Clinical testing in children

Abstract

Clinical trials systematically compare safety and effi cacy of different therapeutic interventions. Since the 1960s proof of effi cacy and safety through appropriate clinical trials are a legal requirement for the registration of drugs, and that made the advent of drug labels in the modern sense of the word. Regulatory clinical trials have become one cornerstone of the drug development process. Pivotal trials are decisive for registration: a drug may show promising results in early trials; if it fails in the pivotal trials, it is abandoned—or developed for another indication. In parallel to industry-sponsored clinical trials with regulatory purposes, academic trials continued. They aim at improving interventions without regulatory concerns. When modern labels were introduced, children were largely excluded from regulatory clinical trials. With increasing understanding of the child’s developing body and how it interacts with drugs, i.e., with the evolvement of pediatric clinical pharmacology, dosing based on mechanical formulas was understood to be insuffi cient. Pediatricians used the increasing number of available, highly effective, adult drugs off-label also in children, but a gap was perceived between the attention given to adults as compared to children. The child version of the British National Formulary (BNF) was a pragmatic attempt for reconciliation. Pediatric oncologists developed new off-label treatment schemes for adult anticancer drugs—also a pragmatic approach. Since 1997, US pediatric legislation encourages pharmaceutical companies to generate additional pediatric data. The 2006 EU pediatric legislation aims at investigating the potential pediatric use of new drugs already during early drug development and at their registration in children. In short, we have at least four developments: (1) a better understanding of the child’s developing body and how it impacts drug treatment; (2) the expansion of the framework and the science of human clinical trials into addressing child-specifi c aspects; (3) facilitation of