Women remain underrepresented in cardiovascular clinical trials despite initiatives to ensure broader inclusivity. This is according to two reports, both published in the last week, suggesting that lack of representation may limit availability of treatment data for combating cardiovascular disease in women.
“Historically, drug therapies for women were determined based on male data that was extrapolated to women,” said Leslie Cho (section head of preventive cardiology and cardiac rehabilitation at Cleveland Clinic, Cleveland, USA) lead author of a study in published in the Journal of the American College of Cardiology (JACC) which sought to understand the current barriers to enrollment and retention of women in clinical trials. The report was commissioned by the American College of Cardiology (ACC) Cardiovascular Disease in Women Committee.
In the report, Cho and colleagues present eight potential barriers to optimal enrollment of women and underrepresented minority women, including:
- Differential care—Low rates of referral to cardiologists and specialty programs for more aggressive care leads to fewer women being treated by specialists recruiting for clinical trials.
- Ageism—Older patients are disproportionately represented in clinical trials overall, which is further compounded in women as cardiovascular disease is very prevalent in older women.
- Lack of awareness, trust and logistical barriers—Previous surveys and studies have shown that women are more reluctant than men to participate in clinical trials.
- Lack of diversity in clinical trial leadership—Women are underrepresented in clinical trial leadership, and research has shown that trials led by women tend to recruit more women participants.
- Underrepresented minority women in cardiovascular clinical trials—Clinical trials that enrolled predominantly racial/ethnic minority groups have proven that it is possible to have representation of underrepresented groups in clinical trial leadership, enrollment and retention; however, rates of minority representation in the majority of major cardiovascular trials remains low.
- Special consideration for pregnant women and women of childbearing age—Pregnant women and women of “child-bearing potential” are frequently excluded from clinical research as a vulnerable population, resulting in not only reduced numbers of eligible women, but a lack of data on how certain drugs impact pregnant patients.
- Sex differences in disease—Women have a higher risk of developing certain types of heart disease and/or present with different symptoms than men when experiencing heart disease, potentially leading to lower numbers of women in clinical trials studying less prevalent types of heart disease.
- Study retention—Little is known about potential sex differences in study drug discontinuation and patient follow up once patients are successfully enrolled since reasons for study drug discontinuation and withdrawal of consent are not routinely captured in clinical trial case reports.
Recommendations for breaking down each barrier were also presented in the report.
“To address barriers to recruitment and retention of women in cardiovascular clinical trials, a comprehensive and targeted approach that involves partnership with all stakeholders—patients, referring clinicians, research teams (investigators and coordinators), healthcare systems, the FDA [US Food and Drug Administration], payers, sponsors, professional and community organisations—is essential,” Cho said. “We owe it to our patients to increase representation of women and underrepresented minorities in cardiovascular disease trials.”
In a separate paper, published in the European Heart Journal, author Jeske van Diemen (Amsterdam University Medical Centre, The Netherlands) and colleauges highlight the barriers to recruiting women into clinical trials and potential solutions.
The authors stated: “Although there have been significant advances in reducing cardiovascular disease-related morbidity and mortality in both sexes, the current guideline-directed therapies are based on data that predominantly include male patients. Consequently, in cardiovascular disease management women patients might currently be treated equally (the same), however, they are not treated based on equity (i.e. based on their health needs).”
“For many years it was usual practice that studies on heart disease primarily included white men,” said van Diemen. “It was assumed that the results were also relevant to women and other races but evidence is emerging that this is not the case. For instance, female heart patients have a greater risk of adverse drug reactions compared with male patients, and these reactions are generally more serious. Similarly, it has been suggested that women with heart failure may need lower doses of medications than their male counterparts.”
She added: “Within our own research group we noticed how hard it was to recruit women. We therefore decided to examine current evidence on reasons to agree or decline participation, with the aim of coming up with solutions to increase gender balance in cardiovascular trials.”
The authors performed an extensive literature search for articles addressing the motivators, facilitators and barriers to enrolment and continued participation. They found just six studies including a total of 846 men and 1,122 women.
Regarding motivators, for both men and women these included the possibility of accessing better and more continuous care, and altruistic values such as the desire to promote science. None of the studies reported on facilitators to improve sign-up rates in women. But the authors noted that a high socioeconomic position was associated with an increased willingness to participate among women. They said that this may marginalise women with a lower socioeconomic position, who stand to benefit the most from better representation.
Regarding barriers, both men and women reported time constraints, apprehension towards being in a clinical trial with an experimental design or therapy, and the potential for an unfavourable outcome or risk of harm. Women declined more often because they perceived a higher risk of harm from trial participation than men. In addition, women more often than men reported transportation problems as a reason to decline trial participation.
As for recommendations, the authors called for more research into the reasons why women agree or decline to take part in cardiovascular studies so that appropriate interventions can be developed to boost attendance. Scientific journals should publish focused issues on sex and gendered data in cardiovascular disease to stimulate research in this area.
Increasing the diversity of research teams was another potential solution—with women constituting just 10% of clinical trial leadership committees in cardiovascular studies published in three medical journals. The authors said that a diverse workforce is better able to understand diverse populations and tailor its research to participants. To this end, involving women in the design and conduct of cardiovascular trials may aid recruitment. Logistical support could also help, such as transportation to clinical trial sites and onsite childcare.
van Diemen said: “It was an eye opener for me that women seem to have a different assessment of the risks involved in participating in trials, and consider it riskier than men do. In addition, women more often have barriers which make it difficult to attend follow-up appointments—such as not holding a driving licence or caring for grandchildren.”
“We are now firm believers in participatory research, which means involving patients in the design and conduct of a trial including what is manageable for those taking part,” she added. “For instance, study interviews could be conducted by video call and research teams could collect samples from patients’ homes to reduce the time commitment and avoid the need to travel.”
She concluded: “Currently we treat many patients as if they were the same, which of course is not the case. Study populations that better represent the demographics of society should lead to more relevant findings that improve cardiovascular outcomes for everyone.”