Health Equity Barriers in Oncology Trials

Health equity in clinical trials is becoming more and more understood across our industry. We have all read the sobering statistics about diversity and access, including the fact that less than 5% of adults in the United States have participated in a clinical trial; and of those, 75% are white.¹ We also know what these numbers tell us: there is a lack of access to effective medical interventions for the very patients they are most intended to treat—compounding health disparities in underrepresented and excluded populations, having a limited understanding of the effects of the therapies we develop in the full population, and hindering innovation at a high societal and economic cost.²

Arturo Loaiza-Bonilla, Co-Founder and Chief Medical Officer, Massive Bio

Among the organizations that have long recognized this issue is FDA, which has called for greater inclusiveness in clinical trials for nearly 35 years. In June 2022, the U.S. House of Representatives followed FDA’s example, passing legislation intended to increase the racial and ethnic diversity of patients enrolled in clinical trials of new drugs. The proposed law would require trial sponsors to develop and submit diversity action plans for achieving demographic equity in Phase III studies of novel therapies. This is a welcome development, as adherence to FDA guidance has been mixed at best, and there have been no negative consequences or retribution from FDA, including from its oncology review divisions for lack of adherence.

Indeed, oncology research faces steeper than average hurdles in terms of health equity—from underrepresentation to outright mistrust. It will take nothing less than global understanding and cooperation, as well as modern innovations, to overcome them.

Cancer clinical trials suffer from inequity

Although understanding of health inequity is growing, the global life sciences industry still has much to learn to bridge the diversity divide in cancer clinical trial participation.

The statistics are bleak. Black Americans are underrepresented in 85% of clinical trials,³ despite the fact that the risk of death from many types of cancer is higher than for white Americans.⁴ While 15% of cancer patients in the U.S. are Black, they only make up 4–6% of participants in investigational oncology trials.⁵ Patients identifying as Hispanic or Latino are underrepresented by similar ratios. Since only one third of cancer trials report race and ethnicity data, the real numbers may be even lower.

In a Health Affairs study last year, researchers collected data on the number of Black patients in 225 trials, one third of which were cancer trials.³ They then compared those figures to the overall population with the diseases being studied and broken down by race. The findings revealed that the representation of Black people in clinical trials was about one third of what it should have been to reflect the makeup of the total patient population.³ This is problematic, as race and ethnicity have been shown to affect a drug’s safety and effectiveness.⁶

When it comes to cancer, earlier screening efforts have led to more diagnoses, yet mortality rates continue to drop—presumably due, in part, to an increase in novel treatments and clinical trials. By boosting representation and equity in cancer trials, we can have an enormous impact on populations who are not yet fully benefiting from these gains.

Roadblocks to equity in oncology research

There are several enormous hurdles standing in the way of health equity in oncology research. While some of these challenges are endemic to clinical trials—regardless of the disease being studied or the patient population—nearly all are more acute among nonwhite populations.

Lack of clinical trial awareness plagues clinical research across the board, where the disconnect between researchers, physicians, and patients results in a lack of awareness around clinical research as a care option. This phenomenon is even more acute among communities of color, which are more affected by low health literacy.⁷ At the same time, education and awareness around trials are proven to increase willingness to participate.

Good work is being done in this area by the likes of Dr. Elena Rios, MD, MSPH, MACP, president and CEO of the National Hispanic Medical Association. Her foundation is building a network of Hispanic and Latino clinicians running clinical trials as well as educating and promoting the research profession among residents.

“Hispanic clinicians tend to attract patients from their own communities,” says Rios. “If more Hispanic clinicians were involved in clinical research, naturally, more of their Hispanic patients would participate in their trials. In the end, it is these physicians who will be instrumental in promoting trial participation in their local communities.”

Rios’s efforts also speak to another significant barrier: system mistrust. In several studies, Black Americans have reported that they believe clinical trial patients were “guinea pigs.”⁸ This is no great surprise considering the egregious past research abuses, including the Tuskegee Syphilis Study in which Black men who had the disease were recruited to participate but never treated. There are also language and cultural barriers to overcome among many racial and ethnic minority populations. As reflected by Rios, efforts to re-establish trust must include clinical staff that reflects the populations they are serving.

