Clinical trials are the gold standard to develop evidence for the efficacy and safety of new therapies and innovative medical approaches. Therefore, clinical trials form the basis of evidence-based care.
An important element of a well-designed clinical trial is to be inclusive of racial and ethnic minorities and other populations that experience health care disparities. Clinical trials that foster diversity in enrollment have the advantage of producing results that are generalizable to the entire population and will also account for the potential differences in experiences and responses to medical interventions, among the different races and ethnic communities. It is, however, widely recognized that racial and ethnic minorities have historically been underrepresented in clinical trials.1
These shortcomings persist despite several interventions by the National Institutes of Health (NIH) and the US government to overcome this discrepancy. A recent report by the US Food and Drug Administration (FDA) showed that while African American individuals account for more than 13% of the US population, their participation in clinical trials is less than 5%.1
The underrepresentation of minority groups has been noted in clinical research across all diseases, but it is particularly predominant in lupus among Black individuals.
Clinical Trials in Lupus and Minority Group Participation
Lupus has been estimated to affect more than 300,000 Americans.2 The prevalence of lupus is higher in African American adults compared with non-Hispanic White adults, with epidemiologic studies demonstrating that approximately 70% of prevalent SLE in the US is seen among Black, Asian, and Hispanic individuals.3,4
Compared with non-Hispanic White populations, African American and Latinx populations are known to experience higher disease severity with more complications and also have a 3-to- 4-fold higher mortality.5
Recent advances in the understanding and treatment of lupus have resulted in an increased duration of mortality. However, the complexity and heterogeneity of lupus results in an ongoing need for better therapeutics and consequently the need for more clinical trials. Ongoing lupus clinical trials report limited success in recruiting Black individuals as well as others from minority populations.
There are currently about 400 centers that actively participate in lupus clinical trials in the US and Canada. Falasinnu et al, in their analysis, noted that while Black patients make up 43% of lupus cases in the US, they only accounted for 14% of the enrollees in randomized clinical trials.6 The low numbers of minority participation has resulted in inconclusive results on the effectiveness of some of the newer treatment options for lupus.
The FDA approved belimumab, a novel biologic medication, for the treatment of SLE in March 2011. The approval was largely based on a phase 3 trial that was conducted in Latin America, Asia Pacific regions and Eastern Europe and did not include participants from the US.7 While there was initial excitement about the approval of a new therapy for SLE, the first such approval in more than 50 years, concerns about the applicability of the results of the trial to the US population was raised, as only 3.5% of the study population was Black in the study.
Subsequently, the results of another study of belimumab in lupus, conducted in North and Central America, were published. The phase 3 study had a larger representation of minority groups but still accounted for only approximately 14% Black patients.8
Pooled results from the 2 phase 3 trials of belimumab showed that Black patients did not benefit from intravenous belimumab treatment. These concerns led to another clinical trial to evaluate the safety and efficacy of belimumab in patients of Black ancestry with SLE (EMBRACE trial [ClinicalTrials.gov Identifier: NCT01632241]).9 The need for the additional study not only delayed the benefits of the new therapy for patients most at need for these novel agents but also potentially contributed to higher financial costs of these medications.
Despite this costly lesson, a more recent phase 3 trial of anifrolumab for the treatment of lupus was also only successful in enrolling about 14% Black patients.10
Low Black Participation in Clinical Trials
There are several barriers that contribute to low participation of minority communities in clinical trials. The reasons can be broadly categorized as systemic, provider-based, or patient-related.
Systemic barriers include the limited number of clinical trials nationally and regionally; hospital infrastructure and lack of resources to support clinical trials; the financial costs of conducting clinical trials borne by hospitals and patients; restrictive study designs including improper eligibility criteria; and the lack of community engagement.
Physician-related barriers include the lack of awareness and knowledge of clinical trials, personal attitudes, and logistic barriers.
Patient barriers include mistrust of the health system, lack of opportunity to enroll in trials, health literacy, access to research studies, and personal attitudes.
The Need for Clinician Education
Physicians are consistently rated as the most trusted source of information for patients. More than 77% of participants enroll in clinical trials because of referral by their primary care physicians (PCPs). PCPs are important because they are often a patients’ first point of contact to learn about clinical trial research. Reports, however, suggest that health care professionals have limited information on ongoing clinical trials and on how to access such trials for their patients.11 Clinician education on the basic fundamentals of clinical trials is, therefore, an important first step to improve minority enrollment in clinical trials.
The legacy of unethical studies such as the Tuskegee syphilis study and negative personal experiences of Black patients within the health care system has created a history of mistrust of research centers and academic institutions. Educating the clinicians on health care disparities and providing methods to improve cultural competency can help overcome this barrier.
Communication training to explain complex research protocol information to those with a low literacy rate or limited English proficiency is also a crucial step in overcoming low minority participation in clinical trials. Clinicians and researchers need to recognize that members of Black communities are eager to participate in research studies.12 Studies however, have underscored the importance of clear and literacy appropriate communication as an essential tool for recruitment of Black individuals in research.
In addition, steps to facilitate collaboration between the diverse groups of community-based physicians and community organizations with physician scientists who traditionally perform clinical trials on behalf of academic and pharmaceutical entities can also help increase Black participation in clinical trials. Clinicians also need to be made aware that clinical trials can help reduce health care disparities. There is evidence that patients in clinical trials have better outcomes than patients not enrolled in trials, including those in the control groups who appear to do better.13
Increasing minority enrollment in clinical trials is, therefore, a key component of efforts to reduce health disparities.
