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The general idea of this article is to develop a Bayesian model with a flexible link function connecting an exponential family treatment response to a linear combination of covariates and a treatment indicator and the interaction between the two. Generalized linear models allowing data-driven link functions are often called "single-index models," and among popular semi-parametric modeling methods. In this article, we will focus on modeling heterogeneous treatment effects, with the goal of developing a treatment benefit index (TBI) incorporating prior information from historical data. This treatment benefit index can be useful for stratifying patients according to their predicted treatment benefit levels and can be especially useful for precision health applications. The proposed method is applied to a COVID-19 treatment study., Comment: 9 pages, 1 figure and 1 table

We consider unsupervised classification by means of a latent multinomial variable which categorizes a scalar response into one of L components of a mixture model. This process can be thought as a hierarchical model with first level modelling a scalar response according to a mixture of parametric distributions, the second level models the mixture probabilities by means of a generalised linear model with functional and scalar covariates. The traditional approach of treating functional covariates as vectors not only suffers from the curse of dimensionality since functional covariates can be measured at very small intervals leading to a highly parametrised model but also does not take into account the nature of the data. We use basis expansion to reduce the dimensionality and a Bayesian approach to estimate the parameters while providing predictions of the latent classification vector. By means of a simulation study we investigate the behaviour of our approach considering normal mixture model and zero inflated mixture of Poisson distributions. We also compare the performance of the classical Gibbs sampling approach with Variational Bayes Inference., Comment: 41 pages; 13 figures, 17 tables

Sparse additive modeling is a class of effective methods for performing high-dimensional nonparametric regression. This paper develops a sparse additive model focused on estimation of treatment effect-modification with simultaneous treatment effect-modifier selection. We propose a version of the sparse additive model uniquely constrained to estimate the interaction effects between treatment and pretreatment covariates, while leaving the main effects of the pretreatment covariates unspecified. The proposed regression model can effectively identify treatment effect-modifiers that exhibit possibly nonlinear interactions with the treatment variable, that are relevant for making optimal treatment decisions. A set of simulation experiments and an application to a dataset from a randomized clinical trial are presented to demonstrate the method., Comment: 30 pages, 5 figures

Dimension reduction lies at the heart of many statistical methods. In regression, dimension reduction has been linked to the notion of sufficiency whereby the relation of the response to a set of predictors is explained by a lower dimensional subspace in the predictor space. In this paper, we consider the notion of a dimension reduction in regression on subspaces that are sufficient to explain interaction effects between predictors and another variable of interest. The motivation for this work is from precision medicine where the performance of an individualized treatment rule, given a set of pretreatment predictors, is determined by interaction effects., Comment: 25 pages, 3 figures

A novel functional additive model is proposed which is uniquely modified and constrained to model nonlinear interactions between a treatment indicator and a potentially large number of functional and/or scalar pretreatment covariates. The primary motivation for this approach is to optimize individualized treatment rules based on data from a randomized clinical trial. We generalize functional additive regression models by incorporating treatment-specific components into additive effect components. A structural constraint is imposed on the treatment-specific components in order to provide a class of additive models with main effects and interaction effects that are orthogonal to each other. If primary interest is in the interaction between treatment and the covariates, as is generally the case when optimizing individualized treatment rules, we can thereby circumvent the need to estimate the main effects of the covariates, obviating the need to specify their form and thus avoiding the issue of model misspecification. The methods are illustrated with data from a depression clinical trial with electroencephalogram functional data as patients' pretreatment covariates., Comment: 24 pages, 7 figures, 2 tables

This paper focuses on the problem of modeling and estimating interaction effects between covariates and a continuous treatment variable on an outcome, using a single-index regression approach. The primary motivation is to estimate an optimal individualized dose rule in an observational study. To model possibly nonlinear interaction effects between patients' covariates and a continuous treatment variable, we employ a two-dimensional penalized spline regression on an index-treatment domain, where the index is defined as a linear projection of the covariates. The method is illustrated using two applications as well as simulation experiments. A unique contribution of this work is in the parsimonious (single-index) parametrization specifically defined for the interaction effect term., Comment: 26 pages, 2 figures

Current source density (CSD) power asymmetry, a measure derived from electroencephalography (EEG), is a potential biomarker for major depressive disorder (MDD). Though this measure is functional in nature (defined on the frequency domain), it is typically reduced to a scalar value prior to analysis, possibly obscuring the relationship between brain function and MDD. To overcome this issue, we sought to fit a functional regression model to estimate the association between CSD power asymmetry and MDD diagnostic status, adjusting for age, sex, cognitive ability, and handedness using data from a large clinical study. Unfortunately, nearly 40\% of the observations were missing either their functional EEG data, their cognitive ability score, or both. In order to take advantage of all of the available data, we propose an extension to multiple imputation by chained equations that handles both scalar and functional data. We also propose an extension to Rubin's Rules for pooling estimates from the multiply imputed data sets in order to conduct valid inference. We investigate the performance of the proposed extensions in a simulation study and apply them to our clinical study data. Our analysis reveals that the association between CSD power asymmetry and diagnostic status depends on both age and sex.