Journal of clinical epidemiology | 2021
Non-inferiority in cancer clinical trials was associated with more lenient margins and higher hypothesized outcome event rates.
Abstract
OBJECTIVE\nTo identify potential bias in non-inferiority design of published cancer trials, and to provide suggestions for future practice.\n\n\nSTUDY DESIGN AND SETTING\nWe systematically searched MEDLINE, Embase and CENTRAL databases (until 17 April 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.\n\n\nRESULTS\nA 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•96, 95%CI 1•03-3•73) and higher hypothesized event rate (OR\u202f=\u202f1•24, 95%CI 1•06-1•25). Trials that established non-inferiority adopted margins that were more dispersedly distributed (dispersion OR\u202f=\u202f2•84, 95%CI 1•85-4.38).\n\n\nCONCLUSION\nAlthough 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.