

2017-03-02

Total hip replacement (THR) is the gold standard treatment for severe hip osteoarthritis. Effectiveness of physical rehabilitation for THR patients following discharge from hospital is supported by evidence; however, barriers such as geographical location and transport can limit access to appropriate health care. One solution to this issue is using an alternative model of care using telerehabilitation technology to deliver rehabilitation programs directly into patients' homes. A telerehabilitation model may also have potential health care cost savings for health care providers. This study aims to determine if a telerehabilitation model of care delivered remotely is as effective as face-to-face rehabilitation in the THR population and cost effective for health care providers and patients. A total of 70 people undergoing THR will be recruited to participate in a randomized, single-blind, controlled noninferiority clinical trial. The trial will compare a technology-based THR rehabilitation program to in-person care. On discharge from hospital, participants randomized to the in-person group will receive usual care, defined as a paper home exercise program (HEP) targeting strengthening exercises for quadriceps, hip abductors, extensors, and flexors; they will be advised to perform their HEP 3 times per day. At 2, 4, and 6 weeks postoperatively, they will receive a 30-minute in-person physiotherapy session with a focus on gait retraining and reviewing and progressing their HEP. The telerehabilitation protocol will involve a program similar in content to the in-person rehabilitation program, except delivery will be directly into the homes of the participants via telerehabilitation technology on an iPad. Outcomes will be evaluated preoperatively, day of discharge from in-patient physiotherapy, 6 weeks and 6 months postoperatively. The primary outcome will be the quality of life subscale of the hip disability and osteoarthritis outcome score, measured at 6 weeks. Both

Setting up a randomized clinical trial in the UK: approvals and process.

Science.gov (United States)

Greene, Louise Eleanor; Bearn, David R

2013-06-01

Randomized clinical trials are considered the 'gold standard' in primary research for healthcare interventions. However, they can be expensive and time-consuming to set up and require many approvals to be in place before they can begin. This paper outlines how to determine what approvals are required for a trial, the background of each approval and the process for obtaining them.

The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial

Directory of Open Access Journals (Sweden)

van den Hout Lieke

2011-11-01

Full Text Available Abstract Background Congenital diaphragmatic hernia (CDH is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH. Methods/design This trial is designed as a multicentre trial in which 400 infants (200 in each arm will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension. Discussion To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity. Trial registration Netherlands Trial Register (NTR: NTR1310

Tools for teen moms to reduce infant obesity: a randomized clinical trial.

Science.gov (United States)

Horodynski, Mildred A; Silk, Kami; Hsieh, Gary; Hoffman, Alice; Robson, Mackenzie

2015-01-21

Unhealthy infant feeding practices, such as a combination of formula feeding and early introduction of solids may lead to rapid or excessive weight gain in early infancy. Adolescent mothers' feeding behaviors are most directly related to infant weight gain in the first year of life. Compared to adult mothers, adolescent mothers are less knowledgeable, less responsive, more controlling, and less skilled in infant feeding, which interferes with infants' healthy growth. The Tools for Teen Moms trial aims to compare the effect of a social media intervention for low-income adolescent, first-time mothers of infants 2 months of age or younger, versus standard care on infant weight, maternal responsiveness, and feeding style and practices. The intervention is conducted during the infant's first four months of life to promote healthy transition to solids during their first year. Tools for Teen Moms is an intervention delivered via a social media platform that actively engages and coaches low-income adolescent mothers in infant-centered feeding to reduce rapid/excessive infant weight gain in the first six months of life. We describe our study protocol for a randomized control trial with an anticipated sample of 100 low-income African- American and Caucasian adolescent, first-time mothers of infants. Participants are recruited through Maternal-Infant Health Programs in four counties in Michigan, USA. Participants are randomly assigned to the intervention or the control group. The intervention provides infant feeding information to mothers via a web-based application, and includes daily behavioral challenges, text message reminders, discussion forums, and website information as a comprehensive social media strategy over 6 weeks. Participants continue to receive usual care during the intervention. Main maternal outcomes include: (a) maternal responsiveness, (b) feeding style, and (c) feeding practices. The primary infant outcome is infant weight. Data collection occurs at

Use of the Tailored Activities Program to reduce neuropsychiatric behaviors in dementia: an Australian protocol for a randomized trial to evaluate its effectiveness.

Science.gov (United States)

O'Connor, C M; Clemson, L; Brodaty, H; Jeon, Y H; Mioshi, E; Gitlin, L N

2014-05-01

Behavioral and psychological symptoms of dementia (BPSD) are often considered to be the greatest challenge in dementia care, leading to increased healthcare costs, caregiver burden, and placement into care facilities. With potential for pharmacological intervention to exacerbate behaviors or even lead to mortality, the development and rigorous testing of non-pharmacological interventions is vital. A pilot of the Tailored Activities Program (TAP) for reducing problem behaviors in people with dementia was conducted in the United States with promising results. This randomized trial will investigate the effectiveness of TAP for reducing the burden of BPSD on persons with dementia and family caregivers within an Australian population. This trial will also examine the cost-effectiveness and willingness to pay for TAP compared with a control group. This randomized trial aims to recruit 180 participant dyads of a person with dementia and their caregivers. Participants will have a diagnosis of dementia, exhibit behaviors as scored by the Neuropsychiatric Inventory, and the caregiver must have at least 7 h per week contact. Participants will be randomly allocated to intervention (TAP) or control (phone-based education sessions) groups, both provided by a trained occupational therapist. Primary outcome measure will be the revised Neuropsychiatric Inventory - Clinician rating scale (NPI-C) to measure BPSD exhibited by the person with dementia. This trial investigates the effectiveness and cost-effectiveness of TAP within an Australian population. Results will address a significant gap in the current Australian community-support base for people living with dementia and their caregivers.

The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial.

Science.gov (United States)

van den Hout, Lieke; Tibboel, Dick; Vijfhuize, Sanne; te Beest, Harma; Hop, Wim; Reiss, Irwin

2011-11-02

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO) to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH. This trial is designed as a multicentre trial in which 400 infants (200 in each arm) will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension. To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity. Netherlands Trial Register (NTR): NTR1310.

Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey.

Science.gov (United States)

Cohen, Myron S; McCauley, Marybeth; Sugarman, Jeremy

2012-06-01

Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications. To describe and analyze the major ethical challenges faced in HPTN 052. The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described. When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the

Kā-HOLO Project: a protocol for a randomized controlled trial of a native cultural dance program for cardiovascular disease prevention in Native Hawaiians

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Joseph Keawe‘aimoku Kaholokula

2017-04-01

Full Text Available Abstract Background As a major risk factor for cardiovascular and cerebrovascular disease (CVD, hypertension affects 33% of U.S. adults. Relative to other US races and ethnicities, Native Hawaiians have a high prevalence of hypertension and are 3 to 4 times more likely to have CVD. Effective, culturally-relevant interventions are needed to address CVD risk in this population. Investigators of the Kā-HOLO Project developed a study design to test the efficacy of an intervention that uses hula, a traditional Hawaiian dance, to increase physical activity and reduce CVD risk. Methods A 2-arm randomized controlled trial with a wait-list control design will be implemented to test a 6-month intervention based on hula to manage blood pressure and reduce CVD risk in 250 adult Native Hawaiians with diagnosed hypertension. Half of the sample will be randomized to each arm, stratified across multiple study sites. Primary outcomes are reduction in systolic blood pressure and improvement in CVD risk as measured by the Framingham Risk Score. Other psychosocial and sociocultural measures will be included to determine mediators of intervention effects on primary outcomes. Assessments will be conducted at baseline, 3 months, and 6 months for all participants, and at 12 months for intervention participants only. Discussion This trial will elucidate the efficacy of a novel hypertension management program designed to reduce CVD risk in an indigenous population by using a cultural dance form as its physical activity component. The results of this culturally-based intervention will have implications for other indigenous populations globally and will offer a sustainable, culturally-relevant means of addressing CVD disparities. Trial registration ClinicalTrials.gov: NCT02620709 , registration date November 23, 2015.

Efficacy of a medical food in mild Alzheimer's disease: a randomized, controlled trial

NARCIS (Netherlands)

Scheltens, P.; Kamphuis, P.J.G.H.; Verhey, F.R.J.; Olde Rikkert, M.G.M.; Wurtman, R.J.; Wilkinson, D.; Twisk, J.W.R.; Kurz, A.

2010-01-01

Objective: To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). Methods: A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a

Grey literature in meta-analyses of randomized trials of health care interventions.

Science.gov (United States)

Hopewell, S; McDonald, S; Clarke, M; Egger, M

2007-04-18

The inclusion of grey literature (i.e. literature that has not been formally published) in systematic reviews may help to overcome some of the problems of publication bias, which can arise due to the selective availability of data. To review systematically research studies, which have investigated the impact of grey literature in meta-analyses of randomized trials of health care interventions. We searched the Cochrane Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20 May 2005), the Science Citation Index (June 2005) and contacted researchers who may have carried out relevant studies. A study was considered eligible for this review if it compared the effect of the inclusion and exclusion of grey literature on the results of a cohort of meta-analyses of randomized trials. Data were extracted from each report independently by two reviewers. The main outcome measure was an estimate of the impact of trials from the grey literature on the pooled effect estimates of the meta-analyses. Information was also collected on the area of health care, the number of meta-analyses, the number of trials, the number of trial participants, the year of publication of the trials, the language and country of publication of the trials, the number and type of grey and published literature, and methodological quality. Five studies met the inclusion criteria. All five studies showed that published trials showed an overall greater treatment effect than grey trials. This difference was statistically significant in one of the five studies. Data could be combined for three of the five studies. This showed that, on average, published trials showed a 9% greater treatment effect than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95% CI 1.03-1.16). Overall there were more published trials included in the meta-analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)). Published trials had more participants on average. The most

Placement Of Cardiac PacemaKEr Trial (POCKET – rationale and design: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Peter Magnusson

2017-04-01

Full Text Available BackgroundA pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET. The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket.MethodsIn October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device.ConclusionsPOCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.

Placement Of Cardiac PacemaKEr Trial (POCKET – rationale and design: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Peter Magnusson

2017-04-01

Full Text Available Background: A pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET. The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket. Methods: In October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device. Conclusions: POCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.

Who is the research subject in cluster randomized trials in health research?

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Brehaut Jamie C

2011-07-01

Full Text Available Abstract This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the first of the questions posed, namely, who is the research subject in a CRT in health research? The identification of human research subjects is logically prior to the application of protections as set out in research ethics and regulation. Aspects of CRT design, including the fact that in a single study the units of randomization, experimentation, and observation may differ, complicate the identification of human research subjects. But the proper identification of human research subjects is important if they are to be protected from harm and exploitation, and if research ethics committees are to review CRTs efficiently. We examine the research ethics literature and international regulations to identify the core features of human research subjects, and then unify these features under a single, comprehensive definition of human research subject. We define a human research subject as any person whose interests may be compromised as a result of interventions in a research study. Individuals are only human research subjects in CRTs if: (1 they are directly intervened upon by investigators; (2 they interact with investigators; (3 they are deliberately intervened upon via a manipulation of their environment that may compromise their interests; or (4 their identifiable private information is used to generate data. Individuals who are indirectly affected by CRT study interventions, including patients of healthcare providers participating in knowledge translation CRTs, are not human research subjects unless at least one of these conditions is met.

Qigong and Fibromyalgia: Randomized Controlled Trials and Beyond

Directory of Open Access Journals (Sweden)

Jana Sawynok

2014-01-01

Full Text Available Introduction. Qigong is currently considered as meditative movement, mindful exercise, or complementary exercise and is being explored for relief of symptoms in fibromyalgia. Aim. This narrative review summarizes randomized controlled trials, as well as additional studies, of qigong published to the end of 2013 and discusses relevant methodological issues. Results. Controlled trials indicate regular qigong practice (daily, 6–8 weeks produces improvements in core domains for fibromyalgia (pain, sleep, impact, and physical and mental function that are maintained at 4–6 months compared to wait-list subjects or baselines. Comparisons with active controls show little difference, but compared to baseline there are significant and comparable effects in both groups. Open-label studies provide information that supports benefit but remain exploratory. An extension trial and case studies involving extended practice (daily, 6–12 months indicate marked benefits but are limited by the number of participants. Benefit appears to be related to amount of practice. Conclusions. There is considerable potential for qigong to be a useful complementary practice for the management of fibromyalgia. However, there are unique methodological challenges, and exploration of its clinical potential will need to focus on pragmatic issues and consider a spectrum of trial designs. Mechanistic considerations need to consider both system-wide and more specific effects.

A randomized controlled trial of an electronic informed consent process.

Science.gov (United States)

Rothwell, Erin; Wong, Bob; Rose, Nancy C; Anderson, Rebecca; Fedor, Beth; Stark, Louisa A; Botkin, Jeffrey R

2014-12-01

A pilot study assessed an electronic informed consent model within a randomized controlled trial (RCT). Participants who were recruited for the parent RCT project were randomly selected and randomized to either an electronic consent group (n = 32) or a simplified paper-based consent group (n = 30). Results from the electronic consent group reported significantly higher understanding of the purpose of the study, alternatives to participation, and who to contact if they had questions or concerns about the study. However, participants in the paper-based control group reported higher mean scores on some survey items. This research suggests that an electronic informed consent presentation may improve participant understanding for some aspects of a research study. © The Author(s) 2014.

Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses.

Science.gov (United States)

Jakobsen, J C; Hansen, J L; Simonsen, S; Simonsen, E; Gluud, C

2012-07-01

Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews. Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors. We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference -1.02, 95% confidence interval (CI) -2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference -1.29, 95% CI -2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events. Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events.

A non-pharmacologic approach to address challenging behaviors of Veterans with dementia: description of the tailored activity program-VA randomized trial.

Science.gov (United States)

Gitlin, Laura N; Mann, William C; Vogel, W Bruce; Arthur, Paul B

2013-09-23

Behavioral symptoms accompanying dementia are associated with increased health care costs, reduced quality of life and daily functioning, heightened family caregiver burden, and nursing home placement. Standard care typically involves pharmacologic agents, but these are, at best, modestly effective, carry serious risks, including mortality, and do not address behavioral symptoms families consider most distressful and which may prompt nursing home placement. Given dementia's devastating effects and the absence of an imminent cure, the Veterans Administration has supported the development and testing of new approaches to manage challenging behaviors at home. The Tailored Activity Program - Veterans Administration is a Phase III efficacy trial designed to reduce behavioral symptoms in Veterans with dementia living with their caregivers in the community. The study uses a randomized two-group parallel design with 160 diverse Veterans and caregivers. The experimental group receives a transformative patient-centric intervention designed to reduce the burden of behavioral symptoms in Veterans with dementia. An occupational therapist conducts an assessment to identify a Veteran's preserved capabilities, deficit areas, previous roles, habits, and interests to develop activities tailored to the Veteran. Family caregivers are then trained to incorporate activities into daily care. The attention-control group receives bi-monthly telephone contact where education on topics relevant to dementia is provided to caregivers. Key outcomes include reduced frequency and severity of behavioral symptoms using the 12-item Neuropsychiatric Inventory (primary endpoint), reduced caregiver burden, enhanced skill acquisition, efficacy using activities, and time spent providing care at 4 months; and long-term effects (8 months) on the Veteran's quality of life and frequency and severity of behavioral symptoms, and caregiver use of activities. The programs' impact of Veterans Administration cost

Sensitivity Analysis for Not-at-Random Missing Data in Trial-Based Cost-Effectiveness Analysis: A Tutorial.

Science.gov (United States)

Leurent, Baptiste; Gomes, Manuel; Faria, Rita; Morris, Stephen; Grieve, Richard; Carpenter, James R

2018-04-20

Cost-effectiveness analyses (CEA) of randomised controlled trials are a key source of information for health care decision makers. Missing data are, however, a common issue that can seriously undermine their validity. A major concern is that the chance of data being missing may be directly linked to the unobserved value itself [missing not at random (MNAR)]. For example, patients with poorer health may be less likely to complete quality-of-life questionnaires. However, the extent to which this occurs cannot be ascertained from the data at hand. Guidelines recommend conducting sensitivity analyses to assess the robustness of conclusions to plausible MNAR assumptions, but this is rarely done in practice, possibly because of a lack of practical guidance. This tutorial aims to address this by presenting an accessible framework and practical guidance for conducting sensitivity analysis for MNAR data in trial-based CEA. We review some of the methods for conducting sensitivity analysis, but focus on one particularly accessible approach, where the data are multiply-imputed and then modified to reflect plausible MNAR scenarios. We illustrate the implementation of this approach on a weight-loss trial, providing the software code. We then explore further issues around its use in practice.

Effect of garlic on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled clinical trials.

Science.gov (United States)

Sahebkar, Amirhossein; Serban, Corina; Ursoniu, Sorin; Banach, Maciej

2016-01-01

Garlic can play an essential role in the prevention of atherosclerosis, but the research addressing the effect of garlic on the concentration of lipoprotein(a) [Lp(a)] has not been fully demonstrated. The aim of this study was to assess the effect of garlic on plasma Lp(a) concentrations through systematic review of literature and meta-analysis of available randomized controlled trials. The literature search included SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases up to March 10, 2015 to identify randomized controlled trials investigating the effect of garlic on plasma Lp(a) concentrations. Two independent reviewers extracted data on study characteristics, methods, and outcomes. Overall, the effect of garlic on plasma Lp(a) levels was reported in six trials. Meta-analysis did not suggest a significant alteration in plasma Lp(a) levels after garlic consumption (weighted mean difference [WMD] = 16.86%; 95% confidence interval, -4.59 to 38.31; P = 0.124). This result was robust in the leave-one-out sensitivity analysis. When the studies were categorized according to the duration of supplementation, there was no effect in the subgroup of trials lasting ≤12 wk (WMD = 2.01%; 95% CI, -14.67 to 18.68; P = 0.813) but a significant elevation of plasma Lp(a) concentrations was found in trials lasting >12 wk (WMD = 54.59%; 95% CI, 30.47-78.71; P meta-regression suggested an inverse association between the changes in plasma concentrations of Lp(a) and duration of supplementation (slope 1.71; 95% CI, 0.46-2.97; P = 0.007). The present meta-analysis did not suggest a significant effect of garlic supplementation on the reduction of Lp(a) levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Whose data set is it anyway? Sharing raw data from randomized trials

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Vickers Andrew J

2006-05-01

Full Text Available Abstract Background Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Discussion Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. Conclusion Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

Whose data set is it anyway? Sharing raw data from randomized trials.

Science.gov (United States)

Vickers, Andrew J

2006-05-16

Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

Science.gov (United States)

Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

2017-01-01

Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

Ipsilateral transversus abdominis plane block provides effective analgesia after appendectomy in children: a randomized controlled trial.

