Stratified Restricted Mean Survival Time Model for Marginal Causal Effect in Observational Survival Data

Abstract

Time to event outcomes is commonly encountered in epidemiologic research. Multiple papers have discussed the inadequacy of using the hazard ratio as a causal effect measure due to its noncollapsibility and the time-varying nature. In this paper, we further clarified that the hazard ratio might be used as a conditional causal effect measure, but it is generally not a valid marginal effect measure, even under randomized design. We proposed to use the restricted mean survival time (RMST) difference as a causal effect measure, since it essentially measures the mean difference over a specified time horizon and has a simple interpretation as the area under survival curves. For observational studies, propensity score adjustment can be implemented with RMST estimation to remove observed confounding bias. We proposed a propensity score stratified RMST estimation strategy, which performs well in our simulation evaluation and is relatively easy to implement for epidemiologists in practice. Our stratified RMST estimation includes two different versions of implementation, depending on whether researchers want to involve regression modeling adjustment, which provides a powerful tool to examine the marginal causal effect with observational survival data.