arXiv subjects

Liangyuan Hu

Publications and source records attributed to Liangyuan Hu.

At least 19 recordsLinked to original sources

arXiv2026

Calibrated Bayes analysis of cluster-randomized trials

In cluster-randomized trials (CRTs), entire clusters of individuals are randomized to treatment, and outcomes within a cluster are typically correlated. While frequentist approaches are standard practice for CRT analysis, Bayesian methods have emerged as a strong alternative. Previous work has investigated the use of Bayesian hierarchical models for continuous, binary, and count outcomes in CRTs, but these approaches focus on model-based treatment effect coefficients as the target estimands, which may have ambiguous interpretation under model misspecification and informative cluster size. In this article, we introduce a calibrated Bayesian procedure for estimand-aligned analysis of CRTs even in the presence of potentially misspecified models. We propose estimators targeting both the cluster-average treatment effect (cluster-ATE) and individual-average treatment effect (individual-ATE), particularly in scenarios with informative cluster sizes. We additionally explore strategies for summarizing the posterior samples that can achieve the frequentist coverage even under working model misspecification. We provide simulation evidence to demonstrate the model-robustness property of the proposed estimators in CRTs, and further investigate the impact of covariate adjustment as well as the use of more flexible Bayesian nonparametric working models in the CRT context.

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arXiv2026

Doubly robust estimators of the restricted mean time in favor estimands in individual- and cluster-randomized trials

Progressive multi-state survival outcomes are common in trials with recurrent or sequential events and require treatment effect estimands that remain interpretable without proportional intensity or Markov assumptions. The restricted mean time in favor of treatment (RMT-IF) extends the restricted mean survival time to ordered multi-state processes and provides such an interpretable estimand. However, existing RMT-IF methods are nonparametric, assume covariate-independent censoring for independent observations, and do not accommodate cluster-randomized trials (CRTs), limiting both efficiency and applicability. We develop a class of doubly robust estimators for RMT-IF under right censoring using an augmented inverse-probability weighting framework that combines stage-specific outcome regression with arm-specific censoring models, yielding consistency when either nuisance model is correctly specified. We further extend the framework to CRTs by formalizing both cluster-level and individual-level average RMT-IF estimands to address informative cluster size and by constructing corresponding doubly robust estimators that account for within-cluster correlation. For inference, we employ model-agnostic jackknife variance estimators in both individually randomized and cluster-randomized settings. Extensive simulation studies demonstrate finite-sample performance, and the methods are illustrated using two randomized trial examples.

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arXiv2025

Estimands and doubly robust estimation for cluster-randomized trials with survival outcomes

Cluster-randomized trials (CRTs) are experimental designs where groups or clusters of participants, rather than the individual participants themselves, are randomized to intervention groups. Analyzing CRT requires distinguishing between treatment effects at the cluster level and the individual level, which requires a clear definition of the estimands under the potential outcomes framework. For analyzing survival outcomes, it is common to assess the treatment effect by comparing survival functions or restricted mean survival times between treatment groups. In this article, we formally characterize cluster-level and individual-level treatment effect estimands with right-censored survival outcomes in CRTs and propose doubly robust estimators for targeting such estimands. Under covariate-dependent censoring, our estimators ensure consistency when either the censoring model or the outcome model is correctly specified, but not necessarily both. We explore different modeling options for the censoring and outcome models to estimate the censoring and survival distributions, and investigate a deletion-based jackknife method for variance and interval estimation. Extensive simulations demonstrate that the proposed methods perform adequately in finite samples. Finally, we illustrate our method by analyzing a completed CRT with survival endpoints.

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arXiv2025

Bayesian Sensitivity Analysis for Causal Estimation with Time-varying Unmeasured Confounding

Causal inference relies on the untestable assumption of no unmeasured confounding. Sensitivity analysis can be used to quantify the impact of unmeasured confounding on causal estimates. Among sensitivity analysis methods proposed in the literature for unmeasured confounding, the latent confounder approach is favoured for its intuitive interpretation via the use of bias parameters to specify the relationship between the observed and unobserved variables and the sensitivity function approach directly characterizes the net causal effect of the unmeasured confounding without explicitly introducing latent variables to the causal models. In this paper, we developed and extended two sensitivity analysis approaches, namely the Bayesian sensitivity analysis with latent confounding variables and the Bayesian sensitivity function approach for the estimation of time-varying treatment effects with longitudinal observational data subjected to time-varying unmeasured confounding. We investigated the performance of these methods in a series of simulation studies and applied them to a multi-center pediatric disease registry data to provide practical guidance on their implementation.

