Universitè Paris Citè, Sorbonne Université, Inserm, Centre de Recherche des Cordeliers, Paris, France.
Inria, HeKA, Paris, France.
Stat Methods Med Res. 2023 May;32(5):963-977. doi: 10.1177/09622802231160554. Epub 2023 Mar 15.
Master protocol designs allow for simultaneous comparison of multiple treatments or disease subgroups. Master protocols can also be designed as seamless studies, in which two or more clinical phases are considered within the same trial. They can be divided into two categories: operationally seamless, in which the two phases are separated into two independent studies, and inferentially seamless, in which the interim analysis is considered an adaptation of the study. Bayesian designs are scarcely studied. Our aim is to propose and compare Bayesian operationally seamless Phase II/III designs using a binary endpoint for the first stage and a time-to-event endpoint for the second stage. At the end of Phase II, arm selection is based on posterior (futility) and predictive (selection) probabilities. The results of the first phase are then incorporated into prior distributions of a time-to-event model. Simulation studies showed that Bayesian operationally seamless designs can approach the inferentially seamless counterpart, allowing for an increasing simulated power with respect to the operationally frequentist design.
主方案设计允许同时比较多种治疗方法或疾病亚组。主方案也可以设计为无缝研究，其中两个或更多的临床阶段被认为是在同一个试验内。它们可以分为两类：操作上的无缝，其中两个阶段被分成两个独立的研究，以及推理上的无缝，其中中期分析被认为是研究的一种适应。贝叶斯设计几乎没有被研究过。我们的目的是提出并比较使用二项终点作为第一阶段和时间事件终点作为第二阶段的贝叶斯操作上无缝的二期/三期设计。在二期结束时，臂的选择基于后验（无效）和预测（选择）概率。然后，第一阶段的结果被纳入时间事件模型的先验分布中。模拟研究表明，贝叶斯操作上的无缝设计可以接近推理上的无缝设计，允许相对于操作上的频率设计增加模拟功效。
