论文标题
通过半竞争风险数据定义和估计亚组调解效应数据
Defining and Estimating Subgroup Mediation Effects with Semi-Competing Risks Data
论文作者
论文摘要
在许多医学研究中，诸如死亡之类的最终失败事件可能会受到其他中级临床事件的发生和时间的影响。这两个事件时间均受到损失至遵循的检查，但非终端事件可能会因主要结果的发生而进一步审查，但反之亦然。为了研究干预对这两个事件的影响，中间事件可能被视为调解人，但是由于半竞争风险的数据结构，直接和间接影响的常规定义不适用于直接和间接效应。我们根据潜在的中间事件是否发生在潜在的故障事件之前，定义三个主要地层，这些事件允许在一个层中正确定义直接和间接效应，而所有层的总效应均定义为所有层。我们讨论了层特异性效应的识别条件，并提出了基于多元逻辑层构件模型和事件时间内层中的层表内构层模型的半参数估计器。通过将未观察到的层成员视为潜在变量，我们提出了一种用于计算的EM算法。我们通过现代经验过程理论研究估计量的渐近性能，并检查估计量在数值研究中的性能。
In many medical studies, an ultimate failure event such as death is likely to be affected by the occurrence and timing of other intermediate clinical events. Both event times are subject to censoring by loss-to-follow-up but the nonterminal event may further be censored by the occurrence of the primary outcome, but not vice versa. To study the effect of an intervention on both events, the intermediate event may be viewed as a mediator, but conventional definition of direct and indirect effects is not applicable due to semi-competing risks data structure. We define three principal strata based on whether the potential intermediate event occurs before the potential failure event, which allow proper definition of direct and indirect effects in one stratum whereas total effects are defined for all strata. We discuss the identification conditions for stratum-specific effects, and proposed a semiparametric estimator based on a multivariate logistic stratum membership model and within-stratum proportional hazards models for the event times. By treating the unobserved stratum membership as a latent variable, we propose an EM algorithm for computation. We study the asymptotic properties of the estimators by the modern empirical process theory and examine the performance of the estimators in numerical studies.
