Pierce Looks to the Future of Trial Diversity, Reflecting on Current and Historical Barriers

Lori J. Pierce, MD, FASTRO, FASCO, started her session with “the obvious.”

The chair of the American Society of Clinical Oncology (ASCO) Board of Directors said, “We know the participation of adult cancer patients on clinical trials in this country is woefully low. “We also know the rate of participation of patients [of racial and ethnic minorities] is even lower than that.

“No matter which trials you look at, the message is the same.”

Pierce, who is professor of radiation oncology at the University of Michigan, painted this stark picture to open her presentation, “Overview of Barriers to Ensuring Racial and Ethnic Diversity in Clinical Trials”¹ at the 2022 ASCO Annual Meeting in a session that focused on strategies to advance equity in cancer clinical trials. She is also co-lead of the ASCO/Association of Community Cancer Centers (ACCC) clinical trials initiative, whose research statement, recently published in the Journal of Clinical Oncology, contains 6 overarching recommendations designed to guide investigators “to improve participation rates among people from racial and ethnic minority populations historically underrepresented in cancer clinical trials.”²

Citing 3 important papers, Pierce highlighted their findings on disparities:
Using 2013 Surveillance, Epidemiology, and End Results data on cancer therapy trials, a 2018 paper showed that although Black and Hispanic patients accounted for 10% and 7%, respectively, of cancer cases that year, only 6% and 2.6% of patients were enrolled in clinical trials listed on the ClinicalTrials.gov website.³

In trials that took place between 2008 and 2018 that led to FDA oncology drug approvals, according to a 2019 paper, upward of 80% of enrollees were White compared with between 10% and 35% Asian and 0% and 10% Black and Hispanic patients.⁴

For precision oncology studies, a paper from 2021 showed that the ratio of observed:expected trial enrollees remained high for Asian and non-Hispanic White patients but low for American Indian/Alaska Native, Black, and Hispanic patients.⁵

“Noting the obvious,” she emphasized, “we have a very, very low number of minorities going on clinical trials.”

Pierce echoed the themes put forth by the ASCO/ACCC clinical trial guidance just released²— communication, education, and understanding of intrinsic and extrinsic factors affecting clinical trial participation—by noting 5 fundamental barriers that affect diversity in trials and delving deeper into each one: clinician, trial, patient, institutional, and financial barriers.

Clinician Barriers
Pierce explained that there are several clinician-related barriers to ensuring racial and ethnic diversity in clinical trials. These include the following:
Physicians do not discuss trial enrollment with their patients; thus, patients do not know they could be a trial candidate or do not understand clinical trials.

Physicians may be biased; for example, not taking the time to discuss a trial with patients of certain ethnicities because of the assumption these patients won’t enroll anyway.

Physicians have limited time and resources; a lack of teams to drum up clinical trial enrollment makes it extremely difficult to communicate about trials with patients.

Physicians may lack knowledge on the trials available to their patients.
Physicians’ institutions do not have diverse workforces.

In particular, communication and encouragement are of utmost importance, Pierce continued. Citing a 2021 meta-analysis of trials that took place between 2000 and 2020, which focused on patient agreement to participate in cancer clinical trials, she noted that race and ethnicity do not affect trial participation.⁶

“If you look at the patients who go on a trial, if you ask them to go on a study, it makes no difference what race or ethnicity they are. They will go on at the same percentage,” Pierce stated about the results. “The thought that certain populations don’t go on a trial could not be further from the truth. If you ask patients to go on a trial, they will go on a trial at similar rates. That is a key principle.”

Having the workforce better mirror the patient population is also important, “although I don’t believe that every patient of color has to have a provider of color,” Pierce underscored. “But there is no reason that, as a workforce, we should not mirror the population that we care for in diversity of thought and diversity of efforts. We need to mirror that population.”

For example, she said, although Black individuals represent 13.4% of the US population, they account for just 6.2% of recent medical school graduates, 3.9% of oncology fellows, and 3% of oncologists, according to a 2021 paper. In addition, just 4.7% of oncologists are Hispanic or Latino and 0.1% are American Indian or Alaska Native.⁷

Trial Barriers
First and foremost among trial-related barriers is their narrow trial eligibility, which Pierce cited as clearly limiting to patients of color. In particular, these patients frequently have comorbidities that preclude their participation in trials.

To open up trial eligibility, ASCO and Friends of Cancer Research published a joint recommendation statement in 2021 that focused on revisions to criteria for washout periods, concomitant medications, prior therapies, laboratory ranges, and performance status.⁸ Unless a scientific basis exists for excluding a patient from a trial, such as potential toxicities from drug-drug interactions, “we need to go from the principle that we need to find the perfect patient to go on a clinical trial to reality, where we broaden the criteria and more patients, especially patients of color, can go in a study,” Pierce said.

The COVID-19 pandemic has had a particular influence on trial eligibility by teaching oncologists several lessons about expanding eligibility. Trials need to be more easily integrated into routine clinical care, treatment should be allowed to be administered remotely, and technology must be leveraged for access and efficiency improvements, as noted in a 2020 Journal of Clinical Oncology paper.⁹ Trials need to not be so boutiquey, Pierce said. “We need to go where the patients are.”

The adverse impact of trial location also should be considered. How do we provide maximal access to clinical trials, she posed, when location can be a barrier whether the trial is taking place at an academic center or a community practice or through telemedicine. Patients living in rural locations may have difficulty traveling to a trial site, so patient location must also be considered.

