Comparison of Signal Detection Using Healthcare Database Network versus Spontaneous Reporting System Database: the EU-ADR Experience

Background: The EU-ADR project aims to exploit different European electronic healthcare records (EHR) databases for drug safety signal detection. Currently, it is unknown what could be the additional value of using EHR databases for signal detection, with respect to traditional pharmacovigilance system. Objectives: To describe the preliminary results of the comparison of signal detection, as conducted in EU-ADR database network versus US Food and Drug Administration and World Health Organization spontaneous reporting databases. Methods: EU-ADR data sources consist of eight databases in four countries (Denmark, Italy, Netherlands, and United Kingdom) that are combined through distributed data network.[1] A custom-built software (Jerboaª) elaborates harmonized input data that are produced locally and generates aggregated data which are then stored in a central repository. These data are subsequently analyzed using a variety of signal detection methods adapted to longitudinal data (e.g., Longitudinal Gamma Poisson Shrinker). As potential signals, all drugs that are associated with ten events of interest (bullous eruptions - BE, acute renal failure - ARF, acute myocardial infarction - AMI, anaphylactic shock - AS, rhabdomyolysis - RHABD, upper gastrointestinal bleeding – UGIB, neutropenia – NEUTROP, pancytopenia – PANCYT, acute liver injury – ALI, and cardiac valve fibrosis) have been detected via different data mining techniques in the two systems. The number of drugs that could be investigated and the potential signals detected for each event of interest were then compared between spontaneous reporting systems (SRS) and EU-ADR network. Results: SRSs could explore, as potential signals, a larger number of drugs for the ten events, in comparison to EU-ADR, particularly for rare events generally thought to be highly drug attributable (i.e. BE: 3393 vs 228). The highest proportion of signals detected in SRSs was found for BE, ARF and AS, while for AMI, ARF, and UGIB in EUADR. When restricted to the same set of drugs, overall EU-ADR could identify a larger number of signals than SRSs, while some signals were detected in both systems. Conclusions: EU-ADR database network may complement traditional pharmacovigilance system, especially for the detection of signals regarding adverse events that are frequent in the general population and are not highly drug attributable.