论文标题
在竞争事件设置中的一般解释和识别可分离效应
Generalized interpretation and identification of separable effects in competing event settings
论文作者
论文摘要
在竞争事件设置中,特定原因累积事件的反事实对比量化了治疗对感兴趣的事件的总因果效应。但是,治疗对竞争事件的影响可能会间接导致这种总效应,从而使其解释变得复杂。我们先前提出了可分离效应(Stensrud等,2019),以定义治疗对感兴趣的直接和间接影响。该定义前提是将处理分解成两个沿两个单独的因果途径作用的组成部分,其中一个仅在竞争事件之外,另一个仅在竞争事件之外。与以前的直接和间接效应的定义不同,可分离效应在一项研究中可能会受到经验审查,在该研究中,可以对治疗组件进行单独的干预措施。在这里,我们以多种方式扩展并概括了可分离效应的概念,从而使假设较弱的解释,识别和估计。我们提出并讨论可分离效应的定义,该定义适用于一般时变结构,即使它们不能被视为直接和间接效应,仍然可以有意义地解释可分离效应。在观察性研究中,我们进一步得出了较弱的条件,以鉴定尚未分解治疗的观察性研究;特别是,这些条件允许发生兴趣事件的时变常见原因,竞争事件和随访的损失。对于这些一般设置,我们建议直接实施的半参数加权估计器。作为例证,我们使用随机临床试验的数据应用了估计量来研究强化血压治疗对急性肾脏损伤的可分离作用。
In competing event settings, a counterfactual contrast of cause-specific cumulative incidences quantifies the total causal effect of a treatment on the event of interest. However, effects of treatment on the competing event may indirectly contribute to this total effect, complicating its interpretation. We previously proposed the separable effects (Stensrud et al, 2019) to define direct and indirect effects of the treatment on the event of interest. This definition presupposes a treatment decomposition into two components acting along two separate causal pathways, one exclusively outside of the competing event and the other exclusively through it. Unlike previous definitions of direct and indirect effects, the separable effects can be subject to empirical scrutiny in a study where separate interventions on the treatment components are available. Here we extend and generalize the notion of the separable effects in several ways, allowing for interpretation, identification and estimation under considerably weaker assumptions. We propose and discuss a definition of separable effects that is applicable to general time-varying structures, where the separable effects can still be meaningfully interpreted, even when they cannot be regarded as direct and indirect effects. We further derive weaker conditions for identification of separable effects in observational studies where decomposed treatments are not yet available; in particular, these conditions allow for time-varying common causes of the event of interest, the competing events and loss to follow-up. For these general settings, we propose semi-parametric weighted estimators that are straightforward to implement. As an illustration, we apply the estimators to study the separable effects of intensive blood pressure therapy on acute kidney injury, using data from a randomized clinical trial.