March 1, 2011 -- Despite federal mandates to include more women in research studies, women are often underrepresented in trials evaluating cardiac stents, implantable defibrillators, and other high-risk cardiac devices.
The findings, which appear in Circulation: Cardiovascular Quality and Outcomes, reflect many of the sentiments expressed in the 2011 update to the American Heart Association’s cardiovascular prevention guidelines for women. The new guidelines call for more male- and female-specific results, especially regarding risks from preventive therapies such as aspirin.
Official efforts aimed at including gender-specific information in studies dates back to 1994, when the Center for Devices and Radiological Health enacted a policy to address gender bias in submission forms for new medical devices. This is the same year that the FDA established the Office of Women’s Heath.
More Than 50% of Studies Don’t Include Gender Analysis
Researchers analyzed 123 studies of 78 cardiac devices that received pre-market approval from the FDA for men and women from 2000 to 2007. Of 123 studies, there was no information on the sex of participants in 28% of studies. Among those that did report gender, 67% of participants were men, on average.
The FDA had instituted a policy to analyze gender bias in all device applications, but more than half of these studies did not include such an analysis. Twelve of 47 studies that did include this summary noted that there was a difference seen in the device’s safety or efficacy in women, compared with men.
There was no uptick seen in the number of women enrolled in studies over the course of the study.
Many Reasons for Gender Gap in Studies
Why the gender gap? The study authors suggest that the number of women with certain heart conditions may be underestimated. Researchers who have had approved applications have also said that their gender breakdown was similar to that of an older study without acknowledging the older study included greater proportions of men. Women may be less likely to be referred to specialists, which could also affect recruitment.
Study authors, who were led by Rita F. Redberg, MD, professor of medicine and the director of Women’s Cardiovascular Services at the University of California in San Francisco, call for meaningful changes to the study review and approval process.
They also suggest that approval applications be returned to the sender unless gender-specific data are included.
Room for Improvement
“We still have a long way to go to make sure that therapies are tested in women,” says Nieca Goldberg, MD, director of the Women’s Heart Program at New York University’s Langone Medical Center in New York City. “We need to make it easier for women to become aware of clinical trials and make it easier for them to enroll.”
She says that “we pretty much have a lot of data on aspirin and statins and a lot of women should be on statins or aspirin and some shouldn’t be,” she says. “This situation is one where we have a therapy indicated for a special reason and we may be using it in women when we don’t have as much information about the risks and benefits for them.”
“There is increased awareness about heart disease in women, and we have come a long way in that many more studies look at women,” she says.
Although there were no encouraging trends seen in the new study, a recent report did show that cardiac resynchronization therapy with a defibrillator is more effective in women than in men.
“We need more studies like this,” she says.
None of the information in the study should be taken as a reason for women to refuse treatment with a heart device. “If women meet guidelines for pacemakers because their heart is too slow or needs a defibrillator because she has a potentially fatal arrhythmia (heart rhythm abnormality), these are important indications and we should not withhold them,” she says.
“We just need to evaluate each candidate individually,” Goldberg says.
“If a woman is being told she needs a device, she almost certainly does,” says Cynthia Tracy, MD, director the Electrophysiology Laboratories at the George Washington University Hospital in Washington, D.C.
Going forward, "we want to resolve some of the unanswered questions about whether women benefit as much as men from these devices,” she says.
The study designs may make it hard to get women into the study because the way women present symptoms can be different than men, which can make recruitment challenging, she says. “We have to have enough women with equivalent disease in order to compare equivalent outcomes to force the issue and make sure that women are being recruited appropriately,” she says.
Women also need to be empowered with information on clinical trials.
“Some women see trials as a way of providing themselves excellent care, but some view clinical trials as human experiments and can be intimidated,” she says. “When we have a patient who has that instinct, we need to explain the risks, benefits, and treatment alternatives and explain why we are trying to recruit.”
Informed consent is paramount. “We must be very sure the person knows what is going on and why they are being recruited,” she says.
Lack of Sex-Specific Data Can Be Dangerous
“It seems like women are still not taking heart disease personally and advocating for themselves [and] this leads to under-referral and under-diagnosis of heart disease, which may lead to delays in discovery of safety and efficacy concerns regarding new devices,” says Pam Marcovitz, MD, medical director of Ministrelli Women’s Heart Center at Beaumont Hospital in Royal Oak, Mich.
“Unfortunately, this lack of sex-specific data reporting only serves to perpetuate the old myth that heart disease is a man's disease,” Marcovitz says.
“This is 15 years after the FDA, National Institutes of Health, and Congress strongly recommended addressing gender-specific issues, and we are still treating women as small men,” she says. “We should all be outraged by this.”