There is a lack of sex-specific safety and effectiveness data for high-risk cardiovascular devices before FDA approval and more rigorous FDA requirements for these data before device approval could present an opportunity to improve cardiovascular outcomes, according to a study published online March 1 in Circulation: Cardiovascular Quality and Outcomes.
The study noted that attempts have been made since 1985 to include more women in research trials. An audit in 2000 by the Government Accountability Office found that NIH-funded trials include women proportionate to their numbers in the general population, "but valid analysis of results by sex was still wanting, and there was scant evidence that NIH staff and reviewers were implementing the requirement."
In 1994, the FDA established the Office of Women's Health and that same year, the Center for Devices and Radiological Health instituted a policy to address the possibility of "gender bias in submissions and review documentation for new medical devices."
However, there have been no analyses of gender bias in studies submitted for FDA approval of medical devices, the study noted.
To help bolster the data, Sanket S. Dhruva, MD, and colleagues from the University of California, San Francisco, performed a systematic review of the demographics, comments on gender bias and analysis of results by sex for all 123 studies from 78 high-risk cardiovascular devices that received premarket approval by the FDA between 2000 and 2007.
"Although gender bias comments or analyses are required by the FDA for all studies, they were present for only 41 percent of studies," researchers found.
In 93 studies where the gender of participants was noted, there was a mean of 67 percent men. Overall, 88 percent of the studies enrolled more men than women and there was no increase in the enrollment of women over the eight-year period.
In addition, researchers found that each increase in mean age of 10 years was associated with a 5 percent decrease in the percentage of women enrolled.
Studies examining electrophysiology devices in particular included more men than those examining intracardiac devices, such as heart valves and atrial and ventricular septal occluders (72 vs. 52 percent, respectively).
Of the overall 123 studies, 51 had a gender bias comment or analysis and only one comment referred to more women enrolled than men, according to the authors. One study was excluded from further analysis because it enrolled fewer than 50 patients. Forty-seven of the 50 with comments discussed an examination of any study results by sex and about one-fourth of these studies described some difference in device safety or effectiveness by sex.
The difference in study sex proportions in about one-fourth of the 123 studies were explained as reflecting the "disease distribution or referral for that or similar procedures." The authors noted that this was sometimes inaccurate.
For instance, a trial enrolling 86 percent men noted that the "occurrence of AAA [abdominal aortic aneurysm] disease is known to be higher in men than women and the ratio of men to women enrolled in this study reflects the general population."
Dhruva et al say that a study referenced by the authors of the AAA trial does not support their assertion about sex distribution in AAA. In studies that do look at demographics, women comprise 22 to 25 percent of patients with AAAs, Dhruva et al said.
They cite another example regarding implantable cardioverter-defibrillators (ICDs) in which 15 women out of 126 patients were enrolled. The authors of the ICD study explained, "The relatively low percentage of females enrolled into the study is related to the incidence of heart disease. If females were just as likely to have heart disease as males, then you would expect the percentage to be much closer to 50 percent."
Dhruva et al said that this statement inaccurately implies that there is a very low percentage of women with heart failure and that is why the trial enrolled few women.
Researchers also noted that some statements simply imply they accept the status quo as the reason for low numbers of women enrolled. Other statements make note of the low referral rate for women for device-related procedures. Dhruva et al suggested that this may be due to "less use of specialist consultation for women with coronary artery disease and congestive heart failure than for men."
The authors concluded that ongoing FDA workshops around the topic and legislation