Cancer patient survival can be parametrized to improve trial precision and reveal time-dependent therapeutic effects.
Nat Commun
; 13(1): 873, 2022 02 15.
Article
in En
| MEDLINE
| ID: mdl-35169116
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Research Design
/
Clinical Trials as Topic
/
Cancer Survivors
/
Neoplasms
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2022
Type:
Article
Affiliation country:
United States