In the article that accompanies this editorial, Riner et al¹ apply pancreatic cancer clinical trial eligibility criteria to a real-world cohort of patients, finding that Black patients are less likely to be eligible to participate compared with White patients. These findings suggest that restrictive eligibility criteria are a structural barrier that disproportionately affects minority populations, which, if addressed, could improve diversity of clinical trial enrollment.

Low rates of minority accrual in clinical trials have been attributed to a multitude of causes, including patient lack of understanding regarding clinical trials, concern about trial conditions, dislike of the random assignment process, suspicion of clinicians’ attitudes, and distrust of medical research related to historical discriminatory events.² However, these explanations attribute responsibility primarily to patients themselves and fail to explore the larger role that the health care system plays in clinical trial disparities. In fact, a recent systematic review and meta-analysis of 35 studies examining patient agreement to participate in cancer clinical trials found that when offered trial participation, Black patients chose to participate at similar rates as White patients (58% v 55%, respectively).³

As Riner et al¹ propose in their study, underlying structural barriers, specifically overly restrictive clinical trial eligibility criteria, may inadvertently disqualify the very patients that we most need to enroll. In an analysis of 20 SWOG clinical trials, the mean number of study eligibility criteria was 16.1, of which 60% (9.8) were directly related to comorbidities or performance status.⁴ When comorbidities are more prevalent within specific population groups, demographic disparities in enrollment will result.

In the associated article, Black patients were significantly less likely to be eligible for pancreatic cancer trials because of HIV, hepatitis C, hepatitis B, or hypoalbuminemia. The prevalence of HIV and hepatitis B is higher among Black compared with White populations in the United States, and death rates from hepatitis B and C are higher among Black populations.^5,6 Hypoalbuminemia—although a sequela of malignancy—may also reflect a social determinant of health, as minority populations may experience delays in access to care, resulting in more advanced disease and worse nutritional status at presentation. In addition, minority patients may experience higher rates of food insecurity related to residential segregation and concentrated poverty.⁷ As the authors point out, poorly controlled diabetes can be a manifestation of limited access to primary and subspecialty endocrinology care, nutritional counseling, and access to healthy foods. Each of the identified comorbidities by Riner et al¹ reflect the historical disadvantage experienced by minorities in the United States, which then amplifies downstream disparities in cancer treatment, including clinical trial representation. Not surprisingly, the only criteria for which White patients were excluded at higher rates was receipt of prior therapy, a likely surrogate for better health care access and more favorable social determinants of health.

Although not the primary focus of this study, it is important to consider the role that clinicians play in assessing patient eligibility for clinical trials, as there is potential for implicit bias to affect which patients are offered participation. In their study, the authors intentionally did not examine exclusion criteria related to history of substance abuse, alcohol abuse, or uncontrolled psychiatric illness because of the risk for introducing subjectivity and bias into the study analysis. This bias likely also exists in practice, as incorporating behavioral criteria into clinical trial eligibility introduces subjectivity that could also exacerbate disparities in enrollment.

Physicians may be less likely to recommend minority patients for eligibility screening because of concerns about the impact on the patient-physician relationship, the likelihood of a patient to participate, and the patient’s anticipated adherence to complex study protocols. Research has shown that Black patients are more likely than White patients to be considered ineligible for cancer clinical trials because of anticipated noncompliance, a subjective assessment made on the basis of prior no-shows for clinic appointments, active substance abuse, or “perceived instability.”^8(p790) Clinician implicit bias can be pervasive, emerging even in the language used for documentation in the medical record. A recent study using natural language processing of more than 40,000 history and physical notes found that Black patients had 2.5 times the odds of being described in the electronic health record with at least one negative descriptor, such as “difficult,” “challenging,”^9(p208) or “non-compliant.”^9(p205) Minimizing or eliminating subjective eligibility criteria is critical to avoid the effects of implicit bias.

The associated article also brings up several additional questions worthy of further investigation. First, although eligibility criteria for a broad range of pancreatic cancer trials were assessed, a minority (27 of 86) were specific to patients with resectable cancer and less than one-third of patients in the study had clinical stage I or II disease. The application of clinical trial eligibility criteria may differ for surgical patients compared with those with advanced disease, and focused efforts to establish which eligibility criteria are necessary in a surgical population should be prioritized. Second, as the authors discuss, the ASCO-Friends of Cancer Research Joint Research Statement published in 2017 recommends the expansion of eligibility criteria to make trial populations more reflective of the general cancer population.¹⁰ It will be important to determine whether trials developed and approved after these guidelines have incorporated these recommendations and whether this translates into improved racial diversity in trial enrollment.

Perhaps the most important finding reported by Riner et al¹ is that when traditional clinical trial eligibility criteria are revised, there is no longer any difference in eligibility among Black and White patients. Despite a plethora of studies identifying and describing racial disparities in cancer treatment and outcomes, few offer specific, tangible solutions like those proposed here. Although modifying eligibility criteria alone will not eliminate disparities, it is a practical first step that should be part of a systematic approach toward cancer health equity.

Fortunately, it is becoming more evident to the broader medical community that intentional efforts are necessary to address health care disparities. As a recent example, an antiracism system–based intervention was recently demonstrated to eliminate racial disparities in timeliness of lung cancer surgery.¹¹ The intervention consisted of a real-time warning system using the electronic health record to measure time-sensitive clinical milestones and enhance race-specific transparency in adhering to standards of care, a physician champion who reviewed quarterly reports on race-specific treatment completion rates, and a nurse navigator trained in racial equity analysis who informed the clinical team of care delays and addressed patient barriers to care such as lack of transportation or misinformation. This type of multilevel intervention serves as a model for reducing racial disparities in treatment and could also be applied to clinical trial enrollment.

To ensure measurable improvement in cancer health equity, it is critical that we vigilantly measure disparities in clinical trial enrollment and address the underlying mechanisms on an individual and health systems level. Automated real-time feedback regarding trial accrual by race, combined with focused efforts by physician champions and clinical navigators, could substantially improve diversity in enrollment, especially if structural barriers such as restrictive and subjective eligibility criteria can be reduced or eliminated. Critical consideration of which eligibility criteria are necessary on the basis of the specific treatment regimens under investigation is paramount to minimize disproportionate exclusion of minority populations.

Finally, instead of excluding patients on the basis of comorbidities such as malnutrition or diabetes, these medical issues could be addressed in combination with experimental therapy within the context of a clinical trial. For example, patients with pancreatic cancer and poorly controlled diabetes or malnutrition could be randomly assigned to the primary therapeutic intervention, while also receiving coordinated care within the clinical trial to address blood glucose control or nutrition. This type of patient-centric trial design could not only increase eligibility but also improve patient adherence to study protocols, reduce therapeutic toxicity, and enhance eligibility for future treatments. Ultimately, with an inclusive and intentional approach, we can more effectively study whether novel therapies will benefit the diverse population of patients with cancer in need of our care.

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