arXiv subjects

Donglin Zeng

Publications and source records attributed to Donglin Zeng.

At least 37 records · Page 2Linked to original sources

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.

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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.

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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.

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arXiv2023

Efficient Nonparametric Estimation of Stochastic Policy Effects with Clustered Interference

Interference occurs when a unit's treatment (or exposure) affects another unit's outcome. In some settings, units may be grouped into clusters such that it is reasonable to assume that interference, if present, only occurs between individuals in the same cluster, i.e., there is clustered interference. Various causal estimands have been proposed to quantify treatment effects under clustered interference from observational data, but these estimands either entail treatment policies lacking real-world relevance or are based on parametric propensity score models. Here, we propose new causal estimands based on modification of the propensity score distribution which may be more relevant in many contexts and are not based on parametric models. Nonparametric sample splitting estimators of the new estimands are constructed, which allow for flexible data-adaptive estimation of nuisance functions and are consistent, asymptotically normal, and efficient, converging at the usual parametric rate. Simulations show the finite sample performance of the proposed estimators. The proposed methods are applied to evaluate the effect of water, sanitation, and hygiene facilities on diarrhea among children in Senegal.

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arXiv2023

Rank Intraclass Correlation for Clustered Data

Clustered data are common in biomedical research. Observations in the same cluster are often more similar to each other than to observations from other clusters. The intraclass correlation coefficient (ICC), first introduced by R. A. Fisher, is frequently used to measure this degree of similarity. However, the ICC is sensitive to extreme values and skewed distributions, and depends on the scale of the data. It is also not applicable to ordered categorical data. We define the rank ICC as a natural extension of Fisher's ICC to the rank scale, and describe its corresponding population parameter. The rank ICC is simply interpreted as the rank correlation between a random pair of observations from the same cluster. We also extend the definition when the underlying distribution has more than two hierarchies. We describe estimation and inference procedures, show the asymptotic properties of our estimator, conduct simulations to evaluate its performance, and illustrate our method in three real data examples with skewed data, count data, and three-level ordered categorical data.

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arXiv2023

A network-based regression approach for identifying subject-specific driver mutations

In cancer genomics, it is of great importance to distinguish driver mutations, which contribute to cancer progression, from causally neutral passenger mutations. We propose a random-effect regression approach to estimate the effects of mutations on the expressions of genes in tumor samples, where the estimation is assisted by a prespecified gene network. The model allows the mutation effects to vary across subjects. We develop a subject-specific mutation score to quantify the effect of a mutation on the expressions of its downstream genes, so mutations with large scores can be prioritized as drivers. We demonstrate the usefulness of the proposed methods by simulation studies and provide an application to a breast cancer genomics study.

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arXiv2023

Exploratory Hidden Markov Factor Models for Longitudinal Mobile Health Data: Application to Adverse Posttraumatic Neuropsychiatric Sequelae

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among veterans and millions of Americans after traumatic exposures, resulting in substantial burdens for trauma survivors and society. Despite numerous studies conducted on APNS over the past decades, there has been limited progress in understanding the underlying neurobiological mechanisms due to several unique challenges. One of these challenges is the reliance on subjective self-report measures to assess APNS, which can easily result in measurement errors and biases (e.g., recall bias). To mitigate this issue, in this paper, we investigate the potential of leveraging the objective longitudinal mobile device data to identify homogeneous APNS states and study the dynamic transitions and potential risk factors of APNS after trauma exposure. To handle specific challenges posed by longitudinal mobile device data, we developed exploratory hidden Markov factor models and designed a Stabilized Expectation-Maximization algorithm for parameter estimation. Simulation studies were conducted to evaluate the performance of parameter estimation and model selection. Finally, to demonstrate the practical utility of the method, we applied it to mobile device data collected from the Advancing Understanding of RecOvery afteR traumA (AURORA) study.

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arXiv2023

Mixed-Response State-Space Model for Analyzing Multi-Dimensional Digital Phenotypes

Digital technologies (e.g., mobile phones) can be used to obtain objective, frequent, and real-world digital phenotypes from individuals. However, modeling these data poses substantial challenges since observational data are subject to confounding and various sources of variabilities. For example, signals on patients' underlying health status and treatment effects are mixed with variation due to the living environment and measurement noises. The digital phenotype data thus shows extensive variabilities between- and within-patient as well as across different health domains (e.g., motor, cognitive, and speaking). Motivated by a mobile health study of Parkinson's disease (PD), we develop a mixed-response state-space (MRSS) model to jointly capture multi-dimensional, multi-modal digital phenotypes and their measurement processes by a finite number of latent state time series. These latent states reflect the dynamic health status and personalized time-varying treatment effects and can be used to adjust for informative measurements. For computation, we use the Kalman filter for Gaussian phenotypes and importance sampling with Laplace approximation for non-Gaussian phenotypes. We conduct comprehensive simulation studies and demonstrate the advantage of MRSS in modeling a mobile health study that remotely collects real-time digital phenotypes from PD patients.

