Making Cardiology Trials Work for Every Patient, With Roxana Mehran, MD

Clinical trials in the cardiovascular sphere have long marginalized the majority of ethnic groups, as well as failing to include half of the population in the form of female participants. To generate clinically applicable evidence for these substantial groups of patients, many clinicians are calling for an overhaul of the structure of recruitment and enrollment.

Ethnic diversity in the clinical setting has made some improvements over the years, but consistent and impactful progress remains unaccomplished. In a study published in ScienceDirect, investigators examined the 32,000 patients who took part in a new drug trial in the US in 2020. Of these participants, 8% were Black, 11% Hispanic, and 6% Asian. This did not align with the US Census, which found that 14.2% of the population was Black, 18.7% Hispanic, and 7.2% Asian.1

Gender diversity is also lagging despite frequent discussion, even on a global scale. A systematic review published in JAMA Cardiology in 2023 examined 139 trials worldwide consisting of 51,527 patients between 2005 and 2020, all of which investigated aortic or mitral valve disease. Of these trials, the overall proportion of enrolled women was 41.1%, with no substantial changes over time.2

“For years, we’ve been talking about diversifying our clinical trials to mirror the patients that we actually treat,” Roxana Mehran, MD, professor of medicine and director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Wiener Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai, said in an exclusive interview with HCPLive. “Unfortunately, when it comes to the final recruitment of the patients into a clinical trial, we often see a completely different picture. We end up having a lack of evidence and data for these more marginalized populations.”

Diversity in clinical trials is critical for several reasons: as published in the New England Journal of Medicine, the advancement of biomedical knowledge relies largely on generalizability, which is, in turn, hindered by a study population primarily composed of White, male patients. A larger, more diverse population allows investigators to account for gender- or age-based differences in responses to new medications, as well as providing a sample by which practicing clinicians can apply the trial data to each patient entering their offices.3

However, the article also acknowledges the necessity for larger trial populations or sample sizes to achieve equivalent measurements of heterogeneity in treatment effects. With a smaller, but more diverse, patient population, such heterogeneity becomes more difficult to detect. Therefore, the authors suggest circumventing the issue by funding studies focused on diseases that disproportionately affect minority groups rather than simply expanding or shifting trial demographics as a whole.3

During the interview, Mehran also discusses alternative methods to encourage diversity without simply increasing the size of patient populations. In particular, she spotlights the exclusion criteria of “women of childbearing age”, which appears frequently in cardiology.

“That’s between the ages of 12 and 50. That’s 38, almost 40 years of life for a woman, and we basically have no evidence of what to do for these women,” Mehran said. “That’s not acceptable. They have conditions, they need to be treated, and we need to know if a treatment is safe and effective.”

Ultimately, many clinicians agree that the backbone of more inclusive trials is acquiring patient trust, understanding norms, and redesigning studies to account for a more diverse population. Mehran also suggests such strategies as capping enrollment once enough patients of a given population have been enrolled or working to include women by accommodating their limited availability, given their myriad responsibilities.

“Educate the masses – patients, practicing physicians, and everybody else – to bring more patients into clinical trials that are representative of the population that we are treating,” Mehran said.

Editor’s Note: Mehran reports disclosures with Elixir Medical, IQVIA, Abbott, Concept Medical, Cordis, Novartis, and others.

References

1. Kelsey MD, Patrick-Lake B, Abdulai R, et al. Inclusion and diversity in clinical trials: Actionable steps to drive lasting change. Contemporary Clinical Trials. 2022;116:106740. doi:10.1016/j.cct.2022.106740

2. Reddy KP, Faggioni M, Eberly LA, et al. Enrollment of Older Patients, Women, and Racial and Ethnic Minority Individuals in Valvular Heart Disease Clinical Trials: A Systematic Review. JAMA Cardiol. 2023;8(9):871–878. doi:10.1001/jamacardio.2023.2098

3. Schwartz AL, Alsan M, Morris AA, Halpern SD. Why diverse clinical trial participation matters. New England Journal of Medicine. 2023;388(14):1252-1254. doi:10.1056/nejmp2215609