Glaring gaps persist in medical researchers’ efforts to understand gender differences in common diseases, two decades after the passage of pivotal legislation mandating that more women be included in government-funded clinical trials, according to a report being released Monday at a women’s health summit in Boston.
The authors said research still lags on understanding how treatments for heart disease — the number one killer of women — affect the sexes differently, because women make up only one-third of the participants in clinical trials to test drugs and medical devices, and most of these studies don’t report results for men and women separately.
Women who don’t smoke are, for unknown reasons, three times more likely than nonsmoking men to get lung cancer but are still less likely than men to enroll in lung cancer studies, notes the report from Brigham and Women’s Hospital. And twice as many women suffer from depression as men, but less than 45 percent of animal studies to better understand anxiety and depression use female lab animals.
“Women are now routinely included in clinical trials, but we are far from achieving equity in biomedical research,” said report leader Dr. Paula Johnson, executive director of the Brigham’s Connors Center for Women’s Health and Gender Biology.
To address research disparities, the authors recommend that government agencies, drug manufacturers, hospital review boards that approve studies, and medical journal editors institute substantial changes to make women’s health a research priority.
They called for:
■ Hospital institutional review boards to require research plans to include a relatively equal number of male and female human and animal subjects;
■ The Food and Drug Administration to require studies that investigate gender differences in how well a new drug, device, or diagnostic test works before it gets approved;
■ Labels of drugs and devices to state whether they were adequately tested in women;
■ Medical journals to insist that studies they publish address gender when reporting results.
“We’ve barely scratched the surface in terms of understanding sex differences across all diseases,” said Brigham president Dr. Elizabeth Nabel, who will be speaking at the summit along with FDA Commissioner Dr. Margaret Hamburg and other health leaders. “This issue needs to stay on the front burner.”
Johnson said many people have grown complacent, thinking “the women’s health issue was taken care of years ago because of all the attention we paid to specific women’s diseases like breast cancer. This has caused some missed opportunities.”
The result is that certain treatments may not work as well in women as in men. For example, women accounted for only 15 percent of the participants in a 2002 study published in the New England Journal of Medicine that examined the effectiveness of a Boston Scientific implantable defibrillator in preventing deaths among people with heart failure. Yet the FDA later approved the device to be used in both genders. A subsequent 2009 study combining all the scant data from females who participated in various defibrillator trials found that the device offered no lifesaving benefits for women, said Dr. Rita Redberg, a cardiologist and editor of the journal JAMA Internal Medicine.
Women get heart disease, on average, about a decade later than men and tend to have diseases such as diabetes and osteoporosis, which could partly explain why the defibrillator device does not work as well in women.
‘We’ve barely scratched the surface in terms of understanding sex differences across all diseases.’
“I attended an FDA workshop five years ago where the agency seemed receptive to mandating that more women be included in medical device trials,” Redberg said. “But that still hasn’t happened. The perception among industry sponsors who attended this workshop was that it’s harder and more expensive to enroll women in these trials.”
Some researchers said they are working to include more women in studies. “I do completely agree that women are under-represented in most clinical trials involving heart devices, but we’re trying to change that,” said Dr. Jagmeet Singh, a cardiac electrophysiologist at Massachusetts General Hospital.
A study Singh is leading to test a Boston Scientific device to correct dangerous arrhythmias in cancer patients whose hearts were damaged by chemotherapy will recruit “at least 80 percent women,” he said, because many of the people with such problems were previously treated for breast cancer. Other device studies Singh is involved in have set 50 percent as the goal for female recruitment, he said.
Adequate testing of new drugs in women also remains a problem. Last year, the FDA had to cut in half the recommended dosage of the insomnia drug zolpidem (Ambien) for women, after the larger dose was associated with auto accidents the next morning blamed on lingering impairment that affected 15 percent of female users compared with only 3 percent of males. That finding was made more than two decades after Ambien was first approved by the FDA.
“Labeling drugs that have not been adequately tested in women would incentivize both companies and the FDA to conduct evaluations to determine gender differences,” said report coauthor Susan Wood, director of the Jacobs Institute of Women’s Health in Washington. Such labels exist for drugs not tested in children, as mandated by Congress. Legislation may also be necessary to require labels based on gender, said Wood, who used to work for the FDA.
The FDA issued a statement saying, “Last year we looked at all of the biological products, drugs, and high-risk medical device applications approved in 2011 and found that every application contained information on the sex of the clinical trial participants.”
The agency added that officials are working on a plan to determine how to ensure that more women and minorities are included in trials of new medical products, which they intend to release in late summer, and that they “have taken note of the Connors Center report and will consider any notable finding as we develop our plan.”Deborah Kotz can be reached at firstname.lastname@example.org. Follow her on Twitter @debkotz2.