Adjusting for covariates in analysis based on restricted mean survival times

We summarize extensions to the analysis of restricted mean survival time (RMST) in the context of time-to-event outcomes. The RMST estimate and its inference are based on the classical Kaplan-Meier curves. When covariate effects are considered, an adjusted RMST (ARMST) estimate can be derived analogously based on adjusted Kaplan-Meier curves. The adjusted Kaplan-Meier Estimator (AKME) was developed to reduce confounding by the method of inverse probability of treatment weighting. We will show how the ARMST method combines the concepts of the RMST and AKME to make inferences. Two regression based methods to adjust for potential covariate effect on the RMST estimates will be compared with the ARMST approach. Simulation studies are performed to compare the different methods with and without covariate adjustments. In addition, we will summarize the extension of RMST and ARMST to the setting with competing risks. The restricted mean time lost (RMTL) and adjusted RMTL (ARMTL) are estimates of interest from cumulative incidence curves. A phase 3 oncology clinical trial example is provided to demonstrate the applications of these methods.