Despite many years of efforts to include more women in cardiovascular studies, there still are not enough women represented in these investigations, according to a recent report from the American College of Cardiology Cardiovascular Disease in Women Committee.1 “We’ve made some progress, but, unfortunately, we’ve been kind of stuck. Most trials continue to have low participation of women,” says Leslie Cho, MD, FACC, lead author of the report.
Currently, women represent more than 51% of the U.S. population, and cardiovascular disease continues to be their No. 1 killer. Still, women only comprise approximately 38% of cardiovascular clinical trial participants.1 For many years, data on male participants mostly were extrapolated to women, despite evidence indicating women respond differently to drug therapies than men.2 “Physicians and regulatory bodies need to really make this a priority. Until we make it a priority, nothing is going to happen,” says Cho, director of the Women’s Cardiovascular Center at the Cleveland Clinic.
Cho and colleagues offered some reasons why this problem persists:
• Participants in cardiovascular trials still are usually recruited only at large centers. “Unfortunately, the status quo of having the same centers enrolling the same population is going nowhere,” Cho says. “Women are less likely to be referred. Minority women are even less likely to be referred.”
Typically, patients at smaller community hospitals cannot access cardiovascular clinical trial enrollment. Most never even hear about the studies. “Most patients receive their care in community centers, where they are unaware of trials. But every patient who goes there should still have the ability to get into a trial if they fit the criteria,” Cho offers.
One way to accomplish that is by advertising cardiovascular clinical trials in community hospitals. Clinicians can refer their patients to the investigators. “If it’s only being done in large centers, then people who never make it to those centers never get access,” Cho explains. “It should be a priority for pharmaceutical companies, regulators, and insurers to mandate that these trials be advertised and widely available to everyone.”
Some investigators have created referral networks to include more women and minorities in the whole process. Other researchers have solicited participants for studies (or asked for input on design of research studies) at neighborhood barbershops.3 “That kind of novel thinking is really important,” Cho adds.
• Many people do not understand the benefits of participating in cardiovascular clinical trials, misunderstand the risks. Cho says it is understandable that minorities may be wary of researchers’ motives or even express the attitude, “I don’t want people to experiment on me.”
“We have to acknowledge that there is an unfortunate, horrible history with African Americans and clinical trials,” Cho notes. “But we need to acknowledge that is no longer the case, and then move forward.”
There is some evidence indicating people who enroll in cardiovascular clinical trials experience better clinical outcomes, regardless of whether they receive the active drug.4 “In part, that’s because there is closer follow-up. If they have a question, people will answer them right away,” Cho observes.
More diversity in cardiovascular trials is even good for pharmaceutical and device companies. “I don’t think they are malintentioned. They are just used to doing things the same way,” Cho suggests.
Demonstrating that there are no adverse events in women could increase profits for drugmakers. Otherwise, drug manufacturers might find out later that women are experiencing more adverse events than expected, and then retrospectively have to change the recommended dosage or put warning labels on the medication. “It’s good for everybody. There’s nobody who doesn’t benefit,” Cho adds.
It is critically important that women “are participating in all aspects of research, from basic to clinical to epidemiological,” says Jennifer H. Mieres, MD, FACC, MASNC, FAHA, senior vice president of the Northwell Health Center for Equity of Care.
Almost 30 years ago, the NIH Revitalization Act of 1993 established guidelines for the inclusion of women and minorities. “We still have a lot of catching up to do,” Mieres notes.
Most cardiovascular studies require physical access to centers participating in trials for enrollment. That means participants need transportation, time off work, and child care. “One can think of IRBs as partners with clinical researchers in ensuring the inclusion and safety of diverse patients in clinical trials,” Mieres says.
The American Heart Association (AHA) Go Red for Women initiative engages women in the research process by using technology. “Women don’t even have to leave their homes to contribute to research through this initiative,” Mieres says.
Also, the AHA launched a Strategically Focused Research Network on Diversity in Clinical Trials. “The goal is to engage underrepresented groups in clinical trials to align with the diversity of our communities,” Mieres says.
There is “an unfortunate, and false, perception that women are more difficult to recruit, and may be more difficult study participants. That may also deter efforts,” says Rita F. Redberg, MD, MSc, FACC, a professor of medicine and Araxe Vilensky Endowed Chair in Cardiology at the University of California, San Francisco.
The fact that most principal investigators for cardiovascular clinical trials are men could lead to lower enrollment rates for women.5 “Gender parity in inclusion should be required for FDA approvals of new drugs and devices,” Redberg argues. “We have had many years of recommendations, and women remain underrepresented in cardiovascular clinical trials.”
To augment the enrollment of women in cardiovascular trials, researchers must build awareness of cardiovascular risk factors and foster trust among women. Redberg suggests increasing the percentage of women who lead clinical trials, modifying inclusion and exclusion criteria, and advertising the risks and benefits of participation to the general population.
“Most importantly, if we hope to make measurable, lasting change, organizations, including the FDA, must statutorily require sex-based analyses and gender parity in trial data reporting,” Redberg says.
Additionally, Redberg says IRBs should require the presentation of specific sex-based analysis data for all clinical trials. In trial design, researchers should specify concrete steps that will be taken to maximize gender representation by disease prevalence, particularly in interventional and procedural specialties. Finally, medical journals should make sex-based analyses data available for published trials. “Sex-based analyses would benefit from the development of a standardized system of reporting for all sexes and genders, including transgender and nonbinary genders,” Redberg adds.
REFERENCES
- Cho L, Vest AR, O’Donoghue ML, et al. Increasing participation of women in cardiovascular trials: JACC Council Perspectives. J Am Coll Cardiol 2021;78:737-751.
- Zucker I, Prendergast BJ. Sex differences in pharmacokinetics predict adverse drug reactions in women. Biol Sex Differ 2020;11:32.
- Balls-Berry J, Watson C, Kadimpati S, et al. Black men’s perceptions and knowledge of diabetes: A church-affiliated barbershop focus group study. J Racial Ethn Health Disparities 2015;2:465-472.
- Majumdar SR, Roe MT, Peterson ED, et al. Better outcomes for patients treated at hospitals that participate in clinical trials. Arch Intern Med 2008;168:657-662.
- Wang TY, DesJardin JT. Time to end “manels” in clinical trial leadership. JAMA Intern Med 2020;180:1383-84.
To augment the enrollment of women in cardiovascular trials, researchers must build awareness of cardiovascular risk factors and foster trust among women. Try increasing the percentage of women who lead clinical trials, modifying inclusion and exclusion criteria, and advertising the risks and benefits of participation to the general population.
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