The clinical trials industry has been slow to respond to the lack of racial and ethnic diversity among trial participants, and this longstanding challenge of underrepresentation has only worsened following the COVID-19 pandemic.  

These trends are unacceptable, not just from a scientific standpoint but from a moral and ethical one.⁴ Sponsors, regulatory bodies, and participants alike are recognizing the urgent need for transformative change to improve diversity, equity, and inclusion in clinical trials. This increasing awareness, accompanied by the call for mitigating actions, has contributed to the rise of decentralized trials (DCTs), which offer an important avenue for expanding access to underserved populations. Read on to explore how DCTs are evolving the industry status quo on inclusion.

Who’s Missing from Clinical Trials—And, Why?

Underrepresentation in clinical trials begins with a long history of mistreatment at the highest levels of research and healthcare. Studies such as the U.S. Public Health Service Syphilis Study at Tuskegee posed major ethical issues that continue to fuel medical mistrust.⁵ To this day, people of color may perceive trials as “experiments” that harm, not help, them.  

However, historical precedent doesn’t fully address the foundation of underrepresentation. Research suggests that while racial and ethnic minorities are just as willing as whites to participate in health research, they far are less likely to be invited to do so.⁶  

Further research⁷ published in the journal Cancer supports this finding. After interviewing stakeholders at five U.S. cancer centers, researchers concluded: “Not only did some respondents view racial and ethnic minorities as less promising participants, some respondents reported withholding trial opportunities from minorities based on these perceptions.”^7(p1958)

To combat blatant discriminations, the industry and healthcare providers must undertake more concerted efforts to engage minorities; the areas of opportunity are legion. Numerous studies show that inequities persist across many disease states and therapeutic modalities, including:

• Vaccines: Black, American Indian or Alaska Native, and Hispanic or Latino adults were underrepresented in vaccine clinical trials compared with the broader U.S. population, according to a study in the Journal of the American Medical Association that examined 230 U.S.-based trials of all phases.⁸
• Cancer: According to research published in the Journal of the Advanced Practitioner in Oncology, less than 20 percent of U.S. adults diagnosed with cancer participate in clinical trials.^9(p756) Of that 20 percent, white middle-class men make up the majority of participants—approximately 85 percent.^9(p756) African Americans represent less than 5 percent of oncology clinical trial participants, and Hispanic Americans only 1 percent.^9(p756)  

• Multiple myeloma: “African Americans are at higher risk of multiple myeloma (MM) yet are underrepresented in clinical trials and reap fewer benefits from novel therapies of the disease,” according to a study in Blood Cancer Discovery.^10(p119) Researchers noted: “Due to underlying genetic and biological differences between African Americans and whites with MM, it is possible that clinical trials may not adequately characterize either the safety or efficacy of approved drugs in these patients.”^10(p119)
• Immunotherapy: A review of 53 completed clinical trials that included more 8,800 patients found that minority women were acutely underrepresented in immunotherapy clinical trials for breast and gynecologic cancers.¹¹ Enrollment of Black or African American women in these studies was especially low, accounting for only 5% of participants—despite the mortality rate for Black women exceeding that of white, Hispanic, and Asian women.^11(p1408)
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The Need for Systemic Change in Clinical Research

To instigate real progress, the industry must first recognize that clinical trial diversity is a matter of health equity. Giving everyone a seat at the table is imperative to developing treatments that meet patients’ needs.  

Research in the Journal of Oncology Practice underscores this necessity, noting that “[d]elivering personalized medicines that account for biologic factors, such as genetics, gender, race, and ethnicity is fundamental to the goal of precision medicine; however, without including adequate representative patient populations, this goal is not achievable.”¹²

People of color must be represented at all stages of therapeutic development, particularly for diseases that affect them disproportionately. For example, African American patients are generally at higher risk for heart diseases, stroke, cancer, asthma, influenza and pneumonia, diabetes, and HIV/AIDS than their white counterparts, according to the Office of Minority Health.¹³ However, clinical research participant pools often fail to reflect the prevalence of disease states in the actual population as accurately they should.  

The FDA¹⁴ has been addressing this issue since the 1980s, and its recent mandates on diversity are pressuring sponsors to demonstrate real efforts, not just intentions.¹⁵ The New England Journal of Medicine¹⁶ has followed suit, requiring researchers to provide diversity statements along with their article submissions.¹⁷

Major sponsors, such as Pfizer¹⁸ and Merck,¹⁹ are also responding to these shifts, prioritizing diversity in their clinical trials and recognizing their business and ethical obligations to do so. And, PhRMA’s Equity Initiative is advocating for “necessary systemic and long-term change to meet the needs of Black and Brown America.”²⁰
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Recommendations for Supporting Diversity in Clinical Trials

As sponsors increasingly acknowledge the problem of underrepresentation in clinical research, how can they commit to being part of the solution? One avenue is to consider a decentralized clinical trial (DCT) as a means of bridging the gap between sponsors and historically underrepresented participants. DCTs bring studies directly to participants, removing many traditional barriers to inclusion and allowing sponsors and clinical research organizations to:  

• Recruit, enroll, engage, and support participants where they are—lowering the burden of geographic or scheduling barriers and creating a safe, accessible environment.
• Generate and provide access to real-time recruitment data to ensure studies are hitting the mark with diverse participant pools.
• Allow for greater flexibility; for example, the need to more easily modify the study protocol based on input from trial participants.

