Survivor average causal effects for continuous time: a principal stratification approach to causal inference with semicompeting risks

Abstract: In semicompeting risks problems, nonterminal time-to-event outcomes such as time to hospital readmission are subject to truncation by death. These settings are often modeled with illness-death models for the hazards of the terminal and nonterminal events, but evaluating causal treatment effects with hazard models is problematic due to conditioning on survival (a post-treatment outcome) that is embedded in the definition of a hazard. Extending an existing survivor average causal effect (SACE) estimand, we frame the evaluation of treatment effects in the context of semicompeting risks with principal stratification and introduce two new causal estimands: the time-varying survivor average causal effect (TV-SACE) and the restricted mean survivor average causal effect (RM-SACE). These principal causal effects are defined among units that would survive regardless of assigned treatment. We adopt a Bayesian estimation procedure that parameterizes illness-death models for both treatment arms. We outline a frailty specification that can accommodate within-person correlation between nonterminal and terminal event times, and we discuss potential avenues for adding model flexibility. The method is demonstrated in the context of hospital readmission among late-stage pancreatic cancer patients.