Risk Difference, Relative Risk, and Odds Ratio for Noninferiority Clinical Trials: Assessment with Negative Event Rate Endpoint

• Activity Number: 166 - Non-Clinical Statistics, Personalized Medicine, and Other Topics
• Type: Contributed
• Date/Time: Tuesday, August 10, 2021 : 10:00 AM to 11:50 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Senmiao Ni and Jingwei Wu* and Quanji Yu and Jianling Bai and Hao Yu
• Companies: Nanjing Medical University and Temple University and Nanjing Medical University and Nanjing Medical University and Nanjing Medical University
• Keywords: Non-inferiority; Risk difference; Relative risk; Odds ratio; Negative event rate

Abstract

Non-inferiority (NI) trials are widely used to evaluate whether the new experimental treatment is not unacceptably worse than the current active-controlled treatment by exceeding a pre-selected non-inferiority margin (NI margin). However, choosing either an absolute difference [risk difference (RD)] or a ratio [relative risk (RR) and odds ratio (OR)] to evaluate efficacy in NI trials is still controversial. In this research, we aim to evaluate the performance of aforementioned three metrics for testing NI in clinical trials with negative event rate endpoint. Herein, extensive Monte Carlo simulations based on various parameter settings (NI margin, as well as event rates in the experimental group and active-controlled group) are conducted to compare the Type I error rate, statistical power, and the necessary sample size to achieve a desired power for testing NI using RD, RR and OR. We show that RD not only controls well the Type I error and achieves the highest statistical power, but also requires the smallest sample size as compare to RR and OR. In practice, however, the choice among three metrics still needs to be based upon clinical interpretations and regulatory perspectives.