ObvioHealth regularly works with clients to achieve diversity in clinical trials. In a recent ObvioHealth hypertension study, African American participants represented nearly 40% of the study population. And, in a recent dermatology study, more than 60% of participants were Asian, reflecting the higher incidence of a specific skin condition within this population. These statistics prove that it is possible to recruit and retain minorities—if sponsors are committed to doing so.

Any strategy for increasing inclusion and diversity in clinical trials using DCT components should begin with these best practices:

• Start with study design: To support the success of the study overall, it’s important to design the study with inclusion as a goal and to set realistic targets for representation across racial and ethnic populations based on the disease state and treatment under study. Eligibility criteria that limit participants with comorbid conditions are a major hurdle to increasing diversity, according to the FDA¹⁵—and sponsors may need to revisit these criteria. Language and technology are other important factors. Obviously, a trial designed in English will immediately exclude certain potential participants—62 million people in the United States speak a language other than English at home, according to the last census.²¹ A design that requires smartphones for ePRO reporting may exclude lower-income communities. Details like these need to be incorporated from the outset to maximize the potential for inclusion.  
• Ensure inclusive recruitment: Work with an experienced digital recruitment team to reach prospective participants based on factors such as audience geography and affinities. Campaigns should be built based on participant insights into trial motivations and barriers and should feature inclusive messaging and imagery to help potential participants feel that studies are relevant to them. Targeting a more diverse audience can impact overall study costs, but online recruitment for DCTs offsets this premium due to its cost efficiencies.
• Listen and learn: Building trust is essential to recruiting and engaging participants from underrepresented groups. For offline studies, the identification of champions who can discuss the benefits of trial participation with their communities is key. Oncology researchers suggest meeting patients where they are: churches, community centers, support groups, and social media.¹⁰ For both offline and online studies, it can also be important to build a diverse study team that reflects the population with whom they work. Research conducted by the Tufts Center for the Study of Drug Development demonstrates that “clinical trial diversity is closely linked with the diversity of site staff.”²² Of course, representation is not everything. Study teams and sponsors must also be willing to consider modifications to trial protocols when patient input suggests there may be important hurdles to inclusion. Fortunately, DCTs offer real-time insights and feedback loops, as well as more flexible designs, that can facilitate any required changes.
• Provide ongoing support: Study participants need to feel supported throughout the trial to improve engagement and compliance—decentralized trials are no exception. Virtual site teams should be included as part of the clinical trial journey to provide support, answer questions, address concerns, and remind participants of upcoming study tasks—all via the mediums that are most convenient for them.

DCTs are not universal solutions for improving diversity—for instance, lack of broadband Internet in some areas can limit participation in virtual trials. It is also important to note that participant diversity is multi-faceted: age, gender, socioeconomic status, physical and mental ability, geography (rural versus urban), and more are all diversity categories. Intersectionality across these dimensions can affect how people perceive and participate in trials. However, DCTs are a proven method for meaningfully addressing issues that have historically hindered people of color, and other underrepresented groups, from participating in trials.  
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Conclusion

Increasing diversity, equity, and inclusion in clinical trials is both a moral imperative and a business differentiator. The most forward-thinking sponsors are already defining the future of engagement—and shifting the industry will require an overhaul of the status quo. Decentralized trials offer a promising avenue for real change, and sponsors striving to lead the industry in systemic transformation have an incredible opportunity to do so with virtual, and ethical, innovation.

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References:

1. Cavazzoni P, Anagnostiadis E, Lolic M. 2020 Drug Trials Snapshots Summary Report. FDA. February 2021. Accessed August 27, 2023. https://www.fda.gov/media/145718/download  

2. Quarshie M, Slack D. Census: US sees unprecedented multiracial growth, decline in the white population for first time in history. USA Today. August 12, 2021. Accessed August 27, 2023. https://www.usatoday.com/story/news/politics/2021/08/12/how-2020-census-change-how-we-look-america-what-expect/5493043001/  

3. Michael K, Jamie P. Global Trends in R&D 2023: Activity, Productivity, and Enablers. IQVIA; 2023. Accessed August 27, 2023. https://www.iqvia.com/insights/the-iqvia-institute/reports/global-trends-in-r-and-d-2023