Diversifying the researcher pool will also help to combat clinician bias, where clinicians may believe people from racial and ethnic minority populations will be unwilling to enroll or unable to comply with trial protocols—a phenomenon recently cited by the American Society of Clinical Oncology (ASCO) and Association of Community Cancer Centers.5 Further, a study published by the ASCO in June 2022 found that 40% of Black patients with metastatic breast cancer said that their care team did not inform them of clinical trial treatment options, as compared to 33% of white patients.⁹

These factors are further exacerbated by restrictive inclusion/exclusion criteria, which are particularly strict among oncology trials. A 2018 report published by the ACS found that eligibility requirements disqualify 40% of patients with cancer trials available to them from participation, suggesting that there can be an unintended bias.⁸ For example, Black patients are more likely to have comorbidities, such as cardiovascular disease, that may preclude them from enrolling in a clinical trial. While these criteria are intended to protect patient safety, organizations like the U.S. National Cancer Institute have concluded that they are excessively arbitrary and rigid, especially in the face of widespread inequity. Some efforts to harmonize these criteria are underway, but they remain limited in scope, adoption, and generalizability.¹⁰

Financial barriers are another endemic challenge in clinical trial participation that is even more acute among underserved communities. Patients with fewer socioeconomic resources may not be able to afford the travel and lodging costs associated with clinical trial participation, and they may not have adequate childcare or paid time off to cover the time commitment.

These financial challenges are closely related to the geographic hurdle of trial access. Novel oncology research in the U.S. takes place at 71 NCI-designated cancer centers, which tend to be in large urban centers. As a result, only 15% of the 1,700,000 Americans diagnosed with cancer in 2021 were treated at one of these state-of-the-art research centers—with the remaining 85% receiving care at community-based practices.¹¹ The Diversifying Investigations Via Equitable Research Studies for Everyone (DIVERSE) Trials Act (H.R. 5030/S.2706) has the potential to result in more efficient, inclusive, and accessible research that will benefit the health of all patients by allowing trial sponsors to cover ancillary costs of trial participation; however, it is yet to be enacted.¹²

We know we can dramatically improve trial diversity and access if we recruit from the entire community of cancer patients rather than a privileged group that lives near an NCI-designated site.

Bringing the science closer to every patient

Fortunately, it appears that the industry is uniting behind clearing away these roadblocks. Modern innovations—from artificial intelligence (AI) to digital tools and analytics software—can help us accelerate the progress we’ve already begun to make and truly move the needle on health equity.

Decentralized, just-in-time, and hybrid clinical trials are already helping to alleviate the issues of location, cost, and time. These trial models allow patients to participate without having to switch oncologists, and some mostly from home—supplementing site visits with telemedicine, apps, and wearable devices among other digital solutions. The trial models may also offer direct delivery of drugs and other materials to patients. Not only are these trials proving to be more efficient than site-based trials, but they are also more inclusive.

AI and machine learning can help cancer patients, physicians, and researchers take advantage of these access improvements by matching patients to appropriate trials in near real-time, regardless of location. For example, Massive Bio’s SYNERGY-AI uses AI to extract information from patients’ electronic health records and quickly identify cancer trial matches. The platform adds 6,000 patients per month and has onboarded more than 102,000 patients in total since 2020.¹³

What’s more, these technologies can help diversify trial participation and increase trust by identifying both patients and clinicians of color. However, Rios added, to make swifter progress, “[w]e need to track ethnicity for everyone so it’s easier to find diverse patient pools and oncologists. We know where doctors work, but we don’t always know their ethnicity.”

Technology and tenacity

The barriers to greater equity in oncology research are intimidating, and the implications are grave. Not only does underrepresentation do a disservice to clinical research—where studies may need to be scrapped if diversity targets are not met—but it also fails the communities that might benefit most from novel treatments.

