The use of Electronic Health Records (EHR) for translational research can be challenging due to difficulty in extracting accurate disease phenotype data. Historically, EHR algorithms for annotating phenotypes have been either rule-based or trained with billing codes and gold standard labels curated via labor intensive medical chart review. These simplistic algorithms tend to have unpredictable portability across institutions and low accuracy for many disease phenotypes due to imprecise billing codes. Recently, more sophisticated machine learning algorithms have been developed to improve the robustness and accuracy of EHR phenotyping algorithms. These algorithms are typically trained via supervised learning, relating gold standard labels to a wide range of candidate features including billing codes, procedure codes, medication prescriptions and relevant clinical concepts extracted from narrative notes via Natural Language Processing (NLP). However, due to the time intensiveness of gold standard labeling, the size of the training set is often insufficient to build a generalizable algorithm with the large number of candidate features extracted from EHR. To reduce the number of candidate predictors and in turn improve model performance, we present an automated feature selection method based entirely on unlabeled observations. The proposed method generates a comprehensive surrogate for the underlying phenotype with an unsupervised clustering of disease status based on several highly predictive features such as diagnosis codes and mentions of the disease in text fields available in the entire set of EHR data. A sparse regression model is then built with the estimated outcomes and remaining covariates to identify those features most informative of the phenotype of interest. Relying on the results of Li and Duan (1989), we demonstrate that variable selection for the underlying phenotype model can be achieved by fitting the surrogate-based model. We explore the performance of our methods in numerical simulations and present the results of a prediction model for Rheumatoid Arthritis (RA) built on a large EHR data mart from the Partners Health System consisting of billing codes and NLP terms. Empirical results suggest that our procedure reduces the number of gold-standard labels necessary for phenotyping thereby harnessing the automated power of EHR data and improving efficiency.
Keywords: electronic medical records; feature selection; prediction accuracy; regularized regression; risk prediction.
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