Diversity in Ophthalmic Clinical Trials

Traditionally, clinical trial recruitment has employed rationales of limited heterogenicity and interindividual variability to establish consistent short-term results; however, diversity and inclusion in ophthalmic clinical trials serve several purposes¹:

It gives researchers more information on how new treatments may affect patients of color or those from different ethnicities and backgrounds.²
It provides access to treatments to a wider range of people. These treatments have the potential to improve vision or reduce or prevent eye disease.²
Participation from diverse groups gives broader data on treatment outcomes.²
More diverse clinical trial participation helps reduce care disparities within ophthalmology.²

An analysis of participation in clinical trials from around the globe completed by the US Food and Drug Administration (FDA) in 2020 found that among nearly 293,000 participants, 76% were White, underrepresenting the diversity of the world.¹ “[D]ata for global populations are lacking, and current guidelines and clinical decisions are based on insufficiently diverse trials and studies,” according to A. Sharma and L. Palaniappan.¹ Within ophthalmology specifically, the lack of diversity within clinical trials also appears to be an overarching trend, based on the following studies:

Analyses of race, ethnicity, and sex reporting in ophthalmology literature demonstrated inconsistent inclusion of race and/or ethnicity data (43% of 2019 manuscripts) and majority participation by women (68%, 2006-2016).^3,4 Enrollment disparities can be unreflective of the representative population and affect the ability to evaluate for biologic variability in treatment response.^3-5
A cohort study examining 20 years of data from participants in age-related macular degeneration (AMD), open-angle glaucoma (OAG), and diabetic retinopathy trials found that Black, Hispanic or Latinx, and other non-White participants were underrepresented.⁵ The trials included in the study were those that led to FDA drug approvals. While there was some improvement in representation between 2000 and 2020, the researchers concluded that more diversity is needed. If the current trends remain, there could be a continued overrepresentation of White participants by 2050, particularly in AMD trials.⁵

Diabetic retinopathy is more likely to blind Blacks and Latinos, but these populations make up only a fraction of those included in related key trials for treatment macular edema).^6,7
In fact, a study reviewing trials supportive of 9 approved ophthalmological New Molecular Entities (NMEs) from 2006-2016 across a variety of eye diseases revealed significant enrollment variation across the trials, with 1%-15% Black participation and 2%-18% Hispanic participation.⁴

Racial and ethnic minority groups had a low participation rate in primary OAG clinical trials, according to a meta-analysis of clinical trials taking place from 1994 to 2019.⁸ Among the 105 trials with a total 33,428 participants, 70.7% were White, 16.8% were Black, 3.4% were Hispanic/Latino, and 9.1% were from other races/ethnicities. This imbalance exists despite the fact that primary OAG (POAG) is most likely to affect Black individuals.
Geographical access is a barrier to trial access. Outside of the Northeastern United States, there was a higher travel burden associated with clinical trial sites for diabetic eye disease, according to researchers in a cross-sectional, retrospective study published in 2021.⁹ Geographical access to trials can have an effect on participant diversity.

Improving Diversity in Clinical Trials: Implications for Ophthalmologists

Increasing diversity within ophthalmic clinical trials, including within the retina subspecialty, has various underlying factors that need to be addressed to foster trust, enhance awareness, and facilitate participation. Efforts on the individual and collective level can do several things to improve diversity within clinical trials.

