Gynecologic cancer clinical trial eligibility criteria as a marker for equitable clinical trial access

Abstract

Background: Racial and ethnic minorities remain underrepresented in gynecologic cancer clinical trials despite disproportionately worse oncologic outcomes. Research shows differential racial enrollment patterns because of comorbidity-based exclusion criteria. Our objective was to evaluate contemporary trends in comorbidity-based exclusion criteria among National Cancer Institute-sponsored gynecologic cancer clinical trials and protocol adherence to broadened eligibility criteria guidelines as an assessment of equitable enrollment access.

Methods: The ClinicalTrials.gov registry was queried for National Cancer Institute-sponsored gynecologic cancer clinical trials (1994-2021). Study characteristics and comorbidity-based exclusion criteria were abstracted from protocols. Descriptive statistics and temporal trends were calculated using χ2 testing with STATA v17 software.

Results: Among 279 clinical trials identified, 65% completed enrollment, 53% were phase II, and 48% focused on ovarian cancer. Pharmaceutical agents (85%) were the primary therapeutic interventions. Several inequitably restrictive exclusion criteria increased over time such as hepatitis infection (17% in 1994-2000 vs 49% in 2015-2021, P < .001) and cardiovascular disease (47% in 1994-2000 vs 66% in 2015-2021, P = .002). A previously rare exclusion, "mental illness and/or social situations," dramatically increased from 5% to 51% (P < .001) over 3 decades. Adherence to broadened eligibility criteria recommendations was mixed. Renal function, cardiovascular disease, and performance status criteria were not broadened, but HIV, prior or concurrent malignancies, and brain metastasis criteria were.

Conclusions: Some, but not all, of the known restrictive comorbidity-based exclusion criteria have increased in gynecologic cancer clinical trial design, despite calls for improving racial and ethnic minority representation. Exclusion criteria are critical for trial safety, however, they must be carefully considered given the differential racial impact on eligibility.