What Can Electronic Healthcare Record Databases do for Paediatric Drug Safety Surveillance?

Background: Traditional pharmacovigilance activities do not focus specifically on children and medicines in children are frequently prescribed off-label based on extrapolating experience from adults.[1] The EU-ADR Project aims to use information from various electronic healthcare record (EHR) databases to produce a computerised integrated system for early detection of drug safety signals.[2] Objectives: To provide estimates of the number of drugs and incidence rates (IRs) of adverse events that can be monitored in children and adolescents in the EU-ADR network. Methods: Demographic, clinical events and outpatient drug prescription/dispensing data were obtained for individuals 0 to 18 years of age from seven databases from Denmark, Italy, and the Netherlands. Data were analysed from 1996–2008. We estimated the number and types of drugs for which specific adverse events can be monitored as function of actual drug use, minimally detectable RR, and empiricallyderived incidence rates for 10 events deemed to be important in pharmacovigilance.[3,4] The same was done for adverse events frequently reported in children, using IRs described in literature. Results: The paediatric population comprised 4 838 146 individuals contributing 25 575 132 person-years (PYs) of follow-up during the study period. Within this population a total of 2170 drugs were prescribed, with a total drug exposure of 1 610 631 PYs. Eighteen of the 2170 drugs (0.8%) comprised half of total drug exposure while 90% of the total drug exposure in PYs was represented by 158 drugs (7.3%). For a relatively frequent event such as upper gastrointestinal bleeding (IR = 14.4/100 000 PYs), there were 39 drugs (comprising 66% of total exposure in PY) for which an association with a RR ‡4, if present, can be investigated. For a rare event such as anaphylactic shock, there were 8 drugs (comprising 35% of total exposure) for which an association of same magnitude can be investigated. Based on literature-derived IR, there was a higher number of drugs that can be monitored for the events febrile convulsions and suicide attempt at the same magnitude of risk. Conclusion: Drug use in children is rare and shows little variation. Signal detection for the paediatric population seems especially promising for events with a high background incidence and for drugs with a large amount of exposure. Intercontinental collaboration will be necessary gain enough statistical power for paediatric drug safety detection.