Importance: As critical determinants of scientific rigor, reproducibility, and equity, sex and gender should be considered in clinical trial design and reporting.
Objective: To evaluate the accuracy of sex and gender reporting and extent of sex- and gender-based analysis in clinical trials associated with US Food and Drug Administration (FDA) drug approvals between January 1, 1995, and December 31, 2022.
Design, setting, and participants: In this cross-sectional study of participants enrolled in FDA ophthalmology trials, the following trial documents were reviewed by pairs of independent reviewers in decreasing order of priority: peer-reviewed publication, ClinicalTrials.gov report, and FDA medical and statistical reviews. Trial protocols and supplementary materials were also reviewed.
Main outcome and measures: The proportion of trials that correctly applied sex and gender terminology, reported the method of assessing sex or gender, and conducted sex- or gender-based data analysis; incorrect application of sex and gender terminology was defined as interchangeable use of sex- and gender-related terms without a clear justification.
Results: Between 1995 and 2022, 34 ophthalmic drugs corresponding to 85 trials (34 740 participants) received FDA approval, of which 16 drugs (47.1%) corresponding to 32 trials (18 535 participants [37.6%]) were associated with peer-reviewed publications. Sixteen trials used sex and gender terminology correctly (19.5%). No trial reported how sex and gender were collected nor enrolled participants from sexual and gender identity minority populations. Most trials reported sex- and gender-disaggregated demographic data (96.5%), but few conducted sex- or gender-based analysis for data on dropout (1.2%), primary outcomes (28.2%), secondary outcomes (2.4%), and adverse events (9.4%). Erroneous sex and gender reporting was associated with later publication year (2008.5 vs 2001.0; median difference, 7.5; 95% CI, -6.0 to 11.0; P < .001) and higher journal influence metrics, including 2022 journal impact factor (13.7 vs 5.9; median difference, 7.8; 95% CI, -1.4 to 152.4, P < .001) and 2022 journal citation indicator (4.9 vs 2.1; median difference, 2.9; 95% CI, 0-20.0, P < .001).
Conclusions and relevance: In this observational study, over three-quarters of ophthalmology trials associated with FDA drug approvals conflated sex and gender and over two-thirds lacked sex- and gender-based analyses. More rigorous integration of sex and gender appears warranted for FDA, and presumably other trials, to improve their validity, reproducibility, and equity.