Moving Beyond the Hazard Ratio in Quantifying the Between-Group Difference in Survival Analysis
Moving Beyond the Hazard Ratio in Quantifying the Between-Group Difference in Survival Analysis
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DOI：
10.1200/jco.2014.55.2208
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发表时间：
2014-08-01
影响因子：
45.3
通讯作者：
Wei, Lee-Jen
中科院分区：
文献类型：
--
作者：
Uno, Hajime;Claggett, Brian;Wei, Lee-Jen
在一项比较两组的纵向临床研究中，主要终点通常是特定事件(例如，疾病进展、死亡)的时间。在假设两个危险函数的比率随着时间的推移大致不变的情况下，危险比估计通常用于经验性地量化组间差异。当这一假设可信时，这样的比率估计可以捕捉到两条生存曲线之间的相对差异。然而，当基本的比例风险假设被违反时，这种比率估计的临床意义很难解释，如果不是不可能的话(即危险比率不是随时间变化的)。尽管这一问题已被广泛研究，在统计文献中也讨论了风险比估计器的各种替代方案，但这些关键信息似乎还没有到达更广泛的卫生科学研究人员社区。在这篇文章中，我们总结了关于这一传统实践的几个关键问题，并讨论了各种众所周知的替代方案，用于量化相对于事件结束时间的组之间的潜在差异。来自最近三个癌症临床试验的数据反映了各种情况，贯穿始终地用来说明我们的讨论。当在研究设计阶段没有关于组间差异的足够信息时，我们鼓励从业者考虑一种预先指定的、具有临床意义的、无模型的测量方法来量化差异，并使用稳健的估计程序来得出初步推论。(C)美国临床肿瘤学会2014年
In a longitudinal clinical study to compare two groups, the primary end point is often the time to a specific event (eg, disease progression, death). The hazard ratio estimate is routinely used to empirically quantify the between-group difference under the assumption that the ratio of the two hazard functions is approximately constant over time. When this assumption is plausible, such a ratio estimate may capture the relative difference between two survival curves. However, the clinical meaning of such a ratio estimate is difficult, if not impossible, to interpret when the underlying proportional hazards assumption is violated (ie, the hazard ratio is not constant over time). Although this issue has been studied extensively and various alternatives to the hazard ratio estimator have been discussed in the statistical literature, such crucial information does not seem to have reached the broader community of health science researchers. In this article, we summarize several critical concerns regarding this conventional practice and discuss various well-known alternatives for quantifying the underlying differences between groups with respect to a time-to-event end point. The data from three recent cancer clinical trials, which reflect a variety of scenarios, are used throughout to illustrate our discussions. When there is not sufficient information about the profile of the between-group difference at the design stage of the study, we encourage practitioners to consider a prespecified, clinically meaningful, model-free measure for quantifying the difference and to use robust estimation procedures to draw primary inferences. (C) 2014 by American Society of Clinical Oncology