Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...
Deborah E Barnes
Full Text Available Current dementia medications have small effect sizes, many adverse effects and do not change the disease course. Therefore, it is critically important to study alternative treatment strategies. The goal of this study was to pilot-test a novel, integrative group exercise program for individuals with mild-to-moderate dementia called Preventing Loss of Independence through Exercise (PLIÉ, which focuses on training procedural memory for basic functional movements (e.g., sit-to-stand while increasing mindful body awareness and facilitating social connection.We performed a 36-week cross-over pilot clinical trial to compare PLIÉ with usual care (UC at an adult day program for individuals with dementia in San Francisco, CA. Assessments of physical performance, cognitive function, physical function, dementia-related behaviors, quality of life and caregiver burden were performed by blinded assessors at baseline, 18 weeks (cross-over and 36 weeks. Our primary outcomes were effect sizes based on between-group comparisons of change from baseline to 18 weeks; secondary outcomes were within-group comparisons of change before and after cross-over.Twelve individuals enrolled (7 PLIÉ, 5 UC and 2 withdrew (1 PLIÉ, 18 weeks; 1 UC, 36 weeks. Participants were 82% women (mean age, 84 ± 4 years; caregivers were 82% daughters (mean age, 56 ± 13 years. Effect sizes were not statistically significant but suggested potentially clinically meaningful (≥ 0.25 SDs improvement with PLIÉ versus UC for physical performance (Cohen's D: 0.34 SDs, cognitive function (0.76 SDs and quality of life (0.83 SDs as well as for caregiver measures of participant's quality of life (0.33 SDs and caregiver burden (0.49 SDs. Results were similar when within-group comparisons were made before and after cross-over.PLIÉ is a novel, integrative exercise program that shows promise for improving physical function, cognitive function, quality of life and caregiver burden in individuals with
Akin, Yigit; Gulmez, Hakan; Ates, Mutlu; Bozkurt, Aliseydi; Nuhoglu, Baris
Background: Premature ejaculation (PE) is the most common sexual disorder in men and studies reported prevalence up to 30% (1, 2). PE is not a life-threatening medical condition but it influences the quality of life (QoL). Objectives: The aim of this study was to compare the efficiency, and safety of alpha blocker drugs in the treatment of patients with premature ejaculation (PE). Additionally we investigated the quality of life (QoL) in patients with PE who were treated with alpha blocker drugs. Materials and Methods: This study was a pilot clinical trial. Prospectively documented 108 patients with PE were treated and were followed-up in urology outpatient clinic. All patients were divided into 5 groups according to used alpha blocker agents which were determined by simple randomization. Silodosin 4mg (Group 1, n = 21), tamsulosin hydrochloride 0.4mg (Group 2, n = 23), alfuzosin 10mg (Group 3, n = 22), terazosin 5mg (Group 4, n = 21), doksazosin mesylate 4mg (Group5, n = 21), were used for treatment. The demographic parameters of patients, pre and post treatment intravaginal ejaculation latency time (IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P IELT and decrease in PEP were provided more in Group 1 than other groups (P IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P < 0.05 was considered statistically significant. PMID:24693363
Krieger, Janice L; Parrott, Roxanne L; Nussbaum, Jon F
Patients often have difficulty understanding what randomization is and why it is needed in Phase III clinical trials. Physicians commonly report using metaphorical language to convey the role of chance in being assignment to treatment; however, the effectiveness of this strategy as an educational tool has not been explored. Guided by W. McGuire's (1972) information-processing model, the purpose of this pilot study was to explore effects of metaphors to explain randomization on message acceptance and behavioral intention to participate in a Phase III clinical trial among a sample of low-income, rural women (N = 64). Participants were randomly assigned to watch a video that explained randomization using 1 of 3 message strategies: a low-literacy definition, standard metaphor (i.e., flip of a coin), or a culturally derived metaphor (i.e., sex of a baby). The influence of attention on behavioral intentions to participate in clinical trials was partially moderated by message strategy. Under conditions of low attention, participants in the culturally derived metaphor condition experienced significantly higher intentions to participate in clinical trials compared with participants in the standard metaphor condition. However, as attention increased, differences in intentions among the conditions diminished. Having a positive affective response to the randomization message was a strong, positive predictor of behavioral intentions to participate in clinical trials. The authors discuss the theoretical and practical implications of these findings.
McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.
No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…
Rahul A. Sheth
Full Text Available White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15–25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1 the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2 the ability of this system to identify polyps as small as 1 mm, and (3 the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps.
Full Text Available Home > Health topics A-Z > Participating in Clinical Trials: About Clinical Trials In This Topic About Clinical Trials Risks ... centers across the country. The National Institutes of Health funds much of this basic research. Screening Trials ...
Kline Lawrence E
Full Text Available Abstract Background In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH. Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes. Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a randomized controlled trial of melatonin or matched placebo. The three randomized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime, melatonin 0.5 mg upon morning awakening, or placebo capsules. Twelve of the women were admitted to the GCRC at baseline and at the end of randomized treatment for 24-hour sampling of blood for LH. Morning urine samples were collected twice weekly to measure LH excretion. Subjective responses measured throughout baseline and treatment included sleep and hot flash logs, the CESD and QIDS depression self-ratings, and the SAFTEE physical symptom inventory. Results Urinary LH tended to increase from baseline to the end of treatment. Contrasts among the 3 randomized groups were statistically marginal, but there was relative suppression combining the groups given melatonin as contrasted to the placebo group (p Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women. An effect related to the duration of nocturnal melatonin elevation is suggested. Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men. Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile.
O. Yu. Leplina
Full Text Available Chronic recurrent infections caused by herpes simplex virus (HSV types 1 and 2 represent a serious medical and social challenge. Given an important role of immune system in surveillance of viral infections, an induced enhancement of antigen-specific immune response seems to be a promising approach to treatment of recurrent HSV infections, in particular, using dendritic cell (DCs vaccines. The present paper contains results of an open pilot study evaluating efficacy and safety of dendritic-cell vaccines in the patients with recurrent HSV infections. Twenty-nine patients including 14 persons with labial herpes, and 15, with genital herpes have been enrolled in this study. DCs were generated in presence of GM-CSF and IFNα and then loaded with recombinant viral proteins (HSV1gD or HSV2gD. These cells were applied in 2 rounds of vaccination performed within 9 months. Immunotherapy with DCs did not induce sufficient side effects, and was accompanied by more than two-fold decrease in relapse rate and increased length of remissions during the 9-month period of treatment. Later on, we revealed a reduced frequency of relapses, and a 3-fold increase in remission duration over the subsequent 6-month follow up. The clinical effect during the treatment and at later terms (a half-year observation was noted with both labial and genital herpes, as registered in the majority of patients, being associated with induction of antigen-specific proliferative response and normalization of reduced mitogenic responsiveness of mononuclear cells towards ConA. The patients’ survey at longer terms (more than 24 months has shown that the beneficial effect of immunotherapy, in terms of reduced relapse rates, was maintained in 77.8% of the respondents by 48 months (a median follow-up term. At this time, the antigen specific proliferative response was maintained in 66.7% of patients. The data obtained suggest that the dendritic-cell vaccines may be a promising approach to the
Putten, E. van der; Velden, J.W. van der; Siers, A.; Hamersma, E.A.M.
Twelve institutional data managers were asked to independently code the data from a patient chart of one patient in an ovarian cancer trial. They abstracted data from the medical record and filled out three types of trial forms (on-study, chemotherapy, and summary forms). The analysis of the process
Barnes, Deborah E.; Wolf Mehling; Eveline Wu; Matthew Beristianos; Kristine Yaffe; Karyn Skultety; Chesney, Margaret A.
Background Current dementia medications have small effect sizes, many adverse effects and do not change the disease course. Therefore, it is critically important to study alternative treatment strategies. The goal of this study was to pilot-test a novel, integrative group exercise program for individuals with mild-to-moderate dementia called Preventing Loss of Independence through Exercise (PLIÉ), which focuses on training procedural memory for basic functional movements (e.g., sit-to-stand) ...
Full Text Available ... Participating in Clinical Trials: About Clinical Trials In This Topic About Clinical Trials Risks and Benefits Terms ... with Your Doctor Taking Medicines The information in this topic was provided by the National Library of ...
Full Text Available ... Participating in Clinical Trials About Clinical Trials A Research Study With Human Subjects A clinical trial is a research study that involves human subjects. The purpose of ...
Full Text Available ... on. Participating in Clinical Trials About Clinical Trials A Research Study With Human Subjects A clinical trial is a research study that involves human subjects. The purpose ...
Full Text Available Background. From the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, autism is considered a pervasive developmental disorder. It manifests as a behavioral syndrome characterised by impairment in social interaction and communication, restricted interests and activities, as well as repetitive and stereotyped patterns. Such profile renders prevention measures and dental care seriously compromised so that usually autistic children are treated and cared following general anesthesia. Aims. We aimed at developing a target-specific educational approach allowing to avoid general anesthesia in autistic patients subjected to dental care treatments (e.g. sealing, plaque ablation, minimal carious lesions etc.; such protocol should also facilitate the implementation of prevention measures. Design. It is proposed a target-specific educational research protocol adopting individual strategies and methodologies, including Augmentative and Alternative Communication (AAC for patients with speech and language impairments. The dentists are trained by the educator, who acts as a filter between the patient and the medical team. The team is required until a relationship of trust with the patient is built and the dentist is able to continue independently. Results. We present a pilot clinical trial in which out of 34 patients between 6 and 12 years old showed a positive response to the application of the protocol, allowing the execution of dental therapies together with a long-term prevention programme and in 32 of them the general anesthesia was avoided. Negative results regarded two patients who had not undergone any behavioral, psychomotor or speech rehabilitation therapy. Conclusions. Though the results should be considered as preliminary, the application of the method with the synergistic action of the people in the team allowed the execution of dental therapies. Given the positive outcomes, the Pediatric Dentistry Unit of the Umberto I Hospital
Full Text Available ... trial is to find out if an experimental drug, therapy, medical device, lifestyle change, or test will ... disease. Phases of Clinical Trials Clinical trials of drugs are usually described based on their phase. The ...
Gordon, Jessica K.; Martyanov, Viktor; Magro, Cynthia; Wildman, Horatio F.; Wood, Tammara A; Huang, Wei-Ti; Crow, Mary K.; Whitfield, Michael L.; Spiera, Robert F.
Introduction Tyrosine kinase inhibitors (TKI) are medications of interest in the treatment of Systemic Sclerosis (SSc) because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous (dc)SSc with the TKI nilotinib (Tasigna™). Methods Ten adult patients with early dcSSc were treated with nilotinib. Primary endpoints were safety...
Full Text Available ... Clinical Trials In This Topic About Clinical Trials Risks and Benefits Terms to Know Finding a Clinical ... researchers may gather information about experimental treatments, their risks, and how well they work compare existing therapies ...
Singab, Abdel-Naser B; El-Hefnawy, Hala M; Esmat, Ahmed; Gad, Haidy A; Nazeam, Jilan A
Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant. PMID:26768148
... Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...
Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki
We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI)…
Full Text Available ... that could identify a disease in its early stages. Usually, trial participants must show signs of the ... Trials Clinical trials of drugs are usually described based on their phase. The U.S. Food and Drug ...
Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.
Paul J Novotny
Full Text Available Paul J Novotny1, Denise J Smith1, Lorna Guse2, Teresa A Rummans3, Lynn Hartmann4, Steven Alberts4, Richard Goldberg5, David Gregory6, Mary Johnson7, Jeff A Sloan11Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2Faculty of Nursing, University of Manitoba, Winnipeg, Manitoba, Canada; 3Psychiatry, Mayo Clinic, Rochester, MN, USA; 4Medical Oncology, Mayo Clinic, Rochester, MN, USA; 5Oncology Services, University of North Carolina, Chapel Hill, NC, USA; 6Faculty of Health Sciences Nursing, University of Lethbridge, Lethbridge, Alberta, Canada; 7Chaplain Services, Mayo Clinic, Rochester, MN, USAPurpose: This study tested the logistical feasibility of obtaining data on social support systems from cancer patients enrolled on clinical trials and compared the social support of older adults (age ≥65 and younger adults (<50 years of age with cancer.Methods: Patients had to be eligible for a phase II or phase III oncology clinical trial and enter the study prior to treatment. Patients filled out the Lubben Social Network Scale (LSNS at baseline. The Symptom Distress Scale (SDS and single-item overall quality of life (QOL Uniscale were assessed at baseline and weekly for 4 weeks.Results: There was no significant difference in overall mean Lubben social support levels by age. Older patients had more relatives they felt close to (85% versus 53% with 5 or more relatives, P = 0.02, heard from more friends monthly (84% versus 53% with 3 or more friends, P = 0.02, less overall symptom distress (P = 0.03, less insomnia (P = 0.003, better concentration (P = 0.005, better outlook (P = 0.01, and less depression (P = 0.005 than younger patients.Conclusions: Younger subjects reported worse symptoms, a smaller social support network, and fewer close friends and relatives than older subjects. Having someone to discuss decisions and seeing friends or relatives often was associated with longer survival. Keywords: social support, Lubben scale, QOL, elderly
Boysen, Gudrun; Krarup, Lars-Henrik; Zeng, Xianrong;
OBJECTIVES: To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity. DESIGN: Multicentre, multinational, randomised clinical trial with masked outcome assessment. SETTING: Stroke units in Denmark, China...... infarction, or falls and fractures. CONCLUSION: Repeated encouragement and verbal instruction in being physically active did not lead to a significant increase in physical activity measured by the PASE score. More intensive strategies seem to be needed to promote physical activity after ischaemic stroke...
Full Text Available ... In This Topic About Clinical Trials Risks and Benefits Terms to Know Finding a Clinical Trial Informed ... for more information Scientists usually do years of experiments in the laboratory and in animals before they even consider testing an experimental treatment ...
Full Text Available ... In This Topic About Clinical Trials Risks and Benefits Terms to Know Finding a Clinical Trial Informed ... years of experiments in the laboratory and in animals before they even ... this early research occurs at universities and medical centers across the ...
Kraus, V B; Blanco, F J; Englund, M;
The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from...... both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials...... and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety...
-test and ANCOVA (P <0.05). Discussion The results of this study will allow evaluation of contralateral acupuncture from two aspects. First, if the contralateral acupuncture shows the effects similar to ipsilateral acupuncture, this will establish clinical basis for contralateral acupuncture. Second, if the effects of contralateral acupuncture are not comparable to the effects of ipsilateral acupuncture, but are shown to be similar to the effects of the sham acupuncture, we can establish the basis for using the same acupoints of the unaffected side as a control in acupuncture clinical studies. Trial registration This trial has been registered with the ‘Clinical Research Information Service (CRIS)’, Republic of Korea: KCT0000628. PMID:23768129
. Conclusions Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results. Trial Registration WHO Clinical Trial Registration ID: ACTRN12610000958088 http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088
Leon, Andrew C.; Davis, Lori L.; Kraemer, Helena C.
Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention.
Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B
This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise. Most chapters have been revised considerably from the fourth edition. A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded. Many contemporary clinical trial examples have been added. There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials. This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...
Full Text Available The aim of this study was to investigate the effects of a virtual reality program combined with conventional therapy in upper limb function in people with tetraplegia and to provide data about patients’ satisfaction with the virtual reality system. Thirty-one people with subacute complete cervical tetraplegia participated in the study. Experimental group received 15 sessions with Toyra® virtual reality system for 5 weeks, 30 minutes/day, 3 days/week in addition to conventional therapy, while control group only received conventional therapy. All patients were assessed at baseline, after intervention, and at three-month follow-up with a battery of clinical, functional, and satisfaction scales. Control group showed significant improvements in the manual muscle test (p = 0,043, partial η2 = 0,22 in the follow-up evaluation. Both groups demonstrated clinical, but nonsignificant, changes to their arm function in 4 of the 5 scales used. All patients showed a high level of satisfaction with the virtual reality system. This study showed that virtual reality added to conventional therapy produces similar results in upper limb function compared to only conventional therapy. Moreover, the gaming aspects incorporated in conventional rehabilitation appear to produce high motivation during execution of the assigned tasks. This trial is registered with EudraCT number 2015-002157-35.
Ports, William C; Feldman, Steven R; Gupta, Pankaj; Tan, Huaming; Johnson, Theodore R; Bissonnette, Robert
Intra-subject, left-right, randomized, controlled study designs are often used for proof-of-concept studies in dermatology. This design was used to evaluate the safety and efficacy of a topical solution of tofacitinib (NCT00678561), a small-molecule Janus kinase inhibitor under investigation for the topical and oral treatment of patients with chronic plaque psoriasis. Eighty-one patients, each with matched left and right target plaques, were randomized to 2%, 0.2%, or 0.02% tofacitinib or vehicle solution once or twice daily. Patients treated one plaque as per their randomization group (2%, 0.2%, 0.02% tofacitinib, or vehicle solution), and used vehicle to treat the contralateral plaque for 4 weeks. Except during clinic visits, study drug applications were performed unsupervised outside the clinical trial site. Intra-subject, vehicle-adjusted mean percent change from baseline in Target Plaque Severity Score at week 4 (primary efficacy endpoint) was not significantly different from baseline for any treatment group (P values of 0.28-0.68). However, skin biopsy analyses detected tofacitinib in both tofacitinib- and vehicle-treated plaques of some patients, suggesting cross-contamination or solution misapplication. Lack of efficacy with tofacitinib relative to vehicle may be due to the intra-subject study design with unsupervised applications. These findings have potential implications for future intra-subject studies of topical treatments.
Dimbwadyo-Terrer, I; Gil-Agudo, A; Segura-Fragoso, A; de los Reyes-Guzmán, A; Trincado-Alonso, F; Piazza, S; Polonio-López, B
The aim of this study was to investigate the effects of a virtual reality program combined with conventional therapy in upper limb function in people with tetraplegia and to provide data about patients' satisfaction with the virtual reality system. Thirty-one people with subacute complete cervical tetraplegia participated in the study. Experimental group received 15 sessions with Toyra(®) virtual reality system for 5 weeks, 30 minutes/day, 3 days/week in addition to conventional therapy, while control group only received conventional therapy. All patients were assessed at baseline, after intervention, and at three-month follow-up with a battery of clinical, functional, and satisfaction scales. Control group showed significant improvements in the manual muscle test (p = 0,043, partial η (2) = 0,22) in the follow-up evaluation. Both groups demonstrated clinical, but nonsignificant, changes to their arm function in 4 of the 5 scales used. All patients showed a high level of satisfaction with the virtual reality system. This study showed that virtual reality added to conventional therapy produces similar results in upper limb function compared to only conventional therapy. Moreover, the gaming aspects incorporated in conventional rehabilitation appear to produce high motivation during execution of the assigned tasks. This trial is registered with EudraCT number 2015-002157-35.
Full Text Available ... experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or tests to those already available or may compare existing ...
Full Text Available ... Clinical Trials Videos quiz yourself MedlinePlus for More Information National Institute on Aging Related Topics Talking with Your Doctor Taking Medicines The information in this topic was provided by the National ...
U.S. Department of Health & Human Services — Provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases...
Full Text Available ... Learn More Participating in Clinical Trials Videos quiz yourself MedlinePlus for More Information National Institute on Aging Related Topics Talking with Your Doctor Taking Medicines The information in ...
Full Text Available Hassan Adalatkhah1, Farhad Pourfarzi2, Homayoun Sadeghi-Bazargani31Department of Dermatology, 2Department of Social Medicine, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil; 3Statistics and Epidemiology Department, Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, IranBackground: The use of oral flutamide is rarely investigated in acne therapy. The aim of this study was to compare the efficacy of oral flutamide with that of a cyproterone-estradiol combination in treating acne lesions.Methods: A randomized clinical trial enrolled patients with moderate acne into two equal groups to receive either oral flutamide or the cyproterone-estradiol combination for 6 months. Lesion count, Acne Severity Index, and Global Acne Grading system (GAGS scores were used to assess improvement in acne lesions. The dichotomous measurement scale for primary endpoint assessment was defined as improvement from moderate to mild acne based on GAGS score. Patient satisfaction and dermal fat were also assessed. Intention to treat and per protocol analyses were done, reporting related effect sizes.Results: Both treatments resulted in substantial improvement in acne lesions. Although flutamide seemed to have higher efficacy, an intention to treat analysis did not find the two treatment protocols to be different. The relative risk in intention to treat analysis was 1.8 (95% confidence interval [CI] 0.89–1.6, and was 1.33 (95% CI 1.03–1.72 for the per protocol analysis. The number needed to treat for flutamide compared with the cyproterone-estradiol combination was 7.7 and 4.2 in the intention to treat and per protocol analyses, respectively.Conclusion: Flutamide appears to be more effective than a cyproterone-estradiol combination in some aspects of acne treatment, but this requires confirmation in a larger trial.Keywords: acne vulgaris, flutamide, cyproterone acetate, ethinyl estradiol, androgen antagonists
Gadi Lalazar; Tomer Adar; Yaron Ilan
AIM: To assess the role of the 13C-methacetin breath test (MBT) in patients with acute liver disease. METHODS: Fifteen patients with severe acute liver disease from diverse etiologies were followed-up with 13C-MBT during the acute phase of their illnesses (range 3-116 d after treatment). Patients fasted for 8 h and ingested 75 mg of methacetin prior to the MBT. We compared results from standard clinical assessment, serum liver enzymes, synthetic function, and breath test scores. RESULTS: Thirteen patients recovered and two patients died. In patients that recovered, MBT parameters improved in parallel with improvements in lab results. Evidence of consistent improvement began on day 3 for MBT parameters and between days 7 and 9 for blood tests. Later convergence to normality occurred at an average of 9 d for MBT parameters and from 13 to 28 d for blood tests. In both patients that died, MBT parameters remained low despite fluctuating laboratory values. CONCLUSION: The 13C-MBT provides a rapid, noninvasive assessment of liver function in acute severe liver disease of diverse etiologies. The results of this pilot clinical trial suggest that the MBT may offer greater sensitivity than standard clinical tests for managing patients with severe acute liver disease.
McAlindon, T. E.; Driban, J. B.; Henrotin, Y.;
The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct......, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After...... and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials...
Lam, Wendy K.K.; Fals-Stewart, William; Kelley, Michelle L.
This pilot study examined preliminary effects of Parent Skills Training with Behavioral Couples Therapy on children’s behavioral functioning. Participants were men (N = 30) entering outpatient alcohol treatment, their female partners, and a custodial child between 8 and 12 years of age. Couples were randomly assigned to one of three equally intensive conditions: (a) Parent Skills with Behavioral Couples Therapy (PSBCT), (b) BCT (without parent training), and (c) Individual-Based Treatment (IB...
Full Text Available ... to find out if an experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or ... universities and medical centers across the country. The National Institutes of ...
... Reports Clinician Tools Clinician Tools Home Guidelines and Best Practices Topic Reviews Algorithms, Screens, Toolkits Provider Education Provider ... about federally and privately supported clinical research in human volunteers. Site gives information about a trial's purpose, who may participate, locations, and phone ... Forms State and Local Resources Strat Plan FY 2014-2020 VA Plans, Budget, & ...
Full Text Available BACKGROUND/OBJECTIVES: Pain-related misbeliefs among health care professionals (HCPs are common and contribute to ineffective postoperative pain assessment. While standardized patients (SPs have been effectively used to improve HCPs’ assessment skills, not all centres have SP programs. The present equivalence randomized controlled pilot trial examined the efficacy of an alternative simulation method – deteriorating patient-based simulation (DPS – versus SPs for improving HCPs’ pain knowledge and assessment skills.
Thiago Saads CARVALHO; Baumann, Tommy; Lussi, Adrian
Background Erosive tooth wear (ETW) is clinically characterized by a loss of tooth surface, and different enamel depths may have different susceptibility to demineralization. Therefore, the aim of this in vitro pilot study was to assess if the progression of erosive demineralization is faster on teeth already presenting signs of ETW when compared to originally sound teeth. Methods We selected 23 central incisors: 14 were clinically sound (Sound) and 9 presented clinical signs of early erosive...
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Meineche-Schmidt, V.; Christensen, E.; Bytzer, P.
Background: Response to proton pump inhibitor (PPI) treatment in dyspepsia is unpredictable. Aim: To identify symptoms associated with response to esomeprazole in order to target patients for empirical treatment. Methods: Eight hundred and five uninvestigated, primary care patients with upper GI ....... Conclusions In patients with uninvestigated dyspepsia, PPI responders can be reliably identified by a simple pocket chart using symptoms and patient characteristics (ClinicalTrials.gov NCT00318968). © 2010 Blackwell Publishing Ltd....
Sruthima N. V. S. Gottumukkala
Full Text Available Aim: The aim of this study is to evaluate the efficacy of 1% curcumin (CU solution and compare it with conventional irrigant i.e., 0.2% chlorhexidine (CHX gluconate and a positive control (saline as an adjunct to thorough scaling and root planing. Materials and Methods: A total of 23 patients with non-adjacent probing pocket depths (PPDs ≥5mm were randomly assigned to CHX, CU and positive control irrigation groups and subjected to randomized single blinded clinical control trial. The clinical parameters bleeding on probing, redness, plaque index, PPD and microbiological parameter N-benzoyl-DL-arginine-2-naphthylamide (BANA test were evaluated at baseline, 1, 3 and 6 months interval. Results: At 1 month evaluation, CU group showed better results compared with the other groups. However, by the end of the study period CHX group showed the best results with as light recurrence in the CU group. The results of BANA test showed similar results for both CU and CHX group throughout the study period. Conclusion: The results of this study show a mild to moderate beneficiary effect of CU irrigation when used as an adjunct to Scaling and root planing. Further studies may be required using varied concentrations of the drug to improve the substantivity of the drug and also to prevent early re-colonization of periodontal pathogens.
Full Text Available ... treatment, screening, diagnostic, prevention, and supportive care trials. Treatment Trials In treatment trials, researchers may gather information about experimental treatments, ...
Full Text Available Gait disorder, a key contributor to fall and poor quality of life, represents a major therapeutic challenge in Parkinson's disease (PD. The efficacy of acupuncture for PD remains unclear, largely due to methodological flaws and lack of studies using objective outcome measures.To objectively assess the efficacy of electroacupuncture (EA for gait disorders using body-worn sensor technology in patients with PD.In this randomized pilot study, both the patients and assessors were masked. Fifteen PD patients were randomly assigned to an experimental group (n = 10 or to a control group (n = 5. Outcomes were assessed at baseline and after completion of three weekly EA treatments. Measurements included gait analysis during single-task habitual walking (STHW, dual-task habitual walking (DTHW, single-task fast walking (STFW, dual-task fast walking (DTFW. In addition, Unified Parkinson's Disease Rating Scale (UPDRS, SF-12 health survey, short Falls Efficacy Scale-International (FES-I, and visual analog scale (VAS for pain were utilized.All gait parameters were improved in the experimental group in response to EA treatment. After adjustment by age and BMI, the improvement achieved statistical significant level for gait speed under STHW, STFW, and DTFW (9%-19%, p0.110. The highest correlation between gait parameters and UPRDS scores at baseline was observed between gait speed during STFW and UPDRS II (r = -0.888, p = 0.004. The change in this gait parameter in response to active intervention was positively correlated with baseline UPDRS (r = 0.595, p = 0.057. Finally, comparison of responses to treatment between groups showed significant improvement, prominently in gait speed (effect size 0.32-1.16, p = 0.001.This study provides the objective proof of concept for potential benefits of non-pharmaceutical based EA therapy on enhancing gait in patients with PD.ClinicalTrials.gov NCT02556164.
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran. PMID:11980386
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort
Tomillero, A; Moral, M A
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline
Tomillero, A; Moral, M A
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil
Tomillero, A; Moral, M A
Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar
Bayes, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T
Tomillero, A; Moral, M A
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa
Kleijnen, J.; Knipschild, P; ter Riet, G
OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURE...
Østervig, R M; Sonne, A; Rasmussen, L S
starting enrolment before 2010 to 63.2% after 2010 (24/38, P clinical trials were registered at clinicaltrials.gov. CONCLUSION: Many published randomized controlled trials from Acta Anaesthesiologica Scandinavica were not adequately registered but the requirement of trial registration has...
Full Text Available ... the body laboratory tests that check samples of blood, urine, or other body tissues genetic tests that look for genes linked to some types of disease. Diagnostic Trials In diagnostic trials, researchers ...
Bayés, M; Rabasseda, X; Prous, J R
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate
Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara
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…
... Meetings, Conferences & Events Partnering & Donating to the NICHD Staff Directory ... Clinical Research Skip sharing on social media links Share this: Page Content Clinical research is research that directly involves a ...
Ayres, Thomas R.
The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)
Full Text Available ... on their phase. The U.S. Food and Drug Administration typically requires Phase 1, 2 and 3 trials ... 000 people. If the U.S. Food and Drug Administration agrees that the trial results are positive, they ...
Full Text Available ... disease or prevent a disease from returning. Supportive Care Trials In supportive care trials, researchers look for ways to make life ... groups, and various types of social interventions. Supportive care interventions are not intended to treat or cure ...
Full Text Available ... care trials, researchers look for ways to make life better for people living with a life threatening disease or chronic health problem. The goal ... IV trial for drugs or devices takes place after the U.S. Food and Drug Administration approves their ...
Thompson, Michael A
Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.
Full Text Available ... out if an experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or ... specific medical problem. These trials find out if lifestyle changes, such as exercising more, getting more sleep, ...
Full Text Available ... radiotherapy. Click for more information Scientists usually do years of experiments in the laboratory and in animals ... term side effects. This phase can last several years. A Phase III trial gathers more information about ...
Full Text Available ... Drug Administration typically requires Phase 1, 2 and 3 trials to be conducted to determine if the ... subjects usually ranges from several hundred to about 3,000 people. If the U.S. Food and Drug ...
Katz, J N; Losina, E; Lohmander, L S
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...
Full Text Available Patello-femoral pain syndrome (PFPS is a common knee joint disability. The integration of hip soft tissue regimens are not always emphasized, although current literature implies that there is a significant relationship between the two and there is a lack of randomized clinical trials to substantiate this relationship in clinical practice. A randomized controlled assessor blinded trial was designed to explore different rehabilitation programs related to PFPS. The study was conducted at RAZIEL institute of physical therapy, Netania, Israel with a total of 30 consecutive patients (mean age 35y, diagnosed with PFPS. All patients were randomly allocated into 3 groups. Group I conventional knee rehabilitation program. Included quadriceps strengthening and Trans Electric Neuromuscular Stimulation (TENS. Group II hip oriented rehabilitation program. included stretching, Hip external rotators strengthening and TENS. Group III a combination of the two above programs. Pain and function were documented on initial of the program and again 3 weeks later, on the completion. Pain was assessed by a numeric visual analogue scale (VAS; function was assessed by Patello-femoral joint evaluation scale (PFJES (0-100 points. At end of trial, all groups showed significant improvements in VAS and PFJES (p<0.0001; these improvements did not vary significantly between the 3 groups. The conclusions were that the explored different rehabilitation programs showed a similar beneficial effect.
Kjaergard, L L; Nikolova, D; Gluud, C
Evidence shows that the quality of randomized clinical trials (RCTs) affects estimates of intervention efficacy, which is significantly exaggerated in low-quality trials. The present study examines the quality of all 235 RCTs published in HEPATOLOGY from the initiation in 1981 through August 1998...
B.A. Kirwan (Bridget Anne)
textabstractThe aim of this thesis is to show how clinical trial conduct can be managed while respecting the underlying scientific principles. Chapter 2 describes the main results of PICO (PImobendan in COngestive heart failure), a trial which investigated a positive inotropic agent in patients with
Ottevanger, P.B.; Therasse, P.; Veld, C.J.H. van de; Bernier, J.; Krieken, J.H.J.M. van; Grol, R.P.T.M.; Mulder, P.H.M. de
From the literature that was initially searched by electronic databases using the keywords quality, quality control and quality assurance in combination with clinical trials, surgery, pathology, radiotherapy, chemotherapy and data management, a comprehensive review is given on what quality assurance
Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: The Seniors Health and Activity Research Program Pilot (SHARP-P Study, a randomized controlled trial
Rejeski W Jack
Full Text Available Abstract Background The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial. Methods SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA and/or cognitive training intervention (CT in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment. Results Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004, the interventions produced marked changes in cognitive and physical performance measures (p≤0.05, and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01. Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome or 2,000 participants (categorical outcome. Conclusions Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible. Trial Registration Clinicaltrials.gov Identifier: NCT00688155
Full Text Available ... care trials, researchers look for ways to make life better for people living with a life threatening disease or chronic health problem. The goal ... experimental treatment on a small group of often healthy people (20 to 80), to judge its safety ...
Full Text Available ... care trials, researchers look for ways to make life better for people living with a life threatening disease or chronic health problem. The goal ... to obtain preliminary data on whether the drug works in people who have a certain disease or ...
Emery, C. A.; Roos, Ewa M.; Verhagen, E.;
The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform...
Full Text Available ... are usually described based on their phase. The U.S. Food and Drug Administration typically requires Phase 1, ... hundred to about 3,000 people. If the U.S. Food and Drug Administration agrees that the trial ...
Reimer, C; Lødrup, A B; Smith, G;
of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. METHODS: This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using...
Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |
Seyedeh Neda Mousavi
Full Text Available Background: Parenteral nutrition (PN is a valuable life saving intervention, which can improve the nutritional status of hospitalized malnourished patients. PN is associated with complications including hyperglycemia. This study was conducted to compare two methods of blood glucose control in traumatic brain injury patients on PN. Materials and Methods: A randomized, open-label, controlled trial with blinded end point assessment was designed. Traumatic brain injury patients (GCS = 4-9 on PN, without diabetes, pancreatitis, liver disease, kidney complication, were participated. Patients were randomly assigned to receive continuous insulin infusion to maintain glucose levels between 4.4 mmol/l (80 mg/dl and 6.6 mmol/l (120 mg/dl (n = 13 or conventional treatment (n = 13. Patients in the conventional group were not received insulin unless glucose levels were greater than 10 mmol/l (>180 mg/dl. These methods were done to maintain normoglycemia in ICU. The primary outcome was hypo/hyperglycemic episodes. Other factors such as C-reactive protein, blood electrolytes, liver function tests, lipid profile and mid-arm circumference were compared. Results: Mean glucose concentration were significantly lower in IIT group (118 ± 28 mg/dl vs conventional group (210 ± 31 mg/dl (P < 0.01. No hypoglycemic episode occurred in two groups. Triglyceride (P = 0.02 and C-reactive protein (P = 0.001 was decreased in the IIT group, significantly. There were also significant differences in the electrolytes, with magnesium and phosphorus being lower in the IIT group (P = 0.05. Conclusion: In this pilot study, blood glucose level, CRP and TG were lower in IIT group. Further data collection is warranted to reach definitive conclusions.
Schwartz Howard I
Full Text Available Abstract Background Recent research has established correlations between stress, anxiety, insomnia and excess body weight and these correlations have significant implications for health. This study measured the effects of a proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense (Relora® on anxiety, stress and sleep in healthy premenopausal women. Methods This randomized, parallel, placebo controlled clinical study was conducted with healthy, overweight (BMI 25 to 34.9, premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scores above the national mean for women on self-reporting anxiety. The intervention was Relora (250 mg capsules or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety. The study was conducted by Miami Research Associates, a clinical research organization in Miami, FL. Results The intent-to-treat population consisted of 40 subjects with 26 participants completing the study. There were no significant adverse events. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments conducted in this study including salivary cortisol and amylase levels, appetite, body morphology and sleep quality/latency were not significantly changed by Relora in comparison to placebo. Conclusion This pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.
Full Text Available Abstract Background It is known that repetitive, skilled, functional movement is beneficial in driving functional reorganisation of the brain early after stroke. This study will investigate a whether pedalling an upright, static exercise cycle, to provide such beneficial activity, will enhance recovery and b which stroke survivors might be able to participate in pedalling. Methods/Design Participants (n = 24 will be up to 30 days since stroke onset, with unilateral weakness and unable to walk without assistance. This study will use a modified exercise bicycle fitted with a UniCam crank. All participants will give informed consent, then undergo baseline measurements, and then attempt to pedal. Those able to pedal will be entered into a single-centre, observer-blinded randomised controlled trial (RCT. All participants will receive routine rehabilitation. The experimental group will, in addition, pedal daily for up to ten minutes, for up to ten working days. Prognostic indicators, measured at baseline, will be: site of stroke lesion, trunk control, ability to ambulate, and severity of lower limb paresis. The primary outcome for the RCT is ability to voluntarily contract paretic lower limb muscle, measured by the Motricity Index. Secondary outcomes include ability to ambulate and timing of onset and offset of activity in antagonist muscle groups during pedalling, measured by EMG. Discussion This protocol is for a trial of a novel therapy intervention. Findings will establish whether there is sufficient evidence of benefit to justify proceeding with further research into clinical efficacy of upright pedalling exercise early after stroke. Information on potential prognostic indicators will suggest which stroke survivors could benefit from the intervention. Trial Registration ISRCTN: ISRCTN45392701
Ebner, Hubert; Hayn, Dieter; Falgenhauer, Markus; Nitzlnader, Michael; Schleiermacher, Gudrun; Haupt, Riccardo; Erminio, Giovanni; Defferrari, Raffaella; Mazzocco, Katia; Kohler, Jan; Tonini, Gian Paolo; Ladenstein, Ruth; Schreier, Guenter
Data from two contexts, i.e. the European Unresectable Neuroblastoma (EUNB) clinical trial and results from comparative genomic hybridisation (CGH) analyses from corresponding tumour samples shall be provided to existing repositories for secondary use. Utilizing the European Unified Patient IDentity Management (EUPID) as developed in the course of the ENCCA project, the following processes were applied to the data: standardization (providing interoperability), pseudonymization (generating distinct but linkable pseudonyms for both contexts), and linking both data sources. The applied procedures resulted in a joined dataset that did not contain any identifiers that would allow to backtrack the records to either data sources. This provided a high degree of privacy to the involved patients as required by data protection regulations, without preventing proper analysis. PMID:27139382
Ashby Rebecca L; Dumville Jo C; Soares Marta O; McGinnis Elizabeth; Stubbs Nikki; Torgerson David J; Cullum Nicky
Abstract Background Negative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NP...
