Estimating heterogeneous treatment effects with censored data via fully nonparametric Bayesian accelerated failure time models

Ann Arbor MI 02-12-2019 02-12-2019

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 timeto-event. By utilizing Bayesian additive regression trees and a meanconstrained 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 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. Light refreshments for seminar guests will be served at 3:10 p.m.

With Nicholas Henderson

icon to add this event to your google calendarFebruary 12, 2019
3:30 pm - 5:00 pm
1755 SPH I
1415 Washington Heights
Ann Arbor, MI 48109-2029

Sponsored by: Department of Biostatistics
Contact Information: Zhenke Wu (zhenkewu@umich.edu) & Peisong Han (peisong@umich.edu)

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 timeto-event. By utilizing Bayesian additive regression trees and a meanconstrained 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 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. Light refreshments for seminar guests will be served at 3:10 p.m.