arXiv subjects

Laine E. Thomas

Publications and source records attributed to Laine E. Thomas.

6 recordsLinked to original sources

arXiv2026

Demystify Doubly-Robust Estimation: The Role of Overlap

The doubly-robust (DR) estimator is popular for evaluating causal effects in observational studies and is often perceived as more desirable than inverse probability weighting (IPW) or outcome modeling alone because it provides extra protection against model misspecification. However, double robustness is an asymptotic property that may not hold in finite samples. We investigate how the finite sample performance of the DR estimator depends on the degree of covariate overlap between comparison groups. Using analytical illustrations and extensive simulations under various scenarios with different degrees of covariate overlap and model specifications, we examine the bias and variance of the DR estimator relative to IPW and outcome modeling estimators. We find that: (i) specification of the outcome model has a stronger influence on the DR estimates than specification of the propensity score model, and this dominance increases as overlap decreases; (ii) with poor overlap, the DR estimator generally amplifies the adverse consequences of extreme weights (large bias and/or variance) regardless of model specifications, and is often inferior to both the IPW and outcome modeling estimators. As a practical guide, we recommend always first checking the degree of overlap in applications. In the case of poor overlap, analysts should consider shifting the target population to a subpopulation with adequate overlap via methods such as trimming or overlap weighting.

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arXiv2026

What is Overlap Weighting, How Has it Evolved, and When to Use It for Causal Inference?

The growing availability of large health databases has expanded the use of observational studies for comparative effectiveness research. Unlike randomized trials, observational studies must adjust for systematic differences in patient characteristics between treatment groups. Propensity score methods, including matching, weighting, stratification, and regression adjustment, address this issue by creating groups that are comparable with respect to measured covariates. Among these approaches, overlap weighting (OW) has emerged as a principled and efficient method that emphasizes individuals at empirical equipoise, those who could plausibly receive either treatment. By assigning weights proportional to the probability of receiving the opposite treatment, OW targets the Average Treatment Effect in the Overlap population (ATO), achieves exact mean covariate balance under logistic propensity score models, and minimizes asymptotic variance. Over the last decade, the OW method has been recognized as a valuable confounding adjustment tool across the statistical, epidemiologic, and clinical research communities, and is increasingly applied in clinical and health studies. Given the growing interest in using observational data to emulate randomized trials and the capacity of OW to prioritize populations at clinical equipoise while achieving covariate balance (fundamental attributes of randomized studies), this article provides a concise overview of recent methodological developments in OW and practical guidance on when it represents a suitable choice for causal inference.

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arXiv2025

Improving Variance and Confidence Interval Estimation in Small-Sample Propensity Score Analyses: Bootstrap vs. Asymptotic Methods

Propensity score (PS) methods are widely used to estimate treatment effects in non-randomized studies. Variance is typically estimated using sandwich or bootstrap methods, which can either treat the PS as estimated or fixed. The latter is thought to be conservative. Comparisons between the sandwich and bootstrap estimators have been compared in moderate to large sample sizes, favoring the bootstrap estimator. With the growing interest in treatments for rare disease and externally controlled clinical trials, very small sample sizes are not uncommon and the asymptotic properties of sandwich estimators may not hold. Bootstrap methods that allow for PS re-estimation can also generate problems with quasi-separation in small samples. It is unclear whether it is safe to prefer sandwich estimators or to assume that treating the PS as fixed is conservative. We conducted a Monte Carlo simulation to compare the performance of bootstrap versus sandwich variance and CI estimators for average treatment effects estimated with PS methods. We systematically evaluated the impact of treating the PS as fixed versus re-estimating it. These methodological comparisons were performed using Inverse Probability of Treatment Weighting (IPTW) and Augmented Inverse Probability of Treatment Weighting (AIPW) estimators. Simulations assessed performance under various conditions, including small sample sizes and different outcome and treatment prevalences. We illustrate the differences in our motivating example, the LIMIT-JIA trial. We show that the sandwich estimators can perform quite poorly in small samples, and fixed PS methods are not necessarily conservative. A stratified bootstrap avoids quasi-separation and performs well. Differences were large enough to alter statistical conclusions in our motivating example, LIMIT-JIA.