Full Text Available Hiroshi Kikuchi,1,2 Nobuyoshi Shiozawa,1 Shingo Takata,1 Kozo Ashida,1 Fumihiro Mitsunobu11Division of Medicine, Misasa Medical Center, Okayama University Hospital, Misasa, Tottori, Japan; 2Division of Internal Medicine, Takamatsu Hospital KKR, Takamatsu, JapanPurpose: Controlled clinical trials evaluating the efficacy of repeated Waon therapy for patients with chronic obstructive pulmonary disease (COPD have yet to be conducted. The purpose of the present study was to evaluate whether repeated Waon therapy exhibits an adjuvant effect on conventional therapy for COPD patients.Patients and methods: This prospective trial comprised 20 consecutive COPD patients who satisfied the criteria of the Global initiative for chronic Obstructive Lung Disease (GOLD guidelines, stages 1–4. They were assigned to either a Waon or control group. The patients in the Waon group received both repeated Waon therapy and conventional therapy, including medications, such as long-acting inhaled β2 agonists, long-acting anticholinergics and xanthine derivatives, and pulmonary rehabilitation. The Waon therapy consisted of sitting in a 60°C sauna room for 15 minutes, followed by 30 minutes of being warmed with blankets once a day, 5 days a week, for a total of 20 times. The patients in the control group received only conventional therapy. Pulmonary function and the 6-minute walk test were assessed before and at 4 weeks after the program.Results: The change in vital capacity (0.30 ± 0.4 L and in peak expiratory flow (0.48 ± 0.79 L/s in the Waon group was larger than the change in the vital capacity (0.02 ± 0.21 L (P=0.077 and peak expiratory flow (−0.11 ± 0.72 L/s (P=0.095 in the control group. The change in forced expiratory flow after 50% of expired forced vital capacity in the Waon group, 0.08 (0.01–0.212 L/s, was larger than that in the control group, −0.01 (−0.075–0.04 L/s (P=0.019. Significant differences were not observed in the change in any
HIV Prevention HIV/AIDS Clinical Trials (Last updated 9/15/2015; last reviewed 9/15/2015) Key Points HIV/AIDS clinical ... safe and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help ...
Gustafsson, Finn; Atar, Dan; Pitt, Bertram;
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...... variable. Generation of trial databases and/or biobanks originating in large randomized clinical trials has successfully increased the knowledge obtained from those trials. At the 10th Cardiovascular Trialist Workshop, possibilities and pitfalls in designing and accessing clinical trial databases were...
Knutson Keith L
induced and boosted Her2-specific antibodies that could be detected for several years after the last vaccine administration in a subgroup of patients. Conclusion This pilot clinical trial demonstrates that Her2-pDNA vaccination in conjunction with GM-CSF and IL-2 administration is safe, well tolerated and can induce long-lasting cellular and humoral immune responses against Her2 in patients with advanced breast cancer. Trial registration The trial registration number at the Swedish Medical Products Agency for this trial is Dnr151:785/2001.
Mani, Ram; Pollard, John; Dichter, Marc A.
Blocking the development of epilepsy (epileptogenesis) is a fundamental research area with the potential to provide large benefits to patients by avoiding the medical and social consequences that occur with epilepsy and lifelong therapy. Human clinical trials attempting to prevent epilepsy (antiepileptogenesis) have been few and universally unsuccessful to date. In this article, we review data about possible pathophysiological mechanisms underlying epileptogenesis, discuss potential intervent...
Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven
To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding
Højskov, Ida E; Moons, Philip; Hansen, Niels V;
BACKGROUND: Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility, pain and insufficient sleep. Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising. However...
Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials.
Gustafsson, Finn; Atar, Dan; Pitt, Bertram;
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...... variable. Generation of trial databases and/or biobanks originating in large randomized clinical trials has successfully increased the knowledge obtained from those trials. At the 10th Cardiovascular Trialist Workshop, possibilities and pitfalls in designing and accessing clinical trial databases were......, in particular with respect to collaboration with the trial sponsor and to analytic pitfalls. The advantages of creating screening databases in conjunction with a given clinical trial are described; and finally, the potential for posttrial database studies to become a platform for training young scientists...
Prayle, A.P.; Hurley, M.N.; Smyth, Alan R
Objective To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Design Registry based study of clinical trial summaries. Data sources ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one...
Accrual to cancer clinical trials (CCT) is imperative to safeguard continued improvement in cancer outcomes. A retrospective chart review was performed of patients (n=140) starting a new anti-cancer agent in a north Dublin cancer centre. This review was performed over a four-month period, beginning in November 2015. Only 29% (n=41) had a CCT option. The overall accrual rate to CCT was 5% (n=7), which is comparable to internationally reported figures. The main reasons for failure to recruit to CCT included the lack of a CCT option for cancer type (n=30, 23%), stage (n=25, 19%), and line of treatment (n=23, 17%). Over the last decade, the rate of accrual to CCTs has in fact doubled and the number of trials open to recruitment has tripled. Ongoing governmental and philanthropic support is necessary to continue this trend to further expand CCT patient options with a target accrual rate of 10%.
The effect of changing movement and posture using motion-sensor biofeedback, versus guidelines-based care, on the clinical outcomes of people with sub-acute or chronic low back pain-a multicentre, cluster-randomised, placebo-controlled, pilot trial
Kent, Peter; Laird, Robert; Haines, Terry
sample size calculations for a fully powered trial. METHODS: A multicentre (8 clinics), cluster-randomised, placebo-controlled pilot trial compared two groups of patients seeking medical or physiotherapy primary care for sub-acute and chronic back pain. It was powered for longitudinal analysis......BACKGROUND: The aims of this pilot trial were to (i) test the hypothesis that modifying patterns of painful lumbo-pelvic movement using motion-sensor biofeedback in people with low back pain would lead to reduced pain and activity limitation compared with guidelines-based care, and (ii) facilitate......, but not for adjusted single-time point comparisons. The intervention group (n = 58) received modification of movement patterns augmented by motion-sensor movement biofeedback (ViMove, dorsaVi.com) plus guidelines-based medical or physiotherapy care. The control group (n = 54) received a placebo (wearing the motion...
Full Text Available Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22% which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society.
Actively Undergoing Cancer Treatment; 4-9 Years of Age; At Least 1 Month From Diagnosis; Able to Speak and Understand English; Presenting to Clinic for at Least a 2nd Subcutaneous Port Needle Insertion
Sharif-Afshar, Ali-Reza; Nguyen, Christopher; Tom S. Feng; Payor, Lucas; Fan, Zhaoyang; Saouaf, Rola; Li, Debiao; Kim, Hyung L.
Objectives High-resolution prostate imaging may allow for detection of subtle changes in tumor size, decrease the reliance on biopsies, and help define tumor boundaries during ablation. This pilot clinical trial evaluates a novel high-resolution prostate MRI for detection of small, biopsy-proven prostate tumors. Methods Our team developed a software that can be loaded on any modern MRI to generate high resolution diffusion-weighted imaging sequences (HR-DWI), which were compared to standard d...
Ali-Reza Sharif-Afshar; Christopher Nguyen; Tom S. Feng; Lucas Payor; Zhaoyang Fan; Rola Saouaf; Debiao Li; Kim, Hyung L.
Objectives: High-resolution prostate imaging may allow for detection of subtle changes in tumor size, decrease the reliance on biopsies, and help define tumor boundaries during ablation. This pilot clinical trial evaluates a novel high-resolution prostate MRI for detection of small, biopsy-proven prostate tumors. Methods: Our team developed a software that can be loaded on any modern MRI to generate high resolution diffusion-weighted imaging sequences (HR-DWI), which were compared to stand...
Stangel, M; Boegner, F.; Klatt, C.; Hofmeister, C.; Seyfert, S.
Currently there is no treatment available to improve a stable deficit in multiple sclerosis. It was shown in animal models that intravenous immunoglobulins (IVIg) can enhance central nervous remyelination, and the first open trials were promising. We therefore conducted a double blind, placebo controlled pilot study to evaluate the effect of IVIg treatment in patients with multiple sclerosis with a stable clinical deficit. The primary outcome parameter was the change in central mo...
Tulledge-Scheitel Sidna M
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
This study was not able to document statistically significant clinical effect of iCBT with minimal therapist contact compared to a waiting list control group in a specialised anxiety clinic in routine care. However, a large and significant effect was seen on self-reported quality of life. Although these results offer an interesting perspective on iCBT in specialised care, they should be interpreted with caution, due to the limitations of the study. A large scale fully powered RCT is recommended.
Ashby Rebecca L
Full Text Available Abstract Background Negative pressure wound therapy (NPWT is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community, pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC (spun hydrocolloid, alginate or foam dressings. Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8% were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group during follow-up (time to healing 79 days. The mean number of treatment visits per week was 3.1 (NPWT and 5.7 (SC; 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT and 5.0 (SC months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034.
The Clinical Trials Transformation Initiative (CTTI) is a public-private partnership created in 2007 between the United States Food and Drug Administration (FDA) and Duke University for the purpose of identifying practices that will increase the quality and efficiency of clinical trials. The initiative was generated from the realization that the clinical trials system in the United States has been suffering as a result of increasingly longer study start-up times, slowing enrollment of patient...
Full Text Available Abstract Background Despite multiple antidepressant options, major depressive disorder (MDD still faces high non-response rates, eventually requiring anticonvulsant augmentation strategies too. The aim of this study was to explore such a potential role for zonisamide. Methods A total of 40 MDD outpatients diagnosed using the Diagnostic and Statistical Manual for Mental Disorders, fourth edition criteria entered a 24 week open trial receiving duloxetine 60 mg/day for the first 12 weeks and subsequently (weeks 12 to 24 augmentation with zonisamide 75 mg/day if they did not respond to the initial monotherapy. Efficacy and tolerability were assessed using the Hamilton Scales for Anxiety and Depression (a 12 week score ≥50% vs baseline defined 'non-response', the Arizona Sexual Experience Scale, the Patient Rated Inventory of Side Effects and the Young Mania Rating Scale. Results At week 12, 15 patients out of 39 (38.5% were responders, and 1 had dropped out; remarkably, 14 patients out of 24 (58.3% had achieved response by week 24. Poor concentration and general malaise were associated with non-response both at week 12 and 24 (P = 0.001, while loss of libido and reduced energy were prominent among final timepoint non-responders. Patients receiving zonisamide also experienced weight reduction (2.09 ± 12.14 kg; P = 0.001 independently of the outcome. Conclusions Although only a preliminary study due to strong methodological limitations, and thus requiring confirmation by further controlled investigations, the current results indicate zonisamide may be a potential augmentation option for some depressed patients receiving low doses of duloxetine.
Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L; Goodman, Steven; Schrandt, Suzanne; Zirkle, Maryan
In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical
Okonta, Patrick I
The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.
Full Text Available Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. In addition to advancing science, clinical trials offer myriad benefits to the participants. The recent hue that created in India about clinical trials is probably an exaggeration of facts. However, these points to the need for ensuring proper compliance with the regulatory norms and proper training of concerned personnel in good clinical practice (GCP. This will ensure that India continues to reap the benefits of clinical trials and also become a world leader in this field.
Poongothai, Subramani; Unnikrishnan, Ranjit; Balasubramanian, Jeyakumar; Nair, Mohan Damodaran; Mohan, Viswanathan
Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. In addition to advancing science, clinical trials offer myriad benefits to the participants. The recent hue that created in India about clinical trials is probably an exaggeration of facts. However, these points to the need for ensuring proper compliance with the regulatory norms and proper training of concerned personnel in good clinical practice (GCP). This will ensure that India continues to reap the benefits of clinical trials and also become a world leader in this field. PMID:24741480
Okonta, Patrick I
The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247
Patrick I Okonta
Full Text Available The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.
Full Text Available Abstract Background Botanical products are frequently used for treatment of nasal allergy. Three of these substances, Cinnamomum zeylanicum, Malpighia glabra, and Bidens pilosa, have been shown to have a number of anti-allergic properties in-vitro. The current study was conducted to determine the effects of these combined ingredients upon the nasal response to allergen challenge in patients with seasonal allergic rhinitis. Methods Twenty subjects were randomized to receive the combination botanical product, (CBP 2 tablets three times a day, loratadine, 10 mg once a day in the morning, or placebo, using a randomized, double-blinded crossover design. Following 2 days of each treatment and during the third day of treatment, subjects underwent a nasal allergen challenge (NAC, in which nasal symptoms were assessed after each challenge dose and every 2 hours for 8 hours. Nasal lavage fluid was assessed for tryptase, prostaglandin D2, and leukotriene E4 concentrations and inflammatory cells. Results Loratadine significantly reduced the total nasal symptom score during the NAC compared with placebo (P = 0.04 while the CBP did not. During the 8 hour period following NAC, loratadine and the CBP both reduced NSS compared with placebo (P = 0.034 and P = 0.029, respectively. Analysis of nasal lavage fluid demonstrated that the CBP prevented the increase in prostaglandin D2 release following NAC, while neither loratadine nor placebo had this effect. None of the treatments significantly affected tryptase or leukotriene E4 release or inflammatory cell infiltration. Conclusion The CBP significantly reduced NSS during the 8 hours following NAC and marginally inhibited the release of prostaglandin D2 into nasal lavage fluid, suggesting potential clinical utility in patients with allergic rhinitis.
Anthony V Nguyen
Full Text Available Anthony V Nguyen1, Micaela Martinez1, Michael J Stamos2, Mary P Moyer3, Kestutis Planutis1, Christopher Hope1 Randall F Holcombe11Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, 2Department of Surgery, University of California, Irvine CA, USA; 3Incell Corporation, San Antonio, TX USAContext: Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro.Design: A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR pre- and post-exposure to resveratrol/GP.Results: Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03 activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001. These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line.Conclusions: These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted.Trial registration: NCT00256334
Full Text Available Abstract Background Acquired brain injury (ABI is the main cause of death and disability among young adults. In most cases, survivors can experience balance instability, resulting in functional impairments that are associated with diminished health-related quality of life. Traditional rehabilitation therapy may be tedious. This can reduce motivation and adherence to the treatment and thus provide a limited benefit to patients with balance disorders. We present eBaViR (easy Balance Virtual Rehabilitation, a system based on the Nintendo® Wii Balance Board® (WBB, which has been designed by clinical therapists to improve standing balance in patients with ABI through motivational and adaptative exercises. We hypothesize that eBaViR, is feasible, safe and potentially effective in enhancing standing balance. Methods In this contribution, we present a randomized and controlled single blinded study to assess the influence of a WBB-based virtual rehabilitation system on balance rehabilitation with ABI hemiparetic patients. This study describes the eBaViR system and evaluates its effectiveness considering 20 one-hour-sessions of virtual reality rehabilitation (n = 9 versus standard rehabilitation (n = 8. Effectiveness was evaluated by means of traditional static and dynamic balance scales. Results The final sample consisted of 11 men and 6 women. Mean ± SD age was 47.3 ± 17.8 and mean ± SD chronicity was 570.9 ± 313.2 days. Patients using eBaViR had a significant improvement in static balance (p = 0.011 in Berg Balance Scale and p = 0.011 in Anterior Reaches Test compared to patients who underwent traditional therapy. Regarding dynamic balance, the results showed significant improvement over time in all these measures, but no significant group effect or group-by-time interaction was detected for any of them, which suggests that both groups improved in the same way. There were no serious adverse events during treatment in either group. Conclusions The
Paul VarnerJohn J Pershing Veterans’ Administration Medical Center, Poplar Bluff, Missouri, USAAbstract: To make clinicians aware of potential sources of error in ophthalmic pharmaceutical clinical trials that can lead to erroneous interpretation of results, a critical review of the study design of various pharmaceutical ophthalmic clinical trials was completed. Discrepancies as a result of study shortcomings may explain observed differences between reported ophthalmic trial data an...
Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A
Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.
Shakuri Seyed Kazem
Full Text Available Introduction: Prevention of pulmonary complications after coronary artery bypass graft is attended as a very important issue. The aim of this study was to evaluate the role of pulmonary rehabilitation before surgery for reducing the risk of pulmonary complications after surgery. Methods: In a randomized clinical trial, 60 patients undergoing heart surgery were randomly divided into two groups A and B. Chest physiotherapy was performed before and after surgery on group A patients however it was done on group B’s, only after surgery. Effects of preoperative pulmonary rehabilitation were compared between two groups, using spirometry and arterial blood gas (ABG. Results: Thirty nine males (65% and 21 females (35% with mean age of 8.10 ± 9.56 were analyzed.The mean differences were statistically significant for predicted forced vital capacity (FVC (CI95%:1.3 to 8.7 and Predicted Peak Flow indices (PEF (CI 95%: 1.9 to 9.4 of spirometry indicator,PCO2 index (of ABG parameter (CI 95%: 1.4 to 8.9 and mean oxygen saturation (mean Spo2 (CI 95%: 0.6 to 1.7 of ABG index in two groups. Conclusion: The performance of pulmonary rehabilitation program before surgery is recommended, as it may result in the reduction of complications of heart surgery.
Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony
The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155
Lund, Henrik Hautop; Jessen, Jari Due
, agility, endurance, and sensor-motoric reaction. A population of 12 elderly (average age: 79) with balancing problems (DGI average score: 18.7) was randomly assigned to control group or tiles training group, and tested before and after intervention. The tiles training group had statistical significant...... increase in balancing performance (DGI score: 21.3) after short-term playful training with the modular interactive tiles, whereas the control group remained with a score indicating balancing problems and risk of falling (DGI score: 16.6). The small pilot randomized controlled trial suggests...
C. A. Caramori
Full Text Available Scientific development that has been achieved through decades finds in clinical research a great possibility of translating findings to human health application. Evidence given by clinical trials allows everyone to have access to the best health services. However, the millionaire world of pharmaceutical industries has stained clinical research with doubt and improbability. Study results (fruits of controlled clinical trials and scientific publications (selective, manipulated and with wrong conclusions led to an inappropriate clinical practice, favoring the involved economic aspect. In 2005, the International Committee of Medical Journal Editors (ICMJE, supported by the World Association of Medical Editors, started demanding as a requisite for publication that all clinical trials be registered at the database ClinicalTrials.gov. In 2006, the World Health Organization (WHO created the International Clinical Trial Registry Platform (ICTRP, which gathers several registry centers from all over the world, and required that all researchers and pharmaceutical industries register clinical trials. Such obligatory registration has progressed and will extend to all scientific journals indexed in all worldwide databases. Registration of clinical trials means another step of clinical research towards transparency, ethics and impartiality, resulting in real evidence to the forthcoming changes in clinical practice as well as in the health situation.
Full Text Available Abstract Background High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics. However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke. Methods Trial Design: Double blind parallel group external pilot randomised controlled trial. Setting: Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals. Participants: Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset and hypertension (systolic BP>160 mmHg. Intervention: Lisinopril 5-10 mg (intervention group, matched placebo (control group, daily for 7 days. Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics. Outcomes: Study feasibility (recruitment rate, compliance with data collection and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function. Discussion This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke
Sandeep K Gupta
Full Text Available There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process.
Gupta, Sandeep K.
There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464
Full Text Available After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1 Adherence measurement in clinical trials, (2 Comprehension of use instructions/Instructions for use, (3 Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4 Partner influence on use, (5 Retention and continuation and (6 Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.
Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044
Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy
The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs.
Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction – a prospective cohort pilot study within a randomized clinical trial
Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. 40 patients participated (chemoradiotherapy, n = 17; chemotherapy, n = 23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p = 0.02, p = 0.01, and p = 0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p = 0.09 and p = 0.09). NT-proBNP increased following chemoradiotherapy (p = 0.05) but not after chemotherapy (p > 0.99), and there was a trend towards an interaction effect (p = 0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p = 0.03) and was more pronounced after
Ellis, Cara E; Korbutt, Gregory S
The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well-publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation.
Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L
A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well.
Entwistle Vikki A
Full Text Available Abstract Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors.
@@ Introduction The mission of the WHO Intemational Clinical Trials Registry Platform is to ensure that a complete view of research is accessible to all those involved in health care decision making.This will improve research transparency and will ultimately strengthen tha validity and value of the scientific evidence base.The registration of all interventional trials is a scientific, ethical and moral responsibility.
Hróbjartsson, A; Boutron, I
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...
Geller, Nancy L; Kim, Dong-Yun; Tian, Xin
This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.
Hróbjartsson, A; Boutron, I
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 and...
Geller, Nancy L; Kim, Dong-Yun; Tian, Xin
This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. PMID:26135330
Woolson Robert F; Hedden Sarra L; Malcolm Robert J
Abstract Background A well designed randomized clinical trial rates as the highest level of evidence for a particular intervention's efficacy. Randomization, a fundamental feature of clinical trials design, is a process invoking the use of probability to assign treatment interventions to patients. In general, randomization techniques pursue the goal of providing objectivity to the assignment of treatments, while at the same time balancing for treatment assignment totals and covariate distribu...
Virani, Shamsuddin; Burke, Lola; Remick, Scot C.; Abraham, Jame
Rates of clinical trial participation are lower among patients in rural areas. Oncologists should be trained to address patient concerns regarding clinical trial availability, utility, and accessibility.
Olga Lidia Cuevas Pérez
Full Text Available Today there are countless examples that illustrate the nature of technoscience, including biotechnology and pharmacology. The clinical trial is the appropriate methodology used by clinical pharmacology to test the efficacy and safety of a treatment or intervention in humans. It constitutes the cornerstone of research. Once the preclinical research is completed, one of the biggest challenges currently facing the Cuban Pharmaceutical and Biotechnological Industry is precisely the clinical evaluation. Therefore, this work aims to provide a reflection on the most significant aspects of clinical trials and their impact on society.
Oud, Johan; Ghidey, Wendimagegn
This book describes various ways of approaching and interpreting the data produced by clinical trial studies, with a special emphasis on the essential role that biostatistics plays in clinical trials. Over the past few decades the role of statistics in the evaluation and interpretation of clinical data has become of paramount importance. As a result the standards of clinical study design, conduct and interpretation have undergone substantial improvement. The book includes 18 carefully reviewed chapters on recent developments in clinical trials and their statistical evaluation, with each chapter providing one or more examples involving typical data sets, enabling readers to apply the proposed procedures. The chapters employ a uniform style to enhance comparability between the approaches.
Ondersma, Steven J.; Beatty, Jessica R.; Svikis, Dace S.; Strickler, Ronald C.; Tzilos, Golfo K.; Chang, Grace; Divine, W.; Taylor, Andrew R.; Sokol, Robert J.
Background Although screening and brief intervention (SBI) for unhealthy alcohol use has demonstrated efficacy in some trials, its implementation has been limited. Technology-delivered approaches are a promising alternative, particularly during pregnancy when the importance of alcohol use is amplified. The present trial evaluated the feasibility and acceptability of an interactive, empathic, video-enhanced, and computer-delivered SBI (e-SBI) plus three separate tailored mailings, and estimated intervention effects. Methods We recruited 48 pregnant women who screened positive for alcohol risk at an urban prenatal care clinic. Participants were randomly assigned to the e-SBI plus mailings or to a control session on infant nutrition, and were reevaluated during their postpartum hospitalization. The primary outcome was 90-day period-prevalence abstinence as measured by timeline follow-back interview. Results Participants rated the intervention as easy to use and helpful (4.7-5.0 on a 5-point scale). Blinded follow-up evaluation at childbirth revealed medium-size intervention effects on 90-day period prevalence abstinence (OR = 3.4); similarly, intervention effects on a combined healthy pregnancy outcome variable (live birth, normal birthweight, and no NICU stay) were also of moderate magnitude in favor of e-SBI participants (OR=3.3). As expected in this intentionally under-powered pilot trial, these effects were non-significant (p = .19 and .09, respectively). Conclusions This pilot trial demonstrated the acceptability and preliminary efficacy of a computer-delivered screening and brief intervention (e-SBI) plus tailored mailings for alcohol use in pregnancy. These findings mirror the promising results of other trials using a similar approach, and should be confirmed in a fully-powered trial. PMID:26010235
An evaluation of knowledge, attitude, and practice of institutional ethics committee members from eastern India regarding ethics committee functioning and pharmacovigilance activities conducted during clinical trials: A pilot study
Full Text Available Purpose of study: The vital responsibility of Institutional Ethics Committee (IEC members is to ensure the safety of the subjects participating in clinical trials. Hence, it is essential for IEC members to be aware of the common pharmacovigilance strategies followed during clinical trials. However, the information about the knowledge, attitude, and practice of IEC members regarding the pharmacovigilance activities followed during clinical trials is scarce worldwide, especially in India. Hence, this cross-sectional study was designed to assess the knowledge, attitude, and practice of IEC members of 10 hospitals of Kolkata, India. Materials and Methods: A cross-sectional study using a self-administered, validated questionnaire was conducted among 10 hospitals (five government and five corporate hospitals in Kolkata conducting active clinical research and having functional Ethics Committees (ECs in the month of September-November, 2012. An IEC approval was taken for this study. Two reminders were given to all EC members through telephone/e-mail for completion and returning of the forms. The filled in forms were returned to their respective Member Secretaries, from whom authors′ collected the forms. Data were analyzed using SPSS version 16.0 software and MS-Excel 2007. Categorical data were analyzed using Chi-square test and a P < 0.05 was considered statistically significant. Results: Out of the 100 distributed questionnaires, 40 were returned of which 10 were not filled properly. Overall awareness regarding different pharmacovigilance terminologies and activities among EC members from nonmedical background (71.43% was found to be more than that of the medical members (68.75%, though the figure was not statistically significant. Majority of the members (75% felt that EC should decide compensation in case of a serious adverse event. Conclusion: The present study signifies that there is a low level of awareness in IEC members of Kolkata regarding
Clark, William F; Sontrop, Jessica M; Huang, Shih-Han; Gallo, Kerri; Moist, Louise; House, Andrew A; Weir, Matthew A; Garg, Amit X
Background and objectives Increased water intake may benefit kidney function. Prior to initiating a larger randomised controlled trial (RCT), we examined the safety and feasibility of asking adults with chronic kidney disease (CKD) to increase their water intake. Design, setting, participants and measurements Beginning in October 2012, we randomly assigned 29 adults with stage 3 CKD (estimated glomerular filtration rate (eGFR) 30–60 mL/min/1.73 m2 and albuminuria) to one of the two groups of water intake: hydration (n=18) or standard (n=11). We asked the hydration group to increase their water intake by 1.0–1.5 L/day (in addition to usual intake, depending on sex and weight) for 6 weeks, while the control group carried on with their usual intake. Participants collected a 24 h urine sample at baseline and at 2 and 6 weeks after randomisation. Our primary outcome was the between-group difference in change in 24 h urine volume from baseline to 6 weeks. Results (63%)of participants were men, 81% were Caucasians and the average age was 61 years (SD 14 years). The average baseline eGFR was 40 mL/min/1.73 m2 (SD 11 mL/min/1.73 m2); the median albumin to creatinine ratio was 19 mg/mmol (IQR 6–74 mg/mmol). Between baseline and 6-week follow-up, the hydration group's average 24 h urine volume increased by 0.7 L/day (from 2.3 to 3.0 L/day) and the control group's 24 h urine decreased by 0.3 L/day (from 2.0 to 1.7 L/day; between-group difference in change: 0.9 L/day (95% CI 0.4 to 1.5; p=0.002)). We found no significant changes in urine, serum osmolality or electrolyte concentrations, or eGFR. No serious adverse events or changes in quality of life were reported. Conclusions A pilot RCT indicates adults with stage 3 CKD can successfully and safely increase water intake by up to 0.7 L/day in addition to usual fluid intake. Trial registration Registered with Clinical Trials—government identifier NCT01753466. PMID:24362012
Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.
Amaryan, G; Astvatsatryan, V; Gabrielyan, E; Panossian, A; Panosyan, V; Wikman, G
Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special extracts standardized for the content of Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in FMF patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with FMF. PMID:12809357
Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L
As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.
Full Text Available Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials.
Martin Schencking; Stefan Wilm; Marcus Redaelli
An increasingly aging population implies an increasing prevalence of osteoarthritis (OA) of hip or knee.It has been ascertained that unspecific hydrotherapy of OA according to Sebastian Kneipp not only improves the range of mobility but also reduces pain significantly and increases the quality of life of the patients affected.OBJECTIVE:The main aim of this pilot study was to determine the effects of hydrotherapy in comparison to conventional physiotherapy,and to analyze the feasibility of the study design under clinical circumstances.DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS:The study design is a prospective randomized controlled three-arm clinical pilot trial,carried out at a specialist clinic for integrative medicine.Thirty patients diagnosed with symptomatic OA of hip or knee and radiologic findings were randomly assigned to one of two intervention groups and a control group:hydrotherapy (group 1),physiotherapy (group 2),and both physiotherapy and hydrotherapy (group 3,control group) of the affected joint.MAIN OUTCOME MEASURES:Primary outcome:pain intensity of the affected joint in the course of inpatient treatment; secondary outcome:health-related quality of life,joint-specific pain and mobility in the course of the study.RESULTS:Concerning the main outcome,intervention group 1 showed most beneficial effects in the course of inpatient treatment,followed by groups 3 and 2,and also the indirect flexion ability of hip or knee together with the general patient mobility through the "timed up and go" test were mainly improved within group 1 followed by groups 3 and 2.CONCLUSION:The results of this pilot study demonstrate beneficial effects of hydrotherapy.The study design is feasible.For statistically significant evidence and a robust conclusion of efficacy of Kneipp's hydrotherapy,a larger sample size is necessary.TRIAL REGISTRATION NUMBER:NCT 00950326.
Holmberg, L; Baum, M; Adami, H O
We have not been able to describe clearly how we generalize findings from a study to our own 'everyday patients'. This difficulty is not surprising, since generalization deals with how empirical observations are related to the growth of scientific knowledge, which is a major philosophical problem. An argument, sometimes used to discard evidence from a trial, is that the patient sample was too selected and therefore not 'representative' enough for the results to be meaningful for generalization. In this paper, we discuss issues of representativeness and generalizability. Other authors have shown that generalization cannot only depend on statistical inference. Then, how do randomized clinical trials contribute to the growth of knowledge? We discuss three aspects of the randomized clinical trial (Mant 1999), First, the trial is an empirical experiment set up to study the intervention on the question as specifically and as much in isolation from other -- biasing and confounding -- factors as possible (Rothman & Greenland 1998). Second, the trial is set up to challenge our prevailing hypotheses (or prejudices) and the trial is above all a help in error elimination (Popper 1992). Third, we need to learn to see new, unexpected and thought-provoking patterns in the data from a trial. Point one -- and partly point two -- refers to the paradigm of the controlled experiment in scientific method. How much a study contributes to our knowledge, with respect to points two and three, relates to its originality. In none of these respects is the representativeness of the patients, or the clinical situations, crucial for judging the study and its possible inferences. However, we also discuss that the biological domain of disease that was studied in a particular trial has to be taken into account. Thus, the inference drawn from a clinical study is not only a question of statistical generalization, but must include a jump from the world of experiences into the world of reason
Entwistle Vikki A; Snowdon Claire; Garcia Jo; Knight Rosemary C; Shakur Haleema; Elbourne Diana R; Roberts Ian; Francis David; McDonald Alison M; Grant Adrian M; Campbell Marion K
Abstract Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, o...
Full Text Available Overweight and obesity is prevalent among women of reproductive age (42% BMI > 25 kg/m2 and parity is associated with risk of weight gain. Weight gain greater than that recommended by the Institute of Medicine (IOM is also associated with lower rates of breastfeeding initiation and duration in women. The aim of this pilot randomised controlled trial is to examine the feasibility of recruiting and maintaining a cohort of pregnant women with the view of reducing postpartum weight retention and improving breastfeeding outcomes. Women (BMI of 25–35 kg/m2 (n = 36 were recruited from the John Hunter Hospital antenatal clinic in New South Wales, Australia. Participants were stratified by BMI and randomised to one of three groups with follow-up to six months postpartum. Women received a dietary intervention with or without breastfeeding support from a lactation consultant, or were assigned to a wait-list control group where the dietary intervention was issued at three months postpartum. Feasibility and acceptability was assessed by participation rates and questionnaire. Analysis of variance and covariance was conducted to determine any differences between groups. Sixty-nine per cent of the participants were still enrolled at six months postpartum. This pilot demonstrated some difficulties in recruiting women from antenatal clinics and retaining them in the trial. Although underpowered; the results on weight; biomarkers and breastfeeding outcomes indicated improved metabolic health.
Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L
Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored.
Schüssler-Lenz, M; Schneider, C K
For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.
Sessler, Daniel I; Imrey, Peter B
Randomized assignment of treatment excludes reverse causation and selection bias and, in sufficiently large studies, effectively prevents confounding. Well-implemented blinding prevents measurement bias. Studies that include these protections are called randomized, blinded clinical trials and, when conducted with sufficient numbers of patients, provide the most valid results. Although conceptually straightforward, design of clinical trials requires thoughtful trade-offs among competing approaches-all of which influence the number of patients required, enrollment time, internal and external validity, ability to evaluate interactions among treatments, and cost.
Full Text Available Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depot-medroxyprogesterone acetate. The first randomized, placebo-controlled clinical trial performed by the pharmaceutical industry demonstrated the effectiveness of a combination of testosterone undecanoate and etonogestrel in suppressing spermatogenesis in volunteers.
Reekie, J; Mocroft, A; J, Neaton;
Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...
Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.
Full Text Available There is a growing awareness that research in primary care is needed to provide excellent clinical and population-based care, to develop effective health systems and policies, and to educate future primary care professionals and researchers. The relevance of research undertaken in primary care is unquestionable: the results of researches conducted in other settings has limited relevance because primary care encounters health problems rarely managed in other sectors of health care (i.e. low probability of major acute disease and high prevalence of comorbidity. From legislative aspects to limits and difficulties of application, the article underlines the importance of research in primary care in the Italian context, where this kind of activity is almost absent. An example, concerning the Genova ASL 3, is reported to suggest strategies to promote and improve research as an integral component of family doctors skills.
Subherwal, Sumeet; Patel, Manesh R.; Chiswell, Karen; Tidemann-Miller, Beth A.; Jones, W. Schuyler; Conte, Michael S.; White, Christopher J.; Bhatt, Deepak L.; Laird, John R.; Hiatt, William R.; Tasneem, Asba; Califf, Robert M.
Background Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); however, until recently it has not been possible to examine the entire clinical trial portfolio of studies for treatment of PVD (both arterial and venous disease). Methods and Results We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower extremity peripheral artery disease and acute stroke (35% and 24%, respectively), while most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients aged >65 years. Enrollment in at least 1 US site decreased from 51% in 2007 to 41% of trials in 2010. Compared with non-cardiology disciplines, PVD trials were more likely to be double-blinded, investigate use of devices and procedures, and have industry sponsorship and assumed funding source, and less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. PMID:25239436
Crerand, William J; Lamb, Jana; Rulon, Vera; Karal, Bilun; Mardekian, Jack
Meaningful data begin with the collection process. Pharmaceutical companies are using several different strategies in clinical trials to ensure the highest quality of data. This article will examine these approaches, with an emphasis on case report form development through database release. PMID:12432815
Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depo...
Full Text Available Abstract Background In the last decade several authors have reviewed the features of pilot and feasibility studies and advised on the issues that should be addressed within them. We extend this literature by examining published pilot/feasibility trials that incorporate random allocation, examining their stated objectives, results presented and conclusions drawn, and comparing drug and non-drug trials. Methods A search of EMBASE and MEDLINE databases for 2000 to 2009 revealed 3652 papers that met our search criteria. A random sample of 50 was selected for detailed review. Results Most of the papers focused on efficacy: those reporting drug trials additionally addressed safety/toxicity; while those reporting non-drug trials additionally addressed methodological issues. In only 56% (95% confidence intervals 41% to 70% were methodological issues discussed in substantial depth, 18% (95% confidence interval 9% to 30% discussed future trials and only 12% (95% confidence interval 5% to 24% of authors were actually conducting one. Conclusions Despite recent advice on topics that can appropriately be described as pilot or feasibility studies the large majority of recently published papers where authors have described their trial as a pilot or addressing feasibility do not primarily address methodological issues preparatory to planning a subsequent study, and this is particularly so for papers reporting drug trials. Many journals remain willing to accept the pilot/feasibility designation for a trial, possibly as an indication of inconclusive results or lack of adequate sample size.
