Clinical trials are the benchmark for determining the effectiveness of medical treatments. They form the foundation for FDA drug approvals and are used to demonstrate a drug’s efficacy and uncover potential safety concerns. In these trials, patients are randomly assigned to different treatments, and their health outcomes are then evaluated.
However, trials are conducted on only a small portion of the population that will ultimately use a treatment. The expectation is that observations made among enrolled patients will be applicable to the broader population receiving the treatment.
While ideally, participants in a clinical trial should reflect the diversity of the population likely to use the drug, this often isn’t the reality. Trials frequently underrepresent women, the elderly, and minority groups.
The insufficient representation of these demographics can have significant repercussions.
For instance, in 1992, the FDA approved Ambien (zolpidem) for treating insomnia. Because women metabolize the drug more slowly than men, they require lower doses to prevent excessive drowsiness. However, due to the limited inclusion of women in the initial clinical trials, this critical fact was overlooked, and it wasn’t until 2013 that the FDA officially recommended a reduced dosage for women. This oversight led to more than 700 reports to the FDA of traffic accidents potentially linked to this dosing issue.
Examples like this emphasize why representative clinical trials are crucial. Regarding women, one approach to address this could be to have more women leading trials.
In a recent study, we explored this idea by examining whether clinical trials led by women were more likely to enroll female participants.
We compiled data from over 10,000 clinical trials conducted across 15 years, linking information on the gender of the investigators who led those trials to data on the gender composition of the patients enrolled.
To address potential bias—as women investigators may be more inclined to study diseases impacting women (e.g., breast cancer), and men may similarly focus on diseases affecting men (e.g., prostate cancer)—we explicitly accounted for the specific disease being studied in each trial.
Our findings showed that trials led by women investigators were more likely to recruit women as trial participants. On average, 54% of trial participants were women in trials where a woman was the lead investigator, compared to 47% for trials led by a man.
We also investigated the reasons why trials led by women might enroll more female subjects.
First, we observed that trials led by women investigators tended to employ more women as staff. Research staff in clinical trials often serve as the front line, playing a crucial role in interacting with and enrolling patients. Having more women on staff could boost the enrollment of women, especially if female trial participants feel more comfortable interacting with other women.
Second, due to increased regulatory demands and perceived legal risks, many clinical trials exclude pregnant women even when there’s no specific reason to do so (e.g., some drugs are harmful to the fetus, making exclusion normal in such trials). We discovered that women investigators were less likely to exclude pregnant women from clinical trials.
So, what do these results indicate?
When women are underrepresented in trials, the overall conclusions of those scientific studies may not generalize effectively to them. The implication of this imbalance in clinical trial representation is that treatments provided to women in real-world settings may not have the same level of evidence as those for men, raising concerns about treatment safety and efficacy.
Our study suggests that one way to increase the enrollment of women into clinical trials and ensure equitable safety and efficacy standards for both men and women is to have more women scientists lead those trials. While organizations like the National Institutes of Health, universities, and companies have initiated promising programs, women’s leadership in clinical trials still lags behind men’s.
Increasing the proportion of women among clinical trial staff may also be helpful. Our study hints at the possibility that one reason trials led by women investigators enroll more women is because women investigators may hire more front-line staff who are women. Female staff may make greater efforts to recruit women into clinical trials, or alternatively, women may be more inclined to enroll if the “face” of the trial to them is female. Training these staff could be an efficient method to increase the enrollment of women into trials.
The importance of recruiting diverse and representative clinical trial populations is driven by the clear fact that medical treatment effects can and do vary across different groups of people. We should strive to ensure that clinical trials accurately reflect the populations for whom treatments are intended, and one way to achieve this may be to ensure that clinical trial teams are representative as well.