Women’s Participation in Cardiovascular Clinical Trials From 2010 to 2017

Abstract

Background: Cardiovascular disease is the leading cause of death among women worldwide, yet, women have historically been underrepresented in cardiovascular trials. Methods: We systematically assessed the participation of women in completed cardiovascular trials registered in ClinicalTrials.gov between 2010 and 2017, and extracted publicly available information including disease type, sponsor type, country, trial size, intervention type, and the demographic characteristics of trial participants. We calculated the female-to-male ratio for each trial and determined the prevalence-adjusted estimates for participation of women by dividing the percentage of women among trial participants by the percentage of women in the disease population (participation prevalence ratio; a ratio of 0.8 to 1.2 suggests comparable prevalence and good representation). Results: We identified 740 completed cardiovascular trials including a total of 862 652 adults, of whom 38.2% were women. The median female-to-male ratio of each trial was 0.51 (25th quartile, 0.32; 75th quartile, 0.90) overall and varied by age group (1.02 in ≤55 year old group versus 0.40 in the 61- to 65-year-old group), type of intervention (0.44 for procedural trials versus 0.78 for lifestyle intervention trials), disease type (0.34 for acute coronary syndrome versus 3.20 for pulmonary hypertension), region (0.45 for Western Pacific versus 0.55 for the Americas), funding/sponsor type (0.14 for government-funded versus 0.73 for multiple sponsors), and trial size (0.56 for smaller [n≤47] versus 0.49 for larger [n≥399] trials). Relative to their prevalence in the disease population, participation prevalence ratio was higher than 0.8 for hypertension, pulmonary arterial hypertension and lower (participation prevalence ratio 0.48 to 0.78) for arrhythmia, coronary heart disease, acute coronary syndrome, and heart failure trials. The most recent time period (2013 to 2017) saw significant increases in participation prevalence ratios for stroke ( P =0.007) and heart failure ( P =0.01) trials compared with previous periods. Conclusions: Among cardiovascular trials in the current decade, men still predominate overall, but the representation of women varies with disease and trial characteristics, and has improved in stroke and heart failure trials.

Sex differences in cardiometabolic risk factors, pharmacological treatment and risk factor control in type 2 diabetes: findings from the Dutch Diabetes Pearl cohort

“…Furthermore, a recently published systematic review studying the participation of women in 740 cardiovascular clinical trials with 862 652 participants showed that, although this has improved over the last decade, men still predominate majority of cardiovascular clinical trials. 37 Reporting sex-specific results from clinical trials is important to obtain more insight into potential sex differences of treatment benefit and medication tolerance. Therefore, novel approaches to the recruitment and enrollment process and novel trial designs are needed to ensure that sex-specific results may be meaningfully obtained and applied to clinical practice.…”

“…Therefore, novel approaches to the recruitment and enrollment process and novel trial designs are needed to ensure that sex-specific results may be meaningfully obtained and applied to clinical practice. 37 Another possible explanation may be found in differences of cardiometabolic risk factor levels at treatment initiation. As discussed earlier, it has been hypothesized that cardiometabolic risk factors need to deteriorate further in women than men before they are diagnosed with overt T2D.…”

Disparities in Cardiovascular Care and Outcomes for Women From Racial/Ethnic Minority Backgrounds

“…The representation of women in clinical CV trials has fluctuated over the past two decades, consistently remaining below 50% [25][26][27]. Studies investigating the representation of women in CV trials over the last decade have reported rates ranging from 33 to 38% [26,27].…”

“…The representation of women in clinical CV trials has fluctuated over the past two decades, consistently remaining below 50% [25][26][27]. Studies investigating the representation of women in CV trials over the last decade have reported rates ranging from 33 to 38% [26,27]. A 2019 study evaluating cohort demographics in CV clinical trials published in three major journals (The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association) found that enrollment of women was 21% between 1986 and 1990 and 33% between 2011 and 2015, with a statistically significant increasing trend in enrollment [27].…”

“…Trials for hypertension, diabetes, hyperlipidemia, coronary artery disease, heart failure, and arrhythmia in recent years had significantly lower participation of women relative to the prevalence of these diseases in women [27][28][29][30][31][32][33]. While some studies show improvement over time in the representation of women relevant to their disease prevalence in stroke and heart failure trials, a gender gap remains [26,27]. Female enrollment also varies significantly with trial type, ranging from 31% in pharmacologic trials to 26% in procedural trials [27].…”