Racial and Ethnic Diversity in Clinical Trials: Improving the Ethics of Data-Gathering

The issue of diversity in clinical trials is not limited to underrepresentation in later-stage clinical trials. People of color are, in fact, overrepresented in Phase 1 clinical trials, which are normally used to establish safety and appropriate dosing. Phase 1 trials typically involve the greatest risk to patients with the lowest likelihood of clinical benefit. Frequently, there is a lack of compensation to those injured because of participation.⁵ Thus, attention must be paid to the composition of clinical trial populations across the spectrum of clinical development.

The factors determining the current lack of diversity in clinical trials are vast, systemic, and historical.

One key factor is that documented unethical medical research practices against marginalized populations has fostered distrust. A landmark example of injustice by the medical research community was the U.S. Public Health Service Syphilis Study at Tuskegee, which denied Black male participants informed consent and withheld standard of care for over 40 years.⁶ Another well-known example is the Holmesburg Prison experiment, in which prisoners were subjected to inhumane experimentation and suffered long-term side effects or death. The government permitted these experiments to continue for 10 years after there was documented evidence of wrongdoing and an ongoing investigation by the FDA.⁷ Past and ongoing patterns of discrimination have led to concerns among vulnerable populations about potential exploitation, poorly- communicated or undisclosed risks of experimental treatment, and the true motivations of researchers.⁸

Importantly, the onus of overcoming this distrust lies not with patients but with the medical and scientific communities, including those conducting clinical trials.

While some people of color are justifiably distrusting of or unwilling to participate in the clinical trial process, additional factors contribute to their lack of representation. A review of cancer trials found that African American/Black and Hispanic/Latinx patients were less likely to be enrolled in trials, in relation to the number of US cancer cases in each subgroup, than their white counterparts. The study highlighted that, based on past research, these populations may be less likely to be offered trial participation.⁸ Potential explanations for this disparity include difficulty accessing underserved populations and cultural or language barriers between investigators and prospective participants.⁸ Socioeconomic factors may present a barrier to recruitment, as structural racism, low income, and lack of access to healthcare can contribute to lower clinical trial participation rates.⁸ Investigator bias also plays a role. In one study, van Ryn et al used survey data from 618 patient encounters with 193 physicians to assess physician perceptions of patient intelligence, feelings of affiliation toward the patient, and beliefs about patients’ likelihood for high-risk behavior and adherence to medical advice. They found that physicians tended to perceive African American/Black patients more negatively than white patients.⁹ Together, these studies demonstrate the many ways in which structural factors and implicit bias, prevalent in our healthcare system, impact the composition of clinical trial populations.

The solution to this complex problem requires a multifactorial approach. Despite ordinances outlined in the Revitalization Act of 1993, which encouraged the inclusion of women and marginalized populations in NIH-funded clinical trials, systemic factors influencing clinical trial recruitment persist.¹⁰ More recently, the FDA Guidance for Industry, issued in 2020, provided recommendations to enhance the diversity of clinical trial populations by broadening eligibility criteria, enrolling participants reflective of disease state populations, and adopting more-inclusive enrollment practices to make trial participation less burdensome for patients.¹ The Patient-Centered Outcomes Research Institute (PCORI) encourages investigators to partner with patient advisors or coinvestigators throughout the research process. Patient advisors can bring value in developing and prioritizing research questions, choosing outcomes that are important to patients, anticipating recruitment barriers, interpreting study data, and deciding how best to disseminate study results.¹¹ Adoption of recommendations put forth by government bodies, such as the FDA and PCORI, is a starting point for changing industry practices.

The healthcare industry must also address the disproportionately small number of principal investigators of color, who are more likely to successfully recruit racially diverse trial participants.

For example, the NIH funding rate for R01 applications is approximately 1.7-fold higher in white versus African American/Black scientists. In addition, Hoppe et al found applications from African American/Black scientists were discussed 24% less frequently as those from white scientists, with poorer overall impact scores (numerical representation of the application’s scientific and technical merit) on average.¹² Organizations dedicated to training female and racially diverse investigators, such as Project Increase Minority Participation and Awareness of Clinical Trials (IMPACT) and the National Hispanic Research Network, are promising examples of current efforts to address this issue.³ Eli Lilly and Company has collaborated with external partners, such as patients, nurses, physicians, and study coordinators, to recruit physicians of color as clinical trial investigators.¹³ While pharmaceutical companies may tend to select established investigators with a proven track-record, providing an opportunity to investigators of color is imperative to improve the racial and ethnic diversity of clinical trials.