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arXiv2025

A flexible Bayesian g-formula for causal survival analyses with time-dependent confounding

In longitudinal observational studies with time-to-event outcomes, a common objective in causal analysis is to estimate the causal survival curve under hypothetical intervention scenarios. The g-formula is a useful tool for this analysis. To enhance the traditional parametric g-formula, we developed an alternative g-formula estimator, which incorporates the Bayesian Additive Regression Trees (BART) into the modeling of the time-evolving generative components, aiming to mitigate the bias due to model misspecification. We focus on binary time-varying treatments and introduce a general class of g-formulas for discrete survival data that can incorporate the longitudinal balancing scores. The minimum sufficient formulation of these longitudinal balancing scores is linked to the nature of treatment strategies, i.e., static or dynamic. For each type of treatment strategy, we provide posterior sampling algorithms. We conducted simulations to illustrate the empirical performance of the proposed method and demonstrate its practical utility using data from the Yale New Haven Health System's electronic health records.

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arXiv2024

Doubly robust estimation and sensitivity analysis for marginal structural quantile models

The marginal structure quantile model (MSQM) provides a unique lens to understand the causal effect of a time-varying treatment on the full distribution of potential outcomes. Under the semiparametric framework, we derive the efficiency influence function for the MSQM, from which a new doubly robust estimator is proposed for point estimation and inference. We show that the doubly robust estimator is consistent if either of the models associated with treatment assignment or the potential outcome distributions is correctly specified, and is semiparametric efficient if both models are correct. To implement the doubly robust MSQM estimator, we propose to solve a smoothed estimating equation to facilitate efficient computation of the point and variance estimates. In addition, we develop a confounding function approach to investigate the sensitivity of several MSQM estimators when the sequential ignorability assumption is violated. Extensive simulations are conducted to examine the finite-sample performance characteristics of the proposed methods. We apply the proposed methods to the Yale New Haven Health System Electronic Health Record data to study the effect of antihypertensive medications to patients with severe hypertension and assess the robustness of findings to unmeasured baseline and time-varying confounding.

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arXiv2023

A new method for clustered survival data]{A new method for clustered survival data: Estimation of treatment effect heterogeneity and variable selection

We recently developed a new method riAFT-BART to draw causal inferences about population treatment effect on patient survival from clustered and censored survival data while accounting for the multilevel data structure. The practical utility of this method goes beyond the estimation of population average treatment effect. In this work, we exposit how riAFT-BART can be used to solve two important statistical questions with clustered survival data: estimating the treatment effect heterogeneity and variable selection. Leveraging the likelihood-based machine learning, we describe a way in which we can draw posterior samples of the individual survival treatment effect from riAFT-BART model runs, and use the drawn posterior samples to perform an exploratory treatment effect heterogeneity analysis to identify subpopulations who may experience differential treatment effects than population average effects. There is sparse literature on methods for variable selection among clustered and censored survival data, particularly ones using flexible modeling techniques. We propose a permutation based approach using the predictor's variable inclusion proportion supplied by the riAFT-BART model for variable selection. To address the missing data issue frequently encountered in health databases, we propose a strategy to combine bootstrap imputation and riAFT-BART for variable selection among incomplete clustered survival data. We conduct an expansive simulation study to examine the practical operating characteristics of our proposed methods. Finally, we demonstrate the methods via a case study of predictors for in-hospital mortality among severe COVID-19 patients and estimating the heterogeneous treatment effects of three COVID-specific medications. The methods developed in this work are readily available in the $\R$ package $\textsf{riAFTBART}$.

