arXiv subjects

Heidi Fischer

Publications and source records attributed to Heidi Fischer.

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.

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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eligibility for more patients, researchers may look back further in time prior to study baseline, and in using outdated values of eligibility-defining covariates may inappropriately be including individuals who, unbeknownst to the researcher, fail to meet eligibility at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.

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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).

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arXiv2023

Causal Quantile Treatment Effects with missing data by double-sampling

Causal weighted quantile treatment effects (WQTE) are a useful complement to standard causal contrasts that focus on the mean when interest lies at the tails of the counterfactual distribution. To-date, however, methods for estimation and inference regarding causal WQTEs have assumed complete data on all relevant factors. In most practical settings, however, data will be missing or incomplete data, particularly when the data are not collected for research purposes, as is the case for electronic health records and disease registries. Furthermore, such data sources may be particularly susceptible to the outcome data being missing-not-at-random (MNAR). In this paper, we consider the use of double-sampling, through which the otherwise missing data are ascertained on a sub-sample of study units, as a strategy to mitigate bias due to MNAR data in the estimation of causal WQTEs. With the additional data in-hand, we present identifying conditions that do not require assumptions regarding missingness in the original data. We then propose a novel inverse-probability weighted estimator and derive its asymptotic properties, both pointwise at specific quantiles and uniformly across a range of quantiles over some compact subset of (0,1), allowing the propensity score and double-sampling probabilities to be estimated. For practical inference, we develop a bootstrap method that can be used for both pointwise and uniform inference. A simulation study is conducted to examine the finite sample performance of the proposed estimators. The proposed method is illustrated with data from an EHR-based study examining the relative effects of two bariatric surgery procedures on BMI loss at 3 years post-surgery.

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arXiv2022

Double sampling for informatively missing data in electronic health record-based comparative effectiveness research

Missing data arise in most applied settings and are ubiquitous in electronic health records (EHR). When data are missing not at random (MNAR) with respect to measured covariates, sensitivity analyses are often considered. These post-hoc solutions, however, are often unsatisfying in that they are not guaranteed to yield concrete conclusions. Motivated by an EHR-based study of long-term outcomes following bariatric surgery, we consider the use of double sampling as a means to mitigate MNAR outcome data when the statistical goals are estimation and inference regarding causal effects. We describe assumptions that are sufficient for the identification of the joint distribution of confounders, treatment, and outcome under this design. Additionally, we derive efficient and robust estimators of the average causal treatment effect under a nonparametric model and under a model assuming outcomes were, in fact, initially missing at random (MAR). We compare these in simulations to an approach that adaptively estimates based on evidence of violation of the MAR assumption. Finally, we also show that the proposed double sampling design can be extended to handle arbitrary coarsening mechanisms, and derive nonparametric efficient estimators of any smooth full data functional.

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