PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Clinical Trials Data Monitoring Committees”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed2004

The voluntary siting process, a case study in New Jersey.

The Low-Level Radioactive Waste Policy Act of 1980 and its 1985 Amendments has not provided new disposal capacity within the United States; however, sufficient disposal capacity currently exists to handle today's disposal needs. Politics, opposition groups, and public mistrust in government have combined to limit the possibilities for establishing new disposal facilities. In 2000, New Jersey (NJ and Connecticut (CT), as members of the Northeast Compact for the disposal of low-level radioactive waste, admitted South Carolina (SC) to their compact, renaming it as the "Atlantic Compact." The advantage to SC is that they are able to prevent disposal of waste from outside the Compact. The advantage to NJ and CT is that they are guaranteed waste disposal for approximately the next 50 years, or until all currently operating nuclear power plants in the states are decommissioned. This paper details the process, much of it not following the scientific method, to try to site a low-level waste facility in NJ. With the formation of the NJ Siting Board in 1987, an effort was made to locate a site using deterministic criteria; however, in 1992, the Board shifted to a voluntary process. In 1998, the Board made the determination that there was adequate capacity for waste disposal and ended active siting. In 2000, the opportunity to form the Atlantic Compact ended siting through an out-of-state solution. While it is not clear that the voluntary process would have ultimately worked in NJ, it has worked in Canada and the process may be one of the few mechanisms for the siting of any type of hazardous material disposal facility. Also, other states still have to decide what they will do after 2008 when Barnwell is no longer open to them.

Clinical Trials Data Monitoring Committees↗
PubMedDate not supplied

Data and safety monitoring during randomized controlled trials of nursing interventions.

BACKGROUND: Principal investigators have a responsibility to ensure and maintain the scientific integrity of their research studies and to protect the safety of the participants. Data and safety monitoring is required for all types of clinical trials, and the nature and degree of the monitoring must be related to the degree of risk involved. OBJECTIVES: This article aims to define the purpose of a data and safety monitoring board (DSMB), to describe the functions of a DSMB and distinguish them from the activities of an institutional review board, and to discuss the development and implementation of a DSMB plan. METHODS: The literature on data and safety monitoring is reviewed, and the process and key issues are illustrated with examples from the authors' clinical trial and others. RESULTS: The principal role of the DSMB is to monitor the data from the trial periodically, to review and assess the performance of its operations, and to make recommendations based on interim results (e.g., modification of the study protocol, or possible early termination of the study). Although the roles of a DSMB and institutional review board complement one another, the main focus of their responsibilities is different and carried out independently of one another. The members of a DSMB are selected on the basis of their methodologic, statistical, or clinical expertise. CONCLUSION: The multiple scientific, ethical, safety, recruitment, intervention, and budgetary responsibilities of a principal investigator can be complex. The role of the DSMB is crucial and offers independent evaluation to ensure participant safety and good science.

Clinical Trials Data Monitoring Committees↗
PubMed2002

Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.

OBJECTIVES: Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD. SUBJECTS AND METHODS: Stereotaxic placements of cell suspensions of human fetal ganglionic eminence were made unilaterally into the striatum of four patients with early to moderate HD. All patients received immunotherapy with cyclosporin A, azathioprine, and prednisolone for at least six months postoperatively. Patients were assessed for safety of the procedure using magnetic resonance imaging (MRI), regular recording of serum biochemistry and haematology to monitor immunotherapy, and clinical assessment according to the Core Assessment Protocol For Intrastriatal Transplantation in HD (CAPIT-HD). RESULTS: During the six month post-transplantation period, the only adverse events related to the procedure were associated with the immunotherapy. MRI demonstrated tissue at the site of implantation, but there was no sign of tissue overgrowth. Furthermore, there was no evidence that the procedure accelerated the course of the disease. CONCLUSIONS: Unilateral transplantation of human fetal striatal tissue in patients with HD is safe and feasible. Assessment of efficacy will require longer follow up in a larger number of patients.

Adult↗
PubMed2005

Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode.

OBJECTIVE: The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic/depressive episode. If so, this would be a strong ethical argument against the conduct of such studies. METHOD: All placebo-controlled, double-blind, randomized trials of medication for the treatment of acute manic episode and the prevention of manic/depressive episode that were part of a registration dossier submitted to the regulatory authority of the Netherlands, the Medicines Evaluation Board, between 1997 and 2003, were reviewed for occurrence of suicide and attempted suicide. RESULTS: In 11 placebo-controlled studies of the treatment of acute manic episode, including 1,506 patients (117 person-years) in the combined active compound group and 1,005 patients (71 person-years) in the combined placebo group, no suicides and no suicide attempts occurred. In four placebo-controlled studies of the prevention of manic/depressive episode, including 943 patients (406 person-years) in the combined active compound group and 418 patients (136 person-years) in the combined placebo group, two suicides (493/100,000 person-years of exposure) and eight suicide attempts (1,969/100,000 person-years of exposure) occurred in the combined active compound group, but no suicides and two suicide attempts (1,467/100,000 person-years of exposure) occurred in the combined placebo group. CONCLUSIONS: Concern about greater risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials for these indications, provided that appropriate precautions are taken.

