March 31, 2022
Inclusion in clinical trials for gender, racial, and ethnic minorities is an oncology-wide effort in the United States. Recent clinical studies and government reports show that inclusion of these minorities in clinical trials is improving in some areas, but still lacking in others. “There are many barriers that exist in clinical trial participation, including access to trials themselves, access to medical practices that have trials, language barriers and need for translation, health literacy barriers, support for completing trial procedures (transportation or center), and historic distrust in practice, Rana McKay, MD, told Targeted Oncology™, in an interview. Multiple experts believe that trials led by initiatives and funded by government and cancer centers of excellence offer the best chance for oncology to improve on inclusion of gender and racial/ethnic minorities in clinical research and improve on disparities in cancer care overall. The Issue With Diversity in Clinical Trials Race/Ethnicity According to McKay, the effort to improve the inclusion of minorities in clinical research must be a systemic one. “We need systematic changes to achieve equality in clinical trials at the level of cancer centers and industry sponsors and support infrastructure to bring trials to patients as opposed to patients coming to trials,” said McKay. A 2019 quantitative survey study collected responses from cancer centers whose accrual patterns matched with The National Minority Quality Forum and Sustainable Healthy Communities Diverse Cancer Communities Working Group developed criteria. Under these criteria, racial and ethnic minorities must represent 10% or more of the patients. The investigators were able to identify 8 cancer centers who met their criteria:1 Academic Centers of Excellence
Community Centers of Excellence
These US centers of excellence reported an increase over time of the inclusion of racial and ethnic minorities in cancer research and the engagement of health care professionals in the community as partners. Further, the cancer centers reported having established processes for obtaining ethnically diverse patients’ and/or caregivers’ input on research projects, as well as engagement of community groups to drive the participation of racial and ethnic minorities. Some of the cancer centers were more successful than others, for example, 7 centers reported increases in research funds allocated to understanding, addressing, and improving health disparities, and an increased amount of research allocated for racial and ethnicity minority group engagement. At 5 of the cancer centers, community-based participatory research strategies were reported as having been used as a measure of progress to engage racial and ethnic minorities. These survey findings led to action at the government level. The FDA’s Oncology Center of Excellence (OCE) launched Project Equity which addresses not only racial and ethnic disparities, but gender disparities and issues in other minority groups. “The FDA issued a guidance in November 2020 with recommendations on enhancing diversity in clinical trials. They provide recommendations on tangible measures that trial sponsors can implement to address barriers to more diverse patient enrollment,” Lola Fashoyin-Aje, MD, MPH, deputy director, Oncology, US Food and Drug Administration, told Targeted Oncology. Gender/Sex According to a study conducted Ethan B. Ludmir, MD, et al, gender minorities, including patients with cancer who identify as lesbian, gay, bisexual, transgender and queer/questioning, are becoming increasingly important to subpopulations to evaluate in clinical research.2
The investigators reviewed 764 trials including a total of 462,449 patients and found that sexual and gender minority status was unreported in all studies. It was also discovered that the language in published research findings often does not mention these groups, and because of this, the investigators called the oncology community to action to carry out initiatives that will lead to an understanding of gender/sex minority groups. In terms of female inclusion in clinical research, the most recent SEER data show low inclusion of women. In particular, of the 1,012 clinical trials analyzed in a study, females represented only 35% of those in melanoma studies, 39% of those in lung cancer studies, and 40% of those in pancreatic cancer studies.3 With Project Equity, the overarching goal is to improve access to clinical trials of oncology drugs and devices for populations that have historically been underrepresented in clinical research, like as racial and ethnic minorities, individuals who live in rural areas, sexual and gender minorities, and individuals with economic, linguistic, or cultural barriers to healthcare services, according to Fashoyin-Aje. “In oncology at the FDA, we are asking sponsors to develop and submit their plans for enrolling diverse populations in their clinical trials and to implement these measures as early as possible, including in pharmacokinetics and pharmacodynamics studies. We are evaluating eligibility criteria and encouraging sponsors to streamline them, as informed by the science and not by cutting and pasting from 1 trial to the next. The OCE has issued several guidances regarding eligibility criteria,” Fashoyin-Aje stated. “One area that is receiving more attention is implementing measures that mitigate some of the burdens of participating in a clinical trial, including ways to reduce participant travel to trial sites, aspects of clinical trial decentralization.” The FDA is one of many government bodies that are leading the way on bridging the inclusion gaps in oncology clinical research.
