Optimal tests of the composite null hypothesis arising in mediation analysis

Abstract

The indirect effect of an exposure on an outcome through an intermediate variable can be identified by a product of two regression coefficients under certain causal and regression modeling assumptions. In this context, the null hypothesis of no indirect effect is a composite null hypothesis, as the null holds if either regression coefficient is zero. A consequence is that traditional hypothesis tests are severely underpowered near the origin (i.e., when both coefficients are small with respect to standard errors). We propose hypothesis tests that (i) preserve level alpha type~1 error, (ii) meaningfully improve power when both true underlying effects are small relative to sample size, and (iii) preserve power when at least one is not. One approach gives a closed-form test that is minimax optimal with respect to local power over the alternative parameter space. Another uses sparse linear programming to produce an approximately optimal test for a Bayes risk criterion. We discuss adaptations for performing large-scale hypothesis testing as well as modifications that yield improved interpretability. We provide an R package that implements our proposed methodology.