Individualized treatment effects with censored data via fully nonparametric Bayesian accelerated failure time models.

Dirichlet process mixture Ensemble methods Heterogeneity of treatment effect Interaction Personalized medicine Subgroup analysis

Journal

Biostatistics (Oxford, England)
ISSN: 1468-4357
Titre abrégé: Biostatistics
Pays: England
ID NLM: 100897327

Informations de publication

Date de publication:
01 01 2020
Historique:
received: 22 09 2017
revised: 24 05 2018
accepted: 14 06 2018
pubmed: 28 7 2018
medline: 27 10 2020
entrez: 28 7 2018
Statut: ppublish

Résumé

Individuals often respond differently to identical treatments, and characterizing such variability in treatment response is an important aim in the practice of personalized medicine. In this article, we describe a nonparametric accelerated failure time model that can be used to analyze heterogeneous treatment effects (HTE) when patient outcomes are time-to-event. By utilizing Bayesian additive regression trees and a mean-constrained Dirichlet process mixture model, our approach offers a flexible model for the regression function while placing few restrictions on the baseline hazard. Our nonparametric method leads to natural estimates of individual treatment effect and has the flexibility to address many major goals of HTE assessment. Moreover, our method requires little user input in terms of model specification for treatment covariate interactions or for tuning parameter selection. Our procedure shows strong predictive performance while also exhibiting good frequentist properties in terms of parameter coverage and mitigation of spurious findings of HTE. We illustrate the merits of our proposed approach with a detailed analysis of two large clinical trials (N = 6769) for the prevention and treatment of congestive heart failure using an angiotensin-converting enzyme inhibitor. The analysis revealed considerable evidence for the presence of HTE in both trials as demonstrated by substantial estimated variation in treatment effect and by high proportions of patients exhibiting strong evidence of having treatment effects which differ from the overall treatment effect.

Identifiants

pubmed: 30052809
pii: 5056258
doi: 10.1093/biostatistics/kxy028
pmc: PMC8972560
doi:

Substances chimiques

Angiotensin-Converting Enzyme Inhibitors 0

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

50-68

Subventions

Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States

Informations de copyright

© The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Nicholas C Henderson (NC)

Oncology Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 550 N. Broadway, Suite 1101, Baltimore, MD, USA.

Thomas A Louis (TA)

Department of Biostatistics, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD, USA.

Gary L Rosner (GL)

Department of Biostatistics, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD, USA.
Oncology Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 550 N. Broadway, Suite 1103, Baltimore, MD, USA.

Ravi Varadhan (R)

Department of Biostatistics, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD, USA.
Oncology Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 550 N. Broadway, Suite 1103, Baltimore, MD, USA.

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Classifications MeSH