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Cancer patient survival can be parametrized to improve trial precision and reveal time-dependent therapeutic effects.
Plana, Deborah; Fell, Geoffrey; Alexander, Brian M; Palmer, Adam C; Sorger, Peter K.
Affiliation
  • Plana D; Laboratory of Systems Pharmacology and the Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Fell G; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School and MIT, Cambridge, MA, USA.
  • Alexander BM; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Palmer AC; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Sorger PK; Foundation Medicine Inc., Cambridge, MA, USA.
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.
Subject(s)

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

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