arXiv subjects

Chung-Chou H. Chang

Publications and source records attributed to Chung-Chou H. Chang.

9 recordsLinked to original sources

arXiv2026

Doubly Robust Targeted Estimation of Subgroup Average Treatment Effects for Time-to-event Outcomes with Competing Risks

In recent years, precision treatment strategies have gained significant attention in medical research, particularly for patient care. We propose a novel framework for estimating subgroup average treatment effects (ATE) in time-to-event data with competing risks, using ICU patients with sepsis as an illustrative example. Our approach, based on cumulative incidence functions and targeted maximum likelihood estimation (TMLE), achieves both asymptotic efficiency and double robustness. The primary contribution of this work lies in our derivation of the efficient influence function for the targeted causal parameter, subgroup ATE. We established the theoretical proofs for these properties, and subsequently confirmed them through simulations. Our TMLE framework is flexible, accommodating various regression and machine learning models, making it applicable in diverse scenarios. In order to identify variables contributing to treatment effect heterogeneity and to facilitate accurate estimation of subgroup ATE, we developed two distinct variable importance measures (VIMs). This work provides a powerful tool for optimizing personalized treatment strategies, furthering the pursuit of precision medicine.

stat.ME↗

arXiv2026

A Bayesian Finite Mixture Model Approach for Mixed-type Data Clustering and Variable Selection with Censored Biomarkers

Clustering mixed-type data remains a major challenge in biomedical research to uncover clinically meaningful subgroups within heterogeneous patient populations. Most existing clustering methods impose restrictive assumptions like local independence, fail to accommodate censored biomarkers, or unable to quantify variable importance. We propose a Bayesian finite mixture model (BFMM) clustering framework that addresses these limitations. BFMM flexibly models both continuous and categorical variables, incorporates three covariance structures to capture cluster-specific dependencies among continuous features, and handles censored observations through likelihood-based imputation. To facilitate feature prioritization, BFMM uses spike-and-slab priors to estimate variable importance on a continuous 0-1 scale. Simulation studies demonstrate that BFMM outperforms existing methods in clustering accuracy, particularly given strong within-cluster correlation or censored variables, and reliably distinguishes informative features from noise under varying conditions. We applied BFMM to two real-world datasets: (1) the SENECA cohort integrating electronic health records from patients with Sepsis; and (2) the EDEN randomized trial of patients with acute lung injury. In both settings, BFMM identified clinically interpretable phenotypes and revealed variable-specific contributions to subgroup differentiation. In the EDEN trial, it also uncovered evidence of treatment heterogeneity. These findings validate BFMM as an effective, interpretable, and practically useful clustering tool for complex biomedical datasets.

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arXiv2025

A Doubly Robust Instrumental Variable Approach for Estimating Average Treatment Effects in Time-to-Event Data with Unmeasured Confounding: Application to Real-World Data on ICU Patients with Septic Shock

Motivated by conflicting conclusions regarding hydrocortisone's treatment effect on ICU patients with vasopressor-dependent septic shock, we developed a novel instrumental variable (IV) estimator to assess the average treatment effect (ATE) in time-to-event data. In real-world data, IV methods are widely used for estimating causal treatment effects in the presence of unmeasured confounding, but existing approaches for time-to-event outcomes are often constrained by strong parametric assumptions and lack desired statistical properties. Based on our derived the efficient influence function (EIF), the proposed estimator possesses double robustness and achieves asymptotic efficiency. It is also flexible to accommodate machine learning models for outcome, treatment, instrument, and censoring for handling complex real-world data. Through extensive simulations, we demonstrate its double robustness, asymptotic normality, and ideal performance in complex data settings. Using electronic health records (EHR) from ICU patients, we identified physician preferences for prescribing hydrocortisone as the IV to evaluate the treatment effect of hydrocortisone on mortality. Our analysis shows no significant benefit or harm of hydrocortisone on these patients. Applying the proposed doubly robust IV method provides reliable estimates in the presence of unmeasured confounders and offers clinicians with valuable evidence-based guidance for prescribing decisions.

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arXiv2023

Sensitivity Analysis of Causal Treatment Effect Estimation for Clustered Observational Data with Unmeasured Confounding

Identifying causal treatment (or exposure) effects in observational studies requires the data to satisfy the unconfoundedness assumption which is not testable using the observed data. With sensitivity analysis, one can determine how the conclusions might change if assumptions are violated to a certain degree. In this paper, we propose a new technique for sensitivity analysis applicable to clusters observational data with a normally distributed or binary outcome. The proposed methods aim to assess the robustness of estimated treatment effects in a single study as well as in multiple studies, i.e., meta-analysis, against unmeasured confounders. Simulations with various underlying scenarios were conducted to assess the performance of our methods. Unlike other existing sensitivity analysis methods, our methods have no restrictive assumptions on the number of unmeasured confounders or on the relationship between measured and unmeasured confounders, and do not exclude possible interactions between measured confounders and the treatment. Our methods are easy to implement using standard statistical software packages.

