Efficiency improvement in a class of survival models through model-free covariate incorporation

In randomized clinical trials, we are often concerned with comparing two-sample survival data. Although the log-rank test is usually suitable for this purpose, it may result in substantial power loss when the two groups have nonproportional hazards. In a more general class of survival models of Yang and Prentice (Biometrika 92:1–17, 2005), which includes the log-rank test as a special case, we improve model efficiency by incorporating auxiliary covariates that are correlated with the survival times. In a model-free form, we augment the estimating equation with auxiliary covariates, and establish the efficiency improvement using the semiparametric theories in Zhang et al. (Biometrics 64:707–715, 2008) and Lu and Tsiatis (Biometrics, 95:674–679, 2008). Under minimal assumptions, our approach produces an unbiased, asymptotically normal estimator with additional efficiency gain. Simulation studies and an application to a leukemia study show the satisfactory performance of the proposed method.