Government Funded Clinical Trials Members of the National Cancer Institute (NCI) National Cancer Advisory Board (NCAB) met in February 2022 for their 16th Virtual Meeting. Along with multiple other initiatives, a big-ticket item on the agenda was the Triennial Gender & Minority in Clinical Trials Inclusion Report.4 The overall number of patients worldwide included in National Institute of Health (NIH)-funded clinical trials between fiscal years (FY) 2019 and 2021 was over 10.4 million. In the US alone, more than 8.9 million patients were enrolled in NIH-funded clinical trials. Excluding female-only and male-only studies, 50.1% of patients in FY19 were male, 47.8% were female, and 2.1% were genders unknown or unreported. In the following 2 years, trends changed: In FY20, 46.6% of patients were male, females represented the majority at 48.4%, and the unknown/unreported rate was 5.0%, followed by rates of 44.1%, 49.8%, and 6.1%, respectively, in FY21. With a focus on all clinical research studies, racial and ethnic minorities represented 28.7% of patients enrolled in clinical trials in FY19, 28.0% in FY20, and 27.9% in FY21. By race/ethnicity in FY19, the clinical trial patient population was 79.8% White, 12.7% Hispanic/Latino, 10.3% Asian, and 7.9% Black. More than 9% of races and ethnicities were unknown or unreported in FY19. Further, patients identifying as American Native/Alaska Native and Native Hawaiian/Pacific Islander represented less than 1% of patients enrolled in clinical trials. In FY20, the patients enrolled in clinical trials were 65.8% White, 9.0% Hispanic/Latino 9.7% Asian, and 7.8% Black, with other groups, once again, making up less than 1% of patients. The percentage of unknown or unreported races and ethnicities in FY20 was 14.3%. Finally, in FY21, patients enrolled in clinical trials were 64.7% White, 9.7% Asian, 8.4% Hispanic/Latino, and 8.3% Black, with a limited number of patients identifying as either American Native/Alaska Native or Native Hawaiian/Pacific Islander. The results for FY19 through FY20 were presented by Meg Mooney, MD, MS, associate director of the Cancer Therapy Evaluation Program and chief of the Clinical Investigations Branch at the NCI, who opened with explaining the history behind the report. “The NIH is mandated by the Public Health Service Act to include women and minority groups in all NIH funded clinical research on the primary goal with this law, which was instituted back in the 1970s is to ensure that research findings can be made generalizable to the entire patient population. The NIH Revitalization Act, which was amended by the 21st Century Cures Act also requires the advisory board of each NIH institute to prepare a triennial report describing the manner in which the institute has complied with NIH guidelines and track and report requirements for inclusion reporting,” Mooney stated during her presentation. Following Mooney’s presentation, several meeting participants raised concern about the rate of unknown/unreported minorities enrolled in clinical trials. “For me, it's always good to see therapeutic versus non-therapeutic. I think that's where we start to see these huge differences and some disparities. That's where they jump out,” said John D. Carpten, professor and chair of translational genomics, director of the Institute of Translational Genomics, and Royce and Mary Trotter Chair in Cancer Research at the Keck School of Medicine of the University of Southern California, associate director of basic sciences at the USC Norris Comprehensive Cancer Center, and chair of the NCAB, during the NCAB meeting. “And without seeing it, you can get a false impression of sorts, that there are no disparities in minority participation in trials.” Other experts in the field stated that the data would be more informative if it showed the number of patients who completed clinical trials rather just the number of enrolled patients. Another important point about the Triennial Gender & Minority in Clinical Trials Inclusion Report is that many of the clinical trials in oncology are not NIH-funded and studies funded by pharmaceutical companies in particular have considerable disparities in terms of minority inclusion while cancer center-run clinical trials appear to be more diverse. “These numbers are higher than what we see in clinical practice. Almost 80% of the patients on clinical trials, if you look