Cardiovascular medicine made impressive advances in the second half of the 20th century, including a 59% reduction in coronary deaths. At the same time, women’s cardiovascular mortality rate increased and surpassed that of men. Women have not realized the same benefits from cardiovascular research as men have. This may be due, in part, to bias in cardiovascular studies.
A recent study highlights the fact that women are underrepresented in some types of cardiovascular drug studies. For example, 35 drugs were approved for multiple cardiovascular conditions between 2005 and 2010. These include treatments for myocardial infarction, atrial fibrillation, coronary artery disease, heart failure, hypertension, and pulmonary arterial hypertension. While women were well-represented in hypertension, atrial fibrillation, and pulmonary arterial hypertension studies, they were underrepresented in heart failure, coronary artery disease, and acute coronary syndrome studies.
An earlier study found similar gender bias in preclinical cardiovascular device studies. This raises questions for medical affairs professionals — specifically, how should Medical Affairs professionals assess and use such studies?
Evaluating Gender Bias in Clinical Studies
The potential of gender bias should be assessed for each individual study. The previously-mentioned research on women’s participation in cardiovascular drug studies found that the percentage of female participants ranged from 22% to 81%, so one cannot make generalizations about participation by gender. For example, while women are underrepresented in some studies, they were overrepresented in pulmonary arterial hypertension. This was true whether the percentage of women was examined using a participation ratio and a participation-to-prevalence ratio. (Since the prevalence of a particular disease may vary by gender, the prevalence of each gender in the disease population should be taken into account by using a participation-to-prevalence ratio.)
Another factor to consider is the age distribution of women in a study. Female participants are predominantly post-menopausal yet women of reproductive age also experience cardiovascular disease.
Biases in Clinical Application
With the increasing importance of real world evidence, researchers should consider the impact of biases that may arise in clinical settings, especially with regards to how drugs are prescribed. For example, cardiology guidelines recommend high-dose statins for male and female patients under 75 years of age with established heart disease. One study found that less than 50% of women who used statins following a heart attack were prescribed high-dose statins. The researchers also noted that “underutilization of these drugs in women was not explained by sex differences in demographics, comorbidities, or health care utilization.”
Implications of Gender Bias in Clinical Studies
The impact of gender bias in clinical studies requires further examination. Studies in which women are underrepresented may still have sufficient statistical power to provide useful information. In the recent study of participation of women in cardiovascular studies, the authors concluded, “In our assessment, for purposes of regulatory decision making, participation of women was sufficient to assess possible gender differences in safety and efficacy.”
However, other studies have noted that, “despite increasing evidence that an individual’s sex is one the most important modulators of disease risk and response to treatment, consideration of the patient’s sex in clinical decision making (including the choice of diagnostic tests, medications, and other treatments) is often lacking.”
Medical Affairs professionals should not be expected to settle open questions in cardiovascular research but awareness of the potential for gender bias and the issues around it may help inform their practice.