arXiv subjects

Donglin Zeng

Publications and source records attributed to Donglin Zeng.

At least 19 recordsLinked to original sources

arXiv2026

Estimating Pathway Treatment Effects in the Presence of Intermediate Events with Multi-State Data

During clinical trials evaluating a drug's effect on a survival endpoint, intermediate events often occur in addition to the primary event. The treatment can exert its effect on the primary endpoint along multiple pathways through intermediate events. Assumptions for identifying mediation effects, such as sequential ignorability in natural effects or the dismissible components condition in separable effects, fail because intermediate events act as treatment-induced confounding. To understand the effect along each pathway, we consider hypothetical interventions in transitions between event statuses to mimic the treatment mechanism. The hypothetical interventions adjust for effects through intermediate events and marginalize over unobserved treatment-induced confounding, if any. Based on the derived efficient influence functions for the counterfactual cumulative incidences under hypothetical interventions, we construct multiply robust and semiparametrically efficient estimators for pathway treatment effects. Our proposed framework enables the examination of treatment effects through each transition, on each event, and along each path. By analyzing data from the LEADER Trial, we find that liraglutide significantly reduces the risk of cardiovascular and microvascular events. The reduction in all-cause mortality is primarily mediated by its effects on expanded major adverse cardiovascular events.

stat.ME↗

arXiv2026

A Distribution Mapping Approach to Counterfactually Fair Reinforcement Learning

Reinforcement learning (RL) seeks to optimize sequential decisions to maximize population-level benefits over time. However, when deployed in high-stakes settings such as healthcare, RL decisions might systematically restrict some subpopulation's access to valuable services in a manner contrary to the values and goals of stakeholders. Counterfactual fairness (CF) offers a promising framework to address this problem based on causal reasoning. This paper develops a data preprocessing algorithm that, when used in tandem with policy learning, enables CF in RL. Our algorithm relies on a novel quantile distribution mapping method for sequentially estimating the counterfactual states and rewards in the data preprocessing step, subsuming common additivity assumptions used for counterfactual prediction as a special case. We theoretically prove that the per-step level of counterfactual unfairness and infinite-horizon suboptimality gap can be bounded under mild regularity conditions. We also empirically test our algorithm in numerical experiments as well as in application to a real-world interventional digital health dataset.

stat.ML↗

arXiv2026

Integrative learning of individualized treatment rules from multiple studies with partially overlapping treatments

An individualized treatment rule (ITR) tailors treatments to a patient's specific characteristics. However, randomized controlled trials (RCTs) are often underpowered to detect the treatment effect heterogeneity needed for reliable ITR estimation. To address this limitation, there is growing interest in leveraging information from multiple studies to improve statistical power and support individualized decision-making. A key challenge in this context is that available RCTs may not evaluate the same set of treatments. In this paper, we propose an integrative learning framework that synthesizes evidence across multiple RCTs that share a common comparator but differ in their alternative treatment arms. Our method integrates information through a regularized weighted misclassification risk function and adaptively determines the contribution of each study to the ITRs of the others. We rigorously study the excess risk of the resulting estimator. Simulation studies demonstrate that the proposed approaches improve the estimation of both value and benefit functions. We illustrate the utility of our methodology using data from two landmark studies of major depressive disorder: the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care study and the International Study to Predict Optimized Treatment in Depression study, both of which include a selective serotonin reuptake inhibitor as a common treatment arm. We find that the separate learning method outperforms one-size-fits-all methods, and our integrative methods further improve performance.

stat.ME↗

arXiv2026

Prediction-Oriented Transfer Learning for Survival Analysis

Transfer learning is beneficial for survival analysis, especially when the target study has a limited number of events. However, existing transfer learning methods rely on the restrictive assumption that the target and source studies share similar parameters under Cox models, and most require access to individual-level source data. In this article, we propose a novel transfer learning framework that enhances model-based survival prediction by transferring predictive rather than distributional knowledge from source studies. Our approach employs flexible semiparametric transformation models for the target data while eliminating the need to model or share the source data. The ingeniously designed penalty enables simple and stable computation via an EM algorithm. We rigorously establish the asymptotic properties of the proposed estimator and show that it achieves a faster convergence rate than the target-only estimator when source knowledge is sufficiently accurate. We demonstrate the advantages of our methods through extensive simulation studies and an application to two major breast cancer studies, with the objective of improving survival prediction in a target cohort using predictive information from an external study.