Kloppenburg, M; Maheu, E; Kraus, V B; Cicuttini, F; Doherty, M; Dreiser, R-L; Henrotin, Y; Jiang, G-L; Mandl, L; Martel-Pelletier, J; Nelson, A E; Neogi, T; Pelletier, J-P; Punzi, L; Ramonda, R; Simon, L S; Wang, S
Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.
Weatherall Mark; Pickering Ruth M; Shanyinde Milensu
Abstract Background In the last decade several authors have reviewed the features of pilot and feasibility studies and advised on the issues that should be addressed within them. We extend this literature by examining published pilot/feasibility trials that incorporate random allocation, examining their stated objectives, results presented and conclusions drawn, and comparing drug and non-drug trials. Methods A search of EMBASE and MEDLINE databases for 2000 to 2009 revealed 3652 papers that ...
Eldridge, Sandra M.; Lancaster, Gillian A.; Michael J. Campbell; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L.; Bond, Christine M
We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of ...
Full Text Available To assess the feasibility and acceptability of a randomized controlled trial compared auricular acupressure (AA on specific acupoints with AA on non-specific acupoints for treating maintenance hemodialysis (MHD patients with insomnia.Sixty three (63 eligible subjects were randomly assigned into either AA group received AA on specific acupoints (n=32, or sham AA (SAA group received AA on points irrelevant to insomnia treatment (n=31 for eight weeks. All participants were followed up for 12 weeks after treatments. The primary outcome was clinical response at eight weeks after randomization, defined as a reduction of Pittsburgh Sleep Quality Index (PSQI global score by 3 points and more.Fifty-eight (58 participants completed the trial and five dropped out. Twenty participants in AA group (62.5% and ten in SAA group (32.3% responded to the eight-week interventions (χ2 = 5.77, P = 0.02. PSQI global score declined 3.75 ± 4.36 (95%CI -5.32, -2.18 and 2.26 ± 3.89 (95%CI -3.68, -0.83 in AA group and SAA group respectively. Three participants died during the follow-up period. No evidence supported their deaths were related to the AA intervention. No other adverse event was observed.Feasibility and logistics of patient recruitment, randomization procedure, blinding approach, interventions application and outcome assessment had been tested in this pilot trial. The preliminary data appeared to show a favorable result on AA treatment. A full-scale trial is warranted.Chinese Clinical Trial Registry ChiCTR-TRC-12002272.
Phil Schumm; Theodore Karrison
In response to the 1997 Food and Drug Administration Modernization Act (FDAMA), the National Institutes of Health (NIH) established ClinicalTrials.gov, an online, publicly-accessible registry for clinical trials. The 2007 Food and Drug Administration Amendments Act (FDAAA) broadened the scope of eligible trials, added outcomes reporting as a requirement, and established penalties for non-compliance. Although ClinicalTrials.gov increased the transparency with which clinical trials are conducte...
Due to ethical reasons, a separated optimization of the two components of BNCT in the frame of clinical investigations can only be performed applying the whole binary system. The ongoing trial at HFR (High Flux Reactor Petten) has proven the feasibility of BNCT under defined conditions. On that basis the European Commission supported a comprehensive research project on boron imaging including three further clinical studies. In the first trial the boron uptake related to the blood boron concentration and surrounding normal tissue in various solid tumours will be examined using BSH (Sodiumborocaptate), BPA (Boronophenylalanine) or both in order to explore tumour entities, which may gain benefit from BNCT. The major objectives of the second trial are to define the maximum tolerated single and cumulative dose, and the dose limiting toxicity of BSH. The third clinical trial, a phase II study is designed to evaluate the anti-tumour effect of fractionated BNCT at the Petten treatment facility against cerebral metastasis of malignant melanoma using BPA. (author)
Benjamin M Davies
Full Text Available There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.
Allmark, P. J.; Spedding, M.
Clinical trials in neonatology often raise complex ethical problems. This paper suggests that in tackling these it is useful to identify and separate out those elements of the problem that are genuinely ethical (e.g. can I enter a child into a trial if I am not in personal equipoise?) from those that are empirical (e.g. what is the evidence for a treatment's effectiveness?) and those that are formal (e.g. what do codes or the law permit?) The genuinely ethical elements are examples of philo...
Full Text Available Abstract Background Recent studies have demonstrated a correlation between perceived stress and oxidative stress. As SOD is the main enzyme of the enzymatic antioxidant defence system of the body, we evaluated the effect of an oral daily intake of a proprietary melon juice concentrate rich in SOD (EXTRAMEL® on the signs and symptoms of stress and fatigue in healthy volunteers. Methods This randomized, double blind, placebo controlled clinical study was conducted with seventy healthy volunteers aged between 30 and 55 years, who feel daily stress and fatigue. They took the dietary supplement based on the melon juice concentrate (10 mg Extramel® corresponding to 140 IU SOD per capsule or a placebo one time daily during 4 weeks. Stress and fatigue were measured using four observational psychometric scales: FARD, PSS-14, SF-12 and Epworth scale. The study was conducted by Isoclin, a clinical research organization, located in Poitiers, France. Results No adverse effect was noted. The supplementation with the proprietary melon juice concentrate bringing 140 IU SOD/day significantly improved signs and symptoms of stress and fatigue linked to performance, physical (pain, sleep troubles, cognitive (concentration, weariness, sleep troubles or behavioural (attitude, irritability, difficulty of contact compared to the placebo. In the same way, quality of life and perceived stress were significantly improved with SOD supplementation. Conclusion This pilot study showed that an oral supplementation with a proprietary melon juice concentrate rich in SOD may have a positive effect on several signs and symptoms of perceived stress and fatigue.
Dal-Ré, Rafael; Moher, David; Gluud, Christian;
Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends.......Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends....
Laber, Eric B; Zhao, Ying-Qi; Regh, Todd; Davidian, Marie; Tsiatis, Anastasios; Stanford, Joseph B; Zeng, Donglin; Song, Rui; Kosorok, Michael R
A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness. PMID:26506890
Woolson Robert F
Full Text Available Abstract Background A well designed randomized clinical trial rates as the highest level of evidence for a particular intervention's efficacy. Randomization, a fundamental feature of clinical trials design, is a process invoking the use of probability to assign treatment interventions to patients. In general, randomization techniques pursue the goal of providing objectivity to the assignment of treatments, while at the same time balancing for treatment assignment totals and covariate distributions. Numerous randomization techniques, each with varying properties of randomness and balance, are suggested in the statistical literature. This paper reviews common randomization techniques often used in substance abuse research and an application from a National Institute on Drug Abuse (NIDA-funded clinical trial in substance abuse is used to illustrate several choices an investigator faces when designing a clinical trial. Results Comparisons and contrasts of randomization schemes are provided with respect to deterministic and balancing properties. Specifically, Monte Carlo simulation is used to explore the balancing nature of randomization techniques for moderately sized clinical trials. Results demonstrate large treatment imbalance for complete randomization with less imbalance for the urn or adaptive scheme. The urn and adaptive randomization methods display smaller treatment imbalance as demonstrated by the low variability of treatment allocation imbalance. For all randomization schemes, covariate imbalance between treatment arms was small with little variation between adaptive schemes, stratified schemes and unstratified schemes given that sample sizes were moderate to large. Conclusion We develop this paper with the goal of reminding substance abuse researchers of the broad array of randomization options available for clinical trial designs. There may be too quick a tendency for substance abuse researchers to implement the fashionable urn
McGraw, Deven; Greene, Sarah M; Miner, Caroline S; Staman, Karen L; Welch, Mary Jane; Rubel, Alan
With pragmatic clinical trials, an opportunity exists to answer important questions about the relative risks, burdens, and benefits of therapeutic interventions. However, concerns about protecting the privacy of this information are significant and must be balanced with the imperative to learn from the data gathered in routine clinical practice. Traditional privacy protections for research uses of identifiable information rely disproportionately on informed consent or authorizations, based on a presumption that this is necessary to fulfill ethical principles of respect for persons. But frequently, the ideal of informed consent is not realized in its implementation. Moreover, the principle of respect for persons—which encompasses their interests in health information privacy—can be honored through other mechanisms. Data anonymization also plays a role in protecting privacy but is not suitable for all research, particularly pragmatic clinical trials. In this article, we explore both the ethical foundation and regulatory framework intended to protect privacy in pragmatic clinical trials. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations. PMID:26374682
McGraw, Deven; Greene, Sarah M; Miner, Caroline S; Staman, Karen L; Welch, Mary Jane; Rubel, Alan
With pragmatic clinical trials, an opportunity exists to answer important questions about the relative risks, burdens, and benefits of therapeutic interventions. However, concerns about protecting the privacy of this information are significant and must be balanced with the imperative to learn from the data gathered in routine clinical practice. Traditional privacy protections for research uses of identifiable information rely disproportionately on informed consent or authorizations, based on a presumption that this is necessary to fulfill ethical principles of respect for persons. But frequently, the ideal of informed consent is not realized in its implementation. Moreover, the principle of respect for persons—which encompasses their interests in health information privacy—can be honored through other mechanisms. Data anonymization also plays a role in protecting privacy but is not suitable for all research, particularly pragmatic clinical trials. In this article, we explore both the ethical foundation and regulatory framework intended to protect privacy in pragmatic clinical trials. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations.
Gilbert, Mark R; Rubinstein, Lawrence; Lesser, Glenn
Clinical outcome assessments (COAs) are increasingly being used in determining the efficacy of new treatment regimens. This was typified in the recent use of a symptom-based instrument combined with an organ-based measure of response for the approval of ruxolitinib in myelofibrosis. There are challenges in incorporating these COAs into clinical trials, including designating the level of priority, incorporating these measures into a combined or composite endpoint, and dealing with issues related to compliance and interpretation of results accounting for missing data. This article describes the results of a recent panel discussion that attempted to address these issues and provide guidance to the incorporation of COAs into clinical trials, including novel statistical designs, so that the testing of new treatments in patients with cancers of the central nervous system can incorporate these important clinical endpoints. PMID:26989129
Full Text Available Abstract Background Previous results with the planar robot MIT-MANUS demonstrated positive benefits in trials with over 250 stroke patients. Consistent with motor learning, the positive effects did not generalize to other muscle groups or limb segments. Therefore we are designing a new class of robots to exercise other muscle groups or limb segments. This paper presents basic engineering aspects of a novel robotic module that extends our approach to anti-gravity movements out of the horizontal plane and a pilot study with 10 outpatients. Patients were trained during the initial six-weeks with the planar module (i.e., performance-based training limited to horizontal movements with gravity compensation. This training was followed by six-weeks of robotic therapy that focused on performing vertical arm movements against gravity. The 12-week protocol includes three one-hour robot therapy sessions per week (total 36 robot treatment sessions. Results Pilot study demonstrated that the protocol was safe and well tolerated with no patient presenting any adverse effect. Consistent with our past experience with persons with chronic strokes, there was a statistically significant reduction in tone measurement from admission to discharge of performance-based planar robot therapy and we have not observed increases in muscle tone or spasticity during the anti-gravity training protocol. Pilot results showed also a reduction in shoulder-elbow impairment following planar horizontal training. Furthermore, it suggested an additional reduction in shoulder-elbow impairment following the anti-gravity training. Conclusion Our clinical experiments have focused on a fundamental question of whether task specific robotic training influences brain recovery. To date several studies demonstrate that in mature and damaged nervous systems, nurture indeed has an effect on nature. The improved recovery is most pronounced in the trained limb segments. We have now embarked on
Grankvist, Hannah; Kimmelman, Jonathan
Launch of clinical investigation represents a substantial escalation in commitment to a particular clinical translation trajectory; it also exposes human subjects to poorly understood interventions. Despite these high stakes, there is little to guide decision-makers on the scientific and ethical evaluation of early phase trials. In this article, we review policies and consensus statements on human protections, drug regulation, and research design surrounding trial launch, and conclude that decision-making is largely left to the discretion of research teams and sponsors. We then review what is currently understood about how research teams exercise this discretion, and close by laying out a research agenda for characterizing the way investigators, sponsors, and reviewers approach decision-making in early phase research.
Full Text Available Objectives: People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs. Methods: We did a randomized, double-blind, placebo-controlled parallel group trial, in SRM Medical College Hospital and Research Centre, Kattankulathur, Kancheepuram, Tamil Nadu, India between April 2013 and September 2013. Fifty-nine epileptic patients taking AEDs with subjective memory complaints were recruited and randomized to either Group 1 to receive 16 weeks of once-daily memantine, (5 mg for first 8 weeks, followed by memantine 10 mg for next 8 weeks or Group 2 to receive once daily placebo. This trial is registered with Clinical Trial Registry of India CTRI/2013/04/003573. Results: Of 59 randomized patients, 55 patients completed the study (26 memantine and 29 placebo. Memantine group showed statistically significant improvement in total mini mental state examination score from baseline (P = 0.765 to 16 th week (P < 0.001 in comparison with the placebo. The Weshler′s Memory Scale total score in memantine group improved significantly after 8 weeks (P = 0.002 compared with baseline (P = 0.873 and highly significant at the end of 16 th week (P < 0.001. The self-rated quality of life and memory in memantine group also significantly improved at the study end. Conclusion: We conclude that once-daily memantine (10 mg treatment significantly improved cognition, memory and quality of life in epileptic patients with mild to moderate cognitive impairment and was found to have a favorable safety profile.
Chen, Junwen; Liu, Xi; Rapee, Ronald M; Pillay, Pallavi
Transdiagnostic interventions present pragmatic benefits in treatment dissemination and training of mental health professionals when faced with emotional disorders such as anxiety and depression. Excessive worry is a common feature across emotional disorders and represents an ideal candidate target for transdiagnostic intervention. The current pilot trial examined the efficacy of a behavioural activation treatment for worry (BAW) in a community population. 49 individuals experiencing excessive worry were randomised to waitlist or BAW receiving an 8 week group based intervention. Results demonstrated that BAW was successful in reducing excessive worry, depressive symptoms, cognitive avoidance, Intolerance of Uncertainty and improving problem solving orientation. Twice as many individuals showed clinically significant reductions in excessive worry after treatment compared to the waitlist control. Despite limitations to sample size and power, this study presents promising support for BAW as a practical transdiagnostic treatment for worry.
ZHANG Zhi-jun; LIU Wei
How to design clinical trials for medical devices is a problem plaguing the industry today. As there are many differences in clinical trials of medical devices and drugs. This paper describes the differences of the two points from the perspectivs of defi-nition of medical devices and drugs, scope, phasing, subjects and design of clinical trials in details, aiming to help the related personnel make scientific decisions while conduct-ing clinical trial design for medical devices.
Santen, Gijs Willem Eduard
To fail or not to fail – Clinical trials in depression investigates the causes of the high failure rate of clinical trials in depression research. Apart from the difficulties in the search for new antidepressants during drug discovery, faulty clinical trial designs hinder their evaluation during dru
... the conduct of clinical trials of FDA-regulated products. Clinical trials are a critical source of... the conduct of clinical trials may result in inefficiencies or increased cost and may not facilitate... is involved in an effort to modernize the regulatory framework that governs clinical trials...
Full Text Available Abstract Background Childhood intermittent exotropia [X(T] is a type of strabismus (squint in which one eye deviates outward at times, usually when the child is tired. It may progress to a permanent squint, loss of stereovision and/or amblyopia (reduced vision. Treatment options for X(T include eye patches, glasses, surgery and active monitoring. There is no consensus regarding how this condition should be managed, and even when surgery is the preferred option clinicians disagree as to the optimal timing. Reports on the natural history of X(T are limited, and there is no randomised controlled trial (RCT evidence on the effectiveness or efficiency of surgery compared with active monitoring. The SamExo (Surgery versus Active Monitoring in Intermittent Exotropia pilot study has been designed to test the feasibility of such a trial in the UK. Methods Design: an external pilot patient randomised controlled trial. Setting: four UK secondary ophthalmology care facilities at Newcastle NHS Hospitals Foundation Trust, Sunderland Eye Infirmary, Moorfields Eye Hospital and York NHS Trust. Participants: children aged between 6 months and 16 years referred with suspected and subsequently diagnosed X(T. Recruitment target is a total of 144 children over a 9-month period, with 120 retained by 9-month outcome visit. Randomisation: permuted blocks stratified by collaborating centre, age and severity of X(T. Interventions: initial clinical assessment; randomisation (eye muscle surgery or active monitoring; 3-, 6- and 9-month (primary outcome clinical assessments; participant/proxy completed questionnaire covering time and travel costs, health services use and quality of life (Intermittent Exotropia Questionnaire; qualitative interviews with parents to establish reasons for agreeing or declining participation in the pilot trial. Outcomes: recruitment and retention rates; nature and extent of participation bias; nature and extent of biases arising from crossover or
Full Text Available ATL is a distinct peripheral T-lymphocytic malignancy associated with human T-cell lymphotropic virus type I (HTLV-1. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types, defined by organ involvement, and LDH and calcium values. In case of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL, intensive chemotherapy like the LSG15 regimen (VCAP-AMP-VECP is usually recommended if outside of clinical trials, based on the results of a phase 3 trial. In case of favorable chronic or smoldering ATL (indolent ATL, watchful waiting until disease progression has been recommended, although the long-term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT is also promising for the treatment of aggressive ATL possibly reflecting graft versus ATL effect. Several new agent trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody, IL2-fused with diphtheria toxin, histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor, and lenalidomide.
Zannad, F; Plétan, Y
France ranks third among European countries as regards the level of investment in clinical R&D and, overall, accounts for a contributive effort proportional to the size of its population and pharmaceutical market respectively. However, there is a trend for phase II and III studies to become proportionally fewer than in the past, while the number of phase IV studies is increasing. In a growing proportion of the mega-trials, which are instrumental for establishing evidence-based practice, French experts, investigators and, even more seriously, French patients, are insufficiently represented. Though studies in France are initiated relatively fast due to a clear regulatory framework and perform equally well as far as quantitative and qualitative factors are concerned, compared with most European countries involved in clinical research the costs incurred per completed patient are higher than those recorded in the other countries. Academic research shares most of these constraints and suffers from a lack of financial and human resources, while it faces additional delays in implementing studies because of longer administrative processes. Given the stakes in play, specific solutions should be implemented to maintain and further develop French competitiveness in clinical R&D. At the patient level, positive perception and awareness of the usefulness and safety of participating in clinical trials need to be emphasized. Education at the school level and using the lay media should be developed. Intervention of institutional and government officials is much needed. Direct patient recruitment should be developed through advertisement and the Internet, as well as within doctors' offices and through collaboration with patients' organizations. Patient information and consent forms should be made much simpler than those imposed within the framework of global studies because of FDA requirements. The French health system discourages the recruitment of patients by investigators who are
Silverberg, Nanette B
Dermoscopy is a noninvasive technique to assess skin architecture. A pilot study was conducted using polarized dermoscopy as a tool to monitor the pediatric skin barrier. Ten pediatric patients (age range, 1-14 years) with mild to moderate atopic dermatitis (AD), ichthyosis vulgaris (IV), and/or keratosis pilaris (KP) participated in a 4-week clinical trial. After a week of emollient usage alone, a mid-potency topical corticosteroid cream was added twice daily if necessary to treat erythema, dermatitis, or pruritus. The participants were assessed at weeks 0, 1, and 4 using the eczema area and severity index (EASI) for atopic dermatitis, investigator global assessment for atopic dermatitis, children dermatology life quality index (CDLQI), and clinical and dermoscopic photography. Dermoscopic appearance demonstrated dermal vascular ectasia in AD and KP, hyperkeratosis and prominence of the interkeratinocyte space in AD and IV and widening of the follicular orifice in KP. Improvements in these dermoscopic abnormalities were noted after emollient usage, mirroring improvements in clinical appearance, EASI, and CDLQI. Dermoscopy is a promising tool to assess localized improvement in skin architecture in pediatric dermatoses. Further studies and development of scoring systems will be needed to apply this technology to clinical practice.
Wang, Lei; Qu, Xintao; Yu, Xiuchun
PDCA cycle was applied in special rectification activities for medical instrument clinical trial, with quality criteria of implementation made. Completed medical instrument clinical trial from January 2011 to December 2012 was believed as control group, from January 2013 to December 2014 as PDCA group, the scores of clinical trial and the score rate of items were compared and analyzed. Results show quality scores of clinical trial in PDCA group are higher than that in control group (51 vs. 81, P rectification activities with PDCA applied in our department are feasible and effective. It significantly improves implement quality of medical instrument clinical trial.
Ethics has often been ignored or evaded in clinical trials, and the conditions under which global clinical trials are conducted make this problem likely to persist. Ethics can, however, have an impact at any of several stages of a trial when the individuals involved are committed. This editorial provides historical examples of ignoring, evading or, alternatively, using ethical help to improve clinical trials, and suggests that the actual role of ethics depends on the individuals involved.
Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C;
for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment...... the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials....
Michael A McDonald
Full Text Available BACKGROUND: Remote ischemic preconditioning (RIPC induced by transient limb ischemia confers multi-organ protection and improves exercise performance in the setting of tissue hypoxia. We aimed to evaluate the effect of RIPC on exercise capacity in heart failure patients. METHODS: We performed a randomized crossover trial of RIPC (4×5-minutes limb ischemia compared to sham control in heart failure patients undergoing exercise testing. Patients were randomly allocated to either RIPC or sham prior to exercise, then crossed over and completed the alternate intervention with repeat testing. The primary outcome was peak VO2, RIPC versus sham. A mechanistic substudy was performed using dialysate from study patient blood samples obtained after sham and RIPC. This dialysate was used to test for a protective effect of RIPC in a mouse heart Langendorff model of infarction. Mouse heart infarct size with RIPC or sham dialysate exposure was also compared with historical control data. RESULTS: Twenty patients completed the study. RIPC was not associated with improvements in peak VO2 (15.6+/-4.2 vs 15.3+/-4.6 mL/kg/min; p = 0.53, sham and RIPC, respectively. In our Langendorff sub-study, infarct size was similar between RIPC and sham dialysate groups from our study patients, but was smaller than expected compared to healthy controls (29.0%, 27.9% [sham, RIPC] vs 51.2% [controls]. We observed less preconditioning among the subgroup of patients with increased exercise performance following RIPC (p<0.04. CONCLUSION: In this pilot study of RIPC in heart failure patients, RIPC was not associated with improvements in exercise capacity overall. However, the degree of effect of RIPC may be inversely related to the degree of baseline preconditioning. These data provide the basis for a larger randomized trial to test the potential benefits of RIPC in patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov +++++NCT01128790.
...: A Video Game About Clinical Trials SUMMARY: In compliance with the requirement of Section 3506(c)(2... Collection: Title: Clinical Mythteries: A Video Game About Clinical Trials. Type of Information...
Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D
Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct.
George, Melvin; Selvarajan, Sandhiya; S, Suresh-Kumar; Dkhar, Steven A; Chandrasekaran, Adithan
The last decade has witnessed a greater transparency in clinical research with the advent of clinical trial registries. The aim of the study was to describe the trends in the globalization of clinical trials in the last five years. We performed an internet search using the WHO International clinical trials registry platform (WHO ICTRP) to identify the clinical trials conducted from January 2007 to December 31, 2011 among 25 countries. Among the 25 countries, the United States, Japan and Germany occupy the top positions in the total number of clinical trials conducted. Clinical trials in the US (36312) constituted 31.5% of the total number of trials performed during this period. However over a period of five years both US and Western Europe appear to show a decline, while the emerging countries show a rise in clinical trials registered. Among the emerging countries China, India and Republic of Korea are most active regions involved in clinical trials. Cancer, diabetes and respiratory diseases were most widely researched areas overall. Although the study confirms the transition in the clinical trials research towards emerging countries, the developed regions of the world still contribute to more than 70% of the trials registered worldwide.
G.A. van Es (Gerrit Anne)
textabstractThe purpose of this dissertation is to evaluate the usefulness of both stopping rules and estimation methods in long-term clinical trials with interim analyses. The ASPECT trial, a long-term clinical trial to assess the effect of anticoagulant therapy on mortality in patients after myoca
... HUMAN SERVICES Food and Drug Administration Dialogues in Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials AGENCY: Food and Drug Administration, HHS... Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials....
Plasma biomarker analysis in pediatric ARDS: generating future framework from a pilot randomized control trial of methylprednisoloneA framework for identifying plasma biomarkers related to clinical outcomes in pediatric ARDS
Full Text Available Objective: Lung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS. Low-dose methylprednisolone therapy (MPT improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial (Ang-2, sICAM-1 or epithelial (sRAGE injury, neutrophil activation (MMP-8, and coagulation (PAI-1. Design: Double-blind, placebo-controlled randomized trialSetting: Tertiary-care Pediatric Intensive Care Unit Patients: Mechanically ventilated children (0-18 years with early ARDS.Interventions: Blood samples were collected on Days 0 (before MPT, 7, and 14 during low-dose MPT (n=17 vs. placebo (n=18 therapy. The MPT group received a 2mg/kg loading dose followed by 1mg/kg/day continuous infusions from days 1-7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for 5 biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier including: P/F ratio on days 8&9, plateau pressure on days 1&2, PaCO2 on days 2&3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge.Results: No differences occurred in biomarker concentrations between the groups on Day 0. On Day 7, reduction in MMP-8 levels (p=0.0016 occurred in the MPT group, whereas increases in sICAM-1 levels (p=0.0005 occurred in the placebo group (no increases in sICAM-1 in the MPT group. sRAGE levels decreased in both MPT and placebo groups (p<0.0001 from Day 0 to Day 7. On Day 7, sRAGE levels were positively correlated with MPT group PaO2/FiO2 ratios on Day 8 (r=0.93, p=0.024. O2 requirements at ICU transfer positively correlated with Day 7 MMP-8 (r=0.85, p=0
Lachin, J M
This is the first of five articles on the properties of different randomization procedures used in clinical trials. This paper presents definitions and discussions of the statistical properties of randomization procedures as they relate to both the design of a clinical trial and the statistical analysis of trial results. The subsequent papers consider, respectively, the properties of simple (complete), permuted-block (i.e., blocked), and urn (adaptive biased-coin) randomization. The properties described herein are the probabilities of treatment imbalances and the potential effects on the power of statistical tests; the permutational basis for statistical tests; and the potential for experimental biases in the assessment of treatment effects due either to the predictability of the random allocations (selection bias) or the susceptibility of the randomization procedure to covariate imbalances (accidental bias). For most randomization procedures, the probabilities of overall treatment imbalances are readily computed, even when a stratified randomization is used. This is important because treatment imbalance may affect statistical power. It is shown, however, that treatment imbalance must be substantial before power is more than trivially affected. The differences between a population versus a permutation model as a basis for a statistical test are reviewed. It is argued that a population model can only be invoked in clinical trials as an untestable assumption, rather than being formally based on sampling at random from a population. On the other hand, a permutational analysis based on the randomization actually employed requires no assumptions regarding the origin of the samples of patients studied. The large sample permutational distribution of the family of linear rank tests is described as a basis for easily conducting a variety of permutation tests. Subgroup (stratified) analyses, analyses when some data are missing, and regression model analyses are also
Phase I of clinical trials is the first stage of clinical pharmacology and body safety evaluation, including body tolerance test and pharmacokinetics test. The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase II of clinical trials. This text discussed the technique and requirement of phase I of new drugs' clinical tolerance trials.
Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua
In scientific writing, positive credits and negative criticisms can often be seen in the text mentioning the cited papers, providing useful information about whether a study can be reproduced or not. In this study, we focus on citation sentiment analysis, which aims to determine the sentiment polarity that the citation context carries towards the cited paper. A citation sentiment corpus was annotated first on clinical trial papers. The effectiveness of n-gram and sentiment lexicon features, and problem-specified structure features for citation sentiment analysis were then examined using the annotated corpus. The combined features from the word n-grams, the sentiment lexicons and the structure information achieved the highest Micro F-score of 0.860 and Macro-F score of 0.719, indicating that it is feasible to use machine learning methods for citation sentiment analysis in biomedical publications. A comprehensive comparison between citation sentiment analysis of clinical trial papers and other general domains were conducted, which additionally highlights the unique challenges within this domain.
Andres E. Morales La Madrid
Full Text Available In spite of major recent advances in DIPG molecular characterization, this body of knowledge has not yet translated into better treatments.To date,more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy as well as newer biologic agents,have failed to improve the dismal outcome when compared to palliative radiation alone.The biology of DIPG remained unknown until recently when the neurosurgical expertise along with the recognition by the scientific and clinical community of the importance of tissue sampling at diagnosis;ideally in the context of a clinical trial and by trained neurosurgical teams to maximize patient safety.These pre-treatment tumor samples,and others coming from tissue obtained post-mortem,have yielded new insights into DIPG molecular biology.We now know that DIPG comprises a heterogeneous disease with variable molecular phenotypes, different from adult high grade glioma,other non-pontine pediatric high grade gliomas and even between pontine gliomas.The discovery of histone H3.3 or H3.1 mutations has been an important step forward in understanding tumor formation,maintenance and progression.Pharmacologic reversal of DIPG histone demethylation therefore offers an important potential intervention strategy for the treatment of DIPG.To date,clinical trials of newly diagnosed or progressive DIPG with epigenetic modifiers have been unsuccessful.Whether this failure represents limited activity of the agents used,their CNS penetration,redundant pathways within the tumor,or the possibility that histone mutations are necessary only to initiate DIPGs but not maintain their growth,suggest that a great deal still needs to be elucidated in both the underlying biology of these pathways,and the drugs designed to target them.In this review, we discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment strategies directed against the unique abnormalities
Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M
We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.
Sandra M Eldridge
Full Text Available We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.
Al-Amleh, B; Lyons, K; Swain, M
Zirconia is unique in its polymorphic crystalline makeup, reported to be sensitive to manufacturing and handling processes, and there is debate about which processing method is least harmful to the final product. Currently, zirconia restorations are manufactured by either soft or hard-milling processes, with the manufacturer of each claiming advantages over the other. Chipping of the veneering porcelain is reported as a common problem and has been labelled as its main clinical setback. The objective of this systematic review is to report on the clinical success of zirconia-based restorations fabricated by both milling processes, in regard to framework fractures and veneering porcelain chipping. A comprehensive review of the literature was completed for in vivo trials on zirconia restorations in MEDLINE and PubMed between 1950 and 2009. A manual hand search of relevant dental journals was also completed. Seventeen clinical trials involving zirconia-based restorations were found, 13 were conducted on fixed partial dentures, two on single crowns and two on zirconia implant abutments, of which 11 were based on soft-milled zirconia and six on hard-milled zirconia. Chipping of the veneering porcelain was a common occurrence, and framework fracture was only observed in soft-milled zirconia. Based on the limited number of short-term in vivo studies, zirconia appears to be suitable for the fabrication of single crowns, and fixed partial dentures and implant abutments providing strict protocols during the manufacturing and delivery process are adhered to. Further long-term prospective studies are necessary to establish the best manufacturing process for zirconia-based restorations. PMID:20406352
Wojtecki, Lars; Groiss, Stefan J.; Ferrea, Stefano; Elben, Saskia; Hartmann, Christian J.; Dunnett, Stephen B; Rosser, Anne; Saft, Carsten; Südmeyer, Martin; Ohmann, Christian; Schnitzler, Alfons; Vesper, Jan
Background Movement disorders in Huntington’s disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial. Methods In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week i...
Lee, Seunghoon; Kim, Joo-Hee; Shin, Kyung-Min; Kim, Jung-Eun; Kim, Tae-Hun; Kang, Kyung-Won; Lee, Minhee; Jung, So-Young; Shin, Mi-Suk; Kim, Ae-Ran; Park, Hyo-Ju; Hong, Kwon-Eui; Choi, Sun-Mi
Background The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research. Methods/design This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean ...
Umscheid, Craig A; Margolis, David J; Grossman, Craig E
The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords "randomized controlled trial," "patient/clinical research," "ethics," "phase IV," "data and safety monitoring board," and "surrogate endpoint." With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform. PMID:21904102
Kuskowski Michael A
Full Text Available Abstract Background This small, pilot study evaluated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin on walking distance, pain and joint mobility in subjects with moderate to severe osteoarthritis of the knee. Methods Subjects (n = 70 with moderate to severe osteoarthritis of the knee were randomized to four double-blinded treatments for 12 weeks: (a Glucosamine sulfate (1500 mg/d; (b Aquamin (2400 mg/d; (c Combined treatment composed of Glucosamine sulfate (1500 mg/d plus Aquamin (2400 mg/d and (d Placebo. Primary outcome measures were WOMAC scores and 6 Minute Walking Distances (6 MWD. Laboratory based blood tests were used as safety measures. Results Fifty subjects completed the study and analysis of the data showed significant differences between the groups for changes in WOMAC pain scores over time (p = 0.009 ANCOVA; however, these data must be reviewed with caution since significant differences were found between the groups at baseline for WOMAC pain and stiffness scores (p = 0.0039 and p = 0.013, respectively, ANOVA. Only the Aquamin and Glucosamine groups demonstrated significant improvements in symptoms over the course of the study. The combination group (like the placebo group did not show any significant improvements in OA symptoms in this trial. Within group analysis demonstrated significant improvements over time on treatment for the WOMAC pain, activity, composite and stiffness (Aquamin only scores as well as the 6 minute walking distances for subjects in the Aquamin and Glucosamine treatment groups. The Aquamin and Glucosamine groups walked 101 feet (+7% and 56 feet (+3.5% extra respectively. All treatments were well tolerated and the adverse events profiles were not significantly different between the groups. Conclusion This small preliminary study suggested that a multi mineral supplement (Aquamin may reduce the pain and stiffness of osteoarthritis of the knee over 12 weeks of treatment and
Krarup, L.H.; Gluud, C.; Truelsen, T.;
. Physical activity is assessed in both groups seven times during follow-up using the Physical Activity Scale for the Elderly (PASE) questionnaire, which quantifies the amount of physical activity done in the last seven days prior to interview. The PASE score constitutes the primary outcome measure......INTRODUCTION: A high level of physical activity is associated with a decreased risk of first stroke and physical activity modifies recognized stroke risk factors and is recommended for stroke survivors. Available research shows that stroke patients can increase their level of physical performance...... over a short period. When the intervention period is over, physical performance often declines towards baseline level. Currently, there is no evidence on the association between physical activity and the risk of recurrent stroke. The ExStroke Pilot Trial is a randomized clinical trial with the aim...
Elad Sharon; Howard Streicher; Priscila Goncalves; Helen XChen
Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called“immune checkpoints.” These checkpoints serve to control or turn off the immune response when it is no longer needed to prevent tissue injury and autoimmunity. Cancer cells have learned or evolved to use these mechanisms to evade immune control and elimination. The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology. Three sets of agents have emerged in clinical trials exploiting this strategy. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen4 (CTLA4), programmed cell death1 (PD-1), and programmed cell death ligand 1 (PD-L1). These inhibitors of immune inhibition have demonstrated extensive activity as single agents and in combinations. Clinical responses have been seen in melanoma, renal cellcarcinoma, non-smal celllung cancer, and several other tumor types. Despite the autoimmune or inflammatory immune-mediated adverse effects which have been seen, the responses and overall survival benefits exhibited thus far warrant further clinical development.
Tandava Krishnan Panakanti
Full Text Available Branch retinal vein occlusion (BRVO is the second most common retinal vascular disorder. The management of macular edema has changed considerably over time. The laser is considered the gold standard treatment for over two decades. However, visual recovery with laser is usually slow and incomplete. The advent of intravitreal agents, specifically anti-vascular endothelial growth factors (VEGF have heralded a new era which promises rapid recovery of vision and quality of vision. Randomized clinical trials have reported optimal results with anti-VEGF agents (ranibizumab, bevacizumab, and aflibercept compared to laser therapy or steroids. However, nearly 50% of the patients require repeat intravitreal anti-VEGF therapy up to 4 years after initiating therapy to sustain the visual gains. The adverse events (systemic and ocular of these agents are minimal. Monotherapy with anti-VEGF agents have been found to provide better results than any combination with laser. This review article summarizes evidence from randomized controlled trials evaluating treatment options for the treatment of macular edema secondary to BRVO with a special focus on anti-VEGF therapy.
Xu, Jiajing; 徐佳静
The primary goal of clinical trials is to collect enough scientific evidence for a new intervention. Despite the widespread use of equal randomization in clinical trials, response-adaptive randomization has attracted considerable interest in terms of ethical concerns. In this thesis, delayed response problems and innovative designs for cytostatic agents in oncology clinical trials are studied. There is typically a prerun of equal randomization before the implementation of response-adaptiv...
