Abstract

Abstract Standard causal mediation analysis decomposes the total effect into a direct effect and an indirect effect in settings with only one single mediator. Under the settings with multiple mediators, all mediators are often treated as one single block of mediators. The effect mediated by a certain combination of mediators, i. e. path-specific effect (PSE), is not always identifiable without making strong assumptions. In this paper, the authors propose a method, defining a randomly interventional analogue of PSE (rPSE), as an alternative approach for mechanism investigation. This method is valid under assumptions of no unmeasured confounding and allows settings with mediators dependent on each other, interaction, and mediator-outcome confounders which are affected by exposure. In addition, under linearity and no-interaction, our method has the same form of traditional path analysis for PSE. Furthermore, under single mediator without a mediator-outcome confounder affected by exposure, it also has the same form of the results of causal mediation analysis. We also provide SAS code for settings of linear regression with exposure-mediator interaction and perform analysis in the Framingham Heart Study dataset, investigating the mechanism of smoking on systolic blood pressure as mediated by both cholesterol and body weight. Allowing decomposition of total effect into several rPSEs, our method contributes to investigation of complicated causal mechanisms in settings with multiple mediators.

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