Women and clinical trials: The importance of inclusion in research studies

Clinical trials are research studies that test if a new therapy is safe and effective for patients. Therapies that make it through the rigorous approval process are tested on tens of thousands of people, and it’s important that the treatment is tested on the populations who will actually use it. Women, however, have been underrepresented in these trials. We look at why women have historically been excluded from clinical trials and why it's so critical that men and women are equally represented in research.

A brief history of women’s participation in studies

Regulators have historically taken a cautious approach to female participation in clinical trials. In 1977, a Food and Drug Administration (FDA) policy recommended excluding women of childbearing potential from Phase I and early Phase II drug trials. This stringent approach was a result of drug-related incidents, particularly in regards to the drug thalidomide, a sedative that was never approved for use in the United States but was widely used throughout Europe and Canada. Thousands of women who took the drug while pregnant gave birth to babies with severe defects. Since early phase trials usually test safety without clearly articulating the medical benefit, the risk of fetal damage led to recommendations that women with childbearing potential are not appropriate participants. 

Can a drug be deemed therapeutic if it leaves out more than half the population in the world during trials? Excluding women from early stages of drug trials caused a lack of data on how drugs affect women. Moral and ethical questions arose, centered around one key issue: should women be allowed to choose whether to take the risk of participating in research? 

The next few decades saw protests and policy change regarding women in trials. In 1986, NIH policy encouraged researchers to include women in studies, and three years later, they issued a Memorandum on Inclusion noting that if women and minorities are excluded from a trial, a rationale needs to be included. In 1990, after it was determined that the policy was not being followed appropriately, the Office of Research on Women’s Health was formed, and a year later, the NIH elected Dr. Bernadine Healy to become the first female NIH Director.

In 1993, Congress passed the NIH Revitalization Act, which mandated the inclusion of women (as well as people of color) in clinical trials. This was the first time that inclusion in research was written into law, and the legislation included the following provisions: 

• NIH ensures that women and minorities are included in all clinical research.
• In trials including women and minorities, the trial should be designed and carried out so that it is possible to analyze whether the variables being studied affect women and minorities differently than other participants.
• Cost is not an acceptable reason for excluding women and minorities.
• NIH initiates programs and support for outreach efforts to recruit and retain women and minorities and their subpopulations as volunteers in clinical studies.

These initiatives paved the way for greater analysis of the gender-related impacts of medical products. Still, many women taking a drug have had to learn about its efficacy or safety through first-hand experience. This is evidenced by the fact that from 1997 to 2001, 80% of drugs pulled from the market due to “unacceptable health risks” were found to be more harmful to women than to men. A 2017 report by the FDA shows progress: women represent approximately 43% of clinical trial participants, and the FDA continues to work for equal representation in studies.

What matters to women taking part in trials and why inclusivity in clinical trial populations is important

People across the gender, sex, race, and socioeconomic spectrum approach trials in unique ways. In our survey of 4,000 clinical trial patients and caregivers about their attitudes towards clinical research, we noticed a few key differences among men and women when it came to main reasons for and against participating. 

Women reported not having to take time away from work, school, or other obligations as much more important than men did (70.9% and 60.6% p<.01). Designing trials with flexible schedules, whether or not through home visits, may be particularly meaningful for women interested in taking part. In the same survey, women rated financial factors as more important than did males:

• for reimbursement, 60.3% female versus 50.4% male
• for payment, 38.4% female versus 31.6% male 
• for receipt of free or reduced-cost healthcare, 67.3% female versus 56.8% male

Accommodating women’s concerns about the time commitment to participate in a trial is particularly important given the history of women’s participation in clinical trials.

One key issue of omitting women from clinical trials is that some diseases present differently in women than they do in men. This can lead to underdiagnosis, undertreatment, and poorer outcomes. Not only does this put women at risk, it makes manufacturers liable for the consequences of unexpected side effects and outcomes. While there has been some improvement in representation in later stage clinical trials, the dosing regimens used in those later stage studies are based on the data collected in the early trials, where women continue to be underrepresented. Since early phase studies are also where scientists learn about how the drug works in the body, it’s critical to include women as early as possible in the drug development process.

The FDA has explicitly stated that “to further promote and protect public health, it is important that people who are in clinical trials represent the populations most likely to use the potential medical product.” Guidance from the FDA also includes other high-level considerations about the inclusion of other important groups, including: women (and pregnant women), racial and ethnic minorities, children, and older adults.

The need for inclusion goes beyond sex and gender differences — people living with chronic comorbidities and disabilities, as well as racial and ethnic communities, are often excluded from clinical trials. The issue of inclusion and clinical trial participation is critically important. Better treatments and potential cures will continue to be out of reach for some segments of the population if trial populations don’t reflect the real world.