Methods for proper handling of overrunning and underrunning in phase II designs for oncology trials
Methods for proper handling of overrunning and underrunning in phase II designs for oncology trials
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DOI：
10.1002/sim.6479
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发表时间：
2015-06-15
影响因子：
2
通讯作者：
Kieser, Meinhard
中科院分区：
文献类型：
--
作者：
Englert, Stefan;Kieser, Meinhard
肿瘤学II期研究通常作为两阶段单臂试验进行，具有指示肿瘤缓解的二元终点。作为这些设计的共同特征，两个阶段的样本量以及中期和最终分析的决策规则必须预先规定并在试验过程中严格遵守，以确保控制I类错误率。然而，在实际应用中，所获得的样本量往往偏离计划的样本量，导致超负荷或欠负荷的情况。目前可用的方法来处理这个问题，要么是基于在实践中很少满足的假设，或不保证保持的重要性水平。然而，严格控制I类错误率对于单臂癌症试验也起着重要作用，因为它们通常是注册信息的基本组成部分。我们提出了一个通用的方法，允许处理无意和有意的超限和欠载，同时严格控制I型错误率。所提出的程序和它的一些特点的应用说明了一个真实的II期肿瘤学试验。版权所有（c）2015约翰威利父子有限公司
Phase II studies in oncology are frequently conducted as two-stage single-arm trials with a binary endpoint indicating tumor response. As a common feature of these designs, the sample sizes of the two stages and the decision rules for the interim and the final analysis have to be pre-specified and adhered to strictly during the course of the trial in order to assure control of the type I error rate. In practice, however, the attained sample sizes often deviate from the planned ones leading to the situation of overrunning or underrunning. The currently available approaches to deal with this problem are either based on assumptions that are rarely met in practice or do not guarantee that the significance level is kept. However, strict control of the type I error rate plays an important role also for single-arm cancer trials, as they are frequently a fundamental part of the registration information. We propose a general methodology that allows handling both unintentional and intentional overrunning and underrunning while strictly controlling the type I error rate. Application of the proposed procedure and some of its characteristics are illustrated with a real phase II oncology trial. Copyright (c) 2015John Wiley & Sons, Ltd.