We propose an approach to conduct mediation analysis for survival data with time-varying exposures, mediators, and confounders. We identify certain interventional direct and indirect effects through a survival mediational g-formula and describe the required assumptions. We also provide a feasible parametric approach along with an algorithm and software to estimate these effects. We apply this method to analyze the Framingham Heart Study data to investigate the causal mechanism of smoking on mortality through coronary artery disease. The risk ratio of smoking 30 cigarettes per day for ten years compared with no smoking on mortality is 2.34 (95 % CI = (1.44, 3.70)). Of the overall effect, 7.91% (95% CI: = 1.36%, 19.32%) is mediated by coronary artery disease. The survival mediational g-formula constitutes a powerful tool for conducting mediation analysis with longitudinal data.
Lin, Sheng-Hsuan; Young, Jessica G.; Logan, Roger; and VanderWeele, Tyler J., "Mediation analysis for a survival outcome with time-varying exposures, mediators, and confounders" (August 2016). Harvard University Biostatistics Working Paper Series. Working Paper 203.