In the Effort to Diversify Clinical Trials, Trust, Access, and Education Play Crucial Roles

While funders and researchers have long held that clinical trials should enroll more diverse patients to better reflect the populations in which approved drugs will eventually be used, patient populations enrolled in clinical trials remain largely homogenous.

As Todd C. Knepper, PharmD, and Howard L. McLeod, PharmD, both of Florida’s Moffitt Cancer Center, reported in a comment recently published in Nature, in 1997, 92% of participants in clinical trials for treatments targeting cancer, central nervous system diseases, and heart disease were white. By 2014, that percentage was not much better, with white patients still comprising 86% of participants.¹

Given the fact that drugs may behave differently in different patient populations, homogenous trial populations are likely hindering the development of effective therapies, whereas trials that enroll more minority patients may lead to conclusions that might not otherwise have been discovered.

For example, the FLAURA trial, which enrolled a high number of Asian patients with non—small cell lung cancer (NSCLC), demonstrated that osimertinib was more effective than standard therapy in treating EGFR-mutated NSCLC, a disease type that affects more Asian patients than white patients. Similarly, the Abi Race clinical trial of abiraterone in black men—who are more likely to die of prostate cancer than are white men—with advanced prostate cancer demonstrated that the therapy was linked to a greater decline in prostate-serum antigen in black men than in their white counterparts.

While clinicians may agree that it is crucial to enroll diverse patient populations in clinical trials, they face significant challenges in doing so. James Hamrick, MD, senior medical director at Flatiron Health, told The American Journal of Managed Care^® that, in part, minority populations have what he termed a justified skepticism about research participation, and pointed to the infamous Tuskegee Syphilis Study—in which black men were denied effective treatment for syphilis in order for government researchers to document the natural history of the disease—as one tragic example of reasons why minority patients might avoid research.

But furthermore, Hamrick said, patients who might be willing to participate in a clinical trial may lack access because of location and/or socioeconomic status. Providers who are caring for patients in rural practices may not be suggesting trials to their patients, in part because patients in these areas might have to travel to a major academic center for monitoring.

“If the patient doesn’t have the freedom from getting off of work or having a family member or friend help with the time and cost associated with travel, that’s going to self-select for a more affluent population, so there are some real barriers there,” according to Hamrick.

In order to address the problem of access, Hamrick says, trials need to be available closer to home for more patients: “We have to bring the trial to the patients as opposed to bringing the patients to the trials.”

Keys to achieving this objective include designing trials that can be conducted in smaller centers and clinics outside of academic centers so that trials can become more a part of patient care rather than a disruption for patient populations who may lack resources.

In his practice, Hossein Borghaei, DO, chief of thoracic oncology at the Fox Chase Cancer Center in Philadelphia, Pennsylvania, also sees patient burden in terms of additional travel (some of his patients must take 2 to 3 different transportation modalities to reach the Center, he noted) and more intensive monitoring as a hinderance to trial participation.

Some patients, he finds—particularly younger patients with greater internet savvy—are beginning ask about participating in trials, particularly for immunotherapies for lung cancer, but he also finds that many patients lack familiarity with the nature of clinical trials and may have misconceptions that lead to concerns that can be resolved through education. Some may fear, for example, that they will be responsible for additional medical bills, which is not typically the case. Others, he says, fear that a clinical trial is only viable for a patient who has run out of other treatment options, which is also not the case. Finally, he notes that some patients are hesitant to even discuss a clinical trial because they fear that, if they decline to participate in a study, their oncologist will no longer treat them—a misconception that he says is crucial to clear up.

To help educate his patients, Borghaei typically addresses the potential of enrolling in a trial with a patient and their family members over the period of several visits. Patients considering a phase 1, first-in-human trial, he says, typically need greater discussion about their decision than do patients considering phase 3 studies, but he asks his patients to take home consent forms and read them over for several days before meeting again to discuss further questions.

This process, he says, can be a lengthy one, but it is crucial to educate patients about the fact that “without trials, we won’t make progress” in treating diseases.

Borghaei sees a need for a better educational methodology—one that is broader than individual efforts at cancer centers across the country—to raise awareness among patients so that they are more open to the possibility of participating in research.

That’s an objective that’s shared by David Charles, MD, chair of the Alliance for Patient Access and Coalition for Clinical Trials Awareness. Charles’ organization is working on a national campaign to raise patient awareness about the benefits of clinical trials.

Public health awareness initiatives, says Charles, have been effective in generating more participation in organ donation, and given the similarity between organ donation programs and clinical trial participation—namely, the opportunity to benefit society, even if the individual does not reap benefits—Charles and the Coalition believe that a similar undertaking can change the public perception of clinical trials so that a broader range of patients view them as a feasible option.

Charles points to the success of educational campaigns in specific disease states—including the success of the Michael J. Fox Foundation for Parkinson’s Fox Trial Finder in enrolling patients in Parkinson disease trials—as evidence that education can change attitudes about research participation.

“What’s working in individual disease states really should be elevated to the public in general,” said Charles. “Our goal would be to elevate the level of understanding of all Americans…about what [clinical trials are] and how they benefit society such that, in the future, if a person had an illness or condition…that it would be more likely that they would at least think of or ask their physician” if there are clinical trials available to them.

Reference

Knepper TC, McLeod HL. When will clinical trials finally reflect diversity? Nature. 2018;557(7704):157-159. doi: 10.1038/d41586-018-05049-5.