Figure 1 presents an overview of the approach used in BioVU and across eMERGE for phenotyping. One early lesson, obvious in retrospect, was that engaging clinical users of the EHR is highly desirable in constructing initial algorithms: these individuals are most familiar with how specific diseases may be represented in the EHR, such as the medications, laboratory test results, free text, etc. that may be useful to identify true cases and controls. Once an initial algorithm is constructed, this is deployed across the EHR system until potential cases are identified. These are then manually reviewed and if the positive predictive value (PPV) for the algorithm is less than 95% it is further refined and the process iterated until the PPV exceeds 95%. For rare phenotypes, an algorithm that captures every potential case can be deployed with manual review to establish which, in the initial dataset, are true cases.13,14 On the other hand for common diseases, where the datasets will include thousands or tens of thousands of subjects, electronic algorithms are clearly required to extract true cases and controls. Resources such
