Sample size calculation based on the difference in restricted mean time lost for clinical trials with competing risks

Computation of sample size is important when designing clinical trials. The presence of competing risks makes the design of clinical trials with time-to-event endpoints cumbersome. A model based on the subdistribution hazard ratio (SHR) is commonly used for trials under competing risks. However, this approach has some limitations related to model assumptions and clinical interpretation. Considering such limitations, the difference in restricted mean time lost (RMTLd) is recommended as an alternative indicator. In this paper, we propose a sample size calculation method based on the RMTLd for the Weibull distribution (RMTLdWeibull) for clinical trials, which considers experimental conditions such as equal allocation, uniform accrual, uniform loss to follow-up, and administrative censoring. Simulation results show that sample size calculation based on the RMTLdWeibull can generally achieve a predefined power level and maintain relative robustness. Moreover, the performance of the sample size calculation based on the RMTLdWeibull is similar or superior to that based on the SHR. Even if the event time does not follow the Weibull distribution, the sample size calculation based on the RMTLdWeibull still performs well. The results also verify the performance of the sample size calculation method based on the RMTLdWeibull. From the perspective of the results of this study, clinical interpretation, application conditions and statistical performance, we recommend that when designing clinical trials in the presence of competing risks, the RMTLd indicator be applied for sample size calculation and subsequent effect size measurement.