LENUS (Irish Health Repository)

Carney, John

2010-10-01

The transversus abdominis plane (TAP) block provides effective postoperative analgesia in adults undergoing major abdominal surgery. Its efficacy in children remains unclear, with no randomized clinical trials in this population. In this study, we evaluated its analgesic efficacy over the first 48 postoperative hours after appendectomy performed through an open abdominal incision, in a randomized, controlled, double-blind clinical trial.

A prospective, randomized, double-blind clinical trial of one nano ...

African Journals Online (AJOL)

Abstract. Background: Recently, manufacturers have introduced bulk‑fill composite resins that reportedly can be placed in increments of 4 mm or greater. Objective: The purpose of this article was to report the results of 12 months prospective randomized clinical trial that evaluated the clinical performance of one ...

Art therapy and music reminiscence activity in the prevention of cognitive decline: study protocol for a randomized controlled trial.

Science.gov (United States)

Mahendran, Rathi; Rawtaer, Iris; Fam, Johnson; Wong, Jonathan; Kumar, Alan Prem; Gandhi, Mihir; Jing, Kenny Xu; Feng, Lei; Kua, Ee Heok

2017-07-12

Attention has shifted to the use of non-pharmacological interventions to prevent cognitive decline as a preventive strategy, as well as for those at risk and those with mild cognitive impairment. Early introduction of psycho-social interventions can address cognitive decline and significantly impact quality of life and the wellbeing of elderly individuals. This pilot study explores the feasibility of using art therapy and music reminiscence activity to improve the cognition of community living elderly with mild cognitive impairment. This open-label, interventional study involves a parallel randomized controlled trial design with three arms (two intervention arms and a control group) over a nine-month period. Participants will be community-living elderly individuals aged 60-85 years, both genders, who meet predefined inclusion and exclusion criteria. In the initial three months, interventions will be provided weekly and for the remaining six months fortnightly. A sample size of 90 participants is targeted based on expected neuropsychological test performance, a primary outcome measure, and drop-out rates. The randomization procedure will be carried out via a web-based randomization system. Interventions will be provided by trained staff with a control group not receiving any intervention but continuing life as usual. Assessments will be done at baseline, three months, and nine months, and include neuroimaging to measure cerebral changes and neuropsychological tests to measure for changes in cognition. Secondary outcome measures will include mood changes in anxiety and depression and telomere lengths. Statistical analysis will be undertaken by statisticians; all efficacy analysis will be carried out on an intention-to-treat basis. Primary and secondary outcomes will be modeled using the linear mixed model for repeated measurements and further analysis may be undertaken to adjust for potential confounders. This will be the first study to compare the effectiveness of

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

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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

[Methodological quality and reporting quality evaluation of randomized controlled trials published in China Journal of Chinese Materia Medica].

Science.gov (United States)

Yu, Dan-Dan; Xie, Yan-Ming; Liao, Xing; Zhi, Ying-Jie; Jiang, Jun-Jie; Chen, Wei

2018-02-01

To evaluate the methodological quality and reporting quality of randomized controlled trials(RCTs) published in China Journal of Chinese Materia Medica, we searched CNKI and China Journal of Chinese Materia webpage to collect RCTs since the establishment of the magazine. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of RCTs. The CONSORT 2010 list was adopted as reporting quality evaluating tool. Finally, 184 RCTs were included and evaluated methodologically, of which 97 RCTs were evaluated with reporting quality. For the methodological evaluating, 62 trials(33.70%) reported the random sequence generation; 9(4.89%) trials reported the allocation concealment; 25(13.59%) trials adopted the method of blinding; 30(16.30%) trials reported the number of patients withdrawing, dropping out and those lost to follow-up;2 trials （1.09%） reported trial registration and none of the trial reported the trial protocol; only 8(4.35%) trials reported the sample size estimation in details. For reporting quality appraising, 3 reporting items of 25 items were evaluated with high-quality,including: abstract, participants qualified criteria, and statistical methods; 4 reporting items with medium-quality, including purpose, intervention, random sequence method, and data collection of sites and locations; 9 items with low-quality reporting items including title, backgrounds, random sequence types, allocation concealment, blindness, recruitment of subjects, baseline data, harms, and funding;the rest of items were of extremely low quality(the compliance rate of reporting item<10%). On the whole, the methodological and reporting quality of RCTs published in the magazine are generally low. Further improvement in both methodological and reporting quality for RCTs of traditional Chinese medicine are warranted. It is recommended that the international standards and procedures for RCT design should be strictly followed to conduct high-quality trials

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

Science.gov (United States)

Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

2017-10-01

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

Acupuncture for treating polycystic ovary syndrome: guidance for future randomized controlled trials

OpenAIRE

Wu, Y; Robinson, N; Hardiman, PJ; Taw, MB; Zhou, J; Wang, FF; Qu, F

2016-01-01

Objective: To provide guidance for future randomized controlled trials (RCTs) based on a review concerning acupuncture for treating polycystic ovary syndrome (PCOS). Methods: A comprehensive literature search was conducted in October 2015 using MEDLINE, EMBASE, SCISEARCH, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Menstrual Disorders and Subfertility Group trials register, Allied and Complementary Medicine (AMED), China National Knowledge Infrastructure (CNKI), and...

Acupuncture for sequelae of Bell's palsy: a randomized controlled trial protocol

Directory of Open Access Journals (Sweden)

Kim Yong-Suk

2011-03-01

Full Text Available Abstract Objective Incomplete recovery from facial palsy has a long-term impact on the quality of life, and medical options for the sequelae of Bell's palsy are limited. Invasive treatments and physiotherapy have been employed to relieve symptoms, but there is limited clinical evidence for their effectiveness. Acupuncture is widely used on Bell's palsy patients in East Asia, but there is insufficient evidence for its effectiveness on Bell's palsy sequelae. The objective is to evaluate the efficacy and safety of acupuncture in patients with sequelae of Bell's palsy. Method/Design This study consists of a randomized controlled trial with two parallel arms: an acupuncture group and a waitlist group. The acupuncture group will receive acupuncture treatment three times per week for a total of 24 sessions over 8 weeks. Participants in the waitlist group will not receive any acupuncture treatments during this 8 week period, but they will participate in the evaluations of symptoms at the start of the study, at 5 weeks and at 8 weeks after randomization, at which point the same treatment as the acupuncture group will be provided. The primary outcome will be analyzed by the change in the Facial Disability Index (FDI from baseline to week eight. The secondary outcome measures will include FDI from baseline to week five, House-Brackmann Grade, lip mobility, and stiffness scales. Trial registration Current Controlled-Trials ISRCTN43104115; registration date: 06 July 2010; the date of the first patient's randomization: 04 August 2010

Acupuncture for sequelae of Bell's palsy: a randomized controlled trial protocol

Science.gov (United States)

2011-01-01

Objective Incomplete recovery from facial palsy has a long-term impact on the quality of life, and medical options for the sequelae of Bell's palsy are limited. Invasive treatments and physiotherapy have been employed to relieve symptoms, but there is limited clinical evidence for their effectiveness. Acupuncture is widely used on Bell's palsy patients in East Asia, but there is insufficient evidence for its effectiveness on Bell's palsy sequelae. The objective is to evaluate the efficacy and safety of acupuncture in patients with sequelae of Bell's palsy. Method/Design This study consists of a randomized controlled trial with two parallel arms: an acupuncture group and a waitlist group. The acupuncture group will receive acupuncture treatment three times per week for a total of 24 sessions over 8 weeks. Participants in the waitlist group will not receive any acupuncture treatments during this 8 week period, but they will participate in the evaluations of symptoms at the start of the study, at 5 weeks and at 8 weeks after randomization, at which point the same treatment as the acupuncture group will be provided. The primary outcome will be analyzed by the change in the Facial Disability Index (FDI) from baseline to week eight. The secondary outcome measures will include FDI from baseline to week five, House-Brackmann Grade, lip mobility, and stiffness scales. Trial registration Current Controlled-Trials ISRCTN43104115; registration date: 06 July 2010; the date of the first patient's randomization: 04 August 2010 PMID:21388554

Design of the Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial (ROBUST): a randomized clinical trial.

Science.gov (United States)

Malas, Mahmoud B; Qazi, Umair; Glebova, Natalia; Arhuidese, Isibor; Reifsnyder, Thomas; Black, James; Perler, Bruce A; Freischlag, Julie A

2014-12-01

To our knowledge, there is no level 1 evidence comparing open bypass with angioplasty and stenting in TransAtlantic Inter-Society Consensus (TASC II) B and C superficial femoral artery lesions. The Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial (ROBUST) is the first prospective randomized clinical trial comparing both treatments. To report the design of the ROBUST trial. The primary aim of the trial is to compare (1) the patency rate (primary, primary assisted, and secondary patency at 6 and 12 months), (2) improvement of quality of life, (3) clinical improvement (at least 1 Rutherford category), and (4) wound healing and limb salvage in patients presenting with critical limb ischemia; secondary aims include (1) cost-effectiveness by factoring procedure and hospital admission costs including rehabilitation, readmission, and reintervention costs, (2) amputation-free survival, (3) reintervention rate, and (4) 30-day operative mortality, morbidity, and wound and access complications. ROBUST is a prospective randomized clinical trial with the aim to enroll 320 patients with intermittent claudication that does not respond to medical management and patients with critical limb ischemia. The maximum level of medical therapy will be administered using antiplatelet agents and statins, as well as measures to control hypertension and diabetes mellitus. Patients with TASC II B or C lesions are prospectively randomized to receive either femoropopliteal bypass or percutaneous transluminal angioplasty and stenting; patients with TASC II A and D lesions are not randomized and receive percutaneous transluminal angioplasty and stenting or femoropopliteal bypass, respectively. All patients will be evaluated at 1, 6, and 12 months postoperatively with physical examination, ankle brachial index, duplex, and a quality-of-life questionnaire. The trial is actively enrolling participants. At the time of writing, 29 patients have been enrolled

Imipramine and Pregabalin Combination for Painful Polyneuropathy. A Randomized Controlled Trial

DEFF Research Database (Denmark)

Holbech, Jakob V; Bach, Flemming W; Finnerup, Nanna B

2015-01-01

Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more...... effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy...... randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain...

The feasibility of progressive resistance training in women with polycystic ovary syndrome: a pilot randomized controlled trial.

Science.gov (United States)

Vizza, Lisa; Smith, Caroline A; Swaraj, Soji; Agho, Kingsley; Cheema, Birinder S

2016-01-01

To evaluate the feasibility of executing a randomized controlled trial of progressive resistance training (PRT) in women with polycystic ovary syndrome (PCOS). Women with PCOS were randomized to an experimental (PRT) group or a no-exercise (usual care) control group. The PRT group was prescribed two supervised and two unsupervised (home-based) training sessions per week for 12 weeks. Feasibility outcomes included recruitment and attrition, adherence, adverse events, and completion of assessments. Secondary outcomes, collected pre and post intervention, included a range of pertinent physiological, functional and psychological measures. Fifteen participants were randomised into the PRT group (n = 8) or control group (n = 7); five women (n = 2 in PRT group and n = 3 in control group) withdrew from the study. The most successful recruitment sources were Facebook (40 %) and online advertisement (27 %), while least successful methods were referrals by clinicians, colleagues and flyers. In the PRT group, attendance to supervised sessions was higher (95 %; standard deviation ±6 %) compared to unsupervised sessions (51 %; standard deviation ±28 %). No adverse events were attributed to PRT. Change in menstrual cycle status was not significantly different between groups over time (p = 0.503). However, the PRT group significantly increased body weight (p = 0.01), BMI (p = 0.04), lean mass (p = 0.01), fat-free mass (p = 0.005) and lower body strength (p = 0.03), while reducing waist circumference (p = 0.03) and HbA1c (p = 0.033) versus the control group. The PRT group also significantly improved across several domains of disease-specific and general health-related quality of life, depression, anxiety and exercise self-efficacy. A randomized controlled trial of PRT in PCOS would be feasible, and this mode of exercise may elicit a therapeutic effect on clinically important outcomes in this cohort. The success of a large

Outcomes in registered, ongoing randomized controlled trials of patient education.

Directory of Open Access Journals (Sweden)

Cécile Pino

Full Text Available BACKGROUND: With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life. METHODS: On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1 patient-important outcomes such as clinical events, functional status, pain, or quality of life or 2 surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge. PRINCIPAL FINDINGS: We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patient-important outcomes represented 54% (178 of 333 of all primary outcomes and 46% (286 of 623 of all secondary outcomes. Overall, 69% of trials (104 of 150 used at least one patient-important outcome as a primary outcome and 66% (99 of 150 as a secondary outcome. Finally, for 31% of trials (46 of 150, primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61 of primary outcomes, as compared with 54% (32 of 59 in malignant neoplasm and 18% (4 of 22 in diabetes mellitus trials. In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months. CONCLUSIONS: There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs.

A quality assessment of randomized controlled trial reports in endodontics.

Science.gov (United States)

Lucena, C; Souza, E M; Voinea, G C; Pulgar, R; Valderrama, M J; De-Deus, G

2017-03-01

To assess the quality of the randomized clinical trial (RCT) reports published in Endodontics between 1997 and 2012. Retrieval of RCTs in Endodontics was based on a search of the Thomson Reuters Web of Science (WoS) database (March 2013). Quality evaluation was performed using a checklist based on the Jadad criteria, CONSORT (Consolidated Standards of Reporting Trials) statement and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials). Descriptive statistics were used for frequency distribution of data. Student's t-test and Welch test were used to identify the influence of certain trial characteristics upon report quality (α = 0.05). A total of 89 RCTs were evaluated, and several methodological flaws were found: only 45% had random sequence generation at low risk of bias, 75% did not provide information on allocation concealment, and 19% were nonblinded designs. Regarding statistics, only 55% of the RCTs performed adequate sample size estimations, only 16% presented confidence intervals, and 25% did not provide the exact P-value. Also, 2% of the articles used no statistical tests, and in 87% of the RCTs, the information provided was insufficient to determine whether the statistical methodology applied was appropriate or not. Significantly higher scores were observed for multicentre trials (P = 0.023), RCTs signed by more than 5 authors (P = 0.03), articles belonging to journals ranked above the JCR median (P = 0.03), and articles complying with the CONSORT guidelines (P = 0.000). The quality of RCT reports in key areas for internal validity of the study was poor. Several measures, such as compliance with the CONSORT guidelines, are important in order to raise the quality of RCTs in Endodontics. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Testing a Violence-Prevention Intervention for Incarcerated Women Using a Randomized Control Trial

Science.gov (United States)

Kubiak, Sheryl Pimlott; Kim, Woo Jong; Fedock, Gina; Bybee, Deborah

2015-01-01

Objective: Beyond Violence (BV), a new prevention program for women with assaultive offenses, demonstrated feasibility in previous studies. This study's purpose is to assess the efficacy of BV using a randomized control trial. Method: Eligible women were randomly assigned to treatment as usual (TAU) and the experimental condition (BV). Measures of…

Timely and complete publication of economic evaluations alongside randomized controlled trials.

Science.gov (United States)

Thorn, Joanna C; Noble, Sian M; Hollingworth, William

2013-01-01

Little is known about the extent and nature of publication bias in economic evaluations. Our objective was to determine whether economic evaluations are subject to publication bias by considering whether economic data are as likely to be reported, and reported as promptly, as effectiveness data. Trials that intended to conduct an economic analysis and ended before 2008 were identified in the International Standard Randomised Controlled Trial Number (ISRCTN) register; a random sample of 100 trials was retrieved. Fifty comparator trials were randomly drawn from those not identified as intending to conduct an economic study. The trial start and end dates, estimated sample size and funder type were extracted. For trials planning economic evaluations, effectiveness and economic publications were sought; publication dates and journal impact factors were extracted. Effectiveness abstracts were assessed for whether they reached a firm conclusion that one intervention was most effective. Primary investigators were contacted about reasons for non-publication of results, or reasons for differential publication strategies for effectiveness and economic results. Trials planning an economic study were more likely to be funded by government (p = 0.01) and larger (p = 0.003) than other trials. The trials planning an economic evaluation had a mean of 6.5 (range 2.7-13.2) years since the trial end in which to publish their results. Effectiveness results were reported by 70 %, while only 43 % published economic evaluations (p economic results included the intervention being ineffective, and staffing issues. Funding source, time since trial end and length of study were not associated with a higher probability of publishing the economic evaluation. However, studies that were small or of unknown size were significantly less likely to publish economic evaluations than large studies (p journal impact factor was 1.6 points higher for effectiveness publications than for the

Participants' Understanding of Informed Consent in a Randomized Controlled Trial for Chronic Knee Pain.

Science.gov (United States)

Guillemin, Marilys; Barnard, Emma; Walker, Hannah; Bennell, Kim; Hinman, Rana; Gillam, Lynn

2015-12-01

This study explored participants' experiences of randomized controlled trial (RCT) participation to examine their understanding of the trial design and whether their consent was indeed informed. A nested qualitative interview study was conducted with 38 participants from a sample of 282 who participated in a complex RCT evaluating the effectiveness of laser compared with needle acupuncture for chronic knee pain. Overall participants had a good understanding of the RCT, and concepts such as randomization and placebo. Their experiences of being in the trial were largely positive, even if they did not experience any knee pain improvement. Their responses to unblinding at the end of the study were accepting. Participants had a good functional understanding of the RCT, sufficient for valid informed consent. © The Author(s) 2015.

Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE: a randomized controlled trial protocol

Directory of Open Access Journals (Sweden)

Winstein Carolee J

2013-01-01

Full Text Available Abstract Background Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting. The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP, compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC. Two secondary objectives are to compare ASAP to a true (active monitoring only usual and customary (UCC therapy group and to compare DEUCC and UCC. Methods/design Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS hand domain is a secondary outcome measure. The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary

Physiotherapy for sleep disturbance in people with chronic low back pain: results of a feasibility randomized controlled trial

NARCIS (Netherlands)

Eadie, J.; van de Water, A.T.; Lonsdale, C.; Tully, M.A.; van Mechelen, W.; Boreham, C.A.; Daly, L.; McDonough, S.M.; Hurley, D.A.

2013-01-01

Objective: To determine the feasibility of a randomized controlled trial investigating the effectiveness of physiotherapy for sleep disturbance in chronic low back pain (CLBP) (≥12wks). Design: Randomized controlled trial with evaluations at baseline, 3 months, and 6 months. Setting: Outpatient

Vision-Related Quality-of-Life Outcomes in the Mycotic Ulcer Treatment Trial I: A Randomized Clinical Trial.

