Inclusion of diverse populations in clinical research broadens our understanding of racial and ethnic differences in treatment responses and helps reduce disparities in outcomes. Yet historically, racial and ethnic minorities have been underrepresented in clinical research. In a study that assessed ophthalmology clinical trials that achieved a health authority’s approval between 2000 and 2020, the levels of enrollment across racial and ethnic groups in the United States differed from the levels of disease burden in those same groups, with overrepresentation of White participants and underrepresentation of Black and Hispanic or Latino participants.¹

Demographic characteristics such as a patient’s ethnicity, race, age, and sex all may contribute to variability in treatment response.² The US Food and Drug Administration (FDA) requires diversity action plans for most pivotal clinical studies, with the expectation that sponsors will enroll participants who are representative of the demographics of the US population that would receive the drug when approved.³

Patients enrolled in clinical trials should reflect the populations affected by the disease. However, this is often not the case for racial and ethnic underserved populations, especially those who are elderly, have comorbidities, or live in rural locations. Although members of racial and ethnic minority populations report similar rates of willingness to participate in clinical trials as White populations, they are often not represented.^4,5 For example, Black and Hispanic populations have higher prevalence of eye disorders like primary open-angle glaucoma, diabetic macular edema, and retinal vein occlusion, yet these populations are frequently underrepresented in clinical trials.^6,7

Several misconceptions contribute to underrepresentation of certain populations in clinical trials. These include:

• A belief that individuals from racial and ethnic minority groups inherently distrust health care and clinical research;
• Assumptions and unconscious bias by principal investigators that patients from underrepresented groups are unlikely to participate in clinical trials and therefore are not invited to enroll; and
• The misconception that establishing a practice in an underserved area or proactively engaging with underserved communities is not a financially viable strategy.

This article addresses and refutes these 3 myths and offers strategies to promote patient inclusion and advance health equity.

Myth 1: Underrepresented People Cannot Trust Medical Teams or Clinical Research

Kapil Kapoor, MD

Distrust in the health care system is prevalent in racial and ethnic minority communities and is a known driver of underrepresentation in clinical trials.^4,5 Historical mistreatment of Black populations in research is a principal contributor to this mistrust in clinical investigators. For example, involuntary participation in medical experimentation occurred in the Tuskegee Syphilis Study, when Black participants were not offered informed consent and were withheld penicillin treatment once it became the standard of care. In another example, forced sterilization laws remained in effect in some US states until the 1970s, again creating mistrust and a barrier to participating in clinical research.^8,9 However, establishing trust and enhancing diversity in clinical trials are obtainable goals toward advancing inclusive and equitable health for all.

Creating a strong presence in, and engagement with, the communities where patients are located is key to building trust and breaking down structural and emotional barriers to care. Mistrust is often rooted in a fear of mistreatment, unknown research procedures, and unintended social or physical consequences.¹⁰ To bridge this communication gap, a community-based approach to educate and recruit patients in underserved communities can be very helpful for clinical trial enrollment. When taking a community-based approach, trust begins far before the clinical encounter and the informed consent process. Several options to achieve this are possible. Research sites meeting and engaging community leaders (“bishop, barber, basketball coach”) who are trusted members of the community can spread the word about using health care services.^11,12 Additionally, bringing the clinic directly to the areas of need through the use of portable equipment in order to screen for cataracts, glaucoma, and other eye disorders provides a more accurate, first-hand assessment of the needs of the community. Ensuring follow-up and returning to the community to provide continuity of care is essential to further engage patients and build their trust.

There are several benefits to using community engagement approaches. The trust established by community leaders is then transferred to the health care team that is working directly in the area. This direct contact between patients, family caregivers, and providers in the setting of a trusted community leader and place of established community engagement makes clinical trial discussions around potential risks and benefits easier to navigate, because trust has already been established.

