arXiv subjects

Zongqi Xia

Publications and source records attributed to Zongqi Xia.

11 recordsLinked to original sources

arXiv2026

Generalized Linear Markov Decision Process

Offline reinforcement learning for longitudinal studies often faces two linked challenges: rewards may be binary or bounded, and reward observations may be available only for a subset of trajectories or time points even when the corresponding state-action-next-state histories are available. Linear Markov decision process methods are tractable because Bellman backups remain linear, but they require linear rewards and do not indicate how transition-only observations should be used. We introduce GRASP-MDP, Generalized Reward And Semi-supervised Pessimism for Markov Decision Processes, a reward-transition separated framework addressing both issues through one Bellman decomposition. It preserves linear transition dynamics while modeling reward means through generalized linear models. Although this breaks the usual linear Bellman form, the backup remains explicit as a nonlinear reward component plus a linear continuation component, yielding a nonlinear-plus-linear Bellman-complete class. In the resulting recursion, observed rewards estimate the generalized reward component, while all available transitions estimate the continuation component. The resulting pessimistic value iteration controls the two estimation errors separately without reward imputation. Finite-sample guarantees show that transition-only observations reduce transition-estimation error while reward uncertainty remains governed by observed rewards. Simulations and a multiple sclerosis electronic health record application illustrate the empirical benefit of retaining transition-only observations.

stat.ML↗

arXiv2026

An Instrumental Variable Approach to Account for Informative Treatment Switching in Real-world Evidence

Reproducible and generalizable assessment of treatment decisions requires principled handling of subsequent treatment switching that may inform expected outcomes and shift across cohorts and over time. To effectively account for informative treatment switching, we propose an instrumental variable approach that characterizes the poorly documented expected outcomes at switching as unmeasured confounding. After establishing the baseline treatment as a viable instrumental variable, we constructed an estimating equation based on the association between the centered instrumental variable and a martingale style residual process that identifies the treatment effect under structural cumulative survival model. Our proposed method is doubly robust, i.e., valid whenever either of baseline propensity model or no-switching outcome model is consistently estimated. A co-training of treatment effect parameter and survival outcome regression model eliminated the requirement of observing a no-switching subset under semi-parametric additive hazards models. We further developed an baseline-survival-corrected cross-fitting approach to incorporate general machine learning models for estimating nuisance models. Numerical results demonstrated the validity of our method in various settings when a basket of benchmark solutions produced biased or contradictory results. We applied our method to comparison of high-efficacy vs standard efficacy disease modifying treatments as the second line therapy of multiple sclerosis.

stat.ME↗

arXiv2026

Enhancing Spectral Embedding through Robust and Flexible Knowledge Transfer in Electronic Health Records

We propose a spectral-based, unsupervised representation learning framework to derive low-dimensional embeddings for clinical concepts and patients in rare disease cohorts from electronic health records, where data are high-dimensional but sample sizes are limited. To overcome this challenge, we incorporate a knowledge matrix extracted from a broader population that shares a partially overlapping subspace with the rare-disease cohort. Our method departs from existing approaches by relaxing restrictive one-to-one signal-alignment assumptions between the latent data matrix and knowledge matrix, allowing more flexible and realistic forms of structured sharing. We introduce a novel two-step spectral embedding procedure: first, we identify and remove irrelevant components from the knowledge matrix; then, we apply a projection-based method to separately recover shared and heterogeneous components. Simulations and an analysis of a real-world multiple sclerosis cohort show that the proposed method outperforms competing approaches, particularly in challenging scenarios where shared signals are weak and only partially aligned, as is common in rare-disease data.

stat.ML↗

arXiv2026

Representation learning to advance multi-institutional studies with electronic health record data from US and France

The widespread adoption of electronic health records has created new opportunities for translational clinical research, yet this promise remains constrained by fragmented data across privacy-siloed institutions and substantial heterogeneity in local coding practices. While privacy-preserving collaborative learning allows institutions to work together without sharing patient-level data, it does not address inconsistencies in how clinical concepts are represented across sites. We introduce a graph-based framework that addresses this gap by treating data harmonization as a scalable representation learning problem. Rather than relying on fixed standards or manual mappings, the framework integrates institution-specific summary statistics from health records, curated biomedical knowledge graphs, and semantic information derived from large language models to learn a shared semantic space. This joint learning approach aligns diverse, site-specific vocabularies while preserving patient privacy. Evaluated across seven institutions and two languages, the framework provides a robust, data-centric foundation for training and deploying clinical models across heterogeneous healthcare systems.