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arXiv2023

Estimating the causal effects of multiple intermittent treatments with application to COVID-19

To draw real-world evidence about the comparative effectiveness of multiple time-varying treatments on patient survival, we develop a joint marginal structural survival model and a novel weighting strategy to account for time-varying confounding and censoring. Our methods formulate complex longitudinal treatments with multiple start/stop switches as the recurrent events with discontinuous intervals of treatment eligibility. We derive the weights in continuous time to handle a complex longitudinal dataset without the need to discretize or artificially align the measurement times. We further use machine learning models designed for censored survival data with time-varying covariates and the kernel function estimator of the baseline intensity to efficiently estimate the continuous-time weights. Our simulations demonstrate that the proposed methods provide better bias reduction and nominal coverage probability when analyzing observational longitudinal survival data with irregularly spaced time intervals, compared to conventional methods that require aligned measurement time points. We apply the proposed methods to a large-scale COVID-19 dataset to estimate the causal effects of several COVID-19 treatments on the composite of in-hospital mortality and ICU admission.

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arXiv2022

CIMTx: An R package for causal inference with multiple treatments using observational data

CIMTx provides efficient and unified functions to implement modern methods for causal inferences with multiple treatments using observational data with a focus on binary outcomes. The methods include regression adjustment, inverse probability of treatment weighting, Bayesian additive regression trees, regression adjustment with multivariate spline of the generalized propensity score, vector matching and targeted maximum likelihood estimation. In addition, CIMTx illustrates ways in which users can simulate data adhering to the complex data structures in the multiple treatment setting. Furthermore, the CIMTx package offers a unique set of features to address the key causal assumptions: positivity and ignorability. For the positivity assumption, CIMTx demonstrates techniques to identify the common support region for retaining inferential units using inverse probability of treatment weighting, Bayesian additive regression trees and vector matching}. To handle the ignorability assumption, CIMTx provides a flexible Monte Carlo sensitivity analysis approach to evaluate how causal conclusions would be altered in response to different magnitude of departure from ignorable treatment assignment.

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arXiv2022

A flexible approach for variable selection in large-scale healthcare database studies with missing covariate and outcome data

Prior work has shown that combining bootstrap imputation with tree-based machine learning variable selection methods can provide good performances achievable on fully observed data when covariate and outcome data are missing at random (MAR). This approach however is computationally expensive, especially on large-scale datasets. We propose an inference-based method, called RR-BART, which leverages the likelihood-based Bayesian machine learning technique, Bayesian additive regression trees, and uses Rubin's rule to combine the estimates and variances of the variable importance measures on multiply imputed datasets for variable selection in the presence of MAR data. We conduct a representative simulation study to investigate the practical operating characteristics of RR-BART, and compare it with the bootstrap imputation based methods. We further demonstrate the methods via a case study of risk factors for 3-year incidence of metabolic syndrome among middle-aged women using data from the Study of Women's Health Across the Nation (SWAN). The simulation study suggests that even in complex conditions of nonlinearity and nonadditivity with a large percentage of missingness, RR-BART can reasonably recover both prediction and variable selection performances, achievable on the fully observed data. RR-BART provides the best performance that the bootstrap imputation based methods can achieve with the optimal selection threshold value. In addition, RR-BART demonstrates a substantially stronger ability of detecting discrete predictors. Furthermore, RR-BART offers substantial computational savings. When implemented on the SWAN data, RR-BART adds to the literature by selecting a set of predictors that had been less commonly identified as risk factors but had substantial biological justifications.

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arXiv2022

A flexible approach for causal inference with multiple treatments and clustered survival outcomes

When drawing causal inferences about the effects of multiple treatments on clustered survival outcomes using observational data, we need to address implications of the multilevel data structure, multiple treatments, censoring and unmeasured confounding for causal analyses. Few off-the-shelf causal inference tools are available to simultaneously tackle these issues. We develop a flexible random-intercept accelerated failure time model, in which we use Bayesian additive regression trees to capture arbitrarily complex relationships between censored survival times and pre-treatment covariates and use the random intercepts to capture cluster-specific main effects. We develop an efficient Markov chain Monte Carlo algorithm to draw posterior inferences about the population survival effects of multiple treatments and examine the variability in cluster-level effects. We further propose an interpretable sensitivity analysis approach to evaluate the sensitivity of drawn causal inferences about treatment effect to the potential magnitude of departure from the causal assumption of no unmeasured confounding. Expansive simulations empirically validate and demonstrate good practical operating characteristics of our proposed methods. Applying the proposed methods to a dataset on older high-risk localized prostate cancer patients drawn from the National Cancer Database, we evaluate the comparative effects of three treatment approaches on patient survival, and assess the ramifications of potential unmeasured confounding. The methods developed in this work are readily available in the $\textsf{R}$ package $\textsf{riAFTBART}$.