On the collective level, the American Academy of Ophthalmology (AAO) has established a task force focused on health equity in eye care. This task force takes a closer look at topics such as the social determinants of health and medical care, access to care, and care outcomes. The AAO is also committed to developing meaningful patient and provider resources to help address this need for greater diversity, equity, and inclusion.¹⁰

Additionally, both pharmaceutical companies and the FDA are making efforts to focus on inclusion within clinical trials for all specialties. In its November 2020 “Enhancing the Diversity of Clinical Trial Populations” document, the FDA suggested several ways that clinical trials can increase diversity and inclusion.¹¹ Some of its recommendations include:

Using more inclusive strategies for trial outreach
Working with community members on trial design to pinpoint where trials may discourage participation, so changes can be made to modify those areas
Using clinical trial sites located in racially and ethnically diverse areas
Holding frequent recruitment events, including evenings and weekends
Considering the use of online and social media recruitment strategies

Do not make assumptions about who may want to participate in a clinical trial. “If we don’t ask our minority patients to participate, they won’t. Trial participation should be offered to everyone,” writes retina physician Joseph M. Coney, MD.¹²
Address patients’ concerns about clinical trials in a culturally competent manner. Some patients may be skeptical about trial participation and have valid reasons for this due to historical problems related to clinical trials.¹²
Identify if the trial offers patient assistance programs for coverage of travel costs to and from trial sites or for unexpected costs such as childcare while taking part in the trial visits.^{11, 12}
Consider recruitment events that are convenient for your patients. Such factors may include off-hours recruitment events, events held at local community centers, or online recruitment.¹¹
Enhance health literacy and encourage trial participation for individuals with limited English comprehension by translating educational and trial resources, as well as related documents (including informed consent), into native languages of community patients.^{11, 12}

Although studies have shown some narrowing of disparities in ophthalmic trial underrepresentation from 2000 to 2020, continued efforts for engagement with underrepresented groups to diversify trial composition are vital to ensure the quality and validity of trial results.⁵

References

Sharma A, Palaniappan L. Improving diversity in medical research. Nat Rev Dis Primers. 2021;7:1-2. https://www.nature.com/articles/s41572-021-00316-8
Younossi A, Sanhai W, Shah S, Chang C. Enhancing clinical trial diversity. November 2021. https://www2.deloitte.com/us/en/insights/industry/life-sciences/lack-of-diversity-clinical-trials.html
Moore DB. Reporting of race and ethnicity in the ophthalmology literature in 2019. JAMA Ophthalmol.2020;138(8):903-906. https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2766933
Birnbaum FA. Gender and ethnicity of enrolled participants in US Food and Drug Administration (FDA) clinical trials for approved ophthalmological new molecular entities. J Natl Med Assoc. 2018;110(5):473-479. https://www.sciencedirect.com/science/article/abs/pii/ S0027968416302036
Berkowitz ST, Groth SL, Gangaputra S. Racial/ethnic disparities in ophthalmology clinical trials resulting in US Food and Drug Administration clinical trials from 2000 to 2020. JAMA Ophthalmol. 2021;139(6):629-637. https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2778782
Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. 2014;121:2247-2254. https://pubmed.ncbi.nlm.nih.gov/25012934/
Nguyen QD, Brown DM, Marcus DM, et al; RIDE and RISE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III trials: RISE and RIDE. Ophthalmology. 2012;119(10):789-801. https://www.aaojournal.org/action/showPdf?pii=S0161-6420%2811%2901242-5
Allison K, Patel DG, Greene L. Racial and ethnic disparities in primary open-angle glaucoma clinical trials: a systemic review and meta-analysis. JAMA Netw Open. 2021;4:e218348. https://pubmed.ncbi.nlm.nih.gov/34003274/
Soares R, Parikh D, Shields CN, et al. Geographic access disparities to clinical trials in diabetic eye disease in the United States. Ophthalmology Retina. 2021;5:879-887. https://www.aao.org/diversity-equity-and-inclusion
American Academy of Ophthalmology. Diversity, equity, and inclusion. https://www.aao.org/diversity-equity-and-inclusion
US Food and Drug Administration. Enhancing the diversity of clinical trial populations—Eligibility criteria, enrollment practices, and trial designs guidance for industry. November 2020. https://www.fda.gov/media/127712/download
Coney JM. Racial bias in clinical trials: what you need to know. Retina Today. March 202. https://retinatoday.com/articles/2021-mar/racial-bias-in-clinical-trials-what-you-need-to-know