Racial/Ethnic Disparities in Ophthalmology Clinical Trials Resulting in US Food and Drug Administration Drug Approvals From 2000 to 2020

Abstract

IMPORTANCE Diverse, representative enrollment in pivotal clinical trials is vital to sufficiently power subgroup analyses and ensure equity and validity of trial results. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTSThis 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. MAIN OUTCOMES AND MEASURESThe 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. RESULTSDuring 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)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(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). CONCLUSIONS AND RELEVANCEIn 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.

Evaluation of sex differences in laser-induced choroidal neovascularization severity, phenotype and disease progression

“…Because basic research uses predominately male animals and women are underrepresented in clinical studies [7], treatment and clinical management of most diseases is biased towards males.…”

“…For example, sexual dimorphism has been well-documented in cardiovascular and autoimmune disease [31–34], yet most basic research studies use only one sex of animals, and the standard of care and clinical management for most diseases, including AMD, is the same for both sexes. Because basic research uses predominately male animals and women are underrepresented in clinical studies [7], treatment and clinical management of most diseases is biased towards males.…”

“…In most studies male animals are used, in part for the sake of convenience, as more female animals are needed to maintain the breeding colony, and excess males can then be used as experimental animals. Women are also underrepresented in many clinical trials, including those that lead to FDA drug approval [7]. Thus, basic mechanistic research and clinical management of disease alike are strongly biased towards male patients; the standard of care for most diseases is based predominately on findings in male animals and patients.…”

Use of Race, Ethnicity, and National Origin in Studies Assessing Cardiovascular Risk in Women With a History of Hypertensive Disorders of Pregnancy

“…The methodologic issues related to the reporting and use of race and/or ethnicity identified in this review align with those reported in several published studies. 32 , 33 , 34 , 35 , 175 , 176 The overrepresentation of white populations in health research has been frequently observed, 34 , 35 , 176 , 177 , 178 and others 179 have noted it as a major limitation of studies examining cardiovascular risk in women with a history of HPD. Like others, 35 we found limited reporting of race and ethnicity information across included studies, and, when authors did report this information, several different terms were used to describe the same construct (eg, Caucasian , white , non-Hispanic white , European descent ).…”

Skin Color Representation in Ophthalmology Textbooks

“…While the US population is becoming increasingly diverse, medical school faculty and textbooks have failed to adequately represent these changes. Previous studies have demonstrated that compared to their white counterparts, Black, Indigenous, and People of Color (BIPOC) are underrepresented in medical schools’ pre-clinical curricula [ 2 ], clinical trials leading to FDA ophthalmology drug approvals [ 3 ], as well as in the ophthalmology workforce [ 4 ]. This underrepresentation in both medical literature and among trainees contributes to unconscious bias, perpetuating racial disparities in patient care, diagnoses, and treatment [ 5 ].…”