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arXiv2023

Asymptotic Properties for Cumulative Probability Models for Continuous Outcomes

Regression models for continuous outcomes often require a transformation of the outcome, which the user either specify {\it a priori} or estimate from a parametric family. Cumulative probability models (CPMs) nonparametrically estimate the transformation and are thus a flexible analysis approach for continuous outcomes. However, it is difficult to establish asymptotic properties for CPMs due to the potentially unbounded range of the transformation. Here we show asymptotic properties for CPMs when applied to slightly modified data where the outcomes are censored at the ends. We prove uniform consistency of the estimated regression coefficients and the estimated transformation function over the non-censored region, and describe their joint asymptotic distribution. We show with simulations that results from this censored approach and those from the CPM on the original data are similar when a small fraction of data are censored. We reanalyze a dataset of HIV-positive patients with CPMs to illustrate and compare the approaches.

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arXiv2022

Elastic Integrative Analysis of Randomized Trial and Real-World Data for Treatment Heterogeneity Estimation

We propose a test-based elastic integrative analysis of the randomized trial and real-world data to estimate treatment effect heterogeneity with a vector of known effect modifiers. When the real-world data are not subject to bias, our approach combines the trial and real-world data for efficient estimation. Utilizing the trial design, we construct a test to decide whether or not to use real-world data. We characterize the asymptotic distribution of the test-based estimator under local alternatives. We provide a data-adaptive procedure to select the test threshold that promises the smallest mean square error and an elastic confidence interval with a good finite-sample coverage property.

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arXiv2022

Maximum Likelihood Estimation for Semiparametric Regression Models with Interval-Censored Multi-State Data

Interval-censored multi-state data arise in many studies of chronic diseases, where the health status of a subject can be characterized by a finite number of disease states and the transition between any two states is only known to occur over a broad time interval. We formulate the effects of potentially time-dependent covariates on multi-state processes through semiparametric proportional intensity models with random effects. We adopt nonparametric maximum likelihood estimation (NPMLE) under general interval censoring and develop a stable expectation-maximization (EM) algorithm. We show that the resulting parameter estimators are consistent and that the finite-dimensional components are asymptotically normal with a covariance matrix that attains the semiparametric efficiency bound and can be consistently estimated through profile likelihood. In addition, we demonstrate through extensive simulation studies that the proposed numerical and inferential procedures perform well in realistic settings. Finally, we provide an application to a major epidemiologic cohort study.

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arXiv2022

Analyzing Clustered Continuous Response Variables with Ordinal Regression Models

Continuous response variables often need to be transformed to meet regression modeling assumptions; however, finding the optimal transformation is challenging and results may vary with the choice of transformation. When a continuous response variable is measured repeatedly for a subject or the continuous responses arise from clusters, it is more challenging to model the continuous response data due to correlation within clusters. We extend a widely used ordinal regression model, the cumulative probability model (CPM), to fit clustered continuous response variables based on generalized estimating equation (GEE) methods for ordinal responses. With our approach, estimates of marginal parameters, cumulative distribution functions (CDFs), expectations, and quantiles conditional on covariates can be obtained without pre-transformation of the potentially skewed continuous response data. Computational challenges arise with large numbers of distinct values of the continuous response variable, and we propose two feasible and computationally efficient approaches to fit CPMs for clustered continuous response variables with different working correlation structures. We study finite sample operating characteristics of the estimators via simulation, and illustrate their implementation with two data examples. One studies predictors of CD4:CD8 ratios in an HIV study. The other uses data from The Lung Health Study to investigate the contribution of a single nucleotide polymorphism to lung function decline.

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arXiv2021

Improving trial generalizability using observational studies

Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces the covariate balance between the RCT and OS, therefore improving the trial-based estimator's generalizability. Exploiting semiparametric efficiency theory, we propose a doubly robust augmented calibration weighting estimator that achieves the efficiency bound derived under the identification assumptions. A nonparametric sieve method is provided as an alternative to the parametric approach, which enables the robust approximation of the nuisance functions and data-adaptive selection of outcome predictors for calibration. We establish asymptotic results and confirm the finite sample performances of the proposed estimators by simulation experiments and an application on the estimation of the treatment effect of adjuvant chemotherapy for early-stage non-small cell lung patients after surgery.

