More Work Is Needed to Bring Clinical Trials to Underserved Patients, ASCO Panel Says

Clinical trials are a crucial aspect of oncology drug development, but when study populations are substantially different from the real-world patient population that a drug is intended to treat, trial findings may not be generalizable to the clinical setting. But including diverse populations—especially those who are historically medically underserved—in clinical trials has thus far been easier said than done, as a panel discussion at the 2023 American Society of Clinical Oncology Annual Meeting highlighted.

The panel included Ana Acuna-Villaorduna, MD, assistant professor of medical equalities at the Icahn School of Medicine at Mount Sinai in New York; Lola Fashoyin-Aje, MD, MPH, associate director of the Oncology Center of Excellence at the FDA; and Steven Gore, MD, program scientist at the Experimental Therapeutics Clinical Trial Network and Cancer Therapy Evaluation Program at the National Cancer Institute (NCI).

Disparities are known, and systemic change is needed

Acuna-Villaorduna opened the presentation by painting a picture of the past and current clinical trial landscape. In 2009, she noted, only 8 drugs were approved for cancer treatment, but the roster of FDA-approved cancer drugs had grown to more than 50 by 2020. And in the past 20 years, the response rates in early-phase clinical trials have more than doubled, she said.

“Unfortunately, there is a mismatch between the patients that participate in clinical trials and the patients that we see in our clinics, and there are 2 factors that are mainly affected by disparities in clinical: generalizability of clinical trial results, and the efficiency of care delivery,” Acuna-Villaorduna said.

In early-phase trials, she explained, the impact of clinical trial disparities is even greater.

"We will be limiting the access to potentially efficacious investigational therapy to patients that do not have other treatment alternatives, and we will be also limiting ourselves in the understanding of drug pharmacodynamics and pharmacokinetics in the population that is excluded.”

Underrepresented groups in clinical trials include racial or ethnic groups, elderly patients, women, patients living in rural areas, those with comorbidities, and more, although most research on disparities in clinical trials has been conducted on phase 3 trials. In early-phase clinical trials, the gaps in trial participation may be even greater, Acuna-Villaorduna said. Race and ethnicity are also underreported in clinical trials, she noted.

Acuna-Villaorduna also described some of the barriers to trial participation, classifying them by levels. Study-level barriers, especially in early-phase trials, can include restrictive inclusion criteria and complex processes that entail multiple study visits. On the institutional level barriers such as insufficient screening and trial matching, a lack of institutional self-assessments, prolonged activation times, and gaps in trials portfolios may keep patients from participating.

There are numerous patient-level barriers, such as unawareness of trial opportunities, distrust, financial limitations, geographic location, or other logistical factors. A lack of social support may also avert patients to committing to trials. And at the provider level, implicit bias, a lack of trial awareness, strained workforces, and the training of researchers may be limiting factors.

At the provider level, interventions to reduce innate bias are crucial, Acuna-Villaorduna said. One such intervention is the “Just Ask” training program for providers. For patients, education that is accessible and feasible is key.

For regulators, equity is about more than morals

“When we discuss clinical trial diversity in the context of clinical trials or clinical studies of FDA-regulated medical products, we're really discussing the broad range of characteristics of a study population that will enable us to be able to infer study outcomes to a broader population that will use those medical products,” Fashoyin-Aje said. “So we are keenly interested in ensuring that the trial population enrolled in these clinical trials and clinical studies is representative of the population with the disease or condition that they are intended to treat.”

While there have been positive trends in drug development in recent years, such as expedited timelines that bring drugs to patients quickly, there are also opportunities to improve evidence quality. “There may not be tension between these considerations if there is prospective planning to take these into account,” Fashoyin-Aje said.

Over time, for example, FDA has seen lower proportions of US patients in pivotal trials, with most approvals based on international trials. Additionally, trials are typically conducted in large academic centers, which is often appropriate due to the resources they provide. However, this limits the reach of studies and can serve as a barrier to those who live far from large academic centers and do not have the means to travel.

The FDA has provided several guidances over the years to encourage diverse trial populations, including patients with comorbidities that are often excluded, such as brain metastases, HIV infection, or organ dysfunction, Fashoyin-Aje said.

She highlighted the Oncology Center of Excellence’s Project Equity public health initiative, which aims improve clinical trial participation rates by focusing on historically underrepresented populations.

“The overarching focus here is to improve outreach, engagement, and collaboration of multiple stakeholders—including patients, community, patient advocacy groups, societies, like the American Society of Clinical Oncology and the American Association of Cancer Research—to ensure that the initiatives that are underway across these multiple stakeholders incorporate the regulatory perspective in the solutions that are being recommended, but also so that we at the Oncology Center of Excellence have an opportunity to learn about broader issues to consider that may impact the kinds of data that we are receiving and the FDA,” Fashoyin-Aje said.

Fashoyin-Aje also highlighted an FDA guidance on diversity planning to ensure enrollment of participants from underrepresented racial and ethnic populations in trials. Since the Consolidated Appropriations Act of 2023 was signed into law, sponsors are required to submit diversity action plans to the FDA based on the guidance when conducting phase 3 or other pivotal trials.

“The FDA has provided a regulatory framework for prospective planning to ensure clinical trial participant diversity, and many sponsors have themselves also adopted similar frameworks within their respective institutions,” she said. “But I want to emphasize that these are very complex issues. Health care inequities are sort of present and this trickles down to clinical research as well.”

Only system-wide improvement will drive sustainable change, she said, and consistent work is needed to stay on track.

Strategies to overcome barriers to equity and access

Gore provided an overview of an NCI Experimental Therapeutics Clinical Trial Network (ETCTN) initiative called Create Access to Targeted Cancer Therapy for Underserved Populations (CATCH-UP.2020).

CATCH-UP.2020 was a congressionally mandated supplement to NCI Cancer Center Support Grants in 2020 and aimed to provide targeted therapies to underserved communities. NCI Cancer Centers that were not part of the ETCTN were eligible to apply, then had to demonstrate their ability to recruit patients from underserved communities by accruing at least 24 patients to their site in one year, 50% of whom had to be part of underserved populations, Gore explained.

Fostering access to trials for underserved populations was a chief goal of the program, which also aimed to facilitate the sharing of best practices, coordination strategies, telemedicine and other technological integration strategies, as well as set new standards for clinic outreach.

The program did well, increasing the proportion of historically underserved patients from about 13% to 23% from October 2020 to August 2022, although the majority population was White by far.

“In part, remember, we were looking for rural participation and we were looking for medically underserved urban populations, which includes White people—so, there's nothing wrong with that. But our ability to really enrich for people of color and other traditional ethnic minorities, I think we came up short still, we have a long way to go,” Gore said.

Effective best practices included the use of patient navigators, immersion into the community, and telemedicine use—including for patient consent, which Gore noted was a major step at the University of Kansas, where telemedicine was used to facilitate care across the entire state with as few visits to Kansas City as possible for patients. They also utilized community doctors to administer treatments.

Screening of genomic data to identify underserved patients with genomic mutations was a less fruitful strategy, Gore noted. Investigators also held monthly meetings to discuss the good and bad, fostering a community that proved beneficial. Engaged cancer center community outreach offices were also key aspects of success.

The conclusion of an accompanying report to the presentation, authored by presenters and colleagues, reiterates a takeaway that all echoed during the session.

“While many efforts may be bottom-up, locally developed and funded, public-private partnerships to incentivize and enable the necessary changes in culture and practice will be needed for larger impact on our national cancer research infrastructure,” they wrote. “An inclusive, diverse clinical trial patient population will lead to cancer treatments that will be feasible across communities.”