Blinded assessment of treatment effects for survival endpoint in an ongoing trial

Abstract

Many assumptions, including assumptions regarding treatment effects, are made at the design stage of a clinical trial for power and sample size calculations. It is desirable to check these assumptions during the trial by using blinded data. Methods for sample size re-estimation based on blinded data analyses have been proposed for normal and binary endpoints. However, there is a debate that no reliable estimate of the treatment effect can be obtained in a typical clinical trial situation. In this paper, we consider the case of a survival endpoint and investigate the feasibility of estimating the treatment effect in an ongoing trial without unblinding. We incorporate information of a surrogate endpoint and investigate three estimation procedures, including a classification method and two expectation-maximization (EM) algorithms. Simulations and a clinical trial example are used to assess the performance of the procedures. Our studies show that the expectation-maximization algorithms highly depend on the initial estimates of the model parameters. Despite utilization of a surrogate endpoint, all three methods have large variations in the treatment effect estimates and hence fail to provide a precise conclusion about the treatment effect.