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arXiv2021

Propensity Score Weighting Analysis of Survival Outcomes Using Pseudo-observations

Survival outcomes are common in comparative effectiveness studies and require unique handling because they are usually incompletely observed due to right-censoring. A ``once for all'' approach for causal inference with survival outcomes constructs pseudo-observations and allows standard methods such as propensity score weighting to proceed as if the outcomes are completely observed. For a general class of model-free causal estimands with survival outcomes on user-specified target populations, we develop corresponding propensity score weighting estimators based on the pseudo-observations and establish their asymptotic properties. In particular, utilizing the functional delta-method and the von Mises expansion, we derive a new closed-form variance of the weighting estimator that takes into account the uncertainty due to both pseudo-observation calculation and propensity score estimation. This allows valid and computationally efficient inference without resampling. We also prove the optimal efficiency property of the overlap weights within the class of balancing weights for survival outcomes. The proposed methods are applicable to both binary and multiple treatments. Extensive simulations are conducted to explore the operating characteristics of the proposed method versus other commonly used alternatives. We apply the proposed method to compare the causal effects of three popular treatment approaches for prostate cancer patients.

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arXiv2021

A flexible sensitivity analysis approach for unmeasured confounding with multiple treatments and a binary outcome with application to SEER-Medicare lung cancer data

In the absence of a randomized experiment, a key assumption for drawing causal inference about treatment effects is the ignorable treatment assignment. Violations of the ignorability assumption may lead to biased treatment effect estimates. Sensitivity analysis helps gauge how causal conclusions will be altered in response to the potential magnitude of departure from the ignorability assumption. However, sensitivity analysis approaches for unmeasured confounding in the context of multiple treatments and binary outcomes are scarce. We propose a flexible Monte Carlo sensitivity analysis approach for causal inference in such settings. We first derive the general form of the bias introduced by unmeasured confounding, with emphasis on theoretical properties uniquely relevant to multiple treatments. We then propose methods to encode the impact of unmeasured confounding on potential outcomes and adjust the estimates of causal effects in which the presumed unmeasured confounding is removed. Our proposed methods embed nested multiple imputation within the Bayesian framework, which allow for seamless integration of the uncertainty about the values of the sensitivity parameters and the sampling variability, as well as use of the Bayesian Additive Regression Trees for modeling flexibility. Expansive simulations validate our methods and gain insight into sensitivity analysis with multiple treatments. We use the SEER-Medicare data to demonstrate sensitivity analysis using three treatments for early stage non-small cell lung cancer. The methods developed in this work are readily available in the R package SAMTx.

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arXiv2021

Discussion on "Bayesian Regression Tree Models for Causal Inference: Regularization, Confounding, and Heterogeneous Effects" by Hahn, Murray and Carvalho

Hahn et al. (2020) offers an extensive study to explicate and evaluate the performance of the BCF model in different settings and provides a detailed discussion about its utility in causal inference. It is a welcomed addition to the causal machine learning literature. I will emphasize the contribution of the BCF model to the field of causal inference through discussions on two topics: 1) the difference between the PS in the BCF model and the Bayesian PS in a Bayesian updating approach, 2) an alternative exposition of the role of the PS in outcome modeling based methods for the estimation of causal effects. I will conclude with comments on avenues for future research involving BCF that will be important and much needed in the era of Big data.

