Standard 6: Age Groups for Pediatric Trials

Abstract

DILEMMAIt has long been an axiom in clinical pediatrics that "children are not just little adults." It has also been recognized that there are many changes from birth through childhood and the adolescent years. However, the full implications of pediatric age groupings for health care and research are still not adequately understood. There is still much to be discovered about children' s biological and psychological development and how these processes affect the effectiveness and efficacy of interventions. Trial design that accounts for age differences and promotes consistency in reporting of age-related data is essential to ensure the validity and clinical usefulness of pediatric trial data.A recent study highlighted variable treatment efficacy in children versus adults. In this study, 128 meta-analyses from Cochrane reviews, containing data on at least 1 adult and 1 pediatric randomized controlled trial (RCT) with a binary primary efficacy outcome, were reviewed. 1 The authors found that in all except 1 case, the 95% confidence intervals could not exclude a relative difference in treatment efficacy between adults and children of .20%; in two-thirds of these cases, the relative difference in observed point estimates was .50%. The study also highlighted the paucity of RCTs in pediatrics; the median number of children per metaanalysis was 2.5 times smaller than the number of adults.Children and adults seem to have distinctive responses to treatments. For example, administration of phenobarbitones is useful for adults with cerebral malaria and is associated with decreased convulsions. However, in children, this drug is associated with increased 6-month mortality. Similarly, corticosteroids may offer survival benefit for adults with bacterial meningitis but not for children with the same condition. In acute traumatic brain injury, corticosteroids did not decrease mortality in adults, but there was a trend for increased mortality in children. 1 In asthma, long-acting b2-agonists decreased exacerbations in adults but tended to increase exacerbations in children. 1 Intravenous lorazepam, when compared with diazepam in status epilepticus, led to significantly more discontinuations of status in adults but not in children. It is not surprising then that although using an algorithm for extrapolation of adult data for use in pediatric drug licensing and development was found to be useful for streamlining drug development and approvals for pediatric use, complete extrapolation from adult data were only appropriate for 6% of drugs reviewed. 2 Beyond the stark contrast in the efficacy of pharmacologic interventions between children and adults, considerable variation of adverse events and morbidity can be anticipated across the pediatric age range. Authors of a recent study of pediatric drug surveillance and adverse event reporting concluded that "suspect drugs and adverse events should be evaluated in the context of age groups" because both drug utilization and the ability to report adverse events vary by age. 3 For example, t...

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