Can Electronic Health Records Databases Complement Spontaneous Reporting System Databases? A Historical-Reconstruction of the Association of Rofecoxib and Acute Myocardial Infarction

Vaishali K. Patadia, Martijn J. Schuemie, Preciosa M. Coloma, Ron Herings, Johan van der Lei, Miriam Sturkenboom, Gianluca Trifirò

Background: Several initiatives have assessed if mining electronic health records (EHRs) may accelerate the process of drug safety signal detection. In Europe, Exploring and Understanding Adverse Drug Reactions (EU-ADR) Project Focused on utilizing clinical data from EHRs of over 30 million patients from several European countries. Rofecoxib is a prescription COX-2 selective Non-Steroidal Anti-Inflammatory Drugs (NSAID) approved in 1999. In September 2004, the manufacturer withdrew rofecoxib from the market because of safety concerns. In this study, we investigated if the signal concerning rofecoxib and acute myocardial infarction (AMI) could have been identified in EHR database (EU-ADR project) earlier than spontaneous reporting system (SRS), and in advance of rofecoxib withdrawal. Methods: Data from the EU-ADR project and WHO-VigiBase (for SRS) were used for the analysis. Signals were identified when respective statistics exceeded defined thresholds. The SRS analyses was conducted two ways- based on the date the AMI events with rofecoxib as a suspect medication were entered into the database and also the date that the AMI event occurred with exposure to rofecoxib. Results: Within the databases participating in EU-ADR it was possible to identify a strong signal concerning rofecoxib and AMI since Q3 2000 [RR LGPS = 4.5 (95% CI: 2.84-6.72)] and peaked to 4.8 in Q4 2000. In WHO-VigiBase, for AMI term grouping, the EB05 threshold of 2 was crossed in the Q4 2004 (EB05 = 2.94). Since then, the EB05 value increased consistently and peaked in Q3 2006 (EB05 = 48.3) and then again in Q2 2008 (EB05 = 48.5). About 93% (2260 out of 2422) of AMIs reported in WHO-VigiBase database actually occurred prior to the product withdrawal, however, they were reported after the risk minimization/risk communication efforts. Conclusion: In this study, EU-EHR databases were able to detect the AMI signal 4 years prior to the SRS database. We believe that for events that are consistently documented in EHR databases, such as serious events or events requiring in-patient medical intervention or hospitalization, the signal detection exercise in EHR would be beneficial for newly introduced medicinal products on the market, in addition to the SRS data.