Science.gov (United States)

Rose-Nussbaumer, Jennifer; Prajna, N Venkatesh; Krishnan, K Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E; O'Brien, Kieran S; Ray, Kathryn J; McLeod, Stephen D; Porco, Travis C; Lietman, Thomas M; Acharya, Nisha R; Keenan, Jeremy D

2015-06-01

Given the limitations in health care resources, quality-of-life measures for interventions have gained importance. To determine whether vision-related quality-of-life outcomes were different between the natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I, as measured by an Indian Vision Function Questionnaire. Secondary analysis (performed October 11-25, 2014) of a double-masked, multicenter, randomized, active comparator-controlled, clinical trial at multiple locations of the Aravind Eye Care System in South India that enrolled patients with culture- or smear-positive filamentous fungal corneal ulcers who had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3). Study participants were randomly assigned to topical voriconazole, 1%, or topical natamycin, 5%. Subscale score on the Indian Vision Function Questionnaire from each of the 4 subscales (mobility, activity limitation, psychosocial impact, and visual function) at 3 months. A total of 323 patients were enrolled in the trial, and 292 (90.4%) completed the Indian Vision Function Questionnaire at 3 months. The majority of study participants had subscale scores consistent with excellent function. After adjusting for baseline visual acuity and organism, we found that study participants in the natamycin-treated group scored, on average, 4.3 points (95% CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P = .046). In subgroup analyses looking at ulcers caused by Fusarium species and adjusting for baseline best spectacle-corrected visual acuity, the natamycin-treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole-treated group (P = .01). Differences in quality of life were not detected for patients with Aspergillus or other non-Fusarium species as the causative organism (1.5 points [95% CI, -3.9 to 6.9]; P = .52). We found evidence of improvement in vision-related quality of life among patients with fungal ulcers

Cryo-thawed embryo transfer: natural versus artificial cycle. A non-inferiority trial.(ANTARCTICA trial

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Groenewoud Eva R

2012-09-01

Full Text Available Abstract Background Frozen thawed embryo transfer (FET is a cost- effective adjunct to IVF or IVF-ICSI treatment. In order to optimize treatment outcome, FET should be carried out during a period of optimal endometrial receptivity. To optimize implantation several methods for endometrium preparation have been proposed. In natural cycle FET (NC-FET, the endometrium develops under endogenous hormonal stimulation. The development of the dominant follicle and endometrium is monitored by ultrasound and FET is timed after triggering ovulation induction or determination of the spontaneous LH surge. In an artificial cycle FET (AC-FET estrogens and progesterone are administered to prepare the endometrium for implantation. While the currently available data show no significant difference in pregnancy rates between these methods, well designed randomized controlled trials are lacking. Moreover there is little literature on difference in cancellation rates, cost-efficiency and adverse events. Methods and design In this randomized, multi-centre, non-inferiority trial we aim to test the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus AC-FET. The primary outcome will be live birth rate per embryo transfer procedure. Secondary outcomes will be ongoing and clinical pregnancy rate, cancellation rate, (serious adverse events and cost-efficiency. Based on a live birth rate of 20% and a minimal clinical important difference of 7,5% (one-sided alpha 2,5%, beta 20% a total of 1150 patients will be needed. Analyzes will be performed using both per protocol as well as intention to treat analyses. Discussion This prospective, randomized, non –inferiority trial aims to address the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus patients undergoing AC-FET. Moreover it addresses cost-efficiency as well as the perceived burden of both treatments

Variations in reporting of outcomes in randomized trials on diet and physical activity in pregnancy

DEFF Research Database (Denmark)

Rogozińska, Ewelina; Marlin, Nadine; Yang, Fen

2017-01-01

AIM: Trials on diet and physical activity in pregnancy report on various outcomes. We aimed to assess the variations in outcomes reported and their quality in trials on lifestyle interventions in pregnancy. METHODS: We searched major databases without language restrictions for randomized controlled...... trials on diet and physical activity-based interventions in pregnancy up to March 2015. Two independent reviewers undertook study selection and data extraction. We estimated the percentage of papers reporting 'critically important' and 'important' outcomes. We defined the quality of reporting...... as a proportion using a six-item questionnaire. Regression analysis was used to identify factors affecting this quality. RESULTS: Sixty-six randomized controlled trials were published in 78 papers (66 main, 12 secondary). Gestational diabetes (57.6%, 38/66), preterm birth (48.5%, 32/66) and cesarian section (60...

A randomized, controlled clinical trial: the effect of mindfulness-based cognitive therapy on generalized anxiety disorder among Chinese community patients: protocol for a randomized trial

Directory of Open Access Journals (Sweden)

Wong Samuel YS

2011-11-01

Full Text Available Abstract Background Research suggests that an eight-week Mindfulness-Based Cognitive Therapy (MBCT program may be effective in the treatment of generalized anxiety disorders. Our objective is to compare the clinical effectiveness of the MBCT program with a psycho-education programme and usual care in reducing anxiety symptoms in people suffering from generalized anxiety disorder. Methods A three armed randomized, controlled clinical trial including 9-month post-treatment follow-up is proposed. Participants screened positive using the Structure Clinical Interview for DSM-IV (SCID for general anxiety disorder will be recruited from community-based clinics. 228 participants will be randomly allocated to the MBCT program plus usual care, psycho-education program plus usual care or the usual care group. Validated Chinese version of instruments measuring anxiety and worry symptoms, depression, quality of life and health service utilization will be used. Our primary end point is the change of anxiety and worry score (Beck Anxiety Inventory and Penn State Worry Scale from baseline to the end of intervention. For primary analyses, treatment outcomes will be assessed by ANCOVA, with change in anxiety score as the baseline variable, while the baseline anxiety score and other baseline characteristics that significantly differ between groups will serve as covariates. Conclusions This is a first randomized controlled trial that compare the effectiveness of MBCT with an active control, findings will advance current knowledge in the management of GAD and the way that group intervention can be delivered and inform future research. Unique Trail Number (assigned by Centre for Clinical Trails, Clinical Trials registry, The Chinese University of Hong Kong: CUHK_CCT00267

Hospital recruitment for a pragmatic cluster-randomized clinical trial: Lessons learned from the COMPASS study.

Science.gov (United States)

Johnson, Anna M; Jones, Sara B; Duncan, Pamela W; Bushnell, Cheryl D; Coleman, Sylvia W; Mettam, Laurie H; Kucharska-Newton, Anna M; Sissine, Mysha E; Rosamond, Wayne D

2018-01-26

Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in "real-world" clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers' increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7-14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources (n = 33, 61%), lack of health system support (n = 16, 30%), and lack of support of individual decision-makers (n = 11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board

A general method for handling missing binary outcome data in randomized controlled trials

OpenAIRE

Jackson, Dan; White, Ian R; Mason, Dan; Sutton, Stephen

2014-01-01

Aims The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes. Design We propose a sensitivity analysis where standard analyses, which could include ‘missing = smoking’ and ‘last observation carried forward’, are embedded in a wider class of models. Setting We apply our general method to data from two smoking cessation trials. Partici...

Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review.

Science.gov (United States)

Taljaard, Monica; Hemming, Karla; Shah, Lena; Giraudeau, Bruno; Grimshaw, Jeremy M; Weijer, Charles

2017-08-01

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants-yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28

A randomized trial of specialized versus standard neck physiotherapy in cervical dystonia.

Science.gov (United States)

Counsell, Carl; Sinclair, Hazel; Fowlie, Jillian; Tyrrell, Elaine; Derry, Natalie; Meager, Peter; Norrie, John; Grosset, Donald

2016-02-01

Anecdotal reports suggested that a specialized physiotherapy technique developed in France (the Bleton technique) improved primary cervical dystonia. We evaluated the technique in a randomized trial. A parallel-group, single-blind, two-centre randomized trial compared the specialized outpatient physiotherapy programme given by trained physiotherapists up to once a week for 24 weeks with standard physiotherapy advice for neck problems. Randomization was by a central telephone service. The primary outcome was the change in the total Toronto Western Spasmodic Torticollis Rating (TWSTR) scale, measured before any botulinum injections that were due, between baseline and 24 weeks evaluated by a clinician masked to treatment. Analysis was by intention-to-treat. 110 patients were randomized (55 in each group) with 24 week outcomes available for 84. Most (92%) were receiving botulinum toxin injections. Physiotherapy adherence was good. There was no difference between the groups in the change in TWSTR score over 24 weeks (mean adjusted difference 1.44 [95% CI -3.63, 6.51]) or 52 weeks (mean adjusted difference 2.47 [-2.72, 7.65]) nor in any of the secondary outcome measures (Cervical Dystonia Impact Profile-58, clinician and patient-rated global impression of change, mean botulinum toxin dose). Both groups showed large sustained improvements compared to baseline in the TWSTR, most of which occurred in the first four weeks. There were no major adverse events. Subgroup analysis suggested a centre effect. There was no statistically or clinically significant benefit from the specialized physiotherapy compared to standard neck physiotherapy advice but further trials are warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pilot randomized controlled trial of dialectical behavior therapy group skills training for ADHD among college students.

Science.gov (United States)

Fleming, Andrew P; McMahon, Robert J; Moran, Lyndsey R; Peterson, A Paige; Dreessen, Anthony

2015-03-01

ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications.

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.

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

Directory of Open Access Journals (Sweden)

Stephanie Coronado-Montoya

Full Text Available A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified.CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses.108 (87% of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88% concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7. Of 21 trial registrations, 13 (62% remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases.The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

Effectiveness of acupuncture for angina pectoris: a systematic review of randomized controlled trials.

Science.gov (United States)

Yu, Changhe; Ji, Kangshou; Cao, Huijuan; Wang, Ying; Jin, Hwang Hye; Zhang, Zhe; Yang, Guanlin

2015-03-28

The purpose of this systematic review is to assess the effectiveness of acupuncture for angina pectoris. Eleven electronic databases were searched until January 2013. The study included randomized controlled trials that the effectiveness of acupuncture alone was compared to anti-angina medicines (in addition to conventional treatment) and the effectiveness of a combination of acupuncture plus anti-angina medicines was compared to anti-angina medicines alone. The trial selection, data extraction, quality assessment and data analytic procedures outlined in the 2011 Cochrane Handbook were involved. The study included 25 randomized controlled trials (involving 2,058 patients) that met our inclusion criteria. The pooled results showed that the number of patients with ineffectiveness of angina relief was less in the combined acupuncture-anti-angina treatment group than in the anti-angina medicines alone group (RR 0.33, 95% CI 0.23-0.47, p angina medicines alone group, fewer patients in the combined treatment group showed no ECG improvement (RR 0.50, 95% CI 0.40-0.62, p angina medicines alone for both outcome measures. Only four trials mentioned adverse effects. One trial found no significant difference between acupuncture and Chinese medicine, and three reported no adverse events. The quality of the trials was found to be low. The findings showed very low evidence to support the use of acupuncture for improving angina symptoms and ECG of angina patients. However, the quality of the trials included in this study was low. Large and rigorously designed trials are needed to confirm the potential benefit and adverse events of acupuncture.

Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial. A randomized clinical trial of integrated treatment and standard treatment

DEFF Research Database (Denmark)

Nordentoft, Merete; Thorup, Anne; Petersen, Lone

2006-01-01

Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms.......Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms....

A combined community- and facility-based approach to improve pregnancy outcomes in low-resource settings: a Global Network cluster randomized trial.

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Pasha, Omrana; McClure, Elizabeth M; Wright, Linda L; Saleem, Sarah; Goudar, Shivaprasad S; Chomba, Elwyn; Patel, Archana; Esamai, Fabian; Garces, Ana; Althabe, Fernando; Kodkany, Bhala; Mabeya, Hillary; Manasyan, Albert; Carlo, Waldemar A; Derman, Richard J; Hibberd, Patricia L; Liechty, Edward K; Krebs, Nancy; Hambidge, K Michael; Buekens, Pierre; Moore, Janet; Jobe, Alan H; Koso-Thomas, Marion; Wallace, Dennis D; Stalls, Suzanne; Goldenberg, Robert L

2013-10-03

Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries. These differences have been related to poor access to and poor quality of obstetric and neonatal care. This trial tested the hypothesis that teams of health care providers, administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations. In seven geographic areas in five low-income and one middle-income country, most with high perinatal mortality rates and substantial numbers of home deliveries, we performed a cluster randomized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport, community birth attendant training in problem recognition, and facility staff training in the management of obstetric and neonatal emergencies. The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Despite extensive effort in all sites in each of the three intervention areas, no differences emerged in the primary or any secondary outcome between the intervention and control clusters. In both groups, the mean perinatal mortality was 40.1/1,000 births (P = 0.9996). Neither were there differences between the two groups in outcomes in the last six months of the project, in the year following intervention cessation, nor in the clusters that best implemented the intervention. This cluster randomized comprehensive, large-scale, multi-sector intervention did not result in detectable impact on the proposed outcomes. While this does not negate the importance of these interventions, we expect that achieving improvement in pregnancy outcomes in these settings will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial, and without them provider training

Randomized controlled trial of SecondStory, an intervention targeting posttraumatic growth, with bereaved adults.

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Roepke, Ann Marie; Tsukayama, Eli; Forgeard, Marie; Blackie, Laura; Jayawickreme, Eranda

2018-06-01

People often report positive psychological changes after adversity, a phenomenon known as posttraumatic growth (PTG). Few PTG-focused interventions have been rigorously tested, and measurement strategies have had significant limitations. This study evaluated the effects of a new group-format psychosocial intervention, SecondStory, aimed at facilitating PTG by helping participants make meaning of the past and plan a purposeful future. In a randomized controlled trial, adults (N = 112, 64% women) bereaved within 5 years were randomly assigned to SecondStory or an active control, expressive writing. The primary outcome, PTG, was measured using two contrasting methods: the Posttraumatic Growth Inventory, which asks participants retrospectively how much they believe they have changed due to struggling with adversity, and the Current-Standing Posttraumatic Growth Inventory, which tracks quantifiable change in participants' standing in PTG domains over time. Secondary outcomes included depression symptoms, posttraumatic stress symptoms, and life satisfaction. Outcomes were measured at 2-week intervals: pretest, posttest, and three follow-up occasions. Hierarchical linear modeling was used to assess whether SecondStory participants experienced greater gains in primary and/or secondary outcomes over the 8-week trial. Results indicated that SecondStory participants did not show significantly greater improvements than control participants on measures of PTG, posttraumatic stress, or life satisfaction, but they did show greater decreases in depression symptoms by the first follow-up. These findings suggest that SecondStory may not facilitate PTG more effectively than existing interventions but may be promising for addressing depression. Positive interventions may productively be refined to support people experiencing trauma and loss. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) – a randomized controlled trial

DEFF Research Database (Denmark)

Jarden, Mary; Møller, Tom; Kjeldsen, Lars

2013-01-01

and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured...... and supervised counseling and exercise program.Methods/design: This paper presents the study protocol: Patient Activation through Counseling and Exercise -- Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction...... chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70 - 80%) on an ergometer cycle...

Randomized controlled trials in children's heart surgery in the 21st century: a systematic review.

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Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-04-01

Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children's heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). The recent literature in children's heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

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Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low

Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials

International Nuclear Information System (INIS)

Vaidya, Jayant S.; Bulsara, Max; Wenz, Frederik; Coombs, Nathan; Singer, Julian; Ebbs, Stephen; Massarut, Samuele; Saunders, Christobel; Douek, Michael; Williams, Norman R.; Joseph, David; Tobias, Jeffrey S.; Baum, Michael

2016-01-01

Purpose: With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). Methods and Materials: We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms “partial breast irradiation” OR “intraoperative radiotherapy” OR “IMRT” OR (“accelerated” AND “radiation”) AND “randomised/randomized,” as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. Results: We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non–breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), −0.7 to +0.7]; P=.999). Non–breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, −2.1% to −0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, −2.5% to 0.0%]; P=.05). Conclusions: Use of PBI instead of WBI in selected patients results in a lower 5-year non–breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when

Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials

Energy Technology Data Exchange (ETDEWEB)

Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Surgery, Royal Free Hospital, London (United Kingdom); Department of Surgery, Whittington Health, London (United Kingdom); Bulsara, Max [Department of Biostatistics, University of Notre Dame, Fremantle, WA (Australia); Wenz, Frederik [Department of Radiation Oncology, University Medical Centre Mannheim, University of Heidelberg, Mannheim (Germany); Coombs, Nathan [Department of Surgery, Great Western Hospital, Swindon (United Kingdom); Singer, Julian [Department of Clinical Oncology, The Princess Alexandra Hospital, Harlow (United Kingdom); Ebbs, Stephen [Croydon University Hospital, Croydon (United Kingdom); Massarut, Samuele [National Cancer Institute, Centro di Riferimento Oncologico, Aviano (Italy); Saunders, Christobel [School of Surgery, University of Western Australia, Perth, WA (Australia); Douek, Michael [Department of Surgery, Kings College London, London (United Kingdom); Williams, Norman R. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Joseph, David [Departments of Radiation Oncology, and Surgery, Sir Charles Gairdner Hospital, Perth, WA (Australia); Tobias, Jeffrey S. [Department of Clinical Oncology, University College London Hospitals, London (United Kingdom); Baum, Michael [Division of Surgery and Interventional Science, University College London, London (United Kingdom)

2016-10-01

Purpose: With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). Methods and Materials: We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms “partial breast irradiation” OR “intraoperative radiotherapy” OR “IMRT” OR (“accelerated” AND “radiation”) AND “randomised/randomized,” as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. Results: We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non–breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), −0.7 to +0.7]; P=.999). Non–breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, −2.1% to −0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, −2.5% to 0.0%]; P=.05). Conclusions: Use of PBI instead of WBI in selected patients results in a lower 5-year non–breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when

Protocol and Recruitment Results from a Randomized Controlled Trial Comparing Group Phone-Based versus Newsletter Interventions for Weight Loss Maintenance among Rural Breast Cancer Survivors

OpenAIRE

Befort, Christie A.; Klemp, Jennifer R.; Fabian, Carol; Perri, Michael G.; Sullivan, Debra K.; Schmitz, Kathryn H.; Diaz, Francisco J.; Shireman, Theresa

2014-01-01

Obesity is a risk factor for breast cancer recurrence and death. Women who reside in rural areas have higher obesity prevalence and suffer from breast cancer treatment-related disparities compared to urban women. The objective of this 5-year randomized controlled trial is to compare methods for delivering extended care for weight loss maintenance among rural breast cancer survivors. Group phone-based counseling via conference calls addresses access barriers, is more cost-effective than indivi...

The Efficacy of Parent-Child Interaction Therapy with Chinese Families: Randomized Controlled Trial

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Leung, Cynthia; Tsang, Sandra; Sin, Tammy C. S.; Choi, Siu-yan

2015-01-01

Objective: This study aimed to examine the efficacy of the Parent-Child Interaction Therapy (PCIT) in Hong Kong Chinese families, using randomized controlled trial design. Methods: The participants included 111 Hong Kong Chinese parents with children aged 2--7 years old, who were randomized into the intervention group (n = 54) and control group (n…

Event Rates in Randomized Clinical Trials Evaluating Cardiovascular Interventions and Devices

NARCIS (Netherlands)

Mahmoud, Karim D.; Lennon, Ryan J.; Holmes, David R.

