What Women Want

The under-representation of women in clinical studies is a topic that comes up time and again. The FDA annually reviews the extent to which women are enrolled in clinical trials supporting new molecular entity submissions, led by the agency’s Office of Women’s Health, and there is definitely an upward trend; women made up 39 percent of late phase trial participants in 2000, but by 2015 this had risen to 52 percent. However, numbers of female participants are significantly lower in cardiovascular trials; for example, acute coronary syndrome, coronary artery disease and heart failure.

Marjorie Jenkins from the FDA’s Office of Women’s Health and co-authors recently examined women’s participation in pivotal cardiovascular disease trials submitted to the FDA in support of marketing applications (1). “In recent surveys of coronary artery disease and ACS trials, participation of women ranged between 25 and 33 percent. Under enrollment of women in these areas has been attributed to under enrollment of elderly patients and the presence of comorbidities, such as diabetes,” says Jenkins.

Men tend to have more heart attacks than women, but women have a higher heart attack death rate and experience higher bleeding rates during percutaneous coronary interventions performed through femoral arterial access. Women are also more susceptible to drug-induced cardiac arrhythmias.

Although women were under-enrolled in several cardiovascular disease areas, the absolute number of women who participated in the clinical trials reviewed was still sufficient to inform FDA approval of safe and effective cardiovascular drug treatments for both men and women. “But a better understanding of the reasons why women are not invited, or if invited do not participate, could lead to more successful engagement and recruitment of women in clinical trials and result in increasing participation of women in certain clinical trial areas,” says Jenkins.

The study analysis indicated that when women are screened and enrolled in clinical trials, their percentage participation is roughly equivalent to that at the conclusion of the study. Jenkins and co-authors hypothesize that there are unknown factors in the “pre-screening” environment whereby women are not being invited or considered for clinical trial participation. “This is a gap in knowledge and an area of research needed in order to better clarify why women’s participation is lower in some types of cardiovascular clinical trials,” says Jenkins. “Advanced age at disease onset may contribute to under-enrollment of women. And so prevalence-adjusted representation of women in cardiovascular clinical trials across relevant age categories is also an area for future inquiry.”

The FDA and its Office of Women’s Health are leading a number of initiatives, with the overarching aim of encouraging the inclusion of more women in clinical trials. “In the past 20 years we have seen great improvement in women’s participation in clinical trials. Since 1998, the FDA has required reporting of clinical trial data for drug approvals by gender, race and ethnicity, and age,” says Jenkins. “When clinically meaningful differences between men and women are seen, these are considered as a part of how we balance risk and benefit, and how we label medicines.”