临床试验非计划样本量重估方法及其性能评价OA

AIM:In clinical trials,external clinical trial results sometimes trigger unplanned interim decisions,which typically involve early termination and sample size re-estimation.This article aims to evaluate the statistical performance of unplanned sample size re-estimation methods in fixed-sample clinical trials.METHODS:Based on the introduction of unplanned sample size re-estimation methods,including the fixed PP method and the Reoptimiza-tion method,a Monte-Carlo simulation study was conducted by setting different true treatment ef-fect between groups,and comparing them with the traditional CPZ method.Statistical performance was evaluated using the Type I error rate,prediction ac-curacy,expected power,expected sample size,and average sample size.RESULTS:The Type I error rates of the three sample size re-estimation meth-ods were well maintained at the preset level,but only the Reoptimization method maintained the ex-pected power.Furthermore,when the initial esti-mated treatment effect was equal to or lower than the true treatment effect,the sample size estimat-ed by the Reoptimization method was larger than that of the fixed PP method.When the initial esti-mated treatment effect was higher than the true treatment effect,the sample size estimated by the Reoptimization method was smaller.CONCLUSION:The Reoptimization method demonstrates better statistical performance and is recommended for un-planned sample size re-estimation in fixed-sample design clinical trials.