Women underrepresented in clinical trials for key disease areas

Participation of women in phase 1-3 clinical trials for drugs and devices continues to lag behind their representation in the specific disease population in many critically important disease areas, despite efforts to improve the situation, according to a new study by investigators from Brigham and Women’s Hospital. Researchers from the Brigham examined female participation in adult cardiovascular, psychiatric, and cancer-related clinical trials and found that among trials for therapeutics in these three areas, the percentage of women enrolled did not reflect the proportion of women affected by the disease. This was especially striking for clinical trials investigating drugs and devices for psychiatric disorders, where women make up 60 percent of the patient population, but just 42 percent of trial participants. Results of this research are published in a special issue of Contemporary Clinical Trials dedicated to Women’s Health.

“Though there are overall improvements in the participation of women in clinical trials, they are still underrepresented in studies that they rightfully belong in,” said middle author Primavera A. Spagnolo, MD, PhD, of the Connors Center of Women’s Heath and Gender Biology and Department of Psychiatry. “To ensure that results of clinical research benefit all the individuals affected by a disease, clinical trial populations should align more closely with the demographics of the population affected by disease.”

Spagnolo and her colleagues analyzed data from ClinicalTrials.gov, a database of both private and public clinical research studies, across a four-year period (2016-2019). The researchers assessed the average number of women enrolled for the specified disease areas and per trial.

After examining 1,433 trials with 302,664 participants, the team discovered that, on average, 41.2 percent of the participants were female. Although 49 percent of the cardiovascular disease patient population is female, only 41.9 percent of trial participants were female. Additionally, while 51 percent of cancer patients are female, just 41 percent of clinical trial participants were female. Psychiatry clinical trials appeared to have the greatest gaps in enrolling female participants with a mean participation of females in clinical trials of 42 percent, even though 60 percent of psychiatry patients are female.

“When designing this study, we decided to assess cardiovascular disease, cancer, and psychiatric illness because the first two are leading causes of mortality among women and the latter is globally the primary disability for women,” said Spagnolo. “We were disturbed to find that women are still underrepresented in clinical trials, which represents an important barrier to uncovering differences between men and women in safety and efficacy of drugs and devices.”

The authors noted a few study limitations. Investigators are required to report biological sex on ClinicalTrials.gov, preventing researchers from examining gender differences. Furthermore, the data available did not allow them to identify the causes of women’s underrepresentation in clinical trials, which should be the focus of future investigations, according to the researchers.                                           

“The rise of female participants in clinical trials is certainly promising, but our work is not complete. We simply cannot rest,” said Spagnolo. “To ensure that our patients are properly cared for and drugs as well as devices are truly safe and effective, we need to continue monitoring women’s representation in clinical trials by disease area and, importantly, we need to develop interventions and approaches ensuring the inclusion of a diverse group of women in clinical research.”

Disclosures: Senior author Hadine Joffe reports having consultant and advisory fees from Eisai and Jazz. Joffe’s spouse is an employee of Arsenal Biosciences and has an equity stake in Merck Research Labs and Tango Therapeutics. No other disclosures were reported.

Funding: This work received funding from the NIH, Merck, and Pfizer.

Paper cited: Sosinsky AZ et al. “Enrollment of Female Participants in United States Drug and Device Phase 1-3 Clinical Trials Between 2016 and 2019” Contemporary Clinical Trials DOI: 10.1016/j.cct.2022.106718