Disproportionality methods for pharmacovigilance in longitudinal observational databases

Data mining disproportionality methods (PRR, ROR, EBGM, IC, etc.) are commonly used to identify drug safety signals in spontaneous report system (SRS) databases. Newer data sources such as longitudinal observational databases (LOD) provide time-stamped patient-level information and overcome some of the SRS limitations such as an absence of the denominator, total number of patients who consume a drug, and limited temporal information. Application of the disproportionality methods to LODs has not been widely explored. The scale of the LOD data provides an interesting computational challenge. Larger health claims databases contain information on more than 50 million patients and each patient has records for up to 10 years. In this article we systematically explore the application of commonly used disproportionality methods to simulated and real LOD data.