2015-01-01

Randomized clinical trials (RCTs) are considered the gold standard for evidence-based medicine. However, an accurate estimation of the event rate is crucial for their ability to test clinical hypotheses. Overestimation of event rates reduces the required sample size but can compromise the

Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence.

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Van Patten, Cheri L; de Boer, Johan G; Tomlinson Guns, Emma S

2008-12-01

We review the effect of diet and dietary supplement interventions on prostate cancer progression, recurrence and survival. A literature search was conducted in MEDLINE, EMBASE and CINAHL to identify diet and dietary supplement intervention studies in men with prostate cancer using prostate specific antigen or prostate specific antigen doubling time as a surrogate serum biomarker of prostate cancer recurrence and/or survival. Of the 32 studies identified 9 (28%) were randomized controlled trials and the focus of this review. In these studies men had confirmed prostate cancer and elevated or increasing prostate specific antigen. Only 1 trial included men with metastatic disease. When body mass index was reported, men were overweight or obese. A significant decrease in prostate specific antigen was observed in some studies using a low fat vegan diet, soy beverage or lycopene supplement. While not often reported as an end point, a significant increase in prostate specific antigen doubling time was observed in a study on lycopene supplementation. In only 1 randomized controlled trial in men undergoing orchiectomy was a survival end point of fewer deaths with lycopene supplementation reported. A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

A randomized trial comparing primary angioplasty versus stent placement for symptomatic intracranial stenosis

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Qureshi, Adnan I; Chaudhry, Saqib A; Siddiq, Farhan; Majidi, Shahram; Rodriguez, Gustavo J; Suri, M Fareed K

2013-01-01

Background: Both primary angioplasty alone and angioplasty with a self-expanding stent have been compared in non-randomized concurrent clinical studies that suggest equivalent results. However, there is no randomized trial that has compared the two procedures in patients with symptomatic high grade intracranial stenosis. Objective: The primary aim of the randomized trial was to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. Methods: The study prospectively evaluated efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥ 50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment. Results: A total of 18 patients were recruited in the study (mean age [±SD] was 64.7 ± 15.1 years); out of these, 12 were men. Of these 18, 10 were treated with primary angioplasty and 8 were treated with angioplasty followed by self-expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The total fluoroscopic time (mean [±SD]) was lower in patients undergoing primary angioplasty 37 [±11] min versus those undergoing angioplasty followed by self-expanding stent 42 [±15] min, P = 0.4321. The stroke and death rate within 1 month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One patient randomized to stent placement continued to have recurrent ischemic symptoms requiring another angioplasty in the vertebral artery on post-procedure Day 2. Conclusions: The trial suggests that a randomized trial comparing primary angioplasty to angioplasty

Components of effective randomized controlled trials of hydrotherapy programs for fibromyalgia syndrome: A systematic review

Directory of Open Access Journals (Sweden)

Luke Perraton

2009-11-01

Full Text Available Luke Perraton, Zuzana Machotka, Saravana KumarInternational Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia, AustraliaAim: Previous systematic reviews have found hydrotherapy to be an effective management strategy for fibromyalgia syndrome (FMS. The aim of this systematic review was to summarize the components of hydrotherapy programs used in randomized controlled trials.Method: A systematic review of randomized controlled trials was conducted. Only trials that have reported significant FMS-related outcomes were included. Data relating to the components of hydrotherapy programs (exercise type, duration, frequency and intensity, environmental factors, and service delivery were analyzed.Results: Eleven randomized controlled trials were included in this review. Overall, the quality of trials was good. Aerobic exercise featured in all 11 trials and the majority of hydrotherapy programs included either a strengthening or flexibility component. Great variability was noted in both the environmental components of hydrotherapy programs and service delivery.Conclusions: Aerobic exercise, warm up and cool-down periods and relaxation exercises are common features of hydrotherapy programs that report significant FMS-related outcomes. Treatment duration of 60 minutes, frequency of three sessions per week and an intensity equivalent to 60%–80% maximum heart rate were the most commonly reported exercise components. Exercise appears to be the most important component of an effective hydrotherapy program for FMS, particularly when considering mental health-related outcomes.Keywords: hydrotherapy, fibromyalgia syndrome, exercise, effective, components

Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

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Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

2018-03-22

Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions.

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Leibovici, Leonard; Paul, Mical; Garner, Paul; Sinclair, David J; Afshari, Arash; Pace, Nathan Leon; Cullum, Nicky; Williams, Hywel C; Smyth, Alan; Skoetz, Nicole; Del Mar, Chris; Schilder, Anne G M; Yahav, Dafna; Tovey, David

2016-09-01

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Home medicines reviews following acute coronary syndrome: study protocol for a randomized controlled trial

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Bernal Daniel DL

2012-04-01

Full Text Available Abstract Background Despite continual improvements in the management of acute coronary syndromes, adherence to guideline-based medications remains suboptimal. We aim to improve adherence with guideline-based therapy following acute coronary syndrome using an existing service that is provided by specifically trained pharmacists, called a Home Medicines Review. We have made two minor adjustments to target the focus of the existing service including an acute coronary syndrome specific referral letter and a training package for the pharmacists providing the service. Methods/Design We will be conducting a randomized controlled trial to compare the directed home medicines review service to usual care following acute coronary syndromes. All patients aged 18 to 80 years and with a working diagnosis of acute coronary syndrome, who are admitted to two public, acute care hospitals, will be screened for enrolment into the trial. Exclusion criteria will include: not being discharged home, documented cognitive decline, non-Medicare eligibility, and presence of a terminal malignancy. Randomization concealment and sequence generation will occur through a centrally-monitored computer program. Patients randomized to the control group will receive usual post-discharge care. Patients randomized to receive the intervention will be offered usual post-discharge care and a directed home medicines review at two months post-discharge. The study endpoints will be six and twelve months post-discharge. The primary outcome will be the proportion of patients who are adherent to a complete, guideline-based medication regimen. Secondary outcomes will include hospital readmission rates, length of hospital stays, changes in quality of life, smoking cessation rates, cardiac rehabilitation completion rates, and mortality. Discussion As the trial is closely based on an existing service, any improvements observed should be highly translatable into regular practice. Possible

Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.

Directory of Open Access Journals (Sweden)

Astrid V Fahlenkamp

Full Text Available Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV. We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis.220 subjects with elevated PONV risk (Apfel score ≥2 undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up.Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044. Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138. After xenon, nausea occurred significantly earlier (p = 0.014, was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups.In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea.EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.

Randomized Trial of 2 Versus 1 Dose of Measles Vaccine

DEFF Research Database (Denmark)

Brønd, Marie; Martins, Cesario L; Byberg, Stine

2018-01-01

Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investig...

Design and rationale of the medical students learning weight management counseling skills (MSWeight) group randomized controlled trial.

Science.gov (United States)

Ockene, Judith K; Ashe, Karen M; Hayes, Rashelle B; Churchill, Linda C; Crawford, Sybil L; Geller, Alan C; Jolicoeur, Denise; Olendzki, Barbara C; Basco, Maria Theresa; Pendharkar, Jyothi A; Ferguson, Kristi J; Guck, Thomas P; Margo, Katherine L; Okuliar, Catherine A; Shaw, Monica A; Soleymani, Taraneh; Stadler, Diane D; Warrier, Sarita S; Pbert, Lori

2018-01-01

Physicians have an important role addressing the obesity epidemic. Lack of adequate teaching to provide weight management counseling (WMC) is cited as a reason for limited treatment. National guidelines have not been translated into an evidence-supported, competency-based curriculum in medical schools. Weight Management Counseling in Medical Schools: A Randomized Controlled Trial (MSWeight) is designed to determine if a multi-modal theoretically-guided WMC educational intervention improves observed counseling skills and secondarily improve perceived skills and self-efficacy among medical students compared to traditional education (TE). Eight U.S. medical schools were pair-matched and randomized in a group randomized controlled trial to evaluate whether a multi-modal education (MME) intervention compared to traditional education (TE) improves observed WMC skills. The MME intervention includes innovative components in years 1-3: a structured web-course; a role play exercise, WebPatientEncounter, and an enhanced outpatient internal medicine or family medicine clerkship. This evidence-supported curriculum uses the 5As framework to guide treatment and incorporates patient-centered counseling to engage the patient. The primary outcome is a comparison of scores on an Objective Structured Clinical Examination (OSCE) WMC case among third year medical students. The secondary outcome compares changes in scores of medical students from their first to third year on an assessment of perceived WMC skills and self-efficacy. MSWeight is the first RCT in medical schools to evaluate whether interventions integrated into the curriculum improve medical students' WMC skills. If this educational approach for teaching WMC is effective, feasible and acceptable it can affect how medical schools integrate WMC teaching into their curriculum. Copyright © 2017 Elsevier Inc. All rights reserved.

Healthy Beyond Pregnancy, a Web-Based Intervention to Improve Adherence to Postpartum Care: Randomized Controlled Feasibility Trial.

Science.gov (United States)

Himes, Katherine Park; Donovan, Heidi; Wang, Stephanie; Weaver, Carrie; Grove, Jillian Rae; Facco, Francesca Lucia

2017-10-10

During the postpartum visit, health care providers address issues with short- and long-term implications for maternal and child health. Women with Medicaid insurance are less likely to return for a postpartum visit compared with women with private insurance. Behavioral economics acknowledges that people do not make exclusively rational choices, rather immediate gratification, cognitive and psychological biases, and social norms influence decision making. Drawing on insights from decision science, behavioral economists have examined how these biases can be modulated through carefully designed interventions. We have developed a Web-based tool, Healthy Beyond Pregnancy, that incorporates empirically derived concepts of behavioral economics to improve adherence rates to the postpartum visit. The primary objectives of this pilot study were to (1) refine and assess the usability of Healthy Beyond Pregnancy and (2) assess the feasibility of a randomized controlled trial (RCT) of the intervention. We used a multistep process and multidisciplinary team of maternal-fetal medicine physicians, a behavioral economist, and researchers with expertise in behavioral interventions to design Healthy Beyond Pregnancy. We assessed the usability of the program with the Post-Study System Usability Questionnaire (PSSUQ), a validated 7-point scale, and semistructured interviews with postpartum women. We then conducted a feasibility trial to determine the proportion of eligible women who were willing to participate in an RCT of Healthy Beyond Pregnancy and the proportion of women willing to complete the Web-based program. Exploratory outcomes of the pilot trial included attendance at the postpartum visit, uptake of long-acting reversible contraception, and uptake of any contraception. The median PSSUQ score for Healthy Beyond Pregnancy was 6.5 (interquartile range: 6.1-7) demonstrating high usability. Semistructured interviews (n=10) provided in-depth comments about users' experience and

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.

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials.

Science.gov (United States)

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley; Danovitch, Itai

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality , VR therapy , treatment , and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78-0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness.

A randomized phase II dose-response exercise trial among colon cancer survivors: Purpose, study design, methods, and recruitment results.

Science.gov (United States)

Brown, Justin C; Troxel, Andrea B; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S; Rickels, Michael R; Rhim, Andrew D; Rustgi, Anil K; Courneya, Kerry S; Schmitz, Kathryn H

2016-03-01

Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the courage trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. The primary objective of the courage trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·week(-1)) and high-dose (300 min·week(-1)) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (Pclinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. Copyright © 2016 Elsevier Inc. All rights reserved.

Empirical evidence of study design biases in randomized trials

DEFF Research Database (Denmark)

Page, Matthew J.; Higgins, Julian P. T.; Clayton, Gemma

2016-01-01

search September 2012), and searched Ovid MEDLINE and Ovid EMBASE for studies indexed from Jan 2012-May 2015. Data were extracted by one author and verified by another. We combined estimates of average bias (e.g. ratio of odds ratios (ROR) or difference in standardised mean differences (dSMD)) in meta......-analyses using the random-effects model. Analyses were stratified by type of outcome ("mortality" versus "other objective" versus "subjective"). Direction of effect was standardised so that ROR SMD ... studies). For these characteristics, the average bias appeared to be larger in trials of subjective outcomes compared with other objective outcomes. Also, intervention effects for subjective outcomes appear to be exaggerated in trials with lack of/unclear blinding of participants (versus blinding) (dSMD...

Gaze-Contingent Music Reward Therapy for Social Anxiety Disorder: A Randomized Controlled Trial.

Science.gov (United States)

Lazarov, Amit; Pine, Daniel S; Bar-Haim, Yair

2017-07-01

Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. Forty patients with social anxiety disorder were randomly assigned to eight sessions of either gaze-contingent music reward therapy, designed to divert patients' gaze toward neutral stimuli rather than threat stimuli, or to a control condition. Clinician and self-report measures of social anxiety were acquired pretreatment, posttreatment, and at 3-month follow-up. Dwell time on socially threatening faces was assessed during the training sessions and at pre- and posttreatment. Gaze-contingent music reward therapy yielded greater reductions of symptoms of social anxiety disorder than the control condition on both clinician-rated and self-reported measures. Therapeutic effects were maintained at follow-up. Gaze-contingent music reward therapy, but not the control condition, also reduced dwell time on threat, which partially mediated clinical effects. Finally, gaze-contingent music reward therapy, but not the control condition, also altered dwell time on socially threatening faces not used in training, reflecting near-transfer training generalization. This is the first randomized controlled trial to examine a gaze-contingent intervention in social anxiety disorder. The results demonstrate target engagement and clinical effects. This study sets the stage for larger randomized controlled trials and testing in other emotional disorders.

After-School Multifamily Groups: A Randomized Controlled Trial Involving Low-Income, Urban, Latino Children

Science.gov (United States)

McDonald, Lynn; Moberg, D. Paul; Brown, Roger; Rodriguez-Espiricueta, Ismael; Flores, Nydia I.; Burke, Melissa P.; Coover, Gail

2006-01-01

This randomized controlled trial evaluated a culturally representative parent engagement strategy with Latino parents of elementary school children. Ten urban schools serving low-income children from mixed cultural backgrounds participated in a large study. Classrooms were randomly assigned either either to an after-school, multifamily support…

Quality of methodological reporting of randomized clinical trials of sodium-glucose cotransporter-2 (sglt2 inhibitors

Directory of Open Access Journals (Sweden)

Hadeel Alfahmi

2017-01-01

Full Text Available Sodium-glucose cotransporter-2 (SGLT2 inhibitors are a new class of medicines approved recently for the treatment of type 2 diabetes. To improve the quality of randomized clinical trial (RCT reports, the Consolidated Standards of Reporting Trials (CONSORT statement for methodological features was created. For achieving our objective in this study, we assessed the quality of methodological reporting of RCTs of SGLT2 inhibitors according to the 2010 CONSORT statement. We reviewed and analyzed the methodology of SGLT2 inhibitors RCTs that were approved by the Food & Drug Administration (FDA. Of the 27 trials, participants, eligibility criteria, and additional analyses were reported in 100% of the trials. In addition, trial design, interventions, and statistical methods were reported in 96.3% of the trials. Outcomes were reported in 93.6% of the trials. Settings were reported in 85.2% of the trials. Blinding and sample size were reported in 66.7 and 59.3% of the trials, respectively. Sequence allocation and the type of randomization were reported in 63 and 74.1% of the trials, respectively. Besides those, a few methodological items were inadequate in the trials. Allocation concealment was inadequate in most of the trials. It was reported only in 11.1% of the trials. The majority of RCTs have high percentage adherence for more than half of the methodological items of the 2010 CONSORT statement.

Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome

DEFF Research Database (Denmark)

Gluud, Lise L; Christensen, Kurt; Christensen, Erik

2010-01-01

Vasoconstrictor drugs may improve renal function in hepatorenal syndrome (HRS), but the effect on mortality has not been established. We therefore performed a systematic review of randomized trials on vasoconstrictor drugs for type 1 or type 2 HRS. Mortality was the primary outcome measure...

Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial

NARCIS (Netherlands)

Lerchbaum, Elisabeth; Pilz, Stefan; Trummer, Christian; Schwetz, Verena; Pachernegg, Oliver; Heijboer, Annemieke C.; Obermayer-Pietsch, Barbara

2017-01-01

Available evidence shows an association of vitamin D with androgen levels in men. However, results from preliminary randomized controlled trials (RCTs) are conflicting. To evaluate whether vitamin D supplementation increases total testosterone (TT) levels in healthy men. The Graz Vitamin D&TT-RCT is

A randomized trial evaluating a block-replacement regimen during radioiodine therapy

DEFF Research Database (Denmark)

Bonnema, Steen J; Grupe, Peter; Boel-Jørgensen, Henrik

2011-01-01

Eur J Clin Invest 2010 ABSTRACT: Background  Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies. Design  Patients with Graves' disease (GD, n = 51) or toxic nodular goitre...

Informed Consent to Study Purpose in Randomized Clinical Trials of Antibiotics, 1991 Through 2011.

Science.gov (United States)

Doshi, Peter; Hur, Peter; Jones, Mark; Albarmawi, Husam; Jefferson, Tom; Morgan, Daniel J; Spears, Patricia A; Powers, John H

2017-10-01

Potential research participants may assume that randomized trials comparing new interventions with older interventions always hypothesize greater efficacy for the new intervention, as in superiority trials. However, antibiotic trials frequently use "noninferiority" hypotheses allowing a degree of inferior efficacy deemed "clinically acceptable" compared with an older effective drug, in exchange for nonefficacy benefits (eg, decreased adverse effects). Considering these different benefit-harm trade-offs, proper informed consent necessitates supplying different information on the purposes of superiority and noninferiority trials. To determine the degree to which the study purpose is explained to potential participants in randomized clinical trials of antibiotics and the degree to which study protocols justify their selection of noninferiority hypotheses and amount of "clinically acceptable" inferiority. Cross-sectional analysis of study protocols, statistical analysis plans (SAPs), and informed consent forms (ICFs) from clinical study reports submitted to the European Medicines Agency. The ICFs were read by both methodologists and patient investigators. Protocols and SAPs were used as the reference standard to determine prespecified primary hypothesis and record rationale for selection of noninferiority hypotheses and noninferiority margins. This information was cross-referenced against ICFs to determine whether ICFs explained the study purpose. We obtained trial documents from 78 randomized trials with prespecified efficacy hypotheses (6 superiority, 72 noninferiority) for 17 antibiotics conducted between 1991 and 2011 that enrolled 39 407 patients. Fifty were included in the ICF analysis. All ICFs contained sections describing study purpose; however, none consistently conveyed study hypothesis to both methodologists and patient investigators. Methodologists found that 1 of 50 conveyed a study purpose. Patient investigators found that 11 of 50 conveyed a study

A novel cognitive behaviour therapy for bipolar disorders (Think Effectively About Mood Swings or TEAMS): study protocol for a randomized controlled trial.

