(Reuters Health) - Pivotal clinical trials used to win U.S. marketing approval for many new heart drugs didn’t include enough women to clearly assess gender differences in how the medications work, a recent study suggests.
While heart disease is the leading killer of both women and men in the U.S., female patients have long been underrepresented in clinical trials testing new medications, devices and treatment approaches, researchers note in the Journal of the American College of Cardiology. This is problematic because there are sex and gender differences in how heart disease impacts the body, symptoms and treatment outcomes.
For the current study, researchers focused on the numbers of women and men who participated in cardiovascular trials submitted to the U.S. Food and Drug Administration (FDA) to win marketing approvals for 35 medications between 2005 and 2015.
On average, less than half of the participants across all of the studies were women, although the proportion of female patients ranged from 22 percent to 81 percent.
“The participation of both women and men in clinical trials is essential in determining potential sex differences in safety or efficacy of medical products. Sex-based differences may be because of physiological, anatomical (such as body weight), or hormonal differences,” study co-author Dr. Marjorie Jenkins of the Office of Women’s Health at the FDA in Silver Spring, Maryland, said by email.
“Women also may have more adverse events than men because of their smaller size when men and women are given the same doses of a drug,” Jenkins added.
To assess how well studies did at including women, researchers divided the percentage of women among trial participants by the percentage of women with the disease in the general population.
They found women were well represented in trials for drugs to treat atrial fibrillation, a heart rhythm disorder, and high blood pressure. Women were underrepresented in trials for medications to treat heart failure, coronary artery disease and heart attack, however.
Researchers also looked for but didn’t find evidence of gender differences in the safety and effectiveness of drugs tested in the trials, apart from three hypertension drugs whose labels did identify clinically meaningful differences.
While some previous research investigating the lack of women in clinical trials has found screening criteria might exclude too many women, the current study examined this issue and found fewer women may be enrolling in studies because they’re not being invited to participate as often as men.
One limitation of the study is that it only looks at the late-stage trials used to win FDA approval, and it’s possible that proportions of women might be different in more preliminary studies. Researchers also lacked some data needed to determine the full impact of screening criteria on how many women enrolled in studies.
Part of the problem could be that the classic heart disease symptoms common in men, but not always in women, may be the criteria used to include patients in clinical trials, said Dr. Louise Pilote, author of an accompanying editorial and a researcher at McGill University Health Center in Montreal. This means even the women who are included may not give an accurate picture of how drugs will work in many other women.
“In contemporary medicine, neither a pharmacological treatment nor a medical device should be prescribed without a clear evidence of benefit and safety for the patients,” Pilote said by email. “Therefore, testing drugs or devices in a group of patients that includes an adequate representation of women is a must that we can’t deny to guarantee the best treatment for men and women.”