ArticleJournal of biomedical informatics2025
Leveraging undecided cases in chart-reviewed phenotypes to enhance EHR-based association studies.
Article in Journal of biomedical informatics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesIn electronic health record (EHR)-based association studies, phenotyping algorithms efficiently classify patient clinical outcomes into binary categories but are susceptible to misclassification errors. The gold standard, manual chart review, involves clinicians determining the true disease status based on their assessment of health records. These clinicians-labeled phenotypes are labor-intensive and typically limited to a small subset of patients, potentially introducing a third "undecided" category when phenotypes are indeterminate. We aim to effectively integrate the algorithm-derived and chart-reviewed outcomes when both are available in EHR-based association studies. MATERIAL AND
methodsWe propose an augmented estimation method that combines the binary algorithm-derived phenotypes for the entire cohort with the trinary chart-reviewed phenotypes for a small, selected subset. Additionally, a cost-effective outcome-dependent sampling strategy is used to address the rare disease scenarios. The proposed trinary chart-reviewed phenotype integrated cost-effective augmented estimation (TriCA) was evaluated across a wide range of simulation settings and real-world applications, including using EHR data on Alzheimer's disease and related dementias (ADRD) from the OneFlorida + Clinical Research Network, and using cohort data on second breast cancer events (SBCE) from the Kaiser Permanente Washington.
resultsCompared to estimation based on random sampling, our augmented method improved mean square error by up to 28.3% in simulation studies; compared to estimation using only trinary chart-reviewed phenotypes, our method improved efficiency by up to 33.3% in ADRD data and 50.8% in SBCE data. DISCUSSION: Our simulation studies and real-world applications demonstrate that, compared to existing methods, the proposed method provides unbiased estimates with higher statistical efficiency.
conclusionThe proposed method effectively combined binary algorithm-derived phenotypes for the whole cohort with trinary chart-reviewed outcomes for a limited validation set, making it applicable to a broader range of applications and enhancing risk factor identification in EHR-based association studies.
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