arXiv subjects

Michael G. Hudgens

Publications and source records attributed to Michael G. Hudgens.

At least 19 recordsLinked to original sources

arXiv2026

Assessing Vaccine Effectiveness in Observational Studies via Nested Trial Emulation

Observational data are frequently used to evaluate real-world vaccine effectiveness (VE). For vaccines such as those developed against COVID-19, VE may vary over calendar time because of changes in circulating viral variants and over time since vaccination because of waning immunity. Nested trial emulation (NTE) provides a framework for estimating causal effects from observational data while reducing biases common to standard observational analyses. NTE involves emulating a sequence of hypothetical trials, each initiated from a different calendar date. This manuscript considers a NTE inverse probability weighted estimator of vaccine effectiveness that may vary over calendar time, time since vaccination, or both. The proposed approach characterizes trial-specific VE and uses those estimates to assess changes in vaccine protection across calendar time. As changes in VE estimates across trials may be attributable to variation in covariate distributions across trial-eligible populations, standardization of trial-specific estimates is considered. Statistical testing for evaluating heterogeneity in VE across trials is also considered. The methods are used to estimate vaccine effectiveness against COVID-19 outcomes using observational data on over 110,000 residents of Abruzzo, Italy during 2021.

stat.ME↗

arXiv2026

Difference-in-differences with stochastic policy shifts of a continuous treatment

Treatment effects of stochastic policy shifts quantify differences in outcomes across counterfactual scenarios with varying treatment distributions. Stochastic policy shifts may be of interest in settings where it is unrealistic or infeasible to deterministically manipulate treatments. In this paper, methods are developed to draw inference about stochastic policy effects under difference-in-differences (DiD) designs with a continuous treatment. The proposed causal estimand is the expected effect of modifying the continuous dose distribution among the treated, i.e., those that received a non-zero dose. Several possible stochastic policies are discussed and a general framework for identification and estimation is proposed. One stochastic policy applicable to many settings is the exponential tilt, which increments the conditional density function of the continuous dose. For the exponential tilt policy, a double/debiased machine learning estimator is proposed that allows for data-adaptive, nonparametric nuisance function estimation. Under mild convergence rate conditions, the estimator is shown to be root-$n$ consistent and asymptotically normal with variance attaining the nonparametric efficiency bound. The proposed method is used to study the effect of hydraulic fracturing activity on employment and income.

stat.ME↗

arXiv2026

Symmetric Vaccine Efficacy

Traditional measures of vaccine efficacy (VE) are inherently asymmetric, constrained above by $1$ but unbounded below. As a result, VE estimates and corresponding confidence intervals can extend far below zero, making interpretation difficult and potentially obscuring whether the apparent effect reflects true harm or simply statistical uncertainty. The proposed symmetric vaccine efficacy (SVE) is a bounded and interpretable alternative to VE that maintains desirable statistical properties while resolving these asymmetries. SVE is defined as a symmetric transformation of infection risks, with possible values within $[-1, 1]$, providing a common scale for both beneficial and harmful vaccine effects. This paper describes the relationship between SVE and traditional VE, considers inference about SVE, and illustrates the utility of the proposed measure by reanalyzing data from a randomized trial of a candidate HIV vaccine. Open-source tools for computing estimates of SVE and corresponding confidence intervals are available in R through the sve package.

stat.ME↗

arXiv2026

Efficient nonparametric estimation with difference-in-differences in the presence of network dependence and interference

Differences-in-differences (DiD) is a causal inference method for observational longitudinal data that assumes parallel expected potential outcome trajectories between treatment groups under the counterfactual scenario where all units receive a specific treatment. In this paper DiD is extended to allow for: (i) non-identically distributed treatment effects and exposure probabilities; (ii) interference, where treatment of one unit can affect outcomes in neighboring units; and (iii) latent variable dependence, where outcomes, treatments, and covariates may exhibit between-unit correlation. The causal estimand of interest is the network-averaged expected exposure effect if units received a specific exposure level, where a unit's exposure is a function of its own treatment and its neighbors' treatments. Under a conditional parallel trends assumption and suitable network dependency and heterogeneity conditions, a doubly robust estimator allowing for data-adaptive nuisance function estimation is proposed and shown to be consistent, asymptotically normal, and efficient. The proposed methods are evaluated in simulations and applied to study the effects of adopting emission control technologies in coal power plants on county-level mortality due to cardiovascular disease.