Shim, Byoung Yong; Park, Se Hoon; Lee, Soonil; Kim, Jin-Soo; Lee, Kyoung Eun; Kang, Yoon-Koo; Ahn, Myung-Ju
Purpose Cancer clinical trials in Korea have rapidly progressed in terms of quantity and quality during the last decade. This study evaluates the current status of cancer clinical trials in Korea and their associated problems. Materials and Methods We analyzed the clinical trials approved by the Korea Food and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey containing 22 questions was also performed with several cooperative study groups and individual researchers...
Bent, Stephen; Bertoglio, Kiah; Ashwood, Paul; Bostrom, Alan; Hendren, Robert L.
We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3-8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (plus or minus…
Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen; Moench, Thomas; Stanberry, Lawrence R.; Rosenthal, Susan L.
A greater understanding of participant views regarding reimbursement will help investigators plan studies that have better potential for reaching target enrollment, maximize efficient recruitment, maintain scientific integrity, and enhance retention over time. As part of a clinical trial in the area of sexual health, healthy women’s perceptions of reimbursement for research participation were investigated. Semi-structured, audio-recorded, qualitative interviews were conducted immediately upon women’s completion of the clinical trial to enable a participant-driven understanding of perceptions about monetary reimbursement. Audio-recordings were transcribed and analyzed using framework analysis. Women (N = 30) had a mean age of 29.5 ± 5.7 years (range 22–45 years). Sixty-three percent of participants (n = 19) were non-Hispanic (white n = 13, black n = 4, and Asian n = 2), while the remaining were Hispanic (n = 11). Seventy-three percent (n = 22) reported previous participation in research. In general, women viewed reimbursement as a benefit to research participation, the amount of which should reflect time, the inconvenience to the research subject, and the potential for unknown risks in the short- and long-term. They believed reimbursement should take into account the degree of risk of the study, with investigations of experimental products offering greater reimbursement. Women believed that monetary reimbursement is unlikely to coerce an individual to volunteer for a study involving procedures or requirements that they found unacceptable. The results of this study can be used to provide guidance to those planning and evaluating reimbursement for research participation. PMID:21931235
Kjaergard, Lise L; Gluud, Christian
The objective of this study was to assess whether trials with a positive (i.e., statistically significant) outcome are cited more often than negative trials. We reviewed 530 randomized clinical trials on hepato-biliary diseases published in 11 English-language journals indexed in MEDLINE from 1985...
Conclusion: We developed a novel DWI and evaluated its improved resolution in a clinical setting. This technology has many potential applications and should be evaluated in future clinical trials as a patient management tool.
Pelto, Debra J.; Sadler, Georgia Robins; Njoku, Ogo; Rodriguez, Maria Carina; Villagra, Cristina; Malcarne, Vanessa L.; Riley, Natasha E.; Behar, Alma I.; Jandorf, Lina
The pilot study reported in this article culturally and linguistically adapted an educational intervention to promote cancer clinical trials (CCTs) participation among Latinas/os and African Americans. The single-session slide presentation with embedded videos, originally developed through a campus-community partnership in Southern California, was…
Mishler, John M.
A pilot program at the University of Missouri-Kansas City included creation of a part-time administrative position to enhance cooperative ventures between the university and the pharmaceutical industry through placement of clinical trials among academic units with interdisciplinary research programs in the health sciences. Sponsored funding levels…
Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: A Crucial Key to Human Health Research Past ... the forefront of human health research today are clinical trials—studies that use human volunteers to help medical ...
West, D A; Balas, E A; West, T D
In addition to providing comparable and verifiable evidence regarding outcomes, clinical trials could also serve as sources of accurate and replicable financial information. Trial reports that identify expenses associated with effective diagnostic and therapeutic interventions enable cost controls. Standardized cost calculations could help clinicians and administrators identify more efficient health care technologies. Unfortunately, relatively few published trials include economic analyses and when they do, data are incomplete. Based on analyses of 97 clinical trial reports, this article proposes a standard costing format. Health care financial managers have the costing expertise necessary to implement and interpret standardized cost calculations for clinical trials. With the active involvement of financial managers, a standard costing format for clinical trials can be achieved. PMID:10961828
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
BACKGROUND: Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. METHODS: We...... conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two......%). Heterogeneity was moderate (I(2) = 46%, p = 0.02) and unexplained by metaregression. INTERPRETATION: We provide empirical evidence for observer bias in randomized clinical trials with subjective measurement scale outcomes. A failure to blind assessors of outcomes in such trials results in a high risk...
Wei, Erin X; Kirsner, Robert S; Eaglstein, William H
Clinical trials are critical for the development of new therapies in dermatology, and their results help determine US Food and Drug Administration (FDA) approval and guide care. Of special relevance is the clinical trial efficacy end point, the metric from which statistically significant outcome is derived. Clinicians' understanding of a clinical trial's end point is necessary for critical analysis of the trial results and for applying those results to daily practice. This review provides practical knowledge and critical evaluation of end points used in treatment approvals by the FDA. The end points for actinic keratosis, acne vulgaris, atopic dermatitis, onychomycosis, and cutaneous ulcer serve as examples. PMID:26936300
developed here is safe, compliance level is good, and a full scale trial is feasible. The data obtained suggest that adult participants may improve their wellness by learning and applying a program based on yoga and yogic breathing exercises; this can be conclusively assessed in a large-scale trial. Trial Registration Australian Clinical Trial Registry ACTRN012607000175471.
Full Text Available Abstract Background Venous thromboembolism (VTE is a common preventable cause of mortality in hospitalized medical patients. Despite rigorous randomized trials generating strong recommendations for anticoagulant use to prevent VTE, nearly 40% of medical patients receive inappropriate thromboprophylaxis. Knowledge-translation strategies are needed to bridge this gap. Methods We conducted a 16-week pilot cluster randomized controlled trial (RCT to determine the proportion of medical patients that were appropriately managed for thromboprophylaxis (according to the American College of Chest Physician guidelines within 24 hours of admission, through the use of a multicomponent knowledge-translation intervention. Our primary goal was to determine the feasibility of conducting this study on a larger scale. The intervention comprised clinician education, a paper-based VTE risk assessment algorithm, printed physicians’ orders, and audit and feedback sessions. Medical wards at six hospitals (representing clusters in Ontario, Canada were included; three were randomized to the multicomponent intervention and three to usual care (i.e., no active strategies for thromboprophylaxis in place. Blinding was not used. Results A total of 2,611 patients (1,154 in the intervention and 1,457 in the control group were eligible and included in the analysis. This multicomponent intervention did not lead to a significant difference in appropriate VTE prophylaxis rates between intervention and control hospitals (appropriate management rate odds ratio = 0.80; 95% confidence interval: 0.50, 1.28; p = 0.36; intra-class correlation coefficient: 0.022, and thus was not considered feasible. Major barriers to effective knowledge translation were poor attendance by clinical staff at education and feedback sessions, difficulty locating preprinted orders, and lack of involvement by clinical and administrative leaders. We identified several factors that may increase uptake of a VTE
Jakobsen, Jan Nyrop; Sørensen, Jens Benn
Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all...... clinical trials evaluating the effect of targeted treatments in MM....
NCI is launching a new clinical trials research network intended to improve treatment for the more than 1.6 million Americans diagnosed with cancer each year. The new system, NCI’s National Clinical Trials Network (NCTN), will facilitate the rapid initia
Lambers Heerspink, Hiddo Jan
Large scale randomized clinical trials are needed to detect small but meaningful effects of new drugs. However, large scale randomized clinical trials are expensive undertakings and they are in imbalance with the scientific output. As a consequence there is a strong voice for more efficacious random
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes.......To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes....
Thomas eFitzGerald, MD
Full Text Available The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial.
Full Text Available Abstract Background Hypnosis treatment in general practice is a rather new concept. This pilot study was performed to evaluate the effect of a standardized hypnosis treatment used in general practice for patients with chronic widespread pain (CWP. Methods The study was designed as a randomized control group-controlled study. Sixteen patients were randomized into a treatment group or a control group, each constituting eight patients. Seven patients in the treatment group completed the schedule. After the control period, five of the patients in the control group also received treatment, making a total of 12 patients having completed the treatment sessions. The intervention group went through a standardized hypnosis treatment with ten consecutive therapeutic sessions once a week, each lasting for about 30 minutes, focusing on ego-strengthening, relaxation, releasing muscular tension and increasing self-efficacy. A questionnaire was developed in order to calibrate the symptoms before and after the 10 weeks period, and the results were interpolated into a scale from 0 to 100, increasing numbers representing increasing suffering. Data were analyzed by means of T-tests. Results The treatment group improved from their symptoms, (change from 62.5 to 55.4, while the control group deteriorated, (change from 37.2 to 45.1, (p = 0,045. The 12 patients who completed the treatment showed a mean improvement from 51.5 to 41.6. (p = 0,046. One year later the corresponding result was 41.3, indicating a persisting improvement. Conclusion The study indicates that hypnosis treatment may have a positive effect on pain and quality of life for patients with chronic muscular pain. Considering the limited number of patients, more studies should be conducted to confirm the results. Trial Registration The study was registered in ClinicalTrials.gov and released 27.08.07 Reg nr NCT00521807 Approval Number: 05032001.
Background Interventions based on meditation and mindfulness techniques have been shown to reduce stress and increase psychological well-being in a wide variety of populations. Self-administrated Internet-based mindfulness training programs have the potential to be a convenient, cost-effective, easily disseminated, and accessible alternative to group-based programs. Objective This randomized controlled pilot trial with 90 university students in Stockholm, Sweden, explored the feasibility, usability, acceptability, and outcomes of an 8-week Internet-based mindfulness training program. Methods Participants were randomly assigned to either an intervention (n=46) or an active control condition (n=44). Intervention participants were invited to an Internet-based 8-week mindfulness program, and control participants were invited to an Internet-based 4-week expressive writing program. The programs were automated apart from weekly reminders via email. Main outcomes in pre- and postassessments were psychological well-being and depression symptoms. To assess the participant’s experiences, those completing the full programs were asked to fill out an assessment questionnaire and 8 of the participants were interviewed using a semistructured interview guide. Descriptive and inferential statistics, as well as content analysis, were performed. Results In the mindfulness program, 28 out of 46 students (60%) completed the first week and 18 out of 46 (39%) completed the full program. In the expressive writing program, 35 out of 44 students (80%) completed the first week and 31 out of 44 (70%) completed the full program. There was no statistically significantly stronger intervention effect for the mindfulness intervention compared to the active control intervention. Those completing the mindfulness group reported high satisfaction with the program. Most of those interviewed were satisfied with the layout and technique and with the support provided by the study coordinators. More
Stensland, Kristian D; McBride, Russell B; Latif, Asma; Wisnivesky, Juan; Hendricks, Ryan; Roper, Nitin; Boffetta, Paolo; Hall, Simon J; Oh, William K; Galsky, Matthew D
The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-limiting factors in the effort to translate preclinical discoveries into the next generation of standard therapeutic approaches. Optimal use of resources requires understanding and ultimately addressing inefficiencies in the cancer clinical trials system. Prior analyses have demonstrated that a large proportion of trials initiated by the National Cancer Institute (NCI) Cooperative Group system are never completed. While NCI Cooperative Group trials are important, they represent only a small proportion of all cancer clinical trials performed. Herein, we explore the problem of cancer clinical trials that fail to complete within the broader cancer clinical trials enterprise. Among 7776 phase II-III adult cancer clinical trials initiated between 2005-2011, we found a seven-year cumulative incidence of failure to complete of approximately 20% (95% confidence interval = 18% to 22%). Nearly 48000 patients were enrolled in trials that failed to complete. These trials likely contribute little to the scientific knowledge base, divert resources and patients from answering other critical questions, and represent a barrier to progress.
As Japan becomes more integrated into the global market, pharmaceutical research and development (R&D) in Japan faces considerable challenges. While global simultaneous development including Asian countries has become a common strategy for multi-national pharmaceutical companies, Japan has been frequently set aside because of its provincial regulatory and clinical trial infrastructure. Meanwhile, many improvement programs in pharmaceutical area have been initiated in Japan. With this increased scrutiny, significant improvements in regulatory process, clinical trial costs, and site performance are anticipated over the next few years. RENAAL is the first multi-national clinical trial involving Japanese patients diabetic nephropathy associated with type II diabetes mellitus. In this article, issues which have been observed in the process of conducting multi-national clinical trial were discussed based on the experience with RENAAL. It is hoped that, as we gain more experiences in multi-national clinical trials, solutions for these issues are found in near future.
Moustgaard, Helene; Bello, Segun; Miller, Franklin G;
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...... providing a classification of clinical trial outcomes and a descriptive study of how outcomes were classified in 200 PubMed indexed clinical trial reports published in 2012. RESULTS: We identified 90 methodological publications with some form of a classification of outcomes. Three distinct definitions were...
Buonansegna, Erika; Salomo, Søren; Maier, Anja;
Clinical trials in the pharmaceutical industry are the most critical part of the drug development process with respect to obtaining the market approval from the authorities. Clinical trials are highly expensive, time-consuming and often unsuccessful. While new product development (NPD) literature...... has extensively investigated success factors in R&D projects, it has not directly addressed success factors in clinical trials, as the late testing stage of a NPD yet. The aim of this paper is to enhance our understanding of the clinical trial management by creating a new conceptual framework...... of success factors. This paper creates the new framework by combining success factors from NPD literature and from empirical evidence collected through 11 semi-structured interviews with experts in clinical trials. The framework of success factors provides managerial guidelines for practitioners to optimize...
Cleeland, Charles S; O'Mara, Ann; Zagari, Martin; Baas, Carole
Cancer-related pain is highly prevalent and often severe, and as a result is often one of the defining experiences for patients with malignancy. Patients and patients' families almost always live with the ever-present reality that cancer treatment and progression may be accompanied by pain. For patients nearing the end of life, most fear that their final days will be spent living with the terrible effects of the disease, the most important of which is pain. Despite this, there is far less systematic research on the mechanisms of cancer-related pain or on the development of new agents to reduce or eliminate pain in cancer patients compared with research to combat the disease itself. Further, even when the focus of research is treatment of the tumor, the effects of anticancer treatments on pain are often underreported in publications and other forums. To illustrate the relative drought in the cancer pain control area, there have been no new drugs approved for cancer-related pain in recent years. A number of methodologic and logistical challenges that hinder the ability to assess pain response in clinical trials are discussed in this article. Possible ways to address these challenges are also discussed. PMID:22046026
Choi, Jeeyae; Choi, Jeungok E
To enhance patient safety from falls, many hospital information systems have been implemented to collect clinical data from the bedside and have used the information to improve fall prevention care. However, most of them use administrative data not clinical nursing data. This necessitated the development of a web-based Nursing Practice and Research Information Management System (NPRIMS) that processes clinical nursing data to measure nurses' delivery of fall prevention care and its impact on patient outcomes. This pilot study developed computer algorithms based on a falls prevention protocol and programmed the prototype NPRIMS. It successfully measured the performance of nursing care delivered and its impact on patient outcomes using clinical nursing data from the study site. Results of the study revealed that NPRIMS has the potential to pinpoint components of nursing processes that are in need of improvement for preventing patient from falls. PMID:27332171
Recently, the complexity and costs of clinical trials have increased dramatically, especially in the area of new drug development. Risk-based monitoring (RBM) has been attracting attention as an efficient and effective trial monitoring approach, which can be applied irrespectively of the trial sponsor, i.e., academic institution or pharmaceutical company. In the RBM paradigm, it is expected that a statistical approach to central monitoring can help improve the effectiveness of on-site monitoring by prioritizing and guiding site visits according to central statistical data checks, as evidenced by examples of actual trial datasets. In this review, several statistical methods for central monitoring are presented. It is important to share knowledge about the role and performance capabilities of statistical methodology among clinical trial team members (i.e., sponsors, investigators, data managers, monitors, and biostatisticians) in order to adopt central statistical monitoring for assessing data quality in the actual clinical trial. PMID:26499195
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
BACKGROUND: Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. METHODS: We...... conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two...... investigators agreed on the inclusion of trials and the outcome scale. For each trial, we calculated the difference in effect size (i.e., standardized mean difference between nonblinded and blinded assessments). A difference in effect size of less than 0 suggested that nonblinded assessors generated more...
Full Text Available Abstract Background Obstetric cholestasis (OC is a serious problem in pregnancy. It affects about 4500 women per year in the UK. Affected women develop itching and occasionally jaundice. More importantly, the condition is associated with premature delivery, fetal distress and is believed to be an important cause of stillbirth. However, even now, there is no clear evidence as to whether the most popular treatment, a drug called ursodeoxycholic acid is beneficial to the baby, or even if it is safe in pregnancy. Nor do we know whether planned early delivery of the baby at 37–38 weeks, another popular treatment, does more good than harm. A randomised trial to evaluate both ursodeoxycholic acid and timed delivery is needed but will be complicated and expensive. We plan a preliminary study, Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis (Acronym PITCH- Pregnancy Intervention Trial in Cholestasis trial, to evaluate the feasibility of a larger trial. The trial is funded by the NHS Research for Patient Benefit (RfPB Programme. Methods PITCH is a multi-centre, double blinded, randomised, controlled, factorial design trial. The trial is being run in six UK centres and women with obstetric cholestasis will be recruited for eighteen months. In this pilot trial we aim to collect data to finalise the design for the main trial. This will include measuring trial recruitment rate, including recruitment to each factorial comparison separately. We will also measure the spectrum of disease among recruits and non-recruits and compliance with the four possible treatment allocations. We will use these data to design the main trial. Discussion The ultimate aim of the main trial is to enable clinicians to manage this condition more effectively. If it transpires that ursodeoxycholic acid and early delivery are both safe and effective then steps will be taken to ensure that all women with OC who could benefit from them
Dimitrios Zardavas; Martine Piccart-Gebhart
The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.
This final rule details the requirements for submitting registration and summary results information, including adverse event information, for specified clinical trials of drug products (including biological products) and device products and for pediatric postmarket surveillances of a device product to ClinicalTrials.gov, the clinical trial registry and results data bank operated by the National Library of Medicine (NLM) of the National Institutes of Health (NIH). This rule provides for the expanded registry and results data bank specified in Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) to help patients find trials for which they might be eligible, enhance the design of clinical trials and prevent duplication of unsuccessful or unsafe trials, improve the evidence base that informs clinical care, increase the efficiency of drug and device development processes, improve clinical research practice, and build public trust in clinical research. The requirements apply to the responsible party (meaning the sponsor or designated principal investigator) for certain clinical trials of drug products (including biological products) and device products that are regulated by the Food and Drug Administration (FDA) and for pediatric postmarket surveillances of a device product that are ordered by FDA. PMID:27658315
Natale, Enrico; Marsocci, Alfiera
Generally in the clinical practice patients are more complex in comparison with those included in the clinical trials. In this article, we discuss three relevant items, which may implement the transferability of the clinical trial results in the real world. The observational studies have fewer restrictions on the number of patients included, due to more relaxed inclusion and exlusion criteria than in randomized clinical trials. The absence of randomization however may lead to potential for bias. The recurrent event analysis may extend the positive results of clinical trials regarding the reductions of the first primary endpoint event to total events, including those beyond the first event. This analysis is of great interest in the clinical practice, where recurrent events are common. Finally the reliability of subgroup analysis is discussed. Pre-specified subgroup analyses are more credible and valuable than post-hoc analyses.
Berry, Donald A
Clinical trials are the final links in the chains of knowledge and for determining the roles of therapeutic advances. Unfortunately, in an important sense they are the weakest links. This article describes two designs that are being explored today: platform trials and basket trials. Both are attempting to merge clinical research and clinical practice.
Britton, Willoughby B.; Lepp, Nathaniel E.; Niles, Halsey F.; Rocha, Tomas; Fisher, Nathan; Gold, Jonathan
Children in the United States are at risk for numerous psychological problems, such as anxiety, attention problems, and mood disorders, and are underserved by current mental health provisions. The current study is a pilot trial to examine the effects of a nonelective, classroom-based, teacher-implemented, mindfulness meditation intervention on standard clinical measures of mental health and affect in middle school children. A total of 101 healthy sixth-grade students (55 boys and 46 girls) we...
Shiovitz, Thomas M; Bain, Earle E; McCann, David J; Skolnick, Phil; Laughren, Thomas; Hanina, Adam; Burch, Daniel
Accounting for subject nonadherence and eliminating inappropriate subjects in clinical trials are critical elements of a successful study. Nonadherence can increase variance, lower study power, and reduce the magnitude of treatment effects. Inappropriate subjects (including those who do not have the illness under study, fail to report exclusionary conditions, falsely report medication adherence, or participate in concurrent trials) confound safety and efficacy signals. This paper, a product of the International Society for CNS Clinical Trial Methodology (ISCTM) Working Group on Nonadherence in Clinical Trials, explores and models nonadherence in clinical trials and puts forth specific recommendations to identify and mitigate its negative effects. These include statistical analyses of nonadherence data, novel protocol design, and the use of biomarkers, subject registries, and/or medication adherence technologies. PMID:26634893
Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R
This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...
Eaton, Margaret L; Kwon, Brian K; Scott, Christopher Thomas
Too often, biopharmaceutical companies stop their clinical trials solely for financial reasons. In this chapter, we discuss this phenomenon against the backdrop of a 2011 decision by Geron Corporation to abandon its stem cell clinical trial for spinal cord injury (SCI), the preliminary results of which were released in May 2014. We argue that the resultant harms are widespread and are different in nature from the consequences of stopping trials for scientific or medical reasons. We examine the ethical and social effects that arise from such decisions and discuss them in light of ethical frameworks, including duties of individual stakeholders and corporate sponsors. We offer ways that sponsors and clinical sites can ensure that trials are responsibly started, and once started adequately protect the interests of participants. We conclude with recommendations that industry sponsors of clinical trials should adopt in order to advance a collective and patient-centered research ethic. PMID:25062706
Luzi, Daniela; Ricci, Fabrizio L. (CNR-IRPPS); Serbanati, Luca D.; GreyNet, Grey Literature Network Service
There are various, important information sources devoted to the diffusion of clinical trials, but they fail to achieve a complete coverage of clinical research. The demand for a mandatory public registration of clinical trials is emerging from different institutions, which are making efforts to develop common metadata schemas to both increase information exchange and make this information publicly available. The paper describes a metadata analysis of the various solutions of CT data represent...
Haynes-Maslow, Lindsey; Godley, Paul; DiMartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William
Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical tri...
Cork Michael J
Full Text Available Abstract Background The vulnerability of newborn babies' skin creates the potential for a number of skin problems. Despite this, there remains a dearth of good quality evidence to inform practice. Published studies comparing water with a skin-cleansing product have not provided adequate data to inform an adequately powered trial. Nor have they distinguished between babies with and without a predisposition to atopic eczema. We conducted a pilot study as a prequel to designing an optimum trial to investigate whether bathing with a specific cleansing product is superior to bathing with water alone. The aims were to produce baseline data which would inform decisions for the main trial design (i.e. population, primary outcome, sample size calculation and to optimize the robustness of trial processes within the study setting. Methods 100 healthy, full term neonates aged Results Forty nine babies were randomized to cleansing product, 51 to water. The 95% confidence intervals (CI for the average TEWL measurement at each time point were: whole sample at baseline: 10.8 g/m2/h to 11.7 g/m2/h; CP group 4 weeks: 10.9 g/m2/h to 13.3 g/m2/h; 8 weeks: 11.4 g/m2/h to 12.9 g/m2/h; W group 4 weeks:10.9 g/m2/h to 12.2 g/m2/h; 8 weeks: 11.4 g/m2/h to 12.9 g/m2/h. Conclusion This pilot study provided valuable baseline data and important information on trial processes. The decision to proceed with a superiority trial, for example, was inconsistent with our data; therefore a non-inferiority trial is recommended. Trial registration ISRCTN72285670
Lachin, J M; Matts, J P; Wei, L J
The statistical properties of simple (complete) randomization, permuted-block (or simply blocked) randomization, and the urn adaptive biased-coin randomization are summarized. These procedures are contrasted to covariate adaptive procedures such as minimization and to response adaptive procedures such as the play-the-winner rule. General recommendations are offered regarding the use of complete, permuted-block, or urn randomization. In a large double-masked trial, any of these procedures may be acceptable. For a given trial, the relative merits of each procedure should be carefully weighed in relation to the characteristics of the trial. Important considerations are the size of the trial, overall as well as within the smallest subgroup to be employed in a subgroup-specific analysis, whether or not the trial is to be masked, and the resources needed to perform the proper randomization-based permutational analysis. PMID:3203526
Greer, Joseph A.; Traeger, Lara; Bemis, Heather; Solis, Jessica; Hendriksen, Ellen S.; Park, Elyse R; Pirl, William F.; Temel, Jennifer S.; Prigerson, Holly G.; Safren, Steven A.
This article presents a pilot randomized controlled trial that examined the feasibility and potential efficacy of brief cognitive-behavioral therapy to reduce anxiety in patients with terminal cancer.
Zoellner, Jamie; Cook, Emily; Chen, Yvonnes; You, Wen; Davy, Brenda; Estabrooks, Paul
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)...
Briken, S.; Gold, S M; S. Patra; Vettorazzi, E; Harbs, D.; Tallner, Alexander; Ketels, G.; Schulz, K. H.; Heesen, C.
Background: Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. Objective: To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. Methods: Patients with pr...
Full Text Available Abstract Background Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. Methods This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000® containing 4 strains of probiotic bacteria (1010 each plus 4 nondigestible, fermentable dietary fibers (2.5 g each was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. Results Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. Conclusions
Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K
Several web-based search engines have been developed to assist individuals to find clinical trials for which they may be interested in volunteering. However, these search engines may be difficult for individuals with low health and computer literacy to navigate. The authors present findings from a usability evaluation of clinical trial search tools with 41 participants across the health and computer literacy spectrum. The study consisted of 3 parts: (a) a usability study of an existing web-based clinical trial search tool; (b) a usability study of a keyword-based clinical trial search tool; and (c) an exploratory study investigating users' information needs when deciding among 2 or more candidate clinical trials. From the first 2 studies, the authors found that users with low health literacy have difficulty forming queries using keywords and have significantly more difficulty using a standard web-based clinical trial search tool compared with users with adequate health literacy. From the third study, the authors identified the search factors most important to individuals searching for clinical trials and how these varied by health literacy level.
Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K
Several web-based search engines have been developed to assist individuals to find clinical trials for which they may be interested in volunteering. However, these search engines may be difficult for individuals with low health and computer literacy to navigate. The authors present findings from a usability evaluation of clinical trial search tools with 41 participants across the health and computer literacy spectrum. The study consisted of 3 parts: (a) a usability study of an existing web-based clinical trial search tool; (b) a usability study of a keyword-based clinical trial search tool; and (c) an exploratory study investigating users' information needs when deciding among 2 or more candidate clinical trials. From the first 2 studies, the authors found that users with low health literacy have difficulty forming queries using keywords and have significantly more difficulty using a standard web-based clinical trial search tool compared with users with adequate health literacy. From the third study, the authors identified the search factors most important to individuals searching for clinical trials and how these varied by health literacy level. PMID:25315593
Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro. A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP. Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line. These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted. NCT00256334
Vaughn, Jacqueline; Lister, Michael; Shaw, Ryan J
We describe a pilot study that incorporated an innovative hybrid simulation designed to increase the perception of realism in a high-fidelity simulation. Prelicensure students (N = 12) cared for a manikin in a simulation lab scenario wearing Google Glass, a wearable head device that projected video into the students' field of vision. Students reported that the simulation gave them confidence that they were developing skills and knowledge to perform necessary tasks in a clinical setting and that they met the learning objectives of the simulation. The video combined visual images and cues seen in a real patient and created a sense of realism the manikin alone could not provide. PMID:27258807
Hahn, Joyce; Bishop, Geri; Fennell, Lenora
The complex dynamics of the current healthcare environment require healthcare delivery systems to become cost effective and quality driven. Educated healthcare consumers expect superior service and timely responses to their needs. For one healthcare system, customer expectations were an integral part of designing, implementing, and measuring the service components of congestive heart failure pathway outcomes. Service excellence can influence overall clinical outcomes when measured by consumer awareness and patient satisfaction. The inclusion of service excellence as an intrinsic piece of the organizational strategic plan laid the groundwork for this integrated pilot project. PMID:11942156
Hahn, Joyce; Bishop, Geri; Fennell, Lenora
The complex dynamics of the current healthcare environment require healthcare delivery systems to become cost effective and quality driven. Educated healthcare consumers expect superior service and timely responses to their needs. For one healthcare system, customer expectations were an integral part of designing, implementing, and measuring the service components of congestive heart failure pathway outcomes. Service excellence can influence overall clinical outcomes when measured by consumer awareness and patient satisfaction. The inclusion of service excellence as an intrinsic piece of the organizational strategic plan laid the groundwork for this integrated pilot project.
Eldridge, Sandra M.; Lancaster, Gillian A.; Michael J. Campbell; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L.; Bond, Christine M
We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of ...
Smaïl-Faugeron, V; Fron-Chabouis, H; Durieux, P
Prospective registration of randomized controlled trials (RCTs) represents the best solution to reporting bias. The extent to which oral health journals have endorsed and complied with RCT registration is unknown. We identified journals publishing RCTs in dentistry, oral surgery, and medicine in the Journal Citation Reports. We classified journals into 3 groups: journals requiring or recommending trial registration, journals referring indirectly to registration, and journals providing no reference to registration. For the 5 journals with the highest 2012 impact factors in each group, we assessed whether RCTs with results published in 2013 had been registered. Of 78 journals examined, 32 (41%) required or recommended trial registration, 19 (24%) referred indirectly to registration, and 27 (35%) provided no reference to registration. We identified 317 RCTs with results published in the 15 selected journals in 2013. Overall, 73 (23%) were registered in a trial registry. Among those, 91% were registered retrospectively and 32% did not report trial registration in the published article. The proportion of trials registered was not significantly associated with editorial policies: 29% with results in journals that required or recommended registration, 15% in those that referred indirectly to registration, and 21% in those providing no reference to registration (P = 0.05). Less than one-quarter of RCTs with results published in a sample of oral health journals were registered with a public registry. Improvements are needed with respect to how journals inform and require their authors to register their trials.
Mentz, Robert J; Hernandez, Adrian F; Berdan, Lisa G; Rorick, Tyrus; O'Brien, Emily C; Ibarra, Jenny C; Curtis, Lesley H; Peterson, Eric D
Randomized, clinical trials are commonly regarded as the highest level of evidence to support clinical decisions. Good Clinical Practice guidelines have been constructed to provide an ethical and scientific quality standard for trials that involve human subjects in a manner aligned with the Declaration of Helsinki. Originally designed to provide a unified standard of trial data to support submission to regulatory authorities, the principles may also be applied to other studies of human subjects. Although the application of Good Clinical Practice principles generally led to improvements in the quality and consistency of trial operations, these principles have also contributed to increasing trial complexity and costs. Alternatively, the growing availability of electronic health record data has facilitated the possibility for streamlined pragmatic clinical trials. The central tenets of Good Clinical Practice and pragmatic clinical trials represent potential tensions in trial design (stringent quality and highly efficient operations). In the present article, we highlight potential areas of discordance between Good Clinical Practice guidelines and the principles of pragmatic clinical trials and suggest strategies to streamline study conduct in an ethical manner to optimally perform clinical trials in the electronic age.
Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques
Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies.
Smed, Marie; Getz, Kenneth A.
Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff...... in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract...... research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites...
Geifman, Nophar; Butte, Atul J.
Open clinical trial data offer many opportunities for the scientific community to independently verify published results, evaluate new hypotheses and conduct meta-analyses. These data provide a springboard for scientific advances in precision medicine but the question arises as to how representative clinical trials data are of cancer patients overall. Here we present the integrative analysis of data from several cancer clinical trials and compare these to patient-level data from The Cancer Genome Atlas (TCGA). Comparison of cancer type-specific survival rates reveals that these are overall lower in trial subjects. This effect, at least to some extent, can be explained by the more advanced stages of cancer of trial subjects. This analysis also reveals that for stage IV cancer, colorectal cancer patients have a better chance of survival than breast cancer patients. On the other hand, for all other stages, breast cancer patients have better survival than colorectal cancer patients. Comparison of survival in different stages of disease between the two datasets reveals that subjects with stage IV cancer from the trials dataset have a lower chance of survival than matching stage IV subjects from TCGA. One likely explanation for this observation is that stage IV trial subjects have lower survival rates since their cancer is less likely to respond to treatment. To conclude, we present here a newly available clinical trials dataset which allowed for the integration of patient-level data from many cancer clinical trials. Our comprehensive analysis reveals that cancer-related clinical trials are not representative of general cancer patient populations, mostly due to their focus on the more advanced stages of the disease. These and other limitations of clinical trials data should, perhaps, be taken into consideration in medical research and in the field of precision medicine. PMID:26776196
Geifman, Nophar; Butte, Atul J
Open clinical trial data offer many opportunities for the scientific community to independently verify published results, evaluate new hypotheses and conduct meta-analyses. These data provide a springboard for scientific advances in precision medicine but the question arises as to how representative clinical trials data are of cancer patients overall. Here we present the integrative analysis of data from several cancer clinical trials and compare these to patient-level data from The Cancer Genome Atlas (TCGA). Comparison of cancer type-specific survival rates reveals that these are overall lower in trial subjects. This effect, at least to some extent, can be explained by the more advanced stages of cancer of trial subjects. This analysis also reveals that for stage IV cancer, colorectal cancer patients have a better chance of survival than breast cancer patients. On the other hand, for all other stages, breast cancer patients have better survival than colorectal cancer patients. Comparison of survival in different stages of disease between the two datasets reveals that subjects with stage IV cancer from the trials dataset have a lower chance of survival than matching stage IV subjects from TCGA. One likely explanation for this observation is that stage IV trial subjects have lower survival rates since their cancer is less likely to respond to treatment. To conclude, we present here a newly available clinical trials dataset which allowed for the integration of patient-level data from many cancer clinical trials. Our comprehensive analysis reveals that cancer-related clinical trials are not representative of general cancer patient populations, mostly due to their focus on the more advanced stages of the disease. These and other limitations of clinical trials data should, perhaps, be taken into consideration in medical research and in the field of precision medicine.
Full Text Available Abstract Background In Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy. Methods Based on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented. Results In Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1 problem analysis, and definition of (2 structural prerequisites and (3 procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs, templates, checklists and other supporting materials for researchers. Conclusion All in all, our problem analyses revealed that
Branda Megan E
Full Text Available Abstract Background Chest pain is a common presenting complaint in the emergency department (ED. Despite the frequency with which clinicians evaluate patients with chest pain, accurately determining the risk of acute coronary syndrome (ACS and sharing risk information with patients is challenging. The aims of this study are (1 to develop a decision aid (CHEST PAIN CHOICE that communicates the short-term risk of ACS and (2 to evaluate the impact of the decision aid on patient participation in decision-making and resource use. Methods/Design This is a protocol for a parallel, 2-arm randomized trial to compare an intervention group receiving CHEST PAIN CHOICE to a control group receiving usual ED care. Adults presenting to the Saint Mary's Hospital ED in Rochester, MN USA with a primary complaint of chest pain who are being considered for admission for prolonged ED observation in a specialized unit and urgent cardiac stress testing will be eligible for enrollment. We will measure the effect of CHEST PAIN CHOICE on six outcomes: (1 patient knowledge regarding their short-term risk for ACS and the risks of radiation exposure; (2 quality of the decision making process; (3 patient and clinician acceptability and satisfaction with the decision aid; (4 the proportion of patients who decided to undergo observation unit admission and urgent cardiac stress testing; (5 economic costs and healthcare utilization; and (6 the rate of delayed or missed ACS. To capture these outcomes, we will administer patient and clinician surveys after each visit, obtain video recordings of the clinical encounters, and conduct 30-day phone follow-up. Discussion This pilot randomized trial will develop and evaluate a decision aid for use in ED chest pain patients at low risk for ACS and provide a preliminary estimate of its effect on patient participation in decision-making and resource use. Trial registration Clinical Trials.gov Identifier: NCT01077037
Melanie Sekeres; Gold, Jennifer L.; An-Wen Chan; Joel Lexchin; David Moher; Van Laethem, Marleen L. P.; James Maskalyk; Lorraine Ferris; Nathan Taback; Rochon, Paula A
BACKGROUND: In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. Th...
Sekeres, Melanie; Jennifer L Gold; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L. P.; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Paula A Rochon
Background In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The...
Atkinson, Nancy L; Saperstein, Sandra L; Massett, Holly A; Leonard, Colleen Ryan; Grama, Lakshmi; Manrow, Rick
Advancing the clinical trial research process to improve cancer treatment necessitates helping people with cancer identify and enroll in studies, and researchers are using the power of the Internet to facilitate this process. This study used a content analysis of online cancer clinical trial search tools to understand what people with cancer might encounter. The content analysis revealed that clinical trial search tools were easy to identify using a popular search engine, but their functionality and content varied greatly. Most required that users be fairly knowledgeable about their medical condition and sophisticated in their web navigation skills. The ability to search by a specific health condition or type of cancer was the most common search strategy. The more complex tools required that users input detailed information about their personal medical history and have knowledge of specific clinical trial terminology. Search tools, however, only occasionally advised users to consult their doctors regarding clinical trial decision-making. This, along with the complexity of the tools suggests that online search tools may not adequately facilitate the clinical trial recruitment process. Findings from this analysis can be used as a framework from which to systematically examine actual consumer experience with online clinical trial search tools.
... HUMAN SERVICES Food and Drug Administration Analgesic Clinical Trials Innovation, Opportunities, and... Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative. The goal of the... major gaps in scientific information, which can slow down analgesic clinical trials and analgesic...
Lee Su Jin
Full Text Available Abstract Background In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied. Methods Between July 1st and November 30th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS score. Results In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%. The awareness of clinical trials was substantially higher in patients who had a higher level of education (pp=0.004, and had a higher economic status (p=0.001. However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%, limited treatment options (n=178, 26.4%, and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%. Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p Conclusions This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.
The process of opening a cancer clinical trial for patient accrual often takes years, and research has shown that trials which are slow to register patients often fail to finish. Following a thorough review, NCI’s Operational Efficiency Working Group prod
Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian;
Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them...
Hietanen, P; Aro, A R; Holli, K;
The aim of this study was to determine the communicative needs of the patients in the context of being invited to participate in a clinical trial. A questionnaire was sent to 299 patients with breast cancer randomised in a trial of adjuvant therapy. It was returned by 261 (87%) of them. Ninety-on...
Pedersen, Allan Gorm; Petersen, O B; Wara, P;
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...
King, G. J.; Spiekerman, C.F.; Greenlee, G.M.; Huang, G J
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.
Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael
Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment. Availability http://www.rfdn.org/bioinfo/CTMS/ctms.html. PMID:21670796
U.S. Department of Health & Human Services — The National Database for Clinical Trials Related to Mental Illness (NDCT) is an extensible informatics platform for relevant data at all levels of biological and...
LeBlanc, Thomas W.; Lodato, Jordan E.; Currow, David C; Abernethy, Amy P.
Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. Through their experience with designing and deploying a social-marketing based protocol, the authors show that a carefully crafted recruitment and retention protocol can be effective.
S. Lees; C. Cook; A. Vallely; N. Desmond; C. Allen; K. Kiro; J. Wamoji; L. Medard; R. Pool; R.J. Hayes; D.A. Ross
Background: The performance of coital diaries (CDs) and clinic-based interviews to measure sexual behavior was compared during a pilot study for a Phase III microbicide trial. Methods: In Mwanza, 59 women were enrolled for 4 weeks and provided with 20 placebo gels. Weekly, women were given CDs to co
Research misconduct and fraud in clinical research is an increasing problem facing the scientific community. This problem is expected to increase due to discoveries in central statistical monitoring and with the increase in first-time clinical trial investigators in the increasingly global reach of oncology clinical trials. This paper explores the most common forms of fraud in clinical trials in order to develop offensive and defensive strategies to deal with fraud. The offensive strategies are used when fraud is detected during a trial and the defensive strategies are those design strategies that seek to minimize or eliminate the effect of fraud. This leads to a proposed fraud recovery plan (FRP) that would be specified before the start of a clinical trial and would indicate actions to be taken upon detecting fraud of different types. Statistical/regulatory issues related to fraud include: dropping all patients from a site that committed fraud, or just the fraudulent data (perhaps replacing the latter through imputation); the role of intent-to-treat analysis; effect on a planned interim analysis; effect on stratified analyses and model adjustment when fraud is detected in covariates; effect on trial-wide randomization, etc. The details of a typical defensive strategy are also presented. It is concluded that it is best to follow a defensive strategy and to have an FRP in place to follow if fraud is detected during the trial.
Østergaard, Mikkel; Møller-Bisgaard, Signe
with rheumatoid arthritis (RA). The question is when and how MRI should be used. The present article reviews our knowledge about, and provides suggestions for, the use of MRI in clinical trials, clinical care and clinical registries. In clinical trials, the OMERACT RA MRI scoring system (RAMRIS) is a thoroughly...
Kerr, Douglas S
Over the last 15 years, some 16 open and controlled clinical trials for potential treatments of mitochondrial diseases have been reported or are in progress, and are summarized and reviewed herein. These include trials of administering dichloroacetate (an activator of pyruvate dehydrogenase complex), arginine or citrulline (precursors of nitric oxide), coenzyme Q10 (CoQ10; part of the electron transport chain and an antioxidant), idebenone (a synthetic analogue of CoQ10), EPI-743 (a novel oral potent 2-electron redox cycling agent), creatine (a precursor of phosphocreatine), combined administration (of creatine, α-lipoate, and CoQ10), and exercise training (to increase muscle mitochondria). These trials have included patients with various mitochondrial disorders, a selected subcategory of mitochondrial disorders, or specific mitochondrial disorders (Leber hereditary optic neuropathy or mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). The trial designs have varied from open-label/uncontrolled, open-label/controlled, or double-blind/placebo-controlled/crossover. Primary outcomes have ranged from single, clinically-relevant scores to multiple measures. Eight of these trials have been well-controlled, completed trials. Of these only 1 (treatment with creatine) showed a significant change in primary outcomes, but this was not reproduced in 2 subsequent trials with creatine with different patients. One trial (idebenone treatment of Leber hereditary optic neuropathy) did not show significant improvement in the primary outcome, but there was significant improvement in a subgroup of patients. Despite the paucity of benefits found so far, well-controlled clinical trials are essential building blocks in the continuing search for more effective treatment of mitochondrial disease, and current trials based on information gained from these prior experiences are in progress. Because of difficulties in recruiting sufficient mitochondrial disease patients
Crittenden, M.; Kohrt, H.; Levy, R.; Jones, J.; Camphausen, K.; Dicker, A.; Demaria, S.; Formenti, S.
Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an absco...
Fürdös, Irene; Fazekas, Judit; Singer, Josef; Jensen-Jarolim, Erika
In human medicine clinical trials are legally required for drug development and approval. In contrast, clinical trials in small animal cancer patients are less common and legally perceived as animal experiments. Comparative oncology has been recognized as a method to speed up the development of medications by introducing animal patients with naturally developing tumours. In such cases, using animal patients would generate more robust data, as their spontaneous disease resembles the “real life...
A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom
革军; 王臻; 刘鹏; 栗向东; 陈国景
目的 针对儿童股骨下段恶性骨肿瘤的诸多治疗方法中存在的问题,本课题组首次提出具有双屈伸运动人工半膝关节(双动半膝关节)的概念,进行其运动轨迹规律及实验性临床研究.方法 以Mimics/Geomagic/Pro-E软件的设计路线为技术路线.基于成人膝关节标本的CT数据,利用数控铣床机加工制作双动半膝关节假体,进行体外实验研究其运动参数特点,最后进行实验性临床研究.结果 离体实验结果:股骨内侧髁屈曲面球心位移在正常膝关节组为(2.59±0.43)mm,双动半膝关节组为(2.22±0.52) mm,全膝关节组为(1.18±0.43) mm；股骨外侧髁屈曲面球心位移在正常膝关节组为(11.95±6.62) mm,双动半膝关节组为(11.25±6.19)mm,全膝关节组为(1.26±0.42) mm；相对胫骨最大旋转角度在正常膝关节组为13.17°±7.58°,双动半膝关节组为11.69°±6.49°,全膝关节组为5.40°±1.29°.完成探索性临床试验,术后患者恢复良好,效果满意.结论 运动参数分析证明双动半膝关节接近正常膝关节运动模式,双动半膝关节为治疗儿童股骨下段恶性肿瘤提供了全新的理念和思路,新型附丽概念和新型韧带附丽装置为膝关节韧带功能重建提出新的解决方案.%Objective Aim at the problems in the treatments of the children malignant bone tumor of distal femur,we put forward the concept of the dual mobility hemi-knee prosthesis and try to perform the motion parameters analysis and the pilot clinical trials.Methods Base on the CT data from samples of knee joint in adult,we adopted the Mimics/Geomagic/Pro-E software and computer numerical control milling machine technology to design and produce the dual mobility hemi-knee artificial prosthesis,and then motion parameters was analyzed in vitro test,and at last pilot clinical trial was performed.Results In vitro experiment showed that the displacement of the internal femoral condyle flexion facet center was (2
Alemayehu, Demissie; Anziano, Richard J; Levenstein, Marcia
The increased demand for transparency and disclosure of data from clinical trials sponsored by pharmaceutical companies poses considerable challenges and opportunities from a statistical perspective. A central issue is the need to protect patient privacy and adhere to Good Clinical and Statistical Practices, while ensuring access to patient-level data from clinical trials to the wider research community. This paper offers options to navigate this dilemma and balance competing priorities, with emphasis on the role of good clinical and statistical practices as proven safeguards for scientific integrity, the importance of adopting best practices for reporting of data from secondary analyses, and the need for optimal collaboration among stakeholders to facilitate data sharing.
Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.
Photodynamic therapy(PDT) has been demonstrated to effectively kill human periopathogens in vitro. To evaluate the efficacy of PDT in vivo a series of clinical trials was carried out in multiple centers and populations. Clinical parameters including clinical attachment level, pocket probing depth and bleeding on probing were all evaluated. All groups received the standard of care, scaling and root planing, and the treatment group additionally received a single treatment of PDT. Of the total 309 patients and over 40,000 pockets treated in these 5 trials it was determined that photodynamic therapy provided a statistically significant improvement in clinical parameters over scaling and root planing alone.
Reekie, J; Mocroft, A; J, Neaton;
and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates...
Muirhead, Robb J
This paper explores an approach to Bayesian sample size determination in clinical trials. The approach falls into the category of what is often called "proper Bayesian", in that it does not mix frequentist concepts with Bayesian ones. A criterion for a "successful trial" is defined in terms of a posterior probability, its probability is assessed using the marginal distribution of the data, and this probability forms the basis for choosing sample sizes. We illustrate with a standard problem in clinical trials, that of establishing superiority of a new drug over a control.
Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos. PMID:20734279
Information on patients' quality of life (QOL) will give a more comprehensive evaluation of the treatment outcome than only measures of tumour response and survival. Psychosocial indicators have rarely been used in clinical trials. This may in part be explained by physicians' lack of familiarity with these measures, methodological insufficiency and a basic philosophical reason, i.e., most doctors tend to focus on curative treatment and not on palliative treatment. A series of QOL questionnaires has been validated in the last decade for use in cancer clinical trials. Selection of the optimal method in the given trial is important. The trial ought to be designed so the proportion of missing data is low. QOL should be used as an end point in selective trials with an optimal study design and with a study coordinator who is willing to collect QOL data.
Smed, Marie; Getz, Kenneth A
Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process. PMID:23454567
Russell Ian T; Linck Pat; Hounsome Barry; Edwards Rhiannon T
Abstract Background There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC) does not require a standard operating procedure (SOP) for economic e...
Full Text Available Abstract Background Since siblings of pediatric cancer patients are at risk for emotional, behavioral, and social problems, there is considerable interest in development of early psychological interventions. This paper aimed at evaluating the effectiveness of a two-session psychological intervention for siblings of newly diagnosed pediatric cancer patients. Methods Thirty siblings age 6-17 years were randomly assigned to an intervention group or an active control group with standard psychosocial care. The manualized intervention provided to siblings in the first 2 months after the cancer diagnosis of the ill child included medical information, promotion of coping skills, and a psychoeducational booklet for parents. At 4 to 6 weeks, 4 months, and 7 months after the diagnosis, all siblings and their parents completed measures (from standardized instruments of social support, quality of life, medical knowledge, posttraumatic stress symptoms, and anxiety. Results At follow-up siblings in the intervention group showed better psychological well-being, had better medical knowledge, and reported receiving social support from more people. However, the intervention had no effects on posttraumatic stress symptoms and anxiety. Conclusions The results of this pilot trial suggest that a two-session sibling intervention can improve siblings' adjustment, particularly psychological well-being, in the early stage after a cancer diagnosis. Trial Registration ClinicalTrials.gov NCT00296907
Hart, Tessa; Bagiella, Emilia
The growth of evidence-based medicine means that both researchers and clinicians must grasp the complex issues involved in implementing clinical trials, which are especially challenging for the behavioral (experience-based) treatments that predominate in rehabilitation. In this article we discuss selected issues germane to the design, implementation, and analysis of group-level clinical trials in rehabilitation. We review strengths, weaknesses, and best applications of 1-sample, between-subjects, and within-subjects study designs, including newer models such as practical clinical trials and point-of-care trials. We also discuss the selection of appropriate control conditions against which to test rehabilitation treatments, as well as issues related to trial blinding. In a section on treatment definition, we discuss the challenges of specifying the active ingredients in the complex interventions that are widely used in rehabilitation, and present an illustration of 1 approach to defining treatments via the learning mechanisms that underlie them. Issues related to treatment implementation are also discussed, including therapist allocation and training, and assessment of treatment fidelity. Finally we consider 2 statistical topics of particular importance to many rehabilitation trials: the use of multiple or composite outcomes, and factors that must be weighed in estimating sample size for clinical trials.
Gluud, Christian; Nikolova, Dimitrinka
The number of publications on clinical trials is unknown as well as the countries publishing most trial reports. To try to examine these questions we performed an ecological study.......The number of publications on clinical trials is unknown as well as the countries publishing most trial reports. To try to examine these questions we performed an ecological study....
Katz, Michael G; Fargnoli, Anthony S; Kendle, Andrew P; Hajjar, Roger J; Bridges, Charles R
The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060
Emma L. Healey
Full Text Available Background: Long-term conditions (LTCs are important determinants of quality of life and healthcare expenditure worldwide. Whilst multimorbidity is increasingly the norm in primary care, clinical guidelines and the delivery of care remain focused on single diseases, resulting in poorer clinical outcomes. Osteoarthritis, and anxiety and/or depression frequently co-occur with other LTCs, yet are seldom prioritized by the patient or clinician, resulting in higher levels of disability, poorer prognosis, and increased healthcare costs. Objective: To examine the feasibility and acceptability of an integrated approach to LTC management, tackling the under-diagnosis and under-management of osteoarthritis-related pain and anxiety and/or depression in older adults with other LTCs in primary care. Design: The ENHANCE study is a pilot stepped-wedge cluster randomized controlled trial to test the feasibility and acceptability of a nurse-led ENHANCE LTC review consultation for identifying, assessing, and managing joint pain, and anxiety and/or depression in patients attending LTC reviews. Specific objectives (process evaluation and research outcomes will be achieved through a theoretically informed mixed-methods approach using participant self-reported questionnaires, a medical record review, an ENHANCE EMIS template, qualitative interviews, and audio recordings of the ENHANCE LTC review. Discussion: Success of the pilot trial will be measured against the level of the primary care team engagement, assessment of training delivery, and degree of patient recruitment and retention. Patient satisfaction and treatment fidelity will also be explored. ISRCTN registry number: 12154418. Journal of Comorbidity 2015;5(1:135–149
SHANG Hong-cai; XU Hong-juan; CHEN Jing; ZHANG Bo-li; LI You-ping; Mike J Clarke
Clinical research methods have been rapidly developing, and the design of clinical trials including traditional Chinese medicine is advancing. To a certain extent, all of these ensure that the results of clinical research are objective and scientific, but whether these results and the resulting guidelines or consensus have much practical significance on clinical practice is still controversial. The authors engage in both clinical practice and clinical research; they strongly feel that it is necessary to discuss the relationship between clinical trials and clinical practice. This essay discusses this relationship in four parts.
... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA), Baltimore District Office,...
FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S; Galvin, James; Knopp, Michael V; Michalski, Jeff M; Rosen, Mark A; Bradley, Jeffrey D; Shankar, Lalitha K; Laurie, Fran; Cicchetti, M Giulia; Moni, Janaki; Coleman, C Norman; Deye, James A; Capala, Jacek; Vikram, Bhadrasain
Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.
Mackiewicz, Jacek; Mackiewicz, Andrzej
Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869
Lessard Martin R
Full Text Available Abstract Background Weaning is the process during which mechanical ventilation is withdrawn and the work of breathing is transferred from the ventilator back to the patient. Prolonged weaning is associated with development of ventilator-related complications and longer stays in the Intensive Care Unit (ICU. Computerized or Automated Weaning is a novel weaning strategy that continuously measures and adapts ventilator support (by frequently measuring and averaging three breathing parameters and automatically conducts Spontaneous Breathing Trials to ascertain whether patients can resume autonomous breathing. Automated Weaning holds promise as a strategy to reduce the time spent on the ventilator, decrease ICU length of stay, and improve clinically important outcomes. Methods/Design A pilot weaning randomized controlled trial (RCT is underway in the ICUs of 8 Canadian hospitals. We will randomize 90 critically ill adults requiring invasive ventilation for at least 24 hours and identified at an early stage of the weaning process to either Automated Weaning (SmartCare™ or Protocolized Weaning. The results of a National Weaning Survey informed the design of the Protocolized Weaning arm. Both weaning protocols are operationalized in Pressure Support mode, include opportunities for Spontaneous Breathing Trials, and share a common sedation protocol, oxygen titration parameters, and extubation and reintubation criteria. The primary outcome of the WEAN study is to evaluate compliance with the proposed weaning and sedation protocols. A key secondary outcome of the pilot RCT is to evaluate clinician acceptance of the weaning and sedation protocols. Prior to initiating the WEAN Study, we conducted a run-in phase, involving two patients per centre (randomizing the first participant to either weaning strategy and assigning the second patient to the alternate strategy to ensure that participating centres could implement the weaning and sedation protocols and
Full Text Available Abstract Background Randomised controlled clinical trials are performed to resolve uncertainty concerning comparator interventions. Appropriate acknowledgment of uncertainty enables the concurrent achievement of two goals : the acquisition of valuable scientific knowledge and an optimum treatment choice for the patient-participant. The ethical recruitment of patients requires the presence of clinical equipoise. This involves the appropriate choice of a control intervention, particularly when unapproved drugs or innovative interventions are being evaluated. Discussion We argue that the choice of a control intervention should be supported by a systematic review of the relevant literature and, where necessary, solicitation of the informed beliefs of clinical experts through formal surveys and publication of the proposed trial's protocol. Summary When clinical equipoise is present, physicians may confidently propose trial enrollment to their eligible patients as an act of therapeutic beneficence.
Arjona, A; Nuskey, B; Rabasseda, X; Arias, E
As the pharmaceutical industry strives to meet the ever-increasing complexity of drug development, new technology in clinical trials has become a beacon of hope. With big data comes the promise of accelerated patient recruitment, real-time monitoring of clinical trials, bioinformatics empowerment of quicker phase progression, and the overwhelming benefits of precision medicine for select trials. Risk-based monitoring stands to benefit as well. With a strengthening focus on centralized data by the FDA and industry's transformative initiative, TransCelerate, a new era in trial risk mitigation has begun. The traditional method of intensive on-site monitoring is becoming a thing of the past as statistical, real-time analysis of site and trial-wide data provides the means to monitor with greater efficiency and effectiveness from afar. However, when it comes to big data, there are challenges that lie ahead. Patient privacy, commercial investment protection, technology woes and data variability are all limitations to be met with considerable thought. At the Annual Meeting of the American Academy of Dermatology this year, clinical trials on psoriasis, atopic dermatitis and other skin diseases were discussed in detail. This review of clinical research reports on novel therapies for psoriasis and atopic dermatitis reveals the impact of these diseases and the drug candidates that have been successful in phase II and III studies. Data-focused highlights of novel dermatological trials, as well as real-life big data approaches and an insight on the new methodology of risk-based monitoring, are all discussed in this edition of Developments in Clinical Trials. PMID:25187907
Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher
Objective Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. Methods We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Results Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. Conclusion No failure risk rate per development phase is available for ATMPs. The discontinuation rate may
Califf, Robert M; Sugarman, Jeremy
The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care. PMID:26374676
Califf, Robert M; Sugarman, Jeremy
The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care.
Tétreault, Pascal; Mansour, Ali; Vachon-Presseau, Etienne; Schnitzer, Thomas J.; Apkarian, A. Vania
Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active
Philip Marcus Sinnett
Full Text Available We examined the use of clinical trials registries in published systematic reviews and meta-analyses from clinical neurology. A review of publications between January 1, 2008 and December 31, 2014 from five neuroscience journals (Annals of Neurology, Brain, Lancet Neurology, Neurology, and The Neuroscientist was performed to identify eligible systematic reviews. The systematic reviews comprising the final sample were independently appraised to determine if clinical trials registries had been included as part of the search process. Studies acknowledging the use of a trials registry were further examined to determine whether trial data had been incorporated into the analysis. The initial search yielded 194 studies, of which 78 systematic reviews met the selection criteria. Of those, five acknowledged the use of a specific clinical trials registry: four reviewed unpublished trial data and two incorporated unpublished trial data into their results. Based on our sample of systematic reviews, there was no increase in the use of trials registries in systematic review searches over time. Few systematic reviews published in clinical neurology journals included data from relevant clinical trials registries.
Veena D Joshi
Full Text Available Context: Studies have reported that clinical research has experienced tremendous growth during past few decades with many multinational pharmaceutical companies recruiting millions of Indians in clinical trials (CTs. However, there is hardly any literature that talks about the participants, their knowledge, and awareness of CTs. It is important that the general public is aware about CTs so that they can take their own informed decision to participate in CTs. Aim: To assess public awareness, perceptions, and attitudes toward CTs and their views on various methods to create awareness about CTs. Materials and Methods: Cross sectional survey was conducted with 200 non trial participants (NTPs and 40 trial participants (TPs. Results: TPs were significantly (P < 0.0001 older than NTPs. More than 80% of both TPs and NTPs mentioned participation in CT helps advance medical science and strongly felt that there is a need to create awareness about CTs. Nearly 70% of TPs could not remember the phase of the trial while 20% did not know which type of trial they had participated . The main reason for participation in the trial was physician′s advice. About 80% of both TPs and NTPs felt that participation in CT will increase with free medications and advice from friends/relatives who had good experience with trial. Conclusion: Results of this pilot study revealed need to create CT awareness among the general public. However, considering ethno-cultural, regional, and literacy-level differences throughout the country, a nationwide study would be appropriate to provide reliable results about awareness of CTs among Indians.
Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua
Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria.
Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua
Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681
Robert D. Chow
Full Text Available Background: To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. Objective: To determine the preferences of patients in the design of cardiovascular trials. Design: Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. Participants: One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Key results: Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004 on a scale of 1–6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001, angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001, and stroke (4.73 vs. 2.43, p<0.001. Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%, incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers, and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect. Conclusions: Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but
Schumacher, Michael; Denier, Christian; Oudinet, Jean-Paul; Adams, David; Guennoun, Rachida
Since the first pioneering studies in the 1990s, a large number of experimental animal studies have demonstrated the neuroprotective efficacy of progesterone for brain disorders, including traumatic brain injury (TBI). In addition, this steroid has major assets: it easily crosses the blood-brain-barrier, rapidly diffuses throughout the brain and exerts multiple beneficial effects by acting on many molecular and cellular targets. Moreover, progesterone therapies are well tolerated. Notably, increased brain levels of progesterone are part of endogenous neuroprotective responses to injury. The hormone thus emerged as a particularly promising protective candidate for TBI and stroke patients. The positive outcomes of small Phase 2 trials aimed at testing the safety and potential protective efficacy of progesterone in TBI patients then provided support and guidance for two large, multicenter, randomized and placebo-controlled Phase 3 trials, with more than 2000 TBI patients enrolled. The negative outcomes of both trials, named ProTECT III and SyNAPSE, came as a big disappointment. If these trials were successful, progesterone would have become the first efficient neuroprotective drug for brain-injured patients. Thus, progesterone has joined the numerous neuroprotective candidates that have failed in clinical trials. The aim of this review is a reappraisal of the preclinical animal studies, which provided the proof of concept for the clinical trials, and we critically examine the design of the clinical studies. We made efforts to present a balanced view of the strengths and limitations of the translational studies and of some serious issues with the clinical trials. We place particular emphasis on the translational value of animal studies and the relevance of TBI biomarkers. The probability of failure of ProTECT III and SyNAPSE was very high, and we present them within the broader context of other unsuccessful trials. PMID:26598278
Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian;
Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them...... to qualify for authorship as defined by the International Committee of Medical Journal Editors. Therefore, rules for authorship in multi-centre trials are strongly recommended. We propose two contracts to prevent conflicts regarding authorship; both are freely available for use without pay but with reference...
Caroline Guilherme; Gabriela Roberta Ribeiro; Sílvia Caldeira; Cristina Mara Zamarioli; Ana Railka de Souza Oliveira-Kumakura; Ana Maria de Almeida; Emilia Campos de Carvalho
This study aimed to evaluate the effect of the spiritual support intervention on spirituality and the clinical parameters of women who have undergone mastectomy. This is a pilot study of a randomized clinical trial. The spiritual support intervention was composed of meditation, guided imagery, music, and respiratory relaxation. The outcomes were: spirituality, blood pressure, heart rate, and oxygen saturation. A total of 27 patients were recruited for the study (intervention group, n = 13; co...
Full Text Available Jean Davignon1, Lawrence A Leiter21Clinical Research Institute of Montreal, Montreal, QC, Canada; 2Division of Endocrinology and Metabolism, St Michael’s Hospital, Toronto, ON, CanadaBackground: The multiple effects (ie, pleiotropic effects of statins have received increasing recognition and may have clinical applicability across a broad range of cardiovascular and noncardiovascular conditions. Objective: To determine the relevance and significance of ongoing clinical trials of the pleiotropic effects of statins, focusing on nonlipid effects. Method: Ongoing trials were identified through personal communication, reports presented at scientific meetings (2000–2004, and queries made to AstraZeneca, Bristol-Myers Squibb Co, Merck & Co, Novartis, and Pfizer, manufacturers of the currently marketed statins. Published trials and other source material were identified through electronic searches on MEDLINE (1990–2003, abstract books, and references identified from bibliographies of pertinent articles. Eligible studies were the clinical trials of statins currently under way in which primary or secondary outcomes included the statins’ nonlipid (ie, pleiotropic effect(s. Data were extracted and trial quality was assessed by the authors. Results: Of the 22 ongoing trials of the nonlipid effects of statins identified, 10 assessed inflammatory markers and plaque stabilization, 4 assessed oxidized low density lipoprotein/vascular oxidant stress, 3 assessed end-stage renal disease, 3 assessed fibrinogen/viscosity, 2 assessed endothelial function, 2 assessed acute coronary syndrome, 2 assessed aortic stenosis progression, and 1 each assessed hypertension, osteoporosis, ischemic burden, Alzheimer’s disease, multiple sclerosis, and stroke (outcomes often overlapped. Conclusion: Given the excellent safety and tolerability of statins as a class, full exploration of their pleiotropic effects has the potential to provide additional benefits to many patients
Brooks, Sandra E; Muller, Carolyn Y; Robinson, William; Walker, Eleanor M; Yeager, Kate; Cook, Elise D; Friedman, Sue; Somkin, Carol P; Brown, Carol Leslie; McCaskill-Stevens, Worta
Racial and ethnic diversity has historically been difficult to achieve in National Cancer Institute-sponsored clinical trials, even while as many as 80% of those trials have faced difficulty in meeting overall recruitment targets. In an attempt to address these issues, NRG Oncology recently convened a comprehensive workshop titled "Clinical Trials Enrollment: Challenges and Opportunities." Discussants at the workshop included representatives of the three legacy groups of the NRG (ie, Gynecologic Oncology Group, National Surgical Adjuvant Breast and Bowel Program, and Radiation Therapy Oncology Group), a minority-based community clinical oncology program, a large integrated health care system, the leadership of the National Cancer Institute, and a large patient advocacy group. This article summarizes the concepts discussed at the workshop, which included: needs assessments, infrastructural support, training of investigators and research staff, specific clinical trial recruitment strategies (both system and community based), and development and mentoring of young investigators. Many new, more specific tactics, including use of diverse cancer care settings, direct-to-consumer communication, and the need for centralized information technology such as the use of software to match trials to special populations, are presented. It was concluded that new, innovative trial designs and the realities of limited funding would require the adoption of effective and efficient recruiting strategies, specialized training, and stakeholder engagement. US clinical research programs must generate and embrace new ideas and pilot test novel recruitment strategies if they are to maintain their historic role as world leaders in cancer care innovation and delivery. PMID:26464496
Sun, Hua-long; Dai, Nan
For pharmaceutical industries, clinical data is one of the most valuable deliverables. It is also the basis of analysis, submission, approval, labeling and marketing of a drug product. To ensure the integrity and reliability of clinical data, a scientific standardized quality control (QC) has to be established at each step of a clinical trial. Data validation is conducted to ensure the reasonability and compliance of clinical data by checking data quality before the data is statistically analyzed. This paper focuses on purpose of data validation, creation of data validation plan, rationale of data validation, types of data validation and performance of user acceptance testing on clinical database. PMID:26911047
The heterogeneity of methods used in multiple sclerosis (MS) clinical trials prevents fair comparison of trials and reduces confidence in the validity of the therapeutic claims made. The validity of recent clinical trials is lessened by the following factors: MS shows variability in type and in rates of disease progression; primary progressive MS may not be the same disease as typical MS, and inclusion of subjects with this condition may have skewed results of trials to date. Using a new model, "relapsing-remitting" and "secondary progressive" MS are considered to represent earlier and later stages of the same disease. The variety of endpoints used in clinical trials impairs comparisons. The differences between EDSS stages vary at different levels and it is concluded that this is no longer the most appropriate tool, although it could be improved by modifying the scoring or scales to assess certain focused items. The clinical significance of a reduction in relapse rate is questioned, as are the inclusion criteria employed in recent trials. Drug doses based upon body mass differ from those based on surface area, making it hard to compare the effects of trial agents. The definitions of "sustained worsening" are not uniform and the concept is complicated by regression to the mean. Trials should continue for long enough to be sure that any beneficial effects noted are permanent. Although extensions provide better long-term data, they are usually statistically underpowered and clinically and demographically imbalanced. Ethically, if benefit is determined to be present, a trial should be stopped so that all subjects may be offered the beneficial agent, but determination of benefit may be imperfect. The "intention to treat" paradigm is a shibboleth, providing data on effectiveness rather than efficacy. The simple listing and addition of unwanted effects (UEs) is unproductive. Trivial UEs detract little from quality of life and are unimportant. The remainder should be
Ahmed A. Zeeneldin
Full Text Available Registering clinical trials (CTs in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP, the continental Pan-African CT Registry (PACTR and the US clinicaltrials.gov (CTGR. In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage was 686 (0.30% in ICTRP, 56 (11.3% in PACTR and 548 (0.34% in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended.
Sánchez-Martín, J; Beltrán-Heredia, J; Solera-Hernández, C
A new tannin-based coagulant-flocculant (Tanfloc) was tested for water treatment at a pilot plant level. Four types of water sample were treated: surface water (collected from a river), and municipal, textile industry (simulated by a 100 mg L(-1) aqueous solution of an acid dye), and laundry (simulated by a 50 mg L(-1) aqueous solution of an anionic surfactant) wastewaters. The pilot plant process consisted of coagulation, sedimentation, and filtration. The experiments were carried out with an average coagulant dosage of 92.2 mg L(-1) (except in the case of the surface water for which the dosage was 2 mg L(-1)). The efficacy of the water purification was notable in every case: total turbidity removal in the surface water and municipal wastewater, about 95% dye removal in the case of the textile industry wastewater, and about 80% surfactant removal in the laundry wastewater. Filtration improved the removal of suspended solids, both flocs and turbidity, and slightly improved the process as a whole. The efficiency of Tanfloc in these pilot studies was similar to or even better than that obtained in batch trials. PMID:20580152
Annapureddy, N; Devilliers, H; Jolly, M
Therapeutic advances in systemic lupus erythematosus (SLE) are greatly needed. Despite advances in our knowledge of pathogenesis of the disease and targets, treatment remains a significant challenge. Finding effective and relatively safe medications remains one of the top priorities. SLE significantly impairs quality of life (QoL), and patient-reported outcomes (PROs) measure a unique aspect of the disease not captured by disease activity. Inclusion of PRO measurements is encouraged in SLE clinical trials, as they allow capturing benefits of a proposed intervention in language patients can relate to and in areas deemed pertinent and important to and by patients. Availability of patient-reported and patient-centric clinical trials data may facilitate patients in informed and shared decision making, and allow for comparative cost-effectiveness evaluation for future resource allocation and reimbursements. Herein we review clinical trials with biologic therapies wherein PRO tools were included in the study design. PMID:27497256
Eskes, Anne M; Brölmann, Fleur E; Sumpio, Bauer E;
The care for chronic and acute wounds is a substantial problem around the world. This has led to a plethora of products to accelerate healing. Unfortunately, the quality of studies evaluating the efficacy of such wound care products is frequently low. Randomized clinical trials are universally...... acknowledged as the study design of choice for comparing treatment effects, as they eliminate several sources of bias. We propose a framework for the design and conduct of future randomized clinical trials that will offer strong scientific evidence for the effectiveness of wound care interventions. While...... 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...
Full Text Available Background. “Fructus Mume or Dark Plum” (pilule form has been used for many years in Traditional Chinese Medicine (TCM and may be a valid treatment for type 2 diabetes mellitus (T2DM. Aim. One aspect toward efficacy validation is the evaluation of the blood glucose-lowering effect of Fructus Mume (FM with T2DM patients in a randomized controlled trial (RCT. Methods. This pilot study uses a RCT procedure to assess efficacy of FM and Metformin. The trial was for 12 weeks, with 80 T2DM subjects. Both groups were standardized in their diet and exercise routine. Comparisons of several variables were analyzed. Results. No significant differences were found between groups in the fasting and postprandial glucose levels although both had significant decreases. The values of glycosylated hemoglobin were significantly reduced in both groups. For patients whose body mass index (BMI was 25, both FM and Metformin significantly reduce the BMI. Conclusions. In this pilot study, it was demonstrated that Fructus Mume formula may reduce the levels of blood glucose in patients with type 2 diabetes.
Full text: Imaging holds a promising place in the drug development process and clinical trials. In recent times, scientists and researchers have realized that imaging enables them to look for new surrogate endpoints and accelerate the process of drug development. As the number of such trials is increasing every year, there is a growing awareness for the need of quality in imaging trials, so as to avoid imaging issues, reduce losses due to non-evaluable imaging and improve subject safety. This paper is an attempt to address the need of standards for good quality image in clinical trials which use imaging. The main focus of the paper is to describe the various acquisition options in PET-CT available for medical imaging, their applicability in drug development process and clinical trials, emphasize the need to identify possible sources that could possibly impact the quality of images, ways of standardizing the equipments and minimizing the variability of different scanners. Additionally this paper will look into the importance of an expert medical imaging group, imaging protocols, quality assurance programs, and image assessment post acquisition for technical compliance and image quality. A reference of standards as prescribed by various scientific bodies and organizations will also be reviewed. In this paper the focus will be mainly to discuss aspects of PET-CT imaging in clinical trials. PET-CT has the potential to be best for response monitoring to therapy and early detection of disease compared to all other imaging modalities such as CT, MRI, gamma camera, SPECT, ultrasonography etc. In research, PET imaging can help in understanding the pharmacokinetics of a molecule, i.e. kinetic modeling and provides various imaging options, qualitative and quantitative. PET-CT provides anatomical as well as functional information and has the potential to be highly reproducible. The paper emphasizes good imaging practices and its relevance, especially when we are not just
Viergever, R.F.; Li, K.
OBJECTIVES: To analyse developments (and their causes) in the number and proportion of clinical trials that were registered in different parts of the world after the International Committee of Medical Journal Editors (ICMJE) announced in 2004 that it would require registration of clinical trials as a condition for publication. SETTING: The International Clinical Trials Registry Platform (ICTRP). DESIGN: The ICTRP database was searched for all clinical trials that were registered up to 31 Dece...
