Sickle Cell Disease Patients Demonstrate a High Willingness to Participate in Randomized Clinical Trials

Background: African Americans are underrepresented in randomized clinical trials (RCTs). Underrepresentation of this patient group may lead to an inadequate analysis of therapy risks and benefits, and study findings may not be generalizable to a diverse patient population. Moreover, low representation of African Americans in existing clinical trials may discourage future trials focused on this population, as such trials are perceived to be infeasible.

Barriers to participation in clinical trials have been extensively studied. Frequently identified factors include: systemic barriers (availability of clinical trials, eligibility barriers, lack of resources), geography (location of the research institution and access to transportation), and individual-level barriers such as low education, poverty, and poor access to healthcare. Willingness to participate has been cited as a major barrier, related to distrust in the US healthcare systemand to cultural and religious beliefs. Yet a dearth of empirical evidence bolsters the assertion that willingness to participate in clinical trials among African Americans is accountable for underrepresentation. We performed a retrospective review of major RCTs focused on sickle cell disease (SCD) in order to measure willingness of African Americans to participate in clinical research.

Methods: We systematically identified landmark peer-reviewed RCTs focused on SCD. We analyzed the results of these trials reported in the medical literature and calculated participation and completion rates for each trial. For each study, we identified the number of subjects screened for participation, the number who agreed to participate, and the number who declined. We calculated ratios for study acceptance and study completion. We identified the number of publications which clearly reported data from which acceptance to participate could be directly calculated, the number from which participation could be inferred, or from which reported data were insufficient.

Results: We identified 13 RCTs published between 1986 and 2018, representing the major clinically impactful studies in children and adults with SCD. Six of the 13 studies reported sufficient data to infer or calculate participation rates. It is notable that more than half (54%; n=7) of the studies provided insufficient data to calculate study acceptance rates. Our analysis encompassing 2407 patients included in six studies indicates that 82% of subjects with SCD demonstrated willingness to participate in an RCT (range 32-94%), and 95% of clinical trial subjects completed study activities (range 92-98%).

Discussion: A minority of publications reported participation data. One of the 13 studies published data on the race of participants, reporting 94% of participants were African American and 3% were Hispanic. However, since SCD predominantly affects African Americans (approximately 90% of those with SCD nationwide are African American and approximately 10% are Hispanic), it is reasonable to estimate that the subjects in our analysis represent a predominantly African American population. We acknowledge that subjects with SCD may not be representative of the US African American population in total. Nonetheless, our findings contradict the assertion that African Americans are less willing to participate in clinical trials, or that African Americans have disproportionately high drop-out rates.

Only a minority of publications reported data required to calculate participation rates. Despite this limitation, available empiric evidence suggests that when participation in high-quality clinical trials is made available, African Americans demonstrate a willingness and capacity to enroll and complete study participation. The generalized assertion that African American patients' willingness to participate in research is a major factor in their underrepresentation in clinical trials is false. Researchers should design high-quality clinical trials that include this underrepresented group at the outset, and investigators should be encouraged to collect and report participation data more carefully so that this disparity can be measured and addressed.