Labeling patients in electronic health records with respect to their statuses of having a disease or condition, i.e. case or control statuses, has increasingly relied on prediction models using high-dimensional variables derived from structured and unstructured electronic health record data. A major hurdle currently is a lack of valid statistical inference methods for the case probability. In this paper, considering high-dimensional sparse logistic regression models for prediction, we propose a novel bias-corrected estimator for the case probability through the development of linearization and variance enhancement techniques. We establish asymptotic normality of the proposed estimator for any loading vector in high dimensions. We construct a confidence interval for the case probability and propose a hypothesis testing procedure for patient case-control labelling. We demonstrate the proposed method via extensive simulation studies and application to real-world electronic health record data.

OBJECTIVE: Phenotyping patients using electronic health record (EHR) data conventionally requires labeled cases and controls. Assigning labels requires manual medical chart review and therefore is labor intensive. For some phenotypes, identifying gold-standard controls is prohibitive. We developed an accurate EHR phenotyping approach that does not require labeled controls. MATERIALS AND METHODS: Our framework relies on a random subset of cases, which can be specified using an anchor variable that has excellent positive predictive value and sensitivity independent of predictors. We proposed a maximum likelihood approach that efficiently leverages data from the specified cases and unlabeled patients to develop logistic regression phenotyping models, and compare model performance with existing algorithms. RESULTS: Our method outperformed the existing algorithms on predictive accuracy in Monte Carlo simulation studies, application to identify hypertension patients with hypokalemia requiring oral supplementation using a simulated anchor, and application to identify primary aldosteronism patients using real-world cases and anchor variables. Our method additionally generated consistent estimates of 2 important parameters, phenotype prevalence and the proportion of true cases that are labeled. DISCUSSION: Upon identification of an anchor variable that is scalable and transferable to different practices, our approach should facilitate development of scalable, transferable, and practice-specific phenotyping models. CONCLUSIONS: Our proposed approach enables accurate semiautomated EHR phenotyping with minimal manual labeling and therefore should greatly facilitate EHR clinical decision support and research.