ABSTRACT
OBJECTIVES: Clinical trials are pillars of modern clinical evidence generation. However, the clinical trial enterprise can be inefficient, and trials often fail before their planned endpoint is reached. We sought to estimate how often urologic oncology trials fail, why trials fail, and associations with trial failure. METHODS: We queried phase 2/3 urologic clinical trial data from ClinicalTrials.gov registered between 2007 and 2019, with status marked as active, completed, or terminated. We extracted relevant trial data, including anticipated and actual accrual, from trial records and ClinicalTrials.gov archives. We manually coded reasons given in the "why stopped" free text field for trial failure into categories (poor accrual, interim results, toxicity/adverse events, study agent unavailable, canceled by the sponsor, inadequate budget, logistics, trial no longer needed, principal investigator left, no reason given, or other). We considered trials terminated for safety or efficacy to be completed trials. Trials marked as terminated for other reasons were considered failed trials. We then estimated the rate of trial failure using competing risks methods. Finally, we assessed associations with trial failure using a Cox proportional hazards model. RESULTS: A total of 1,869 urologic oncology trials were included. Of these, 225 (12.0%) failed, and 51 (2.7%) were terminated for "good" reasons (e.g., toxicity, efficacy). Of the 225 failed trials, 122 (54%) failed due to poor accrual. Failed trials had a lower anticipated accrual than successfully completed trials (55 vs. 63 patients, P<0.001). A total of 6,832 patients were actually accrued to failed trials. The 10-year estimated risk of trial failure was 17% (95% CI 15%-22%). Single center trials, phase 3 trials, drug trials, and trials with exclusively USA sites were more likely to fail. CONCLUSION: We estimate that 17%, or roughly 1 in 6, of urologic oncology trials fail, most frequently for poor accrual. Further investigations are needed into systemic, trial, and site-specific factors that may impact accrual and successful trial completion.