GUZhi-Ping; ZHANGRcn-An; WANGYi-Xin; DANGYong-Zhi; CHENGZhen-Xing; S.J.Scgal
Hypokalemia and irreversible infertility induced by the gossypol treatment have prcvented its clinical use on a large scale as a male contraceptive. In order to avoid these serious side effects, doses of gossypol, both in the loading phase and in the maintenance phase were
Godskesen, T M; Kihlbom, U; Nordin, K; Silén, M; Nygren, P
While participants in clinical oncology trials are essential for the advancement of cancer therapies, factors decisive for patient participation have been described but need further investigation, particularly in the case of phase 3 studies. The aim of this study was to investigate differences in trial knowledge and motives for participation in phase 3 clinical cancer trials in relation to gender, age, education levels and former trial experience. The results of a questionnaire returned from 88 of 96 patients (92%) were analysed using the Mann-Whitney U-test. There were small, barely relevant differences in trial knowledge among patients when stratified by gender, age or education. Participants with former trial experience were less aware about the right to withdraw. Male participants and those aged ≥65 years were significantly more motivated by a feeling of duty, or by the opinions of close ones. Men seem more motivated than women by external factors. With the awareness that elderly and single male participants might be a vulnerable group and participants with former trial experience are less likely to be sufficiently informed, the information consent process should focus more on these patients. We conclude that the informed consent process seems to work well, with good results within most subgroups. PMID:25904313
Russell Ian T
Full Text Available Abstract Background There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC does not require a standard operating procedure (SOP for economic evaluation as a prerequisite for trial unit registration. We judge that such a SOP facilitates the integration of health economics into trials. Methods A collaboration between health economists and trialists at Bangor University led to the development of a SOP for economic evaluation alongside pragmatic trials, in addition to the twenty SOPs required by UKCRC for registration, which include randomisation, data management and statistical analysis. Results Our recent telephone survey suggests that no other UKCRC-registered trials unit currently has an economic SOP. Conclusion We argue that UKCRC should require, from all Trials Units undertaking economic evaluation and seeking registration or re-registration, a SOP for economic evaluation as one of their portfolio of supporting SOPs.
Kočevar Glavač, Nina; Stojilkovski, Katja
In modern medicine and pharmacy, clinical trials represent an important tool for evaluation of safety and efficacy of drugs, including herbal medicines. Specific features of designing and conducting clinical trials in phytotherapy originate in complex chemical composition of medicinal plants or bioactive compounds. The article represents the basics of clinical trials, specific features of clinical trials in phytotherapy, and cases of clinical trials assessing the effectiveness of Echinacea dr...
Soral, P.; Pal, U.; Larson, H. R.; Schroeder, B.
A laboratory-scale galvanic deoxidation technology developed by earlier workers has been improved, with the aim of developing a prototype pilot-scale deoxidation unit. Each deoxidation cell consists of a one end-closed yttria-stabilized zirconia (YSZ) tube coated with a Ni-YSZ cermet anode on the inner walls. The YSZ tube is immersed, with its closed end in the metallic melt, and an oxygen-chemical-potential gradient across the tube is established by passing a reducing gas through the tube. The melt is then deoxidized by short circuiting it with the anode. Through laboratory experimentation, the nature of the anode/electrolyte interface adhesion was identified to be an important factor in obtaining enhanced deoxidation kinetics. The kinetics of oxygen removal from the melt was increased by an order of magnitude with an improved anode/electrolyte interface. A pilot-scale refining unit consisting of 53 cells with the improved anode/electrolyte interface was manufactured, and a field evaluation of the galvanic deoxidation of copper was conducted. The deoxidation-process model was modified to include multiple deoxidation cells, which were required for the pilot-scale trials, and to analyze the effect of electrolyte/electrode adhesion on deoxidation kinetics. Preliminary studies on process component lifetimes were conducted by investigating the thermal cycling, corrosion behavior of the electrolyte, and stability of the cermet anode structure. Based on the results of the field trial and the analyses of the process component lifetime, future work needed toward commercializing the technology is discussed.
Proschan, Michael A; Dodd, Lori E
This paper presents a simple procedure for clinical trials comparing several arms with control. Demand for streamlining the evaluation of new treatments has led to phase III clinical trials with more arms than would have been used in the past. In such a setting, it is reasonable that some arms may not perform as well as an active control. We introduce a simple procedure that takes advantage of negative results in some comparisons to lessen the required strength of evidence for other comparisons. We evaluate properties analytically and use them to support claims made about multi-arm multi-stage designs.
Goodwin, Andrew J
Optimizing care in the ICU is an important goal. The heightened severity of illness in patients who are critically ill combined with the tremendous costs of critical care make the ICU an ideal target for improvement in outcomes and efficiency. Incorporation of evidence-based medicine into everyday practice is one method to optimize care; however, intensivists have struggled to define optimal practices because clinical trials in the ICU have yielded conflicting results. This article reviews examples where such conflicts have occurred and explores possible causes of these discrepant data as well as strategies to better use critical care clinical trials in the future. PMID:22948575
Rossi, Paolo; Fiermonte, Giancarlo; Pierelli, Francesco
The efficacy and tolerability of cinnarizine (75 mg, at bedtime) in migraine prophylaxis and the presence of possible predictive factors for therapeutic responsiveness were evaluated in an open-label pilot trial. Eighty consecutive outpatients suffering from migraine with or without aura participated in the study. After 12 weeks of therapy, 55 patients experienced a greater than 66% reduction in headache frequency and were considered responders. A significant reduction in the number of migraine days (mean reduction 58 +/- 8%) and in intake of medication to treat acute attacks (mean reduction 55 +/- 11%) was also observed. Cinnarizine was well tolerated, as documented by the low number of adverse effects. Failure to respond to previous prophylactic treatments was a negative predictive factor correlated with a poor prognosis. This study, even bearing in mind its limitations as an open-label trial, suggests that cinnarizine might be an effective prophylactic anti-migraine agent. The clinical characteristics of migraine patients do not help to predict response to treatment. PMID:14703897
Full Text Available Abstract Background Patellofemoral pain syndrome is a highly prevalent musculoskeletal overuse condition that has a significant impact on participation in daily and physical activities. A recent systematic review highlighted the lack of high quality evidence from randomised controlled trials for the conservative management of patellofemoral pain syndrome. Although foot orthoses are a commonly used intervention for patellofemoral pain syndrome, only two pilot studies with short term follow up have been conducted into their clinical efficacy. Methods/design A randomised single-blinded clinical trial will be conducted to investigate the clinical efficacy and cost effectiveness of foot orthoses in the management of patellofemoral pain syndrome. One hundred and seventy-six participants aged 18–40 with anterior or retropatellar knee pain of non-traumatic origin and at least six weeks duration will be recruited from the greater Brisbane area in Queensland, Australia through print, radio and television advertising. Suitable participants will be randomly allocated to receive either foot orthoses, flat insoles, physiotherapy or a combined intervention of foot orthoses and physiotherapy, and will attend six visits with a physiotherapist over a 6 week period. Outcome will be measured at 6, 12 and 52 weeks using primary outcome measures of usual and worst pain visual analogue scale, patient perceived treatment effect, perceived global effect, the Functional Index Questionnaire, and the Anterior Knee Pain Scale. Secondary outcome measures will include the Lower Extremity Functional Scale, McGill Pain Questionnaire, 36-Item Short-Form Health Survey, Hospital Anxiety and Depression Scale, Patient-Specific Functional Scale, Physical Activity Level in the Previous Week, pressure pain threshold and physical measures of step and squat tests. Cost-effectiveness analysis will be based on treatment effectiveness against resource usage recorded in treatment logs and
Cesari, Matteo; Pahor, Marco
The term “sarcopenia” describes the progressive decline of muscle mass, strength and function occurring with aging. It is not considered a disease, but the direct consequence of the aging process on the skeletal muscle. Multiple demographic (e.g. gender, race), biological (e.g. inflammatory status) and clinical (e.g. diabetes, metabolic syndrome, congestive heart failure, medications) factors are able to influence (positively or negatively) the skeletal muscle quality and quantity. The extrem...
Chen J; Runyan SA; Robinson MR
June Chen1, Stephen A Runyan1, Michael R Robinson21Department of Biological Sciences, 2Ophthalmology Clinical Research, Allergan, Inc, Irvine, CA, USAIntroduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in gla...
Full Text Available Shourav Yathindranath,1 Amar Kureishi,2 Simranjit Singh,3 Spencer Yeow,3 Grace Geng,4 Karen Wai,1 Audrey Ho,1 Elvira Zenaida Lansang,1 Ken J Lee5 1Feasibility and Site Identification Asia, 2Drug Development Asia, 3Strategic Planning Asia, Quintiles East Asia Private Limited, Singapore; 4People’s Republic of China Site Services, Quintiles, Beijing, People’s Republic of China; 5Asia Site Services, Quintiles East Asia Private Limited, Singapore Introduction: Asia Pacific has and continues to be one of the fastest-growing pharmaceutical markets in the world. This growth has a carry-over effect of driving pharmaceutical research and development investment in the region. Coupled with this, there have been multiple initiatives conducted by governments and other research focused organizations and societies in the region to help support this growth in research. In this report, we discuss the latest developments in pharmaceutical research and development in Asia Pacific and how these various initiatives have made an impact. Methods: An extensive search of the major clinical trial registries, along with the literature and Internet review of the recent developments in clinical trials, was performed comparing two time periods – 2009–2010 and 2011–2012. Results: In overall numbers, the clinical trial industry in Asia Pacific has remained stable when comparing the two time periods, with stable volumes of clinical trial numbers and site numbers. However, on closer inspection, a dynamic change in geography, nature, and therapeutic areas of the trials being conducted is observed. Japan, South Korea, People’s Republic of China, and Taiwan continue to be major clinical trial destinations. Developing countries, such as Indonesia, Vietnam, and Philippines, have seen rising standards of living and medical care; this is starting to impact their contribution to trials. Also, there are an increasing number of local trials in Asia Pacific with a bigger role
Full Text Available Abstract Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.
Full Text Available Shosaku Nomura, Noboru Tanigawa, Yo Kinoshita, Koichi TomodaFirst Department of Internal Medicine, Kansai Medical University, Shinmachi, Hirakata, Osaka, JapanUndergraduate medical education has several problems.1,2 In particular, clinical training, which is the unique feature of medical education, tends to be performed less extensively. In Japan, the current clinical training method is clinical clerkship (CC. CC differs from conventional clinical training, which is study by observation. In CC, the student is a member of the medical team and participates in actual medical care. The student is allowed to practice medical actions in the definite range under the guidance and monitoring of a teaching doctor. Therefore, students can acquire practical clinical abilities. In their study of medical care, students are required to have their own sense of identity and personal responsibility. Clinical training is performed by CC following the original curriculum for diagnoses and treatments in various medical departments.
Díaz Gómez, L; García Villar, C; Seguro Fernández, Á
A clinical trial is an experimental study to evaluate the efficacy and safety of a treatment or diagnostic technique in human beings. To ensure the methodological quality of a clinical trial and the validity of its results, various checklists have been elaborated to identify biases that could invalidate its conclusions. This article focuses on the points we need to consider in the critical evaluation of a clinical trial. We can usually find this information in the "materials and methods" and "results" sections of articles. Randomization, follow-up (or analysis of losses), blinding, and equivalence between groups (apart from the intervention itself) are some key aspects related to design. In the "results" section, we need to consider what measures of clinical efficacy were used (relative risk, odds ratio, or number needed to treat, among others) and the precision of the results (confidence intervals). Once we have confirmed that the clinical trial fulfills these criteria, we need to determine whether the results can be applied in our environment and whether the benefits obtained justify the risks and costs involved.
Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan
Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.
Demirel, Sibel; Argo, Colby; Agarwal, Aniruddha; Parriott, Jacob; Sepah, Yasir Jamal; Do, Diana V; Nguyen, Quan Dong
In this era of evidence-based medicine, significant progress has been made in the field of pharmacotherapeutics for the management of diabetic macular edema (DME). A. number of landmark clinical trials have provided strong evidence of the safety and efficacy of agents such as anti-vascular endothelial growth factors for the treatment of DME. Decades of clinical research, ranging from the early treatment of diabetic retinopathy study to the present-day randomized clinical trials (RCTs) testing novel agents, have shifted the goal of therapy from preventing vision loss to ensuring a maximum visual gain. Systematic study designs have provided robust data with an attempt to optimize the treatment regimens including the choice of the agent and timing of therapy. However, due to a number of challenges in the management of DME with approved agents, further studies are needed. For the purpose of this review, an extensive database search in English language was performed to identify prospective, RCTs testing pharmacological agents for DME. In order to acquaint the reader with the most relevant data from these clinical trials, this review focuses on pharmacological agents that are currently approved or have widespread applications in the management of DME. An update on clinical trials presently underway for DME has also been provided.
Full Text Available In this era of evidence.based medicine, significant progress has been made in the field of pharmacotherapeutics for the management of diabetic macular edema. (DME. A. number of landmark clinical trials have provided strong evidence of the safety and efficacy of agents such as anti.vascular endothelial growth factors for the treatment of DME. Decades of clinical research, ranging from the early treatment of diabetic retinopathy study to the present.day randomized clinical trials. (RCTs testing novel agents, have shifted the goal of therapy from preventing vision loss to ensuring a maximum visual gain. Systematic study designs have provided robust data with an attempt to optimize the treatment regimens including the choice of the agent and timing of therapy. However, due to a number of challenges in the management of DME with approved agents, further studies are needed. For the purpose of this review, an extensive database search in English language was performed to identify prospective, RCTs testing pharmacological agents for DME. In order to acquaint the reader with the most relevant data from these clinical trials, this review focuses on pharmacological agents that are currently approved or have widespread applications in the management of DME. An update on clinical trials presently underway for DME has also been provided.
Weng, Chunhua; Bigger, J Thomas; Busacca, Linda; Wilcox, Adam; Getaneh, Asqual
This paper reports a case study comparing the relative efficiency of using a Diabetes Registry or a Clinical Data Warehouse to recruit participants for a diabetes clinical trial, TECOS. The Clinical Data Warehouse generated higher positive predictive accuracy (31% vs. 6.6%) and higher participant recruitment than the Registry (30 vs. 14 participants) in a shorter time period (59 vs. 74 working days). We identify important factors that increase clinical trial recruitment efficiency and lower cost.
Wildt, Signe; Krag, Aleksander; Gluud, Liselotte
Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published...
López-Sendón Moreno, Jose Luis; García Caldentey, Juan; Trigo Cubillo, Patricia; Ruiz Romero, Carolina; García Ribas, Guillermo; Alonso Arias, M A Alonso; García de Yébenes, María Jesús; Tolón, Rosa María; Galve-Roperh, Ismael; Sagredo, Onintza; Valdeolivas, Sara; Resel, Eva; Ortega-Gutierrez, Silvia; García-Bermejo, María Laura; Fernández Ruiz, Javier; Guzmán, Manuel; García de Yébenes Prous, Justo
Huntington's disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex(®), a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex(®) and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex(®) as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex(®) is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations.Clincaltrals.gov identifier: NCT01502046. PMID:27159993
Jiang, Silis Y; Weng, Chunhua
Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities.
... Medicines for Children The Importance of Children in Clinical Trials Past Issues / Winter 2012 Table of Contents Dr. ... to a parent who asks you why children’s clinical trials are important? Clinical research is critically important to ...
Ghert, M.; Bhandari, M.; Deheshi, B.; Guyatt, G.; Holt, G.; O'Shea, T.; Randall, R. L.; Thabane, L.; Wunder, J.; Evaniew, N.; McKay, P.; Schneider, P.; Turcotte, R.; Madden, K.; Scott, T.; Sprague, S.; Simunovic, N.; Swinton, M.; Racano, A.; Heels-Ansdell, D.; Buckingham, L.; Rose, P.; Brigman, B.; Pullenayegum, E.; Ghert, M.; Evaniew, N.; Mckay, P.; Schneider, P.; Sobhi, G.; Chan, R.; Biljan, M.; Ferguson, P.; Wunder, J.; Griffin, A.; Mantas, I.; Wylie, A.; Han, A.; Grewal, G.; Turcotte, R.; Goulding, K.; Dandachli, F.; Matte, G.; Werier, J.; Abdelbary, H.; Paquin, K.; Cosgrove, H.; Dugal, A-M.; Fetzer, S.; Aikens, W.; Clarkson, P.; Wang, B.; Kondo, L.; Yip, J.; Isler, M.; Mottard, S.; Barry, J.; St Yves, H.; Quach, M.; Assayag, H.; Daoust, K.; Goyette, K.; Projean, D.; Dion, N.; Arteau, A.; Turmel, S.; Bertrand, A.; Gagnon, N.; Labbe, V.; Holt, G.; Halpern, J.; Schwartz, H.; Atkinson, A.; Daniels, J.; Moore, M. S.; Anderson, M.; Gebhardt, M.; Wagner, K.; Patel, H.; Jolin, H.; Anderson, M.; Gebhardt, M.; Allar, B.; Naqvi, M.; Bennett, J.; Albuquerque, S.; Randall, R. L.; Jones, K.; Crabtree, S.; Davis, R.; Sorenson, S.; Healey, J. H.; Galle, J.; O'Neill, G.; Del Corral, B.; Lopez, S.; Galli Serra, M.; Parizzia, W.; Podrzaj, A.; Foa Torres, M.; Clayer, M.; Chai, Y.; Slobodian, P.; Balach, T.; Coyle, K.; LaCasse, R.; Abraham, J.; Morrison, T.; Angelos, M.; Sailor, L.; Sadaka, R.; Miller, B.; Milhem, M.; McCurdy, N.; Kain, J.; Nohr, J.; Johnson, K.; Merriss, A.; Cheng, E.; Luke, D. G.; Scharschmidt, T. J.; Crist, M. K.; Dimeo, A.; Marmon, L.; Reimer, N.; Monson, D.; Oskouei, S.; Lomba, C.; Rogers, S.; Avedian, R.; Jordan, L.; Chinn, S.; Hamilton, M.; Ghert, M.; Evaniew, N.; McKay, P.; Schneider, P.; Sobhi, G.; Chan, R.; Bil-Jan, M.; Ferguson, P.; Wunder, J.; Griffin, A.; Mantas, I.; Wylie, A.; Han, A.; Grewal, G.; Turcotte, R.; Goulding, K.; Dandachli, F.; Matte, G.; Werier, J.; Abdelbary, H.; Paquin, K.; Cosgrove, H.; Dugal, A-M.; Fetzer, S.; Aikens, W.; Clarkson, P.; Wang, B.; Kondo, L.; Yip, J.; Isler, M.; Mottard, S.; Barry, J.; Yves, H. St.; Quach, M.; Assayag, H.; Daoust, K.; Goyette, Kristine; Projean, D.; Dion, N.; Arteau, A.; Turmel, S.; Bertrand, A.; Gagnon, N.; Labbe, V.; Holt, G.; Halpern, J.; Schwartz, H.; Atkinson, A.; Daniels, J.; Moore, M. S.; Anderson, M.; Gebhardt, M.; Wagner, K.; Patel, H.; Jolin, H.; Anderson, M.; Gebhardt, M.; Allar, B.; Naqvi, M.; Bennett, J.; Albuquerque, S.; Randall, R. L.; Jones, K.; Crabtree, S.; Davis, R.; Sorenson, S.; Healey, J. H.; Galle, J.; O'Neill, G.; Del Corral, B.; Lopez, S.; Galli Serra, M.; Parizzia, W.; Podrzaj, A.; Foa Torres, M.; Clayer, M.; Tran, N.; Slobodian, P.; Balach, T.; Coyle, K.; LaCasse, R.; Abraham, J.; Morrison, T.; Angelos, M.; Sailor, L.; Sadaka, R.; Miller, B.; Milhem, M.; McCurdy, N.; Kain, J.; Nohr, J.; Johnson, K.; Merriss, A.; Cheng, E.; Luke, D. G.; Scharschmidt, T. J.; Crist, M. K.; Dimeo, A.; Marmon, L.; Reimer, N.; Monson, D.; Oskouei, S.; Lomba, C.; Rogers, S.; Geller, D.; Hoang, B.; Tingling, J.; Solorzano, C.; Avedian, R.; Jordan, L.; Chinn, S.; Hamilton, M.; Puloski, S.; Monument, M.; Carcary, K.; Cameron, C.; Aboulafia, A.; Loo-Mis, M.; Bosley, J.; Bonvegna, R.; Kassa, M.; Damron, T.; Craig, T.; Reale, M.; Goodman, H. J.; Culbertson, M. Deza; Caruso, P.; Garling, E.; Schwab, J.; Fiore, A.; Phukan, R.; Park, C.; Joshi, L.; Aboulafia, A.; Wallace, M.; Flack, J.; Vaughan, K.; Avergas, A.; Brady, M.; Brown, S.; Schadie, N.; Battersby, R.; Weiss, K.; Goodman, M.; Heyl, A.; Yeschke, C. A.; Sumic, P.; Dudgeon, M.; Prosser, R.; Korenoski, C.; DiCaprio, M.; Palmer, B.; Cioppa, E.; Schaeffer, T. M.; Paul, P.; Toreson, J.; Cummings, J.; Schwartz, L.; Zahner, B.; Morris, C.; Laljani, V.; Mesko, N.; Joyce, M.; Lietman, S.; Wustrack, R.; O'Donnell, R.; Stevenson, C.; Carmody, E.; Tyler, W.; McIntyre, A.; Spiguel, A.; Scarborough, M.; Gibbs, C. P.; Steshyn, J.; Nunn, B.; Rosenthal, H.; Haynes, K.; Leddy, L.; Walton, Z.; Doung, Y-C.; Hayden, J.; Velez, R.; Aguirre, M.; Perez, M.; Barrera, S.; Garca Lopez, A.; Grimer, R.; Dunn, K.; Virdee, H.; Rankin, K.; Beckingsale, T.; Gerrand, C.; Campbell, I.; Allen, M.; Khan, S. Alam; Bakshi, S.; Rastogi, S.; Poudel, R.; Kumar, V. Sampath; Rai, A.; Baptista, A. M.; de Camargo, O. P.; Marais, L.; Rodseth, R.; Ferreira, N.; Rajah, C.; Gumede, S.; Gortzak, Y.; Sternheim, A.; Bickels, J.; Kolander, Y.; Lev, S.; Hettwer, W.; Petersen, M. M.; Grum-Schwensen, T.; Jutte, P.; Ploegmakers, J. J. W.; Stevens, M.; Mahendra, A.; Gupta, S.; Bergovec, M.; Leithner, A.; Funovics, P.; Dijkstra, P. D. S.; Van De Sande, M.; Hoogenstraaten, A.; Leijerzapf, N.; Steadman, P.; Steadman, P.; Boffano, M.; Piana, R.; Marone, S.; Albertini, U.; Boux, E.; Maiello, A.; Repsa, L.; Zile, S.; Aston, W.; Pollock, R.; Cool, P.; Gibbons, M.; Whit-Well, D.; Cosker, T.; Hemingway, J.; Porter, D.; Patton, S.; Navia, J.; Betancur, A. F.; Laitenen, M.; Pakarinen, K.; Nieminen, J.; Yla-Mononen, S.; Rautiainen, S.; Fiorenza, F.
Objective Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-da
Norenberg, Jeffrey P; Petry, Neil A; Schwarz, Sally
Clinical investigations of radiopharmaceuticals are undertaken to advance promising compounds toward approval by the Food and Drug Administration (FDA) as "legend drugs." This FDA approval requires that the safety and efficacy of the investigational drug (ID) be demonstrated through clinical trials. The investigational radiopharmaceutical drug service (IRDS) is a pharmacy service that plays a critical role in the acquisition, preparation, accountability, and distribution of radiopharmaceuticals used in clinical research. Due to their radioactive and other unique properties, and their potential role as biomarkers or tools in clinical trials of other therapeutic drugs, radiopharmaceutical drugs must be managed by a qualified IRDS rather than by a typical pharmacy-based investigational drug service (IDS). The IRDS is responsible for establishing study-specific procedures for appropriate radiopharmaceutical drug accountability, billing, procurement, storage, preparation, dispensing and destruction of investigational drugs within the hospital. All drugs, and particularly parenteral drug products, must be safe for administration to human subjects enrolled in clinical trials regardless of their FDA regulatory status as approved or investigational new drug products. The United States Pharmacopeia (USP) sterile compounding requirements provides enforceable minimum practice and quality standards for compounded sterile preparations of drug products based on current scientific information and best sterile compounding practices. Consequently, they apply equally to facilities dedicated to IDS and IRDS operations. The FDA also regulates drug manufacturing through current Good Manufacturing Practices (cGMP). This rule (21CFR Part 212) establishes cGMP regulations specific to positron emission tomography radiopharmaceuticals, separate from the regular drug cGMP rule (Parts 210 and 211). Compliance with regulatory, statutory, and sponsor requirements is a major consideration in the
Wang, Jinping; Logovinsky, Veronika; Hendrix, Suzanne B; Stanworth, Stephanie H; Perdomo, Carlos; Xu, Lu; Dhadda, Shobha; Do, Ira; Rabe, Martin; Luthman, Johan; Cummings, Jeffrey; Satlin, Andrew
Background Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials. Methods Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients’ early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations. Results ADCOMS consists of 4 Alzheimer's Disease Assessment Scale–cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating—Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials. Conclusions ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD. PMID:27010616
... HUMAN SERVICES Food and Drug Administration Clinical Trial Design for Intravenous Fat Emulsion Products... ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support registration of intravenous fat...
Hamasaki, Toshimitsu; Evans, Scott R; Ochiai, Toshimitsu
This book focuses on group sequential methods for clinical trials with co-primary endpoints based on the decision-making frameworks for: (1) rejecting the null hypothesis (stopping for efficacy), (2) rejecting the alternative hypothesis (stopping for futility), and (3) rejecting the null or alternative hypothesis (stopping for either futility or efficacy), where the trial is designed to evaluate whether the intervention is superior to the control on all endpoints. For assessing futility, there are two fundamental approaches, i.e., the decision to stop for futility based on the conditional probability of rejecting the null hypothesis, and the other based on stopping boundaries using group sequential methods. In this book, the latter approach is discussed. The book also briefly deals with the group sequential methods for clinical trials designed to evaluate whether the intervention is superior to the control on at least one endpoint. In addition, the book describes sample size recalculation and the resulting ef...
Natarajan, Pradeep; Oelschlager, Ashley; Agah, Arvin; Pohl, Patricia S; Ahmad, S Omar; Liu, Wen
This study was aimed at understanding the current physical and occupational therapy practices in stroke rehabilitation in the Midwest. The insights gained from this pilot study will be used in a future study aimed at understanding stroke rehabilitation practices across the nation. Researchers and clinicians in the field of stroke rehabilitation were interviewed, and past studies in the literature were analyzed. Through these activities, we developed a 37-item questionnaire that was sent to occupational and physical therapists practicing in Kansas and Missouri who focus on the care of people who have had a stroke (n = 320). A total of 107 respondents returned a com pleted questionnaire, which gives a response rate of about 36%. The majority of respondents had more than 12 years of experience treating patients with stroke. Consensus of 70% or more was found for 80% of the items. The preferred approaches for the rehabilitation of people who have had a stroke are the Bobath and Brunnstrom methods, which are being used by 93% and 85% of the physical and occupational therapists, respectively. Even though some variability existed in certain parts of the survey, in general clinicians agreed on different treatment approaches in issues dealing with muscle tone, weakness, and limited range of motion in stroke rehabilitation. Some newer treatment approaches that have been proven to be effective are practiced only by a minority of clinicians. The uncertainty among clinicians in some sections of the survey reveals that more evidence on clinical approaches is needed to ensure efficacious treatments. PMID:19009470
Fisher, Jill A.
In this paper I explore the politics of trust in the clinical testing of pharmaceuticals in the US. Specifically, I analyze trust in terms of its institutional manifestations in the pharmaceutical clinical trials industry. In the process of testing new drugs, pharmaceutical companies must (1) protect their proprietary information from the clinicians who conduct their studies, and (2) find a way to ensure human subjects' compliance to study protocols. Concern with these two critical issues lea...
Wicklund, Matthew P
The limb-girdle muscular dystrophies (LGMDs) encompass a collection of genetic muscle diseases with proximal-predominant weakness of the limbs. Thirty-two of these disorders are named via the common nomenclature, including 8 autosomal-dominant (LGMD1A-H) and 24 autosomal-recessive (LGMD2A-X) disorders.(1) In addition, numerous other genetic muscle diseases, including Bethlem myopathy, dystrophinopathies, ryanodine receptor-associated myopathies, and many more, may clinically present with similar proximal-predominant weakness.(2) Therefore, current genetic testing panels targeting neuromuscular weakness frequently encompass >75 genes. These disorders are quite rare, each with minimum prevalence estimates of 0.01-0.60 cases per 100,000 persons.(3) LGMD2A (attributable to mutations in the gene for calpain-3) and LGMD2B (attributable to mutations in the gene for dysferlin) consistently are the 2 most prevalent LGMD subtypes in a variety of ethnic cohorts. PMID:27540592
The research community has alternatively embraced then repudiated exploratory analyses since the inception of clinical trials in the middle of the twentieth century. After a series of important but ultimately unreproducible findings, these non-prospectively declared evaluations were relegated to hypothesis generating. Since the majority of evaluations conducted in clinical trials with their rich data sets are exploratory, the absence of their persuasive power adds to the inefficiency of clinical trial analyses in an atmosphere of fiscal frugality. However, the principle argument against exploratory analyses is not based in statistical theory, but pragmatism and observation. The absence of any theoretical treatment of exploratory analyses postpones the day when their statistical weaknesses might be repaired. Here, we introduce examination of the characteristics of exploratory analyses from a probabilistic and statistical framework. Setting the obvious logistical concerns aside (i.e., the absence of planning produces poor precision), exploratory analyses do not appear to suffer from estimation theory weaknesses. The problem appears to be a difficulty in what is actually reported as the p-value. The use of Bayes Theorem provides p-values that are more in line with confirmatory analyses. This development may inaugurate a body of work that would lead to the readmission of exploratory analyses to a position of persuasive power in clinical trials. PMID:26390962
Herr, Harry W
In 1784, a Royal Commission headed by Benjamin Franklin and Antoine Lavoisier designed a series of ingenious experiments to debunk France's greatest medical rogue, Anton Mesmer, and his bizarre healing of illnesses based on his bogus theory of animal magnetism. Using intentional subject ignorance and sham interventions to investigate mesmerism, Franklin's commission provided a model for the controlled clinical trial.
Barnes, P J; Casale, T B; Dahl, Ronald;
these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly...
Gluud, C; Sørensen, T I
, ways of organising and staffing clinical trial units were investigated. The present proposal is based on this experience from which an attempt to extract a composite set of minimal requirements has been made regarding pertinent objectives and aims, organisational aspects, staffing, and estimated costs...
Cohen, Jeffrey A; Reingold, Stephen C; Polman, Chris H;
Many of the available disability outcome measures used in clinical trials of multiple sclerosis are insensitive to change over time, inadequately validated, or insensitive to patient-perceived health status or quality of life. Increasing focus on therapies that slow or reverse disability...
Brölmann, Fleur E; Eskes, Anne M; Sumpio, Bauer E;
. Randomized clinical trials (RCTs) are universally acknowledged as the study design of choice for comparing treatment effects. To give high-level evidence the appreciation it deserves in wound care, we propose a step-by-step reporting standard for comprehensive and transparent reporting of RCTs in wound care...
Schroll, Jeppe Bennekou; Maund, Emma; Gøtzsche, Peter C
Misclassification of adverse events in clinical trials can sometimes have serious consequences. Therefore, each of the many steps involved, from a patient's adverse experience to presentation in tables in publications, should be as standardised as possible, minimising the scope for interpretation...
Vitiello, Benedetto; Kratochvil, Christopher J.
Optimal treatment of adolescent depression requires the use of antidepressants such as fluoxetine, and the addition of cognitive-behavioral therapy (CBT) offers better potential. Second-step pharmacological treatment of the disorder offers a success rate of around 50%. Clinical trial for the use of sertraline and CBT in treating…
van der Naalt, Joukje
BACKGROUND: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clin
The development of new drugs is increasingly costly and ineffective. Most time and money is accounted for by late-stage clinical trials that aim to confirm the safety and efficacy of the investigated drug. To assure the continued arrival of new and affordable therapies, it is therefore essential to
The research community has alternatively embraced then repudiated exploratory analyses since the inception of clinical trials in the middle of the twentieth century. After a series of important but ultimately unreproducible findings, these non-prospectively declared evaluations were relegated to hypothesis generating. Since the majority of evaluations conducted in clinical trials with their rich data sets are exploratory, the absence of their persuasive power adds to the inefficiency of clinical trial analyses in an atmosphere of fiscal frugality. However, the principle argument against exploratory analyses is not based in statistical theory, but pragmatism and observation. The absence of any theoretical treatment of exploratory analyses postpones the day when their statistical weaknesses might be repaired. Here, we introduce examination of the characteristics of exploratory analyses from a probabilistic and statistical framework. Setting the obvious logistical concerns aside (i.e., the absence of planning produces poor precision), exploratory analyses do not appear to suffer from estimation theory weaknesses. The problem appears to be a difficulty in what is actually reported as the p-value. The use of Bayes Theorem provides p-values that are more in line with confirmatory analyses. This development may inaugurate a body of work that would lead to the readmission of exploratory analyses to a position of persuasive power in clinical trials.
Morrison, Anthony P; Burke, Eilish; Murphy, Elizabeth; Pyle, Melissa; Bowe, Samantha; Varese, Filippo; Dunn, Graham; Chapman, Nicola; Hutton, Paul; Welford, Mary; Wood, Lisa J
We aimed to evaluate the feasibility of Cognitive Therapy (CT) as an intervention for internalised stigma in people with psychosis. We conducted a single-blind randomised controlled pilot trial comparing CT plus treatment as usual (TAU) with TAU only. Participants were assessed at end of treatment (4 months) and follow-up (7 months). Twenty-nine participants with schizophrenia spectrum disorders were randomised. CT incorporated up to 12 sessions over 4 months (mean sessions=9.3). Primary outcome was the Internalised Stigma of Mental Illness Scale - Revised (ISMI-R) total score, which provides a continuous measure of internalised stigma associated with mental health problems. Secondary outcomes included self-rated recovery, internalised shame, emotional problems, hopelessness and self-esteem. Recruitment rates and retention for this trial were good. Changes in outcomes were analysed following the intention-to-treat principle, using ANCOVAs adjusted for baseline symptoms. There was no effect on our primary outcome, with a sizable reduction observed in both groups, but several secondary outcomes were significantly improved in the group assigned to CT, in comparison with TAU, including internalised shame, hopelessness and self-rated recovery. Stigma-focused CT appears feasible and acceptable in people with psychosis who have high levels of internalised stigma. A larger, definitive trial is required. PMID:27092862
Full Text Available Abstract Objective Few methodological studies address the prioritization of clinical topics for the development of Clinical Practice Guidelines (CPGs. The aim of this study was to validate a methodology for Priority Determination of Topics (PDT of CPGs. Methods and results Firstly, we developed an instrument for PDT with 41 criteria that were grouped under 10 domains, based on a comprehensive systematic search. Secondly, we performed a survey of stakeholders involved in CPGs development, and end users of guidelines, using the instrument. Thirdly, a pilot testing of the PDT procedure was performed in order to choose 10 guideline topics among 34 proposed projects; using a multi-criteria analysis approach, we validated a mechanism that followed five stages: determination of the composition of groups, item/domain scoring, weights determination, quality of the information used to support judgments, and finally, topic selection. Participants first scored the importance of each domain, after which four different weighting procedures were calculated (including the survey results. The process of weighting was determined by correlating the data between them. We also reported the quality of evidence used for PDT. Finally, we provided a qualitative analysis of the process. The main domains used to support judgement, having higher quality scores and weightings, were feasibility, disease burden, implementation and information needs. Other important domains such as user preferences, adverse events, potential for health promotion, social effects, and economic impact had lower relevance for clinicians. Criteria for prioritization were mainly judged through professional experience, while good quality information was only used in 15% of cases. Conclusion The main advantages of the proposed methodology are supported by the use of a systematic approach to identify, score and weight guideline topics selection, limiting or exposing the influence of personal biases
Full Text Available Abstract In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies.
Califf, Robert M
Patients, clinicians, and policymakers alike need access to high-quality scientific evidence in order to make informed choices about health and healthcare, but the current national clinical trials enterprise is not yet optimally configured for the efficient creation and dissemination of such evidence. However, new technologies and methods hold significant potential for accelerating the rate at which we are able to translate raw findings gathered from both patient care and clinical research into actionable knowledge. We are now entering a period in which the quantitative sciences are emerging as the critical disciplines for advancing knowledge about health and healthcare, and statisticians will increasingly serve as critical mediators in transforming data into evidence. In this new, data-centric era, biostatisticians not only need to be expert at analyzing data but should also be involved directly in diverse efforts, including the review and analysis of research portfolios in order to optimize the relevance of research questions, the use of "quality by design" principles to improve reliability and validity of each individual trial, and the mining of aggregate knowledge derived from the clinical research enterprise as a whole. In order to meet these challenges, it is imperative that we (1) nurture and build the biostatistical workforce, (2) develop a deeper understanding of the biological and clinical context among statisticians, (3) facilitate collaboration among biostatisticians and other members of the clinical trials enterprise, (4) focus on communication skills in training and education programs, and (5) enhance the quantitative capacity of the research and clinical practice worlds. PMID:27378791
Jenny E. Han
Conclusions: In this pilot study, high-dose vitamin D3 safely increased plasma 25(OHD concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes.