stat.ME↗

arXiv2026

Learning Optimal Individualized Decision Rules with Conditional Demographic Parity

Individualized decision rules (IDRs) have become increasingly prevalent in societal applications such as personalized marketing, healthcare, and public policy design. However, a critical ethical concern arises from the potential discriminatory effects of IDRs trained on biased data. These algorithms may disproportionately harm individuals from minority subgroups defined by sensitive attributes like gender, race, or language. To address this issue, we propose a novel framework that incorporates demographic parity (DP) and conditional demographic parity (CDP) constraints into the estimation of optimal IDRs. We show that the theoretically optimal IDRs under DP and CDP constraints can be obtained by applying perturbations to the unconstrained optimal IDRs, enabling a computationally efficient solution. Theoretically, we derive convergence rates for both policy value and the fairness constraint term. The effectiveness of our methods is illustrated through comprehensive simulation studies and an empirical application to the Oregon Health Insurance Experiment.

stat.ML↗

arXiv2026

Semiparametric Analysis of Interval-Censored Data Subject to Inaccurate Diagnoses with A Terminal Event

Interval-censoring frequently occurs in studies of chronic diseases where disease status is inferred from intermittently collected biomarkers. Although many methods have been developed to analyze such data, they typically assume perfect disease diagnosis, which often does not hold in practice due to the inherent imperfect clinical diagnosis of cognitive functions or measurement errors of biomarkers such as cerebrospinal fluid. In this work, we introduce a semiparametric modeling framework using the Cox proportional hazards model to address interval-censored data in the presence of inaccurate disease diagnosis. Our model incorporates sensitivity and specificity of the diagnosis to account for uncertainty in whether the interval truly contains the disease onset. Furthermore, the framework accommodates scenarios involving a terminal event and when diagnosis is accurate, such as through postmortem analysis. We propose a nonparametric maximum likelihood estimation method for inference and develop an efficient EM algorithm to ensure computational feasibility. The regression coefficient estimators are shown to be asymptotically normal, achieving semiparametric efficiency bounds. We further validate our approach through extensive simulation studies and an application assessing Alzheimer's disease (AD) risk. We find that amyloid-beta is significantly associated with AD, but Tau is predictive of both AD and mortality.

stat.ME↗

arXiv2025

Debiased Inference for High-Dimensional Regression Models Based on Profile M-Estimation

Debiased inference for high-dimensional regression models has received substantial recent attention to ensure regularized estimators have valid inference. Many existing methods focus on achieving Neyman orthogonality through explicitly constructing projections onto the space of nuisance parameters, which is infeasible when an explicit form of the projection is unavailable. We introduce a general debiasing framework, Debiased Profile $M$-Estimation (DPME), which applies to a broad class of models and does not require model-specific Neyman orthogonalization or projection derivations as in existing methods. Our approach begins with obtaining an initial estimator of the parameters by optimizing a penalized objective function. To correct for the bias introduced by penalization, we construct a one-step estimator using the Newton--Raphson update, applied to the gradient of a profile function defined as the optimal objective function with the parameter of interest held fixed. We use numerical differentiation without requiring explicit calculation of the gradients. The resulting DPME estimator is shown to be asymptotically linear and normally distributed. Through extensive simulations, we demonstrate that the proposed method achieves better coverage rates than existing alternatives with largely reduced computational cost. Finally, we illustrate the utility of our method by applying it to estimate a treatment rule for multiple myeloma.

stat.ME↗

arXiv2025

PyCFRL: A Python library for counterfactually fair offline reinforcement learning via sequential data preprocessing

