Getting More Women in CV Research Will ‘Take a Village’

The low proportion of women contributing to clinical trials, primarily as participants but also as researchers, is not helping the progress of cardiovascular medicine and needs to be rectified through a big-picture strategy, according to experts from the American College of Cardiology’s Cardiovascular Disease in Women Committee.

“We know from numerous studies, too many to mention, that women have different pharmacokinetics compared to men and women tend to have more side effects,” lead author Leslie Cho, MD (Cleveland Clinic, OH), told TCTMD. “There are lots of instances where drug dosing is different between men and women, and yet these trials are 70% done in men and the recommendation is always carte blanche for both.”

In the paper, published as a JACC council perspective in the August 17, 2021, issue of the Journal of the American College of Cardiology, Cho and colleagues outline eight barriers contributing to the disparity. Their aim, she said, is “to galvanize not just physicians but everybody involved, which is the payers, the regulators, and patients and communities, to really try to help them understand and raise awareness [about] why it's important to get women into trials.”

Fewer Referrals, More Ageism

First, women are significantly less likely to be referred for specialty care, where clinical trial recruitment often takes place, compared with men. “We know that when women get referred to centers, they do sign up for trials. But when they don't even get into specialty clinics, how can they sign up for trials?” Cho asked.

To fix this, the authors suggest increasing awareness of ongoing trials to primary care providers and community hospitals and using new recruitment models to reach the underrepresented.

I think it takes a village to raise this bar because the bar has been stuck here for a while. Leslie Cho

The next largest issue in the way of women enrolling in cardiovascular trials is ageism, in that studies often have a maximum age cutoff even though disease in women occurs later than in men. “It is essential that we insist on including broad age-group participation in CVD clinical trials by expanding the inclusion criteria, not only to achieve greater generalizability to our aging population, but also to improve representation of women in CVD trials,” the authors write.

Logistical Barriers, Absence of Leadership

The third issue relates to a lack of awareness and trust among would-be female participants, on top of logistical barriers. “Women tend to also be caregivers for their children, spouses, and parents, and lots of these trials have very onerous in-person follow-up,” Cho said. “Now, in the era of virtual visits and this revolution in healthcare, really those things can be relaxed so that it’s not so onerous so they can enroll in clinical trials.”

Another large barrier that has come up multiple times in the past is the dearth of female leaders overseeing cardiology clinical trials. While the number of women as first authors has increased of late and protocols are in place to aid their advancement in the field, the fact remains that representation remains low, the authors say. “Because of evidence that female representation in clinical trial leadership is associated with both greater female enrollment and higher rates of reporting sex-based outcomes, it is essential that women are included in trial leadership and design,” they write. “In addition, there is ample evidence that sex heterogeneity within research teams leads to higher quality research.”

Similarly, Cho and colleagues also recommend an increase in the participation of unrepresented minorities in trials in order to “have adequate representation of racial/ethnic minority groups as investigators and participants and to use successful culturally tailored recruitment strategies.” With this input, researchers can “better understand and address the barriers and identify opportunities for enrollment and retention,” they write.

Specific Populations, Need for Retention

Turning to pregnant women and those of childbearing age, the sixth barrier relates to historical events that led the US Food and Drug Administration to ban this population from clinical trials. Though the ban hasn’t been in place for almost 50 years, younger women still tend to be viewed as vulnerable and are often excluded, but the authors recommend a shift in thinking to consider them “scientifically complex” in order to gain needed information. “Data from postmenopausal women are not similarly applicable to the premenopausal population, and a focus on inclusion of young women in CVD trials is likely to uncover novel data on this high-risk group,” they write. “As such, CV trials should strive to explicitly recruit women of childbearing age.”

Further, Cho and colleagues cite known sex differences in cardiovascular disease—namely, a greater prevalence of coronary artery dissection, heart failure with preserved ejection fraction, stress-induced cardiomyopathy, and microvascular disease in women. Increased research of these conditions, as well as the different ways women may present with ACS compared to men, is warranted, they say.

Finally, the authors point out that study retention has been harder with women, though little is known about why. To address this in the future, they encourage researchers to “include reasons for study drug discontinuation and withdrawal of consent in clinical trial case reports and report it by sex and race. These will bring further insights into reason for discontinuation that may lead to novel solutions for mitigation.”

There is not one specific responsible party to fix the larger problem, Cho commented to TCTMD. “I think it takes a village to raise this bar, because the bar has been stuck here for a while.”

The authors conclude: “To address barriers to recruitment and retention of women in CVD clinical trials, a comprehensive and targeted approach that involves partnership with all stakeholders—patients, referring clinicians, research teams (investigators and coordinators), health care systems, the FDA, payers, sponsors, professional, and community organizations—is essential. We owe it to our patients to increase representation of women and underrepresented minorities in CVD trials.”