Less Than One in Five CVD Trials Led by Women
When female PIs do run the trials, though, they are much better at achieving gender equity in enrollment.
Women are significantly less likely than men to lead cardiovascular clinical trials, but when they do take the reins, those trials include a higher proportion of female participants, according to the results of a new study.
In more than 600 cardiovascular clinical trials, an area of medicine where women have historically been underrepresented in studies, researchers showed female PIs led trials that included 44.9% women as opposed to just 37.9% in studies run by men (P < 0.001).
“Overall, we saw that just 18.4% of trials were led by women and there was, unfortunately, no significant change over time,” lead researcher Celina Yong, MD (Stanford University School of Medicine, CA), told TCTMD. “There were also fewer device- and industry-sponsored trials led by women PIs. But what was most interesting to me is that we’re seeing the potential collateral benefit of improving gender equity in trial leadership, since we found that studies led by women PIs had significantly better recruitment of women patients compared with those led by male PIs.”
The unequal representation of women in cardiovascular trials is a well-documented problem, one that has significant implications because the translation of research evidence into clinical practice can only occur if women are adequately studied. There is also a glaring gender-equity problem in the leadership of those very trials. For example, previous research has shown that women are less likely than men to be first and senior authors. In one study, researchers found that more than half of cardiovascular clinical trials published in the Lancet, JAMA, and New England Journal of Medicine lacked women on their steering committees and only one in ten were led by female principal investigators.
“We’ve known for a long time that cardiovascular clinical trials have underenrolled women patients, but there has been little data on the gender representation of clinical trial leadership over time, and whether PI gender might have any relationship with equity in patient recruitment,” said Yong. “We went back to look at almost a decade of clinical trials.”
Harriet Van Spall, MD (McMaster University/Population Health Research Institute, Hamilton, Canada), who wasn’t involved in the study but who has studied gender equity in cardiovascular clinical trials, said these new findings, as well as other work, “give pause to consider the importance of creating capacity for clinical trial leadership among women, who currently represent a small minority of those who lead cardiovascular clinical trials.”
The results, she added, are consistent with their previous work in heart failure, where they showed that female participants were underrepresented in nearly 72% of all studies conducted between 2000 and 2019. That analysis also showed that after “adjusting for the type of intervention, funding source, recruitment location, and region of trial coordination, trial leadership by a woman was associated with more gender-representative trial populations,” Van Spall told TCTMD.
Struggling to Achieve Better Gender Representation
For the study, which was published January 24, 2023, in the Journal of the American College of Cardiology, Yong and colleagues identified 620 cardiovascular trials, including those funded by industry and by the National Institutes of Health (NIH), published between 2010 and 2019. Of these, just 114 were led by women. Over this time period, there was no change in percentage of women PIs.
Overall, 23.9% of studies of ischemic heart disease were led by women, compared with just 11.5% and 10.6% of stroke and arrhythmia studies, respectively. Less than 10% of device trials were led by women, while 18.9% of drug trials had a female PI. Other intervention studies, such as those in cardiac rehabilitation and nutrition, had the highest representation of female PIs (29.6%). Women were more likely to lead trials funded by the NIH than those funded by industry (28.9% vs 14.7%; P < 0.0001).
We’re seeing the potential collateral benefit of improving gender equity in trial leadership since we found that studies led by women PIs had significantly better recruitment of women patients. Celina Yong
Studies led by women enrolled more female participants, an increase in representation seen across study types. In drug trials led by women, 48.9% of study participants were women compared with 40.1% in drug studies led by men (P = 0.01). In other intervention studies led by women, 47.6% of participants were female compared with 35.4% in studies led by men (P = 0.02). There was no significant difference in the number of female participants in device trials led by women or men.
“In a field where we have really been struggling for years to achieve better gender representation in our clinical trials to guide our understanding of sex differences in cardiovascular care, this gives us a direction to look for answers,” said Yong. “For me, the questions are: do female PIs use different strategies to recruit diverse patient populations or do they have access to places where women patients are seen more, such as women’s heart centers or clinics?”
“It is possible women leaders of clinical trials direct more effort towards recruiting and retaining female participants via the study protocol, consent process, and follow-up plan,” added Van Spall. “The role of consent in the underrepresentation of some demographic groups in clinical trials, and how the consent process and outcomes may be influenced by trial leaders, is not clear.”
By learning what factors are leading to more equitable recruitment of patients, Yong said the hope is that that approach or strategy will translate to all studies regardless of PI gender.
Unresolved Barriers to Trial Leadership
Overall, less than 15% of cardiologists are women while roughly 30% of neurologists are women, and the trial leadership in cardiovascular studies is often composed of both specialties. However, Yong pointed out that trial types do not track directly with subspecialties so it’s difficult to know if the percentage of women leading trials aligns with their representation in the field. With device trials, which are more closely aligned with invasive subspecialties, such as interventional cardiology and electrophysiology, female trial leadership is more aligned with the percentage of women in those subspecialties.
“This definitely points to the pipeline as the major limiting factor here,” said Yong.
Although there was a lack of change in trial leadership over the 10-year period, Yong said it’s possible things might be different in more-recent years given that there is increased awareness about the importance of gender equity in clinical trial leadership. However, the present study suggests there may be barriers for women that are yet to be resolved, such as lack of adequate mentorship or access to funding, among other things. “There’s still a need for more work to understand what the fundamental issues are,” she said.
To TCTMD, Van Spall pointed out that trials with a female senior author are more likely to have a female first author, and that female trial leadership is also associated with greater inclusion of women on executive committees. In 2021, Van Spall and colleagues published an “actionable road map” to address and fix the imbalance in trial leadership, including strategies to ensure that cardiovascular trials get more female PIs and study chairs.
Yong C, Suvanna A, Harrington R, et al. Temporal trends in gender of principal investigators and patients in cardiovascular trials. J Am Coll Cardiol. 2023; 81:428-430.
- The researchers report no relevant conflicts of interest.