论文标题
免疫肿瘤学中的非比例危害:是否需要旧观点?
Non-proportional hazards in immuno-oncology: is an old perspective needed?
论文作者
论文摘要
两臂非参数生存分析中的一个基本概念是比较观察到的一个治疗臂上事件的预期数量与预期的事件数量(武器是任意的选择),在这种情况下,假设两个臂上的真正生存曲线是相同的。这个概念是计数过程理论的核心,该理论为诸如对数秩检验之类的方法提供了严格的基础。因此,自然要在扩展对数秩检验以应对非比例危害时保持这种观点是很自然的,例如,通过考虑“观察到的 - 预期”术语的加权总和,其中将较大的权重与期望有利于实验性治疗的时间段相对于时间段。但是,这样做可能会偶然发现一些相当微妙的问题,这与将因果解释归因于危害比率的困难有关,这可能会导致奇怪的结论。另一种方法是将非参数生存比较视为置换测试。从这个角度来看,人们可以轻松地提高对数秩检验的效率,同时彻底控制误报率。特别是,对于免疫肿瘤学领域,研究人员通常会预期延迟的治疗效果,可以大大减少样本量而不会损失权力。
A fundamental concept in two-arm non-parametric survival analysis is the comparison of observed versus expected numbers of events on one of the treatment arms (the choice of which arm is arbitrary), where the expectation is taken assuming that the true survival curves in the two arms are identical. This concept is at the heart of the counting-process theory that provides a rigorous basis for methods such as the log-rank test. It is natural, therefore, to maintain this perspective when extending the log-rank test to deal with non-proportional hazards, for example by considering a weighted sum of the "observed - expected" terms, where larger weights are given to time periods where the hazard ratio is expected to favour the experimental treatment. In doing so, however, one may stumble across some rather subtle issues, related to the difficulty in ascribing a causal interpretation to hazard ratios, that may lead to strange conclusions. An alternative approach is to view non-parametric survival comparisons as permutation tests. With this perspective, one can easily improve on the efficiency of the log-rank test, whilst thoroughly controlling the false positive rate. In particular, for the field of immuno-oncology, where researchers often anticipate a delayed treatment effect, sample sizes could be substantially reduced without loss of power.