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Female Underrepresentation Persists Among Patients Enrolled in Hematologic, Solid Tumor Trials

December 30, 2021

While clinical trials have increasingly included female participants over the past 40 years, women are underrepresented in clinical trials of cancer treatments compared with overall cancer incidence in the U.S., a new study published in The Oncologist suggests. The disparity was slight among trials in hematologic malignancies, and more substantial in trials of solid tumors, indicating that many cancer trials do not reflect demographics seen in practice. Breast cancer, prostate cancer, testicular cancer, and gynecologic cancers were excluded from the analysis.

"We all need to be aware that these inequities persist and that sex remains a social determinant of health, even in developed countries," said lead author Shehara Mendis, MBBS, BMedSci, from Cabrini Health in Melbourne, Australia, "so that we can devise strategies that reduce these systemic issues in clinical trial care access and, ultimately, overall health outcomes."

The researchers identified 222 trials leading to FDA cancer drug approvals between 2008 and 2018. The 222 trials involved a pooled population of 109,842 patients. Using International Agency for Research on Cancer data, the investigators compared the ratio of female-to-male trial enrollment with cancer incidence and mortality in the U.S.

"Women probably continue to face more barriers to trial enrollment despite policy directives that have tried to rectify historical imbalances."

—Shehara Mendis, MBBS, BMedSci

A total of 186 trials associated with 170 FDA drug approvals and involving 78,840 patients was included in the final analysis after exclusion of 36 sex-specific trials and 145 patients from 10 trials with missing sex data.

Of this group of participants, 31,743 (40.3%) were women. The largest proportion of patients in the overall cohort were involved in lung cancer trials (n=17,079), whereas the smallest proportion of patients were concentrated in thyroid cancer trials (n=1,486).

The investigators found a slight yet significant underrepresentation of female participants in 186 trials leading to 170 FDA cancer drug approvals compared with the overall cancer incidence in the U.S. (odds ratio [OR] = 0.97; 95% CI 0.95-0.98; p<0.0001). "Although the magnitude of difference is small, this equates to there being nearly 1,000 [fewer] women enrolled than expected within the trial cohort reviewed here," the authors noted.

No differences were observed in the distribution of female and male enrollment in trials that led to drug approvals between 2008 to 2013 and 2014 to 2018 (OR=1.02; 95% CI 0.99-1.05; p=0.25). "Despite increasing awareness of sex disparity and numerous policy statements from organizations such as the FDA, little has changed in the past 20 years, and disparity in trial enrollment is still an important area for improvement in our society," the researchers reported.

Compared with incidence of the diseases in the U.S. population, there was a slight underrepresentation of women in trials of leukemia and lymphoma, but substantial female underrepresentation in colorectal, pancreatic, lung, kidney, and thyroid cancers (TABLE).

In contrast, bladder cancer trials overenrolled women compared with the incidence in the U.S. (OR=1.34; 95% CI 1.21–1.48; p<0.0001), but no significant difference was found when compared with mortality. Similarly, in the context of melanoma trials, women were overenrolled compared with mortality (OR=1.37; 95% CI 1.29-1.45; p<0.0001) but not when compared with the U.S. incidence.

A limitation of this study is the lack of reporting on gender minority representation, such as patients who identify as transgender and nonbinary. In addition, the investigators did not examine or report on adverse event data stratified by sex.

"The findings make us wonder if there are systemic barriers to trial enrollment that disproportionately affect women in the outpatient setting more so than an inpatient setting, as the former is where most chronic leukemia trials would occur," Dr. Mendis concluded. "I think this study highlights the fact that women probably continue to face more barriers to trial enrollment despite policy directives that have tried to rectify historical imbalances. This is likely due to systemic barriers like access to transport, career responsibilities, and so forth."

Study authors report no relevant conflicts of interest.


Mendis S, Anand S, Karasinska JM, et al. Sex representation in clinical trials associated with FDA cancer drug approvals differs between solid and hematologic malignancies. Oncologist. 2020 September 22. [Epub ahead of print]

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