title: Population-based analysis of non-steroidal anti-inflammatory drug use among children in four European countries in the SOS project: what size of data platforms and which study designs do we need to assess safety issues?
abstract: BACKGROUND
  Data on utilization patterns and safety of non-steroidal anti-inflammatory drugs (NSAIDs) in children are scarce. The purpose of this study was to investigate the utilization of NSAIDs among children in four European countries as part of the Safety Of non-Steroidal anti-inflammatory drugs (SOS) project.
  
  
  METHODS
  We used longitudinal patient data from seven databases (GePaRD, IPCI, OSSIFF, Pedianet, PHARMO, SISR, and THIN) to calculate prevalence rates of NSAID use among children (0-18 years of age) from Germany, Italy, Netherlands, and United Kingdom. All databases contained a representative population sample and recorded demographics, diagnoses, and drug prescriptions. Prevalence rates of NSAID use were stratified by age, sex, and calendar time. The person-time of NSAID exposure was calculated by using the duration of the prescription supply. We calculated incidence rates for serious adverse events of interest. For these adverse events of interest, sample size calculations were conducted (alpha = 0.05; 1-beta = 0.8) to determine the amount of NSAID exposure time that would be required for safety studies in children.
  
  
  RESULTS
  The source population comprised 7.7 million children with a total of 29.6 million person-years of observation. Of those, 1.3 million children were exposed to at least one of 45 NSAIDs during observation time. Overall prevalence rates of NSAID use in children differed across countries, ranging from 4.4 (Italy) to 197 (Germany) per 1000 person-years in 2007. For Germany, United Kingdom, and Italian pediatricians, we observed high rates of NSAID use among children aged one to four years. For all four countries, NSAID use increased with older age categories for children older than 11. In this analysis, only for ibuprofen (the most frequently used NSAID), enough exposure was available to detect a weak association (relative risk of 2) between exposure and asthma exacerbation (the most common serious adverse event of interest).
  
  
  CONCLUSIONS
  Patterns of NSAID use in children were heterogeneous across four European countries. The SOS project platform captures data on more than 1.3 million children who were exposed to NSAIDs. Even larger data platforms and the use of advanced versions of case-only study designs may be needed to conclusively assess the safety of these drugs in children.
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Dr, Molewaterplein, Rotterdam, The Netherlands. r.schade@erasmusmc.nl.
authors.forename: Vera E
authors.initials: VE
authors.lastname: Valkhoff
authors.forename: René
authors.initials: R
authors.lastname: Schade
authors.forename: Geert W
authors.initials: GW
authors.lastname: 't Jong
authors.forename: Silvana
authors.initials: S
authors.lastname: Romio
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Schuemie
authors.forename: Andrea
authors.initials: A
authors.lastname: Arfe
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Garbe
authors.forename: Ron
authors.initials: R
authors.lastname: Herings
authors.forename: Silvia
authors.initials: S
authors.lastname: Lucchi
authors.forename: Gino
authors.initials: G
authors.lastname: Picelli
authors.forename: Tania
authors.initials: T
authors.lastname: Schink
authors.forename: Huub
authors.initials: H
authors.lastname: Straatman
authors.forename: Marco
authors.initials: M
authors.lastname: Villa
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D062313:Databases, Pharmaceutical; D004363:Drug Utilization / Q000706:statistics & numerical data*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D061214:Patient Safety / Q000706:statistics & numerical data*; D017891:Pharmacoepidemiology / Q000379:methods*; D012107:Research Design; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal