Traditional eligibility criteria for pancreatic cancer clinical trials reinforce underrepresentation of racial and ethnic minorities in clinical trial candidacy and skew standards of care in favor of non-Hispanic White participants.
Traditional eligibility criteria for pancreatic cancer clinical trials reinforce underrepresentation of racial and ethnic minorities in clinical trial candidacy and skew standards of care in favor of non-Hispanic White participants, according to findings from a study published in the Journal of Clinical Oncology.
This study focused on the previously under-investigated effects of eligibility criteria for clinical trials investigating pancreatic ductal adenocarcinoma (PDAC). When using traditional criteria obtained from ClinicalTrials.gov, Black patients, who made up 42.5% of the studied population, were less likely to be eligible for participation compared with White patients, who made up 51.6% of the population (42.4% vs 33.2; P = .023).
Racial inequalities are clear in the cancer clinical trial space, where minority participation has been historically low when compared with that of White patients. Knowledge of molecular profile differences across racial and ethnic populations that may affect treatment guidelines is limited by a lack of diversity in clinical trial participants, potentially affecting disease survivorship. The study authors aimed to investigate the potential effects of less restrictive criteria on racial/ethnic minority eligibility in pancreatic cancer clinical trials.
The study retrospectively identified 676 patients at least 18 years of age who were diagnosed with PDAC and received care at Virginia Commonwealth University (VCU) between January 1, 2010, and December 31, 2019. Of these patients, 287 were Black and 349 were White (n = 636). The percentages of all other racial or ethnic groups were relatively small (n = 40) and were excluded from further analysis.
To gain authentic eligibility criteria, the study authors searched ClinicalTrials.gov for US phase 2 and 3 clinical trials that enrolled patients with pancreatic adenocarcinoma from January 1, 2010, through November 20, 2017, and obtained common inclusion and exclusion criteria across these trials.
A simulated patient screening process based on traditional eligibility information was then conducted for the VCU patients. When these trial eligibility criteria were applied, Black patients were less likely to be eligible for treatment because of hypoalbuminemia (odds ratio [OR], 1.90; 95% CI, 1.12-3.25), which was the condition that led to the highest number of ineligible Black patients.
Black patients were also less likely to be eligible for participation based on HIV (OR, 11.30; 95% CI, 1.42-89.7), and hepatitis C (OR, 2.81; 95% CI, 1.39-5.67) infections. Regarding prior hepatitis B infection, 1.7% of Black patients were disqualified compared with 0% of White patients (P = .043).
Similarly, 1.4% of Black patients and 0% of White patients were excluded based on coronary stenting within the past 6 months (P = .087).
Trial ineligibility was equal among Black and White patients because of renal dysfunction (OR, 1.95; 95% CI, 0.87-4.38) and uncontrolled diabetes mellitus (OR, 1.48; 95% CI, 0.80-2.74).
Regarding previous cancer rates, percentages were similar between Black (2.4%) and White (2.6%) patients. However, prior cancer treatment levels were disparate across the 2 groups, with 14.0% of White patients being excluded based on these criteria compared with 9.1% of Black patients (P = .072).
Revised eligibility criteria for this simulated patient population were created based on American Society of Clinical Oncology (ASCO) and Friends of Cancer Research guidelines that were published in 2017, as well as FDA guidelines that were released in 2020. Physician members of the study team contributed clinical judgement to further adapt these revised criteria.
These revisions included removing manageable medical conditions such as HIV, hepatitis C, hepatitis B, diabetes mellitus, previous cancer, and coronary stenting from exclusion lists. After applying the revised criteria to the study population, there was no difference in eligibility rates between Black and White patients (26.8% vs 24.8%; P = .581).
These results indicate that traditional eligibility criteria for PDAC clinical trials disproportionately exclude patients based on medical conditions. Restrictive criteria create study results that are only applicable to the healthiest patients and therefore not generalizable across various populations.
Additionally, many of the medical conditions that exclude patients from clinical trials are also associated with race-based health disparities. In particular, HIV, hepatitis, chronic kidney disease, diabetes mellitus, heart disease, and obesity are disproportionately prevalent in Black and Hispanic populations. This study found that patients from minority backgrounds, who are more likely to have comorbidities, are less likely to have opportunities to participate in clinical trials. Revised criteria provide the potential to increase equity in trial eligibility, thus allowing for more generalizable results and reducing disparities in treatment access.
The investigators also considered the medical justification of each exclusion criterion in the context of treatment possibilities. Many newer FDA-approved PDAC therapies are administered to patients with comorbidities, despite the exclusion of patients with those conditions from clinical trials. The study authors propose that, with proper disease status consideration and comorbidity management, patients with medical conditions such as hypoalbuminemia, diabetes mellitus, HIV, hepatitis, and some cardiovascular diseases should have the opportunity to participate in clinical trials, as trial exclusion based on comorbidities will continue to uphold racial inequity in clinical trial populations.
This study also considered differences in demographics, insurance provider, and disease stage between Black and White patients. Overall, Black patients tend to be diagnosed with PDAC at a more advanced stage and younger age than White patients. Black patients are also less likely to have Medicare coverage and more likely to have Medicaid coverage or no insurance. As Medicaid coverage of testing and treatment in clinical trials can vary, patients covered by Medicaid may face financial barriers to participation, even if they are medically eligible.
The results of this study are likely translatable to clinical trials studying various types of cancer, as they reflect common ineligibility factors that are not specific to PDAC, the authors noted. However, if used, the proposed revised criteria will need to consider the unique risks and toxicities associated with individual novel therapies.
Additionally, the study authors acknowledged the need for further analysis of clinical trial eligibility in Hispanic/Latinx patients and other minority racial groups. The authors also recognized the need for investigating a more comprehensive list of eligibility criteria.
Going forward, the authors concluded that regulatory authorities and stakeholders, in collaboration with medical specialists, should consider and challenge the medical necessity of each exclusion criterion in clinical trials to assess benefits, risks, and potential comanagement throughout the trial. In addition, funders of clinical trials should require and approve of justification for eligibility criteria before providing their support. The study authors also highlighted the responsibilities of patient advocacy groups and professional societies to instigate policy change that increases eligibility of underserved populations and creates trials that are more reflective of the real-world patients they seek to benefit.