Sex Representation in Clinical Trials Associated with FDA Cancer Drug Approvals Differs Between Solid and Hematologic Malignancies

Abstract

Background: Proportionate female representation in health research is necessary for scientific rigor and health equity. We aimed to assess the representation of women in clinical trials leading to U.S. Food and Drug Administration (FDA) cancer drug approvals.

Materials and methods: Trials supporting FDA cancer drug approvals between July 2008 and June 2018 were sourced from PubMed and ClinicalTrials.gov. The ratio of female to male trial enrollment was compared with cancer incidence and mortality in the U.S. using International Agency for Research on Cancer data. Reproductive tract and breast cancers were excluded. Odds ratios (ORs) and 95% confidence intervals (CIs) comparing trial enrollment with population incidence and mortality were calculated.

Results: A total of 186 trials leading to 170 FDA cancer drug approvals showed slight female underrepresentation compared with overall cancer incidence in the U.S. (OR, 0.97; 95% CI, 0.95-0.98, p < .0001). Female enrollment for drugs approved between 2008-2013 and 2014-2018 was unchanged (OR, 1.02; 95% CI, 0.99-1.05, p = .25). There was slight female underrepresentation in hematological trials (OR, 0.95; 95% CI, 0.91-0.998; p = .040 for leukemia; OR, 0.95; 95% CI, 0.90-0.997; p = .040 for lymphoma) and significant female underrepresentation in colorectal (OR, 0.72; 95% CI, 0.69-0.76; p < .0001), pancreas (OR, 0.85; 95% CI, 0.78-0.93; p = .0004), lung (OR, 0.77; 95% CI, 0.75-0.80; p < .0001), kidney (OR, 0.63; 95% CI, 0.60-0.67; p < .0001), and thyroid cancer trials (OR, 0.26; 95% CI, 0.23-0.28; p < .0001) compared with U.S. incidence.

Conclusion: Female underrepresentation has persisted within solid organ tumor trials but is less notable in hematologic trials. Additional work is required to identify drivers of such disparity.

Implications for practice: Adequate gender representation in clinical trials is a matter of health equity. This study demonstrates that women remain underrepresented in trials across hematological and solid organ trials compared with cancer incidence and mortality in women, with the disparity worse in a number of solid organ tumor types. There are thus still significant improvements to be made regarding adequate representation of women in trials. Studies exploring the reasons for ongoing disparity in gender representation are warranted to help clinicians to rectify this.

Keywords: Clinical trial; Healthcare disparities; Neoplasms; Sex.

Figure 1

Distribution of female and male trial enrollment between July 2008 and June 2018. (A): Distribution of female and male enrollment for trials leading to cancer drug approvals between July 2008 and June 2018. Sex‐specific cancers have been excluded. (B): Distribution of female and male enrollment in trials associated with drug approvals that occurred between 2008 and 2013 and 2014 and 2018 did not differ (odds ratio, 1.02; 95% confidence interval, 0.99–1.05; p = .25).

Figure 2

Odds ratio for female trial enrollment versus U.S. incidence or mortality. (A): Odds ratio (OR) with 95% confidence intervals for female trial enrollment compared with U.S. incidence by tumor type. “All cancers” includes all non–sex‐specific cancer types. Female to male ratios (female/male) for trial enrollment and US incidence, ORs, and p values are shown on the right. (B): OR for female trial enrollment compared with U.S. mortality by tumor type.

Figure 3

Female and male distribution across U.S. incidence, U.S. mortality, and trialenrollment across 10 tumor types. Graphical representation of the ratio of female to male (female/male) within trials leading to U.S. Food and Drug Administration drug approvals during the period reviewed for the 10 most common tumor types in the US. The inner ring denotes the female/male U.S. incidence for the tumor type denoted below the circle, and the middle ring denotes female/male U.S mortality for that tumor type. The outer ring of each circle represents female/male enrollment across all trials for that tumor type.