Dissecting the restricted mean time in favor of treatment

Abstract

ABSTRACT The restricted mean time in favor (RMT-IF) summarizes the treatment effect on a hierarchical composite endpoint with mortality at the top. Its crude decomposition into “stage-wise effects,” i.e., the net average time gained by the treatment prior to each component event, does not reveal the patient state in which the extra time is spent. To obtain this information, we break each stage-wise effect into subcomponents according to the specific state to which the reference condition is improved. After re-expressing the subcomponents as functionals of the marginal survival functions of outcome events, we estimate them conveniently by plugging in the Kaplan -- Meier estimators. Their robust variance matrices allow us to construct joint tests on the decomposed units, which are particularly powerful against component-wise differential treatment effects. By reanalyzing a cancer trial and a cardiovascular trial, we acquire new insights into the quality and composition of the extra survival times, as well as the extra time with fewer hospitalizations, gained by the treatment in question. The proposed methods are implemented in the rmt package freely available on the Comprehensive R Archive Network (CRAN).