Reporting of Noninferiority Margins on ClinicalTrials.gov: A Systematic Review.

Abstract

Importance: The noninferiority margin is a key methodological parameter in noninferiority trials that affects both sample size calculation and interpretation of results.

Objective: To assess (1) the reporting of the noninferiority margin on ClinicalTrials.gov, including when it was reported; (2) the consistency of the noninferiority margin between registration and publication; and (3) the reporting of the noninferiority margin at registration in a sample of recent trials.

Evidence review: This systematic review was conducted in 2 stages. Stage 1 involved identifying all noninferiority trials registered on ClinicalTrials.gov with a primary completion date of January 1, 2010, to January 1, 2015, and searching for corresponding publications. Stage 2 included all noninferiority trials registered between January 1, 2022, and June 30, 2023. Two reviewers independently and manually extracted methodological characteristics related to the noninferiority design for each trial at registration and, when available, in results posted on ClinicalTrials.gov and in publications. The time points for reporting the noninferiority margin were at registration, during the patient enrollment phase (between start date and primary completion date), after the primary completion date, or in results posted.

Findings: Among the 266 trials completed between 2010 and 2015, only 8 (3.0%) reported the noninferiority margin at registration. The noninferiority margin was reported after registration for 31 of 266 trials (11.7%), with 11 (4.1%) reporting it during the patient enrollment phase and 20 (7.5%) reporting it after the primary completion date. Of the 132 trials with results posted on ClinicalTrials.gov, 79 (59.8%) reported the noninferiority margin. A corresponding publication was found for 208 trials, with 196 (94.2%) reporting the noninferiority margin. For 5 trials reporting the margin at both registration and in publication, the noninferiority margin was consistent in both sources. Among the 327 noninferiority trials first posted between 2022 and 2023, 30 (9.2%) reported the noninferiority margin at registration.

Conclusions and relevance: In this systematic review, the reporting of the noninferiority margin on ClinicalTrials.gov was low. Mandatory reporting of the design and the noninferiority margin at registration could enhance the transparency and favor more reliable results.