First, the good news: Twenty-two years after Congress ordered the National Institutes of Health to include all women in the clinical trials it funds, women make up more than half the participants.
Now the bad news: According to a new report from the Government Accountability Office, NIH still isn’t able to tell Congress — or anyone else — whether researchers are examining outcomes by sex to see whether men and women are affected differently by what’s being tested. Scientists are required to analyze results by sex in most cases, but NIH has no central process for collecting the information or making it available.
Yet such differences are the reason to include a mix of men and women in clinical trials. A drug or other treatment that works for a man might be less effective for a woman or even harm her. For example, in 2013, the Food and Drug Administration lowered the recommended dose for the popular sleeping pill Ambien after it became clear that the drug took longer to leave women’s systems and could pose a danger the next morning.
The GAO says that NIH can’t assure Congress that it’s supporting research that can “shape improved medical practice for both women and men.” NIH reports spending $30 billion a year on medical research. Most of the money goes to grants to more than 300,000 researchers at about 2,500 medical schools, universities and other research facilities. The agency also supports projects by its own scientists, most of them at NIH’s Bethesda campus.
This is not the first time the GAO has criticized NIH for its implementation of the 1993 mandate that women be included in research trials. In 2000, it said the agency needed to do a better job ensuring “that certain clinical trials be designed and carried out to permit valid analysis by sex.”
NIH officials, reacting to the new report, said improvements are in the works, but they did not specify a timetable. The agency has 60 days to formally respond to the GAO.
Meanwhile, those who fought to require parity in clinical trials have been left sputtering.
“It’s just very frustrating,” said Patricia Schroeder, a Democrat who represented Colorado in the U.S. House. “It reminds me of when you ask your children to move the clothes from the washer to the dryer. Then you go back, and the clothes are still wet, and they say, ‘Well, you didn’t tell me to turn the dryer on.’ ”
Schroeder said she became interested in the subject in the early 1990s, when studies came out showing that a daily aspirin could prevent heart attacks — and when she learned that all the test subjects had been male. “They didn’t even use female rats,” she said.
In fact, under 1977 FDA guidelines that were not changed until 1993, women of childbearing age were not even allowed to participate in drug trials. The ban reflected concerns about the potential for birth defects if a woman was pregnant.
Today, there is growing scientific evidence of just how biologically different men and women are, as well as how differently they sometimes react to drugs and other medical interventions.
“We’re finally able to include women well enough to understand that they express disease differently, that certain risk for disease was different and certain outcomes for disease were different,” said Paula Johnson, a professor at Harvard Medical School and head of the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital in Boston.
Heart disease, Alzheimer’s and lung cancer are examples of how women and men are affected in different ways, she said. “But they’re just examples. These differences occur across all diseases where we’ve asked the question.”
Other research has shown that biological differences go to the most basic level.
“The truth of the matter is men and women are very different at the cellular level, at the molecular level, at the systemic level,” said Doris Taylor, director of regenerative medicine research at the Texas Heart Institute.
Taylor, who has been studying the use of stem cells to treat heart disease, said that there were “very different results if you gave male cells or female cells.”
Given the significant differences recently discovered, it’s actually dangerous not to stratify research results by sex, experts say.
“If you’re mixing those results [from men and women], there will be more noise in the system,” Taylor said. “And you’re going to miss what you might otherwise see as an effect or lack of effect. That is the danger.”
Leaders at NIH say they agree with the GAO’s recommendations and will try to do better. But, as usual in science, it’s complicated.
“It’s a problem because we don’t get to understand whether treatments work as well in women as they do in men, and when things are not reported separately by sex, we also don’t get to see whether there might be some indication of differences in toxicity or adverse events,” said Janine Clayton, head of the NIH Office of Research on Women’s Health.
One big problem, Clayton said, is the lack of information on differences by sex reported in leading medical journals. Of the large clinical trials described in journals, she said, “fewer than one-third had any sex-specific information in the publication.”
Often, that’s because the numbers are so small that the results may not be statistically significant, “and it’s difficult to publish non-statistically-significant results,” Taylor said.
But if those results are made available, researchers could combine them into what’s called a meta-analysis. “We’ve been trying to work with the journal editors for many years on this,” Clayton said.
And NIH is not the only funder of medical research. Private industry, including pharmaceutical companies, pays for many — if not most — later-stage clinical studies. Privately funded studies also do not follow all NIH rules.
Meanwhile, in light of recent discoveries about biological differences by sex, Clayton says NIH is moving to require more basic, preclinical studies to use both male and female animals or cells in an effort “to make sure that sex as a biological variable is accounted for in the design, analysis and reporting” of all research funded by the agency.
That requirement takes effect in January.
This article was produced by Kaiser Health News, an editorially independent news service of the nonpartisan Henry J. Kaiser Family Foundation.