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arXiv2021

PSweight: An R Package for Propensity Score Weighting Analysis

Propensity score weighting is an important tool for comparative effectiveness research.Besides the inverse probability of treatment weights (IPW), recent development has introduced a general class of balancing weights, corresponding to alternative target populations and estimands. In particular, the overlap weights (OW) lead to optimal covariate balance and estimation efficiency, and a target population of scientific and policy interest. We develop the R package PSweight to provide a comprehensive design and analysis platform for causal inference based on propensity score weighting. PSweight supports (i) a variety of balancing weights, (ii) binary and multiple treatments,(iii) simple and augmented weighting estimators, (iv) nuisance-adjusted sandwich variances, and(v) ratio estimands. PSweight also provides diagnostic tables and graphs for covariate balance assessment. We demonstrate the functionality of the package using a data example from the NationalChild Development Survey (NCDS), where we evaluate the causal effect of educational attainment on income.

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arXiv2021

Covariate adjustment in subgroup analyses of randomized clinical trials: A propensity score approach

Background: Subgroup analyses are frequently conducted in randomized clinical trials to assess evidence of heterogeneous treatment effect across patient subpopulations. Although randomization balances covariates within subgroups in expectation, chance imbalance may be amplified in small subgroups and harm the precision. Covariate adjustment in overall analysis of RCT is often conducted, via either ANCOVA or propensity score weighting, but for subgroup analysis has been rarely discussed. In this article, we develop propensity score weighting methodology for covariate adjustment to improve the precision and power of subgroup analyses in RCTs. Methods: We extend the propensity score weighting methodology to subgroup analyses by fitting a logistic propensity model with pre-specified covariate-subgroup interactions. We show that, by construction, overlap weighting exactly balances the covariates with interaction terms in each subgroup. Extensive simulations were performed to compare the operating characteristics of unadjusted, different propensity score weighting and the ANCOVA estimator. We apply these methods to the HF-ACTION trial to evaluate the effect of exercise training on 6-minute walk test in pre-specified subgroups. Results: Standard errors of the adjusted estimators are smaller than those of the unadjusted estimator. The propensity score weighting estimator is as efficient as ANCOVA, and is often more efficient when subgroup sample size is small (e.g.<125), and/or when outcome model is misspecified. The weighting estimators with full-interaction propensity model consistently outperform the standard main-effect propensity model. Conclusion: Propensity score weighting is a transparent and objective method to adjust chance imbalance of important covariates in subgroup analyses of RCTs. It is crucial to include the full covariate-subgroup interactions in the propensity score model.

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arXiv2021

Propensity Score Weighting for Causal Subgroup Analysis

A common goal in comparative effectiveness research is to estimate treatment effects on pre-specified subpopulations of patients. Though widely used in medical research, causal inference methods for such subgroup analysis remain underdeveloped, particularly in observational studies. In this article, we develop a suite of analytical methods and visualization tools for causal subgroup analysis. First, we introduce the estimand of subgroup weighted average treatment effect and provide the corresponding propensity score weighting estimator. We show that balancing covariates within a subgroup bounds the bias of the estimator of subgroup causal effects. Second, we design a new diagnostic graph -- the Connect-S plot -- for visualizing the subgroup covariate balance. Finally, we propose to use the overlap weighting method to achieve exact balance within subgroups. We further propose a method that combines overlap weighting and LASSO, to balance the bias-variance tradeoff in subgroup analysis. Extensive simulation studies are presented to compare the proposed method with several existing methods. We apply the proposed methods to the Patient-centered Results for Uterine Fibroids (COMPARE-UF) registry data to evaluate alternative management options for uterine fibroids for relief of symptoms and quality of life.

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