论文标题
控制通用错误率的图形方法
Graphical approaches for the control of generalised error rates
论文作者
论文摘要
当同时检验多个假设时,在验证性临床试验的背景下,通常的方法是控制家庭误差率(FWER),这限制了至少进行一种虚假拒绝的概率。在许多试验环境中,这些假设还将具有层次结构,以反映不同临床目标之间的相对重要性和联系。 Bretz等人的图形方法。 (2009年)是一种控制FWER的灵活且易于交流的方式,同时尊重复杂的试验目标和多个结构化假设。但是,FWER可能是一个非常严格的标准,可导致低功率的程序,并且在探索性试验环境中可能不合适。这激发了控制通用错误率,尤其是当测试假设的数量不再少时。我们考虑普遍的家庭误差率(K-FWER),这是进行K或更多错误拒绝的概率,以及错误发现比例(FDP)的尾巴概率,这是错误拒绝比例比某些阈值大的概率。我们还考虑对错误发现率(FDR)的渐近控制,这是FDP的期望。在本文中,我们展示了在使用图形方法及其扩展时如何控制这些广义错误率。我们在三个临床试验案例研究中证明了所得图形程序的实用性。
When simultaneously testing multiple hypotheses, the usual approach in the context of confirmatory clinical trials is to control the familywise error rate (FWER), which bounds the probability of making at least one false rejection. In many trial settings, these hypotheses will additionally have a hierarchical structure that reflects the relative importance and links between different clinical objectives. The graphical approach of Bretz et al. (2009) is a flexible and easily communicable way of controlling the FWER while respecting complex trial objectives and multiple structured hypotheses. However, the FWER can be a very stringent criterion that leads to procedures with low power, and may not be appropriate in exploratory trial settings. This motivates controlling generalised error rates, particularly when the number of hypotheses tested is no longer small. We consider the generalised familywise error rate (k-FWER), which is the probability of making k or more false rejections, as well as the tail probability of the false discovery proportion (FDP), which is the probability that the proportion of false rejections is greater than some threshold. We also consider asymptotic control of the false discovery rate (FDR), which is the expectation of the FDP. In this paper, we show how to control these generalised error rates when using the graphical approach and its extensions. We demonstrate the utility of the resulting graphical procedures on three clinical trial case studies.