Estimation and inference for the mediation effect in a time-varying mediation model

Background: Traditional mediation analysis typically examines the relations among an intervention, a time-invariant mediator, and a time-invariant outcome variable. Although there may be a total effect of the intervention on the outcome, there is a need to understand the process by which the intervention affects the outcome (i.e., the indirect effect through the mediator). This indirect effect is frequently assumed to be time-invariant. With improvements in data collection technology, it is possible to obtain repeated assessments over time resulting in intensive longitudinal data. This calls for an extension of traditional mediation analysis to incorporate time-varying variables as well as time-varying effects. Methods: We focus on estimation and inference for the time-varying mediation model, which allows mediation effects to vary as a function of time. We propose a two-step approach to estimate the time-varying mediation effect. Moreover, we use a simulation-based approach to derive the corresponding point-wise confidence band for the time-varying mediation effect. Results: Simulation studies show that the proposed procedures perform well when comparing the confidence band and the true underlying model. We further apply the proposed model and the statistical inference procedure to data collected from a smoking cessation study. Conclusions: We present a model for estimating time-varying mediation effects that allows both time-varying outcomes and mediators. Simulation-based inference is also proposed and implemented in a user-friendly R package.