Science.gov (United States)

Mansell, Warren; Tai, Sara; Clark, Alexandra; Akgonul, Savas; Dunn, Graham; Davies, Linda; Law, Heather; Morriss, Richard; Tinning, Neil; Morrison, Anthony P

2014-10-24

Existing psychological therapies for bipolar disorders have been found to have mixed results, with a consensus that they provide a significant, but modest, effect on clinical outcomes. Typically, these approaches have focused on promoting strategies to prevent future relapse. An alternative treatment approach, termed 'Think Effectively About Mood Swings' (TEAMS) addresses current symptoms, including subclinical hypomania, depression and anxiety, and promotes long-term recovery. Following the publication of a theoretical model, a range of research studies testing the model and a case series have demonstrated positive results. The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial. A target number of 84 patients with a diagnosis of bipolar I or II disorder, or bipolar disorder not-otherwise-specified are screened, allocated to a baseline assessment and randomized to either 16 sessions of TEAMS therapy plus treatment-as-usual (TAU) or TAU. Patients complete self-report inventories of depression, anxiety, recovery status and bipolar cognitions targeted by TEAMS. Assessments of diagnosis, bipolar symptoms, medication, access to services and quality of life are conducted by assessors blind to treatment condition at 3, 6, 12 and 18 months post-randomization. The main aim is to evaluate recruitment and retention of participants into both arms of the study, as well as adherence to therapy, to determine feasibility and acceptability. It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization. The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety, reduce bipolar cognitions, improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up. The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of

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.

Sleep disorders in patients with depression or schizophrenia: A randomized controlled trial using acupuncture treatment

NARCIS (Netherlands)

Bosch, M.P.C.; Noort, M.W.M.L. van den; Staudte, H.; Lim, S.; Yeo, S.; Coenen, A.M.L.; Luijtelaar, E.L.J.M. van

2016-01-01

Introduction: The purpose of this preliminary clinical trial was to investigate whether acupuncture has a positive influence on sleep and symptomatology in patients with schizophrenia or depression. Methods: A randomized controlled trial was used. One hundred participants were recruited: 40

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial: rationale and design

Directory of Open Access Journals (Sweden)

Schuler Gerhard

2011-02-01

Full Text Available Abstract Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO, but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age ( Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011. Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA

A preliminary randomized controlled trial of a behavioral exercise intervention for smoking cessation.

Science.gov (United States)

Abrantes, Ana M; Bloom, Erika Litvin; Strong, David R; Riebe, Deborah; Marcus, Bess H; Desaulniers, Julie; Fokas, Kathryn; Brown, Richard A

2014-08-01

Previous exercise intervention studies for smoking cessation have been challenged by a number of methodological limitations that confound the potential efficacy of aerobic exercise for smoking cessation. The preliminary efficacy of a behavioral exercise intervention that incorporated features designed to address prior limitations was tested in a randomized controlled trial (RCT). Sixty-one smokers (65.6% female, mean age = 47.3 years, smoked a mean of 19.7 cigarettes/day) were randomized to receive either a 12-week exercise intervention or a 12-week health education contact control. Participants in both conditions received an 8-week telephone-delivered, standard smoking cessation protocol (with the transdermal nicotine patch). Follow-ups were conducted at the end of treatment (EOT), 6- and 12-month timepoints. There were no differences between conditions with respect to the number of weekly exercise or health education sessions attended (9.3±2.8 vs. 9.3±3.0, respectively). While not statistically significant, participants in the exercise condition demonstrated higher verified abstinence rates (EOT: 40% vs. 22.6%, odds ratio [OR] = 2.28; 6- and 12-month follow-ups: 26.7% vs. 12.9%, OR = 2.46). Irrespective of treatment condition, higher levels of moderate-to-vigorous exercise were associated with lower levels of depressive symptoms during the intervention. The results of this small RCT point toward the benefit of a behavioral exercise intervention designed to address previous methodological limitations for smoking cessation. Given the potential public health impact of the demonstrated efficacy of exercise for smoking cessation, the continued development and optimization of exercise interventions for smokers through larger RCTs merits pursuit. © The Author 2014. 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.

Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial.

Science.gov (United States)

Foglia, Elizabeth E; Owen, Louise S; Thio, Marta; Ratcliffe, Sarah J; Lista, Gianluca; Te Pas, Arjan; Hummler, Helmut; Nadkarni, Vinay; Ades, Anne; Posencheg, Michael; Keszler, Martin; Davis, Peter; Kirpalani, Haresh

2015-03-15

Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth. Sustained inflation (SI) combined with positive end expiratory pressure (PEEP) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation (IPPV) with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs (SAIL) trial was designed to study this question. This multisite prospective randomized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth. Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation. The study intervention consists of performing an initial SI (20 cm H20 for 15 seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with or without IPPV, as needed. The control group will be treated with initial IPPV with PEEP. The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age. www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014.

Recruitment barriers in a randomized controlled trial from the physicians' perspective – A postal survey

Directory of Open Access Journals (Sweden)

Karrer Werner

2009-03-01

Full Text Available Abstract Background The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment. Methods We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier to 7 (no agreement with statement = no recruitment barrier. Results 38 of 55 recruiting physicians returned questionnaires (69% response rate, of which 35 could be analyzed (64% useable response rate. Recruiting physicians reported that "time constraints" (median agreement of 3, interquartile range 2–5 had the most negative impact on recruitment followed by "difficulties including identified eligible patients" (median agreement of 5, IQR 3–6. Other barriers such as "trial design barriers", "lack of access to treatment", "individual barriers of recruiting physicians" or "insufficient training of recruiting physicians" were perceived to have little or no impact on patient recruitment. Conclusion Physicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be

PRagmatic trial Of Video Education in Nursing homes: The design and rationale for a pragmatic cluster randomized trial in the nursing home setting.

Science.gov (United States)

Mor, Vincent; Volandes, Angelo E; Gutman, Roee; Gatsonis, Constantine; Mitchell, Susan L

2017-04-01

Background/Aims Nursing homes are complex healthcare systems serving an increasingly sick population. Nursing homes must engage patients in advance care planning, but do so inconsistently. Video decision support tools improved advance care planning in small randomized controlled trials. Pragmatic trials are increasingly employed in health services research, although not commonly in the nursing home setting to which they are well-suited. This report presents the design and rationale for a pragmatic cluster randomized controlled trial that evaluated the "real world" application of an Advance Care Planning Video Program in two large US nursing home healthcare systems. Methods PRagmatic trial Of Video Education in Nursing homes was conducted in 360 nursing homes (N = 119 intervention/N = 241 control) owned by two healthcare systems. Over an 18-month implementation period, intervention facilities were instructed to offer the Advance Care Planning Video Program to all patients. Control facilities employed usual advance care planning practices. Patient characteristics and outcomes were ascertained from Medicare Claims, Minimum Data Set assessments, and facility electronic medical record data. Intervention adherence was measured using a Video Status Report embedded into electronic medical record systems. The primary outcome was the number of hospitalizations/person-day alive among long-stay patients with advanced dementia or cardiopulmonary disease. The rationale for the approaches to facility randomization and recruitment, intervention implementation, population selection, data acquisition, regulatory issues, and statistical analyses are discussed. Results The large number of well-characterized candidate facilities enabled several unique design features including stratification on historical hospitalization rates, randomization prior to recruitment, and 2:1 control to intervention facilities ratio. Strong endorsement from corporate leadership made randomization

Test of a workforce development intervention to expand opioid use disorder treatment pharmacotherapy prescribers: protocol for a cluster randomized trial

Directory of Open Access Journals (Sweden)

Todd Molfenter

2017-11-01

Full Text Available Abstract Background Overdoses due to non-medical use of prescription opioids and other opiates have become the leading cause of accidental deaths in the USA. Buprenorphine and extended-release naltrexone are key evidence-based pharmacotherapies available to addiction treatment providers to address opioid use disorder (OUD and prevent overdose deaths. Treatment organizations’ efforts to provide these pharmacotherapies have, however, been stymied by limited success in recruiting providers (physicians, nurse practitioners, and physician assistants to prescribe these medications. Historically, the addiction treatment field has not attracted physicians, and many barriers to implementing OUD pharmacotherapy exist, ranging from lack of confidence in treating OUD patients to concerns regarding reimbursement. Throughout the USA, the prevalence of OUD far exceeds the capacity of the OUD pharmacotherapy treatment system. Poor access to OUD pharmacotherapy prescribers has become a workforce development need for the addiction treatment field and a significant health issue. Methods This cluster randomized controlled trial (RCT is designed to increase buprenorphine and extended-release naltrexone treatment capacity for OUD. The implementation intervention to be tested is a bundle of OUD pharmacotherapy capacity building practices called the Prescriber Recruitment Bundle (PRB, which was developed and piloted in a previous statewide buprenorphine implementation study. For this cluster RCT, organizational sites will be recruited and then randomized into one of two arms: (1 control, with treatment as usual and access to a website with PRB resources, or (2 intervention, with organizations implementing the PRB using the Network for the Improvement of Addiction Treatment organizational change model over a 24-month intervention period and a 10-month sustainability period. The primary treatment outcomes for each organizational site are self-reported monthly counts of

A quantum-like model of homeopathy clinical trials: importance of in situ randomization and unblinding.

Science.gov (United States)

Beauvais, Francis

2013-04-01

The randomized controlled trial (RCT) is the 'gold standard' of modern clinical pharmacology. However, for many practitioners of homeopathy, blind RCTs are an inadequate research tool for testing complex therapies such as homeopathy. Classical probabilities used in biological sciences and in medicine are only a special case of the generalized theory of probability used in quantum physics. I describe homeopathy trials using a quantum-like statistical model, a model inspired by quantum physics and taking into consideration superposition of states, non-commuting observables, probability interferences, contextuality, etc. The negative effect of blinding on success of homeopathy trials and the 'smearing effect' ('specific' effects of homeopathy medicine occurring in the placebo group) are described by quantum-like probabilities without supplementary ad hoc hypotheses. The difference of positive outcome rates between placebo and homeopathy groups frequently vanish in centralized blind trials. The model proposed here suggests a way to circumvent such problems in masked homeopathy trials by incorporating in situ randomization/unblinding. In this quantum-like model of homeopathy clinical trials, success in open-label setting and failure with centralized blind RCTs emerge logically from the formalism. This model suggests that significant differences between placebo and homeopathy in blind RCTs would be found more frequently if in situ randomization/unblinding was used. Copyright © 2013. Published by Elsevier Ltd.

Shared Care in Monitoring Stable Glaucoma Patients: A Randomized Controlled Trial

NARCIS (Netherlands)

Holtzer-Goor, Kim M.; van Vliet, Ellen J.; van Sprundel, Esther; Plochg, Thomas; Koopmanschap, Marc A.; Klazinga, Niek S.; Lemij, Hans G.

2016-01-01

Comparing the quality of care provided by a hospital-based shared care glaucoma follow-up unit with care as usual. This randomized controlled trial included stable glaucoma patients and patients at risk for developing glaucoma. Patients in the Usual Care group (n=410) were seen by glaucoma

Oral Medication for Agitation of Psychiatric Origin: A Scoping Review of Randomized Controlled Trials.

Science.gov (United States)

Mullinax, Samuel; Shokraneh, Farhad; Wilson, Michael P; Adams, Clive E

2017-10-01

Understanding more about the efficacy and safety of oral second-generation antipsychotic medications in reducing the symptoms of acute agitation could improve the treatment of psychiatric emergencies. The objective of this scoping review was to examine the evidence base underlying expert consensus panel recommendations for the use of oral second-generation antipsychotics to treat acute agitation in mentally ill patients. The Cochrane Schizophrenia Group's Study-Based Register was searched for randomized controlled trials comparing oral second-generation antipsychotics, benzodiazepines, or first-generation antipsychotics with or without adjunctive benzodiazepines, irrespective of route of administration of the drug being compared. Six articles were included in the final review. Two oral second-generation antipsychotic medications were studied across the six included trials. While the studies had relatively small sample sizes, oral second-generation antipsychotics were similarly effective to intramuscular first-generation antipsychotics in treating symptoms of acute agitation and had similar side-effect profiles. This scoping review identified six randomized trials investigating the use of oral second-generation antipsychotic medications in the reduction of acute agitation among patients experiencing psychiatric emergencies. Further research will be necessary to make clinical recommendations due to the overall dearth of randomized trials, as well as the small sample sizes of the included studies. Copyright © 2017 Elsevier Inc. All rights reserved.

HEART: heart exercise and remote technologies: A randomized controlled trial study protocol

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Kira Geoffrey

2011-05-01

Full Text Available Abstract Background Cardiovascular disease (CVD is the leading cause of death worldwide. Cardiac rehabilitation (CR is aimed at improving health behaviors to slow or reverse the progression of CVD disease. Exercise is a central element of CR. Technologies such as mobile phones and the Internet (mHealth offer potential to overcome many of the psychological, physical, and geographical barriers that have been associated with lack of participation in exercise-based CR. We aim to trial the effectiveness of a mobile phone delivered exercise-based CR program to increase exercise capacity and functional outcomes compared with usual CR care in adults with CVD. This paper outlines the rationale and methods of the trial. Methods A single-blinded parallel two-arm randomized controlled trial is being conducted. A total of 170 people will be randomized at 1:1 ratio either to receive a mHealth CR program or usual care. Participants are identified by CR nurses from two metropolitan hospitals in Auckland, New Zealand through outpatient clinics and existing databases. Consenting participants are contacted to attend a baseline assessment. The intervention consists of a theory-based, personalized, automated package of text and video message components via participants' mobile phones and the Internet to increase exercise behavior, delivered over six months. The control group will continue with usual CR. Data collection occurs at baseline and 24 weeks (post-intervention. The primary outcome is change in maximal oxygen uptake from baseline to 24 weeks. Secondary outcomes include post-intervention measures on self-reported physical activity (IPAQ, cardiovascular risk factors (systolic blood pressure, weight, and waist to hip ratio, health related quality of life (SF-36, and cost-effectiveness. Discussion This manuscript presents the protocol for a randomized controlled trial of a mHealth exercise-based CR program. Results of this trial will provide much needed

Does mass azithromycin distribution impact child growth and nutrition in Niger? A cluster-randomized trial.

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Abdou Amza

2014-09-01

Full Text Available Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth.In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6-60 months of age.We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49.We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association.

Improving Prospective Memory in Persons With Parkinson Disease: A Randomized Controlled Trial.

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Foster, Erin R; McDaniel, Mark A; Rendell, Peter G

2017-05-01

Prospective memory (PM) is essential for productive and independent living and necessary for compliance with prescribed health behaviors. Parkinson disease (PD) can cause PM deficits that are associated with activity limitations and reduced quality of life. Forming implementation intentions (IIs) is an encoding strategy that may improve PM in this population. To determine the effect of IIs on PM performance in PD. This was a laboratory-based randomized controlled trial. Participants with mild to moderate PD without dementia (n = 62) performed a computerized PM test (Virtual Week) under standard instructions. One week later they were randomly allocated to perform it again while using either IIs or a rehearsal (RR) encoding strategy. PM performance was better with the use of both strategies relative to standard instructions. This effect was larger for tasks with event-based compared with time-based cues. In addition, IIs resulted in a larger effect than RR for the nonrepeated tasks. Strategies that support full encoding of PM cues and actions can improve PM performance among people with PD, particularly for tasks with cues that are readily available in the environment. IIs may be more effective than RR for nonrepeated tasks, but this finding warrants verification. Future work should address transfer of strategy use from the laboratory to everyday life. Targeted strategies to manage PM impairment could improve function and quality of life and significantly affect clinical care for people with PD.

Assessing quality of reports on randomized clinical trials in nursing journals.

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Parent, Nicole; Hanley, James A

2009-01-01

Several surveys have presented the quality of reports on randomized clinical trials (RCTs) published in general and specialty medical journals. The aim of these surveys was to raise scientific consciousness on methodological aspects pertaining to internal and external validity. These reviews have suggested that the methodological quality could be improved. We conducted a survey of reports on RCTs published in nursing journals to assess their methodological quality. The features we considered included sample size, flow of participants, assessment of baseline comparability, randomization, blinding, and statistical analysis. We collected data from all reports of RCTs published between January 1994 and December 1997 in Applied Nursing Research, Heart & Lung and Nursing Research. We hand-searched the journals and included all 54 articles in which authors reported that individuals have been randomly allocated to distinct groups. We collected data using a condensed form of the Consolidated Standards of Reporting Trials (CONSORT) statement for structured reporting of RCTs (Begg et al., 1996). Sample size calculations were included in only 22% of the reports. Only 48% of the reports provided information about the type of randomization, and a mere 22% described blinding strategies. Comparisons of baseline characteristics using hypothesis tests were abusively produced in more than 76% of the reports. Excessive use and unstructured reports of significance testing were common (59%), and all reports failed to provide magnitude of treatment differences with confidence intervals. Better methodological quality in reports of RCTs will contribute to increase the standards of nursing research.

Revisiting the Quality of Reporting Randomized Controlled Trials in Nursing Literature.

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Adams, Yenupini Joyce; Kamp, Kendra; Liu, Cheng Ching; Stommel, Manfred; Thana, Kanjana; Broome, Marion E; Smith, Barbara

2018-03-01

To examine and update the literature on the quality of randomized controlled trials (RCTs) as reported in top nursing journals, based on manuscripts' adherence to the CONsolidated Standards of Reporting Trials (CONSORT) guidelines. Descriptive review of adherence of RCT manuscript to CONSORT guidelines. Top 40 International Scientific Indexing (ISI) ranked nursing journals that published 20 or more RCTs between 2010 and 2014, were included in the study. Selected articles were randomly assigned to four reviewers who assessed the quality of the articles using the CONSORT checklist. Data were analyzed using descriptive and inferential statistics. A total of 119 articles were included in the review. The mean CONSORT score significantly differed by journal but did not differ based on year of publication. The least consistently reported items included random allocation, who randomly assigned participants and whether those administering the interventions were blinded to group assignment. Although progress has been made, there is still room for improvement in the quality of RCT reporting in nursing journals. Special attention must be paid to how adequately studies adhere to the CONSORT prior to publication in nursing journals. Evidence from (RCTs) are thought to provide the best evidence for evaluating the impact of treatments and interventions by the U.S. Preventive Services Task Force. Since the evidence may be used for the development of clinical practice guidelines, it is critical that RCTs be designed, conducted, and reported appropriately and precisely. © 2017 Sigma Theta Tau International.

Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial.