stat.ME↗

arXiv2025

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↗

arXiv2025

Addressing Confounding and Continuous Exposure Measurement Error Using Corrected Score Functions

Confounding and exposure measurement error can introduce bias when drawing inference about the marginal effect of an exposure on an outcome of interest. While there are broad methodologies for addressing each source of bias individually, confounding and exposure measurement error frequently co-occur, and there is a need for methods that address them simultaneously. In this paper, corrected score methods are derived under classical additive measurement error to draw inference about marginal exposure effects using only measured variables. Three estimators are proposed based on g-formula, inverse probability weighting, and doubly-robust estimation techniques. The estimators are shown to be consistent and asymptotically normal, and the doubly-robust estimator is shown to exhibit its namesake property. The methods, which are implemented in the R package mismex, perform well in finite samples under both confounding and measurement error as demonstrated by simulation studies. The proposed doubly-robust estimator is applied to study the effects of two biomarkers on HIV-1 infection using data from the HVTN 505 preventative vaccine trial.

stat.ME↗

arXiv2024

G-Formula for Observational Studies under Stratified Interference, with Application to Bed Net Use on Malaria

Assessing population-level effects of vaccines and other infectious disease prevention measures is important to the field of public health. In infectious disease studies, one person's treatment may affect another individual's outcome, i.e., there may be interference between units. For example, the use of bed nets to prevent malaria by one individual may have an indirect effect on other individuals living in close proximity. In some settings, individuals may form groups or clusters where interference only occurs within groups, i.e., there is partial interference. Inverse probability weighted estimators have previously been developed for observational studies with partial interference. Unfortunately, these estimators are not well suited for studies with large clusters. Therefore, in this paper, the parametric g-formula is extended to allow for partial interference. G-formula estimators are proposed for overall effects, effects when treated, and effects when untreated. The proposed estimators can accommodate large clusters and do not suffer from the g-null paradox that may occur in the absence of interference. The large sample properties of the proposed estimators are derived assuming no unmeasured confounders and that the partial interference takes a particular form (referred to as `weak stratified interference'). Simulation studies are presented demonstrating the finite-sample performance of the proposed estimators. The Demographic and Health Survey from the Democratic Republic of the Congo is then analyzed using the proposed g-formula estimators to assess the effects of bed net use on malaria.

stat.ME↗

arXiv2024

Finite sample performance of optimal treatment rule estimators with right-censored outcomes

Patient care may be improved by recommending treatments based on patient characteristics when there is treatment effect heterogeneity. Recently, there has been a great deal of attention focused on the estimation of optimal treatment rules that maximize expected outcomes. However, there has been comparatively less attention given to settings where the outcome is right-censored, especially with regard to the practical use of estimators. In this study, simulations were undertaken to assess the finite-sample performance of estimators for optimal treatment rules and estimators for the expected outcome under treatment rules. The simulations were motivated by the common setting in biomedical and public health research where the data is observational, survival times may be right-censored, and there is interest in estimating baseline treatment decisions to maximize survival probability. A variety of outcome regression and direct search estimation methods were compared for optimal treatment rule estimation across a range of simulation scenarios. Methods that flexibly model the outcome performed comparatively well, including in settings where the treatment rule was non-linear. R code to reproduce this study's results are available on Github.

stat.ME↗

arXiv2023

Exposure Effects on Count Outcomes with Observational Data, with Application to Incarcerated Women

