Clinical trials : journal of the Society for Clinical Trials
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Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. ⋯ The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors.
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Given the growing attention to quality improvement, comparative effectiveness research, and pragmatic trials embedded within learning health systems, the use of the cluster randomization design is bound to increase. The number of clusters available for randomization is often limited in such trials. Designs that incorporate pre-intervention measurements (e.g. cluster cross-over, repeated parallel arm, and stepped wedge designs) can substantially reduce the required numbers of clusters by decreasing between-cluster sources of variation. ⋯ This is in contrast with methods for the cluster cross-over design that explicitly allow for a smaller inter-period correlation. Failing to similarly allow for the inter-period correlation in the design of a stepped wedge trial may yield perilously low sample sizes. Further methodological and empirical work is required to inform sample size methods and guidance for the stepped wedge trial and to provide minimum thresholds for this design.
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Randomized Controlled Trial
Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.
Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. ⋯ This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies.