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

TL;DR

This study finds that noninferiority margins are rarely reported at registration on ClinicalTrials.gov, raising concerns about transparency in clinical trial reporting.

Contribution

The study systematically evaluates the reporting of noninferiority margins on ClinicalTrials.gov across two time periods and highlights inconsistencies between registration and publication.

Findings

Only 3.0% of trials from 2010-2015 and 9.2% of trials from 2022-2023 reported noninferiority margins at registration.

Most trials reported the margin after registration, often during or after the patient enrollment phase.

Consistency between registration and publication was low, with only 5 trials showing consistent reporting.

Abstract

This systematic review evaluates the proportion, time point, and consistency between registration and publication of noninferiority margin reporting.

What proportion of noninferiority trials report the noninferiority margin at registration and in results posted on ClinicalTrials.gov compared with corresponding publications?

In this systematic review of 266 trials completed between 2010 and 2015 and 327 trials first posted between 2022 and 2023, only 3.0% and 9.2% of trials, respectively, reported the noninferiority margin at registration on ClinicalTrials.gov. For the 2010 to 2015 sample, the proportions were higher for reporting in results posted on ClinicalTrials.gov and in corresponding publications.

The findings indicate that, despite its importance in trial planning and interpretation of results, the noninferiority margin is poorly reported on ClinicalTrials.gov.

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

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.

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.

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.

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.

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