Ongoing Efforts to Increase Minority Participation in Clinical Trials
Increasing the proportion of underrepresented groups in randomized clinical trials is a critical component of eliminating health disparities and is a priority of the US national health agenda.14
Towards these efforts, the National Institutes of Health (NIH) mandates that research proposals for NIH-defined phase 3 randomized clinical trials create processes for identifying differences in treatment responses among racial/ethnic groups, if the intervention effect is expected to vary among them. A recent revision requires that applicable NIH-defined phase 3 clinical trials submit valid subgroup analyses by race/ethnicity and sex/gender to ClinicalTrials.gov.15
There are also various ongoing efforts to improve Black participation in lupus clinical trials.
The American College of Rheumatology (ACR) developed The Lupus Initiative, a multifaceted educational program that is designed to reduce disparities and improve outcomes among people with lupus.16
As part of the initiative, the ACR developed and successfully completed the Materials to Increase Minority Involvement in Clinical Trials (MIMICT) programs, which were directed to help clinical trial sites and health care providers work together to deliver accurate, trusted, and understandable information to those with lupus and help them make informed decisions about participation in lupus clinic trials.17
In September 2021, the ACR launched the Training to Increase Minority Enrollment in Lupus Clinical Trials With Community Engagement (TIMELY) project,18 which aims to overcome provider- and patient-reported barriers to lupus clinical trial participation using lessons learned from previous projects, including the MIMICT program.
Overcoming the lack of diversity in clinical trials is an essential moral and scientific issue in the practice of medicine. A more representative patient population in lupus clinical trials will provide more accurate outcomes in real-world patients. In addition, the racial and ethnic minority groups affected by lupus will benefit with increased access to clinical trials and cutting-edge health care opportunities.
In summary, diverse participation in clinical trials can improve the robustness of scientific studies for the researchers, improve the health of all communities, overcome health care disparities, and curtail the costs of pharmaceutical and national research institutes.
- US Food and Drug Administration. 2018 drug trials snapshots summary report. Published January 2019. Accessed January 19. 2023. https://www.fda.gov/files/drugs/published/Drug-Trials-Snapshot-Report-2018.pdf
- Helmick CG, Felson DT, Lawrence RC, et al. Estimate of the prevalence of arthritis and other rheumatic conditions in the United States. Part 1. Arthritis Rheum. 2008;58:15-25. doi:10.1002/art.23177
- Chakravarty EF, Bush TM, Manzi S, Clarke AE, Ward MM. Prevalence of adult systemic lupus erythematosus in California and Pennsylvania in 2000: estimates obtained using hospitalization data. Arthritis Rheumatol. 2007;56:2092-2094. doi:10.1002/art.22641
- Falasinnu T, Chaichian Y, Palaniappan L, Simard JF. Unraveling race, socioeconomic factors, and geographical context in the heterogeneity of lupus mortality in the United States. ACR Open Rheumatol. 2019;1(3):164-172. doi:10.1002/acr2.1024
- Anandarajah AP. Designing an intervention to improve management of high-risk lupus patients through care coordination. Rheum Dis Clin North Am. 2020;46:723-734. doi:10.1016/j.rdc.2020.07.012
- Falasinnu T, Chaichian Y, Bass MB, Simard, JF. The representation of gender and race/ethnic groups in randomized clinical trials of individuals with systemic lupus erythematosus. Curr Rheumatol Rep. 2018;20:20. doi:10.1007/s11926-018-0728-2
- Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:721-731. doi:10.1016/S0140-6736(10)61354-2
- Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits b lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:3918-3930. doi:10.1002/art.30613
- Ginzler E, Barbosa LSG, D’Cruz D, et al. Phase III/IV, randomized, fifty-two-week study of the efficacy and safety of belimumab in patients of Black African ancestry with systemic lupus erythematosus. Arthritis Rheumatol. Published online June 23, 2021. doi:10.1002/art.41900
- Morand EF, Furie R, Tanaka Y, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382:211-221. doi:10.1056/NEJMoa1912196
- Brown DR, Fouad MN, Based-Engquist MA, et al. Recruitment and retention of minority women in cancer screening, prevention and treatment trials. Ann Epidemiol. 2000;10:813-821. doi:10.1016/S1047-2797(00)00197-6
- Baquet CR, Henderson K, Commiskey P, Morrow J. Clinical trials: the art of enrollment. Semin Oncol Nurs. 2008;24:262-269. doi:10.1016/j.soncn.2008.08.006
- Heiat A, Gross CP, Krumholz HM. Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med. 2002;162:1682-1688. doi:10.1001/archinte.162.15.1682
- National Institutes of Health. NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research. Updated December 6, 2017. Accessed December 18, 2022. https://grants.nih.gov/policy/inclusion/women-and-minorities/guidelines.htm
- National Institutes of Health. Amendment: NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research. Published November 28, 2017. Accessed December 18, 2022. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-014.html
- American College of Rheumatology. New American College of Rheumatology initiatives aim to close the gap on racial disparities in lupus clinical trials. News release. Published February 23, 2022. Accessed January 19, 2023. https://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/1203
- The Lupus Initiative. Materials to Increase Minority Involvement in Clinical Trials. Accessed January 19, 2023. https://thelupusinitiative.org/mimict-2/
- The Lupus Initiative. Training to Increase Minority Enrollment in Lupus Clinical Trials with CommunitY Engagement (TIMELY). Accessed January 19, 2023. https://thelupusinitiative.org/patients-caregivers/patient-database/