This seamless, community-based approach has helped increase enrollment of more diverse populations within ophthalmology practices. For example, through the Sight Forever outreach program, Wagner Kapoor Institute (WKI) partnered with rural health care organizations and worked to provide access to areas of unmet need with ocular screenings in churches, community centers, and nursing homes. During the COVID-19 pandemic, WKI offered free vaccinations paired with ocular screenings.¹³ By engaging directly with the community through known community leaders, and building trust outside the walls of the clinic space, WKI increased the percentage of active clinical trial participants who are members of underrepresented racial and ethnic groups to 48%.¹³ This combination of social communication and ambulatory care can foster trust between underserved communities and their health care providers, and therefore increase these communities’ participation in clinical research.

Myth 2: Underrepresented Patients Will Not Want to Participate in Clinical Trials

Jeremiah Brown, MD

There are many factors that influence a patient’s decision to participate in a clinical trial, including socioeconomic, demographic, and cultural considerations. By understanding the barriers that underrepresented patients may face to participate in a clinical trial and addressing them by changing site behavior, the recruitment of a diverse population of study participants will be more successful.¹⁴ The principal investigator (PI) must understand the importance of approaching all patients in the practice and not making assumptions about a patient’s willingness to participate. The clinical research staff must be instructed similarly. The PI should introduce the study goal and concept to the patient with enthusiasm and a belief that, if given the opportunity, this patient will want to participate. The patient should feel that the PI believes in the study, is committed to its success, and considers the patient a strong candidate for participation.

The demonstrated commitment of the PI to their patients and the clinical trial is essential to having patients interested and willing to join.¹⁵ One way to do this is at the practice and staff level, with materials educating patients about clinical research. All employees should be educated on the value of clinical research for all patient populations, and the message should be regularly reinforced by the leadership of the practice. The office should highlight current studies across internal media channels (eg, office-wide newsletters) so that all staff are aware of the enrolling studies and are prepared to answer basic questions. Schedulers should also be made aware of high-priority studies so that all patients with those diagnoses are promptly given new patient appointments and asked if they would be willing to be screened for a study.

Many patients may not understand the complexity of their disease and the limitations of current treatment options. Cultural and language barriers may also lead to a patient having poor understanding of their disease and how to participate in clinical research.¹⁶ Providing disease education and clinical trials materials such as videos, brochures, study-specific informed consent handouts, and, if available, a condensed version of the informed consent form in their native language, can help patients learn more about their disease and encourage them to participate. Consider hiring staff who speak the native language of patients in the target demographic and consider designating a staff member as a patient advocate. One study demonstrated a significant correlation between staff diversity and patient enrollment diversity.¹⁷ It is notable that racial and ethnic minority PIs are also underrepresented in clinical trial staff. Advocacy is needed for PIs and staff to better reflect the communities they serve and help patients feel more comfortable with participating in clinical trials.¹⁷

Participating in a clinical trial may be costly for some patients. They may not attend appointments because of a lack of transportation or inability to miss work. Providing support for patients’ clinical trial visits—such as an appropriate stipend, transportation allowance, or allowance for childcare for children or daycare visits for senior parents at home—can give patients more flexibility to participate. Study sponsors or sites may reimburse expenses incurred due to study participation. Another factor is the number of appointments required in a clinical trial, which can add to the financial and social burden for patients. Some ways to alleviate this burden are to provide late afternoon or weekend study appointments so patients can still work the day of their study visit or ensure the clinical trial protocols are streamlined and easier to get started. For example, in the ELEVATUM study for diabetic eye disease, if patients met the screening criteria they could start treatment that day, eliminating the need for another visit and minimizing the time burden.¹⁸ 

Setting up a practice with strong beliefs in clinical research and making it accessible for underrepresented patients to participate can overcome the myth that they are not willing to be a part of clinical trials.

Myth 3: Investing in Underserved Areas Is a Losing Business Proposition 

Stephen Huddleston, MD

Starting an ophthalmology practice requires a substantial investment of time and financial resources. Key considerations during the start-up phase include the costs of location, build-out, and staffing. Among these, selecting the right geographic location is often the most critical decision—especially when expanding an existing practice.