Clinical test cases to facilitate the commissioning process of radiotherapy treatment planning system (TPS) were developed by participants of the IAEA coordinated research project (CRP) on 'Development of procedures for quality assurance for dosimetry calculation in radiotherapy'. The tests cover basic treatment techniques in typical radiotherapy installations and are based on the use of CIRS torso phantom. The practicability of the commissioning tests is assured through their trial use in the clinical facilities of different sizes. All hospitals used the same type of phantom which was scanned twice with computer tomography (CT). At the first scan different inserts were introduced into the phantom to derive the CT number to relative electron density conversion curve. At the second scan the phantom CT slices were acquired for planning of different clinical test cases on TPS. The dose was measured with ionization chamber placed inside the phantom. In this work we present the results from eleven hospitals which are using fifteen different TPSs. Altogether there are 37 different combinations of algorithms and beam qualities. The use of the phantom and the tests proposed in the CRP enabled the evaluation of accuracy and limitations of different algorithms as well as inconsistencies in the loaded data. The differences between TPS dose calculations and measurements for different photon beam algorithms and inhomogeneity correction methods which exceed 3% tolerance limit are shown. More results for different clinical test cases as well as test descriptions will be presented at the conference. Results of the pilot study have shown that proposed test cases can not only serve to ensure the safe use of the TPS in a specific clinic, but may also help the user to appreciate the possibilities of their system and understand its limitations. The set of tests for clinical commissioning can be performed in reasonable time in the majority of hospitals, particularly in those with
Sampaio, Cristina; Borowsky, Beth; Reilmann, Ralf
Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field.
Sampaio, Cristina; Borowsky, Beth; Reilmann, Ralf
Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field. PMID:25216371
Background: Clinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. Methods: We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. Results: The treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23–0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30–0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39–1.23, vs. HR 0.94; 95% CI, 0.68–1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36–0.82, vs. HR 0.77; 95% CI, 0.58–1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30% shorter (8.4 vs. 12.0 years). Conclusion: Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability
Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison
Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial
... Mythteries: A Video Game About Clinical Trials SUMMARY: Under the provisions of Section 3507(a)(1)(D) of the... Clinical Trials. Type of Information Collection Request: NEW. Need and Use of Information Collection:...
Steenhoff, Andrew P.; Schall, Joan I.; Samuel, Julia; Seme, Boitshepo; Marape, Marape; Ratshaa, Bakgaki; Goercke, Irene; Tolle, Michael; Nnyepi, Maria S.; Mazhani, Loeto; Zemel, Babette S.; Rutstein, Richard M.; Stallings, Virginia A.
Objectives Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D). Design Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years. Methods Sixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores. Results Subjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of 1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03). Conclusions In a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers. Trial Registration ClinicalTrials.gov NCT02189902 PMID:25706751
Full Text Available World Health Organization (WHO has defined herbal medicines as finished labeled medicinal product that contain an active ingredient, aerial, or underground parts of the plant or other plant material or combinations. According to a report of WHO, about 80% of the world population is reported to rely on traditional medicine for their primary health care needs. Even in the developed countries, complementary or alternative medicine is gaining popularity. A report of a global survey on national policy on traditional medicine and regulation of herbal medicines indicated that about 50 countries including China, Japan, and Germany already have their national policy and laws on regulations of traditional medicines. Herbal drugs possess a long history of its use and better patient tolerance. These are cheaper and easily available in countries like India due to rich agro culture conditions. However, reckless utilization of resources threatens the sustainability of several plant species. Traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules of 1945. In 1959, the Government of India amended the Drugs and Cosmetics Act to include drugs that are derived from traditional Indian medicine. In 1993, the guidelines for the safety and efficacy of herbal medicines developed by an expert committee directed that the procedures laid down by the office of the Drug Controller General of India for allopathic drugs should be followed for all traditional and herbal products to enter into clinical trials for any therapeutic condition. However, there are certain loop holes in the clinical trials of herbal drugs as the lack of stringent bylaws and regulations. Hence, a deep insight of important challenges and major regulatory guidelines for clinical trial of herbal drugs and botanicals is discussed in the present communication. There is lack of scientific evidence to evaluate safety and efficacy of herbal drugs. The quality
Diana de la Iglesia; Miguel García-Remesal; Alberto Anguita; Miguel Muñoz-Mármol; Casimir Kulikowski; Víctor Maojo
BACKGROUND: Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this inf...
Drug development has been globalized, and multi-regional clinical trial (MRCT) for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH) has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017. PMID:27141471
Full Text Available Rare neurodegenerative diseases are fatal and no therapy is available to cure or slow down the progression of disease. We report possibly weaknesses in the management of clinical studies in these diseases, ranging from poor preclinical studies, difficulties in the recruitment of patients, delay in the onset of treatment because of lack in early disease-specific biomarkers, and suboptimal design of Phase II clinical trials. The adoption of innovative statistical approaches in early Phase II trials might improve the screening of drugs in rare neurodegenerative disorders, but this implicates efforts from clinical researchers, statisticians, and regulatory people to the development of new strategies that should maintain rigorous scientific integrity together with a more ethical approach to human experimentations.
Full Text Available Drug development has been globalized, and multi-regional clinical trial (MRCT for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017.
Cutter, Christopher J; Schottenfeld, Richard S; Moore, Brent A; Ball, Samuel A; Beitel, Mark; Savant, Jonathan D; Stults-Kolehmainen, Matthew A; Doucette, Christopher; Barry, Declan T
Few studies have examined exercise as a substance use disorder treatment. This pilot study investigated the feasibility and acceptability of an exercise intervention comprising the Wii Fit Plus™ and of a time-and-attention sedentary control comprising Wii™ videogames. We also explored their impact on physical activity levels, substance use, and psychological wellness. Twenty-nine methadone-maintained patients enrolled in an 8-week trial were randomly assigned to either Active Game Play (Wii Fit Plus™ videogames involving physical exertion) or Sedentary Game Play (Wii™ videogames played while sitting). Participants had high satisfaction and study completion rates. Active Game Play participants reported greater physical activity outside the intervention than Sedentary Game Play participants despite no such differences at baseline. Substance use decreased and stress and optimism improved in both conditions. Active Game Play is a feasible and acceptable exercise intervention, and Sedentary Game Play is a promising time-and-attention control. Further investigations of these interventions are warranted.
Cutter, Christopher J; Schottenfeld, Richard S; Moore, Brent A; Ball, Samuel A; Beitel, Mark; Savant, Jonathan D; Stults-Kolehmainen, Matthew A; Doucette, Christopher; Barry, Declan T
Few studies have examined exercise as a substance use disorder treatment. This pilot study investigated the feasibility and acceptability of an exercise intervention comprising the Wii Fit Plus™ and of a time-and-attention sedentary control comprising Wii™ videogames. We also explored their impact on physical activity levels, substance use, and psychological wellness. Twenty-nine methadone-maintained patients enrolled in an 8-week trial were randomly assigned to either Active Game Play (Wii Fit Plus™ videogames involving physical exertion) or Sedentary Game Play (Wii™ videogames played while sitting). Participants had high satisfaction and study completion rates. Active Game Play participants reported greater physical activity outside the intervention than Sedentary Game Play participants despite no such differences at baseline. Substance use decreased and stress and optimism improved in both conditions. Active Game Play is a feasible and acceptable exercise intervention, and Sedentary Game Play is a promising time-and-attention control. Further investigations of these interventions are warranted. PMID:25012555
Carson, James W; Carson, Kimberly M; Jones, Kim D; Bennett, Robert M; Wright, Cheryl L; Mist, Scott D
A mounting body of literature recommends that treatment for fibromyalgia (FM) encompass medications, exercise and improvement of coping skills. However, there is a significant gap in determining an effective counterpart to pharmacotherapy that incorporates both exercise and coping. The aim of this randomized controlled trial was to evaluate the effects of a comprehensive yoga intervention on FM symptoms and coping. A sample of 53 female FM patients were randomized to the 8-week Yoga of Awareness program (gentle poses, meditation, breathing exercises, yoga-based coping instructions, group discussions) or to wait-listed standard care. Data were analyzed by intention to treat. At post-treatment, women assigned to the yoga program showed significantly greater improvements on standardized measures of FM symptoms and functioning, including pain, fatigue, and mood, and in pain catastrophizing, acceptance, and other coping strategies. This pilot study provides promising support for the potential benefits of a yoga program for women with FM.
Kimber, L; McNabb, M; Mc Court, C; Haines, A; Brocklehurst, P
Research on massage therapy for maternal pain and anxiety in labour is currently limited to four small trials. Each used different massage techniques, at different frequencies and durations, and relaxation techniques were included in three trials. Given the need to investigate massage interventions that complement maternal neurophysiological adaptations to labour and birth pain(s), we designed a pilot randomised controlled trial (RCT) to test the effects of a massage programme practised during physiological changes in pain threshold, from late pregnancy to birth, on women's reported pain, measured by a visual analogue scale (VAS) at 90 min following birth. To control for the potential bias of the possible effects of support offered within preparation for the intervention group, the study included 3 arms--intervention (massage programme with relaxation techniques), placebo (music with relaxation techniques) and control (usual care). The placebo offered a non-pharmacological coping strategy, to ensure that use of massage was the only difference between intervention and placebo groups. There was a trend towards slightly lower mean pain scores in the intervention group but these differences were not statistically significant. No differences were found in use of pharmacological analgesia, need for augmentation or mode of delivery. There was a trend towards more positive views of labour preparedness and sense of control in the intervention and placebo groups, compared with the control group. These findings suggest that regular massage with relaxation techniques from late pregnancy to birth is an acceptable coping strategy that merits a large trial with sufficient power to detect differences in reported pain as a primary outcome measure. PMID:18304848
Lee, Bonnie K; Awosoga, Olu
A multi-site pilot randomized controlled trial of Congruence Couple Therapy (CCT) for problem gambling was conducted in Ontario and Alberta, Canada from 2009 to 2011. The purpose was to assess the feasibility of a full trial and to identify methodological modifications to enhance future trials. The sample (N = 30; 15 couples) consisted of 66% male gamblers and 34% female. Mean age of sample was 49.1 years. Baseline mean DSM-IV gambling score was 8.7/10. Retention of the treatment couples was 89% at 2-month follow-up. Retention of control couples was 78%. A randomized controlled design compared the status of couples in treatment condition to control condition. Treatment couples received 12-week CCT while control couples received three brief check-ins over 12 weeks. No significant difference was found between treatment and control group at baseline on all measures. At (1) week 12 post-treatment, and (2) week 20 follow-up, significant treatment effects were found for gambling symptoms (p = 0.008; p = 0.041), mental distress (p = 0.001; p = 0.035), and family systems function (p = 0.023; p = 0.054) between treatment and control group. Within group changes for treatment couples over time were significant for mental distress (p = 0.000), dyadic adjustment (p = 0.002), and family systems function (p = 0.000). On similar measures, control group showed non-significant improvement. Future methodological changes, advantages and disadvantages of multi-site partnerships with community treatment agencies are discussed. Of interest is that control participants showed unintended improvement. CCT as a treatment was favourably accepted by counselors, problem gamblers and their spouses. Positive outcome trends ranging from small to large effect size on key measures indicate that a full-scaled trial will require approximately 140 couples and is an investment worth pursuing.
Goldacre, Ben; Gray, Jonathan
OpenTrials is a collaborative and open database for all available structured data and documents on all clinical trials, threaded together by individual trial. With a versatile and expandable data schema, it is initially designed to host and match the following documents and data for each trial: registry entries; links, abstracts, or texts of academic journal papers; portions of regulatory documents describing individual trials; structured data on methods and results extracted by systematic reviewers or other researchers; clinical study reports; and additional documents such as blank consent forms, blank case report forms, and protocols. The intention is to create an open, freely re-usable index of all such information and to increase discoverability, facilitate research, identify inconsistent data, enable audits on the availability and completeness of this information, support advocacy for better data and drive up standards around open data in evidence-based medicine. The project has phase I funding. This will allow us to create a practical data schema and populate the database initially through web-scraping, basic record linkage techniques, crowd-sourced curation around selected drug areas, and import of existing sources of structured and documents. It will also allow us to create user-friendly web interfaces onto the data and conduct user engagement workshops to optimise the database and interface designs. Where other projects have set out to manually and perfectly curate a narrow range of information on a smaller number of trials, we aim to use a broader range of techniques and attempt to match a very large quantity of information on all trials. We are currently seeking feedback and additional sources of structured data. PMID:27056367
Full Text Available Barbara P Yawn,1 Suzanne Madison,1 Susan Bertram,1 Wilson D Pace,2 Anne Fuhlbrigge,3 Elliot Israel,3 Dawn Littlefield,1 Margary Kurland,1 Michael E Wechsler41Olmsted Medical Center, Department of Research, Rochester, MN, 2UCDHSC, Department of Family Medicine, University of Colorado Health Science Centre, Aurora, CO, 3Brigham and Women's Hospital, Pulmonary and Critical Care Division, Boston, MA, 4National Jewish Medical Center, Division of Pulmonology, Denver, CO, USABackground: Published reports and studies related to patient compensation for clinical trials focus primarily on the ethical issues related to appropriate amounts to reimburse for patient's time and risk burden. Little has been published regarding the method of payment for patient participation. As clinical trials move into widely dispersed community practices and more complex designs, the method of payment also becomes more complex. Here we review the decision process and payment method selected for a primary care-based randomized clinical trial of asthma management in Black Americans.Methods: The method selected is a credit card system designed specifically for clinical trials that allows both fixed and variable real-time payments. We operationalized the study design by providing each patient with two cards, one for reimbursement for study visits and one for payment of medication costs directly to the pharmacies.Results: Of the 1015 patients enrolled, only two refused use of the ClinCard, requesting cash payments for visits and only rarely a weekend or fill-in pharmacist refused to use the card system for payment directly to the pharmacy. Overall, the system has been well accepted by patients and local study teams. The ClinCard administrative system facilitates the fiscal accounting and medication adherence record-keeping by the central teams. Monthly fees are modest, and all 12 study institutional review boards approved use of the system without concern for patient
Cornelissen, G.; Braendli, R. C.; Eek, E.; Henriksen, T.; Hartnik, T.; Breedveld, G. D.
Background Activated char BC binds organic contaminants and possibly mercury so strongly that their bioaccumulation and transport to other environmental compartments are reduced. The advantages of black carbon amendment over many other remediation methods include i) it can be used as an in situ risk reduction method, ii) the price is low, and iii) it overcomes significant controversies associated with disposal of dredged and excavated materials. In this study BC amendment is used in pilot trials in the field for soil and sediment amelioration. Quantification of amended char BC Two methods for char BC quantification were tested: i) chemothermal oxidation (CTO) at a range of temperatures and ii) wet chemical oxidation with a potassium dichromate/sulfuric acid solution. The amount of BC amended to three soils was accurately determined by CTO at 375°C. For two sediments, much of the BC disappeared during combustion at 375°C, which could probably be explained by catalytic effects caused by sediment constituents such as metals, mineral oxides and salts. Attempts to avoid these effects through rinsing with acid before combustion did not result in higher char BC recoveries. CTO at lower temperatures (325-350°C) was a feasible alternative for one of the sediments. Wet oxidation with potassium dichromate/sulfuric acid proved to effectively function for BC quantification in sediments, since almost complete BC recovery (81-92 %) was observed for both sediments, while the amount of organic carbon remaining was low (5-16 %). Field pilots Earlier, we showed the effectiveness of BC amendment in the laboratory. In the laboratory it was shown that BC amendments (2 %) reduced freely dissolved porewater concentrations (factor of 10-50) and bioaccumulation (factor of 5). This presentation will describe 50 × 50 m pilot field trials in Norway (2007-2008): Trondheim Harbor (sediment) and Drammen (soil). The presentation will focus on physical monitoring (distribution of BC in the
Pragmatic clinical trials (PCTs) are today an increasingly prominent means of measuring the 'effectiveness' of healthcare interventions in 'real world' clinical settings, in order to produce evidence on which to base regulatory and clinical decision-making. Although several sociological studies have shown persuasively how PCTs are co-constructed within particular healthcare systems in which they are based, they have tended to focus on relatively later stages in careers of trials. The paper contributes to literature by considering how the 'real world' of the UK National Health Service (NHS) is incorporated into the design of a research protocol. Drawing on a meeting held just prior to patient recruitment for a PCT in maternal health, the paper analyses a trial collective's efforts to purify the messy domain of NHS clinical care into the orderly confines of the protocol (Law 2004), which meant satisfying demands for both scientific and social robustness (c.f. Nowotny et al. 2001). The findings show how efforts to inscribe robustness into the PCT protocol were themselves mediated through epistemic and regulatory conventions surrounding protocols as devices in healthcare research. Finally it is argued that meetings constitute an important epistemic instrument through which to settle various emerging tensions in PCT protocol design. PMID:26235211
Mijoule, Guillaume; Savy, Stéphanie; Savy, Nicolas
Taking a decision on the feasibility and estimating the duration of patients' recruitment in a clinical trial are very important but very hard questions to answer, mainly because of the huge variability of the system. The more elaborated works on this topic are those of Anisimov and co-authors, where they investigate modelling of the enrolment period by using Gamma-Poisson processes, which allows to develop statistical tools that can help the manager of the clinical trial to answer these questions and thus help him to plan the trial. The main idea is to consider an ongoing study at an intermediate time, denoted t(1). Data collected on [0,t(1)] allow to calibrate the parameters of the model, which are then used to make predictions on what will happen after t(1). This method allows us to estimate the probability of ending the trial on time and give possible corrective actions to the trial manager especially regarding how many centres have to be open to finish on time. In this paper, we investigate a Pareto-Poisson model, which we compare with the Gamma-Poisson one. We will discuss the accuracy of the estimation of the parameters and compare the models on a set of real case data. We make the comparison on various criteria : the expected recruitment duration, the quality of fitting to the data and its sensitivity to parameter errors. We discuss the influence of the centres opening dates on the estimation of the duration. This is a very important question to deal with in the setting of our data set. In fact, these dates are not known. For this discussion, we consider a uniformly distributed approach. Finally, we study the sensitivity of the expected duration of the trial with respect to the parameters of the model : we calculate to what extent an error on the estimation of the parameters generates an error in the prediction of the duration.
Ibrahim, Joseph G; Chen, Ming-Hui; Lakshminarayanan, Mani; Liu, Guanghan F; Heyse, Joseph F
Developing sophisticated statistical methods for go/no-go decisions is crucial for clinical trials, as planning phase III or phase IV trials is costly and time consuming. In this paper, we develop a novel Bayesian methodology for determining the probability of success of a treatment regimen on the basis of the current data of a given trial. We introduce a new criterion for calculating the probability of success that allows for inclusion of covariates as well as allowing for historical data based on the treatment regimen, and patient characteristics. A new class of prior distributions and covariate distributions is developed to achieve this goal. The methodology is quite general and can be used with univariate or multivariate continuous or discrete data, and it generalizes Chuang-Stein's work. This methodology will be invaluable for informing the scientist on the likelihood of success of the compound, while including the information of covariates for patient characteristics in the trial population for planning future pre-market or post-market trials. PMID:25339499
Rosenberger, William F; Haines, Linda M
Phase I clinical trials are typically small, uncontrolled studies designed to determine a maximum tolerated dose of a drug which will be used in further testing. Two divergent schools have developed in designing phase I clinical trials. The first defines the maximum tolerated dose as a statistic computed from data, and hence it is identified, rather than estimated. The second defines the maximum tolerated dose as a parameter of a monotonic dose-response curve, and hence is estimated. We review techniques from both philosophies. The goal is to present these methods in a single package, to compare them from philosophical and statistical grounds, to hopefully clear up some common misconceptions, and to make a few recommendations. This paper is not a review of simulation studies of these designs, nor does it present any new simulations comparing these designs.
Zhu, Hongjian; 10.1214/10-AOS796
Clinical trials are complex and usually involve multiple objectives such as controlling type I error rate, increasing power to detect treatment difference, assigning more patients to better treatment, and more. In literature, both response-adaptive randomization (RAR) procedures (by changing randomization procedure sequentially) and sequential monitoring (by changing analysis procedure sequentially) have been proposed to achieve these objectives to some degree. In this paper, we propose to sequentially monitor response-adaptive randomized clinical trial and study it's properties. We prove that the sequential test statistics of the new procedure converge to a Brownian motion in distribution. Further, we show that the sequential test statistics asymptotically satisfy the canonical joint distribution defined in Jennison and Turnbull (\\citeyearJT00). Therefore, type I error and other objectives can be achieved theoretically by selecting appropriate boundaries. These results open a door to sequentially monitor res...
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Albumin is a frequently prescribed drug in hospitalized patients, and its effect on clinical outcomes has been scrutinized in recent years. Data from meta-analyses has suggested harm related to albumin therapy in critically ill patients, and new observational data are consistent with these results. However, appropriately powered randomized, controlled trials have shown albumin to be safe in broad groups of critically ill patients. This article will discuss the reasons for differences between ...
The James Lind Library, named after the 18th-century Scottish naval surgeon whose experiments showed that citrus fruits cured scurvy, was launched in 2003 to broaden understanding of clinical trials involving humans by explaining their fundamental principles and their historical development. The online repository receives over 60 000 visitors every three months, and WHO Regional Offices have translated its introductory materials into Arabic, French, Portuguese and Spanish. The library provide...
Khin-Maung-U; Myo-Khin; Nyunt-Nyunt-Wai; Aye-Kyaw; Tin-U
Four hundred adults presenting with acute watery diarrhoea were entered into a randomised, placebo controlled, double blind clinical trial of berberine, tetracycline, and tetracycline and berberine to study the antisecretory and vibriostatic effects of berberine. Of 185 patients with cholera, those given tetracycline or tetracycline and berberine had considerably reduced volume and frequency of diarrhoeal stools, duration of diarrhoea, and volumes of required intravenous and oral rehydration ...
Jelic, V.; Kivipelto, M.; Winblad, B.
Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agent...
Migdacelys Arboláez Estrada.
Full Text Available SUMMARYCuba has extensive experience about herbal drugs, however only a few products get to the clinical phase of drug development. Our objective was to design new guidelines for clinical trials with herbal drugs.A detailed bibliographic search about regulatory aspects about clinical trials in Cuba and the world was done for development of the guideline. The guideline's proposed format includes: 1 Index, including the classification of the content. 2 Summary, 3 Fifteen chapters, related to the clinical trials. The guideline also propose the inclusion of annexes.A new guideline containing 15 chapters allows for writing more clear and detailed clinical trial protocols. The guideline contains the information required to guide the research staff who is interested in the validation of herbal drugs pharmacological activations from the perspective of clinical trials. RESUMEN Cuba tiene experiencia extensa sobre plantas medicinales, aunque solo algunos productos llegan a una fase clínica del desarrollo. Nuestro objetivo fué diseñar una nueva guía para ensayos clínicos con plantas medicinales.Hemos realizado una detallada búsqueda bibliográfica sobre aspectos reguladores de ensayos clínicos en Cuba y el resto del mundo para el desarrollo de la guía. El formato propuesto de la guia incluye: 1 Índice, incluyendo la clasificación de los contenidos. 2 Resumen, 3 Quince capítulos, relacionados con los ensayos clínicos. La guía también propone la inclusión de anexos.La nueva guía que contiene 15 capítulos que orientan la redacción de protocolos de ensayos clínicos más claros y más detallados. La guía contiene la información requerida para orientar al personal investigador interesado en la validación de la actividad farmacológica de las plantas medicinales desde la perspectiva de los ensayos clínicos.
Full Text Available BACKGROUND: Pharmaceutical trials are mainly initiated by sponsors and investigators in the United States, Western Europe and Japan. However, more and more patients are enrolled in Central and Eastern Europe, Latin America and Asia. The involvement of patients in new geographical settings raises questions about scientific and ethical integrity, especially when experience with those settings is lacking at the level of trial management. We therefore studied to what extent the geographical shift in patient enrolment is anticipated in the composition of trial management teams using the author nationalities on the primary outcome publication as an indicator of leadership. METHODS AND FINDINGS: We conducted a cohort-study among 1,445 registered trials in www.clinicaltrials.gov that could be matched with a primary outcome publication using clinical trial registry numbers listed in publications. The name of the sponsor and the enrolment countries were extracted from all registrations. The author-addresses of all authors were extracted from the publications. We searched the author-address of all publications to determine whether enrolment countries and sponsors listed on registrations also appeared on a matched publication. Of all sponsors, 80.1% were listed with an author-address on the publication. Of all enrolment countries, 50.3% appeared with an author-address on the publication. The listing of enrolment countries was especially low for industry-funded trials (39.9% as compared to government (90.4% and not-for-profit funding (93.7%. We found that listing of enrolment countries in industry-funded trials was higher for traditional research locations such as the United States (98.2% and Japan (72.0% as compared to nontraditional research locations such as Poland (27.3% and Mexico (14.1%. CONCLUSIONS: Despite patient enrolment efforts, the involvement of researchers from nontraditional locations in trial management as measured by their contribution to
Rashid, M Mushfiqur; McKean, Joseph W; Kloke, John D
This article reviews nonparametric alternatives to the mixed model normal theory analysis for the analyses of multicenter clinical trials. Under a mixed model, the traditional analysis is based on maximum likelihood theory under normal errors. This analysis, though, is not robust to outliers. Robust, rank-based, Wilcoxon-type procedures are reviewed for a multicenter clinical trial for the mixed model but without the assumption of normality. These procedures retain the high efficiency of Wilcoxon methods for simple location problems and are based on a fitting criterion which is robust to outliers in response space. A simple weighting scheme can be employed so that the procedures are robust to outliers in factor (design) space as well as response space. These rank-based analyses offer a complete analysis, including estimation of fixed effects and their standard errors, and tests of linear hypotheses. Both rank-based estimates of contrasts and individual treatment effects are reviewed. We illustrate the analyses using real data from a clinical trial. PMID:24138428
Caon, Martin [School of Nursing and Midwifery, Flinders University, Adelaide (Australia)], E-mail: email@example.com
Examples of the statements about the radiation from medical imaging in the information for participants provided to the Human Research Ethics Committee (HREC) for approval are presented and discussed. There is considerable scope for improvement in the information about radiation that is presented to potential participants in clinical trials. Many radiation statements seem only intended to allay fear and anxiety about radiation rather than providing accurate information. This situation cannot be said to be conducive to allowing the participant to give informed consent to their involvement in a clinical trial in which ionising radiation is used. As many clinical trials are international and conducted at many sites (sometimes over 100), we would expect the same statements to have been seen by members of HRECs in many countries. Few HRECs include a member who is an expert in radiation. Hence, to ensure that the information is sound, those sections of the participant information that refer to radiation should be written or reviewed by a specialist in radiation protection such as a medical physicist, a health physicist or a radiation safety officer. (opinion)
Pachaly, Maria Aparecida; Baena, Cristina Pellegrino; Carvalho, Mauricio de
The prevalence of kidney stone disease is increasing worldwide with significant health and economic burden. Newer research is finding that stones are associated with several serious morbidities. Yet, few randomized clinical trials or high quality observational studies have assessed whether clinical interventions decrease the recurrence of kidney stones. Therefore, in this review we analyze the available evidence on medical expulsive therapy for ureteral stones; describe the evidence about non-pharmacological stone therapy including dietary modifications and citrus juice-based therapy; and discuss the efficacy of thiazide diuretics for the treatment of hypercalciuria in recurrent nephrolithiasis. PMID:27049371
Korn, E L; Baumrind, S
The standard design for randomised clinical trials may be inappropriate when the clinician believes that one of the treatments being tested is superior for the patient, or when the clinician has a preference for one of the treatments. For such instances the suggestion is that the patient is randomly allocated to treatment only when there is clinical disagreement about treatment of choice for that patient, and then the patient is assigned to a clinician who had thought that the regimen allocated is the one most appropriate for that patient.
Pachaly, Maria Aparecida; Baena, Cristina Pellegrino; Carvalho, Mauricio de
The prevalence of kidney stone disease is increasing worldwide with significant health and economic burden. Newer research is finding that stones are associated with several serious morbidities. Yet, few randomized clinical trials or high quality observational studies have assessed whether clinical interventions decrease the recurrence of kidney stones. Therefore, in this review we analyze the available evidence on medical expulsive therapy for ureteral stones; describe the evidence about non-pharmacological stone therapy including dietary modifications and citrus juice-based therapy; and discuss the efficacy of thiazide diuretics for the treatment of hypercalciuria in recurrent nephrolithiasis.
Chen, Feng; Sun, Hua-long; Shen, Tong; Yu, Hao
A perfect clinical trial must nave a solid study design, strict conduction, complete quality control, non-interference of statistical result, and acceptable risk-benefit ratio. To reach the target, the quality control (QC) should be performed from the study design to conduction, from the analysis to conclusion. We discuss the relationship between data management and biostatistics from the statistical point of view, and emphasize the importance of the statistical concept and methods in the improvement of data quality in clinical data management.
Full Text Available To evaluate the current evidence for effectiveness of acupuncture for posttraumatic stress disorder (PTSD in the form of a systematic review, a systematic literature search was conducted in 23 electronic databases. Grey literature was also searched. The key search terms were “acupuncture” and “PTSD.” No language restrictions were imposed. We included all randomized or prospective clinical trials that evaluated acupuncture and its variants against a waitlist, sham acupuncture, conventional therapy control for PTSD, or without control. Four randomized controlled trials (RCTs and 2 uncontrolled clinical trials (UCTs out of 136 articles in total were systematically reviewed. One high-quality RCT reported that acupuncture was superior to waitlist control and therapeutic effects of acupuncture and cognitive-behavioral therapy (CBT were similar based on the effect sizes. One RCT showed no statistical difference between acupuncture and selective serotonin reuptake inhibitors (SSRIs. One RCT reported a favorable effect of acupoint stimulation plus CBT against CBT alone. A meta-analysis of acupuncture plus moxibustion versus SSRI favored acupuncture plus moxibustion in three outcomes. This systematic review and meta-analysis suggest that the evidence of effectiveness of acupuncture for PTSD is encouraging but not cogent. Further qualified trials are needed to confirm whether acupuncture is effective for PTSD.
Kjaergard, Lise L; Frederiksen, Sarah L; Gluud, Christian
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....
Turton, Ailie J; O'Leary, Kelly; Gabb, Judith; Woodward, Rebecca; Gilchrist, Iain D
Prism adaptation has been shown to alleviate the symptoms of unilateral spatial neglect following stroke in single case and small group studies. The purposes of this single blinded pilot randomised controlled trial were to determine the feasibility of delivering prism adaptation treatment in a clinically valid sample and to assess its impact on self-care. Thirty seven right hemisphere stroke patients with unilateral spatial neglect were randomised into either prism adaptation (using 10 dioptre, 6 degree prisms) or sham treatment (using plain glasses) groups. Treatment was delivered each weekday for two weeks. Pointing accuracy, without vision of the finger, was recorded each day before treatment. Outcome was measured, by blinded assessors, four days and eight weeks after the end of treatment using the Catherine Bergego Scale (CBS) and the conventional neuropsychological tests from the Behavioural Inattention Test (BIT). Thirty four patients received treatment: 16 with prisms, 18 sham. Mean compliance was 99% and 97%, respectively. Over the treatment days only the prism treated group showed increased leftward bias in open loop pointing to targets on a touch screen. However, despite the group level changes in pointing behaviour no overall effect of the treatment on self-care or BIT were found.
Andrew P Steenhoff
Full Text Available Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃ in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D.Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0-50.9 years.Sixty subjects randomized within five age groups to either 4000 or 7000 IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D ≥32 ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL, CD4%, anti-retroviral therapy (ART regime, and height-adjusted (HAZ, weight-adjusted (WAZ and Body Mass Index (BMIZ Z scores.Subjects were 50% male, age (mean±SD 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of 1.4 in 22%. From baseline to 12 weeks, 25D increased from 36±9 ng/ml to 56±18 ng/ml (p<0.0001 and 68% and 90% had 25D ≥32 ng/ml, respectively (p = 0.02. Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04. HAZ and CD4% increased and VL decreased in the 7000 IU/d group (p<0.04. Younger (5-13y and older (30-50y subjects had greater Δ25D than those 14-29y (26±17 and 28±12 vs. 11±11 ng/ml, respectively, p≤0.001. Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03.In a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.ClinicalTrials.gov NCT02189902.
Amelia O Clive
Full Text Available Animal studies have shown Zoledronic Acid (ZA may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD. We performed a pilot study to evaluate its effects in humans.We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1 to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI from randomisation to week 5. Multiple secondary endpoints were also evaluated.Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline. At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD 4.16 (95%CI -4.7 to 13.0 or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3. Two of nine (22% in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo. There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9, side effects or serious adverse event rates.This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further.UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.
Bayne, C G; Hunt, W S; Johanson, D C; Flynn, E T; Weathersby, P K
Decompression sickness in human beings exposed to high ambient pressure is thought to follow from gas bubble formation and growth in the body during return to low pressure. Detection of Doppler-shifted ultrasonic reflections in major blood vessels has been promoted as a noninvasive and sensitive indicator of the imminence of decompression sickness. We have conducted a double-blind, prospective clinical trial of Doppler ultrasonic bubble detection in simulated diving using 83 men, of whom 8 were stricken and treated for the clinical disease. Diagnosis based only on the Doppler signals had no correlation with clinical diagnosis. Bubble scores were only slightly higher in the stricken group. The Doppler technique does not appear to be of diagnostic value in the absence of other clinical information.
Full Text Available Abstract Background Following the successful introduction of five topic-specific research networks in the UK, the Comprehensive Local Research Network (CLRN was established in 2008 in order to provide a blanket level of support across the whole country regardless of the clinical discipline. The role of the CLRN was to facilitate recruitment into clinical trials, and to encourage greater engagement in research throughout the National Health Service (NHS. Methods This report evaluates the impact of clinical research networks in supporting clinical trials in the UK, with particular reference to our experiences from two non-commercial dermatology trials. It covers our experience of engaging with the CLRN (and other research networks using two non-commercial dermatology trials as case studies. We present the circumstances that led to our approach to the research networks for support, and the impact that this support had on the delivery of these trials. Results In both cases, recruitment was boosted considerably following the provision of additional support, although other factors such as the availability of experienced personnel, and the role of advertising and media coverage in promoting the trials were also important in translating this additional resource into increased recruitment. Conclusions Recruitment into clinical trials is a complex task that can be influenced by many factors. A world-class clinical research infrastructure is now in place in England (with similar support available in Scotland and Wales, and it is the responsibility of the research community to ensure that this unique resource is used effectively and responsibly.
Ross, Joseph S.; Mulvey, Gregory K.; Hines, Elizabeth M.; Nissen, Steven E.; Krumholz, Harlan M.
Editors' Summary Background People assume that whenever they are ill, health care professionals will make sure they get the best available treatment. But how do clinicians know which treatment is most appropriate? In the past, clinicians used their own experience to make treatment decisions. Nowadays, they rely on evidence-based medicine—the systematic review and appraisal of the results of clinical trials, studies that investigate the efficacy and safety of medical interventions in people. H...
Carolina Riveros; Agnes Dechartres; Elodie Perrodeau; Romana Haneef; Isabelle Boutron; Philippe Ravaud
Editors' Summary Background When patients consult a doctor, they expect to be recommended what their doctor believes is the most effective treatment with the fewest adverse effects. To determine which treatment to recommend, clinicians rely on sources that include research studies. Among studies, the best evidence is generally agreed to come from systematic reviews and randomized controlled clinical trials (RCTs), studies that test the efficacy and safety of medical interventions by comparing...
Ross, Joseph S.; Mulvey, Gregory K.; Hines, Elizabeth M.; Steven E. Nissen; Krumholz, Harlan M.
Editors' Summary Background People assume that whenever they are ill, health care professionals will make sure they get the best available treatment. But how do clinicians know which treatment is most appropriate? In the past, clinicians used their own experience to make treatment decisions. Nowadays, they rely on evidence-based medicine—the systematic review and appraisal of the results of clinical trials, studies that investigate the efficacy and safety of medical interventions in people. H...
Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe
Editors' Summary Background When patients consult a doctor, they expect to be recommended what their doctor believes is the most effective treatment with the fewest adverse effects. To determine which treatment to recommend, clinicians rely on sources that include research studies. Among studies, the best evidence is generally agreed to come from systematic reviews and randomized controlled clinical trials (RCTs), studies that test the efficacy and safety of medical interventions by comparing...
... clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... and evaluation of clinical trials. For drugs covered under this section, the Commissioner and other agency officials will monitor the progress of the conduct and evaluation of clinical trials and...
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... HUMAN SERVICES Food and Drug Administration Cell and Gene Therapy Clinical Trials in Pediatric... public workshop entitled ``Cell and Gene Therapy Clinical Trials in Pediatric Populations.'' The purpose... therapy clinical trials in pediatric populations, as well as challenges and considerations in the...
