Non-inferiority in Cancer Clinical Trials Was Associated with More Lenient Margins and Higher Hypothesized Outcome Event Rates.

Objective: To identify potential bias in non-inferiority design of published cancer trials, and to provide suggestions for future practice. Study Design and Setting: We systematically searched MEDLINE, Embase and CENTRAL databases (until April 17, 2020) to obtain non-inferiority phase III cancer trials and protocols. Distribution of essential characteristics and study design parameters was compared between trials with and without concluding non-inferiority using multivariable logistic regression. Results: A total of 291 eligible trials were included. We observed that increased odds of concluding non-inferiority was significantly associated with more lenient non-inferiority margins (OR = 1.94, 95% CI 1.02-3.69) and higher hypothesized event rate (OR = 1.24, 95% CI 1.06-1.47). Trials that established non-inferiority adopted margins that were more dispersedly distributed (dispersion OR = 2.90, 95% CI 1.88-4.48). Conclusion: Although limited by the exploratory nature, our study demonstrated existence of possible distorted non-inferiority design which could incur excess non-inferiority in cancer clinical trials. Pre-registration and transparent reporting of detailed non-inferiority design is imperative for future research. (C) 2021 Elsevier Inc. All rights reserved.