Ophthalmology practices have a higher concentration in zip codes with higher income and economic attainment levels. As a result, they are typically located in medically overserved metropolitan areas and coastal regions with advanced medical facilities and hospitals. This has resulted in a tremendous need for ophthalmology practices in areas with lower economic and medical development. Patients burdened by economic and social inequalities suffer with an increased risk of visual impairment, blindness, and sudden vision loss due to disease.¹⁹ 

In a recent analysis of eyecare access, higher unemployment rates and lower education levels were associated with poorer local access to providers after adjusting for socioeconomic factors.²⁰ Patient-centric location planning coupled with proactive engagement in communities they serve (as discussed in myths 1 and 2) leads to the strengthening of social responsibility initiatives such as preventive care and education, accessible treatments, and community engagement.²¹

There are several benefits to creating new clinical practices in underserved communities These areas are often referred to as “health care deserts” and can be either urban or rural regions. The defining characteristic is a dearth of health care providers and a lack of mature   industry. Health care deserts have greater percentages of uncared-for patients and are associated with lower costs of living, lower property values, and lower average salaries.

These factors lead to lower practice start-up costs. Due to economic, educational, cultural, and language barriers, patients may be apprehensive or unable to travel to central main offices. Offering care in smaller satellite clinics closer to where the patients are located reduces the burden of distance, facilitates greater access to care, and increases the likelihood that patients will seek care and maintain compliance with treatment plans. This combination makes establishing a clinical practice in these underserved areas a strong financial investment, with less risk and faster growth than in overserved areas.

Another important consideration when setting up an ophthalmology practice is access to clinical trials.^22,23 If the clinic is in an area with a diverse demographic representation of patients, the likelihood of being able to recruit from these patient populations will increase. Underserved populations provide a pool of participants for clinical trials that enhances the advancement of medical research as well as ensures that research includes data from diverse patient populations. Clinical practices that serve more diverse patients can lead to increased referral rates for a clinical trial, which ultimately enables quicker enrollment in clinical trials. Satellite offices closer to patients makes it easier for patients to be a part of any clinical trials offered by the provider group and be able to follow the clinical trial schedules. This also helps fulfill FDA requirements regarding diversity in clinical trials,³ making the site attractive to sponsors. Additional benefits of offering a clinical trial include sponsor-covered patient care costs, supplemental clinic revenue, differentiation from competitors, and the ability to offer patients access to care they might not otherwise receive.²⁴

Conclusions

There are many opportunities to increase the inclusion of underrepresented populations in clinical studies and ensure that trials reflect real-world patient demographics (Table 1). Identifying where these populations are located and establishing practices in those areas can improve community access and make participation in clinical research more feasible. Investigators who are committed to diversity and representation—along with patient education, trust-building, and community engagement—are essential to achieving the inclusivity needed to develop effective therapies for all patients. RP

Jeremiah Brown, MD, FASRS, is a vitreoretinal surgeon at Retina Consultants of Texas in San Antonio. He is a consultant to Genentech, Outlook Therapeutics, Apellis, and 4DMT; reports research funding from Genentech, Regeneron, Apellis, Astellas, Annexon, Outlook Therapeutics, and EyePoint; and has received speaking fees from Genentech, Apellis, and Astellas.

Stephen Huddleston, MD, is a vitreoretinal surgeon at the Charles Retina Institute in Germantown, Tennessee. His relevant disclosures include Apellis, Belite Bio (HK), Boehringer Ingelheim, Chengdu Origen Biotechnology, Eclipse Life Sciences, EyeBio, Genentech, Gyroscope, iLumen, Janssen, Kodiak Sciences, Kyowa Kirin, Oculis, ONL, Opthea, Outlook, Regenxbio, Roche, Bayer, EyePoint, Novartis, OcuTerra, Regeneron, and Novartis. Reach him at stevehudd@gmail.com.

Kapil G. Kapoor, MD, FACS, FICS, FASRS, is a vitreoretinal surgeon and president of research at the Wagner Kapoor Institute, located in the Hampton Roads region of Virginia and North Carolina, and an AIR Site Alliance champion. He is a consultant to Genentech.

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