Sample size for a non-inferiority clinical trial with time-to-event data in the presence of competing risks

Abstract: The analysis and planning methods for competing risks model have been described in the literatures in recent decades, and non-inferiority clinical trials are helpful in current pharmaceutical practice. Analytical methods for non-inferiority clinical trials in the presence of competing risks were investigated by Parpia et al., who indicated that the proportional sub-distribution hazard model is appropriate in the context of biological studies. However, the analytical methods of competing risks model differ from those appropriate for analyzing non-inferiority clinical trials with a single outcome; thus, a corresponding method for planning such trials is necessary. A sample size formula for non-inferiority clinical trials in the presence of competing risks based on the proportional sub-distribution hazard model is presented in this paper. The primary endpoint relies on the sub-distribution hazard ratio. A total of 120 simulations and an example based on a randomized controlled trial verified the empirical performance of the presented formula. The results demonstrate that the empirical power of sample size formulas based on the Weibull distribution for non-inferiority clinical trials with competing risks can reach the targeted power.