If the industry can coalesce behind equity and patient centricity, these barriers are surmountable. Few understand this better than Ramita Tandon, chief clinical trials officer of Walgreens.

“As an industry, we must come together in relentless pursuit of equitable, patient-centered clinical research that gives opportunity and access to all patients, in all communities,” says Tandon in a Walgreens YouTube video.¹⁴ “This goal will require an ecosystem of partners working together to move the needle in terms of access and diversity. By reaching patients in their own communities, through providers they trust, we can move that needle at a rapid pace—transforming the patient experience and ultimately improving human health.”

The technology already exists that can help finally overcome many of the biggest barriers to population representation in cancer clinical trials. That technology, however, must also be paired with sensitive, patient-centric care that engenders trust, eliminates participation barriers, facilitates enrollment, and maintains patient engagement through exhausting periods of symptoms and side effects. We hope to help increase access for patients who are typically underserved. This balance of high tech and high touch will be our perfect formula—a cure for clinical research inequity in oncology and beyond.

References

1. Flores LE, Frontera WR, Andrasik MP, et al. Assessment of the inclusion of racial/ethnic minority, female, and older individuals in vaccine clinical trials. JAMA Network Open. 2021;4:e2037640. See resource here.

2. Goldman, Dana P. et al, “Lack of diversity in clinical trials costs billions of dollars. Incentives can spur innovation,” STAT News (August 3, 2022).

3. Green, A, et al. Despite The FDA’s Five-Year Plan, Black Patients Remain Inadequately Represented In Clinical Trials For Drugs. Health Affairs, 2022 Mar;41(3). See resource here.

4. Rivers, D, et al. A systematic review of the factors influencing African Americans' participation in cancer clinical trials. Contemporary Clinical Trials, 2013 Jul;35(2):13-32. See resource here.

5. Oyer, RA, 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. Journal of Clinical Oncology. 40:2163-2171. See resource here.

6. Ramamoorthy, A, et al. Racial/ethnic differences in drug disposition and response: Review of recently approved drugs. American Society for Clinical Pharmacology & Therapeutics, 2014 December, 97(3). See resource here.

7. Muvuka, B, et al. Health Literacy in African-American Communities: Barriers and Strategies. Health Literacy Research and Practice, 2020 Jul;4(3):e138-e143. See resource here.

8. American Cancer Society, Cancer Action Network, “Barriers to Patient Enrollment in Therapeutic Clinical Trials,” by members of project steering committee including Jeff Allen, PhD, Kendall Bergman, Suanna Bruinooge, MPH, et al (January 2018). See resource here.

9. Walker, S, et al. Increasing Black patient participation in metastatic breast cancer clinical trials: The BECOME (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement) project. American Society of Clinical Oncology. See resource here.

10. News Medical Life Sciences, “New recommendations on how to determine eligibility criteria for lung cancer clinical trials,” reviewed by Emily Henderson, B.Sc. (August 5, 2022). See resource here.

11. National Cancer Institute at the National Institutes of Health, “NCI-Designated Cancer Centers,” (June 24, 2019). See resource here.

12. Congress.gov, “H.R. 5030 Diverse Trials Act,” 117th Congress (August 13, 2021). See resource here.

13. Applied Clinical Trials, “Massive Bio Onboards Over 100,000 Cancer Patients,” by Staff (October 31, 2022). See resource here.

14. Walgreens YouTube Channel, “Building the future of clinical trials with Walgreens,” Dec 7, 2022, https://youtu.be/YMIUyDg18T0.

About the author

Dr. Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical officer of Massive Bio, a company that connects patients to clinical trials using artificial intelligence. Loaiza-Bonilla has a distinguished academic and clinical career in precision medicine oncology, immunotherapy, clinical trial design, digital health, entrepreneurship, and patient advocacy. He is board certified in both medical oncology and hematology and has extensive experience in the diagnosis and treatment of genomic biomarker-driven cancers and serves as enterprise medical director of oncology research at Capital Health.