Omnibus test for restricted mean survival time based on influence function

Abstract

The restricted mean survival time (RMST), which evaluates the expected survival time up to a pre-specified time point [Formula: see text], has been widely used to summarize the survival distribution due to its robustness and straightforward interpretation. In comparative studies with time-to-event data, the RMST-based test has been utilized as an alternative to the classic log-rank test because the power of the log-rank test deteriorates when the proportional hazards assumption is violated. To overcome the challenge of selecting an appropriate time point [Formula: see text], we develop an RMST-based omnibus Wald test to detect the survival difference between two groups throughout the study follow-up period. Treating a vector of RMSTs at multiple quantile-based time points as a statistical functional, we construct a Wald [Formula: see text] test statistic and derive its asymptotic distribution using the influence function. We further propose a new procedure based on the influence function to estimate the asymptotic covariance matrix in contrast to the usual bootstrap method. Simulations under different scenarios validate the size of our RMST-based omnibus test and demonstrate its advantage over the existing tests in power, especially when the true survival functions cross within the study follow-up period. For illustration, the proposed test is applied to two real datasets, which demonstrate its power and applicability in various situations.