Clinical trials : journal of the Society for Clinical Trials
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Randomized Controlled Trial
Increasing trial efficiency by early reallocation of placebo nonresponders in sequential parallel comparison designs: application to antidepressant trials.
The sequential parallel comparison (SPC) design was proposed to improve the efficiency of psychiatric clinical trials by reducing the impact of placebo response. It consists of two consecutive placebo-controlled comparisons of which the second is only entered by placebo nonresponders from the first. Previous studies suggest that in antidepressant trials, nonresponse to placebo can already be predicted after 2 weeks of follow-up. This would allow to reduce the first phase of the SPC design to further increase its efficiency. ⋯ This study suggests that SPC designs are highly efficient alternatives to a conventional RCT in indications where placebo response is high and substantial treatment effects are established after a relatively short follow-up period (i.e., after the first SPC design phase). We conclude that SPC designs can reduce sample size requirements and increase success rates of antidepressant trials.
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Historical Article
Parental consent to participation in a randomised trial in children: associated child, family, and physician factors.
Low participation rates in randomised controlled trials involving children are almost a universal problem, leading to high cost and low statistical power. Trial, parent/family, child, and physician factors have been reported to influence parental willingness to consent for paediatric trials. ⋯ Parent, child, and physician factors are associated with consent for trial participation, with most not being modifiable. Having a member of the research study team approach the parent for consent appears to be the only feasible strategy for increasing recruitment to randomised trials in this setting.
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The objective of a non-inferiority trial is to determine whether a new or existing treatment is not less effective than another existing or current treatment by more than a pre-specified margin, Δ, usually with the requirement that the new treatment has some other advantage such as reduced cost or lower toxicity. A possible but unusual result in a non-inferiority trial is for the confidence interval for the treatment effect to lie between zero and Δ, implying that the new treatment is both inferior and non-inferior to the control. Such a result could occur in non-inferiority trials with large sample sizes or large non-inferiority margins. The possibility of this scenario occurring has implications for interim analyses. In standard superiority trials, stopping guidelines are often based on the p value obtained from testing whether treatments are equally effective. In non-inferiority trials, however, even if a new treatment is found to be inferior to the control at an interim analysis, there may still be a reasonable chance of demonstrating non-inferiority in the final analysis. ⋯ Conditional power is an appropriate tool for defining stopping guidelines for futility in non-inferiority trials, particularly those with large non-inferiority margins.
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The Institute of Medicine (IOM) has recommended that each person with cancer should have access to clinical trials, which have been associated with improving care quality and disparities. With no effective enrollment monitoring system, patterns of trial enrollment remain unclear. ⋯ Model stability and consistency suggest that this system is effective for population-based enrollment surveillance. For North Carolina, it suggests a worsening disparity in minority trial enrollment, though our analyses elucidate targets for intervention. Regional enrollment variation suggests the importance of access to clinical research networks and infrastructure. Substantial gender differences merit further examination.
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There is a growing appreciation that our current approach to clinical research leaves important gaps in evidence from the perspective of patients, clinicians, and payers wishing to make evidence-based clinical and health policy decisions. This has been a major driver in the rapid increase in interest in comparative effectiveness research (CER), which aims to compare the benefits, risks, and sometimes costs of alternative health-care interventions in 'the real world'. While a broad range of experimental and nonexperimental methods will be used in conducting CER studies, many important questions are likely to require experimental approaches - that is, randomized controlled trials (RCTs). ⋯ Pragmatic RCTs (or 'pRCTs') are intended to maintain the internal validity of RCTs while being designed and implemented in ways that would better address the demand for evidence about real-world risks and benefits for informing clinical and health policy decisions. While the level of interest and activity in conducting pRCTs is increasing, many challenges remain for their routine use. This article discusses those challenges and offers some potential ways forward.