Adaptive Enrichment Trials aim to make efficient use of data in a pivotal trial of a new targeted therapy to both (a) more precisely identify who benefits from that therapy and (b) improve the likelihood of successfully concluding that the drug is effective, while controlling the probability of false positives. There are a number of frameworks for conducting such a trial and decisions that must be made regarding how to identify that target subgroup. Among those decisions, one must choose how aggressively to restrict enrollment criteria based on the accumulating evidence in the trial. In this article, we empirically evaluate the impact of aggressive versus conservative enrollment restrictions on the power of the trial to detect an effect of treatment. We identify that, in some cases, a more aggressive strategy can substantially improve power. This additionally raises an important question regarding label indication: To what degree do we need a formal test of the hypothesis of no treatment effect in the exact population implied by the label indication? We discuss this question and evaluate how our answer for adaptive enrichment trials may relate to the answer implied by current practice for broad eligibility trials.

中文翻译：

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在适应性富集试验中确定“正确”亚组的注意事项。

适应性富集试验旨在在新的靶向治疗的关键试验中有效利用数据，以（a）更准确地确定谁从该治疗中受益，以及（b）提高成功得出药物有效结论的可能性，同时控制误报的概率。有许多用于进行此类试验的框架，并且必须就如何识别目标亚组做出决定。在这些决定中，必须根据试验中积累的证据来选择限制入组标准的力度。在本文中，我们根据经验评估了积极与保守的入组限制对试验检测治疗效果的影响。我们发现，在某些情况下，更激进的策略可以显着提高实力。这还提出了一个关于标签指示的重要问题：我们需要在多大程度上对标签指示所暗示的确切人群中没有治疗效果的假设进行正式检验？我们讨论这个问题并评估我们对适应性丰富试验的答案如何与广泛资格试验的当前实践所暗示的答案相关。