Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that primarily affects women of childbearing age, and disproportionately affects Black/African American and Hispanic/Latinx populations who experience greater morbidity and mortality from the disease. Lupus was the fifth leading cause of death among Black and Hispanic women aged between 15 and 24 years and the top 20 leading causes of death in the US among girls and women aged between 15 and 64 years, from 2000 to 2015.1
To address these disparities, it is imperative that we develop safe and effective treatments for patients with SLE based on representative and robust clinical trials. However, achieving progress toward these aims for SLE clinical trials has proven to be difficult thus far.
Despite a higher prevalence among diverse racial and ethnic groups, marked gaps exist between populations affected by SLE and those enrolled in clinical trials. White patients comprise about one-thirds of the prevalent SLE cases in the US but represent the majority (51%) of SLE randomized controlled trial (RCT) participants.2 Conversely, Black patients comprise 43% of the prevalent SLE cases but only represent 14% of RCT participants.2 The differences between SLE prevalence and RCT representation are much smaller for Hispanic/Latinx (16% of prevalent SLE cases vs 21% RCT enrollees, respectively) and Asian patients (13% of prevalent SLE cases and 10% of RCT enrollees, respectively).2
There are a multitude of patient and provider barriers to achieving racial and ethnic representation in lupus clinical trials. These barriers include patients’ awareness about clinical trial opportunities, lack of access to referring physicians (particularly rheumatologists), and logistic challenges to accessing and participating in clinical trials. On the provider side, barriers include treating physicians’ lack of access to clinical trial information and effective referral pathways, limited time to discuss trial opportunities with patients, and attitudes and biases that limit referrals to clinical trials.3 Barriers among patients and providers are widespread and engrained in the past and present context of structural racism and discrimination, both within and beyond the health care and research continuum.4 There has been growing attention in research to elucidate the barriers and facilitators of clinical trial participation among groups underrepresented in lupus clinical trials,5,6 but there are still substantial knowledge gaps in this area.
Identifying and Addressing Barriers in Lupus Clinical Trial Participation
An abstract presented at the American College of Rheumatology (ACR) Convergence 2021 aimed to identify barriers in engaging diverse racial and ethnic patient populations in lupus clinical trials and explore potential approaches to ensure equitable representation.
Semi-structured interviews were conducted to understand patients’ and physicians’ barriers and potential solutions to improving racial and ethnic representation in lupus clinical trials. Participants were asked open-ended questions about their awareness of clinical trials and motivating factors/barriers for clinical trials participation.
A total of 33 patients with lupus and 20 physicians (investigators or referring physicians in dermatology or rheumatology) from across the US participated in the study.
Approximately half of the patient participants identified as being Black/African American (48%), followed by Latinx (30%), Asian/Pacific Islander (15%), and Native American (6%). The majority of physician participants identified as being White (60%), Asian/Pacific Islander (20%), and Black/African American (10%). Physicians practiced in rheumatology (55%) and dermatology (45%), and were treating physicians who referred patients to clinical trials (70%) vs clinical trial investigators (30%).
Patient-Reported Barriers in Clinical Trial Participation
The main theme of patients’ reported barriers in clinical trial participation was a concern around the safety and efficacy of investigational drugs, including potential side effects. Conversely, patients also reported unfavorable views around being randomly assigned to a placebo group and missing out on potential benefits from the treatment, which was in line with previous research findings.5,6
Clinical trials were also described as burdensome in terms of being time- and labor- intensive, with challenges such as transportation and traveling to and from research visits. Day-to-day challenges were identified as being more impactful barriers in clinical trial participation; some patients reported social and structural barriers, such as mistrust in the health care system and historic mistreatment of groups underrepresented in clinical trials today.
Provider-Reported Barriers in Increasing Representation in Clinical Trials
Less than half of physicians who were interviewed knew of any current lupus clinical trial opportunities in their area, highlighting a gap in communication between treating/practicing physicians and clinical trial investigators/sites. When clinical trial opportunities were present, some physicians reported a lack of information and instruction on appropriate steps to refer patients to a trial. Physicians also reported biases as barriers to referring patients to clinical trials, such as having preconceived notions that patients wouldn’t want to participate or be adherent to the trial protocol.
Potential Solutions: Patient and Physician Recommendations
To overcome these barriers, patients recommended minimizing the burden of clinical trial participation (eg, fewer visits). Suggestions also included using culturally competent approaches to communicate the value of clinical trials (eg, altruistic and potential personal benefits) to patients and their communities. Patients also highlighted the need to increase trust in the health care system as well as in clinical trial sponsors and investigators, suggesting that recommendations from patients’ treating physician could be a valuable way to build this trust.
To overcome informational and procedural barriers to clinical trial referrals, physicians reported a desire for a centralized online clinical trial resource to raise awareness of trial opportunities and provide networking support to refer patients to clinical trials. Physicians also highlighted the value of raising patients’ awareness of clinical trial opportunities through local outreach with trusted community organizations (eg, churches and community centers). Additionally, some physicians highlighted the potential for diversification of clinical trial investigators to better reflect the communities they engage with, particularly among underrepresented groups.
The key takeaways from this study were that it is prudent to address proximal barriers to clinical trial enrollment, such as investigational drug education and reducing the time and resource costs of participation, in addition to building trust in the health care system. This collaborative work also highlights the importance of patient, physician, and sponsor partnerships in identifying and addressing these critical barriers to representation of diverse groups in lupus clinical trials. This work is part of a growing effort to recognize and understand disparities in lupus clinical trial participation and was strengthened by the inclusion of perspectives from both patients with lupus and referring physicians. Additional work is necessary to identify strategies to build communication, collaboration, and connections to address these barriers.
Note from the authors: We would like to thank all the patients with lupus and physicians who participated in this study and acknowledge all individuals living with lupus for their courage and determination. We would also like to acknowledge the commitment to diversity, equity, and inclusion, and the collaborative nature of this work as a sponsor-led initiative between Biogen and academic researchers at the University of North Carolina at Chapel Hill.
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2. Falasinnu T, Chaichian Y, Bass MB et al. 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
3. Sheikh SZ, Wanty NI, Stephens J et al. The state of lupus clinical trials: minority participation needed. J Clin Med. 2019;8(8):1245. doi:10.3390/jcm8081245
4. George S, Duran N, Norris K. A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders. Am J Public Health. 2014;104:e16-e31. doi:10.2105/AJPH.2013.301706
5. Arriens C, Aberle T, Carthen F et al. Lupus patient decisions about clinical trial participation: a qualitative evaluation of perceptions, facilitators and barriers. Lupus Sci & Med. 2020;7:e000360. doi:10.1136/lupus-2019-000360
6. Sneed RS, Mason M, Williams JN et al. Using Critical Race Theory to understand trial participation among black individuals with systemic lupus erythematosus: a qualitative study of patients and caregivers. Arthritis Care Res (Hoboken). 2021;73(10):1387-1395. doi:10.1002/acr.24635