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

BackgroundData 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.MethodsWe 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.ResultsThe 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).ConclusionsPatterns 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.

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

“…Acetaminophen and ibuprofen use during infancy have also been implicated in asthma inception (65). These drugs are likely used during infant respiratory viral illnesses.…”

Progress in understanding hypersensitivity reactions to nonsteroidal anti‐inflammatory drugs

“…1 Thus, 57.8% of the Danish 2 and 43.6% of the French 3 populations claimed at least one NSAID prescription during 1997-2005 and 2009-2010, respectively, and 16.9% of children are exposed to at least one NSAID in Europe. 4 NSAIDs are the main elicitors of drug hypersensitivity reactions (DHRs). [5][6][7] NSAIDs hypersensitivity among general population is frequent (0.5%-5.7%), overcoming antibiotics allergy in some studies.…”

Pediatric Drug Safety Signal Detection: A New Drug–Event Reference Set for Performance Testing of Data-Mining Methods and Systems

“…Although useful for efficacy, such trials are usually too small and with too short a follow-up to yield adequate information on rare adverse drug reactions (ADR) and long-term safety [ 11 ]. Therefore, other and preferably existing data sources should be utilized to provide information on the safety of drugs in pediatrics [ 12 ]. Existing sources with lots of data comprise spontaneous reporting system (SRS) and electronic healthcare record (EHR) databases.…”