PHILADELPHIA – A simulated pancreatic cancer clinical trial screening process showed that Black patients were significantly more likely than white patients to be excluded from clinical trials for a wide range of eligibility criteria, according to results presented at the virtual 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held October 6-8, 2021.
Clinical trials determine the safety and efficacy of cancer therapeutics and pave the way to approval by the U.S. Food and Drug Administration. Previous research has proven that racial and ethnic minorities are significantly underrepresented in clinical trials.
Clinical trials that do not include diverse populations may present an incomplete or inaccurate picture of how patients will respond to various medications, explained the study's lead author, Andrea N. Riner, MD, MPH, a research fellow and general surgery resident at the University of Florida in Gainesville. "Inequitable representation of participants leaves gaps in our knowledge, limits opportunities to receive investigational therapeutics, and subsequently perpetuates disparities in survivorship."
In this study, Riner and colleagues at VCU, under the mentorship of Jose G. Trevino, MD, surgeon in chief of VCU Massey Cancer Center, examined the criteria that are typically used to determine whether a patient will qualify for a trial. She explained that many trials use criteria that have been in place for a long time. However, depending on several factors, "these criteria may not be medically justifiable."
Riner and colleagues simulated a screening process for a pancreatic cancer clinical trial, using data from patients with pancreatic ductal adenocarcinoma who sought care at VCU Massey Cancer Center in Richmond, Virginia, from 2010-2019. They compiled common eligibility criteria for phase II and phase III pancreatic cancer trials listed in clinicaltrials.gov, and modeled inclusion and exclusion based on clinical variables determined from billing codes and medical records.
The criteria that had the highest propensity for exclusion of Black patients were related to nutrition and infectious diseases. They included:
- Albumin, a marker of nutrition (14.07 percent of Black patients were excluded, compared with vs. 7.91 percent of white patients)
- HIV (3.136 percent of Black patients were excluded, compared with 0.286 percent of white patients.)
- Hepatitis B (1.742 percent of Black patients were excluded, compared with 0 percent of white patients.)
- Hepatitis C (9.06 percent of Black patients were excluded, compared with 3.43 percent of white patients.)
Several other criteria also disproportionately excluded Black patients, although the results did not reach statistical significance. The only criteria that excluded more white patients than Black patients was a history of prior cancer treatment. Fourteen percent of white patients were excluded based on prior cancer treatment, compared with 9.06 percent of Black patients. This difference reflects more white patients receiving neoadjuvant therapy for their current pancreatic cancer, Riner explained.
When researchers removed certain criteria that they felt were not crucial to patient safety or well-being, the difference in eligibility was minimized, Riner said.
"The results of our study confirmed our suspicion that standard criteria lead to significantly fewer Black patients being eligible for pancreatic cancer clinical trials than white patients," Riner said. "We are creating bias in who may even qualify to participate, and we are sometimes doing so without a truly valid medical reason to exclude someone."
Riner said the study could be used to inform modifications to existing clinical trial enrollment.
"Modifications should be made on a trial-by-trial basis given the range of therapeutics being investigated," Riner said, noting that chemotherapy trials may require different criteria than immunotherapy trials based upon how the drugs work. "These decisions could be made between the sponsor of the trial and an advisory board of medical experts that would be able to decide which criteria are absolutely necessary."
"Alternative eligibility criteria can improve the diversity of participants, provide more equitable access to investigational therapeutics, and reduce disparities in survivorship, without compromising patient safety or study results," Riner added.
One limitation of the study is that it was based on data from a single cancer center, so the results may not be generalizable to the broader public. Also, based on the demographics of the patients in the study, researchers were only able to compare eligibility between patients who identified as Black or white. Riner said the team suspects their findings may be applicable to other minority groups, but further research would be necessary to confirm the results.
Members of the research team received salary and research support from the National Human Genome Research Institute (Riner), the National Cancer Institute (Riner, Trevino, and VCU Massey Cancer Center Informatics Core), and the Joseph and Ann Matella Fund for Pancreatic Cancer Research (Trevino). Riner declares no conflicts of interest.
Abstract
Title: Eligibility criteria perpetuate disparities in enrollment and participation in pancreatic cancer clinical trials
Introduction: Clinical trials determine efficacy and safety of cancer therapeutics and set the standard of care. Inequitable representation of participants leaves gaps in our knowledge, limits opportunities to investigational therapeutics and subsequently perpetuates disparities in survivorship. Clinical trial eligibility criteria have been postulated to differentially impact certain racial/ethnic groups which have higher prevalence of infectious and chronic diseases. We aimed to determine the impact of eligibility criteria on disparities in pancreatic cancer clinical trial candidacy.
Methods: Common eligibility criteria for Phase 2 and 3 pancreatic cancer trials listed in clinicaltrials.gov were compiled for simulation of a clinical trial screening process. Patients with pancreatic ductal adenocarcinoma who sought care at VCU Massey Cancer Center (Richmond, VA) from 2010-2019 were included. Clinical variables pertaining to eligibility criteria were obtained from billing codes and discrete values in the medical record. Inclusion/exclusion criteria were applied to determine overall eligibility and for individual criterion. Chi-squared tests were utilized to identify statistically significant differences in patient eligibility between racial groups.
Results: A total of 676 patients with pancreatic cancer were identified, with Black (42%) and White (52%) patients comprising the majority of the patient population. Black patients were significantly more likely than White patients to be deemed ineligible based on Creatinine (6.08% vs 2.27%, p = 0.036), HIV (3.136% vs 0.286%, p = 0.01), Hepatitis B (1.742% vs 0%, p = 0.043), and Hepatitis C (9.06 vs 3.43%, p = 0.005). Black patients were also more likely to be ineligible based on Albumin (12.45% vs 7.47%, p = 0.076), history of coronary stenting in the past 6 months (1.39% vs 0%, p = 0.087), and uncontrolled diabetes (8.96% vs 6.07%, p = 0.244), although differences in these criteria did not achieve statistical significance at 5% level. History of prior cancer treatment was the only variable that excluded less Black patients than White patients (9.06% vs 14.0%, p = 0.072) and was attributable to more White patients initiating neoadjuvant chemotherapy for their pancreatic cancer prior to seeking care at VCU. After applying all criteria, Black patients were more likely to be ineligible for participation compared to White patients (42.0% vs 33.3%, p = 0.039).
Conclusion: Standard pancreatic cancer clinical trial eligibility criteria differentially exclude Black patients from participating in clinical trials. These criteria perpetuate racial disparities, limit generalizability to real world clinical scenarios, and are often not medically justifiable. Alternative eligibility criteria can improve representation of diverse participants, provide more equitable access to investigational therapeutics and reduce disparities in survivorship, without compromising patient safety or study results.
