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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.
Afiliação
  • 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 em 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Projetos de Pesquisa / Ensaios Clínicos como Assunto / Sobreviventes de Câncer / Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Projetos de Pesquisa / Ensaios Clínicos como Assunto / Sobreviventes de Câncer / Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos