A comparison of testing methods in non-inferiority clinical trials

A general non-inferiority (NI) clinical trial is typically conducted using parametric testing methods with large samples. However, patient recruitment challenges often hinder rare disease trials, leading to enrollment failures. In this study, we introduce current parametric and nonparametric NI trial testing methods and propose modifications to enhance the performance of the nonparametric approach. Through a comprehensive simulation study with various sample sizes, data distributions, and sample ratios, we compare empirical levels and statistical powers as criteria for evaluating performance. Our findings indicate that the modified nonparametric methods outperformed the existing methods, particularly under conditions of small sample sizes and non-normal distributions, offering valuable insights for improving the reliability and sensitivity of NI trials in the context of rare diseases.