cs.AI↗

arXiv2026

Knowledge-Embedded Latent Projection for Robust Representation Learning

Latent space models are widely used for analyzing high-dimensional discrete data matrices, such as patient-feature matrices in electronic health records (EHRs), by capturing complex dependence structures through low-dimensional embeddings. However, estimation becomes challenging in the imbalanced regime, where one matrix dimension is much larger than the other. In EHR applications, cohort sizes are often limited by disease prevalence or data availability, whereas the feature space remains extremely large due to the breadth of medical coding system. Motivated by the increasing availability of external semantic embeddings, such as pre-trained embeddings of clinical concepts in EHRs, we propose a knowledge-embedded latent projection model that leverages semantic side information to regularize representation learning. Specifically, we model column embeddings as smooth functions of semantic embeddings via a mapping in a reproducing kernel Hilbert space. We develop a computationally efficient two-step estimation procedure that combines semantically guided subspace construction via kernel principal component analysis with scalable projected gradient descent. We establish estimation error bounds that characterize the trade-off between statistical error and approximation error induced by the kernel projection. Furthermore, we provide local convergence guarantees for our non-convex optimization procedure. Extensive simulation studies and a real-world EHR application demonstrate the effectiveness of the proposed method.

cs.LG↗

arXiv2026

Learning Sequential Decisions from Multiple Sources via Group-Robust Markov Decision Processes

We often collect data from multiple sites (e.g., hospitals) that share common structure but also exhibit heterogeneity. This paper aims to learn robust sequential decision-making policies from such offline, multi-site datasets. To model cross-site uncertainty, we study distributionally robust MDPs with a group-linear structure: all sites share a common feature map, and both the transition kernels and expected reward functions are linear in these shared features. We introduce feature-wise (d-rectangular) uncertainty sets, which preserve tractable robust Bellman recursions while maintaining key cross-site structure. Building on this, we then develop an offline algorithm based on pessimistic value iteration that includes: (i) per-site ridge regression for Bellman targets, (ii) feature-wise worst-case (row-wise minimization) aggregation, and (iii) a data-dependent pessimism penalty computed from the diagonals of the inverse design matrices. We further propose a cluster-level extension that pools similar sites to improve sample efficiency, guided by prior knowledge of site similarity. Under a robust partial coverage assumption, we prove a suboptimality bound for the resulting policy. Overall, our framework addresses multi-site learning with heterogeneous data sources and provides a principled approach to robust planning without relying on strong state-action rectangularity assumptions.

stat.ME↗

arXiv2025

DANIEL: A Distributed and Scalable Approach for Global Representation Learning with EHR Applications

Classical probabilistic graphical models face fundamental challenges in modern data environments, which are characterized by high dimensionality, source heterogeneity, and stringent data-sharing constraints. In this work, we revisit the Ising model, a well-established member of the Markov Random Field (MRF) family, and develop a distributed framework that enables scalable and privacy-preserving representation learning from large-scale binary data with inherent low-rank structure. Our approach optimizes a non-convex surrogate loss function via bi-factored gradient descent, offering substantial computational and communication advantages over conventional convex approaches. We evaluate our algorithm on multi-institutional electronic health record (EHR) datasets from 58,248 patients across the University of Pittsburgh Medical Center (UPMC) and Mass General Brigham (MGB), demonstrating superior performance in global representation learning and downstream clinical tasks, including relationship detection, patient phenotyping, and patient clustering. These results highlight a broader potential for statistical inference in federated, high-dimensional settings while addressing the practical challenges of data complexity and multi-institutional integration.

stat.ME↗

arXiv2025

Latent Factor Point Processes for Patient Representation in Electronic Health Records

Electronic health records (EHR) contain valuable longitudinal patient-level information, yet most statistical methods reduce the irregular timing of EHR codes into simple counts, thereby discarding rich temporal structure. Existing temporal models often impose restrictive parametric assumptions or are tailored to code level rather than patient-level tasks. We propose the latent factor point process model, which represents code occurrences as a high-dimensional point process whose conditional intensity is driven by a low dimensional latent Poisson process. This low-rank structure reflects the clinical reality that thousands of codes are governed by a small number of underlying disease processes, while enabling statistically efficient estimation in high dimensions. Building on this model, we introduce the Fourier-Eigen embedding, a patient representation constructed from the spectral density matrix of the observed process. We establish theoretical guarantees showing that these embeddings efficiently capture subgroup-specific temporal patterns for downstream classification and clustering. Simulations and an application to an Alzheimer's disease EHR cohort demonstrate the practical advantages of our approach in uncovering clinically meaningful heterogeneity.

