A Systematic Review of Sex-Based Reporting in Topical Glaucoma Medication Clinical Trials.

TOPIC

The National Institutes of Health (NIH) issued guidance in 2016 that sex should be treated as a biological variable in clinical studies; however, previous research has shown that biomedical studies still fail to include sex as a biological variable (SABV) in study design and analysis. We hypothesize that despite evidence for sex-specific glaucoma risk factors, clinical trials for glaucoma topical medications also fail to treat SABV.

CLINICAL RELEVANCE

Prior studies have found sex-specific genetic and hormonal risk factors for glaucoma suggesting that biological sex may influence the disease course.

METHODS

We performed a systematic review on Pubmed and Google Scholar using terms including generic names of common glaucoma medications, and filters "randomized control trial" and "clinical trial." Resulting studies were reviewed and included if they met inclusion criteria including randomized controlled trial design, testing of topical glaucoma medications in patients with open-angle glaucoma or ocular hypertension, and published between 2002-2022. Included studies were read and assessed on metrics pertinent to SABV including sex reporting and matching, sex-based analysis of medication efficacy, adverse events (AEs), and mention of SABV in the discussion and conclusion.

RESULTS

We identified 543 studies; 122/543 (22.5%) met inclusion criteria representing 31 644 subjects; 16 656/31 644 (52.6%) were women. Sex of subjects was reported in 109/122 (89%) studies. However, only 5/122 (4%) mentioned sex in data analysis, including efficacy (1), AEs (1), and mention of sex in the discussion or conclusion (4). We found that studies published after the NIH guidance on SABV in 2016 and studies funded by the NIH were not more likely to include SABV, however only 3 of 122 (2.5%) studies were NIH-funded. Pregnancy or lactation were exclusion criteria for 31/122 (25%) studies.

CONCLUSIONS

While the majority of glaucoma topical medication clinical trials reported sex and achieved sex-matching, they failed to include sex-based analysis of medication efficacy or AEs. Opportunities remain to include SABV to improve our understanding of the impact of biological sex on glaucoma treatment, although that may require increases in sample size.

FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.