The Path to Perfect Pediatric Posology - Drug Development in Pediatrics.

Reluctance to enroll pediatric subjects in clinical trials has left gaps in information about dosing, safety, and efficacy of medications. Pharmacotherapeutic information for pediatric patients may be available for only a small range of ages and may be deficient, as children respond differently as they grow and mature from prematurity to adolescence. Current regulations, however, require early planning for the participation of children in drug development, as pediatric plans must be submitted at the end of phase 1 (European Union) or the end of phase 2 (United States). These plans are extensive, outlining planned studies, subjects to be enrolled, dose and dosage form justification, planned observations, and statistical analysis as well as planned modeling, simulation, and extrapolation analyses. The extent to which efficacy information in adults can be extrapolated to children depends on how similar the disease is in adults and each of the 5 pediatric age groups. Extrapolation may not be possible for conditions that do not occur in adults, requiring a complete development plan in adults, or extrapolation may be complete because of similar pathology and response to treatment. Pharmacokinetic and safety information cannot be extrapolated and must be collected in children of all ages, unless a waiver is granted. Physiologically based pharmacokinetic modeling, optimal design, population pharmacokinetics, and scavenged samples are all examples of new methodologies being used to study pediatric therapeutics. Clinicaltrials.gov and EU Clinical Trials registry are good sources of results of pediatric trials, although sponsors are also working toward prompt publication of study results in peer-reviewed journals.