论文标题
篮子试验中的贝叶斯样本量确定在子集之间借用信息
Bayesian sample size determination in basket trials borrowing information between subsets
论文作者
论文摘要
篮子试验越来越多地用于在一个总体方案下同时评估各种患者亚组的新治疗方法。我们在篮子试验中提出了一种贝叶斯方法来确定样本量的方法,该方法允许在相应的子集之间借用信息。具体而言,我们考虑了一种随机篮试验设计,该设计将患者随机分配到新的治疗方法或每个试验子集中的对照(简称为“亚调”)。得出封闭形式的样本量公式,以确保每个下部的下调查都有指定的机会,可以正确确定新处理是否优于某些临床相关差异,而不是比对照更好。给定预先指定水平的成对(IN)可相当性,下审判样本量同时求解。提出的贝叶斯方法类似于该问题的常见主义表述,在无借贷情况下产生可比的样本量。当在相应的亚调查之间启用借贷时,与无借贷的广泛实施方法相比,需要较小的试验样本量。我们说明了基于实际篮子试验的两个示例的样本量公式的使用。一项全面的仿真研究进一步表明,所提出的方法可以在所需水平上保持真正的正和假阳性率。
Basket trials are increasingly used for the simultaneous evaluation of a new treatment in various patient subgroups under one overarching protocol. We propose a Bayesian approach to sample size determination in basket trials that permit borrowing of information between commensurate subsets. Specifically, we consider a randomised basket trial design where patients are randomly assigned to the new treatment or a control within each trial subset (`subtrial' for short). Closed-form sample size formulae are derived to ensure each subtrial has a specified chance of correctly deciding whether the new treatment is superior to or not better than the control by some clinically relevant difference. Given pre-specified levels of pairwise (in)commensurability, the subtrial sample sizes are solved simultaneously. The proposed Bayesian approach resembles the frequentist formulation of the problem in yielding comparable sample sizes for circumstances of no borrowing. When borrowing is enabled between commensurate subtrials, a considerably smaller trial sample size is required compared to the widely implemented approach of no borrowing. We illustrate the use of our sample size formulae with two examples based on real basket trials. A comprehensive simulation study further shows that the proposed methodology can maintain the true positive and false positive rates at desired levels.