arXiv subjects

Luke Benz

Publications and source records attributed to Luke Benz.

5 recordsLinked to original sources

arXiv2025

A Statistical Framework for Understanding Causal Effects that Vary by Treatment Initiation Time in EHR-based Studies

Standard practice in electronic health record (EHR)-based studies evaluating the comparative effectiveness of bariatric surgery relative to no surgery is to estimate and report a constant treatment effect across calendar time. However, real-world treatment strategies can evolve, particularly when comparators include standard of care or surgical procedures where techniques may improve, making it clinically important to ascertain whether efficacy of bariatric surgery has changed over time. Efforts to determine whether treatment efficacy itself is evolving are complicated by changing patient populations, with potential covariate shift in key effect modifiers. Through a comprehensive analysis of EHR data from Kaiser Permanente following two bariatric surgical procedures compared to standard of care, we develop a statistical framework to estimate calendar time-specific average treatment effects and describe both how and why effects vary across treatment initiation time in EHR-based studies. Our approach projects doubly robust, time-specific treatment effect estimates onto candidate marginal structural models and uses a model selection procedure to best describe how effects vary by treatment initiation time. We further introduce a novel summary metric, based on standardization analysis, to quantify the role of covariate shift in explaining observed effect changes and disentangle changes in treatment effects from changes in the patient population receiving treatment.

stat.ME↗

arXiv2025

Robust Causal Inference for EHR-based Studies of Point Exposures with Missingness in Eligibility Criteria

Missingness in variables that define study eligibility criteria is a seldom addressed challenge in electronic health record (EHR)-based settings. It is typically the case that patients with incomplete eligibility information are excluded from analysis without consideration of (implicit) assumptions that are being made, leaving study conclusions subject to potential selection bias. In an effort to ascertain eligibility for more patients, researchers may look back further in time prior to study baseline, and in using outdated values of eligibility-defining covariates may inappropriately be including individuals who, unbeknownst to the researcher, fail to meet eligibility at baseline. To the best of our knowledge, however, very little work has been done to mitigate these concerns. We propose a robust and efficient estimator of the causal average treatment effect on the treated, defined in the study eligible population, in cohort studies where eligibility-defining covariates are missing at random. The approach facilitates the use of flexible machine-learning strategies for component nuisance functions while maintaining appropriate convergence rates for valid asymptotic inference. This method is directly motivated by, and applied throughout to EHR data from Kaiser Permanente to analyze differences between two common bariatric surgical interventions for long-term weight and glycemic outcomes among a cohort of severely obese patients with type II diabetes mellitus.

stat.ME↗

arXiv2024

Comparing Causal Inference Methods for Point Exposures with Missing Confounders: A Simulation Study

Causal inference methods based on electronic health record (EHR) databases must simultaneously handle confounding and missing data. Vast scholarship exists aimed at addressing these two issues separately, but surprisingly few papers attempt to address them simultaneously. In practice, when faced with simultaneous missing data and confounding, analysts may proceed by first imputing missing data and subsequently using outcome regression or inverse-probability weighting (IPW) to address confounding. However, little is known about the theoretical performance of such $\textit{ad hoc}$ methods. In a recent paper Levis $\textit{et al.}$ outline a robust framework for tackling these problems together under certain identifying conditions, and introduce a pair of estimators for the average treatment effect (ATE), one of which is non-parametric efficient. In this work we present a series of simulations, motivated by a published EHR based study of the long-term effects of bariatric surgery on weight outcomes, to investigate these new estimators and compare them to existing $\textit{ad hoc}$ methods. While the latter perform well in certain scenarios, no single estimator is uniformly best. We conclude with recommendations for good practice in the face of partially missing confounders.

stat.ME↗

arXiv2024

Adjusting for Selection Bias Due to Missing Eligibility Criteria in Emulated Target Trials

Target trial emulation (TTE) is a popular framework for observational studies based on electronic health records (EHR). A key component of this framework is determining the patient population eligible for inclusion in both a target trial of interest and its observational emulation. Missingness in variables that define eligibility criteria, however, presents a major challenge towards determining the eligible population when emulating a target trial with an observational study. In practice, patients with incomplete data are almost always excluded from analysis despite the possibility of selection bias, which can arise when subjects with observed eligibility data are fundamentally different than excluded subjects. Despite this, to the best of our knowledge, very little work has been done to mitigate this concern. In this paper, we propose a novel conceptual framework to address selection bias in TTE studies, tailored towards time-to-event endpoints, and describe estimation and inferential procedures via inverse probability weighting (IPW). Under an EHR-based simulation infrastructure, developed to reflect the complexity of EHR data, we characterize common settings under which missing eligibility data poses the threat of selection bias and investigate the ability of the proposed methods to address it. Finally, using EHR databases from Kaiser Permanente, we demonstrate the use of our method to evaluate the effect of bariatric surgery on microvascular outcomes among a cohort of severely obese patients with Type II diabetes mellitus (T2DM).

stat.ME↗

arXiv2021

A Machine Learning Approach for Recruitment Prediction in Clinical Trial Design

Significant advancements have been made in recent years to optimize patient recruitment for clinical trials, however, improved methods for patient recruitment prediction are needed to support trial site selection and to estimate appropriate enrollment timelines in the trial design stage. In this paper, using data from thousands of historical clinical trials, we explore machine learning methods to predict the number of patients enrolled per month at a clinical trial site over the course of a trial's enrollment duration. We show that these methods can reduce the error that is observed with current industry standards and propose opportunities for further improvement.

cs.LG↗