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Mujagic, Edin; Zwimpfer, Tibor; Marti, Walter R; Zwahlen, Marcel; Hoffmann, Henry; Kindler, Christoph; Fux, Christoph; Misteli, Heidi; Iselin, Lukas; Lugli, Andrea Kopp; Nebiker, Christian A; von Holzen, Urs; Vinzens, Fabrizio; von Strauss, Marco; Reck, Stefan; Kraljević, Marko; Widmer, Andreas F; Oertli, Daniel; Rosenthal, Rachel; Weber, Walter P

2014-05-24

Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis. In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5% surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. The results of this

Workplace sitting and height-adjustable workstations: a randomized controlled trial.

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Neuhaus, Maike; Healy, Genevieve N; Dunstan, David W; Owen, Neville; Eakin, Elizabeth G

2014-01-01

Desk-based office employees sit for most of their working day. To address excessive sitting as a newly identified health risk, best practice frameworks suggest a multi-component approach. However, these approaches are resource intensive and knowledge about their impact is limited. To compare the efficacy of a multi-component intervention to reduce workplace sitting time, to a height-adjustable workstations-only intervention, and to a comparison group (usual practice). Three-arm quasi-randomized controlled trial in three separate administrative units of the University of Queensland, Brisbane, Australia. Data were collected between January and June 2012 and analyzed the same year. Desk-based office workers aged 20-65 (multi-component intervention, n=16; workstations-only, n=14; comparison, n=14). The multi-component intervention comprised installation of height-adjustable workstations and organizational-level (management consultation, staff education, manager e-mails to staff) and individual-level (face-to-face coaching, telephone support) elements. Workplace sitting time (minutes/8-hour workday) assessed objectively via activPAL3 devices worn for 7 days at baseline and 3 months (end-of-intervention). At baseline, the mean proportion of workplace sitting time was approximately 77% across all groups (multi-component group 366 minutes/8 hours [SD=49]; workstations-only group 373 minutes/8 hours [SD=36], comparison 365 minutes/8 hours [SD=54]). Following intervention and relative to the comparison group, workplace sitting time in the multi-component group was reduced by 89 minutes/8-hour workday (95% CI=-130, -47 minutes; pworkplace sitting. These findings may have important practical and financial implications for workplaces targeting sitting time reductions. Australian New Zealand Clinical Trials Registry 00363297. © 2013 American Journal of Preventive Medicine Published by American Journal of Preventive Medicine All rights reserved.

Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

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Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

2016-01-01

This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual…

Healthy Children, Strong Families 2: A randomized controlled trial of a healthy lifestyle intervention for American Indian families designed using community-based approaches.

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Tomayko, Emily J; Prince, Ronald J; Cronin, Kate A; Parker, Tassy; Kim, Kyungmann; Grant, Vernon M; Sheche, Judith N; Adams, Alexandra K

2017-04-01

Background/Aims Few obesity prevention trials have focused on young children and their families in the home environment, particularly in underserved communities. Healthy Children, Strong Families 2 is a randomized controlled trial of a healthy lifestyle intervention for American Indian children and their families, a group at very high risk of obesity. The study design resulted from our long-standing engagement with American Indian communities, and few collaborations of this type resulting in the development and implementation of a randomized clinical trial have been described. Methods Healthy Children, Strong Families 2 is a lifestyle intervention targeting increased fruit and vegetable intake, decreased sugar intake, increased physical activity, decreased TV/screen time, and two less-studied risk factors: stress and sleep. Families with young children from five American Indian communities nationwide were randomly assigned to a healthy lifestyle intervention ( Wellness Journey) augmented with social support (Facebook and text messaging) or a child safety control group ( Safety Journey) for 1 year. After Year 1, families in the Safety Journey receive the Wellness Journey, and families in the Wellness Journey start the Safety Journey with continued wellness-focused social support based on communities' request that all families receive the intervention. Primary (adult body mass index and child body mass index z-score) and secondary (health behaviors) outcomes are assessed after Year 1 with additional analyses planned after Year 2. Results To date, 450 adult/child dyads have been enrolled (100% target enrollment). Statistical analyses await trial completion in 2017. Lessons learned Conducting a community-partnered randomized controlled trial requires significant formative work, relationship building, and ongoing flexibility. At the communities' request, the study involved minimal exclusion criteria, focused on wellness rather than obesity, and included an active

An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.

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Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J Mark G

2014-04-01

Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited, and trials often fail to report sufficient details about the recruitment sources and resources utilized. We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of (1) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial; (2) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants; and (3) comparison of sociodemographic characteristics of individuals recruited from different sources. Poster advertising, web-based advertising, and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters, and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in

The risk of unblinding was infrequently and incompletely reported in 300 randomized clinical trial publications

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Bello, Segun; Moustgaard, Helene; Hróbjartsson, Asbjørn

2014-01-01

randomized clinical trials indexed in PubMed in 2010. Two authors read the trial publications and extracted data independently. RESULTS: Twenty-four trial publications, or 8% (95% confidence interval [CI], 5, 12%), explicitly reported the risk of unblinding, of which 16 publications, or 5% (95% CI, 3, 8......%), reported compromised blinding; and 8 publications, or 3% (95% CI, 1, 5%), intact blinding. The reporting on risk of unblinding in the 24 trial publications was generally incomplete. The median proportion of assessments per trial affected by unblinding was 3% (range 1-30%). The most common mechanism...

Quality of Reporting of Randomized Clinical Trials in Tai Chi Interventions—A Systematic Review

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Jing-Yi Li

2011-01-01

Full Text Available Objectives. To evaluate the reporting quality of published randomized clinical trials (RCTs in the Tai Chi literature following the publication of the CONSORT guidelines in 2001. Data Sources. The OVID MEDLINE and PUBMED databases. Review Methods. To survey the general characteristics of Tai Chi RCTs in the literature, we included any report if (i it was an original report of the trial; (ii its design was RCT; (iii one of the treatments being tested was Tai Chi; and (iv it was in English. In addition, we assessed the reporting quality of RCTs that were published between 2002 and 2007, using a modified CONSORT checklist of 40 items. The adequate description of Tai Chi interventions in these trials was examined against a 10-item checklist adapted from previous reviews. Results. The search yielded 31 Tai Chi RCTs published from 2002 to 2007 and only 11 for 1992–2001. Among trials published during 2002–2007, the most adequately reported criteria were related to background, participant eligibility and interpretation of the study results. Nonetheless, the most poorly reported items were associated with randomization allocation concealment, implementation of randomization and the definitions of period of recruitment and follow-up. In addition, only 23% of RCTs provided adequate details of Tai Chi intervention used in the trials. Conclusion. The findings in this review indicated that the reporting quality of Tai Chi intervention trials is sub-optimal. Substantial improvement is required to meet the CONSORT guidelines and allow assessment of the quality of evidence. We believe that not only investigators, but also journal editors, reviewers and funding agencies need to follow the CONSORT guidelines to improve the standards of research and strengthen the evidence base for Tai Chi and for complementary and alternative medicine.

Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials

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de Labra, Carmen; Guimaraes-Pinheiro, Christyanne; Maseda, Ana; Lorenzo, Trinidad; Mill?n-Calenti, Jos? C.

2015-01-01

Background Low physical activity has been shown to be one of the most common components of frailty, and interventions have been considered to prevent or reverse this syndrome. The purpose of this systematic review of randomized, controlled trials is to examine the exercise interventions to manage frailty in older people. Methods The PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched using specific keywords and Medical Subject Headings for random...

Randomized trial to examine procedure-to-procedure transfer in laparoscopic simulator training

DEFF Research Database (Denmark)

Bjerrum, F; Sorensen, J L; Konge, L

2016-01-01

-centre educational superiority trial. Surgical novices practised basic skills on a laparoscopic virtual reality simulator. On reaching proficiency, participants were randomized to proficiency-based training. The intervention group practised two procedures on the simulator (appendicectomy followed by salpingectomy...

Quality of reporting randomized controlled trials (RCTs) in diabetes in Iran; a systematic review.

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Gohari, Faeze; Baradaran, Hamid Reza; Tabatabaee, Morteza; Anijidani, Shabnam; Mohammadpour Touserkani, Fatemeh; Atlasi, Rasha; Razmgir, Maryam

2015-01-01

To determine the quality of randomized controlled clinical trial (RCT) reports in diabetes research in Iran. Systematized review. We included RCTs conducted on diabetes mellitus in Iran. Animal studies, educational interventions, and non-randomized trials were excluded. We excluded duplicated publications reporting the same groups of participants and intervention. Two independent reviewers identify all eligible articles specifically designed data extraction form. We searched through international databases; Scopus, ProQuest, EBSCO, Science Direct, Web of Science, Cochrane Library, PubMed; and national databases (In Persian language) such as Magiran, Scientific Information Database (SID) and IranMedex from January 1995 to January of 2013 Two investigators assessed the quality of reporting by CONSORT 2010 (Consolidated Standards of Reporting Trials) checklist statemen.t,. Discrepancies were resolved by third reviewer consulting. One hundred and eight five (185) studies were included and appraised. Half of them (55.7 %) were published in Iranian journals. Most (89.7 %) were parallel RCTs, and being performed on type2 diabetic patients (77.8 %). Less than half of the CONSORT items (43.2 %) were reported in studies, totally. The reporting of randomization and blinding were poor. A few studies 15.1 % mentioned the method of random sequence generation and strategy of allocation concealment. And only 34.8 % of trials report how blinding was applied. The findings of this study show that the quality of RCTs conducted in Iran in diabetes research seems suboptimal and the reporting is also incomplete however an increasing trend of improvement can be seen over time. Therefore, it is suggested Iranian researchers pay much more attention to design and methodological quality in conducting and reporting of diabetes RCTs.

Characteristics of randomized trials published in Latin America and the Caribbean according to funding source.

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Ludovic Reveiz

Full Text Available INTRODUCTION: Few studies have assessed the nature and quality of randomized controlled trials (RCTs in Latin America and the Caribbean (LAC. METHODS AND FINDINGS: The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author's affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants. English was the dominant publication language (93% and most of the RCTs were published in non-LAC journals (84.2%. Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%. Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7% or high priority infectious diseases (3.8%. Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358 was assessed for funding source: exclusively public (33.8%; private (e.g. pharmaceutical company (15.3%; other (e.g. mixed, NGO (15.1%; no funding (35.8%. Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting. CONCLUSION: Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health

Characteristics of randomized trials published in Latin America and the Caribbean according to funding source.

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Reveiz, Ludovic; Sangalang, Stephanie; Glujovsky, Demian; Pinzon, Carlos E; Asenjo Lobos, Claudia; Cortes, Marcela; Cañón, Martin; Bardach, Ariel; Bonfill, Xavier

2013-01-01

Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC). The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author's affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting. Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems.

Statistical Analysis for Multisite Trials Using Instrumental Variables with Random Coefficients

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Raudenbush, Stephen W.; Reardon, Sean F.; Nomi, Takako

2012-01-01

Multisite trials can clarify the average impact of a new program and the heterogeneity of impacts across sites. Unfortunately, in many applications, compliance with treatment assignment is imperfect. For these applications, we propose an instrumental variable (IV) model with person-specific and site-specific random coefficients. Site-specific IV…

The Relaxation Exercise and Social Support Trial (RESST: a community-based randomized controlled trial to alleviate medically unexplained vaginal discharge symptoms

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Kobeissi Loulou

2012-11-01

Full Text Available Abstract Background Symptoms such as medically unexplained vaginal discharge (MUVD are common and bothersome, leading to potentially unnecessary use of resources. Methods A community-based individually randomized controlled trial to assess the effectiveness of a relatively simple, culturally appropriate multi-component intervention on reducing reported MUVD, among women suffering from low-moderate levels of common mental distress. The setting was a socio-economically deprived, informal settlement in the southern suburbs of Beirut, Lebanon. The intervention comprised up to 12 group sessions implemented over a six-week period, each divided into a psychosocial and a relaxation exercise component. The primary outcome was self-reported MUVD, which was defined as a complaint of vaginal discharge upon ruling out reproductive tract infections (RTIs, through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25. Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Blinding on the intervention status was not possible for both logistic and ethical reasons, especially as knowledge of involvement in the intervention was integral to its delivery. Intent to treat analysis was used. Results Of 75 women randomized to the intervention, 48% reported MUVD at 6 months compared with 63% of 73 in the control group (difference of -15%, 95% confidence interval (CI -31%, 0%, p=0.067. Adjustments for baseline imbalances and any factors relating to consent had no appreciable effect on these results. The risk of MUVD was reduced in absolute terms by 2.4% for each intervention session attended (95% CI -4.9%, 0.0%, p=0.049. While there was also marginal evidence of a beneficial effect on anxiety, there was

Online distribution channel increases article usage on Mendeley: a randomized controlled trial.

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Kudlow, Paul; Cockerill, Matthew; Toccalino, Danielle; Dziadyk, Devin Bissky; Rutledge, Alan; Shachak, Aviv; McIntyre, Roger S; Ravindran, Arun; Eysenbach, Gunther

2017-01-01

Prior research shows that article reader counts (i.e. saves) on the online reference manager, Mendeley, correlate to future citations. There are currently no evidenced-based distribution strategies that have been shown to increase article saves on Mendeley. We conducted a 4-week randomized controlled trial to examine how promotion of article links in a novel online cross-publisher distribution channel (TrendMD) affect article saves on Mendeley. Four hundred articles published in the Journal of Medical Internet Research were randomized to either the TrendMD arm ( n  = 200) or the control arm ( n  = 200) of the study. Our primary outcome compares the 4-week mean Mendeley saves of articles randomized to TrendMD versus control. Articles randomized to TrendMD showed a 77% increase in article saves on Mendeley relative to control. The difference in mean Mendeley saves for TrendMD articles versus control was 2.7, 95% CI (2.63, 2.77), and statistically significant ( p  < 0.01). There was a positive correlation between pageviews driven by TrendMD and article saves on Mendeley (Spearman's rho r  = 0.60). This is the first randomized controlled trial to show how an online cross-publisher distribution channel (TrendMD) enhances article saves on Mendeley. While replication and further study are needed, these data suggest that cross-publisher article recommendations via TrendMD may enhance citations of scholarly articles.

The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial.

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Scherer, Roberta W; Drye, Lea; Mintzer, Jacobo; Lanctôt, Krista; Rosenberg, Paul; Herrmann, Nathan; Padala, Prasad; Brawman-Mintzer, Olga; Burke, William; Craft, Suzanne; Lerner, Alan J; Levey, Allan; Porsteinsson, Anton; van Dyck, Christopher H

2018-01-18

Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events. However, the trial only enrolled 60 participants who were followed for only 6 weeks. A larger, longer-lasting trial is required to confirm these promising findings. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6-month, multi-center, randomized clinical trial targeted to enroll 200 participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg methylphenidate per day prepared as four over-encapsulated tablets or to matching placebo. The primary outcomes include (1) the mean difference in the Neuropsychiatric Inventory Apathy subscale scores measured as change from baseline to 6 months, and (2) the odds of having a given rating or better on the modified AD Cooperative Study Clinical Global Impression of Change ratings at month 6 compared with the baseline rating. Other outcomes include change in cognition, safety, and cost-effectiveness measured at monthly follow-up visits up to 6 months. Given the prevalence of apathy in AD and its impact on both patients and caregivers, an intervention to alleviate apathy would be of great benefit to society. ADMET 2 follows on the promising results from the original ADMET to evaluate the efficacy of methylphenidate as a

A randomized trial of rosuvastatin in the prevention of venous thromboembolism

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Glynn, Robert J; Danielson, Eleanor; Fonseca, Francisco A H

2009-01-01

BACKGROUND: Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin...... therapy on the risk of venous thromboembolism, and evidence from randomized trials is lacking. METHODS: We randomly assigned 17,802 apparently healthy men and women with both low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C...

Citation bias of hepato-biliary randomized clinical trials

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Kjaergard, Lise L; Gluud, Christian

2002-01-01

-1996. From each trial, we extracted the statistical significance of the primary study outcome (positive or negative), the disease area, and methodological quality (randomization and double blinding). The number of citations during two calendar years after publication was obtained from Science Citation Index....... There was a significant positive association between a statistically significant study outcome and the citation frequency (beta, 0.55, 95% confidence interval, 0.39-0.72). The disease area and adequate generation of the allocation sequence were also significant predictors of the citation frequency. We concluded...

Breast Cancer Outreach for Underserved Women: A Randomized Trial and Cost-Effectiveness Analysis

National Research Council Canada - National Science Library

Pasick, Rena

1999-01-01

The current study, BACCIS-II, is a randomized controlled trial of an outreach intervention model designed to increase the rate of periodic mammography and clinical breast exam among underserved women...

Randomized, controlled clinical trial evaluating the efficacy of pulsed signal therapy in dogs with osteoarthritis.

Science.gov (United States)

Sullivan, Meghan O; Gordon-Evans, Wanda J; Knap, Kim E; Evans, Richard B

2013-04-01

To evaluate the efficacy of pulsed signal therapy (PST) in reducing pain and increasing function in dogs with osteoarthritis (OA) using a randomized, blinded, controlled clinical trial. Randomized, controlled, blinded clinical trial. Adult dogs (n = 60) with moderate-to-severe clinical signs of OA. Dogs were randomized by age into 2 groups: dogs ≥ 9 years and dogs Goniometry and gait analysis were performed, and the Canine Brief Pain Inventory (CBPI) questionnaire was given to the owners to fill out without supervision. Outcome measures were repeated at the end of treatment (Day 11) and 6 weeks after beginning treatment (Day 42). The PST group performed significantly better than the control group as measured by the CBPI Severity and Interference scores (P Veterinary Surgeons.

Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

Science.gov (United States)

Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor

2016-11-01

Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

Randomized clinical trial of symptom control after stapled anopexy or diathermy excision for haemorrhoid prolapse

DEFF Research Database (Denmark)

Nyström, P-O; Qvist, N; Raahave, D

2010-01-01

BACKGROUND: : This multicentre randomized clinical trial studied how symptoms improved after either stapled anopexy or diathermy excision of haemorrhoids. METHODS: : The study involved 18 hospitals in Sweden, Denmark and the UK. Some 207 patients were randomized to either anopexy or Milligan-Morg...

Randomized controlled trials in children’s heart surgery in the 21st century: a systematic review

Science.gov (United States)

Drury, Nigel E; Patel, Akshay J; Oswald, Nicola K; Chong, Cher-Rin; Stickley, John; Barron, David J; Jones, Timothy J

2018-01-01

Abstract OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice. PMID:29186478

Arthrocentesis as initial treatment for temporomandibular joint arthropathy : A randomized controlled trial

NARCIS (Netherlands)

Vos, L. M.; Huddleston Slater, J. J. R.; Stegenga, B.

