Abstract

Response-adaptive randomization (RAR) has recently gained popularity in clinical trials. The intent is noble: minimize the number of participants randomized to inferior treatments and increase the amount of information about better treatments. Unfortunately, RAR causes many problems, including (1) bias from temporal trends, (2) inefficiency in treatment effect estimation, (3) volatility in sample-size distributions that can cause a nontrivial proportion of trials to assign more patients to an inferior arm, (4) difficulty of validly analyzing results, and (5) the potential for selection bias and other issues inherent to being unblinded to ongoing results. The problems of RAR are most acute in the very setting for which RAR has been proposed, namely long-duration “platform” trials and infectious disease settings where temporal trends are ubiquitous. Response-adaptive randomization can eliminate the benefits that randomization, the most powerful tool in clinical trials, provides. Use of RAR is discouraged.

中文翻译：

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抵制响应自适应随机化的诱惑

 抽象的

响应自适应随机化 (RAR) 最近在临床试验中越来越受欢迎。其目的是崇高的：最大限度地减少随机接受较差治疗的参与者数量，并增加有关更好治疗的信息量。不幸的是，RAR 会导致许多问题，包括（1）时间趋势的偏差，（2）治疗效果估计效率低下，（3）样本量分布的波动性可能导致相当一部分试验将更多患者分配到劣势组，（4）有效分析结果的困难，以及（5）潜在的选择偏差和其他对正在进行的结果不知情所固有的问题。 RAR 的问题在 RAR 提出的环境中最为严重，即长期“平台”试验和时间趋势普遍存在的传染病环境。响应自适应随机化可以消除随机化（临床试验中最强大的工具）所提供的好处。不鼓励使用 RAR。