arXiv subjects

Laine Thomas

Publications and source records attributed to Laine Thomas.

4 recordsLinked to original sources

arXiv2025

Weight a Minute: Understanding Variability in PATE Estimates Across Target Populations

Clinical study populations often differ meaningfully from the broader populations to which results are intended to generalize. Weighting methods such as inverse probability of sampling weights (IPSW) reweight study participants to resemble a target population, but the accuracy of these estimates depends heavily on how well the chosen population represents the population of substantive interest. We conduct a simulation study grounded in empirical covariate distributions from several real-world data sources spanning a continuum from highly selective to broadly inclusive populations. Using treatment effect scenarios with varying levels of effect modification, we evaluate IPSW estimators of the population average treatment effect (PATE) across multiple candidate target populations. We quantify the bias that arises when the dataset used to operationalize the target population differs from the intended inference population, even when IPSW is correctly specified. Our results show that bias increases systematically as target populations diverge from a well-representative population, and that weighting to a poorly aligned target can introduce more bias than not weighting at all. These findings highlight that selecting an appropriate target population dataset is a critical design choice for valid generalization.

stat.ME↗

arXiv2025

Leveraging External Controls in Clinical Trials: Estimands, Estimation, Assumptions

It is increasingly common to augment randomized controlled trial with external controls from observational data, to evaluate the treatment effect of an intervention. Traditional approaches to treatment effect estimation involve ambiguous estimands and unrealistic or strong assumptions, such as mean exchangeability. We introduce a double-indexed notation for potential outcomes to define causal estimands transparently and clarify distinct sources of implicit bias. We show that the concurrent control arm is critical in assessing the plausibility of assumptions and providing unbiased causal estimation. We derive a consistent and locally efficient estimator for a class of weighted average treatment effect estimands that combines concurrent and external data without assuming mean exchangeability. This estimator incorporates an estimate of the systematic difference in outcomes between the concurrent and external units, of which we propose a Frish-Waugh-Lovell style partial regression method to obtain. We compare the proposed methods with existing methods using extensive simulation and applied to cardiovascular clinical trials.

stat.ME↗

arXiv2022

Addressing Extreme Propensity Scores in Estimating Counterfactual Survival Functions via the Overlap Weights

The inverse probability weighting approach is popular for evaluating treatment effects in observational studies, but extreme propensity scores could bias the estimator and induce excessive variance. Recently, the overlap weighting approach has been proposed to alleviate this problem, which smoothly down-weighs the subjects with extreme propensity scores. Although advantages of overlap weighting have been extensively demonstrated in literature with continuous and binary outcomes, research on its performance with time-to-event or survival outcomes is limited. In this article, we propose two weighting estimators that combine propensity score weighting and inverse probability of censoring weighting to estimate the counterfactual survival functions. These estimators are applicable to the general class of balancing weights, which includes inverse probability weighting, trimming, and overlap weighting as special cases. We conduct simulations to examine the empirical performance of these estimators with different weighting schemes in terms of bias, variance, and 95% confidence interval coverage, under various degree of covariate overlap between treatment groups and censoring rate. We demonstrate that overlap weighting consistently outperforms inverse probability weighting and associated trimming methods in bias, variance, and coverage for time-to-event outcomes, and the advantages increase as the degree of covariate overlap between the treatment groups decreases.

stat.ME↗

arXiv2020

Propensity score weighting under limited overlap and model misspecification

Propensity score (PS) weighting methods are often used in non-randomized studies to adjust for confounding and assess treatment effects. The most popular among them, the inverse probability weighting (IPW), assigns weights that are proportional to the inverse of the conditional probability of a specific treatment assignment, given observed covariates. A key requirement for IPW estimation is the positivity assumption, i.e., the PS must be bounded away from 0 and 1. In practice, violations of the positivity assumption often manifest by the presence of limited overlap in the PS distributions between treatment groups. When these practical violations occur, a small number of highly influential IPW weights may lead to unstable IPW estimators, with biased estimates and large variances. To mitigate these issues, a number of alternative methods have been proposed, including IPW trimming, overlap weights (OW), matching weights (MW), and entropy weights (EW). Because OW, MW, and EW target the population for whom there is equipoise (and with adequate overlap) and their estimands depend on the true PS, a common criticism is that these estimators may be more sensitive to misspecifications of the PS model. In this paper, we conduct extensive simulation studies to compare the performances of IPW and IPW trimming against those of OW, MW, and EW under limited overlap and misspecified propensity score models. Across the wide range of scenarios we considered, OW, MW, and EW consistently outperform IPW in terms of bias, root mean squared error, and coverage probability.

stat.ME↗