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arXiv2021

A Parsimonious Personalized Dose Finding Model via Dimension Reduction

Learning an individualized dose rule in personalized medicine is a challenging statistical problem. Existing methods often suffer from the curse of dimensionality, especially when the decision function is estimated nonparametrically. To tackle this problem, we propose a dimension reduction framework that effectively reduces the estimation to a lower-dimensional subspace of the covariates. We exploit that the individualized dose rule can be defined in a subspace spanned by a few linear combinations of the covariates, leading to a more parsimonious model. The proposed framework does not require the inverse probability of the propensity score under observational studies due to a direct maximization of the value function. This distinguishes us from the outcome weighted learning framework, which also solves decision rules directly. Under the same framework, we further propose a pseudo-direct learning approach that focuses more on estimating the dimensionality-reduced subspace of the treatment outcome. Parameters in both approaches can be estimated efficiently using an orthogonality constrained optimization algorithm on the Stiefel manifold. Under mild regularity assumptions, the results on the asymptotic normality of the proposed estimators are established, respectively. We also derive the consistency and convergence rate for the value function under the estimated optimal dose rule. We evaluate the performance of the proposed approaches through extensive simulation studies and a warfarin pharmacogenetic dataset.

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arXiv2021

Evaluating Effectiveness of Public Health Intervention Strategies for Mitigating COVID-19 Pandemic

Coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global public health challenge. In the United States (US), state governments have implemented various non-pharmaceutical interventions (NPIs), such as physical distance closure (lockdown), stay-at-home order, mandatory facial mask in public in response to the rapid spread of COVID-19. To evaluate the effectiveness of these NPIs, we propose a nested case-control design with propensity score weighting under the quasi-experiment framework to estimate the average intervention effect on disease transmission across states. We further develop a method to test for factors that moderate intervention effect to assist precision public health intervention. Our method takes account of the underlying dynamics of disease transmission and balance state-level pre-intervention characteristics. We prove that our estimator provides causal intervention effect under assumptions. We apply this method to analyze US COVID-19 incidence cases to estimate the effects of six interventions. We show that lockdown has the largest effect on reducing transmission and reopening bars significantly increase transmission. States with a higher percentage of non-white population are at greater risk of increased $R_t$ associated with reopening bars.

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arXiv2021

A General Framework of Nonparametric Feature Selection in High-Dimensional Data

Nonparametric feature selection in high-dimensional data is an important and challenging problem in statistics and machine learning fields. Most of the existing methods for feature selection focus on parametric or additive models which may suffer from model misspecification. In this paper, we propose a new framework to perform nonparametric feature selection for both regression and classification problems. In this framework, we learn prediction functions through empirical risk minimization over a reproducing kernel Hilbert space. The space is generated by a novel tensor product kernel which depends on a set of parameters that determine the importance of the features. Computationally, we minimize the empirical risk with a penalty to estimate the prediction and kernel parameters at the same time. The solution can be obtained by iteratively solving convex optimization problems. We study the theoretical property of the kernel feature space and prove both the oracle selection property and the Fisher consistency of our proposed method. Finally, we demonstrate the superior performance of our approach compared to existing methods via extensive simulation studies and application to a microarray study of eye disease in animals.

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arXiv2020

Representation Learning for Integrating Multi-domain Outcomes to Optimize Individualized Treatments

For mental disorders, patients' underlying mental states are non-observed latent constructs which have to be inferred from observed multi-domain measurements such as diagnostic symptoms and patient functioning scores. Additionally, substantial heterogeneity in the disease diagnosis between patients needs to be addressed for optimizing individualized treatment policy in order to achieve precision medicine. To address these challenges, we propose an integrated learning framework that can simultaneously learn patients' underlying mental states and recommend optimal treatments for each individual. This learning framework is based on the measurement theory in psychiatry for modeling multiple disease diagnostic measures as arising from the underlying causes (true mental states). It allows incorporation of the multivariate pre- and post-treatment outcomes as well as biological measures while preserving the invariant structure for representing patients' latent mental states. A multi-layer neural network is used to allow complex treatment effect heterogeneity. Optimal treatment policy can be inferred for future patients by comparing their potential mental states under different treatments given the observed multi-domain pre-treatment measurements. Experiments on simulated data and a real-world clinical trial data show that the learned treatment polices compare favorably to alternative methods on heterogeneous treatment effects, and have broad utilities which lead to better patient outcomes on multiple domains.

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arXiv2020

Assessing Impact of Unobserved Confounders with Sensitivity Index Probabilities through Pseudo-Experiments

Unobserved confounders are a long-standing issue in causal inference using propensity score methods. This study proposed nonparametric indices to quantify the impact of unobserved confounders through pseudo-experiments with an application to real-world data. The study finding suggests that the proposed indices can reflect the true impact of confounders. It is hoped that this study will lead to further discussion on this important issue and help move the science of causal inference forward.

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