Women—especially those in their early-to-mid-sixties and those with a heart failure diagnosis—continue to be underrepresented in cardiovascular clinical trials, according to a study that found just over 38% of all CV trial enrollees between 2010 and 2017 were female.
Xurui Jin, MD, and colleagues called the appropriate representation of women in clinical trials “a worrisome issue” in their Circulation report, noting that CVD remains the leading cause of death for women in just about every developed country. Previous studies have suggested that a minority of clinical trial patients are female, with one systematic review of 325 cardiovascular trials estimating that one in every three study enrollees were women. After adjusting for age- and sex-specific differences in disease prevalence, though, the study’s authors revealed their estimates were actually lower than expected, ranging from 3% to 13% female participation across a spectrum of heart conditions.
“Previous studies have analyzed trials based only on the journal or regulatory agency size, potentially biasing results and explaining the inconsistencies among different studies,” Jin et al. wrote in the present analysis. “Conversely, none of them have performed a comprehensive review of all registered trials regardless of journal impact factor, geography or size.”
So the team drew on data from ClinicalTrials.gov for their study, extracting publicly available information about disease type, sponsor type, country, trial size, intervention type and demographics from cardiovascular trials completed between 2010 and 2017. They identified 740 completed trials that comprised a total of 862,652 adults.
Of those hundreds of thousands of patients, the authors reported, around 38.2% were women. The median female-to-male ratio for each trial was 0.51—0.32 in the 25th quartile and 0.90 in the 75th quartile—but varied by age group, type of intervention and disease type. Calculated ratios were:
- 1.02 in women 55 years old and up vs. 0.40 in women aged 61-65 years
- 0.44 for procedural trials vs. 0.78 for lifestyle intervention trials
- 0.34 for acute coronary syndrome vs. 3.20 for pulmonary hypertension
- 0.45 for trials located in the Western Pacific vs. 0.55 for trials in the Americas
- 0.14 for government-funded trials vs. 0.73 for multiple sponsors
- 0.56 for smaller trials vs. 0.49 for larger trials
Jin and colleagues said that, relative to women’s prevalence in the disease population, their participation prevalence ratio was higher than 0.8 for hypertension and pulmonary arterial hypertension trials, suggesting comparable prevalence and good female representation. However, it was lower than 0.8 for arrhythmia, coronary heart disease, acute coronary syndrome and heart failure trials.
“The lower participation rate of women in cardiovascular clinical trials logically begs the question, ‘Why don’t women participate in trials at rates similar to men?’” the authors wrote. “Hypothetically, multiple opportunities exist for a patient to fall out of the enrollment pathway, and several of these opportunities can likely be influenced by both patient-related and trial site-related factors.”
The team said women need to first be made aware of the opportunity to participate in clinical trials, which they often aren’t. They also need to have sufficient access to centers participating in trials, which can require referrals and create challenges for work, transportation and child care—and they need to be comfortable with the clinical trial process itself.
“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,” Jin et al. wrote.
“These findings provide key insights into factors impacting women’s representation in cardiovascular trials, including both success factors as well as areas where women remain underrepresented. Future efforts should build on previous successes and target key areas for improvement with multifactorial approaches to enhance recruitment of women.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.