A critical analysis of neuro-oncology clinical trials.
clinical trial design trends
leveraging of trial registry data
primary central nervous system malignancies
treatment effect size assumptions
trial accrual
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
05 09 2023
05 09 2023
Historique:
pmc-release:
09
02
2024
medline:
6
9
2023
pubmed:
10
2
2023
entrez:
9
2
2023
Statut:
ppublish
Résumé
Limitations in trial design, accrual, and data reporting impact efficient and reliable drug evaluation in cancer clinical trials. These concerns have been recognized in neuro-oncology but have not been comprehensively evaluated. We conducted a semi-automated survey of adult interventional neuro-oncology trials, examining design, interventions, outcomes, and data availability trends. Trials were selected programmatically from ClinicalTrials.gov using primary malignant central nervous system tumor classification terms. Regression analyses assessed design and accrual trends; effect size analysis utilized survival rates among trials investigating survival. Of 3038 reviewed trials, most trials reporting relevant information were nonblinded (92%), single group (65%), nonrandomized (51%), and studied glioblastomas (47%) or other gliomas. Basic design elements were reported by most trials, with reporting increasing over time (OR = 1.24, P < .00001). Trials assessing survival outcomes were estimated to assume large effect sizes of interventions when powering their designs. Forty-two percent of trials were completed; of these, 38% failed to meet their enrollment target, with worse accrual over time (R = -0.94, P < .00001) and for US versus non-US based trials (OR = 0.5, P < .00001). Twenty-eight percent of completed trials reported partial results, with greater reporting for US (34.6%) versus non-US based trials (9.3%, P < .00001). Efficacy signals were detected by 15%-23% of completed trials reporting survival outcomes. Low randomization rates, underutilization of controls, and overestimation of effect size, particularly pronounced in early-phase trials, impede generalizability of results. Suboptimal designs may be driven by accrual challenges, underscoring the need for cooperative efforts and novel designs. The limited results reporting highlights the need to incentivize data reporting and harmonization.
Sections du résumé
BACKGROUND
Limitations in trial design, accrual, and data reporting impact efficient and reliable drug evaluation in cancer clinical trials. These concerns have been recognized in neuro-oncology but have not been comprehensively evaluated. We conducted a semi-automated survey of adult interventional neuro-oncology trials, examining design, interventions, outcomes, and data availability trends.
METHODS
Trials were selected programmatically from ClinicalTrials.gov using primary malignant central nervous system tumor classification terms. Regression analyses assessed design and accrual trends; effect size analysis utilized survival rates among trials investigating survival.
RESULTS
Of 3038 reviewed trials, most trials reporting relevant information were nonblinded (92%), single group (65%), nonrandomized (51%), and studied glioblastomas (47%) or other gliomas. Basic design elements were reported by most trials, with reporting increasing over time (OR = 1.24, P < .00001). Trials assessing survival outcomes were estimated to assume large effect sizes of interventions when powering their designs. Forty-two percent of trials were completed; of these, 38% failed to meet their enrollment target, with worse accrual over time (R = -0.94, P < .00001) and for US versus non-US based trials (OR = 0.5, P < .00001). Twenty-eight percent of completed trials reported partial results, with greater reporting for US (34.6%) versus non-US based trials (9.3%, P < .00001). Efficacy signals were detected by 15%-23% of completed trials reporting survival outcomes.
CONCLUSION
Low randomization rates, underutilization of controls, and overestimation of effect size, particularly pronounced in early-phase trials, impede generalizability of results. Suboptimal designs may be driven by accrual challenges, underscoring the need for cooperative efforts and novel designs. The limited results reporting highlights the need to incentivize data reporting and harmonization.
Identifiants
pubmed: 36757281
pii: 7033133
doi: 10.1093/neuonc/noad036
pmc: PMC10484169
doi:
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1658-1671Informations de copyright
Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2023.
Références
Ann Oncol. 2014 Nov;25(11):2284-2289
pubmed: 25193993
Clin Cancer Res. 2022 Feb 15;28(4):594-602
pubmed: 34561269
Neuro Oncol. 2020 Oct 30;22(12 Suppl 2):iv1-iv96
pubmed: 33123732
Bioinformatics. 2017 Mar 15;33(6):901-908
pubmed: 27993785
J Clin Oncol. 2018 Dec 10;36(35):3477-3484
pubmed: 30351999
Neuro Oncol. 2020 Aug 17;22(8):1073-1113
pubmed: 32328653
Clin Cancer Res. 2018 Feb 15;24(4):737-743
pubmed: 28814435
Neuro Oncol. 2019 Sep 6;21(9):1100-1117
pubmed: 31175826
Clin Pharmacol Ther. 2018 Feb;103(2):202-205
pubmed: 29214638
Radiat Oncol. 2017 Jan 3;12(1):1
pubmed: 28049492
Am Soc Clin Oncol Educ Book. 2016;35:185-98
pubmed: 27249699
Lancet Oncol. 2012 May;13(5):e196-204
pubmed: 22554547
Lancet Oncol. 2021 Oct;22(10):e456-e465
pubmed: 34592195
JAMA Oncol. 2022 Sep 1;8(9):1352-1354
pubmed: 35797031
BMJ. 2018 Jun 6;361:k2130
pubmed: 29875212
Neurooncol Adv. 2022 Apr 09;4(1):vdac048
pubmed: 35571987
Neuro Oncol. 2017 Apr 1;19(4):469-474
pubmed: 28388713
Lancet Oncol. 2016 May;17(5):e209-19
pubmed: 27301048
Nat Rev Clin Oncol. 2019 Aug;16(8):509-520
pubmed: 30733593
Lancet. 2018 Aug 4;392(10145):432-446
pubmed: 30060998
Biometrics. 1983 Jun;39(2):499-503
pubmed: 6354290
Neuro Oncol. 2018 Jan 10;20(1):113-122
pubmed: 29016865
Nat Rev Drug Discov. 2021 Apr;20(4):254-255
pubmed: 33633370
J Clin Oncol. 2010 Apr 10;28(11):1963-72
pubmed: 20231676
Neuro Oncol. 2021 Nov 2;23(23 Suppl 5):S30-S38
pubmed: 34725696
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Neuro Oncol. 2018 Jul 5;20(8):1034-1043
pubmed: 29518210
Neuro Oncol. 2020 May 15;22(5):601-612
pubmed: 31974566