Study Proves Importance Of Patient Diversity In Clinical Trials

By Ed Miseta, Chief Editor, Clinical Leader

Originally published in Life Science Leader magazine

Drs. Roxana Mehran, Wayne Batchelor, and Paul Underwood were frustrated. They knew there was a big problem with clinical trials in the cardiovascular space — namely, that a very small percentage of trial participants were women or minorities. That left all conclusions regarding outcomes of even successful trials mostly tied to white males. Their frustration, and the need for diversity in these trials, was underscored by two key facts:

• Coronary disease is the leading killer in America.
• The U.S. Census Bureau estimates that by the year 2050, more than half of the U.S. population will be non-white.

Mehran, professor of medicine, population health science and policy at the Icahn School of Medicine at Mount Sinai, and Batchelor, interventional cardiologist at Southern Medical Group, P.A. and associate professor of medicine at the Florida State University College of Medicine, had spent a lot of time investigating race and gender differences in cardiology trials. Mehran and Batchelor describe it as “a bit of a perfect storm” when they started working with Underwood, who is medical director of interventional cardiology for Boston Scientific, is African American, and has focused on the lack of knowledge the industry has on minority patients. “The key to fully understanding the safety and efficacy of new medical and device therapies is developing clinical trial databases that adequately reflect the diversity of the U.S. population. Together, we wanted to understand how women and minorities in trials could be impacted differently than white males. Up until now, the lack of women and minorities in trials has prevented us from having clear answers,” says Batchelor.

UNDERSTANDING BARRIERS TO CARE
The starting point for the partnership was Close The Gap, a health inequity initiative started by Boston Scientific. Close The Gap representatives would work with hospitals and healthcare providers to determine any barriers preventing patients from getting access to care, particularly advanced care like coronary stents or valves. The team would then identify ways those barriers could be addressed and overcome.

Partnering with advocacy groups such as the Association of Black Cardiologists, the Women’s Heart Alliance, and the National Forum for Heart Disease and Stroke Prevention also helped this initiative better understand the needs of minority communities. For instance, they produced video modules on clinical trial recruitment that are directed toward patients, physicians, and clinical investigators, with each one focusing on diverse patient enrollment.

“One of the barriers we immediately recognized was that entry into clinical trials was heavily skewed toward white males,” notes Underwood. “If you wanted meaningful data to describe patients other than white males, it was difficult to find.”

Underwood felt with more women and minority patients participating in trials, different metrics, such as sociodemographic factors, could be explored. This information had not been collected in the past, and could possibly have a positive impact on patients. This information also could help researchers understand how coronary disease progresses in all patient populations.

A UNIQUE POST-MARKET STUDY
Mehran and Batchelor decided to become co-principal investigators in the PLATINUM Diversity trial, a post-market study sponsored by Boston Scientific. The goal was to determine the effect of Boston Scientific’s Promus PREMIER™ stent system on women and minorities, who were significantly underrepresented in the pre-approval studies.

“We came up with a unique trial design that included everyone except white men,” explains Underwood. “Most participants were women, African- Americans, and Latinos. We wanted to evaluate the social, behavioral, and economic determinants of the health outcomes of these patients. We then wanted to compare that data to the data we had from white males and understand if there are sex and race issues in the outcomes.”

In designing the study, researchers carefully chose sites that would have access to the desired patients. By doing so, they were able to enroll 1,500 patients in record time at 52 sites.

"If you wanted meaningful data to describe patients other than white males, it was difficult to find."

Paul Underwood
Medical Director, Interventional Cardiology
Boston Scientific

GO BEYOND THE DEVICE-RELATED RESULTS
The results of the study showed that the stent performed as expected, just as it did in the white male patient population. However, there were differences in “non-stent-related ischemic events.” For example, in women and minorities, there were more deaths and heart attacks that were not related to the stent. “This was a very interesting finding,” says Mehran. “African American women seemed to have the highest rate of these events, which means this is something the industry really needs to pay more attention to when faced with these patients in the future.”

When designing the study, researchers expected they would encounter such non-stent differences in outcomes for this more diverse population, so they decided to record a lot of data that is generally not collected in clinical trials. For example, they collected information on household income and access to health insurance. This was done to determine if access to, and affordability of, needed medicines had anything to do with patient outcomes.

“If complications are noted that are not related to the stent, we wanted to know what might be causing them,” says Mehran. “Income, insurance, blood pressure, and diabetes all could impact patient outcomes. The trial data discovered a strong correlation of heart attacks and deaths in patients with a household income of less than $25,000 a year, as compared to those who made $100,000 a year or more.” The study also found that women who were widows – and thus, did not have a significant other to take care of them – also had a higher incidence of heart attack and death.

ONE UNDENIABLE CONCLUSION
Mehran, Batchelor, and Underwood acknowledge that the results of the trial will require further studies to better enhance outcomes for these patients and deliver care equitably across races and genders. Still, they believe there is one unambiguous conclusion that can be made now: Trials can no longer be filled with white male patients. “There are no more excuses,” Mehran says. “We’ve demonstrated that female and minority patients are out there and are accessible to clinicians. There simply needs to be a greater effort made to creatively choose sites, go after the desired patients, get involved in their communities, and educate them on the purpose of clinical trials and the benefits that can be had from taking part in them.”

Underwood echoes those thoughts. “It’s absolutely possible to get these patients to participate in trials, and the excuses we hear about them not being willing to take part are simply not founded. There are certainly some hurdles in the way, but nothing that cannot be overcome. It is primarily a matter of selecting sites that can ensure a diverse patient representation.

“We will only get more diverse patients in clinical trials when we properly understand the factors involved in decisions related to trial participation. Additionally, we believe the disparities we see in a clinical trial are reflective of the disparities that exist in clinical practice. If women and minorities are having problems getting into a study, they are likely having problems getting into a physician’s office as well.”

The primary results of the PLATINUM Diversity study were published in JAMA Cardiology in October 2017.