Diverse, representative enrollment in pivotal clinical trials is vital to sufficiently power subgroup analyses and ensure equity and validity of trial results.
To evaluate the racial/ethnic representation, trends, and disparities in clinical trials leading to US Food and Drug Administration (FDA) ophthalmology drug approvals from 2000 to 2020.
This cohort study used data from participants in clinical trials of drugs for neovascular age-related macular degeneration (AMD), open-angle glaucoma (OAG), and expanded indications for diabetic retinopathy (DR) from January 1, 2000, to December 31, 2020. Trial data were sourced from FDA reviews, ClinicalTrials.gov, and relevant linked studies. National expected racial/ethnic proportions were sourced from public National Eye Institute prevalence data as well as published rates scaled using US Census Bureau data.
The primary outcome measures were the distribution of and change over time in the racial/ethnic proportion of participants in clinical trials leading to FDA approval of drugs for AMD, OAG, and DR.
During the 20-year period, 31 clinical trials were identified for 13 medications with 18 410 participants. The distribution of trial participants was different from the expected trial distribution for most approvals with regard to race/ethnicity (12 drugs) and sex (10 drugs). Compared with the first decade (2000-2010), trials conducted in the second decade (2011-2020) showed increases in enrollment of Asian (odds ratio [OR], 2.30; 95% CI, 1.97-2.68; P < .001) and Hispanic or Latinx participants (OR, 1.74; 95% CI, 1.49-2.03; P < .001) for AMD, Asian participants (OR, 2.21; 95% CI, 1.46-3.42; P < .001) for DR, and Black (OR, 1.60; 95% CI, 1.43-1.78; P < .001) and Hispanic or Latinx participants (OR, 10.31; 95% CI, 8.05-13.35; P < .001) for OAG. There was a decrease in Black participants in DR trials (OR, 0.58; 95% CI, 0.42-0.79; P < .001). Based on these trends, the enrollment incidence ratio is expected to worsen by 2050, with overrepresentation of white participants vs underrepresentation of Black and Hispanic or Latinx participants in trials of drugs for AMD (1.08 vs 0.04 vs 0.77), DR (1.83 vs 0.87 vs 0.59), and OAG (1.62 vs 0.90 vs 0.37).
In this cohort study, Black, Hispanic or Latinx, and other non-White participants were underrepresented in clinical trials leading to FDA ophthalmology drug approvals compared with the expected disease burden and racial/ethnic distribution in the US. Although there was meaningful improvement from 2000 to 2020, further efforts to increase minority enrollment in clinical trials seem to be warranted.