Bruce A. Feinberg, DO, of Cardinal Health Specialty Solutions, leads a panel discussion on how far randomized clinical trials have come, how they could be better, and how using real-world evidence could make research more representative of the population.
Criticism about disparities in cancer care often starts with the clinical trial: too few people of color enroll, not enough is done to build trust in communities, and trials are too inaccessible. All this leads to enrollment rates of 3% to 5% of all patients with cancer, and trials for cancer therapies often represent minority populations at levels well below the numbers of individuals known to have the disease.
Still, Bruce A. Feinberg, DO, vice president and chief medical officer, Cardinal Health Specialty Solutions, based in Dublin, Ohio, reminded the audience at Patient-Centered Oncology Care® that clinical trials have accomplished a lot, and fixing them starts with remembering what things were like before randomized clinical trials became the gold standard for bringing new drugs to market.
“Literally 5 decades ago, medicine was based on anecdote. It wasn’t based on hard science; it wasn’t evidence-based,” Feinberg said. In writing a prescription for better studies, he said, “We’ve got to figure out what is good about clinical trials, what is not working in clinical trials, and what can be done to change them and what’s already being done to change them.”
Feinberg moderated the panel “Building Better Clinical Trials for Better Clinical Outcomes.” Joining him were:
• IULIANA SHAPIRA, MD, chief medical offi cer of Regional Cancer Care Associates, based in Hackensack, New Jersey
• MIRUNA SASU, PHD, MBA, chief strategy offi cer for Life Sciences, COTA Healthcare, New York, New York
• RICK KITTLES, PHD, associate director of health equities of the Comprehensive Cancer Center; and professor and director, Division of Health Equities in the Department of Population Sciences, City of Hope, Duarte, California.
Of the group, Sasu came to work on clinical trials by the least traditional route. A biologist and statistician, she was employed by the US Department of Agriculture’s Food Safety and Inspection Service when a close family member was diagnosed with stage IV lung cancer. That experience opened Sasu to the world of pharmaceutical research. She worked for Bristol Myers Squibb and later Johnson & Johnson in roles related to digital health and innovation.
She saw how long it takes to bring a therapy to market—up to 12 years. So, more recently, Sasu left for COTA, which is creating databases that can be used as real-world evidence, and comparator arms, as the FDA creates pathways to bring drugs from the laboratory to patients in shorter time frames.
Shapira agreed with Feinberg’s assessment that cancer care would not be where it is today without clinical trials, adding that the most important “partner” in the process is the patient. Trial participation can be arduous for patients and families—unnecessarily so, she said. There should be more opportunities for patients to take part through their community oncology clinic, so that they can avoid the cost and discomfort of traveling while dealing with the eff ects of chemotherapy.
At City of Hope, Kittles runs a program focused on engagement and outreach. He began his career at Howard University as a researcher. “We didn’t call it disparities work; I was just working on diseases that disproportionately impact [individuals] of African descent,” he said. “And what emerged was this discussion around health disparities—and now we have these comprehensive programs around that—which is all great, but my initial focus on what brought me to where I’m at now was my attention and
desire to make an impact as it relates to the cancer in the African American community.”
Kittles spent time at the University of Chicago before coming to City of Hope, and a diff erence he saw compared with his time at Howard University was the need to build trust and proactively create a “bidirectional relationship with the community.” City of Hope represents a diff erent level of challenge, given the broad, multiracial, multiethnic team that serves a very diverse area of 14 million individuals.
Patients may seek a clinical trial because it is the best financial option—in her family’s case, that was true, Sasu said. Kittles said that when he was at Howard, the main challenge was helping patients and families understand the criteria, including the issues of comorbidity. Barriers could be diff erent from place to place.
“There’s opportunity at certain institutions that have a very strong connection with the communities they serve—that many of those barriers that we see exist and many of us write about are lowered or eliminated because of that trust, because of that commitment to the community,” Kittles said.
Shapira agreed that barriers for some trials seem arbitrary and do not allow drugs to be tested on the kinds of patients who would take them in real-world settings. She pointed to a meta-analysis about structural barriers to trials, such as refusing to allow patients to participate if they had brain metastases, diabetes, or HIV. Trials, she said, seemed to want “athletes with cancer.”
Today, she said, “We have huge computing power. So we shouldn’t be burdened with this very strict eligibility criteria—we should enroll patients who are real-life patients, with their hypertension and their obesity,” because researchers can use algorithms to control for these factors afterward.
Feinberg and Shapira discussed the fact that as far back as 1992, the FDA realized that trials took too long, that trial populations skewed younger and healthier, and that expedited pathways were needed for lifesaving drugs, especially in oncology. As much as these pathways are used, however, many see a need to do more, given the escalating cost of new therapies.
Only in recent years has talk turned to synthetic control arms, Shapira said, because the technology now exists to make this possible. “Every 10 years, there is improvement in our ability to execute clinical trials better, because technology is better.
However, the albatross around our necks is the [regulators],” she said. “We cannot overcome that with technology.”
She pointed to rules that limit which institutions can conduct trials when technology allows so much connectivity among physicians. Sasu said that, from the pharma side, the burden of regulation pushes drug sponsors to work with larger institutions that can assemble patient populations quickly and help bring drugs to market as soon as possible.
Feinberg asked whether adaptive designs would work, including provisions that would allow for synthetic control arms in phase 3 with long-term
follow-up. Kittles said that model exists—it was used to approve the COVID-19 vaccines, which by necessity had a greatly accelerated approval process.
Kittles sees opportunities for regulators to learn from this example.
But the big issues going forward will be opportunity and access, Kittles said. “When one talks about disparities, especially if…you’re doing a drug trial that may interact with some environmental stressor or stimulus, [if] you’re not taking that context into consideration, then that’s a missed opportunity. So, I think that there, we really need to think about opportunity—the opportunity
for getting into these trials, and then also the access issue.”
Shapira said decentralized trials off er a solution, but the regulatory atmosphere must allow them to fl ourish. “[An individual] who has cancer in a rural area should not have to suff er the burden of driving 3 hours to the recognized [Comprehensive] Cancer Center,” she said. Patients cannot afford gasoline for long trips, a babysitter for an entire day, or extra time off from work, she said. “The entire health care system has been geared toward helping the big hospital center—they’re paid better, [whereas] the community oncology community practices [are] under water.”
Sasu said that in her efforts to improve diversity of trials, she found the challenges were very complex—doctors’ time was scarce, the shock of diagnosis for patients took time to absorb, and education of communities had to be ongoing. For physicians, she said, “They might not have the time to read 30 protocols and figure out which is the right one for the 2 patients that they’re seeing.”
Technology, education, and collaboration all offer possibilities, and getting it right is going to take many solutions. No single company is doing everything correctly, she said.
Kittles, however, is optimistic. “I’m excited, mainly because of what I’m seeing now from pharma,” he said. “What I’m seeing from pharma is a level of
engagement around inclusive research that I haven’t seen before. And this is very important, because it’s going to allow not only pharma to learn, but it’s also going to provide the community and institutions an opportunity to engage around these issues.”