title: Combining electronic healthcare databases in Europe to allow for large-scale drug safety monitoring: the EU-ADR Project.
abstract: OBJECTIVE
  In this proof-of-concept paper we describe the framework, process, and preliminary results of combining data from European electronic healthcare record (EHR) databases for large-scale monitoring of drug safety.
  
  
  METHODS
  Aggregated demographic, clinical, and prescription data from eight databases in four countries (Denmark, Italy, Netherlands, the UK) were pooled using a distributed network approach by generation of common input data followed by local aggregation through custom-built software, Jerboa(©). Comparison of incidence rates of upper gastrointestinal bleeding (UGIB) and nonsteroidal anti-inflammatory drug (NSAID) utilization patterns were used to evaluate data harmonization and quality across databases. The known association of NSAIDs and UGIB was employed to demonstrate sensitivity of the system by comparing incidence rate ratios (IRRs) of UGIB during NSAID use to UGIB during all other person-time.
  
  
  RESULTS
  The study population for this analysis comprised 19,647,445 individuals corresponding to 59,929,690 person-years of follow-up. 39,967 incident cases of UGIB were identified during the study period. Crude incidence rates varied between 38.8 and 109.5/100,000 person-years, depending on country and type of database, while age-standardized rates ranged from 25.1 to 65.4/100,000 person-years. NSAID use patterns were similar for databases within the same country but heterogeneous among different countries. A statistically significant age- and gender-adjusted association between use of any NSAID and increased risk for UGIB was confirmed in all databases, IRR from 2.0 (95%CI:1.7-2.2) to 4.3 (95%CI: 4.1-4.5).
  
  
  CONCLUSIONS
  Combining data from EHR databases of different countries to identify drug-adverse event associations is feasible and can set the stage for changing and enlarging the scale for drug safety monitoring.
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. p.coloma@erasmusmc.nl
authors.forename: Preciosa M
authors.initials: PM
authors.lastname: Coloma
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Schuemie
authors.forename: Gianluca
authors.initials: G
authors.lastname: Trifirò
authors.forename: Rosa
authors.initials: R
authors.lastname: Gini
authors.forename: Ron
authors.initials: R
authors.lastname: Herings
authors.forename: Julia
authors.initials: J
authors.lastname: Hippisley-Cox
authors.forename: Giampiero
authors.initials: G
authors.lastname: Mazzaglia
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
authors.forename: Lars
authors.initials: L
authors.lastname: Pedersen
authors.forename: Johan
authors.initials: J
authors.lastname: van der Lei
authors.forename: Miriam
authors.initials: M
authors.lastname: Sturkenboom
mesh_terms: D017327:Clinical Trials, Phase IV as Topic; D015331:Cohort Studies; D016208:Databases, Factual; D004363:Drug Utilization; D064420:Drug-Related Side Effects and Adverse Reactions; D001330:Electronic Data Processing; D005060:Europe; D006801:Humans; D016347:Medical Records Systems, Computerized; D011358:Product Surveillance, Postmarketing; D009626:Terminology as Topic