论文标题
建模半竞争风险将数据作为纵向双变量过程
Modeling semi-competing risks data as a longitudinal bivariate process
论文作者
论文摘要
成人思想变化(ACT)研究是一项长期进行全因痴呆和阿尔茨海默氏病(AD)的前瞻性研究。随着队列年龄的增长,死亡(终端事件)是AD(非终端事件)的重要竞争风险,尽管情况并非如此。因此,可以将来自ACT的数据的分析放置在半竞争风险框架内。与标准竞争风险相比,半竞争风险的中心是人们可以了解这两个事件之间的依赖性结构。然而,迄今为止,半竞争风险的大多数方法都将依赖视为滋扰,而不是潜在的新临床知识来源。我们提出了一个新颖的基于回归的框架,该框架通过时间尺度的分配方式通过纵向双变量过程的镜头来查看事件的两个时间结果。该框架的一个关键创新是,依赖性以两种不同的形式表示,$ \ textit {local} $和$ \ textit {global} $依赖性都具有直观的临床解释。估计和推理是通过惩罚的最大似然性进行的,并且可以容纳右审查,左截断和随时间变化的协变量。该框架用于调查性别的作用,并具有$ \ ge $ 1 apoe-$ \ epsilon4 $等位基因在AD和死亡的共同风险中。
The Adult Changes in Thought (ACT) study is a long-running prospective study of incident all-cause dementia and Alzheimer's disease (AD). As the cohort ages, death (a terminal event) is a prominent competing risk for AD (a non-terminal event), although the reverse is not the case. As such, analyses of data from ACT can be placed within the semi-competing risks framework. Central to semi-competing risks, and in contrast to standard competing risks, is that one can learn about the dependence structure between the two events. To-date, however, most methods for semi-competing risks treat dependence as a nuisance and not a potential source of new clinical knowledge. We propose a novel regression-based framework that views the two time-to-event outcomes through the lens of a longitudinal bivariate process on a partition of the time scale. A key innovation of the framework is that dependence is represented in two distinct forms, $\textit{local}$ and $\textit{global}$ dependence, both of which have intuitive clinical interpretations. Estimation and inference are performed via penalized maximum likelihood, and can accommodate right censoring, left truncation and time-varying covariates. The framework is used to investigate the role of gender and having $\ge$1 APOE-$\epsilon4$ allele on the joint risk of AD and death.