Validation of Electronic Health Record Phenotyping of Bipolar Disorder and Controls

Objective— To validate the use of electronic health records (EHRs) for the diagnosis of bipolar disorder (BD) and controls. Methods— EHR data were obtained from a healthcare system of more than 4.2 million patients spanning more than 20 years. Chart review by experienced clinicians was used to identify text features and coded data consistent or inconsistent with a diagnosis of BD. Natural language processing (NLP) was used to train a diagnostic algorithm with 95% specificity for classifying BD. Filtered coded data were used to derive three additional classification rules for cases and one for controls. The positive predictive value (PPV) of EHR-based BD and subphenotype diagnoses was calculated against direct semi-structured interview diagnoses by trained clinicians blind to EHR diagnosis in a sample of 190 patients. Results— The PPV of NLP-defined BD was 0.85. A coded classification based on strict filtering achieved a PPV of 0.79, but BD classifications based on less stringent criteria performed less well. None of the EHR-classified controls was given a diagnosis of BD on direct interview (PPV = 1.0). For most subphenotypes, PPVs exceeded 0.80. The EHR-based classifications were used to accrue 4500 BD cases and 5000 controls for genetic analyses. Conclusions— Semi-automated mining of EHRs can be used to ascertain BD cases and controls with high specificity and predictive value compared to a gold-standard diagnostic interview. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.