Acute Disease↗
PubMed2004

Designing a data and safety monitoring plan.

Evidence-based nursing practice is now the expected standard of care intensifying the need to conduct clinical research studies to investigate the efficacy of nursing interventions. To ensure that the urgency to document such efficacy does not compromise human participant safety, government research funding agencies are advocating special procedures to protect individuals who voluntarily participate in research studies. The National Institutes of Health application for clinical trial funding requires a data and safety monitoring plan (DSMP) to enhance human participant safety and clinical research integrity. This article describes an approach to developing a DSMP that includes a study risk assessment and a monitoring design based on that assessment.

Clinical Trials Data Monitoring Committees↗
PubMed2004

Study conduct, monitoring and data management in a trinational trial: the OPTIMA model.

The OPTions In Management with Antiretrovirals (OPTIMA) Trial, a collaboration between three governmental agencies in the USA, UK and Canada is a large-scale, multicenter, randomized controlled trial designed to compare the relative efficacy of different therapeutic strategies in HIV disease. The collaboration of three coordinating centers introduced unique data management issues including: a) use of different data systems for managing "country" trial data; b) two-way data transfer between the coordinating centers and the center where OPTIMA data is merged and analysis files are generated; and c) translation of certain data forms (mainly patient completed questionnaires) into French and Spanish. The involvement of three data centers provided a challenge in planning, designing and executing data management procedures in OPTIMA. Processes were implemented to ensure the trial's successful execution at the trinational level, without disregarding country-specific requirements and regulations. The OPTIMA model required a significant time and resource investment on behalf of all agencies involved, but allowed for autonomy and a sense of joint ownership of data in different countries.

Anti-Retroviral Agents↗
PubMed2004

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Clinical Protocols↗
PubMed2005

Equipoise in the enhanced supression of the platelet IIb/IIIa receptor with integrilin trial (ESPRIT): a critical appraisal.

Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial (ESPRIT) was a multicenter randomized controlled clinical trial in which participants were randomized between eptifibatide and placebo. A "clinical hold" was initially placed on the trial by the US Food and Drug Administration (FDA), which was concerned about the placebo-only control arm. The hold was lifted after additional information concerning the use of platelet glycoprotein IIb/IIIa inhibitors in clinical practice, derived from a survey of interventional cardiologists, was provided. The trial's principal investigator and colleagues have described how these issues were resolved, and advance a claim of equipoise for the trial. In this critical appraisal we examine the information and arguments proffered in support of the trial design and conclude that they evidence a misunderstanding of equipoise. We believe that a placebo-only control arm was not justified by the information provided by the trialists.

Angioplasty, Balloon, Coronary↗
PubMed2006

Data and safety monitoring in social behavioral intervention trials: the REACH II experience.

BACKGROUND: Psychosocial and behavioral interventions trials targeting a broad range of complex social and behavioral problems such as smoking, obesity and family caregiving have proliferated in the past 30 years. At the same time the use of Data and Safety Monitoring Boards (DSMBs) to monitor the progress and quality of intervention trials and the safety of study participants has increased substantially. Most of the existing literature and guidelines for safety monitoring and reporting of adverse events focuses on medical interventions. Consequently, there is little guidance for investigators conducting social and behavior trials. PURPOSE: This paper summarizes how issues associated with safety monitoring and adverse event reporting were handled in the Resources for Enhancing Alzheimer's Caregiver Health (REACH II) program, a multi-site randomized clinical trial, funded by the National Institutes on Aging (NIA) and the National Institutes of Nursing Research (NINR), that tested the efficacy of a multicomponent social/behavioral intervention for caregivers of persons with Alzheimer's disease. METHODS: A task force was formed to define adverse events for the trial and protocols for reporting and resolving events that occurred. The task force conducted a review of existing polices and protocols for data and safety monitoring and adverse event reporting and identified potential risks particular to the study population. An informal survey regarding data and safety monitoring procedures with investigators on psychosocial intervention trials was also conducted. RESULTS: Two categories of events were defined for both caregivers and patients; adverse events and safety alerts. A distinction was also made between events detected at baseline assessment and those detected post-randomization. Standardized protocols were also developed for the reporting and resolution of events that occurred and training of study personnel. Results from the informal survey indicated wide variability in practices for data safety and monitoring across psychosocial intervention trials. CONCLUSIONS: Overall, the REACH II experience demonstrates that existing guidelines regarding safety monitoring and adverse event reporting pose unique challenges for social/behavioral intervention trials. Challenges encountered in the REACH II program included defining and classifying adverse events, defining "resolution" of adverse events and attributing causes for events that occurred. These challenges are highlighted and recommendations for addressing them in future studies are discussed.