Reinforcement learning (RL) aims to learn and evaluate a sequential decision rule, often referred to as a "policy", that maximizes the population-level benefit in an environment across possibly infinitely many time steps. However, the sequential decisions made by an RL algorithm, while optimized to maximize overall population benefits, may disadvantage certain individuals who are in minority or socioeconomically disadvantaged groups. To address this problem, we introduce PyCFRL, a Python library for ensuring counterfactual fairness in offline RL. PyCFRL implements a novel data preprocessing algorithm for learning counterfactually fair RL policies from offline datasets and provides tools to evaluate the values and counterfactual unfairness levels of RL policies. We describe the high-level functionalities of PyCFRL and demonstrate one of its major use cases through a data example. The library is publicly available on PyPI and Github (https://github.com/JianhanZhang/PyCFRL), and detailed tutorials can be found in the PyCFRL documentation (https://pycfrl-documentation.netlify.app).

stat.ML↗

arXiv2025

A New Class of Mark-Specific Proportional Hazards Models for Recurrent Events: Application to Opioid Refills Among Post-Surgical Patients

Prescription opioids relieve moderate-to-severe pain after surgery, but overprescription can lead to misuse and overdose. Understanding factors associated with post-surgical opioid refills is crucial for improving pain management and reducing opioid-related harms. Conventional methods often fail to account for refill size or dosage and capture patient risk dynamics. We address this gap by treating dosage as a continuously varying mark for each refill event and proposing a new class of mark-specific proportional hazards models for recurrent events. Our marginal model, developed on the gap-time scale with a dual weighting scheme, accommodates event proximity to dosage of interest while accounting for the informative number of recurrences. We establish consistency and asymptotic normality of the estimator and provide a sandwich variance estimator for robust inference. Simulations show improved finite-sample performance over competing methods. We apply the model to data from the Michigan Surgical Quality Collaborative and Michigan Automated Prescription System. Results show that high BMI, smoking, cancer, and open surgery increase hazards of high-dosage refills, while inpatient surgeries elevate refill hazards across all dosages. Black race is associated with higher hazards of low-dosage but lower hazards of high-dosage refills. These findings may inform personalized, dosage-specific pain management strategies.

stat.ME↗

arXiv2025

Cumulative Marginal Mean Model for Assessing Sequential Effects Using Digital Health Data

Mobile health (mHealth) leverages digital technologies, such as mobile phones, to capture objective, frequent, and real-world digital phenotypes from individuals, enabling the delivery of tailored interventions to accommodate substantial between-subject and temporal heterogeneity. However, evaluating heterogeneous treatment effects (HTEs) using digital phenotype data is challenging because treatments are delivered dynamically over time and may generate carryover effects that persist beyond the immediate response. Additionally, modeling observational data is complicated by confounding factors. To address these challenges, we propose a double machine learning (DML) method for estimating time-varying HTEs using digital phenotypes under a cumulative marginal mean model that separates current instantaneous effects from lagged carryover effects. Our approach uses a sequential estimation procedure together with Neyman-orthogonal scores to obtain robust inference for the time-varying HTEs. We establish the asymptotic normality of the proposed estimator. Extensive simulation studies validate the finite-sample performance of our approach, demonstrating the advantages of DML and the decomposition of treatment effects. We apply the method to an mHealth study of Parkinson's disease (PD), where we find that treatment is significantly more effective for younger patients. Our results highlight the potential of the proposed approach for advancing precision medicine in mHealth studies.

stat.ME↗

arXiv2025

Model positive and unlabeled data with a generalized additive density ratio model

We address learning from positive and unlabeled (PU) data, a common setting in which only some positives are labeled and the rest are mixed with negatives. Classical exponential tilting models guarantee identifiability by assuming a linear structure, but they can be badly misspecified when relationships are nonlinear. We propose a generalized additive density-ratio framework that retains identifiability while allowing smooth, feature-specific effects. The approach comes with a practical fitting algorithm and supporting theory that enables estimation and inference for the mixture proportion and other quantities of interest. In simulations and analyses of benchmark datasets, the proposed method matches the standard exponential tilting method when the linear model is correct and delivers clear gains when it is not. Overall, the framework strikes a useful balance between flexibility and interpretability for PU learning and provides principled tools for estimation, prediction, and uncertainty assessment.

