Clinical trials : journal of the Society for Clinical Trials
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Accurate information on harms arising from medical interventions is essential for assessing benefit-risk ratios. Since 2004, there has been an extension of the Consolidated Standards of Reporting Trials statement for reporting harms data in publications on randomized clinical trials. The objective of our study was to assess the quality of this reporting from academic randomized clinical trials on drugs. ⋯ Reporting of harms in French academic drug randomized clinical trials is suboptimal; moreover, this shortcoming is a critical barrier to evaluating the benefit-risk ratio of drug randomized clinical trials. Thus, the authors should be encouraged to adhere to the Consolidated Standards of Reporting Trials Harms extension.
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Background/aims In clinical trials with time-to-event outcomes, usually the significance tests and confidence intervals are based on a proportional hazards model. Thus, the temporal pattern of the treatment effect is not directly considered. This could be problematic if the proportional hazards assumption is violated, as such violation could impact both interim and final estimates of the treatment effect. ⋯ The average hazard ratio and its confidence interval indicates a treatment effect nearly a year earlier than a restricted mean survival time-based approach. Conclusion When the hazards are proportional between the comparison groups, the new methods yield results very close to the traditional approaches. When the proportional hazards assumption is violated, the new methods continue to be applicable and can potentially be more sensitive to departure from the null hypothesis.
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The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs. ⋯ In the premarket period, validity of the surrogate markers can be improved by more rigorously evaluating their correlation with patient-relevant clinical outcomes. Opportunities to reduce the duration, complexity, and cost of postmarket randomized trials should not compromise their validity and instead incorporate pragmatic "real-world" design elements. Despite recent enthusiasm for widely using real-world evidence, adaptive designs, and pragmatic trials in the regulatory setting, caution is warranted until large-scale empirical evaluations demonstrate their validity compared to more traditional trial designs.