Objective: To determine the effectiveness of arthrocentesis compared to conservative treatment as initial treatment with regard to temporomandibular joint pain and mandibular movement. Patients and methods: In this randomized controlled trial, 80 patients with arthralgia of the TMJ (classified

A randomized controlled trial of daily sedation interruption in critically ill children

NARCIS (Netherlands)

Vet, N.J.; Wildt, S.N. de; Verlaat, C.W.; Knibbe, C.A.; Mooij, M.G.; Woensel, J.B. van; Rosmalen, J. van; Tibboel, D.; Hoog, M. de

2016-01-01

PURPOSE: To compare daily sedation interruption plus protocolized sedation (DSI + PS) to protocolized sedation only (PS) in critically ill children. METHODS: In this multicenter randomized controlled trial in three pediatric intensive care units in the Netherlands, mechanically ventilated critically

A randomized controlled trial of daily sedation interruption in critically ill children

NARCIS (Netherlands)

N.J. Vet (Nienke); S.N. de Wildt (Saskia); C.W.M. Verlaat (Carin); C.A.J. Knibbe (Catherijne); M.G. Mooij (Miriam); J.B. van Woensel (Job); J.M. van Rosmalen (Joost); D. Tibboel (Dick); M. de Hoog (Matthijs)

2016-01-01

textabstractPurpose: To compare daily sedation interruption plus protocolized sedation (DSI + PS) to protocolized sedation only (PS) in critically ill children. Methods: In this multicenter randomized controlled trial in three pediatric intensive care units in the Netherlands, mechanically

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

Science.gov (United States)

Landolfi, R; Marchioli, R

1997-01-01

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

NARCIS (Netherlands)

E.C. Townsend (Elizabeth); M.A. Murakami (Mark); A. Christodoulou (Alexandra); A.L. Christie (Amanda); J. Köster (Johannes); T.A. DeSouza (Tiffany); E.A. Morgan (Elizabeth); S.P. Kallgren (Scott); H. Liu (Huiyun); S.-C. Wu (Shuo-Chieh); O. Plana (Olivia); J. Montero (Joan); K.E. Stevenson (Kristen); P. Rao (Prakash); R. Vadhi (Raga); M. Andreeff (Michael); P. Armand (Philippe); K.K. Ballen (Karen); P. Barzaghi-Rinaudo (Patrizia); S. Cahill (Sarah); R.A. Clark (Rachael); V.G. Cooke (Vesselina); M.S. Davids (Matthew); D.J. DeAngelo (Daniel); D.M. Dorfman; H. Eaton (Hilary); B.L. Ebert (Benjamin); J. Etchin (Julia); B. Firestone (Brant); D.C. Fisher (David); A.S. Freedman (Arnold); I.A. Galinsky, () (Ilene); H. Gao (Hui); J.S. Garcia, () (Jacqueline); F. Gamache-Ottou (Francine); T.A. Graubert (Timothy); A. Gutierrez (Alejandro); E. Halilovic (Ensar); M.H. Harris (Marian); Z.T. Herbert (Zachary); S.M. Horwitz (Steven); G. Inghirami (Giorgio); A.M. Intlekofer (Andrew); M. Ito (Moriko); S. Izraeli (Shai); E.D. Jacobsen (Eric); C.A. Jacobson (Caron); S. Jeay (Sébastien); I. Jeremias (Irmela); M.A. Kelliher (Michelle); R. Koch (Raphael); M. Konopleva (Marina); N. Kopp (Nadja); S.M. Kornblau (Steven); A.L. Kung (Andrew); T.S. Kupper (Thomas); N.R. LeBoeuf (Nicole); A.S. LaCasce (Ann); E. Lees (Emma); L.S. Li (Loretta); A.T. Look (Thomas); M. Murakami (Masato); M. Muschen (Markus); D. Neuberg (Donna); S.Y. Ng (Samuel); O.O. Odejde (Oreofe); S.H. Orkin (Stuart); R.R. Paquette (Rachel); A.A. Place (Andrew); J.E. Roderick (Justine); J.A. Ryan (Jeremy); S.E. Sallan (Stephen); B. Shoji (Brent); L.B. Silverman (Lewis); R.J. Soiffer (Robert); D.P. Steensma (David); K. Stegmaier (Kimberley); R.M. Stone (Richard); J. Tamburini (Jerome); A.R. Thorner (Aaron); P. van Hummelen (Paul); M. Wadleigh (Martha); M. Wiesmann (Marion); A.P. Weng (Andrew); J.U. Wuerthner (Jens); D.A. Williams (David); B.M. Wollison (Bruce); A.A. Lane (Andrew); A. Letai (Anthony); M.M. Bertagnolli (Monica); J. Ritz (Jerome); M. Brown (Myles); H. Long (Henry); J.C. Aster (Jon); M.A. Shipp (Margaret); J.D. Griffin (James); D.M. Weinstock (David)

2016-01-01

textabstractMore than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address

Testing the efficacy of a brief sexual risk reduction intervention among high-risk American Indian adults: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Rachel Chambers

2016-04-01

Full Text Available Abstract Background American Indian adults are more likely to experience co-occurring mental health and substance use disorders than adults of other racial/ethnic groups and are disproportionately burdened by the most common sexually transmitted infections, namely chlamydia and gonorrhea. Several behavioral interventions are proven efficacious in lowering risk for sexually transmitted infection in various populations and, if adapted to address barriers experienced by American Indian adults who suffer from mental health and substance use problems, may be useful for dissemination in American Indian communities. The proposed study aims to examine the efficacy of an adapted evidence-based intervention to increase condom use and decrease sexual risk-taking and substance use among American Indian adults living in a reservation-based community in the Southwestern United States. Methods/Design The proposed study is a randomized controlled trial to test the efficacy of an adapted evidence-based intervention compared to a control condition. Participants will be American Indian adults ages 18–49 years old who had a recent episode of binge substance use and/or suicide ideation. Participants will be randomized to the intervention, a two-session risk-reduction counseling intervention or the control condition, optimized standard care. All participants will be offered a self-administered sexually transmitted infection test. Participants will complete assessments at baseline, 3 and 6 months follow-up. The primary outcome measure is condom use at last sex. Discussion This is one of the first randomized controlled trials to assess the efficacy of an adapted evidence-based intervention for reducing sexual risk behaviors among AI adults with substance use and mental health problems. If proven successful, there will be an efficacious program for reducing risk behaviors among high-risk adults that can be disseminated in American Indian communities as well as other

Prevention of low back pain and its consequences among nurses’ aides in elderly care: a stepped-wedge multi-faceted cluster-randomized controlled trial

Science.gov (United States)

2013-01-01

Background A high prevalence of low back pain has persisted over the years despite extensive primary prevention initiatives among nurses’ aides. Many single-faceted interventions addressing just one aspect of low back pain have been carried out at workplaces, but with low success rate. This may be due to the multi-factorial origin of low back pain. Participatory ergonomics, cognitive behavioral training and physical training have previously shown promising effects on prevention and rehabilitation of low back pain. Therefore, the main aim of this study is to examine whether a multi-faceted workplace intervention consisting of participatory ergonomics, physical training and cognitive behavioral training can prevent low back pain and its consequences among nurses’ aides. External resources for the participating workplace and a strong commitment from the management and the organization support the intervention. Methods/design To overcome implementation barriers within usual randomized controlled trial designed workplace interventions, this study uses a stepped-wedge cluster-randomized controlled trial design with 4 groups. The intervention is delivered to the groups at random along four successive time periods three months apart. The intervention lasts three months and integrates participatory ergonomics, physical training and cognitive behavioral training tailored to the target group. Local physiotherapists and occupational therapists conduct the intervention after having received standardized training. Primary outcomes are low back pain and its consequences measured monthly by text messages up to three months after initiation of the intervention. Discussion Intervention effectiveness trials for preventing low back pain and its consequences in workplaces with physically demanding work are few, primarily single-faceted, with strict adherence to a traditional randomized controlled trial design that may hamper implementation and compliance, and have mostly been

Missing data in trial-based cost-effectiveness analysis: An incomplete journey.

Science.gov (United States)

Leurent, Baptiste; Gomes, Manuel; Carpenter, James R

2018-06-01

Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial-based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty-two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing-at-random assumption. Further improvements are needed to address missing data in cost-effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing-at-random assumption. © 2018 The Authors Health Economics published by John Wiley & Sons Ltd.

A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial.

Science.gov (United States)

Cevallos, Myriam; Züllig, Stephanie; Christen, Andri; Meier, Brigitte E; Goetz, Martin; Coslovsky, Michael; Trelle, Sven

2015-12-01

Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. We included 142 of 231 protocols in the final analysis (concept=78; ad hoc=64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval=0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p=0.67). The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application. © The Author(s) 2015.

A randomized controlled trial of daily sedation interruption in critically ill children

NARCIS (Netherlands)

Vet, Nienke J.; de Wildt, Saskia N.; Verlaat, Carin W. M.; Knibbe, Catherijne A. J.; Mooij, Miriam G.; van Woensel, Job B. M.; van Rosmalen, Joost; Tibboel, Dick; de Hoog, Matthijs

2016-01-01

To compare daily sedation interruption plus protocolized sedation (DSI + PS) to protocolized sedation only (PS) in critically ill children. In this multicenter randomized controlled trial in three pediatric intensive care units in the Netherlands, mechanically ventilated critically ill children with

Standardized Effect Size Measures for Mediation Analysis in Cluster-Randomized Trials

Science.gov (United States)

Stapleton, Laura M.; Pituch, Keenan A.; Dion, Eric

2015-01-01

This article presents 3 standardized effect size measures to use when sharing results of an analysis of mediation of treatment effects for cluster-randomized trials. The authors discuss 3 examples of mediation analysis (upper-level mediation, cross-level mediation, and cross-level mediation with a contextual effect) with demonstration of the…

Children's Healthy Living (CHL) Program for remote underserved minority populations in the Pacific region: rationale and design of a community randomized trial to prevent early childhood obesity.

Science.gov (United States)

Wilken, Lynne R; Novotny, Rachel; Fialkowski, Marie K; Boushey, Carol J; Nigg, Claudio; Paulino, Yvette; Leon Guerrero, Rachael; Bersamin, Andrea; Vargo, Don; Kim, Jang; Deenik, Jonathan

2013-10-09

Although surveillance data are limited in the US Affiliated Pacific, Alaska, and Hawaii, existing data suggest that the prevalence of childhood obesity is similar to or in excess of other minority groups in the contiguous US. Strategies for addressing the childhood obesity epidemic in the region support the use of community-based, environmentally targeted interventions. The Children's Healthy Living Program is a partnership formed across institutions in the US Affiliated Pacific, Alaska, and Hawaii to design a community randomized environmental intervention trial and a prevalence survey to address childhood obesity in the region through affecting the food and physical activity environment. The Children's Healthy Living Program community randomized trial is an environmental intervention trial in four matched-pair communities in American Samoa, the Commonwealth of the Northern Mariana Islands, Guam, and Hawaii and two matched-pair communities in Alaska. A cross-sectional sample of children (goal n = 180) in each of the intervention trial communities is being assessed for outcomes at baseline and at 24 months (18 months post-intervention). In addition to the collection of the participant-based measures of anthropometry, diet, physical activity, sleep and acanthosis nigricans, community assessments are also being conducted in intervention trial communities. The Freely Associated States of Micronesia (Federated States of Micronesia, and Republics of Marshall Islands and Palau) is only conducting elements of the Children's Healthy Living Program sampling framework and similar measurements to provide prevalence data. In addition, anthropometry information will be collected for two additional communities in each of the 5 intervention jurisdictions to be included in the prevalence survey. The effectiveness of the environmental intervention trial is being assessed based on the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. The Children

Children’s Healthy Living (CHL) Program for remote underserved minority populations in the Pacific region: rationale and design of a community randomized trial to prevent early childhood obesity

Science.gov (United States)

2013-01-01

Background Although surveillance data are limited in the US Affiliated Pacific, Alaska, and Hawaii, existing data suggest that the prevalence of childhood obesity is similar to or in excess of other minority groups in the contiguous US. Strategies for addressing the childhood obesity epidemic in the region support the use of community-based, environmentally targeted interventions. The Children’s Healthy Living Program is a partnership formed across institutions in the US Affiliated Pacific, Alaska, and Hawaii to design a community randomized environmental intervention trial and a prevalence survey to address childhood obesity in the region through affecting the food and physical activity environment. Methods/Design The Children’s Healthy Living Program community randomized trial is an environmental intervention trial in four matched-pair communities in American Samoa, the Commonwealth of the Northern Mariana Islands, Guam, and Hawaii and two matched-pair communities in Alaska. A cross-sectional sample of children (goal n = 180) in each of the intervention trial communities is being assessed for outcomes at baseline and at 24 months (18 months post-intervention). In addition to the collection of the participant-based measures of anthropometry, diet, physical activity, sleep and acanthosis nigricans, community assessments are also being conducted in intervention trial communities. The Freely Associated States of Micronesia (Federated States of Micronesia, and Republics of Marshall Islands and Palau) is only conducting elements of the Children’s Healthy Living Program sampling framework and similar measurements to provide prevalence data. In addition, anthropometry information will be collected for two additional communities in each of the 5 intervention jurisdictions to be included in the prevalence survey. The effectiveness of the environmental intervention trial is being assessed based on the RE-AIM (reach, effectiveness, adoption, implementation, maintenance

Randomized Pilot Trial of Two Modified Endotracheal Tubes To Prevent Ventilator-associated Pneumonia.

Science.gov (United States)

Deem, Steven; Yanez, David; Sissons-Ross, Laura; Broeckel, Jo Ann Elrod; Daniel, Stephen; Treggiari, Miriam

2016-01-01

Ventilator-associated pneumonia (VAP) is a prevalent and costly nosocomial infection related to instrumentation of the airway with an endotracheal tube (ETT), enabling microaspiration of contaminated secretions. Modification of the ETT design to reduce microaspiration and/or biofilm formation may play an important role in VAP prevention. However, there is insufficient evidence to provide strong recommendations regarding the use of modified ETT and unaddressed safety concerns. We performed a pilot randomized controlled trial comparing two modified ETTs designed specifically to prevent VAP, with the standard ETT, to test the feasibility of and inform planning for a large, pivotal, randomized trial. This study was conducted with institutional review board approval under exception from informed consent. We randomized in a blinded fashion patients undergoing emergency endotracheal intubation both out of and in hospital to receive one of three different ETT types: (1) a polyurethane-cuffed tube (PUC-ETT), (2) a polyurethane-cuffed tube equipped with a port for continuous aspiration of subglottic secretions (PUC-CASS-ETT), or a (3) standard polyvinylchloride-cuffed tube (PVC-ETT). In addition to investigating feasibility and safety, the study coprimary end points were tracheal bacterial colonization reaching a cfu count >10(6) cfu per milliliter and the incidence of invasively diagnosed VAP. A total of 102 subjects were randomized and met the eligibility criteria. Randomization procedures performed well and integrity of blinding at randomization was maintained. The majority of intubations occurred in the hospital setting (n = 77), and the remainder occurred out of hospital (n = 25). Compared with the PVC-ETT, there were no significant differences in tracheal colonization for PUC-ETT (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.31-3.09) or for PUC-CASS-ETT (OR, 1.26; 95% CI, 0.42-3.76). There were no differences in the risk of invasively diagnosed VAP

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

Directory of Open Access Journals (Sweden)

Gasparovic Hrvoje

2012-08-01

Full Text Available Abstract Background Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Methods Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology as well as bleeding events will be recorded. Discussion This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639.

Partner randomized controlled trial: study protocol and coaching intervention

Directory of Open Access Journals (Sweden)

Garbutt Jane M

2012-04-01

Full Text Available Abstract Background Many children with asthma live with frequent symptoms and activity limitations, and visits for urgent care are common. Many pediatricians do not regularly meet with families to monitor asthma control, identify concerns or problems with management, or provide self-management education. Effective interventions to improve asthma care such as small group training and care redesign have been difficult to disseminate into office practice. Methods and design This paper describes the protocol for a randomized controlled trial (RCT to evaluate a 12-month telephone-coaching program designed to support primary care management of children with persistent asthma and subsequently to improve asthma control and disease-related quality of life and reduce urgent care events for asthma care. Randomization occurred at the practice level with eligible families within a practice having access to the coaching program or to usual care. The coaching intervention was based on the transtheoretical model of behavior change. Targeted behaviors included 1 effective use of controller medications, 2 effective use of rescue medications and 3 monitoring to ensure optimal control. Trained lay coaches provided parents with education and support for asthma care, tailoring the information provided and frequency of contact to the parent's readiness to change their child's day-to-day asthma management. Coaching calls varied in frequency from weekly to monthly. For each participating family, follow-up measurements were obtained at 12- and 24-months after enrollment in the study during a telephone interview. The primary outcomes were the mean change in 1 the child's asthma control score, 2 the parent's quality of life score, and 3 the number of urgent care events assessed at 12 and 24 months. Secondary outcomes reflected adherence to guideline recommendations by the primary care pediatricians and included the proportion of children prescribed controller medications

Cinnamon Bark, Water Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

Science.gov (United States)

2016-12-14

Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus : A Randomized, Controlled Trial. Paul Crawford, MD Clinical Investigation...Title: “Cinnamon Bark, Water-Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus : A Randomized, Controlled...as initial treatment for Type 2 diabetes mellitus : A randomized, controlled trial. IRB #: FWH20110004H Principal Investigator (PI) Rank / Civ

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial

DEFF Research Database (Denmark)

Frederiksen, Pernille; Indahl, Aage; Andersen, Lars L

2017-01-01

-randomized controlled trial. METHODS: Publically employed workers (n = 505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non...

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

Directory of Open Access Journals (Sweden)

Zielinski Stephanie M

2012-01-01

Full Text Available Abstract Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures. Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139 in the Netherlands to 232 days (P25-P75 98-423 in Canada (p = 0.027. The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21 per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28, representing 3.9% of eligible patients (p Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813

Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial--the NeuroMorfeo trial.

Science.gov (United States)

Citerio, Giuseppe; Franzosi, Maria Grazia; Latini, Roberto; Masson, Serge; Barlera, Simona; Guzzetti, Stefano; Pesenti, Antonio

2009-04-06

Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaesthesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score > or = 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia; intraoperative

Randomized Controlled Trial to Evaluate Splenectomy in Total Gastrectomy for Proximal Gastric Carcinoma.

Science.gov (United States)

Sano, Takeshi; Sasako, Mitsuru; Mizusawa, Junki; Yamamoto, Seiichiro; Katai, Hitoshi; Yoshikawa, Takaki; Nashimoto, Atsushi; Ito, Seiji; Kaji, Masahide; Imamura, Hiroshi; Fukushima, Norimasa; Fujitani, Kazumasa

2017-02-01

To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer. Splenectomy in total gastrectomy is associated with increased operative morbidity and mortality, but its survival benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive. We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%. Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67-1.16) (splenectomy should be avoided as it increases operative morbidity without improving survival.

