title: Pharmacoepidemiological safety studies in children: a systematic review.
abstract: In order to identify challenges in pediatric pharmacoepidemiological safety studies, we assessed the characteristics of such (published) studies.
  
  
  
  Relevant articles from inception to 2013 were retrieved from Embase and Medline. We sequentially screened titles, abstracts and full texts with independent validation. We systematically collected data regarding general information, study methods and results.
  
  
  
  Out of 4825 unique articles, 268 full texts (5.6%) were retained; 147 (54.9%) pertained to drugs rather than vaccines. Considering the 268 studies, 202 (75.4%) concerned children and adolescents (2 to 11 years) and 14 (5.3%) included preterm newborns. Most studies originated from North America (154 [57.5%]) or Europe (92 [34.3%]). Only 47 studies (17.5%) were privately funded. The majority (174 [64.9%]) were cohort studies. Out of 268 studies, 196 (73.1%) collected data retrospectively; paper medical charts were the most common data source for the exposures (85 [31.7%]) and outcomes (122 [45.5%]). Only 3 (2.0%) drug-only studies investigated rarely used drugs. Considering all 268 studies, only 27 (10.1%) reported sample size or power calculation. Most (75 [51.0%]) drug-only studies corrected confounding by multivariate modeling unlike stratification in 66 (55.9%) vaccine-only studies. Considering 75 child-only studies without any statistically significant result, 41 (54.7%) did not discuss lack of power.
  
  
  
  Although the field of pediatric pharmacoepidemiology is steadily developing evaluation seldom includes neonates, is mainly focused on few drug classes and safety outcomes and concerns mainly drug use in developed countries. Small study size is a specific challenge in pediatrics. Reporting should be improved. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Osemeke U
authors.initials: OU
authors.lastname: Osokogu
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Julijana
authors.initials: J
authors.lastname: Dukanovic
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ferrajolo
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Dodd
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Pacurariu
authors.affiliation: Medical Library, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Wichor M
authors.initials: WM
authors.lastname: Bramer
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
authors.forename: Geert
authors.initials: G
authors.lastname: 'tJong
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weibel
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Univ Paris 7-Diderot, Sorbonne Paris Cité, EA08, INSERM CIC1426, Paris, France.
authors.forename: Florentia
authors.initials: F
authors.lastname: Kaguelidou
mesh_terms: D000293:Adolescent; D002648:Child; D015986:Confounding Factors, Epidemiologic; D003625:Data Collection / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D015340:Epidemiologic Research Design; D006801:Humans; D007231:Infant, Newborn; D015999:Multivariate Analysis; D010372:Pediatrics; D017891:Pharmacoepidemiology / Q000379:methods*; D012109:Research Support as Topic / Q000706:statistics & numerical data
keywords: pediatrics; pharmacoepidemiology; systematic review; ‘adverse drug reaction’