论文标题
一种务实的适应性富集设计，用于为癌症免疫疗法选择合适的目标人群
A pragmatic adaptive enrichment design for selecting the right target population for cancer immunotherapies
论文作者
论文摘要
确认试验设计的挑战之一是处理有关新药物的最佳目标人群的不确定性。在这种情况下，在临时分析中提出了一个或多个预先指定的生物标志物亚群的自适应富集设计（AED），但是在这种情况下，AEDS的实际案例研究仍然相对较少。我们在高度动态的癌症免疫疗法环境中介绍了具有二元端点的AED的设计。该试验是作为早期三阴性乳腺癌的常规试验开始的，但根据该试验外部的新兴数据进行了修订，这表明PD-L1状态可能是一种预测性的生物标志物。讨论了操作特征，包括最小可检测差的概念，即最小观察到的治疗效果，在AED设置中，在临时或最终分析中，至少一个目标人群将在至少一个目标人群中产生统计学意义的结果。
One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more pre-specified biomarker subpopulations at an interim analysis have been proposed in this setting but practical case studies of AEDs are still relatively rare. We present the design of an AED with a binary endpoint in the highly dynamic setting of cancer immunotherapy. The trial was initiated as a conventional trial in early triple-negative breast cancer but amended to an AED based on emerging data external to the trial suggesting that PD-L1 status could be a predictive biomarker. Operating characteristics are discussed including the concept of a minimal detectable difference, that is, the smallest observed treatment effect that would lead to a statistically significant result in at least one of the target populations at the interim or the final analysis, respectively, in the setting of AED.