stat.ME↗

arXiv2025

SMART-MC: Characterizing the Dynamics of Multiple Sclerosis Therapy Transitions Using a Covariate-Based Markov Model

Treatment switching is a common occurrence in the management of Multiple Sclerosis (MS), where patients transition across various disease-modifying therapies (DMTs) due to heterogeneous treatment responses, differences in disease progression, patient characteristics, and therapy-associated adverse effects. To investigate how patient-level covariates influence the likelihood of treatment transitions among DMTs, we adopt a Markovian framework, Sparse Matrix Estimation with Covariate-Based Transitions in Markov Chain Modeling (SMART-MC), in which the transition probabilities are modeled as functions of these covariates. Modeling real-world treatment transitions under this framework presents several challenges, including ensuring parameter identifiability and handling sparse transitions without overfitting. To address identifiability, we constrain each transition-specific covariate coefficient vectors to have a fixed L2 norm. Furthermore, our method automatically estimates transition probabilities for sparsely observed transitions as constants and enforces zero transition probabilities for transitions that are empirically unobserved. This approach mitigates the need for additional model complexity to handle sparsity while maintaining interpretability and efficiency. To optimize the multi-modal likelihood function, we develop a scalable, parallelized global optimization routine, which is validated through benchmark comparisons and supported by key theoretical properties. Our analysis uncovers meaningful patterns in DMT transitions, revealing variations across MS patient subgroups defined by age, race, and other clinical factors.

stat.ME↗

arXiv2025

Semi-supervised Clustering Through Representation Learning of Large-scale EHR Data

Electronic Health Records (EHR) offer rich real-world data for personalized medicine, providing insights into disease progression, treatment responses, and patient outcomes. However, their sparsity, heterogeneity, and high dimensionality make them difficult to model, while the lack of standardized ground truth further complicates predictive modeling. To address these challenges, we propose SCORE, a semi-supervised representation learning framework that captures multi-domain disease profiles through patient embeddings. SCORE employs a Poisson-Adapted Latent factor Mixture (PALM) Model with pre-trained code embeddings to characterize codified features and extract meaningful patient phenotypes and embeddings. To handle the computational challenges of large-scale data, it introduces a hybrid Expectation-Maximization (EM) and Gaussian Variational Approximation (GVA) algorithm, leveraging limited labeled data to refine estimates on a vast pool of unlabeled samples. We theoretically establish the convergence of this hybrid approach, quantify GVA errors, and derive SCORE's error rate under diverging embedding dimensions. Our analysis shows that incorporating unlabeled data enhances accuracy and reduces sensitivity to label scarcity. Extensive simulations confirm SCORE's superior finite-sample performance over existing methods. Finally, we apply SCORE to predict disability status for patients with multiple sclerosis (MS) using partially labeled EHR data, demonstrating that it produces more informative and predictive patient embeddings for multiple MS-related conditions compared to existing approaches.

stat.ME↗

arXiv2023

Clustering sequence data with mixture Markov chains with covariates using multiple simplex constrained optimization routine (MSiCOR)

Mixture Markov Model (MMM) is a widely used tool to cluster sequences of events coming from a finite state-space. However the MMM likelihood being multi-modal, the challenge remains in its maximization. Although Expectation-Maximization (EM) algorithm remains one of the most popular ways to estimate the MMM parameters, however convergence of EM algorithm is not always guaranteed. Given the computational challenges in maximizing the mixture likelihood on the constrained parameter space, we develop a pattern search-based global optimization technique which can optimize any objective function on a collection of simplexes, which is eventually used to maximize MMM likelihood. This is shown to outperform other related global optimization techniques. In simulation experiments, the proposed method is shown to outperform the expectation-maximization (EM) algorithm in the context of MMM estimation performance. The proposed method is applied to cluster Multiple sclerosis (MS) patients based on their treatment sequences of disease-modifying therapies (DMTs). We also propose a novel method to cluster people with MS based on DMT prescriptions and associated clinical features (covariates) using MMM with covariates. Based on the analysis, we divided MS patients into 3 clusters. Further cluster-specific summaries of relevant covariates indicate patient differences among the clusters.

math.OC↗