at the recently published phase 3 trials are Caucasian. So, the numbers for women and minorities are even lower in industry-sponsored research. So, I think in terms of gender, we are making progress. And we are on the right track in terms of racial and ethnic minorities,” said Muhammad Umair Mushtaq, MD, assistant professor of medicine, Division of Hematologic Malignancies & Cellular Therapeutics , University of Kansas Medical Center, in an interview with Targeted Oncology. Mushtaq and colleagues have been instrumental in investigating how funds are allocated for clinical research and identified that minorities may be less likely to receive grants. Disparities Among Clinical Trial Investigators With a focus on gender inequality in NIH funding for hematologic malignancies and cellular therapies, Mushtaq et al collected data from the NIH Research Portfolio Online Reporting Tools. Data from 2018 to 2019 was the focus, during which time 1834 grants totaling $799 million were awarded to 975 principal investigators.5 The study found that female principal investigators were less likely to receive grants than their male counter parts. Specifically, 71% of the principal investigators awarded grants were male compared with 29% of females (P < .001). “We did not have data about the proportion of applicants. So it may be that there were less female applicants. But when we looked into more factors, males were also likely to have [an increased] number of publications, and more years of active research,” explained Mushtaq. “In recent years, the trend is changing. But we still need to prioritize women for clinical trials or research grants from the NIH.” Even with diverse government funding for principal investigators better inclusion of minorities in clinical research, many experts believe that more is needed to truly have equity in oncology. Building an Equitable Environment for Oncology Research Mushtaq said “I think it’s about more than just funding. So, there are these structural issues. It's access to care, and the communities with lower socioeconomic status, they are less likely to seek care at a tertiary care center where most of the clinical research is being conducted. One way to fix this problem may be to incentivize minority enrollment into clinical trials or having some sort of funding for the social part of the trial. For example, we can fund the drug part of the trial or the clinical investigation reporting part of the trial. If we could include some funding that could be used to help disadvantaged patients, that may improve the situation.” Improving minority inclusion in clinical trials may also involve setting an oncology-wide standard, according to McKay. “We absolutely need to set metrics and standards that pharmaceutical companies need to align to,” McKay stated. Other oncology experts at the government level believe that to make cancer research more inclusive, there is a need to have a more diverse clinical investigator population, design clinical trials that are reflective of the US patient population and explore solutions beyond clinical trial enrollment.6 REFERENCES: 1. Regnante JM, Richie NA, Fashoyin-Aje L, et al. US cancer centers of excellence strategies for increased inclusion of racial and ethnic minorities in clinical trials. J Oncol Pract. 2019;15(4):e289-e299. doi: 10.1200/JOP.18.00638. 2. Ludmir EB, Espinoza AF, Jethanandani A, et al. Reporting and exclusion of sexual and gender minorities in cancer clinical trials. Int J Cancer. 2020;15;146(8):2360-2361. doi: 10.1002/ijc.32700. 3. Duma N, Aguilera JV, Paludo J, et al. Representation of minorities and women in oncology clinical trials: review of the past 14 years. J Oncol Pract. 2018;14(1):e1-e10. doi: 10.1200/JOP.2017.025288. 4. National Cancer Institute Triennial Report: Monitoring Adherence to the NIH Policy on the Inclusion of Women and Minorities in Clinical Research as Reported in FY2019 – FY2021. Presented at National Cancer Advisory Board 16th Virtual Meeting; February 10, 2022.. 5. Siddiqui RS, Chaudhary SG, Shahzad M, et al. Gender disparities in the National Institutes of Health funding for hematologic malignancies and cellular therapies. Leuk Lymphoma. 2022; 10;1-6. doi: 10.1080/10428194.2022.2038378. 6. Carpten JD, Fashoyin-Aje, Garraway LA, et al. Making cancer research more inclusive. Nat Rev Cancer. 2021;21(10):613-618. doi: 10.1038/s41568-021-00369-7