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 due to comorbidity-based exclusion criteria (CEC). Our objective was to evaluate contemporary trends in CECs among NCI-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 NCI-sponsored gynecologic cancer clinical trials (1994-2021). Study characteristics and CECs were abstracted from protocols. Descriptive statistics and temporal trends were calculated using chi-square 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/social situations," dramatically increased from 5% to 51% (p < .001) over three decades.Adherence to broadened eligibility criteria recommendations was mixed. Renal function, cardiovascular disease, and performance status criteria were not broadened but HIV, prior/concurrent malignancies, and brain metastasis criteria were.

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