Causal inference methods can be applied to estimate the effect of a point exposure or treatment on an outcome of interest using data from observational studies. For example, in the Women's Interagency HIV Study, it is of interest to understand the effects of incarceration on the number of sexual partners and the number of cigarettes smoked after incarceration. In settings like this where the outcome is a count, the estimand is often the causal mean ratio, i.e., the ratio of the counterfactual mean count under exposure to the counterfactual mean count under no exposure. This paper considers estimators of the causal mean ratio based on inverse probability of treatment weights, the parametric g-formula, and doubly robust estimation, each of which can account for overdispersion, zero-inflation, and heaping in the measured outcome. Methods are compared in simulations and are applied to data from the Women's Interagency HIV Study.

stat.ME↗

arXiv2023

Quantifying the HIV reservoir with dilution assays and deep viral sequencing

People living with HIV on antiretroviral therapy often have undetectable virus levels by standard assays, but "latent" HIV still persists in viral reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The quantitative viral outgrowth assay (QVOA) is commonly used to estimate the reservoir size, i.e., the infectious units per million (IUPM) of HIV-persistent resting CD4+ T cells. A new variation of the QVOA, the Ultra Deep Sequencing Assay of the outgrowth virus (UDSA), was recently developed that further quantifies the number of viral lineages within a subset of infected wells. Performing the UDSA on a subset of wells provides additional information that can improve IUPM estimation. This paper considers statistical inference about the IUPM from combined dilution assay (QVOA) and deep viral sequencing (UDSA) data, even when some deep sequencing data are missing. Methods are proposed to accommodate assays with wells sequenced at multiple dilution levels and with imperfect sensitivity and specificity, and a novel bias-corrected estimator is included for small samples. The proposed methods are evaluated in a simulation study, applied to data from the University of North Carolina HIV Cure Center, and implemented in the open-source R package SLDeepAssay.

stat.ME↗

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.

stat.ME↗

arXiv2023

Fusing Trial Data for Treatment Comparisons: Single versus Multi-Span Bridging

While randomized controlled trials (RCTs) are critical for establishing the efficacy of new therapies, there are limitations regarding what comparisons can be made directly from trial data. RCTs are limited to a small number of comparator arms and often compare a new therapeutic to a standard of care which has already proven efficacious. It is sometimes of interest to estimate the efficacy of the new therapy relative to a treatment that was not evaluated in the same trial, such as a placebo or an alternative therapy that was evaluated in a different trial. Such multi-study comparisons are challenging because of potential differences between trial populations that can affect the outcome. In this paper, two bridging estimators are considered that allow for comparisons of treatments evaluated in different trials using data fusion methods to account for measured differences in trial populations. A "multi-span'' estimator leverages a shared arm between two trials, while a "single-span'' estimator does not require a shared arm. A diagnostic statistic that compares the outcome in the standardized shared arms is provided. The two estimators are compared in simulations, where both estimators demonstrate minimal empirical bias and nominal confidence interval coverage when the identification assumptions are met. The estimators are applied to data from the AIDS Clinical Trials Group 320 and 388 to compare the efficacy of two-drug versus four-drug antiretroviral therapy on CD4 cell counts among persons with advanced HIV. The single-span approach requires fewer identification assumptions and was more efficient in simulations and the application.

stat.AP↗

arXiv2022

Estimating SARS-CoV-2 Seroprevalence

Governments and public health authorities use seroprevalence studies to guide responses to the COVID-19 pandemic. Seroprevalence surveys estimate the proportion of individuals who have detectable SARS-CoV-2 antibodies. However, serologic assays are prone to misclassification error, and non-probability sampling may induce selection bias. In this paper, nonparametric and parametric seroprevalence estimators are considered that address both challenges by leveraging validation data and assuming equal probabilities of sample inclusion within covariate-defined strata. Both estimators are shown to be consistent and asymptotically normal, and consistent variance estimators are derived. Simulation studies are presented comparing the estimators over a range of scenarios. The methods are used to estimate SARS-CoV-2 seroprevalence in New York City, Belgium, and North Carolina.

stat.AP↗

arXiv2020

On variance of the treatment effect in the treated using inverse probability weighting

