Heart Failure RCTs Lack Women Principal Investigators

For their analysis, Van Spall and colleagues set out to evaluate the temporal trends in representation of women among authors of HF RCTs published in high-impact medical journals from 2000-2019.

“This systematic review demonstrated that among 403 HF RCTs published in high-impact medical journals between 2000 and 2019, women comprised only 15.6%, 12.9%, and 11.4% of lead, senior, and corresponding authors, respectively,” they reported. “There was no significant temporal change in the proportion of women in these authorship positions. Among a total of 4,346 authors in any authorship position in these RCTs, 19.6% were women. The proportion of women authors in any authorship position did not change over time. Women had lower odds of lead authorship in RCTs that were multicenter, coordinated in North America or Europe, tested drug interventions, or had men as senior author.”

In an accompanying editorial, Michelle M. Kittleson, MD, PhD, of the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, applauded the review by Van Spall and colleagues, noting that “On first glance, the numbers indicate near proportional representation: 25% of HF cardiologists are women, as were 19.6% of trial authors. But look deeper and proportional representation falls apart: in the past 2 decades, only 1 in 7 trials had a female lead author and only 1 in 10 had a female corresponding author.”

For their review, Van Spall and colleagues searched MEDLINE, EMBASE, and CINAHL for RCTs focused on HF that were published in journals with an impact factor ≥10 from Jan. 1, 2000 through May 7, 2019. Full-text manuscripts reporting primary outcomes were included; protocols and publications subsequent to the initial manuscript reporting primary outcomes — post hoc, intermediate, and secondary analyses — were excluded.

“Our systematic search produced 10,596 unique manuscripts, of which 8,278 were excluded on the basis of title and/or abstract review,” they wrote. “We assessed 2,318 full-text articles, of which 403 met eligibility criteria.”

The 403 RCTs included in the final analysis involved a total of 4,346 authors, (median 10 authors; interquartile range 6-13 authors per trial), most of which were conducted in Europe (54.3%), limited to single countries (74.9%), involved multiple centers (57.3%), and tested drug interventions (67.2%), they found. And, most significantly, “men comprised a majority of lead (84.4%), senior (87.1%), and corresponding authors (88.6%),” they wrote.

Van Spall and colleagues found that women had lower odds of lead authorship in RCTs that:

• Were multicenter (odds ratio [OR]: 0.58; 95% CI: 0.18 to 0.96; P=0.037).
• Were coordinated in North America (OR: 0.21; 95% CI 0.08-0.70; P=0.011) or Europe (OR: 0.33; 95% CI 0.09-0.91; P=0.039).
• Tested drug interventions (OR: 0.42; 95% CI 0.16-0.97; P=0.043).
• Had men as the senior author (OR: 0.50; 95% CI: 0.21 to 0.93; P=0.043).

Van Spall and colleagues pointed to a number of gender-based inequities that hamper women’s ability to participate in clinical research, including less support from research institutions, underrepresentation in editorial boards, and “a gender association—either intended or unintended—between mentees and mentors.” They also noted that pharmaceutical companies tend to offer funding to men more often than women.

“The importance of women as leaders in clinical trials is multifold,” they wrote. “In a survey of 1,123 internal medicine trainees, most women perceived the field of cardiology to lack the mentors they desired. A vast majority of women researchers (77%) have men, rather than women, as their mentors according to a survey of young researchers at the National Institute of Health. The gender association between senior and lead authors and the under-representation of women as mentors in clinical trials—assessed using the surrogate status of senior author—may deprive women from leading clinical trials themselves, creating a cycle of under-representation of women as leaders in clinical trials. In addition, other associated benefits of having women as lead authors in clinical trials—increased enrollment of women as trial participants and increased citations per publication relative to men—may be lost.”

As for what should be done to help resolve these disparities, Van Spall and colleagues had several recommendations:

• For early- and mid-career women cardiologists: Engage in online and social media networks, limiting content to science; Participate in national and international research networks or registries that offer women research collaboration, mentorship, and sponsorship opportunities; Invest in clinical research training.
• For senior men and women cardiologists: Mentor and sponsor the next generation of women trialists; Create a supportive culture to ensure equal opportunity; Learn to recognize and intervene during harassment.
• For academic and departmental leadership: Receive education about gender disparities; Eliminate inappropriate questions during interviews, and mitigate implicit bias in selection process; Develop mentoring and sponsoring programs; Include women as board or executive committee members; Ensure equal opportunity and recognition for researchers based on objective criteria; Encourage self-nominations for awards and advancement opportunities; Implement a zero-tolerance policy for workplace harassment; Implement flexible promotion policies that recognize familial and child rearing demands; Encourage women to apply for funding opportunities; and participate in anti-bias training.
• For industry and grant funding agencies: Conduct blind reviews of applications and use more equitable review criteria; Provide gender breakdown of applicants and awards; Include women as reviewers and chairs on funding committees; Include women in luminary networks.
• For journals: Provide equitable peer review; Set objective criteria and avoid informal networks for the selection of editors and editorial boards.

In her editorial, Kittleson argued that these recommendations — which she called “concrete and actionable solutions” — “should be printed out and framed in all of our offices.” She also noted that it is likely that many female cardiologists have experienced disparities, and that male cardiologists have witnessed them. “In 2016, women made up 46.4% of U.S. medical school graduates and 42.6% of internal medicine resident physicians but only 21.5% of general cardiology fellows and 12.6% of practicing cardiologists,” she pointed out. “Not only is there this residency-to-fellowship cliff, but whether by dint of a sticky floor or glass ceiling, their professional advancement also lags. Among U.S. cardiologists with faculty appointments in 2014, 16.5% were women and only 15.8% of those were full professors.”

“The weight of evidence of unequal representation is frustrating, but negative emotion will not shore up cliffs, mop up sticky floors, or break glass ceilings,” she wrote. “The avalanche of data is our res ipsa loquitor—defining the problems is the first step to devising the solutions.”

Van Spall and colleagues pointed to the restriction of their review to English language studies as a potential limitation to their analysis. Other limitations included not accounting for gender nonbinary authors, clustering of authorship teams across clinical trials, the degrees of study authors, or the race or ethnicity of authors. They also noted that the multivariable analysis is exploratory in nature, and that the results should be interpreted with caution.

1. Less than 20% of heart failure RCT authors from 2000-2019 were women, with women representing 15.6%, 12.9%, and 11.4% of lead, senior, and corresponding authors, respectively.

2. Female cardiologists were less likely to be authors in RCTs that were multicenter, were coordinated in North American or Europe, tested drug interventions, or had men as the senior author.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 3

Topic ID: 74,3,3,192,925