Cancer patient survival can be parametrized to improve trial precision and reveal time-dependent therapeutic effects.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
14
06
2021
accepted:
06
01
2022
entrez:
16
2
2022
pubmed:
17
2
2022
medline:
3
3
2022
Statut:
epublish
Résumé
Individual participant data (IPD) from oncology clinical trials is invaluable for identifying factors that influence trial success and failure, improving trial design and interpretation, and comparing pre-clinical studies to clinical outcomes. However, the IPD used to generate published survival curves are not generally publicly available. We impute survival IPD from ~500 arms of Phase 3 oncology trials (representing ~220,000 events) and find that they are well fit by a two-parameter Weibull distribution. Use of Weibull functions with overall survival significantly increases the precision of small arms typical of early phase trials: analysis of a 50-patient trial arm using parametric forms is as precise as traditional, non-parametric analysis of a 90-patient arm. We also show that frequent deviations from the Cox proportional hazards assumption, particularly in trials of immune checkpoint inhibitors, arise from time-dependent therapeutic effects. Trial duration therefore has an underappreciated impact on the likelihood of success.
Identifiants
pubmed: 35169116
doi: 10.1038/s41467-022-28410-9
pii: 10.1038/s41467-022-28410-9
pmc: PMC8847344
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
873Subventions
Organisme : NCI NIH HHS
ID : F30 CA260780
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM107618
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA225088
Pays : United States
Informations de copyright
© 2022. The Author(s).
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