论文标题

使用受控效应的临床相关调解分析

Clinically Relevant Mediation Analysis using Controlled Indirect Effect

论文作者

Sun, Haoqi, Leone, Michael J., Liu, Lin, Mukerji, Shabani S., Robbins, Gregory K., Westover, M. Brandon

论文摘要

调解分析允许人们使用观察数据来估计暴露对结果的因果效应所涉及的每种潜在介导途径的重要性。但是,当前使用多个介体进行调解分析的方法要么涉及实验无法验证的假设,要么在共同操纵介体时估计效果,从而排除了由于维度的诅咒而导致实验的实际设计,或者在存在任意因果依赖性时很难解释。我们提出了一种针对具有任意因果关系的多个可操纵介体的调解方法。该方法在临床上是相关的,因为总效应的分解不涉及跨世界假设下的效果,并着重于操纵(即治疗)一个单一介体后的效果,这在临床情况下更相关。我们使用模拟数据,政治学的“框架”数据集以及临床回顾性队列研究中的HIV-Brain Age Age数据集说明了这种方法。我们的结果为临床实践者提供了潜在的指导,以做出合理的选择来操纵一个调解人以优化结果。

Mediation analysis allows one to use observational data to estimate the importance of each potential mediating pathway involved in the causal effect of an exposure on an outcome. However, current approaches to mediation analysis with multiple mediators either involve assumptions not verifiable by experiments, or estimate the effect when mediators are manipulated jointly which precludes the practical design of experiments due to curse of dimensionality, or are difficult to interpret when arbitrary causal dependencies are present. We propose a method for mediation analysis for multiple manipulable mediators with arbitrary causal dependencies. The proposed method is clinically relevant because the decomposition of the total effect does not involve effects under cross-world assumptions and focuses on the effects after manipulating (i.e. treating) one single mediator, which is more relevant in a clinical scenario. We illustrate the approach using simulated data, the "framing" dataset from political science, and the HIV-Brain Age dataset from a clinical retrospective cohort study. Our results provide potential guidance for clinical practitioners to make justified choices to manipulate one of the mediators to optimize the outcome.

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