Ongoing Minority Underrepresentation in Clinical Research Leads to Efforts to Bridge the Divide

Of late, broad attention in the health care community has shifted toward disparities in adequate care delivery, bringing to light deep-rooted biases across fields of medicine. As a result, inequities in patient enrollment to cancer clinical trials has once again bubbled to the surface, resulting in collaboration between clinicians to address and overcome the barriers observed.

“We recognize that there are complex forces and systems that have created disparities in cancer research and that solving these problems will take a multifaceted integrated approach reflecting the best current thinking and expertise from the entire cancer community,” said Association of Community Cancer Centers (ACCC) president Randall A. Oyer, MD. “By working together, we can significantly extend the reach of this effort and help ensure that we pursue promising strategies that have a lasting and meaningful impact.”

One analysis of patients and clinicians at Roswell Park Comprehensive Cancer Center in 2018 demonstrated that the single most influential barrier to clinical trial enrollment was stringent eligibility criteria, leading investigators to conclude that broader standards may yield greater enrollment.¹

In July 2020, the FDA issued 4 separate draft guidance documents in an effort to expand cancer clinical eligibility criteria for pediatric patients and all patients with brain metastases, organ dysfunction or prior/concurrent malignancies, and HIV or hepatitis B or C infections.^2-5 These recommendations stemmed from a joint project between the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research intended as a guide for modifying rigid enrollment criteria; such criteria have been criticized for restricting patient access to clinical trials, thereby limiting the generalizability of study results to real-world patient populations.⁶

Despite recent efforts to combat low clinical trial enrollment, disparities in study populations leading to subsequent underrepresentation of certain patient subgroups in scientific findings continue to affect trial investigators, their patients, and clinicians within the field.

Inequities In Enrollment

One study that looked at data derived from electronic health records noted that the prevalence of exclusion criteria was a significant limiting factor for potential enrollees, and that individuals who identified as Black or African American, or Latino or Hispanic, and those aged more than 70 years were less likely to be treated on a clinical trial.⁷

A variety of reasons may contribute to lack of diversity in cancer clinical trials, including narrow eligibility standards and other study design barriers. However, a document issued jointly by ASCO and the ACCC—one requesting novel strategies and practical solutions for increased participation of racial and ethnic minorities in cancer clinical trials—states that the reasons are likely multifactorial, including such other reasons as clinician bias and challenges with cultural competence; access challenges related to cost of care and insurance; lack of trust between patients and clinicians and the health system as a whole; linguistic, cultural, and literary-related barriers; and factors with family and community engagement.⁸

Qualitative research findings from interviews conducted in 2010 at cancer centers affiliated with the Consortium for Enhancing Minority Participation in Clinical Trials—the goals of which are to address systemically limited enrollment of minorities in cancer clinical trials—focused on the experiences of staff responsible for referring patients to potentially appropriate studies. Staff members included principal investigators, research staff, referring clinicians, and cancer center leaders. Men and women were represented equally among all interviewees and more than 70% of participants were White. Perceptions of challenging interactions with minority patients and practices of withholding trial opportunities due to clinical-based barriers and negative opinions were themes heard again and again in the interviews. To some, race was viewed as irrelevant when screening for potential minority participants (TABLE).⁹

In their discussion, the investigators said the results demonstrated that referral and recruitment biases existed in the sample cohort, thus supporting hypotheses asserting that clinical trials are not being offered to minority patients based on negative stereotypes. Furthermore, clinicians who claim to approach clinical trial recruitment with a “color-blind” strategy may be negatively affecting communications in racially discordant professional–patient interactions, thereby perpetuating these issues and reinforcing ideals that disparities exist organically.

Disparities in Patient-Reported Outcomes

Issues that arise from the lack of minority representation in clinical trials include cancer therapies that have not been adequately tested for efficacy in certain patient subsets and not enough novel therapies in the treatment of advanced cancers that disproportionately affect minorities. According to some investigators, using patient-reported outcomes (PROs) as a way to address diversity in drug development may help ensure that clinical trials reflect heterogeneity of patient populations as well as give voice to patients of diverse backgrounds.10 PROs aid investigators by collecting data related to patients’ overall quality of life, adverse effects associated with the study drug, and physiological status.

A retrospective analysis of 10 clinical trials was performed to determine which patients are most likely to complete PROs. Results suggested that race, age, and education were associated with whether or not patients choose to consent or were offered the chance to participate in PRO data capture. Specifically, Whites versus nonWhites (odds ratio [OR], 0.53; 95% CI, 0.45-0.63; P <.001) and those with education after high school versus those with less education (OR, 1.71; 95% CI, 1.46-2.02; P <.001) were more likely to consent. Furthermore, patients younger than 65 years (OR, 0.63; 95% CI, 0.47-0.85; P = .002), those who were White (OR, 0.60; 95% CI, 0.44-0.82; P = .001), and never or former smokers (OR, 0.57; 95% CI, 0.41-0.78; P = .001) were more likely to participate in electronic PRO capture. Patient refusal was the most common reason for not participating and tools not validated in a patient’s language accounted for about 17% of patients who did not participate in PRO measures.¹¹

Moving Forward to Address Imbalances

Knowledge of these disparities may not come as a surprise to many practicing clinicians, but strategies for overcoming barriers to the problem are vexing and continue to elude the oncology community.

A recent study collected from survey data indicated that willingness to participate in clinical trials was not specific to any particular patient subgroups, and patients considered to be from “underrepresented” populations showed similar willingness to enroll. Specifically, patient age, area of residence, and race were not determinants of clinical trial participation willingness as some previous data may have suggested. In fact, patients who answered their questionnaires in Spanish demonstrated the highest willingness to participate in cancer clinical trials.¹²

In late 2019, the National Coalition for Cancer Survivorship held its Cancer Policy Roundtable—composed of patient advocates, a cancer survivor, investigators in health disparities, and a physician—to discuss current challenges at hand. Medical ethicists said that trial structures and conditions often are to blame for limiting or totally eliminating minority group participation, and the assumption that disparities are mainly due to socioeconomic and educational barriers is flawed. There was agreement within the group that using channels such as social media and television to encourage trial participation can be more effective than traditional contact methods like phone calls.¹³

Multilevel interventions at both the systemic and individual levels may be necessary to overcome barriers to minority enrollment. A model introduced by Lauren M. Hamel, PhD, of Wayne State University and Karmanos Cancer Institute in Detroit, and colleagues describes how effective, high-quality communication can address individual-based barriers between clinical investigators and potential patient participants and their families. These efforts, in addition to those aimed at overcoming systemic barriers, are needed to reduce disparities.¹⁴

To combat the multitude of barriers at hand, ASCO and ACCC issued a Request for Ideas in July 2020 for novel strategies and practical solutions for addressing enrollment and retention issues.8 Existing programs, such as the “Just Ask” Minority Participation in Research program at the Duke Cancer Institute in Durham, North Carolina,15 are referenced in the document as initiatives to aid in combating these disparities.

“We are committed to providing evidence- based high-quality cancer care to every patient, every day, everywhere,” Lori J. Pierce, MD, who is ASCO president as well as co-chair of the ASCO-ACCC Steering Group overseeing this initiative, said in a press release. “But, if clinical trials don’t represent the individuals we treat, including those from racial and ethnic minority populations, the state of science suffers and patients with life-threatening conditions may miss out on the best—perhaps only—treatment option for their condition. This initiative is of critical importance and we’re honored to be working with ACCC to address longstanding barriers to diversity in cancer treatment trials.”