Patient Barriers
Among the patient barriers preventing racial and ethnic diversity in clinical trials, Pierce again listed 5, paying particular attention to the last 2:

• Lack of information regarding trials
• No trial available at patient’s care site
• Available trials do not match patient disease type and stage
• Social determinants of health (SDOH)
• Distrust

Not only do SDOH adversely affect patient care and access to care and clinical trials, she pointed out, but these are intertwined with patient distrust in the medical system. Economic stability (eg, expenses, debt, medical bills), neighborhood and physical environment (eg, housing, safety, walkability), and community and social context (eg, support systems, discrimination, stress)—among others—all affect the patient’s trust level.

To illustrate this point, Pierce cited a study jointly conducted by the Kaiser Family Foundation and The Undefeated (now Andscape), which asked respondents, “Can you trust these institutions to do what is right for you or your community all or almost all of the time?” Regarding trust in doctors, local hospitals and schools, the health care system, the police, and the courts, Black individuals overwhelmingly had the least amount of trust and White individuals had the most; Hispanic individuals fell in the middle. For example, 59% of Black respondents trusted their doctors vs 78% of White and 72% of Hispanic respondents, and 56% vs 70% and 62%, respectively, trusted their local hospitals.¹⁰

“We know that we need to do more,” Pierce said. “I think that more is having open communication with our patients and having open communication with the community, so even when a person doesn’t have cancer, there’s a comfort level with that institution so that when they do have cancer, they feel more comfortable coming in.”

Institutional and Financial Barriers
Here Pierce concentrated on finances and gaps in coverage as areas to focus on. As SDOH are intertwined with patient distrust, so are patient financial barriers ensnared by insurance coverage decisions. Nowhere is this more apparent than when comparing routine cost coverage decisions between patients with private insurance or Medicare and those using Medicaid, as well as when patients incur nonmedical costs.

“We [have known] that for many, many years, patients who are on clinical trials…incur costs when they see their doctor, when they get laboratory studies, when they get x-rays—[all] routine costs within a clinical trial,” Pierce stated.

However, whereas these costs are typically covered by Medicare and private insurers, they are not covered by Medicaid. It was because of this noteworthy gap in payer coverage decisions that ASCO was the driving force behind the Clinical Treatment Act, which guarantees that patients with Medicaid coverage will have qualifying clinical trial–related routine care costs covered. This is regardless of whether the trial is a cancer trial or focused on other life-threatening injuries.¹¹

Beyond medical costs, too, are those that are nonmedical, such as food, lodging, dependent care, transportation—and now gas. Patients, and their families, are responsible for all of these. And although trial sponsors may often be willing to assist, ethical and compliance concerns can complicate that process, Pierce noted. Thus, ASCO is putting its might behind the Diverse Trials Act,¹² which is aiming to clarify “what sponsors can ethically cover.” The ultimate goal, she emphasized, is to even the playing field in terms of cost of going on a clinical trial.

“To increase the enrollment of racial and ethnic minorities in clinical trials,” Pierce concluded, “interventions must address the multiple barriers from different perspectives.”

References
1. Pierce L. Overview of barriers to ensuring racial and ethnic diversity in clinical trials. Presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Accessed June 5, 2022. https://meetings.asco.org/2022-asco-annual-meeting/14319?presentation=203990#203990
2. Oyer RA, Hurley P, Boehmer L, et al. Increasing racial and ethnic diversity in cancer clinical trials: an American Society of Clinical Oncology and Association of Community Cancer Centers joint research statement. J Clin Oncol. Published online May 19, 2022. doi:10.1200/JCO.22.00754
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. Loree JN, Anand S, Dasari A, et al. Disparity of race reporting and representation in clinical trials leading to cancer drug approvals from 2008 to 2018. JAMA Oncol. 2019;5(10):e191870. doi:10.1001/jamaoncol.2019.1870
5. Aldrighetti CM, Niemierko A, Allen EV, Willers H, Kamran SC. Racial and ethnic disparities among participants in precision oncology clinical studies. JAMA Netw Open. 2021;4(11):e2133205. doi:10.1001/jamanetworkopen.2021.33205
6. Unger JM, Hershman DL, Till C, et al. “When offered to participate”: a systematic review and meta-analysis of patient agreement to participate in cancer clinical trials. J Natl Cancer Inst. 2021;113(3):244-257. doi:10.1093/jnci/djaa155
7. 2021 snapshot: state of the oncology workforce in America. JCO Oncol Pract. 2021;17(5):249. doi:10.1200/OP.21.00166
8. Kim ES, Uldrick TS, Schenkel C, et al. Continuing to broaden eligibility criteria to make clinical trials more representative and inclusive: ASCO-Friends of Cancer Research joint research statement. Clin Cancer Res. 2021;27(9):2394-2399. doi:10.1158/1078-0432.CCR-20-3852
9. Pennell NA, Dillmon M, Levit LA, et al. American Society of Clinical Oncology road to recovery report: learning from the COVID-19 experience to improve clinical research and cancer care. J Clin Oncol. 2021;39(2):155-169. doi:10.1200/JCO.20.02953
10. Hamel L, Lopes L, Muñana C, Artiga S, Brodie M. KFF/The Undefeated survey on race and health. Kaiser Family Foundation. October 13, 2020. Accessed June 5, 2022. https://www.kff.org/report-section/kff-the-undefeated-survey-on-race-and-health-main-findings/
11. Clinical Treatment Act, HR 913, 116th Cong (2019). Accessed June 5, 2022. https://www.congress.gov/bill/116th-congress/house-bill/913
12. Diverse Trials Act, S 2706, 117th Cong (2021). Accessed June 5, 2022. https://www.congress.gov/bill/117th-congress/senate-bill/2706