Department of Mathematics and Statistics, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Biostatistics. 2013 Jan;14(1):60-74. doi: 10.1093/biostatistics/kxs022. Epub 2012 Jul 3.
For time-to-event data with finitely many competing risks, the proportional hazards model has been a popular tool for relating the cause-specific outcomes to covariates (Prentice and others, 1978. The analysis of failure time in the presence of competing risks. Biometrics 34, 541-554). Inspired by previous research in HIV vaccine efficacy trials, the cause of failure is replaced by a continuous mark observed only in subjects who fail. This article studies an extension of this approach to allow a multivariate continuum of competing risks, to better account for the fact that the candidate HIV vaccines tested in efficacy trials have contained multiple HIV sequences, with a purpose to elicit multiple types of immune response that recognize and block different types of HIV viruses. We develop inference for the proportional hazards model in which the regression parameters depend parametrically on the marks, to avoid the curse of dimensionality, and the baseline hazard depends nonparametrically on both time and marks. Goodness-of-fit tests are constructed based on generalized weighted martingale residuals. The finite-sample performance of the proposed methods is examined through extensive simulations. The methods are applied to a vaccine efficacy trial to examine whether and how certain antigens represented inside the vaccine are relevant for protection or anti-protection against the exposing HIVs.
对于具有有限个竞争风险的事件时间数据,比例风险模型一直是将特定原因的结果与协变量相关联的流行工具(Prentice 等人,1978 年。存在竞争风险时的失效时间分析。生物统计学 34,541-554)。受 HIV 疫苗功效试验中先前研究的启发,失效的原因被替换为仅在失败的受试者中观察到的连续标记。本文研究了这种方法的扩展,以允许多变量连续竞争风险,以更好地说明在功效试验中测试的候选 HIV 疫苗包含多个 HIV 序列的事实,目的是引发多种免疫反应,识别和阻止不同类型的 HIV 病毒。我们为依赖于标记的比例风险模型开发了推断,以避免维度的诅咒,并且基线风险同时依赖于时间和标记的非参数。基于广义加权鞅残差构建了拟合优度检验。通过广泛的模拟检验了所提出方法的有限样本性能。该方法应用于疫苗功效试验,以检验疫苗内的某些抗原是否以及如何与针对暴露的 HIV 的保护或反保护相关。