Too few clinical trials of cardiac devices adequately address safety and efficacy in women, despite long-standing requirements by the FDA to do so, a review of premarket approvals showed.
Women consistently made up only about one-third of participants in clinical trials of 78 high-risk cardiovascular devices that made it to market from 2000 through 2007, reported Rita F. Redberg, MD, MSc, of the University of California San Francisco and colleagues.
Only 41% of the studies reviewed by the FDA made some mention of gender bias in summaries of evidence, and only 26% of those that did noted some difference in safety or effectiveness by sex -- supporting the importance of such analyses, Redberg's group wrote in the March issue of Circulation: Cardiovascular Quality and Outcomes.
Such incomplete safety and efficacy data for women "may mean that more women are experiencing adverse events for a device lacking a mortality benefit," the researchers warned.
Redberg's group pointed to implantable cardioverter-defibrillator registry data showing a higher likelihood of in hospital and major adverse events for women compared with men.
The researchers also found no mortality benefit in primary prevention for women with heart failure.
The justifications given for the failure to adequately address gender just perpetuate the status quo, Redberg's team added.
For example, they noted, one heart failure study enrolled only 22% women -- despite equal representation of women among Medicare patients with impaired left ventricular function, which the study gave as an explanation that these demographics were typical for a U.S. device trial.
The National Institutes of Health and the FDA have been calling for inclusion of women in trials since the mid-'80s, including a specific directive from the FDA in 1994 requiring that device approval applications address the ratio of men and women in premarket studies and differences in safety and effectiveness by gender.
The researchers systematically reviewed all 78 such data summaries released to the public for class III cardiovascular devices approved from 2000 through 2007.
Men accounted for 67% of patients in the studies included in the FDA's Summaries of Safety and Effectiveness Data (SSED), ranging from 28% to 92% across the studies -- but without any increase in the proportion of women across the entire eight-year span (P=0.957).
Nor did the proportion of studies with analyses by sex or comments on gender bias increase over the review period (P=0.490).
Of the 123 studies, 28% did not even report the proportions of men and women. Of those that did, almost half didn't report the proportion for all the patients enrolled, "which suggests an important source of missing data," according to the researchers.
"Raw data or statistical analyses rarely were provided, and sex-specific analyses of study primary end points were even less common," they added in the paper.
Resolving this situation may take further action by the FDA, Redberg and her colleagues suggested.
The agency has been working on a guidance document for study and analysis of gender differences in cardiovascular device trials; an act pending in Congress could go even further in mandating an end to the disparities, they noted.
Redberg's group cited several limitations to their study, including reliance on the publicly available SSEDs and Circulatory System Device Panel meeting materials as data sources, so "it is possible that these data are not comprehensive and that sex-specific data were reviewed and taken into consideration during device review but not included in the SSED or panel notes."
They further noted that SSEDs and the device panel meeting notes "are the only publicly available data source and, thus, provide the only available sex-specific data ..." and although they used the specific language in SSEDs referring to gender bias, the study did not evaluate bias in the device approval process itself "but, rather, gender-specific and related data."
