A Seamless Hybrid Phase II/III Design With Bayesian Interim Subgroup Selection.

IF 1.8 4区 医学 Q3 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Benjamin Duputel, Nigel Stallard, François Montestruc, Sarah Zohar, Moreno Ursino
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引用次数: 0

Abstract

Population selection is a crucial subject in clinical development nowadays as personalized medicine is growing in interest. Evolution in biomarker scanning techniques allows for the composition and detection of sub-populations of interest when analyzing new drug responses in a disease. Seamless adaptive trials could allow for subgroup analysis with the selection of the most promising population at interim analysis. We propose a hybrid Bayesian design for seamless Phase II/III trials with binary and time-to-event outcomes for the first and second phases, respectively. In this work, at interim analysis, several prior distributions, including shrinkage prior, are compared to possibly select/discard a population, and a final test using a conditional error function as a combination method testing procedure to control the frequentist type I error is used. Simulation studies showed that the logistic regression model performs better than frequentist testing for the population selection problem when the subgroup should be selected. Shrinkage prior distributions tend to be more conservative than simpler normal distributions as studies that would have ended positively are stopped at interim analysis.

基于贝叶斯中间子群选择的无缝混合II/III阶段设计。
随着个性化医疗日益受到人们的关注,人群选择是当今临床发展的一个重要课题。生物标记物扫描技术的发展允许在分析疾病中的新药反应时对感兴趣的亚群进行组成和检测。无缝适应性试验可以允许在中期分析中选择最有希望的人群进行亚组分析。我们提出了一种混合贝叶斯设计,用于无缝II/III期试验,分别为第一阶段和第二阶段提供二进制和事件时间结果。在这项工作中,在中期分析中,将几个先验分布(包括收缩先验)与可能选择/丢弃的总体进行比较,并使用条件误差函数作为组合方法测试程序进行最终测试,以控制频率主义者I型误差。仿真研究表明,对于需要选择子群的总体选择问题,逻辑回归模型优于频率检验。收缩先验分布往往比简单的正态分布更保守,因为本应以正结果结束的研究在中期分析时停止了。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Statistics in Medicine
Statistics in Medicine 医学-公共卫生、环境卫生与职业卫生
CiteScore
3.40
自引率
10.00%
发文量
334
审稿时长
2-4 weeks
期刊介绍: The journal aims to influence practice in medicine and its associated sciences through the publication of papers on statistical and other quantitative methods. Papers will explain new methods and demonstrate their application, preferably through a substantive, real, motivating example or a comprehensive evaluation based on an illustrative example. Alternatively, papers will report on case-studies where creative use or technical generalizations of established methodology is directed towards a substantive application. Reviews of, and tutorials on, general topics relevant to the application of statistics to medicine will also be published. The main criteria for publication are appropriateness of the statistical methods to a particular medical problem and clarity of exposition. Papers with primarily mathematical content will be excluded. The journal aims to enhance communication between statisticians, clinicians and medical researchers.
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