title: Risk of bias in randomized trials of pharmacological interventions in children and adults.
abstract: OBJECTIVE
  To determine whether randomized controlled trials of pharmacologic interventions in children are more likely to be biased than similar trials in adults.
  
  
  METHODS
  Trials involving only children and published in MEDLINE between January 2008 and October 2009 (n=100) were randomly selected and matched, by drug class and therapeutic area, with a similar trial completed in adults. The Cochrane risk of bias tool was used to compare the pediatric and adult trials.
  
  
  RESULTS
  The characteristics of adult and pediatric trials included were similar, except that adult studies were more likely to be conducted in Europe and published in specialty journals. Two-thirds of all trials were single center, and 62% had 100 or fewer participants. Many trials had an unclear risk of bias for allocation concealment (65% adult, 52% pediatric). More pediatric trials had a low risk of bias for random sequence generation (59% pediatric, 41% adult, P=.002) and blinding of outcome assessment (63% pediatric, 48% adult, P=.04) than adult trials; however, a sensitivity analysis of trials published since 2008 (and so matched by year of publication) did not confirm this finding, suggesting year of publication was an important confounder.
  
  
  CONCLUSIONS
  When randomized controlled trials are matched for drug class and therapeutic area, trials involving children display a similar risk of bias. Differences in the risk of bias between pediatric and adult trials are not caused by differences in the capacity of researchers to conduct and report trials of high quality.
authors.affiliation: Center for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia.
authors.forename: Yashwant K
authors.initials: YK
authors.lastname: Sinha
authors.affiliation: Center for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia; School of Public Health, University of Sydney, Westmead, Australia.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Australian Pediatric Surveillance Unit, The Children's Hospital at Westmead, Westmead, Australia.
authors.forename: Premala
authors.initials: P
authors.lastname: Sureshkumar
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, Kensington NSW, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hayen
authors.affiliation: Faculty of Pharmacy, University of Sydney, St. Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of New South Wales, Kensington NSW, Australia.
authors.forename: Jo-anne E
authors.initials: JA
authors.lastname: Brien
mesh_terms: D000328:Adult; D015982:Bias; D002648:Child; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*; D018570:Risk Assessment / Q000379:methods*