Ludovic Trinquart PhD, Assistant Professor of Biostatistics, Boston University School of Public Health
“Counterfactual mediation analysis with illness-death model for right-censored surrogate and clinical outcomes”
We introduce a counterfactual-based mediation analysis for surrogate outcome evaluation when both the surrogate and clinical endpoint are subject to right-censoring. We use a multistate model for risk prediction to account for both direct transitions towards the clinical endpoint and transitions through the surrogate endpoint. We use the counterfactual framework to define natural direct and indirect effects and the proportion of the treatment effect on the clinical endpoint mediated by the surrogate endpoint. We define these quantities for the cumulative risk and restricted mean survival time. We illustrate our approach using 18-year follow-up data from the SPCG-4 randomized controlled trial of radical prostatectomy for prostate cancer. We assess time to metastasis as a potential surrogate outcome for all-cause mortality.