stat.ME↗

arXiv2025

Demographic Parity-aware Individualized Treatment Rules

There has been growing interest in developing optimal individualized treatment rules (ITRs) in various fields, such as precision medicine, business decision-making, and social welfare distribution. The application of ITRs within a societal context raises substantial concerns regarding potential discrimination over sensitive attributes such as age, gender, or race. To address this concern directly, we introduce the concept of demographic parity in ITRs. However, estimating an optimal ITR that satisfies the demographic parity requires solving a non-convex constrained optimization problem. To overcome these computational challenges, we employ tailored fairness proxies inspired by demographic parity and transform it into a convex quadratic programming problem. Additionally, we establish the consistency of the proposed estimator and the risk bound. The performance of the proposed method is demonstrated through extensive simulation studies and real data analysis.

stat.ME↗

arXiv2025

Counterfactually Fair Reinforcement Learning via Sequential Data Preprocessing

When applied in healthcare, reinforcement learning (RL) seeks to dynamically match the right interventions to subjects to maximize population benefit. However, the learned policy may disproportionately allocate efficacious actions to one subpopulation, creating or exacerbating disparities in other socioeconomically-disadvantaged subgroups. These biases tend to occur in multi-stage decision making and can be self-perpetuating, which if unaccounted for could cause serious unintended consequences that limit access to care or treatment benefit. Counterfactual fairness (CF) offers a promising statistical tool grounded in causal inference to formulate and study fairness. In this paper, we propose a general framework for fair sequential decision making. We theoretically characterize the optimal CF policy and prove its stationarity, which greatly simplifies the search for optimal CF policies by leveraging existing RL algorithms. The theory also motivates a sequential data preprocessing algorithm to achieve CF decision making under an additive noise assumption. We prove and then validate our policy learning approach in controlling unfairness and attaining optimal value through simulations. Analysis of a digital health dataset designed to reduce opioid misuse shows that our proposal greatly enhances fair access to counseling.

stat.ML↗

arXiv2024

Dynamic Classification of Latent Disease Progression with Auxiliary Surrogate Labels

Disease progression prediction based on patients' evolving health information is challenging when true disease states are unknown due to diagnostic capabilities or high costs. For example, the absence of gold-standard neurological diagnoses hinders distinguishing Alzheimer's disease (AD) from related conditions such as AD-related dementias (ADRDs), including Lewy body dementia (LBD). Combining temporally dependent surrogate labels and health markers may improve disease prediction. However, existing literature models informative surrogate labels and observed variables that reflect the underlying states using purely generative approaches, limiting the ability to predict future states. We propose integrating the conventional hidden Markov model as a generative model with a time-varying discriminative classification model to simultaneously handle potentially misspecified surrogate labels and incorporate important markers of disease progression. We develop an adaptive forward-backward algorithm with subjective labels for estimation, and utilize the modified posterior and Viterbi algorithms to predict the progression of future states or new patients based on objective markers only. Importantly, the adaptation eliminates the need to model the marginal distribution of longitudinal markers, a requirement in traditional algorithms. Asymptotic properties are established, and significant improvement with finite samples is demonstrated via simulation studies. Analysis of the neuropathological dataset of the National Alzheimer's Coordinating Center (NACC) shows much improved accuracy in distinguishing LBD from AD.