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arXiv2021

Variable selection with missing data in both covariates and outcomes: Imputation and machine learning

The missing data issue is ubiquitous in health studies. Variable selection in the presence of both missing covariates and outcomes is an important statistical research topic but has been less studied. Existing literature focuses on parametric regression techniques that provide direct parameter estimates of the regression model. Flexible nonparametric machine learning methods considerably mitigate the reliance on the parametric assumptions, but do not provide as naturally defined variable importance measure as the covariate effect native to parametric models. We investigate a general variable selection approach when both the covariates and outcomes can be missing at random and have general missing data patterns. This approach exploits the flexibility of machine learning modeling techniques and bootstrap imputation, which is amenable to nonparametric methods in which the covariate effects are not directly available. We conduct expansive simulations investigating the practical operating characteristics of the proposed variable selection approach, when combined with four tree-based machine learning methods, XGBoost, Random Forests, Bayesian Additive Regression Trees (BART) and Conditional Random Forests, and two commonly used parametric methods, lasso and backward stepwise selection. Numeric results suggest that when combined with bootstrap imputation, XGBoost and BART have the overall best variable selection performance with respect to the $F_1$ score and Type I error across various settings. In general, there is no significant difference in the variable selection performance due to imputation methods. We further demonstrate the methods via a case study of risk factors for 3-year incidence of metabolic syndrome with data from the Study of Women's Health Across the Nation.

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arXiv2021

Estimating heterogeneous survival treatment effect in observational data using machine learning

Methods for estimating heterogeneous treatment effect in observational data have largely focused on continuous or binary outcomes, and have been relatively less vetted with survival outcomes. Using flexible machine learning methods in the counterfactual framework is a promising approach to address challenges due to complex individual characteristics, to which treatments need to be tailored. To evaluate the operating characteristics of recent survival machine learning methods for the estimation of treatment effect heterogeneity and inform better practice, we carry out a comprehensive simulation study presenting a wide range of settings describing confounded heterogeneous survival treatment effects and varying degrees of covariate overlap. Our results suggest that the nonparametric Bayesian Additive Regression Trees within the framework of accelerated failure time model (AFT-BART-NP) consistently yields the best performance, in terms of bias, precision and expected regret. Moreover, the credible interval estimators from AFT-BART-NP provide close to nominal frequentist coverage for the individual survival treatment effect when the covariate overlap is at least moderate. Including a non-parametrically estimated propensity score as an additional fixed covariate in the AFT-BART-NP model formulation can further improve its efficiency and frequentist coverage. Finally, we demonstrate the application of flexible causal machine learning estimators through a comprehensive case study examining the heterogeneous survival effects of two radiotherapy approaches for localized high-risk prostate cancer.

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arXiv2020

Estimation of causal effects of multiple treatments in healthcare database studies with rare outcomes

The preponderance of large-scale healthcare databases provide abundant opportunities for comparative effectiveness research. Evidence necessary to making informed treatment decisions often relies on comparing effectiveness of multiple treatment options on outcomes of interest observed in a small number of individuals. Causal inference with multiple treatments and rare outcomes is a subject that has been treated sparingly in the literature. This paper designs three sets of simulations, representative of the structure of our healthcare database study, and propose causal analysis strategies for such settings. We investigate and compare the operating characteristics of three types of methods and their variants: Bayesian Additive Regression Trees (BART), regression adjustment on multivariate spline of generalized propensity scores (RAMS) and inverse probability of treatment weighting (IPTW) with multinomial logistic regression or generalized boosted models. Our results suggest that BART and RAMS provide lower bias and mean squared error, and the widely used IPTW methods deliver unfavorable operating characteristics. We illustrate the methods using a case study evaluating the comparative effectiveness of robotic-assisted surgery, video-assisted thoracoscopic surgery and open thoracotomy for treating non-small cell lung cancer.

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arXiv2020

The Estimation of Causal Effects of Multiple Treatments in Observational Studies Using Bayesian Additive Regression Trees

There is currently a dearth of appropriate methods to estimate the causal effects of multiple treatments when the outcome is binary. For such settings, we propose the use of nonparametric Bayesian modeling, Bayesian Additive Regression Trees (BART). We conduct an extensive simulation study to compare BART to several existing, propensity score-based methods and to identify its operating characteristics when estimating average treatment effects on the treated. BART consistently demonstrates low bias and mean-squared errors. We illustrate the use of BART through a comparative effectiveness analysis of a large dataset, drawn from the latest SEER-Medicare linkage, on patients who were operated via robotic-assisted surgery, video-assisted thoratic surgery or open thoracotomy.

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