In the analysis of observational studies, inverse probability weighting (IPW) is commonly used to consistently estimate the average treatment effect (ATE) or the average treatment effect in the treated (ATT). The variance of the IPW ATE estimator is often estimated by assuming the weights are known and then using the so-called "robust" (Huber-White) sandwich estimator, which results in conservative standard error (SE) estimation. Here it is shown that using such an approach when estimating the variance of the IPW ATT estimator does not necessarily result in conservative SE estimates. That is, assuming the weights are known, the robust sandwich estimator may be conservative or anti-conservative. Thus confidence intervals of the ATT using the robust SE estimate will not be valid in general. Instead, stacked estimating equations which account for the weight estimation can be used to compute a consistent, closed-form variance estimator for the IPW ATT estimator. The two variance estimators are compared via simulation studies and in a data analysis of the effect of smoking on gene expression.

stat.ME↗

arXiv2020

diproperm: An R Package for the DiProPerm Test

High-dimensional low sample size (HDLSS) data sets emerge frequently in many biomedical applications. A common task for analyzing HDLSS data is to assign data to the correct class using a classifier. Classifiers which use two labels and a linear combination of features are known as binary linear classifiers. The direction-projection-permutation (DiProPerm) test was developed for testing the difference of two high-dimensional distributions induced by a binary linear classifier. This paper discusses the key components of the DiProPerm test, introduces the diproperm R package, and demonstrates the package on a real-world data set.

stat.CO↗

arXiv2020

Power and Sample Size for Marginal Structural Models

Marginal structural models fit via inverse probability of treatment weighting are commonly used to control for confounding when estimating causal effects from observational data. When planning a study that will be analyzed with marginal structural modeling, determining the required sample size for a given level of statistical power is challenging because of the effect of weighting on the variance of the estimated causal means. This paper considers the utility of the design effect to quantify the effect of weighting on the precision of causal estimates. The design effect is defined as the ratio of the variance of the causal mean estimator divided by the variance of a naive estimator if, counter to fact, no confounding had been present and weights were not needed. A simple, closed-form approximation of the design effect is derived that is outcome invariant and can be estimated during the study design phase. Once the design effect is approximated for each treatment group, sample size calculations are conducted as for a randomized trial, but with variances inflated by the design effects to account for weighting. Simulations demonstrate the accuracy of the design effect approximation, and practical considerations are discussed.

stat.AP↗

arXiv2019

Balanced Policy Evaluation and Learning for Right Censored Data

Individualized treatment rules can lead to better health outcomes when patients have heterogeneous responses to treatment. Very few individualized treatment rule estimation methods are compatible with a multi-treatment observational study with right censored survival outcomes. In this paper we extend policy evaluation methods to the right censored data setting. Existing approaches either make restrictive assumptions about the structure of the data, or use inverse weighting methods that increase the variance of the estimator resulting in decreased performance. We propose a method which uses balanced policy evaluation combined with an imputation approach to remove right censoring. We show that the proposed imputation approach is compatible with a large number of existing survival models and can be used to extend any individualized treatment rule estimation method to the right censored data setting. We establish the rate at which the imputed values converge to the conditional expected survival times, as well as consistency guarantees and regret bounds for the combined balanced policy with imputation approach. In simulation studies, we demonstrate the improved performance of our approach compared to existing methods. We also apply our method to data from the University of North Carolina Center for AIDS Research HIV Clinical Cohort.

stat.ME↗

arXiv2019

Average treatment effects in the presence of unknown interference

We investigate large-sample properties of treatment effect estimators under unknown interference in randomized experiments. The inferential target is a generalization of the average treatment effect estimand that marginalizes over potential spillover effects. We show that estimators commonly used to estimate treatment effects under no interference are consistent for the generalized estimand for several common experimental designs under limited but otherwise arbitrary and unknown interference. The rates of convergence depend on the rate at which the amount of interference grows and the degree to which it aligns with dependencies in treatment assignment. Importantly for practitioners, the results imply that if one erroneously assumes that units do not interfere in a setting with limited, or even moderate, interference, standard estimators are nevertheless likely to be close to an average treatment effect if the sample is sufficiently large. Conventional confidence statements may, however, not be accurate.

math.ST↗