Medical research has for years disproportionately focused on male subjects, resulting in a lack of data on women’s health. Even in the preclinical phase, the animals and cells used in research are mostly male. Scientists say that despite decades of concern about exclusion from clinical trials, women remain underrepresented. And there is evidence that women suffer as a result.
A history of the exclusion of women from medical research
Women have always been overlooked in medical research, but their deliberate exclusion became enshrined in policy in the 1970s. In 1977, the Food and Drug Administration issued a policy recommending that women of childbearing age be excluded from Phase I and early Phase II drug trials. This was in response to a widespread tragedy involving the drug thalidomide, according to the National Institutes of Health (NIH) Office of Women’s Health Research (ORWH).
The morning sickness drug was used in Europe and Australia and caused more than 10,000 deaths and birth defects in babies in the 1960s. Although the drug was not approved in the United States, the incident prompted researchers to become more cautious about including women in trials. FDA guidelines were broad, including “women who used contraception, who were single, or whose husbands had undergone vasectomies.”
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This policy was a major setback for the inclusion of women in medical research, but nearly a decade later, after protests and pushback, the NIH reversed its decision. In 1986, the NIH issued a policy encouraging researchers to include women in their studies, and three years later, it issued a memorandum on inclusion that stated that research requests should encourage the inclusion of women and minorities. Still, this policy change was not enough to turn the tide after decades of exclusion.
In 1990, the Congressional Caucus for Women’s Issues asked the General Accounting Office (GAO) to investigate the implementation of NIH guidelines on including women and people of color in the studies it funded. The GAO reported that the policy had been “poorly communicated and inconsistently applied” and “applied only to outside research,” according to the NIH Office of Research on Women’s Health. It also found that the NIH had “done little to encourage researchers to analyze study results by sex.” Two months later, the NIH created the ORWH to oversee implementation of the policy. It was not until 1993 that Congress wrote the policy into a section of the NIH Revitalization Act of 1993.
The consequences of ignoring women in clinical trials
Despite changes in the law, progress has been slow over the past 30 years. Bias against female subjects begins to creep in “in the development phase, years before drugs reach patients,” according to the Financial Times. Scientists say that at times preclinical testing has disproportionately focused on male animals and male cells. When drugs reach the human testing stage, women are still underrepresented. Part of this ongoing exclusion stems from the thalidomide scandal, which “casts a long shadow,” the newspaper said. “On a more prosaic note: caregiving responsibilities may make it difficult for women to commit the time a trial often requires.”
As a result, women are prescribed drugs that are sometimes less safe and less effective than those for men, researchers say. By focusing safety and tolerability studies on male bodies, “you develop doses of these drugs based on the male body,” which “is generally larger and heavier but also has a different percentage of fat,” Jill Fisher, a professor of social medicine at the University of North Carolina’s Center for Bioethics, told the Financial Times.
Research supports the notion that women suffer from this male-centered approach to drug development. Since 2000, women in the U.S. have been 52 percent more likely than men to report “adverse events,” defined as “any untoward medical occurrence,” and 36 percent more likely to report serious or fatal events, according to Food and Drug Administration data collected by the McKinsey Health Institute.
“Historically, the white male body was seen as the scientific norm, so there was a sense that ‘everything we find in men also applies to women,'” Fisher said. This assumption, which is also reflected in the lack of ethnic diversity, is “very difficult to change in scientific culture.”
The underrepresentation becomes “particularly striking” when compared with the “proportion of women suffering from the disease that a particular drug is intended to treat,” according to the Financial Times. Study 2022 A study conducted by researchers at Harvard Medical School found that women made up about 40% of clinical trials for three diseases that most commonly affect women, even though they make up 51% of the U.S. population.
Researchers and clinicians include men and women in their clinical trials, but not in a “balanced manner or in a way that reflects the prevalence of the disease,” Melina Kibbe, a surgeon and dean of the University of Virginia School of Medicine and a longtime advocate of gender-equitable research, told the news agency.
Trying to reverse the trend
The White House has noted the lack of attention to women’s health in medical research. In November 2023, the President and First Lady launched the White House Women’s Health Research Initiative, with First Lady Jill Biden taking the lead. “Women’s health research has been underfunded for decades, and many conditions that primarily or only affect women, or affect women differently, have received little to no attention,” the First Lady said in announcing the initiative. The gaps are “even greater for communities that have historically been excluded from research — including women of color and women with disabilities.” In February, she announced $100 million in funding for women’s health research and development as part of the initiative, and the President signed a Implementing Regulation in March, including an additional $200 million for research at the NIH.
Although there are policies in place to encourage more comprehensive research, the NIH has struggled to enforce them. “We know less about female biology and are struggling to catch up,” Janine Clayton, director of the NIH Office of Women’s Health Research, told The GuardianTo break this pattern and increase the number of places available to excluded populations, federal policies would need to be better enforced and more women scientists would need to be hired for research, especially in senior positions. “Women, people from different backgrounds, ask different questions,” Clayton said.
To make medical research more diverse, researchers need to rethink how they recruit and retain participants and potential collaborators. In medical clinics, “people often don’t see anyone who looks like them,” Danielle Mitchell, CEO and founder of Black Women in Clinical Research, told the Association of American Medical SchoolsThis is a missed opportunity to build trust, especially in communities that have historically faced health care disparities, she argued. “From my perspective, we need to have these difficult conversations with people about what happened in the past in order for people to consider clinical trials as a health option.”
Progress is slow, but in the meantime, underrepresented groups should continue to ask questions and put pressure on drug development as a whole. “Pharmaceutical companies – and all of us – need to recognize that the group most at risk of side effects is the gender that is often left out,” Teresa Woodruff, president emeritus and MSU Foundation professor at Michigan State University, told the Financial Times. “And right now, that’s women.”
