Bayesian and frequentist two-stage treatment strategies based on sequential failure times subject to interval censoring
Bayesian and frequentist two-stage treatment strategies based on sequential failure times subject to interval censoring
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DOI：
10.1002/sim.2894
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发表时间：
2007-11-20
影响因子：
2
通讯作者：
Tannir, Nizar M.
中科院分区：
文献类型：
--
作者：
Thall, Peter F.;Wooten, Leiko H.;Tannir, Nizar M.
对于许多疾病，治疗涉及多个阶段，每个阶段的治疗根据患者当前的疾病状态和先前治疗的历史以及临床结果进行适应性选择。医生通常使用这种多阶段治疗策略，也称为动态治疗方案或治疗策略。我们提出了一个贝叶斯框架的临床试验比较两个阶段的战略的基础上的时间，以全面失败，定义为第二次疾病恶化或停止治疗。每例患者在入组时随机分配到一组治疗中，如果发生疾病恶化，则将患者重新随机分配到一组治疗中，不包括最初接受的治疗。目标是选择具有最大平均总故障时间的两阶段策略。制定参数模型以解释非恒定故障时间危害、第二次故障时间对患者第一次恶化时间的回归以及任何阶段中的故障时间可能被间隔删失并且第一次恶化和第二阶段治疗开始之间可能存在延迟的并发症。四个不同的标准，两个贝叶斯和两个频率论，选择一个最佳的策略。该方法被应用到一个试验比较两个阶段的战略，用于治疗转移性肾癌，并在本试验的背景下，模拟研究。与标准方法相比，这种设计的优点和缺点进行了讨论。版权所有（C）2007约翰威利父子有限公司
For many diseases, therapy involves multiple stages, with the treatment in each stage chosen adaptively based on the patient's current disease status and history of previous treatments and clinical outcomes. Physicians routinely use such multi-stage treatment strategies, also called dynamic treatment regimes or treatment policies. We present a Bayesian framework for a clinical trial comparing two-stage strategies based on the time to overall failure, defined as either second disease worsening or discontinuation of therapy. Each patient is randomized among a set of treatments at enrollment, and if disease worsening occurs the patient is then re-randomized among a set of treatments excluding the treatment received initially. The goal is to select the two-stage strategy having the largest average overall failure time. A parametric model is formulated to account for non-constant failure time hazards, regression of the second failure time on the patient's first worsening time, and the complications that the failure time in either stage may be interval censored and there may be a delay between first worsening and the start of the second stage of therapy. Four different criteria, two Bayesian and two frequentist, for selecting a best strategy are considered. The methods are applied to a trial comparing two-stage strategies for treating metastatic renal cancer, and a simulation study in the context of this trial is presented. Advantages and disadvantages of this design compared to standard methods are discussed. Copyright (C) 2007 John Wiley & Sons, Ltd.