Preoperative clonidine use in trans-sphenoidal pituitary adenoma surgeries - a randomized controlled trial.

Science.gov (United States)

Bajaj, Jitin; Mittal, Radhe Shyam; Sharma, Achal

2017-02-01

Pituitary masses are common lesions accounting for about 15-20% of all brain tumours. Oozing blood is an annoyance in microscopic sublabial trans-sphenoidal approach for these masses. There have been many ways of reducing the ooze, having their own pros and cons. To find out the efficacy and safety of clonidine in reducing blood loss in pituitary adenoma surgery through a randomized masked trial. It was a prospective randomized controlled trial done. Total 50 patients of pituitary adenomas were randomized into two groups. Group A (25 patients) was given 200 μg clonidine orally, while Group B (25 patients) was given placebo. Surgeon, anaesthesiologist and patient were blinded for the trial. Sublabial trans-septal trans-sphenoidal approach to sella and excision of mass was performed in each patient. Patients were studied for pre-, intra- and post-operative blood pressure and heart rate, pre- and post-operative imaging findings, intra-operative blood loss, bleeding grading by surgeon, surgeon's satisfaction about condition of specific part and quality of surgical field, operative time and extent of resection. Blood loss during the surgery, operative time and bleeding grading by the surgeon were found significantly less in the clonidine group, while quality of surgical field, condition of the specific part and extent of resection were found significantly better in the clonidine group (p value trans-sphenoidal microscopic pituitary adenoma surgeries.

Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial.

Science.gov (United States)

de Rooij, Thijs; van Hilst, Jony; Vogel, Jantien A; van Santvoort, Hjalmar C; de Boer, Marieke T; Boerma, Djamila; van den Boezem, Peter B; Bonsing, Bert A; Bosscha, Koop; Coene, Peter-Paul; Daams, Freek; van Dam, Ronald M; Dijkgraaf, Marcel G; van Eijck, Casper H; Festen, Sebastiaan; Gerhards, Michael F; Groot Koerkamp, Bas; Hagendoorn, Jeroen; van der Harst, Erwin; de Hingh, Ignace H; Dejong, Cees H; Kazemier, Geert; Klaase, Joost; de Kleine, Ruben H; van Laarhoven, Cornelis J; Lips, Daan J; Luyer, Misha D; Molenaar, I Quintus; Nieuwenhuijs, Vincent B; Patijn, Gijs A; Roos, Daphne; Scheepers, Joris J; van der Schelling, George P; Steenvoorde, Pascal; Swijnenburg, Rutger-Jan; Wijsman, Jan H; Abu Hilal, Moh'd; Busch, Olivier R; Besselink, Marc G

2017-04-08

Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Dutch Trial Register, NTR5188 . Registered on 9 April 2015.

The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression

DEFF Research Database (Denmark)

Krogh, Jesper; Saltin, Bengt; Gluud, Christian

2009-01-01

OBJECTIVE: To assess the benefit and harm of exercise training in adults with clinical depression. METHOD: The DEMO trial is a randomized pragmatic trial for patients with unipolar depression conducted from January 2005 through July 2007. Patients were referred from general practitioners or psych......: Our findings do not support a biologically mediated effect of exercise on symptom severity in depressed patients, but they do support a beneficial effect of strength training on work capacity. TRIAL REGISTRATION: (ClinicalTrials.gov) Identifier: NCT00103415.......OBJECTIVE: To assess the benefit and harm of exercise training in adults with clinical depression. METHOD: The DEMO trial is a randomized pragmatic trial for patients with unipolar depression conducted from January 2005 through July 2007. Patients were referred from general practitioners...... or psychiatrists and were eligible if they fulfilled the International Classification of Diseases, Tenth Revision, criteria for unipolar depression and were aged between 18 and 55 years. Patients (N = 165) were allocated to supervised strength, aerobic, or relaxation training during a 4-month period. The primary...

Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials.

Science.gov (United States)

Quist-Nelson, Johanna; Parker, Pamela; Mokhtari, Neggin; Di Sarno, Rossana; Saccone, Gabriele; Berghella, Vincenzo

2018-03-31

Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate

Prospective randomized clinical studies involving reirradiation. Lessons learned

International Nuclear Information System (INIS)

Nieder, Carsten; Langendijk, Johannes A.; Guckenberger, Matthias; Grosu, Anca L.

2016-01-01

Reirradiation is a potentially useful option for many patients with recurrent cancer. The purpose of this study was to review all recently published randomized trials in order to identify methodological strengths and weaknesses, comment on the results, clinical implications and open questions, and give advice for the planning of future trials. Systematic review of trials published between 2000 and 2015 (databases searched were PubMed, Scopus and Web of Science). We reviewed 9 trials, most of which addressed reirradiation of head and neck tumours. The median number of patients was 69. Trial design, primary endpoint and statistical hypotheses varied widely. The results contribute mainly to decision making for reirradiation of nasopharynx cancer and bone metastases. The trials with relatively long median follow-up confirm that serious toxicity remains a concern after high cumulative total doses. Multi-institutional collaboration is encouraged to complete sufficiently large trials. Despite a paucity of large randomized studies, reirradiation has been adopted in different clinical scenarios by many institutions. Typically, the patients have been assessed by multidisciplinary tumour boards and advanced technologies are used to create highly conformal dose distributions. (orig.) [de

Do randomized controlled trials discuss healthcare costs?

Directory of Open Access Journals (Sweden)

G Michael Allan

Full Text Available BACKGROUND: Healthcare costs, particularly pharmaceutical costs, are a dominant issue for most healthcare organizations, but it is unclear if randomized controlled trials (RCTs routinely discuss costs. Our objective was to assess the frequency and factors associated with the inclusion of costs in RCTs. METHODS AND FINDINGS: We randomly sampled 188 RCTs spanning three years (2003-2005 from six high impact journals. The sample size for RCTs was based on a calculation to estimate the inclusion of actual drug costs with a precision of +/-3%. Two reviewers independently extracted cost data and study characteristics. Frequencies were calculated and potential characteristics associated with the inclusion of costs were explored. Actual drug costs were included in 4.7% (9/188 of RCTs; any actual costs were included in 7.4% (14/188 of RCTs; and any mention of costs was included in 27.7% (52/188 of RCTs. As the amount of industry funding increased across RCTs, from non-profit to mixed to fully industry funded RCTs, there was a statistically significant reduction in the number of RCTs with any actual costs (Cochran-Armitage test, p = 0.005 and any mention of costs (Cochran-Armitage test, p = 0.02. Logistic regression analysis also indicated funding was associated with the inclusion of any actual cost (OR = 0.34, p = 0.009 or any mention of costs (OR = 0.63, p = 0.02. Journal, study conclusions, study location, primary author's country and product age were not associated with inclusion of cost information. CONCLUSION: While physicians are encouraged to consider costs when prescribing drugs for their patients, actual drug costs were provided in only 5% of RCTs and were not mentioned at all in 72% of RCTs. Industry funded trials were less likely to include cost information. No other factors were associated with the inclusion of cost information.

Do randomized controlled trials discuss healthcare costs?

Science.gov (United States)

Allan, G Michael; Korownyk, Christina; LaSalle, Kate; Vandermeer, Ben; Ma, Victoria; Klein, Douglas; Manca, Donna

2010-08-23

Healthcare costs, particularly pharmaceutical costs, are a dominant issue for most healthcare organizations, but it is unclear if randomized controlled trials (RCTs) routinely discuss costs. Our objective was to assess the frequency and factors associated with the inclusion of costs in RCTs. We randomly sampled 188 RCTs spanning three years (2003-2005) from six high impact journals. The sample size for RCTs was based on a calculation to estimate the inclusion of actual drug costs with a precision of +/-3%. Two reviewers independently extracted cost data and study characteristics. Frequencies were calculated and potential characteristics associated with the inclusion of costs were explored. Actual drug costs were included in 4.7% (9/188) of RCTs; any actual costs were included in 7.4% (14/188) of RCTs; and any mention of costs was included in 27.7% (52/188) of RCTs. As the amount of industry funding increased across RCTs, from non-profit to mixed to fully industry funded RCTs, there was a statistically significant reduction in the number of RCTs with any actual costs (Cochran-Armitage test, p = 0.005) and any mention of costs (Cochran-Armitage test, p = 0.02). Logistic regression analysis also indicated funding was associated with the inclusion of any actual cost (OR = 0.34, p = 0.009) or any mention of costs (OR = 0.63, p = 0.02). Journal, study conclusions, study location, primary author's country and product age were not associated with inclusion of cost information. While physicians are encouraged to consider costs when prescribing drugs for their patients, actual drug costs were provided in only 5% of RCTs and were not mentioned at all in 72% of RCTs. Industry funded trials were less likely to include cost information. No other factors were associated with the inclusion of cost information.

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

Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

NARCIS (Netherlands)

de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study; a multicenter randomized placebo controlled trial

Directory of Open Access Journals (Sweden)

Onland Wes

2011-11-01

Full Text Available Abstract Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD. However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR: NTR2768

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Krüger Matthias

2011-02-01

Full Text Available Abstract Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

Science.gov (United States)

Nishi, Daisuke; Su, Kuan-Pin; Usuda, Kentaro; Chiang, Yi-Ju Jill; Guu, Tai-Wei; Hamazaki, Kei; Nakaya, Naoki; Sone, Toshimasa; Sano, Yo; Tachibana, Yoshiyuki; Ito, Hiroe; Isaka, Keiich; Hashimoto, Kenji; Hamazaki, Tomohito; Matsuoka, Yutaka J

2016-09-15

Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. Clinicaltrials.gov: NCT

Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials.

Science.gov (United States)

Sims, Susan E G; Miller, Katherine; Elfar, John C; Hammert, Warren C

2014-12-01

Non-surgical approaches to treatment of lateral epicondylitis are numerous. The aim of this systematic review is to examine randomized, controlled trials of these treatments. Numerous databases were systematically searched from earliest records to February 2013. Search terms included "lateral epicondylitis," "lateral elbow pain," "tennis elbow," "lateral epicondylalgia," and "elbow tendinopathy" combined with "randomized controlled trial." Two reviewers examined the literature for eligibility via article abstract and full text. Fifty-eight articles met eligibility criteria: (1) a target population of patients with symptoms of lateral epicondylitis; (2) evaluation of treatment of lateral epicondylitis with the following non-surgical techniques: corticosteroid injection, injection technique, iontophoresis, botulinum toxin A injection, prolotherapy, platelet-rich plasma or autologous blood injection, bracing, physical therapy, shockwave therapy, or laser therapy; and (3) a randomized controlled trial design. Lateral epicondylitis is a condition that is usually self-limited. There may be a short-term pain relief advantage found with the application of corticosteroids, but no demonstrable long-term pain relief. Injection of botulinum toxin A and prolotherapy are superior to placebo but not to corticosteroids, and botulinum toxin A is likely to produce concomitant extensor weakness. Platelet-rich plasma or autologous blood injections have been found to be both more and less effective than corticosteroid injections. Non-invasive treatment methods such as bracing, physical therapy, and extracorporeal shockwave therapy do not appear to provide definitive benefit regarding pain relief. Some studies of low-level laser therapy show superiority to placebo whereas others do not. There are multiple randomized controlled trials for non-surgical management of lateral epicondylitis, but the existing literature does not provide conclusive evidence that there is one preferred method

Couple-Based Psychosexual Support Following Prostate Cancer Surgery: Results of a Feasibility Pilot Randomized Control Trial.

Science.gov (United States)

Robertson, Jane; McNamee, Phillip; Molloy, Gerry; Hubbard, Gill; McNeill, Alan; Bollina, Prasad; Kelly, Daniel; Forbat, Liz

2016-08-01

Surgery for prostate cancer can result in distressing side effects such as sexual difficulties, which are associated with lower levels of dyadic functioning. The study developed and tested an intervention to address sexual, relational, and emotional aspects of the relationship after prostate cancer by incorporating elements of family systems theory and sex therapy. To develop and test the feasibility and acceptability of relational psychosexual treatment for couples with prostate cancer, determine whether a relational-psychosexual intervention is feasible and acceptable for couples affected by prostate cancer, and determine the parameters for a full-scale trial. Forty-three couples were recruited for this pilot randomized controlled trial and received a six-session manual-based psychosexual intervention or usual care. Outcomes were measured before, after, and 6 months after the intervention. Acceptability and feasibility were established from recruitment and retention rates and adherence to the manual. The primary outcome measurement was the sexual bother subdomain of the Expanded Prostate Cancer Index Composite. The Hospital Anxiety and Depression Scale and the 15-item Systemic Clinical Outcome and Routine Evaluation (SCORE-15) were used to measure emotional and relational functioning, respectively. The intervention was feasible and acceptable. The trial achieved adequate recruitment (38%) and retention (74%) rates. The intervention had a clinically and statistically significant effect on sexual bother immediately after the intervention. Small decreases in anxiety and depression were observed for the intervention couples, although these were not statistically significant. Practitioners reported high levels of adherence to the manual. The clinically significant impact on sexual bother and positive feedback on the study's feasibility and acceptability indicate that the intervention should be tested in a multicenter trial. The SCORE-15 lacked specificity for this

Tailored approaches to stroke health education (TASHE): study protocol for a randomized controlled trial.

Science.gov (United States)

Ravenell, Joseph; Leighton-Herrmann, Ellyn; Abel-Bey, Amparo; DeSorbo, Alexandra; Teresi, Jeanne; Valdez, Lenfis; Gordillo, Madeleine; Gerin, William; Hecht, Michael; Ramirez, Mildred; Noble, James; Cohn, Elizabeth; Jean-Louis, Giardin; Spruill, Tanya; Waddy, Salina; Ogedegbe, Gbenga; Williams, Olajide

2015-04-19

Stroke is a leading cause of adult disability and mortality. Intravenous thrombolysis can minimize disability when patients present to the emergency department for treatment within the 3 - 4½ h of symptom onset. Blacks and Hispanics are more likely to die and suffer disability from stroke than whites, due in part to delayed hospital arrival and ineligibility for intravenous thrombolysis for acute stroke. Low stroke literacy (poor knowledge of stroke symptoms and when to call 911) among Blacks and Hispanics compared to whites may contribute to disparities in acute stroke treatment and outcomes. Improving stroke literacy may be a critical step along the pathway to reducing stroke disparities. The aim of the current study is to test a novel intervention to increase stroke literacy in minority populations in New York City. In a two-arm cluster randomized trial, we will evaluate the effectiveness of two culturally tailored stroke education films - one in English and one in Spanish - on changing behavioral intent to call 911 for suspected stroke, compared to usual care. These films will target knowledge of stroke symptoms, the range of severity of symptoms and the therapeutic benefit of calling 911, as well as address barriers to timely presentation to the hospital. Given the success of previous church-based programs targeting behavior change in minority populations, this trial will be conducted with 250 congregants across 14 churches (125 intervention; 125 control). Our proposed outcomes are (1) recognition of stroke symptoms and (2) behavioral intent to call 911 for suspected stroke, measured using the Stroke Action Test at the 6-month and 1-year follow-up. This is the first randomized trial of a church-placed narrative intervention to improve stroke outcomes in urban Black and Hispanic populations. A film intervention has the potential to make a significant public health impact, as film is a highly scalable and disseminable medium. Since there is at least one

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

Science.gov (United States)

Inoue, Takuya; Takagi, Hironori; Owada, Yuki; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Yokouchi, Hiroshi; Kanazawa, Kenya; Ohbuchi, Katsuya; Fukushima, Takahisa; Munakata, Mitsuru; Suzuki, Hiroyuki

2017-10-18

Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: an update.

Science.gov (United States)

Majure, David T; Greco, Teresa; Greco, Massimiliano; Ponschab, Martin; Biondi-Zoccai, Giuseppe; Zangrillo, Alberto; Landoni, Giovanni

2013-04-01

The long-term use of milrinone is associated with increased mortality in chronic heart failure. A recent meta-analysis suggested that it might increase mortality in patients undergoing cardiac surgery. The authors conducted an updated meta-analysis of randomized trials in patients undergoing cardiac surgery to determine if milrinone impacted survival. A meta-analysis. Hospitals. One thousand thirty-seven patients from 20 randomized trials. None. Biomed, Central, PubMed, EMBASE, the Cochrane central register of clinical trials, and conference proceedings were searched for randomized trials that compared milrinone versus placebo or any other control in adult and pediatric patients undergoing cardiac surgery. Authors of trials that did not include mortality data were contacted. Only trials for which mortality data were available were included. Overall analysis showed no difference in mortality between patients receiving milrinone versus control (12/554 [2.2%] in the milrinone group v 10/483 [2.1%] in the control arm; relative risk [RR] = 1.15; 95% confidence interval [CI], 0.55-2.43; p = 0.7) or in analysis restricted to adults (11/364 [3%] in the milrinone group v 9/371 [2.4%] in the control arm; RR = 1.17; 95% CI, 0.54-2.53; p = 0.7). Sensitivity analyses in trials with a low risk of bias showed a trend toward an increase in mortality with milrinone (8/153 [5.2%] in the milrinone arm v 2/152 [1.3%] in the control arm; RR = 2.71; 95% CI, 0.82-9; p for effect = 0.10). Despite theoretic concerns for increased mortality with intravenous milrinone in patients undergoing cardiac surgery, the authors were unable to confirm an adverse effect on survival. However, sensitivity analysis of high-quality trials showed a trend toward increased mortality with milrinone. Copyright © 2013 Elsevier Inc. All rights reserved.

Critical concepts in adaptive clinical trials

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Park JJH

2018-03-01

Full Text Available Jay JH Park,1 Kristian Thorlund,2,3 Edward J Mills2,3 1Department of Medicine, University of British Columbia, Vancouver, BC, Canada; 2Department of Health Research Methods, Evidence, and Impact (HEI, McMaster University, Hamilton, ON, Canada; 3The Bill and Melinda Gates Foundation, Seattle, WA, USA Abstract: Adaptive clinical trials are an innovative trial design aimed at reducing resources, decreasing time to completion and number of patients exposed to inferior interventions, and improving the likelihood of detecting treatment effects. The last decade has seen an increasing use of adaptive designs, particularly in drug development. They frequently differ importantly from conventional clinical trials as they allow modifications to key trial design components during the trial, as data is being collected, using preplanned decision rules. Adaptive designs have increased likelihood of complexity and also potential bias, so it is important to understand the common types of adaptive designs. Many clinicians and investigators may be unfamiliar with the design considerations for adaptive designs. Given their complexities, adaptive trials require an understanding of design features and sources of bias. Herein, we introduce some common adaptive design elements and biases and specifically address response adaptive randomization, sample size reassessment, Bayesian methods for adaptive trials, seamless trials, and adaptive enrichment using real examples. Keywords: adaptive designs, response adaptive randomization, sample size reassessment, Bayesian adaptive trials, seamless trials, adaptive enrichment