Jared D. Huling

Elena Casiraghi, Rachel Wong, Margaret Hall et al.

Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful to assess associations between patients' predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases and the simple removal of these cases may introduce severe bias. For these reasons, several multiple imputation algorithms have been proposed to attempt to recover the missing information. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithms works best in a given scenario. Furthermore, the selection of each algorithm parameters and data-related modelling choices are also both crucial and challenging. In this paper, we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. The experiments presented here show that our approach could effectively highlight the most valid and performant missing-data handling strategy for our case study. Moreover, our methodology allowed us to gain an understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.

Jay Jojo Cheng, Jared D. Huling, Guanhua Chen

Medical treatments tailored to a patient's baseline characteristics hold the potential of improving patient outcomes while reducing negative side effects. Learning individualized treatment rules (ITRs) often requires aggregation of multiple datasets(sites); however, current ITR methodology does not take between-site heterogeneity into account, which can hurt model generalizability when deploying back to each site. To address this problem, we develop a method for individual-level meta-analysis of ITRs, which jointly learns site-specific ITRs while borrowing information about feature sign-coherency via a scientifically-motivated directionality principle. We also develop an adaptive procedure for model tuning, using information criteria tailored to the ITR learning problem. We study the proposed methods through numerical experiments to understand their performance under different levels of between-site heterogeneity and apply the methodology to estimate ITRs in a large multi-center database of electronic health records. This work extends several popular methodologies for estimating ITRs (A-learning, weighted learning) to the multiple-sites setting.

Rui Chen, Jared D. Huling, Guanhua Chen et al.

Learning individualized treatment rules (ITRs) is an important topic in precision medicine. Current literature mainly focuses on deriving ITRs from a single source population. We consider the observational data setting when the source population differs from a target population of interest. Compared with causal generalization for the average treatment effect which is a scalar quantity, ITR generalization poses new challenges due to the need to model and generalize the rules based on a prespecified class of functions which may not contain the unrestricted true optimal ITR. The aim of this paper is to develop a weighting framework to mitigate the impact of such misspecification and thus facilitate the generalizability of optimal ITRs from a source population to a target population. Our method seeks covariate balance over a non-parametric function class characterized by a reproducing kernel Hilbert space and can improve many ITR learning methods that rely on weights. We show that the proposed method encompasses importance weights and overlap weights as two extreme cases, allowing for a better bias-variance trade-off in between. Numerical examples demonstrate that the use of our weighting method can greatly improve ITR estimation for the target population compared with other weighting methods.