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Keith Barnatchez

Publications and source records attributed to Keith Barnatchez.

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Causal Inference with Multiple Misclassified Exposures: A Control Variate-Adjusted Calibration Weighting Approach

Exposure misclassification is a common issue prevalent in studies of respiratory infections in cystic fibrosis. Throat swabs are frequently used in place of expectorated or induced sputum cultures, although they have imperfect sensitivity and specificity to detect Pseudomonas aeruginosa and Staphylococcus aureus. We develop calibration weighting and control variate estimators for causal inference with multiple misclassified binary exposures and clustered observations. The calibration approach treats misclassification as a missing data problem, achieving consistency without modeling the misclassification mechanism. The control variate adjustment integrates information from error-prone observations to reduce variance while preserving the consistency of the gold-standard estimator. We show that the resulting estimator inherits double robustness from its component estimators. We also characterize a structural ceiling on efficiency gains in the bivariate setting, where joint correct classification of both exposures limits the variance reduction achievable relative to univariate applications. Simulation studies confirm the consistency and double robustness of the proposed estimators under model misspecification. We then apply these methods to a cohort of $651$ cystic fibrosis patients ages $6$--$21$. Swab-based estimates attenuate the effect of P. aeruginosa on percent predicted FEV$_1$ by approximately $79\%$ relative to sputum-based estimates ($-1.68$ vs. $-7.88$ percentage points; $95\%$ confidence interval for sputum: $-10.08$, $-5.67$). These findings suggest that relying on throat swabs may lead to under-treatment of P. aeruginosa infections. More broadly, the methods provide a framework for causal inference with multiple misclassified exposures.

stat.ME

Debiased Machine Learning for Conformal Prediction of Counterfactual Outcomes Under Runtime Confounding

Data-driven decision making frequently relies on predicting counterfactual outcomes. In practice, researchers commonly train counterfactual prediction models on a source dataset to inform decisions on a possibly separate target population. Conformal prediction has arisen as a popular method for producing assumption-lean prediction intervals for counterfactual outcomes that would arise under different treatment decisions in the target population of interest. However, existing methods require that every confounding factor of the treatment-outcome relationship used for training on the source data is additionally measured in the target population, risking miscoverage if important confounders are unmeasured in the target population. In this paper, we introduce a computationally efficient debiased machine learning framework that allows for valid prediction intervals when only a subset of confounders is measured in the target population, a common challenge referred to as runtime confounding. Grounded in semiparametric efficiency theory, we show the resulting prediction intervals achieve desired coverage rates with faster convergence compared to standard methods. Through numerous synthetic and semi-synthetic experiments, we demonstrate the utility of our proposed method.

stat.ML

Efficient Estimation of Causal Effects Under Two-Phase Sampling with Error-Prone Outcome and Treatment Measurements

Measurement error is a common challenge for causal inference studies using electronic health record (EHR) data, where clinical outcomes and treatments are frequently mismeasured. Researchers often address measurement error by conducting manual chart reviews to validate measurements in a subset of the full EHR data -- a form of two-phase sampling. To improve efficiency, phase-two samples are often collected in a biased manner dependent on the patients' initial, error-prone measurements. In this work, motivated by our aim of performing causal inference with error-prone outcome and treatment measurements under two-phase sampling, we develop solutions applicable to both this specific problem and the broader problem of causal inference with two-phase samples. For our specific measurement error problem, we construct two asymptotically equivalent doubly-robust estimators of the average treatment effect and demonstrate how these estimators arise from two previously disconnected approaches to constructing efficient estimators in general two-phase sampling settings. We document various sources of instability affecting estimators from each approach and propose modifications that can considerably improve finite sample performance in any two-phase sampling context. We demonstrate the utility of our proposed methods through simulation studies and an illustrative example assessing effects of antiretroviral therapy on occurrence of AIDS-defining events in patients with HIV from the Vanderbilt Comprehensive Care Clinic.

stat.ME

Flexible and Efficient Estimation of Causal Effects with Error-Prone Exposures: A Control Variates Approach for Measurement Error

Exposure measurement error is a ubiquitous but often overlooked challenge in causal inference with observational data. Existing methods accounting for exposure measurement error largely rely on restrictive parametric assumptions, while emerging data-adaptive estimation approaches allow for less restrictive assumptions but at the cost of flexibility, as they are typically tailored towards rigidly-defined statistical quantities. There remains a critical need for assumption-lean estimation methods that are both flexible and possess desirable theoretical properties across a variety of study designs. In this paper, we introduce a general framework for estimation of causal quantities in the presence of exposure measurement error, adapted from the control variates approach of Yang and Ding (2019). Our method can be implemented in various two-phase sampling study designs, where one obtains gold-standard exposure measurements for a small subset of the full study sample, called the validation data. The control variates framework leverages both the error-prone and error-free exposure measurements by augmenting an initial consistent estimator from the validation data with a variance reduction term formed from the full data. We show that our method inherits double-robustness properties under standard causal assumptions. Simulation studies show that our approach performs favorably compared to leading methods under various two-phase sampling schemes. We illustrate our method with observational electronic health record data on HIV outcomes from the Vanderbilt Comprehensive Care Clinic.

stat.ME