Gynecologic oncology clinical trials: study the studies to terminate the terminations

Abstract

<h3>Objectives:</h3> Clinical trials are paramount to safely advancing the standard of care. Trials that are not completed represent a potential misallocation of resources. The objectives of this study are to assess reasons for clinical trial non-completion, and to identify attributes associated with non-completion for trials in gynecologic oncology. <h3>Methods:</h3> Clinical trials in gynecologic oncology were identified by searching ClinicalTrials.gov for the following cancer types: ovarian, uterine, endometrial, cervical, vaginal, and vulvar. Data collection was performed in February 2020. Data on these trials were downloaded from the website and supplemented with manual codification. We excluded trials that were currently active, duplicative, and/or not enrolling patients with gynecologic malignancies. Unadjusted and adjusted logistic regression models were fit to identify trial attributes associated with trial non-completion. Attributes assessed include cancer type, trial phase, sponsor, funding, geography, size, intervention type, purpose, primary outcomes, and NCI involvement. <h3>Results:</h3> A total of 1882 trials met inclusion criteria. Overall, 1480 (79%) of trials were completed and 402 (21%) were either withdrawn, suspended, or terminated. The most common reasons for non-completion were low accrual (n=124, 31%), no reason given (n=89, 22%) or discretion of study principal investigator (n=52, 13%). Thirty-five trials (9%) were not completed due to lack of efficacy at interim analysis, and 17 (4%) due to safety concerns. In unadjusted analysis, trials that were associated with a higher odds of non-completion were those that (1) enrolled ovarian cancer patients, (2) evaluated drug/biologic interventions, (3) had survival as a primary outcome, (4) were early phase 1/2 or 2, and (5) received industry funding. Cervical cancer, NIH funding, and screening/prevention trials were all associated with lower odds of trial non-completion. After mutual adjustment, phase 1/2 or 2 trials (OR = 1.54; 95% CI=1.13 - 2.11, ref=early phase 1 or 1), industry funded trials (OR = 1.45; 95% CI=1.03 - 2.03), and exclusive domestic enrollment (OR = 1.35; 95% CI=1.02 - 1.77) were all associated with higher odds of non-completion. Trials that enrolled at 2-5 sites (OR = 0.66; 95% CI=0.47 - 0.93), as compared to single site, was the only attribute associated with lower odds of non-completion. <h3>Conclusions:</h3> Over 20% of gynecologic oncology clinical trials are not completed. The most common reason for trial non-completion is inadequate accrual. Trials are rarely terminated for safety or efficacy concerns. In multivariate analysis, trials located exclusively in the United States had 35% higher odds of not being completed compared to international trials, and industry funded trials had 45% higher odds of non-completion when compared to trials without industry funding. Insights into why trials are not completed may inform future clinical trial design and ultimately maximize likelihood of completion.