Women Underrepresented in Late-breaking Cardiovascular Clinical Trials, a New Analysis Finds

Women continue to be underenrolled in cardiology-related clinical trials, including studies presented as late-breaking clinical trials (LBCT) at major cardiology meetings, according to a recent analysis published in the Journal of Women’s Health.

Specifically study authors reported an inclusion-to-prevalence ratio for women of 0.76 for all trials in the analysis with the ratio significantly lower for studies evaluating cardiac procedures than for trials of medication.

Martha Gulati, MD, MS

Courtesy Smidt Heart Institute Cedars-Sinai

LBCT can have an impact on novel drug and device approvals, intervention indications, and patient management, according to corresponding author Martha Gulati, MD, MS, director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, in Los Angeles, and colleagues. The persistent dearth of sex-specific data pertaining to women, however, makes risk-benefit decisions for all types of therapy uncertain and may limit application of the therapies, they added.

“LBCTs present novel, practice-changing evidence to the medical community on a prominent stage and as such, should represent the gold standard for diversity, equity, and inclusion in clinical trial enrollment,” wrote Gulati et al. Given ongoing evidence that women remain underrepresented in cardiology research, the investigators designed the current analysis to characterize the inclusion of women in LBCT, and specifically those presented at 3 key meetings of cardiology professionals, to better understand the barriers to enrollment, reporting, and retention.

For their analysis, study authors identified LBCTs presented in 2021 at the American College of Cardiology, American Heart Association, and European Society of Cardiology annual scientific meetings.

Characteristics of trials of interest to the researchers included subspeciality, type of intervention, funding source, and authorship data. Participant data extracted for all trials included total participants, median age, gender, and racial/ethnic distribution. Also of interest were characteristics of authorship which included data on total number of authors, number of female-identifying authors in the author block, and gender of first, last, and presenting authors. (Gender was characterized on the basis of publicly available biographic data.)

The outcome of interest, the inclusion-to-prevalence ratio (IPR), represented the percentage of women in each trial/percentage of women within the specific disease population, using combined US and global data. Disease state denominators were collected from large population-based data. IPRs <1.0 indicate underenrollment of women as defined by existing research.

FINDINGS

The investigator's final analysis included 68 trials among which inclusion of women ranged from 0% to 71%, with a mean of 35.2%.

Overall, 29.4% of trials enrolled <25% women and 85.3% of trials enrolled <50% women. Less than half (47.1%) of the trials reported sex-specific analyses.

Among trials that reported racial demographics, investigators reported on average 72.9% of participants were White. Overall mean participant age was 65.1 years, according to the findings. (See Figure, right, for cardiology issues addressed across trials).

Gulati and colleagues reported that only 15 trials exceeded an IPR of 1 with the average ratio being 0.76. The average did not vary significantly, they added, based on the specific conference at which a study was presented, the trial center, geographic region, or the funding source. There was variation in average IPR by subspecialty, however, and authors noted a statistical difference between interventional cardiology (0.65) and hear failure studies (0.88; P=0.02).

Results of other comparisons included a significantly lower IPR for procedure-based trials vs medication trials; for trials with a participant mean age <65 years vs ≥65 years; and for those with <1500 vs ≥1500 participants.

In addition, the researchers found that less than one-quarter (21.2%) of the authorship block was women, with 4/68 women presenting authors and 8/55 women senior authors, although without statistical difference in IPR by presenting or senior author gender.

In addition, the researchers found that less than one-quarter (21.2%) of the authorship block was women, with 4/68 women presenting authors and 8/55 women senior authors.

“This analysis of three major cardiovascular conferences in 2021 suggests that previously documented low inclusion of women in clinical trials, particularly in interventional and procedural spheres, persists for LBCTs despite ongoing efforts to achieve gender parity,” concluded the authors. They observe, too, that factors contributing to limited enrollment of women “may fall into several spheres of influence, including the patient, clinical care team, local research team, clinical trial infrastructure, and broader societal expectations.”

Limitations to their study noted by the authors include sole use of the term LBCT to identify studies presenting pivotal data and the use of a single year of trials, the latter of which may limit generalizability of findings. Also, the sample size may preclude detection of statistically significant differences.

Reference: Holtzman JN, Kaur G, Power JE, Barkhordarian M, Mares A, et al. Underrepresentation of women in late-breaking cardiovascular clinical trials. J Womens Health. Published online April 17, 2023. doi:10.1089/jwh.2022.0536