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arXiv2022

Bayesian response adaptive randomization design with a composite endpoint of mortality and morbidity

Allocating patients to treatment arms during a trial based on the observed responses accumulated prior to the decision point, and sequential adaptation of this allocation,, could minimize the expected number of failures or maximize total benefit to patients. In this study, we developed a Bayesian response adaptive randomization (RAR) design targeting the endpoint of organ support-free days (OSFD) for patients admitted to the intensive care units (ICU). The OSFD is a mixture of mortality and morbidity assessed by the number of days of free of organ support within a predetermined time-window post-randomization. In the past, researchers treated OSFD as an ordinal outcome variable where the lowest category is death. We propose a novel RAR design for a composite endpoint of mortality and morbidity, e.g., OSFD, by using a Bayesian mixture model with a Markov chain Monte Carlo sampling to estimate the posterior probability of OSFD and determine treatment allocation ratios at each interim. Simulations were conducted to compare the performance of our proposed design under various randomization rules and different alpha spending functions. The results show that our RAR design using Bayesian inference allocated more patients to the better performing arm(s) compared to other existing adaptive rules while assuring adequate power and type I error rate control for the across a range of plausible clinical scenarios.

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arXiv2022

A Tree-based Model Averaging Approach for Personalized Treatment Effect Estimation from Heterogeneous Data Sources

Accurately estimating personalized treatment effects within a study site (e.g., a hospital) has been challenging due to limited sample size. Furthermore, privacy considerations and lack of resources prevent a site from leveraging subject-level data from other sites. We propose a tree-based model averaging approach to improve the estimation accuracy of conditional average treatment effects (CATE) at a target site by leveraging models derived from other potentially heterogeneous sites, without them sharing subject-level data. To our best knowledge, there is no established model averaging approach for distributed data with a focus on improving the estimation of treatment effects. Specifically, under distributed data networks, our framework provides an interpretable tree-based ensemble of CATE estimators that joins models across study sites, while actively modeling the heterogeneity in data sources through site partitioning. The performance of this approach is demonstrated by a real-world study of the causal effects of oxygen therapy on hospital survival rate and backed up by comprehensive simulation results.

stat.ML↗

arXiv2019

A Bayesian Finite Mixture Model with Variable Selection for Data with Mixed-type Variables

Finite mixture model is an important branch of clustering methods and can be applied on data sets with mixed types of variables. However, challenges exist in its applications. First, it typically relies on the EM algorithm which could be sensitive to the choice of initial values. Second, biomarkers subject to limits of detection (LOD) are common to encounter in clinical data, which brings censored variables into finite mixture model. Additionally, researchers are recently getting more interest in variable importance due to the increasing number of variables that become available for clustering. To address these challenges, we propose a Bayesian finite mixture model to simultaneously conduct variable selection, account for biomarker LOD and obtain clustering results. We took a Bayesian approach to obtain parameter estimates and the cluster membership to bypass the limitation of the EM algorithm. To account for LOD, we added one more step in Gibbs sampling to iteratively fill in biomarker values below or above LODs. In addition, we put a spike-and-slab type of prior on each variable to obtain variable importance. Simulations across various scenarios were conducted to examine the performance of this method. Real data application on electronic health records was also conducted.

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arXiv2019

Hybrid Density- and Partition-based Clustering Algorithm for Data with Mixed-type Variables

Clustering is an essential technique for discovering patterns in data. The steady increase in amount and complexity of data over the years led to improvements and development of new clustering algorithms. However, algorithms that can cluster data with mixed variable types (continuous and categorical) remain limited, despite the abundance of data with mixed types particularly in the medical field. Among existing methods for mixed data, some posit unverifiable distributional assumptions or that the contributions of different variable types are not well balanced. We propose a two-step hybrid density- and partition-based algorithm (HyDaP) that can detect clusters after variables selection. The first step involves both density-based and partition-based algorithms to identify the data structure formed by continuous variables and recognize the important variables for clustering; the second step involves partition-based algorithm together with a novel dissimilarity measure we designed for mixed data to obtain clustering results. Simulations across various scenarios and data structures were conducted to examine the performance of the HyDaP algorithm compared to commonly used methods. We also applied the HyDaP algorithm on electronic health records to identify sepsis phenotypes.

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arXiv2019

Landmark Proportional Subdistribution Hazards Models for Dynamic Prediction of Cumulative Incidence Functions

An individualized risk prediction model that dynamically updates the probability of a clinical event from a specific cause is valuable for physicians to be able to optimize personalized treatment strategies in real-time by incorporating all available information collected over the follow-up. However, this is more complex and challenging when competing risks are present, because it requires simultaneously updating the overall survival and the cumulative incidence functions (CIFs) while adjusting for the time-dependent covariates and time-varying covariate effects. In this study, we developed a landmark proportional subdistribution hazards (PSH) model and a more comprehensive supermodel by extending the landmark method to the Fine-Gray model. The performance of our models was assessed via simulations and through analysis of data from a multicenter clinical trial for breast cancer patients. Our proposed models have appealing advantages over other dynamic prediction models for data with competing risks. First, our models are robust against violations of the PSH assumption and can directly predict the conditional CIFs bypassing the estimation of overall survival and greatly simplify the prediction procedure. Second, our landmark PSH supermodel enables researchers to make predictions at a set of landmark points in one step. Third, the proposed models can easily incorporate various types of time-dependent information using existing standard software without computational burden.

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