stat.ME↗

arXiv2024

Nonparametric Causal Survival Analysis with Clustered Interference

Inferring treatment effects on a survival time outcome based on data from an observational study is challenging due to the presence of censoring and possible confounding. An additional challenge occurs when a unit's treatment affects the outcome of other units, i.e., there is interference. In some settings, units may be grouped into clusters such that it is reasonable to assume interference only occurs within clusters, i.e., there is clustered interference. In this paper, methods are developed which can accommodate confounding, censored outcomes, and clustered interference. The approach avoids parametric assumptions and permits inference about counterfactual scenarios corresponding to any stochastic policy which modifies the propensity score distribution, and thus may have application across diverse settings. The proposed nonparametric sample splitting estimators allow for flexible data-adaptive estimation of nuisance functions and are consistent and asymptotically normal with parametric convergence rates. Simulation studies demonstrate the finite sample performance of the proposed estimators, and the methods are applied to a cholera vaccine study in Bangladesh.

stat.ME↗

arXiv2024

Learning Optimal Dynamic Treatment Regimens Subject to Stagewise Risk Controls

Dynamic treatment regimens (DTRs) aim at tailoring individualized sequential treatment rules that maximize cumulative beneficial outcomes by accommodating patients' heterogeneity in decision-making. For many chronic diseases including type 2 diabetes mellitus (T2D), treatments are usually multifaceted in the sense that aggressive treatments with a higher expected reward are also likely to elevate the risk of acute adverse events. In this paper, we propose a new weighted learning framework, namely benefit-risk dynamic treatment regimens (BR-DTRs), to address the benefit-risk trade-off. The new framework relies on a backward learning procedure by restricting the induced risk of the treatment rule to be no larger than a pre-specified risk constraint at each treatment stage. Computationally, the estimated treatment rule solves a weighted support vector machine problem with a modified smooth constraint. Theoretically, we show that the proposed DTRs are Fisher consistent, and we further obtain the convergence rates for both the value and risk functions. Finally, the performance of the proposed method is demonstrated via extensive simulation studies and application to a real study for T2D patients.

stat.ME↗

arXiv2024

Doubly robust causal inference through penalized bias-reduced estimation: combining non-probability samples with designed surveys

Causal inference on the average treatment effect (ATE) using non-probability samples, such as electronic health records (EHR), faces challenges from sample selection bias and high-dimensional covariates. This requires considering a selection model alongside treatment and outcome models that are typical ingredients in causal inference. This paper considers integrating large non-probability samples with external probability samples from a design survey, addressing moderately high-dimensional confounders and variables that influence selection. In contrast to the two-step approach that separates variable selection and debiased estimation, we propose a one-step plug-in doubly robust (DR) estimator of the ATE. We construct a novel penalized estimating equation by minimizing the squared asymptotic bias of the DR estimator. Our approach facilitates ATE inference in high-dimensional settings by ignoring the variability in estimating nuisance parameters, which is not guaranteed in conventional likelihood approaches with non-differentiable L1-type penalties. We provide a consistent variance estimator for the DR estimator. Simulation studies demonstrate the double robustness of our estimator under misspecification of either the outcome model or the selection and treatment models, as well as the validity of statistical inference under penalized estimation. We apply our method to integrate EHR data from the Michigan Genomics Initiative with an external probability sample.

stat.ME↗

arXiv2024

Fusing Individualized Treatment Rules Using Secondary Outcomes

An individualized treatment rule (ITR) is a decision rule that recommends treatments for patients based on their individual feature variables. In many practices, the ideal ITR for the primary outcome is also expected to cause minimal harm to other secondary outcomes. Therefore, our objective is to learn an ITR that not only maximizes the value function for the primary outcome, but also approximates the optimal rule for the secondary outcomes as closely as possible. To achieve this goal, we introduce a fusion penalty to encourage the ITRs based on different outcomes to yield similar recommendations. Two algorithms are proposed to estimate the ITR using surrogate loss functions. We prove that the agreement rate between the estimated ITR of the primary outcome and the optimal ITRs of the secondary outcomes converges to the true agreement rate faster than if the secondary outcomes are not taken into consideration. Furthermore, we derive the non-asymptotic properties of the value function and misclassification rate for the proposed method. Finally, simulation studies and a real data example are used to demonstrate the finite-sample performance of the proposed method.

stat.ME↗