4. Gray DM, Nolan TS, Gregory J, Joseph JJ. Diversity in clinical trials: an opportunity and imperative for community engagement. Lancet Gastroenterol Hepatol. 2021;6(8):605-607. doi: 10.1016/S2468-1253(21)00228-4

5. CDC. Tuskegee Study: Timeline. Centers for Disease Control and Prevention. Updated December 5, 2022. Accessed August 26, 2023. https://www.cdc.gov/tuskegee/timeline.htm

6. Nazha B, Mishra M, Pentz R, Owonikoko TK. Enrollment of Racial Minorities in Clinical Trials: Old Problem Assumes New Urgency in the Age of Immunotherapy. Am Soc Clin Oncol educ book. 2019;39:3-10. doi: 10.1200/edbk_100021

7. Niranjan SJ, Martin MY, Fouad MN, et al. Bias and stereotyping among research and clinical professionals: Perspectives on minority recruitment for oncology clinical trials. Cancer. 2020;126(9):1958-1968. doi: 10.1002/cncr.32755

8. Flores LE, Frontera WR, Andrasik MP, et al. Assessment of the Inclusion of Racial/Ethnic Minority, Female, and Older Individuals in Vaccine Clinical Trials. JAMA Netw Open. 2021;4(2):e2037640. doi: 10.1001/jamanetworkopen.2020.37640

9. Mutale F. Inclusion of Racial and Ethnic Minorities in Cancer Clinical Trials: 30 Years After the NIH Revitalization Act, Where Are We? J Adv Pract Oncol. 2022;13(8):755-757. doi: 10.6004/jadpro.2022.13.8.2

10. Gormley N, Fashoyin-Aje L, Locke T, et al. Recommendations on Eliminating Racial Disparities in Multiple Myeloma Therapies: A Step toward Achieving Equity in Healthcare. Blood Cancer Discov. 2021;2(2):119-124. doi: 10.1158/2643-3230.bcd-20-0123

11. Sims TT, Jazaeri AA. Recruiting for diversity in immunotherapy trials for breast and gynecologic cancers: moving beyond under-representation. Int J Gynecol Cancer. 2021;31(11):1408-1409. doi: 10.1136/ijgc-2021-003088

12. Regnante JM, Richie NA, Fashoyin-Aje L, et al. US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials. J Oncol Pract. 2019;15(4):e289-e299. doi: 10.1200/jop.18.00638

13. U.S. Department of Health and Human Services, Office of Minority Health. Profile: Black/African American. HHS.gov. Updated February 24, 2023. Accessed August 28, 2023. https://www.minorityhealth.hhs.gov/omh/browse.aspx?lvl=3&lvlid=61  

14. Clinical Trial Diversity. FDA. Updated November 4, 2022. Accessed August 24, 2023. https://www.fda.gov/consumers/minority-health-and-health-equity/clinical-trial-diversity  

15. The National Press Club. Public Workshop: Evaluating Inclusion and Exclusion Criteria in Clinical Trials. FDA. April 16, 2018. Accessed August 27, 2023. https://www.fda.gov/media/134754/download  

16. Schwartz AL, Alsan M, Morris AA, Halpern SD. Why Diverse Clinical Trial Participation Matters. N Engl J Med. 2023;388(14):1252-1254. doi: 10.1056/nejmp2215609

17. Editorial Policies | About NEJM. New England Journal of Medicine. Updated 2023. Accessed August 26, 2023. https://www.nejm.org/about-nejm/editorial-policies  

18. Diversity in Clinical Trials. Pfizer. Updated 2023. Accessed August 25, 2023. https://www.pfizer.com/science/clinical-trials/diversity  

19. Diversity in Clinical Trials. Merck. Updated 2023. Accessed August 25, 2023. https://www.merck.com/research/diversity-in-clinical-trials/  

20. PhRMA’s Equity Initiative. PhRMA. Updated 2023. Accessed August 25, 2023. https://phrma.org/equity  

21. Dietrich S, Hernandez E. Nearly 68 Million People Spoke a Language Other Than English at Home in 2019. United States Census Bureau. December 6, 2022. Accessed August 26, 2023. https://www.census.gov/library/stories/2022/12/languages-we-speak-in-united-states.html  

22. Macdonald G. Site staff diversity vital for trial participant diversity according to Tufts. Clinical Insider. November 8, 2021. Accessed August 28, 2023. https://informaconnect.com/site-staff-diversity-vital-for-trial-participant-diversity-according-to-tufts/?utm_medium=email&utm_campaign=ClinicalTrialsInsider%2F2021%2FNov11%2FSubscribe&utm_source=Clinical%20Trials%20Content%20Newsletters&user_id=900076810987&tracker_id=02URPYUAB&segments=none&esp=adestra&utm_term=Read%20Now%203  

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