Improving the Power to Detect Indirect Effects in Mediation Analysis

Causal mediation analysis seeks to determine whether an independent variable affects a response variable directly or whether it does so indirectly, by way of a mediator. The existing statistical tests to determine the existence of an indirect effect are overly conservative or have inflated type I error. In this article, we propose two methods based on the principle of intersection-union tests that offer improvements in power while controlling the type I error. We demonstrate the advantages of the proposed methods through extensive simulation. Finally, we provide an application to a large proteomic study.