使用复发和终止事件的联合模型进行临床试验的贝叶斯设计。

IF 1.8 3区 数学 Q3 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Jiawei Xu, Matthew A Psioda, Joseph G Ibrahim
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引用次数: 0

摘要

复发事件和终止事件数据的联合模型越来越多地用于临床试验的分析。然而,很少有人提出使用这些模型设计临床试验的方法。在这篇文章中,我们开发了一种贝叶斯临床试验设计方法,重点是使用多轨道关节模型评估研究药物(IP)对被视为多个主要终点的复发事件和终止事件过程的影响。使用共同的弱点来解释重复事件过程和终止事件过程之间的依赖性。对多个主要结果的推断基于后验模型概率,该后验模型对应于关于IP相对于复发和终止事件过程的益处的互斥假设。我们提出了一种确定样本量的方法,以确保试验设计具有高功率和良好控制的I型错误率,这两种操作特征都是从贝叶斯角度定义的。我们还考虑了所提出的参数模型的推广,该模型使用狄利克雷过程的非参数混合来对脆弱性分布进行建模,并将其性能与所提出的方法进行比较。我们通过设计癌症结直肠癌临床试验来证明该方法,目的是证明IP对两种结果中的至少一种产生有利影响,但对任何一种都没有损害。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bayesian design of clinical trials using joint models for recurrent and terminating events.

Joint models for recurrent event and terminating event data are increasingly used for the analysis of clinical trials. However, few methods have been proposed for designing clinical trials using these models. In this article, we develop a Bayesian clinical trial design methodology focused on evaluating the effect of an investigational product (IP) on both recurrent event and terminating event processes considered as multiple primary endpoints, using a multifrailty joint model. Dependence between the recurrent and terminating event processes is accounted for using a shared frailty. Inferences for the multiple primary outcomes are based on posterior model probabilities corresponding to mutually exclusive hypotheses regarding the benefit of IP with respect to the recurrent and terminating event processes. We propose an approach for sample size determination to ensure the trial design has a high power and a well-controlled type I error rate, with both operating characteristics defined from a Bayesian perspective. We also consider a generalization of the proposed parametric model that uses a nonparametric mixture of Dirichlet processes to model the frailty distributions and compare its performance to the proposed approach. We demonstrate the methodology by designing a colorectal cancer clinical trial with a goal of demonstrating that the IP causes a favorable effect on at least one of the two outcomes but no harm on either.

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来源期刊
Biostatistics
Biostatistics 生物-数学与计算生物学
CiteScore
5.10
自引率
4.80%
发文量
45
审稿时长
6-12 weeks
期刊介绍: Among the important scientific developments of the 20th century is the explosive growth in statistical reasoning and methods for application to studies of human health. Examples include developments in likelihood methods for inference, epidemiologic statistics, clinical trials, survival analysis, and statistical genetics. Substantive problems in public health and biomedical research have fueled the development of statistical methods, which in turn have improved our ability to draw valid inferences from data. The objective of Biostatistics is to advance statistical science and its application to problems of human health and disease, with the ultimate goal of advancing the public''s health.
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