Phenome based analysis as a means for discovering context dependent clinical reference ranges

Robust electronic medical records (EMR's) have made large-scale phenome-based analysis feasible. The context-dependent phenome of a large ICU-based EMR database (MIMIC II) was explored, as a function of a clinical feature: white blood cell count (WBC). Phenome visualization led to the discovery that peak WBC in the range 15-45 K/μl was highly associated with the diagnoses of Clostridium difficile and bacterial sepsis; thus, it is conceivable that clinicians might delay ordering targeted antimicrobials towards C. difficile for patients with peak WBC in this range. This hypothesis was confirmed, with significant delays in this group (median 135 vs. 85 hours, p = 0.002). These delays could be associated with adverse effects on patient health and high hospitalization costs (e.g. an additional $3,000,000 for the MIMIC II cohort). In conclusion, context-dependent clinical reference ranges are critical to clinical decision making; furthermore, important findings can be discovered through EMR-driven phenome association studies.