A new study has found that the vast majority of heart devices, including heart valves, pacemakers, defibrillators and stents, approved for use in the U.S. were not adequately tested in women. This is a problem because differences between men and women in size and bleeding tendencies can impact how these heart devices perform, according to the study’s authors. The heart device study was published online March 1 in Circulation: Cardiovascular Quality and Outcomes.
A press release announcing the publication of “Gender Bias in Studies for Food and Drug Administration Premarket Approval of Cardiovascular Devices” points out that in 1994, the U.S. Food & Drug Administration (FDA) issued a directive requiring that submissions seeking new device approval must contain a gender-bias statement explaining whether the proportion of men and women in the study reflects the proportion of men and women who have the condition being treated. The directive also required that approval submissions detail differences in the safety and effectiveness of the device in women.
But it appears many heart device manufacturers are flouting the FDA’s 1994 directive. To reach their conclusions, Dr. Rita F. Redberg of the University of California San Francisco and colleagues conducted a systematic review of the demographics, comments on gender bias, and analysis of results by sex for 78 high-risk cardiovascular devices that received premarket approval by the FDA between 2000 and 2007. They found that only 41 percent of all the studies even had a gender bias statement, and of those, 26 percent identified some difference in safety or effectiveness by sex.
According to the researchers, 34 of 123 studies did not even report the sex of the subjects enrolled. Of the studies that did report the sex of participants, the study populations were, on average, 67 percent men. There was no increase in the enrollment of women over time.
In the applications for approved devices they reviewed, the study’s authors found instances in which researchers used inaccurate grounds to exclude women. In some cases, the proportion of women with a heart condition was understated. In others, applicants declared their gender breakdown to be equivalent to previous studies without acknowledging that the previous studies included a disproportionately low number of women.
The researchers conclude:
“There is a lack of sex-specific safety and effectiveness data for high-risk cardiovascular devices before FDA approval. The justifications for this lack of evidence may perpetuate the status quo. More rigorous FDA requirements for sex-specific data before device approval could present an opportunity to improve cardiovascular outcomes.”
“We found no encouraging trends,” lead author Redberg said. “Failure to include women in clinical trials has been a big problem for a long time and it isn’t improving, so further action is needed.”
Redberg advocates strict enforcement of the current FDA requirements, and said the agency should send medical device applications back without review until the required statements are submitted.