The overarching goal of this project is to develop Bayesian non-parametric (BNP) methods for estimating causal effects from complex data. We focus on two broad areas: survival analysis with time-varying treatments and mediation. For survival outcomes, we develop BNP methods for estimating causal parameters from structural nested failure time models, both for discrete and continuous-time problems. Likelihood-based methods have generally not been implemented for these models, because it would require many parametric modeling assumptions. Our BNP approach should provide greater flexibility than parametric models, while maintaining computational advantages. We will develop these methods for a wide array of scenarios (e.g., multinomial or continuous-valued treatment, known or unknown censoring times) and develop sensitivity analysis methods and informative priors related to untestable assumptions. For causal mediation analysis, we will extend our previous work in a variety of ways. Most importantly, we will weaken identifying assumptions with the inclusion of covariates in the models. In addition, we will generalize to a wider variety of outcomes and types of mediation (e.g. longitudinal or multiple mediators). We will also develop methods for handling non-ignorable dropout in settings with mediation. Our methods have broad applications, and we will utilize them to draw novel clinical inference from several behavioral intervention trials and from a study on the hepatic safety of classes of antiretroviral medications

Public Health Relevance

In clinical research studies involving treatment comparisons, there is often interest in the comparative effectiveness of various treatment strategies, or on the effect of mediating variables. It is therefore of great importance to have statistical methods that can handle the complexities of these data, without relying on strong modeling assumptions. This project develops new, robust Bayesian methods for inferring causal effects from complex studies of this nature.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM112327-02
Application #
8925116
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Marcus, Stephen
Project Start
2014-09-10
Project End
2018-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
$344,001
Indirect Cost
$71,476
Name
University of Pennsylvania
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Roy, Jason; Lum, Kirsten J; Zeldow, Bret et al. (2018) Bayesian nonparametric generative models for causal inference with missing at random covariates. Biometrics :
Spieker, Andrew; Roy, Jason; Mitra, Nandita (2018) Analyzing medical costs with time-dependent treatment: The nested g-formula. Health Econ 27:1063-1073
Kim, Chanmin; Daniels, Michael; Li, Yisheng et al. (2018) A Bayesian semiparametric latent variable approach to causal mediation. Stat Med 37:1149-1161
Kim, Chanmin; Daniels, Michael J; Marcus, Bess H et al. (2017) A framework for Bayesian nonparametric inference for causal effects of mediation. Biometrics 73:401-409
Vajravelu, Ravy K; Osterman, Mark T; Aberra, Faten N et al. (2017) Indeterminate QuantiFERON-TB Gold Increases Likelihood of Inflammatory Bowel Disease Treatment Delay and Hospitalization. Inflamm Bowel Dis 24:217-226
Roy, Jason; Lum, Kirsten J; Daniels, Michael J (2017) A Bayesian nonparametric approach to marginal structural models for point treatments and a continuous or survival outcome. Biostatistics 18:32-47
Xu, Dandan; Daniels, Michael J; Winterstein, Almut G (2016) Sequential BART for imputation of missing covariates. Biostatistics 17:589-602