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Full Text Available Abstract The existence of effective therapies for most cardiovascular disease states, coupled with increased requirements that potential benefits of new drugs be evaluated on clinical rather than surrogate endpoints, makes it increasingly difficult to substantiate any incremental improvements in efficacy that these new drugs might offer. Compounding the problem is the highly controversial issue of comparing new agents with placebos rather than active pharmaceuticals in drug efficacy trials. Despite the recent consensus that placebos may be used ethically in well-defined, justifiable circumstances, the problem persists, in part because of increased scrutiny by ethics committees but also because of considerable lingering disagreement regarding the propriety and scientific value of placebo-controlled trials (and trials of antihypertensive drugs in particular. The disagreement also substantially affects the most viable alternative to placebo-controlled trials: actively controlled equivalence/noninferiority trials. To a great extent, this situation was prompted by numerous previous trials of this type that were marked by fundamental methodological flaws and consequent false claims, inconsistencies, and potential harm to patients. As the development and use of generic drugs continue to escalate, along with concurrent pressure to control medical costs by substituting less-expensive therapies for established ones, any claim that a new drug, intervention, or therapy is "equivalent" to another should not be accepted without close scrutiny. Adherence to proper methods in conducting studies of equivalence will help investigators to avoid false claims and inconsistencies. These matters will be addressed in the third article of this three-part series.
Williamson Paula R
Full Text Available Abstract Background Randomised controlled trials (RCTs represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. Methods National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. Results Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. Conclusion Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias
INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?: study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing
Full Text Available Abstract Background Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness. The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. Methods/design This is a mixed methods pragmatic multicentre feasibility pilot study with four components:- (a A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial. (b Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience. (c A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial. (d Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. Discussion The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will
Bhaswat S Chakraborty
Full Text Available This paper reviews the critical issues in the control and design of antihypertension (anti-HT clinical trials. The international guidelines and current clinical and biostatistical practices were reviewed for relevant clinical, design, end-point assessments and regulatory issues. The results are grouped mainly into ethical, protocol and assessment issues. Ethical issues arise as placebo-controlled trials (PCTs for HT-lowering agents in patients with moderate to severe HT are undertaken. Patients with organ damage due to HT should not be included in long-term PCT. Active-control trials, however, are suitable for all randomized subsets of patients, including men and women, and different ethnic and age groups. Severity subgroups must be studied separately with consideration to specific study design. Mortality and morbidity outcome studies are not required in anti-HT trials except when significant mortality and cardiovascular morbidity are suspected. Generally, changes in both systolic and diastolic blood pressures (BP at the end of the dosing interval from the baseline are compared between the active and the control arms as the primary endpoint of anti-HT effect. Onset of the anti-HT effect can be studied as the secondary endpoint. For maintenance of efficacy, long-term studies of ≥6 months need to be undertaken. Error-free measurement of BP is a serious issue as spontaneous changes in BP are large and active drug effect on diastolic BP is often small. Placebo-controlled short-term studies (of ~12 weeks for dose-response and titration are very useful. Safety studies must be very vigilant on hypotension, orthostatic hypotension and effects on heart. In dose-response studies, at least three doses in addition to placebo should be used to well characterize the benefits and side-effects.
Rodrigo Pessoa Cavalcanti Lira
Full Text Available PURPOSE: To compare clinical trials published in Brazilian journals of ophthalmology and in foreign journals of ophthalmology with respect to the number of citations and the quality of reporting [by applying the Consolidated Standards for Reporting Trials (CONSORT statement writing standards]. METHODS: The sample of this systematic review comprised the two Brazilian journals of ophthalmology indexed at Science Citation Index Expanded and six of the foreign journals of ophthalmology with highest Impact Factor® according ISI. All clinical trials (CTs published from January 2009 to December 2010 at the Brazilians journals and a 1:1 randomized sample of the foreign journals were included. The primary outcome was the number of citations through the end of 2011. Subgroup analysis included language. The secondary outcome included likelihood of citation (cited at least once versus no citation, and presence or absence of CONSORT statement indicators. RESULTS: The citation counts were statistically significantly higher (P<0.001 in the Foreign Group (10.50 compared with the Brazilian Group (0.45. The likelihood citation was statistically significantly higher (P<0.001 in the Foreign Group (20/20 - 100% compared with the Brazilian Group (8/20 - 40%. The subgroup analysis of the language influence in Brazilian articles showed that the citation counts were statistically significantly higher in the papers published in English (P<0.04. Of 37 possible CONSORT items, the mean for the Foreign Group was 20.55 and for the Brazilian Group was 13.65 (P<0.003. CONCLUSION: The number of citations and the quality of reporting of clinical trials in Brazilian journals of ophthalmology still are low when compared with the foreign journals of ophthalmology with highest Impact Factor®.
Full Text Available Abstract Background Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs. Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion Previous studies in adults
Full Text Available Many prescribed treatments for children have not been adequately tested in children, sometimes resulting in harmful treatments being given and beneficial treatments being withheld. In the absence of specific trial-based data in children, results of studies in adults are extrapolated, which is often inappropriate because children have different range of diseases and metabolize medications differently. Trials in children are more challenging than those in adults and the pool of eligible children entering trials is often small. Children must have at last the same rights as adults in relation to receiving treatment with medicinal products that have been fully tested. The need for more studies to obtain paediatric information for medicines used in children is now a matter of consensus on a global basis and is considered a public health priority. Therfore a survey was performed in university hospitals in Germany targeting the current and future situation of children in clinical trials. The questionnaire of this survey was sent to 68 paediatric departments in 31 university clinics in Germany with a respond rate of 27% with respect to 18 returned questionnaires. With regard to new laws, guidelines and strong governmental support and funding an increasing number of clinical trials is expected. Surprisingly, the number of trials in the paediatric population remains unchanged within a period of 4 years (2005-2008. Added to the surveys performed within the pharmaceutical industry from Heinrich and Hark the number of trials in children remains unchanged even within a period of 9 years (2000-2008. The efforts undertaken by the government regarding funding and supporting KKS (Coordinating Centers for Clinical Trials and affiliated PAED-Net (Pediatric Network on Medication Development and Testing in Children and Adolescents at KKS appear to be insufficient. Beginning of this year the legal framework with the urgent expected “Paediatric Regulation” was
de Glas, N A; Hamaker, M E; Kiderlen, M; de Craen, A J M; Mooijaart, S P; van de Velde, C J H; van Munster, B C; Portielje, J E A; Liefers, G J; Bastiaannet, E
With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of older patients. The aim of this study was to present an overview of trial characteristics and endpoints of all currently running clinical trials in breast cancer, particularly in older patients. The clinical trial register of the United States National Institutes of Health Differences was searched for all current clinical trials on breast cancer treatment. Trial characteristics and endpoints were retrieved from the register and differences in characteristics between studies in older patients specifically (defined as a lower age-limit of 60 years or older) and trials in all patients were assessed using χ(2) tests. We included 463 clinical trials. Nine trials (2 %) specifically investigated breast cancer treatment in older patients. Ninety-one breast cancer trials included any patient-related endpoint (20 %), while five trials specifically addressing older patients included any patient-related endpoint (56 %, P = 0.02). Five of the trials in older patients incorporated a geriatric assessment (56 %). Clinical trials still rarely incorporate patient-related endpoints, even in trials that specifically address older patients. Trials that are specifically designed for older patients do not often incorporate a geriatric assessment in their design. This implicates that current clinical studies are not expected to fill the gap in knowledge concerning treatment of older breast cancer patients in the next decade.
Full Text Available Lisa Marie Saldanha,1 Saumya Nayak,1 Adeline Sng,1 Mei-Ling Long,1 Elisabeth Schrader,2 Amanur Rahman,3 Elvira Zenaida Lansang,1 Karen Wai,1 Ken Lee41Feasibility and Site Identification Asia, Quintiles East Asia Private Limited, Singapore; 2Quintiles Pediatric Center of Excellence, Durham, NC, USA; 3Faculty of Engineering, National University of Singapore, Singapore; 4Asia Site Services, Quintiles East Asia Private Limited, SingaporeObjective: This site survey was conducted to understand the current pediatric clinical trial landscape across countries in the Asia Pacific region, specifically in terms of interest, experience, capabilities, requirements of the ethics committee, patient availability, and overall challenges involved in conducting pediatric trials.Methods and materials: Between May and June 2012, an English language survey form was sent to sites (identified through Quintiles’ internal database with pediatric capability and referrals from doctors during a preliminary outreach. In July 2012, the responses from the completed survey forms were entered into SurveyMethods, a web-based central repository. Data analysis was performed in August–September 2012 using SurveyMethods.Results: Seventy-seven sites were contacted for this survey across the Asia Pacific region. Sixty-four percent (49 sites completed 63 surveys and confirmed interest to participate in clinical trials in the pediatric population. Seventy-one percent of the sites had prior experience. Eighty percent confirmed needing an assent from pediatric patients; 81%–95% confirmed acceptance of placebo-controlled and pharmacokinetic studies by ethics committees; and 37% cited challenges in conducting studies in this population.Conclusion: This survey indicates that there is a high level of interest among sites in the Asia Pacific region in conducting pediatric trials across various therapeutic indications. No major insurmountable challenges were identified in conducting
Full Text Available Kristian Thorlund,1–3 Eric Druyts,1,4 Kabirraaj Toor,1,5 Jeroen P Jansen,1,6 Edward J Mills1,3 1Redwood Outcomes, Vancouver, BC, 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Stanford Prevention Research Center, Stanford University, Stanford, CA, USA; 4Department of Medicine, Faculty of Medicine, 5School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; 6Department of Public Health and Community Medicine, Tufts University, Boston, MA, USA Introduction: Network meta-analysis (NMA is an extension of conventional pairwise meta-analysis that allows for simultaneous comparison of multiple interventions. Well-established drug class efficacies have become commonplace in many disease areas. Thus, for reasons of ethics and equipoise, it is not practical to randomize patients to placebo or older drug classes. Unique randomized clinical trial designs are an attempt to navigate these obstacles. These alternative designs, however, pose challenges when attempting to incorporate data into NMAs. Using ulcerative colitis as an example, we illustrate an example of a method where data provided by these trials are used to populate treatment networks. Methods: We present the methods used to convert data from the PURSUIT trial into a typical parallel design for inclusion in our NMA. Data were required for three arms: golimumab 100 mg; golimumab 50 mg; and placebo. Golimumab 100 mg induction data were available; however, data regarding those individuals who were nonresponders at induction and those who were responders at maintenance were not reported, and as such, had to be imputed using data from the rerandomization phase. Golimumab 50 mg data regarding responses at week 6 were not available. Existing relationships between the available components were used to impute the expected proportions in this missing subpopulation. Data for placebo maintenance
Hall R David
Full Text Available Abstract Background The National Institute of Diabetes and Digestive and Kidney Diseases have established central repositories for the collection of DNA, biological samples, and clinical data to be catalogued at a single site. Here we present an overview of the site which stores the clinical data and links to biospecimens. Description The NIDDK Data repository is a web-enabled resource cataloguing clinical trial data and supporting information from NIDDK supported studies. The Data Repository allows for the co-location of multiple electronic datasets that were created as part of clinical investigations. The Data Repository does not serve the role of a Data Coordinating Center, but rather as a warehouse for the clinical findings once the trials have been completed. Because both biological and genetic samples are collected from many of the studies, a data management system for the cataloguing and retrieval of samples was developed. Conclusion The Data Repository provides a unique resource for researchers in the clinical areas supported by NIDDK. In addition to providing a warehouse of data, Data Repository staff work with the users to educate them on the datasets as well as assist them in the acquisition of multiple data sets for cross-study analysis. Unlike the majority of biological databases, the Data Repository acts both as a catalogue for data, biosamples, and genetic materials and as a central processing point for the requests for all biospecimens. Due to regulations on the use of clinical data, the ultimate release of that data is governed under NIDDK data release policies. The Data Repository serves as the conduit for such requests.
Full Text Available Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.
Full Text Available Abstract Background In consideration of patients seeking to use traditional Chinese medicine, an evidence-based potentiality for safe and effective use of herbal medicine and acupuncture in treatment of acne vulgaris has been suggested. However, despite common use of a combination of herbal medicine and acupuncture in clinical practice, the current level of evidence is insufficient to draw a conclusion for an interaction and efficacy of herbal medicine and acupuncture. Therefore, considering these methodological flaws, this study was designed to assess the interaction and efficacy of an available herbal medicine, Keigai-rengyo-to extract (KRTE, and acupuncture for treatment of acne using the 2 × 2 factorial design and the feasibility of a large clinical trial. Methods/Design A randomized, assessor single blinded, 2 × 2 factorial pilot trial will be conducted. Forty four participants with acne vulgaris will be randomized into one of four groups: waiting list group (WL, KRTE only group (KO, acupuncture only group (AO, and KRTE and acupuncture combined treatment group (KA. After randomization, a total of 8 sessions of acupuncture treatment will be performed twice a week in the AO- and KA groups, respectively. Patients in the KO- and KA groups will be prescribed KRTE 3 times a day at a dose of 7.4 g after meals for 4 weeks. The following outcome measurements will be used in examination of subjects: the mean percentage change and the count change of inflammatory and non-inflammatory acne lesions, the Skindex 29, visual analogue scale (VAS and investigator global assessment (IGA from baseline to the end of the trial. Trial Registration The trial is registered with the Clinical Research Information Service (CRiS, Republic of Korea: KCT0000071.
Gordon, Michael; Russo, Kate
This pilot study explored the experiences and understanding of clinical psychology practices and services of children and adolescents attending clinical psychology outpatient appointments. Fifteen young participants took part in the study. A content analysis indicated that young children and adolescents have an appropriate understanding of the…
Kerner, T.; Machottas, A.; Kerner, S.; Ahlers, O.; Haberl, H.; Riess, H.; Hildebrandt, B.
Poediatric craniofacial surgery (pCFS) regularly requires transfusion of packed red blood cells (pRBC). In this clinical pilot study two different transfusion regimens were prospectively compared concerning pRBC transfusions, postoperative bleeding and other clinical parameters. Thirty infants (aged
Edwards, Sarah J L
Current orthodoxy in research ethics assumes that subjects of clinical trials reserve rights to withdraw at any time and without giving any reason. This view sees the right to withdraw as a simple extension of the right to refuse to participate all together. In this paper, however, I suggest that subjects should assume some responsibilities for the internal validity of the trial at consent and that these responsibilities should be captured by contract. This would allow the researcher to impose a penalty on the subject if he were to withdraw without good reason and on a whim. This proposal still leaves open the possibility of withdrawing without penalty when it is in the subject's best interests to do so. Giving researchers recourse to legal remedy may now be necessary to protect the science, as existing methods used to increase retention are inadequate for one reason or another.
This study considers the detection of treatment-by-subset interactions in a stratified, randomised clinical trial with a binary-response variable. The focus lies on the detection of qualitative interactions. In addition, the presented method is useful more generally, as it can assess the inconsistency of the treatment effects among strata by using an a priori-defined inconsistency margin. The methodology presented is based on the construction of ratios of treatment effects. In addition to multiplicity-adjusted p-values, simultaneous confidence intervals are recommended to use in detecting the source and the amount of a potential qualitative interaction. The proposed method is demonstrated on a multi-regional trial using the open-source statistical software R. PMID:25049176
Yung, C Y
Since the approval of lithium use in treatment of acute mania, there have been numerous clinical trials of lithium in medical and psychiatric disorders. This paper gives a brief review of the literature on lithium trials in approximately fourteen medical conditions. These are: hyperthyroidism, metabolizing thyroid cancer, syndrome of inappropriate secretion of antidiuretic hormone, premenstrual tension syndrome, anorexia nervosa, Felty's syndrome, chemotherapy-induced neutropenia, aplastic anemia, seborrheic dermatitis, eczematoid dermatitis, cyclic vomiting, diabetes mellitus and asthma. Most of the case reports cited showed the efficacy of the side effects from lithium salt in the management of the symptoms and signs of these disorders, however, well-designed and controlled studies give negative results. The positive results are reported in the group of disorders having an underlying subdromal affective syndrome such as premenstrual tension syndrome and anorexia nervosa. Other encouraging reports include the effect of lithium to induce leucocytosis in Felty's syndrome and chemotherapy-induced neutropenia. PMID:6395135
Singh, Narendra; Gupta, Milan
Randomized clinical trials (RCTs) remain the foundation for assessing and introducing evidence-based therapies into cardiovascular (CV) medicine. In 2015, a number of RCTs were reported and published that have great potential to improve CV outcomes and thus to change clinical practice. We highlight the results and implications of major RCTs in the areas of acute coronary syndrome (ACS), interventional cardiology, atrial fibrillation, lipids, heart failure, diabetes, and hypertension. Among the trials we discuss, PEGASUS and DAPT provide guidance regarding the potential benefits and hazards of longer-term dual-antiplatelet therapy after percutaneous coronary intervention (PCI) or myocardial infarction (MI). The BRIDGE study evaluated the role of bridging patients with atrial fibrillation who underwent noncardiac surgery with low-molecular-weight heparin while temporarily discontinuing their oral anticoagulant. The REVERSE-AD trial addressed the highly relevant issue of the first reversal agent (idarucizumab) for the direct oral anticoagulant dabigatran. The IMPROVE-IT assessed the benefits of adding ezetimibe to a statin in patients with ACS. Coupled with the latest studies involving proprotein convertase subtilisin/kexin type 9 inhibitors, the lipid field was particularly active in 2015. The year ended with major headlines in hypertension and diabetes. The SPRINT may lead to a new era in hypertension, with lowered blood pressure (BP) targets, and EMPA-REG became the first study ever to demonstrate a convincing reduction in CV events with a glucose-lowering agent, in this case empagliflozin. The results of these and other trials will likely impact practice guidelines and improve outcomes for our patients. PMID:27038506
Full Text Available Abstract Background Clinical trial and epidemiological studies need high quality biospecimens from a representative sample of participants to investigate genetic influences on treatment response and disease. Obtaining blood biospecimens presents logistical and financial challenges. As a result, saliva biospecimen collection is becoming more frequent because of the ease of collection and lower cost. This article describes an assessment of saliva biospecimen samples collected through the mail, trial participant demographic and behavioral characteristics, and their association with saliva and DNA quantity and quality. Methods Saliva biospecimens were collected using the Oragene® DNA Self-Collection Kits from participants in a National Cancer Institute funded smoking cessation trial. Saliva biospecimens from 565 individuals were visually inspected for clarity prior to and after DNA extraction. DNA samples were then quantified by UV absorbance, PicoGreen®, and qPCR. Genotyping was performed on 11 SNPs using TaqMan® SNP assays and two VNTR assays. Univariate, correlation, and analysis of variance analyses were conducted to observe the relationship between saliva sample and participant characteristics. Results The biospecimen kit return rate was 58.5% among those invited to participate (n = 967 and 47.1% among all possible COMPASS participants (n = 1202. Significant gender differences were observed with males providing larger saliva volume (4.7 vs. 4.5 ml, p = 0.019, samples that were more likely to be judged as cloudy (39.5% vs. 24.9%, p 0.21, P Conclusion Findings from this study show that demographic and behavioral characteristics of smoking cessation trial participants have significant associations with saliva and DNA metrics, but not with the performance of TaqMan® SNP or VNTR genotyping assays. Trial registration COMPASS; registered as NCT00301145 at clinicaltrials.gov.
Callahan Christopher M
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
Elvira Zenaida Lansang,1 Kenneth Tan,2 Saumya Nayak,1 Ken J Lee,1 Karen Wai1 1Feasibility and Site Identification – Asia, Quintiles East Asia Pte Ltd, Singapore; 2National University of Singapore, Singapore Introduction: Conducting clinical trial feasibility is an important first step in initiating a clinical trial. A robust feasibility process ensures that a realistic capability assessment is made before conducting a trial. A retrospective analysis of vaccine clinical trials was p...
Lansang EZ; Tan K; Nayak S; Lee KJ; Wai K
Elvira Zenaida Lansang,1 Kenneth Tan,2 Saumya Nayak,1 Ken J Lee,1 Karen Wai1 1Feasibility and Site Identification – Asia, Quintiles East Asia Pte Ltd, Singapore; 2National University of Singapore, Singapore Introduction: Conducting clinical trial feasibility is an important first step in initiating a clinical trial. A robust feasibility process ensures that a realistic capability assessment is made before conducting a trial. A retrospective analysis of vaccine clinical trials was pe...
Tillie, Nicole A.; Parker, Jayson L.; Feld, Jordan J.
Background and Aims. This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015. Methods. Hepatitis C drug development trials that were in phases I–III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treate...
Full Text Available This pilot study aimed to inform future research evaluating the effectiveness of Platelet Rich Plasma (PRP injection for tendinopathy.Randomized control trial (RCT and synchronous observational cohort studies. For the RCT, consecutive consenting patients treated at an academic sports medicine clinic were randomly assigned to either a PRP or placebo control group.The Glen Sather Sport Medicine Clinic, Edmonton, Canada.The RCT included 9 participants with rotator cuff tendinopathy. The cohort study included 178 participants with a variety of tendinopathies.Patients receiving PRP were injected with 4 ml of platelets into the supraspinatus and/or infraspinatus, while patients in the placebo group were injected with 4 ml of saline. All participants undertook a 3-month standardized, home-based, daily exercise program.Participants in the RCT were re-evaluated 3, and 6 months post-injection. Change scores before and after injection on pain, disability and MRI-documented pathology outcomes were compared. In the cohort study, pain and disability were measured at 1, 2 and 3 months post-injection.For the RCT, 7 participants received PRP and 2 received placebo injections. Patients receiving PRP reported clinically important improvements in pain (>1.5/10 on VAS, disability (>15 point DASH change, and tendon pathology while those receiving placebo injections did not. In the observational cohort, statistically and clinically significant improvements in pain and disability were observed.This pilot study provides information for planning future studies of PRP effectiveness. Preliminary results indicate intratendinous, ultrasound-guided PRP injection may lead to improvements in pain, function, and MRI-documented tendon pathology.Controlled-Trials.com ISRCTN68341698.
Neilson, Aileen R; Bruhn, Hanne; Christine M. Bond; Elliott, Alison M; Smith, Blair H; Hannaford, Philip C; Holland, Richard; Amanda J Lee; Watson, Margaret; Wright, David; McNamee, Paul
Objectives To explore differences in mean costs (from a UK National Health Service perspective) and effects of pharmacist-led management of chronic pain in primary care evaluated in a pilot randomised controlled trial (RCT), and to estimate optimal sample size for a definitive RCT. Design Regression analysis of costs and effects, using intention-to-treat and expected value of sample information analysis (EVSI). Setting Six general practices: Grampian (3); East Anglia (3). Participants 125 pat...
G. P. Guens
Full Text Available In this pilot trial we analyzed the correlation between neoangiogenesis and psychological status in ovarian cancer patients. We found the correlation between depression levels and serum vascular endothelial growth factor levels in ovarian cancer patients – coefficient of rank correlation (ρ was 0.42 (95 % confidence interval 0.01–0.72; р < 0,05, that suggests the relationship between this parameters.
Naylor, Jennifer C; Dolber, Trygve R.; Strauss, Jennifer L.; Kilts, Jason D.; Strauman, Timothy J.; Bradford, Daniel W.; Szabo, Steven T; Youssef, Nagy A.; Connor, Kathryn M.; Davidson, Jonathan R.T.; Marx, Christine E.
Subthreshold posttraumatic stress disorder (PTSD) is associated with increased risk for suicidality, depression, and functional impairment. We thus conducted a small (N=12) pilot randomized controlled trial (RCT) with paroxetine for subthreshold PTSD in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) era veterans. Hospital Anxiety and Depression Scale (HADS) scores improved by 30.4% in the paroxetine group. Paroxetine may have promise for subthreshold PTSD.
Full Text Available Background: It is unclear whether local anesthetic eye drops can be safely used for the topical anesthesia of patients with minor corneal injury who are discharged from the emergency department (ED. Objectives: To assess whether topical 0.4% amethocaine self-administered to a maximum recommended frequency of once every hour for 36-48 h is safe in the management of uncomplicated corneal injury in patients discharged from the ED. Patients and Methods: A pilot randomized double-blinded trial comparing topical 0.4% amethocaine with topical normal saline. Results: Forty-seven subjects were recruited, with 22 randomized to receive amethocaine and 25 to receive placebo (normal saline . Baseline characteristics, including corneal injury type, were similar in both groups. There were no significant functional or clinical adverse sequelae in the majority of enrolled patients who could be contacted at 2 weeks (17/22 for amethocaine and 21/25 for placebo. Follow-up for the primary study outcome was suboptimal, with only 7/22 from the amethocaine group and 9/25 from the saline group presenting for 36-48 h review; there was a statistically nonsignificant trend for persistence of the corneal defect in the amethocaine group as compared with the saline group (2/7 and 1/9, respectively. Conclusion: Compared with saline drops, amethocaine eye drops are not definitely safe but they are effective for topical analgesia in minor corneal injury. Until further definitive studies, topical nonsteroidal agents or long-lasting artificial tears may be preferred for the topical analgesia of minor corneal injury. Return for corneal re-evaluation will necessarily remain suboptimal in an otherwise self-limiting condition, leading to a bias even if study recruitment is good.
Bazarbashi, Shouki; Hassan, Anees; Eldin, Ahmed Mohi; Soudy, Hussein; Hussain, Fazal
Despite the increasing number of medical articles being published from the Middle East, clinical research is still lagging behind compared to other regions. Enrolling participants into clinical trials presents an important challenge. We wanted to explore the perception, knowledge, and willingness of cancer patients to participate in oncology clinical trials and to recommend strategies to overcome these challenges. A 31-item questionnaire was administered to cancer patients and their family members in an outpatient clinic. Two hundred four patients and family members were enrolled between December 2011 and February 2013. Fifty-eight percent of the participants were aware of clinical trials. Some misconceptions included the following: 22% believed that no clinical trials were conducted in the Arab world, 19% believed that clinical trials in the Arab world were not under any regulatory authority supervision, and 15% believed that local clinical trials are conducted on subjects without their consent. One third of patients assumed that clinical trials are executed on animals instead of humans, and greater than 40% believed that clinical trials are performed for new medications only. Finally, 61% of the survey participants who were aware of clinical trials expressed their willingness to participate in trials. This large cohort survey demonstrated that a relatively significant number of Saudi cancer patients and their families are aware of clinical trials and a similarly high number of participants are willing to participate in clinical trials. This leads us to believe that patients' awareness and perception of clinical trials are not a significant limiting factor in clinical trial recruitment in our region.
Full Text Available Background: The most common mental health problems among refugees are depression and posttraumatic stress disorder (PTSD. Eye movement desensitization and reprocessing (EMDR is an effective treatment for PTSD. However, no previous randomized controlled trial (RCT has been published on treating PTSD symptoms in a refugee camp population. Objective: Examining the effect of EMDR to reduce the PTSD and depression symptoms compared to a wait-list condition among Syrian refugees. Method: Twenty-nine adult participants with PTSD symptoms were randomly allocated to either EMDR sessions (n=15 or wait-list control (n=14. The main outcome measures were Impact of Event Scale-Revised (IES-R and Beck Depression Inventory (BDI-II at posttreatment and 4-week follow-up. Results: Analysis of covariance showed that the EMDR group had significantly lower trauma scores at posttreatment as compared with the wait-list group (d=1.78, 95% CI: 0.92–2.64. The EMDR group also had a lower depression score after treatment as compared with the wait-list group (d=1.14, 95% CI: 0.35–1.92. Conclusion: The pilot RCT indicated that EMDR may be effective in reducing PTSD and depression symptoms among Syrian refugees located in a camp. Larger RCTs to verify the (cost- effectiveness of EMDR in similar populations are needed.
Rowe, Lorelei Simpson; Jouriles, Ernest N; McDonald, Renee
Despite extensive efforts to develop and implement programs to prevent sexual violence, few programs have empirically-demonstrated efficacy. The primary exceptions are programs that emphasize risk-reduction skills; yet even these programs are not consistently effective. This study seeks to add to the literature by evaluating the effects of My Voice, My Choice (MVMC), a 90-minute assertive resistance training program that emphasizes skill practice in an immersive virtual environment (IVE). We hypothesized that MVMC would reduce male-to-female sexual victimization among adolescent girls over a 3-month follow-up period. We also examined whether these results would generalize to other forms of male-to-female relationship violence and to girls' psychological distress. Eighty-three female students from an urban public high school were randomized to MVMC (n=47) or to a wait-list control condition (n=36); 78 provided data over the 3-month follow-up period. Participants assigned to MVMC were less likely than control participants to report sexual victimization during the follow-up period. Our results also suggest that MVMC reduced risk for psychological victimization and for psychological distress among participants with greater prior victimization at baseline. The promising results of this pilot trial suggest that MVMC may help girls evade male-to-female relationship violence. PMID:25892168
Livia M. M. Pontes
Full Text Available Cognitive deficits in schizophrenia can massively impact functionality and quality of life, furthering the importance of cognitive training. Despite the development of the field in Europe and in the United States, no programmes have been developed and tested in developing countries. Different cultural backgrounds, budget restrictions, and other difficulties may render treatment packages created in high income countries difficult for adoption by developing nations. We performed a pilot double-blind, randomized, controlled trial in order to investigate the efficacy and feasibility of an attention and memory training programme specially created in a developing nation. The intervention used simple, widely available materials, required minimal infrastructure, and was conducted in groups. The sample included seventeen stable Brazilians with schizophrenia. Sessions were conducted weekly during five months. The cognitive training group showed significant improvements in inhibitory control and set-shifting over time. Both groups showed improvements in symptoms, processing speed, selective attention, executive function, and long-term visual memory. Improvements were found in the control group in long-term verbal memory and concentration. Our findings reinforce the idea that cognitive training in schizophrenia can be constructed using simple resources and infrastructure, facilitating its adoption by developing countries, and it may improve cognition.
Mrakotsky, Christine; Masek, Bruce; Biederman, Joseph; Raches, Darcy; Hsin, Olivia; Forbes, Peter; de Moor, Carl; DeMaso, David Ray; Gonzalez-Heydrich, Joseph
Mirtazapine is indicated for major depression and used for anxiety in adults; however, little is known about its application in pediatric populations. This is an 8-week open-label pilot study of mirtazapine in children with social phobia age 8-17 years. Primary outcomes were symptom improvement based on clinician rating and self-report, as well as tolerability based on rates of discontinuation due to adverse effects. Fifty-six percent (10/18) responded to treatment, 17% (3/18) achieved full remission. Social phobia symptoms improved significantly during the first 2 weeks of treatment, as did comorbid symptoms of depression and anxiety. Eleven patients (61%) did not complete all 8 weeks of treatment; four patients (22%) discontinued due to adverse effects including fatigue and irritability. The others discontinued due to study burden (28%), insufficient response (6%), or to pursue herbal treatment (6%). Significant weight gain was observed. Larger controlled trials are needed to further evaluate efficacy and safety. PMID:17419001
Allon, Michael; Lok, Charmaine E
The Fistula First Initiative has strongly encouraged nephrologists, vascular access surgeons, and dialysis units in the United States to make valiant efforts to increase fistula use in the hemodialysis population. Unfortunately, the rigid "fistula first" recommendations are not based on solid, current, evidence-based data and may be harmful to some hemodialysis patients by subjecting them to prolonged catheter dependence with its attendant risks of bacteremia and central vein stenosis. Once they are successfully cannulated for dialysis, fistulas last longer than grafts and require fewer interventions to maintain long-term patency for dialysis. However, fistulas have a much higher primary failure rate than grafts, require more interventions to achieve maturation, and entail longer catheter dependence, thereby leading to more catheter-related complications. Given the tradeoffs between fistulas and grafts, there is equipoise about their relative merits in patients with moderate to high risk of fistula nonmaturation. The time is right for definitive, large, multicenter randomized clinical trials to compare fistulas and grafts in various subsets of chronic kidney disease patients. Until the results of such clinical trials are known, the optimal vascular access for a given patients should be determined by the nephrologist and access surgeon by taking into account (1) whether dialysis has been initiated, (2) the patient's life expectancy, (3) whether the patient has had a previous failed vascular access, and (4) the likelihood of fistula nonmaturation. Careful clinical judgment should optimize vascular access outcomes and minimize prolonged catheter dependence among hemodialysis patients. PMID:21030576
Singh, Romi; Wang, Ouhong
Clinical studies are being placed in emerging markets as part of global drug development programs to access large pool of eligible patients and to benefit from a cost effective structure. However, over the last few years, the definition of "emerging markets" is being revisited, especially from a regulatory perspective. For purposes of this article, countries outside US, EU and the traditional "western countries" are discussed. Multiple factors are considered for placement of clinical studies such as adherence to Good Clinical Practice (GCP), medical infrastructure & standard of care, number of eligible patients, etc. This article also discusses other quantitative factors such as country's GDP, patent applications, healthcare expenditure, healthcare infrastructure, corruption, innovation, etc. These different factors and indexes are correlated to the number of clinical studies ongoing in the "emerging markets". R&D, healthcare expenditure, technology infrastructure, transparency, and level of innovation, show a significant correlation with the number of clinical trials being conducted in these countries. This is the first analysis of its kind to evaluate and correlate the various other factors to the number of clinical studies in a country. PMID:24070788
Singh, Romi; Wang, Ouhong
Clinical studies are being placed in emerging markets as part of global drug development programs to access large pool of eligible patients and to benefit from a cost effective structure. However, over the last few years, the definition of "emerging markets" is being revisited, especially from a regulatory perspective. For purposes of this article, countries outside US, EU and the traditional "western countries" are discussed. Multiple factors are considered for placement of clinical studies such as adherence to Good Clinical Practice (GCP), medical infrastructure & standard of care, number of eligible patients, etc. This article also discusses other quantitative factors such as country's GDP, patent applications, healthcare expenditure, healthcare infrastructure, corruption, innovation, etc. These different factors and indexes are correlated to the number of clinical studies ongoing in the "emerging markets". R&D, healthcare expenditure, technology infrastructure, transparency, and level of innovation, show a significant correlation with the number of clinical trials being conducted in these countries. This is the first analysis of its kind to evaluate and correlate the various other factors to the number of clinical studies in a country.
Muir, Keith W; Macrae, I Mhairi
Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a "responder" population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4-6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis. PMID:27543177
Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana
Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML. PMID:26643920
Bhagat, Seema; Kapatkar, Vaibhavi K; Mourya, Meenakshi; Roy, Sucheta; Jha, Shailendra; Reddy, Rajasekhar; Kadhe, Ganesh; Mane, Amey; Sawant, Sandesh
Conduct of clinical trials has undergone substantial changes over the last two decades. Newer markets, evolving guidelines and documentation and high cost involved in conducting the trials have led pharmaceutical companies to prepare a risk mitigation plan. Extensive monitoring of potential risks is an essential element of clinical trials which helps to ensure quality and integrity of a clinical investigation. Every clinical trial has pre (before the trial), conduct and post phase. This article which has been developed as a result of extensive research at ground level by a reputed pharmaceutical company to identify the potential stages of risks that could affect the overall quality and safety of a trial and its outcome during the pre-phase of trial (the stage of the trial where the study design is being planned before initiation of the clinical trial). It includes risks associated with basic study concept, protocol design, Confidential Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application signing, vendors of central drug laboratory, site and investigator selection, Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC) submission, etc. have been highlighted. The risk based mitigation strategy (to develop an effective risk monitoring plan before staring a clinical trial) has also been suggested by authors. A well-tailored and integrated plan, recognition of potential risks and their mitigation strategy can result in the pre exclusion or end to end solution of all the risks associated with pre- phase of clinical trials. PMID:26435140
Platt, Jennica; Baxter, Nancy; Jones, Jennifer; Metcalfe, Kelly; Causarano, Natalie; Hofer, Stefan OP; ONeill, Anne; Cheng, Terry; Starenkyj, Elizabeth; Zhong, Toni
Background The Pre-Consultation Educational Group Intervention pilot study seeks to assess the feasibility and inform the optimal design for a definitive randomized controlled trial that aims to improve the quality of decision-making in postmastectomy breast reconstruction patients. Methods/design This is a mixed-methods pilot feasibility randomized controlled trial that will follow a single-center, 1:1 allocation, two-arm parallel group superiority design. Setting: The University Health Netw...
Khushalani, Nikhil I
Gastric cancer remains a global public health problem with considerable heterogeneity in pathogenesis and clinical presentation across geographic regions. Improved understanding of the molecular biology of this disease has opened avenues for targeted intervention. An individualized treatment approach is required for optimal management of this cancer. Overcoming resistance to therapy requires combining targeted agents with the traditional options of chemotherapy/radiation therapy, and also targeting more than 1 pathway of carcinogenesis at a time. Encouraging molecular hypothesis and biomarker-driven trials will lead to improved patient outcomes and may eventually enable the therapeutic nihilism associated with gastric cancer to be overcome. PMID:22098835
Xia, H Amy; Ma, Haijun; Carlin, Bradley P
Detection of safety signals from clinical trial adverse event data is critical in drug development, but carries a challenging statistical multiplicity problem. Bayesian hierarchical mixture modeling is appealing for its ability to borrow strength across subgroups in the data, as well as moderate extreme findings most likely due merely to chance. We implement such a model for subject incidence (Berry and Berry, 2004 ) using a binomial likelihood, and extend it to subject-year adjusted incidence rate estimation under a Poisson likelihood. We use simulation to choose a signal detection threshold, and illustrate some effective graphics for displaying the flagged signals.