论文标题

贝叶斯自适应平台研究中代孕的灵活评估

Flexible evaluation of surrogacy in Bayesian adaptive platform studies

论文作者

Sachs, Michael C, Gabriel, Erin E, Crippa, Alessio, Daniels, Michael J

论文摘要

试验水平替代物是提高试验速度和成本效益的有用工具,但是尚未正确评估的替代物可能会引起误导性结果。评估程序通常是上下文的,取决于试验设置的类型。对于贝叶斯自适应平台研究的具体设置,有许多提议的试验水平替代评估的方法,但据我们所知。随着自适应研究变得越来越流行,需要使用它们的替代评估方法。这些研究还提供了丰富的数据资源来替代评估,通常是不可能的。但是,他们还提供了一系列统计问题,包括研究人群的异质性,治疗,实施,甚至可能是代理人的质量。我们建议使用分层贝叶斯半参数模型使用非参数先验来评估潜在的替代物,以基于Dirichlet工艺混合物的形式分布真实效果。这种方法的动机是灵活地模拟对替代物的治疗效果与对结果的治疗效果之间的关系,并以数据驱动的方式鉴定具有差异替代价值的潜在群集。在模拟中,我们发现我们提出的方法优于一种简单但相当标准的层次贝叶斯方法。我们演示了如何在模拟说明性示例(基于Probio试验)中使用我们的方法,在该示例中,我们能够在其中识别替代物所在的簇,并且没有用。我们计划将我们的方法应用于Probio试验后。

Trial level surrogates are useful tools for improving the speed and cost effectiveness of trials, but surrogates that have not been properly evaluated can cause misleading results. The evaluation procedure is often contextual and depends on the type of trial setting. There have been many proposed methods for trial level surrogate evaluation, but none, to our knowledge, for the specific setting of Bayesian adaptive platform studies. As adaptive studies are becoming more popular, methods for surrogate evaluation using them are needed. These studies also offer a rich data resource for surrogate evaluation that would not normally be possible. However, they also offer a set of statistical issues including heterogeneity of the study population, treatments, implementation, and even potentially the quality of the surrogate. We propose the use of a hierarchical Bayesian semiparametric model for the evaluation of potential surrogates using nonparametric priors for the distribution of true effects based on Dirichlet process mixtures. The motivation for this approach is to flexibly model relationships between the treatment effect on the surrogate and the treatment effect on the outcome and also to identify potential clusters with differential surrogate value in a data-driven manner. In simulations, we find that our proposed method is superior to a simple, but fairly standard, hierarchical Bayesian method. We demonstrate how our method can be used in a simulated illustrative example (based on the ProBio trial), in which we are able to identify clusters where the surrogate is, and is not useful. We plan to apply our method to the ProBio trial, once it is completed.

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