Alzheimer Disease↗
PubMed2005

Preliminary data release for randomized clinical trials of noninferiority: a new proposal.

Noninferiority trials often require a long follow-up period for the data to reach the maturity needed for definitive analysis. A proposal is presented that allows for early release of outcome data from a carefully specified subset of noninferiority trials. This subset is defined so that the early release of the data will be potentially useful to patients who face a treatment decision but will not compromise the integrity of the trial or interfere with the completion of the trial to its definitive analysis. In particular, the release of the data will only occur after the last participant has been randomly assigned and is off treatment-arm-specific therapy and only if it is unlikely that subsequent treatment and/or follow-up practices will change based on the knowledge of released data. In contrast to standard interim monitoring, (1) the release of the data would be automatic and independent of the observed data, and (2) the trial would continue on to its planned final analysis and not be stopped. Examples are given demonstrating how the proposal would work, along with a discussion of possible objections to the proposal.

Clinical Trials Data Monitoring Committees↗
PubMed2002

Control groups in psychosocial intervention research: ethical and methodological issues.

This article summarizes a National Institute of Mental Health (NIMH) workshop that was convened to address the ethical and methodological issues that arise when conducting controlled psychosocial interventions research and introduces 6 thoughtful and inspiring papers presented by workshop participants. These papers, on topics ranging from informed consent to ethnic minority issues, reflect the depth and breadth of expertise represented by the multidisciplinary group of scientists and ethicists present at the meeting. More extensive follow-up, particularly from federal research applications and publications, of how investigators balance the need for strong research design with ethical considerations may help advance the science of psychosocial intervention research.

Clinical Trials Data Monitoring Committees↗
PubMedDate not supplied

Randomized trials stopped early for harm in HIV/AIDS: a systematic survey.

PURPOSE: The decision to stop trials early because of the harmful effects of the intervention is complex and requires weighing statistical, logistical, and ethical considerations. We assessed the prevalence of randomized clinical trials (RCTs) stopped early for harm in HIV/AIDS and determined the quality of reporting of methods to inform the decision to stop the trial. METHOD: We searched 11 electronic databases and major conference abstract databases, contacted trialist and advocacy groups, and searched the Internet. We selected RCTs stopped early for harm. We extracted data on journal and year of publication, reporting of methods and funding, planned sample size, number and planning of interim analyses, stopping rules, and effect size of the harm outcomes. RESULTS: We found 10 RCTs stopped early for harm (median, n = 85; range, 7-1227). Most interventions (n = 9) were antiviral drugs; one trial studied vitamins to prevent vertical transmission of HIV. Five studies reported a priori defined adverse events, and only 1 trial reported planned stopping guidelines. The primary harm outcomes reported across trials included toxicity, death, and increased mother-to-child transmission. Two trials were stopped due to sudden unanticipated adverse events (Stevens-Johnson syndrome, death, and encephalopathy). Relative risk point estimates for harm ranged from 1 to 6.18. Six studies reported the presence of a data safety and monitoring board. CONCLUSION: The reporting of methods to inform the decision to stop trials for harm in this population is deficient in a variety of ways, including lack of stopping guidelines. Clinicians should interpret RCTs stopped early for harm with caution and interpret the results in light of related evidence. Trialists should improve the transparency of their decision-making regarding early stopping for harmful effects.

Anti-HIV Agents↗
PubMed2006

Neural transplantation in Huntington's disease: the NEST-UK donor tissue microbiological screening program and review of the literature.

Neural transplantation of human fetal tissue for Huntington's disease (HD) is now entering the clinical arena. The safety of the procedure has now been demonstrated in a number of studies, although the efficacy of such an approach is still being investigated. Stringent but practicable screening of the donor tissue for potential pathogens is an essential prerequisite for successful implementation of any novel transplant program that uses human fetal tissue. In this article we summarize the UK-NEST protocol for the screening of human fetal tissue being grafted to patients with mild to moderate HD. We describe the results of microbiological screening of 87 potential tissue donors in a pilot study, and of the first four donor-recipient patients included in the UK-NEST series. The rationale for the adoption and interpretation of the various tests is described and our methodology is compared with those previously used by other centers. This article therefore presents a comprehensive, logical yet pragmatic screening program that could be employed in any clinical studies that use human fetal tissue for neurotransplantation.

Brain Tissue Transplantation↗