Estimating the rate and reasons of clinical trial failure in urologic oncology.
Clinical trials
Evidence generation
Trial accrual
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
17
07
2020
revised:
23
09
2020
accepted:
23
10
2020
pubmed:
2
12
2020
medline:
23
7
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 33257221
pii: S1078-1439(20)30560-3
doi: 10.1016/j.urolonc.2020.10.070
pmc: PMC7902467
mid: NIHMS1653006
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-160Subventions
Organisme : NCI NIH HHS
ID : T32 CA180984
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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