Abstract
Purpose :
The National Institutes of Health (NIH) issued guidance in 2016 stating that sex should be treated as a biological variable in clinical studies; however, previous research has shown many studies fail to include sex in study design and analysis. We hypothesize that many clinical trials for glaucoma topical medications fail to treat sex as a biological variable.
Methods :
A systematic review was conducted on Pubmed using search terms “glaucoma”, “medication”, names of glaucoma medications (brand and generic) with the filters “randomized control trial”, “clinical trial”, “human”, “2002-2022”. Resulting studies were reviewed and included if they met inclusion criteria including randomized controlled trial design, study of topical glaucoma medications in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
Results :
The search resulted in 482 studies, 120 (24.9%) of which met inclusion criteria representing 31,454 subjects; 53.8% were women (Figure 1.) 80/120 (67%) were published prior to 2016 and none were NIH funded. Sex of subjects was reported in 108/120 (90%) studies. However, only 5/120 (4%) mentioned sex in data analysis; including efficacy (1, 0.8%), adverse event (AE) (1, 0.8%), and mention of sex in the discussion or conclusion (4, 3.3%). Of note, the study that included sex-based efficacy data reported the number and percentage of male and female subjects per treatment group who achieved IOP reduction of ≥2 but did not test for statistical significance. The five trials with the most detailed sex-based reporting were published prior to 2016, evaluated prostaglandin analogues and originated in Japan, United States, Serbia, and Korea. Pregnancy and/or lactation were mentioned as exclusion criteria for 31/120 (26%) studies.
Conclusions :
While the majority of glaucoma topical medication clinical trials report sex of subjects and enroll an equal proportion of male and female subjects, they fail to address sex-based differences with respect to exclusion criteria, effectiveness and AE analysis. We recommend future studies follow NIH guidance and treat sex as a biological variable for study design, and reporting of efficacy and AEs to improve understanding of the impact of biological sex on glaucoma treatment.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.