Clinical trials : journal of the Society for Clinical Trials
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Cluster randomized trials (CRTs) complicate the interpretation of standard research ethics guidelines for several reasons. For one, the units of allocation, intervention, and observation often may differ within a single trial. In the absence of tailored and internationally accepted ethics guidelines for CRTs, researchers and research ethics committees have no common standard by which to judge ethically appropriate practices in CRTs. Moreover, lack of familiarity with and consideration of the unique features of the CRT design by research ethics committees may cause difficulties in the research ethics review process, and amplify problems such as variability in the requirements and decisions reached by different research ethics committees. ⋯ CRT investigators are experiencing challenges in the research ethics review of their trials, including excessive delays, variability in process and outcome, and imposed requirements that can have negative consequences for study conduct. Investigators identified a clear need for ethics guidelines for CRTs and education of research ethics committees about distinct ethical issues in CRTs.
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Randomized Controlled Trial
IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies.
The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease. ⋯ A complex randomized analgesic trial was initiated within a multisite disease network seeking to provide an evidence base for clinical care. A number of design considerations were shown to be feasible in this setting, and several pain intensity and pain interference measures were shown to be sensitive to time- and treatment-related improvements. While the premature closure and small sample size precluded definitive conclusions regarding treatment efficacy, this trial furnishes a template for design and implementation considerations that should improve future SCD analgesic trials.
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According to the International Conference on Harmonisation (ICH) and Food and Drug Administration (FDA) guidelines for paediatric clinical trials, bridging procedures can be used if disease progression, exposure-response relationships, and clinical endpoints are similar in adults and children. In these circumstances, confirmatory efficacy trials are not necessary; the evaluation of pharmacokinetics and safety ought to be sufficient for drug approval. ⋯ Paediatric trials are desirable and necessary to address important unmet medical needs. However, the types of studies supporting regulatory approval do not always reflect the recommendations available in paediatric guidelines, which allow for extrapolation and bridging approaches. This situation may be explained by the lack of awareness about the prerequisites for the use of bridging concepts and of a clear process for evaluating different strategies in paediatric development.
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Randomized Controlled Trial Multicenter Study
National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: advancing the science of recruitment and breast cancer risk assessment in minority communities.
One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. ⋯ Recruitment strategies used in STAR for racial and ethnic minorities contributed to doubling the minority enrollment compared to that in the BCPT and increased the awareness of breast cancer risk assessment in minority communities. Incorporation of new information into models to improve the risk estimation of diverse populations should prove beneficial.
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Currently, a growing placebo response rate has been observed in clinical trials for antidepressant drugs, a phenomenon that has made it increasingly difficult to demonstrate efficacy. The sequential parallel comparison design (SPCD) is a clinical trial design that was proposed to address this issue. The SPCD theoretically has the potential to reduce the sample-size requirement for a clinical trial and to simultaneously enrich the study population to be less responsive to the placebo. ⋯ It is possible to make an already complex design such as the SPCD adaptive, and thus more efficient, potentially overcoming the problem of placebo response at lower cost. Ultimately, such a design may expedite the approval of future effective treatments.