Pediatric Clinical Research: Legislation Has Brought Progress, But More Is Needed

Progress has been made in pediatric medication development since the implementation of pediatric legislation in the U.S. from 1979 on, and through implementation of the Regulation in the EU, starting in 2006. Today, all applications for marketing authorization for new medicines must include data in children as described in the pediatric plan, unless the medicine is exempt, or benefits from a deferral or waiver.

New trial methodologies such as extrapolation, modeling and simulation techniques are well accepted to optimize and reduce the number of pediatric study subjects to the minimum necessary to obtain adequate results. Both the FDA and EMA have published Pediatric Extrapolation Guidances that permit the extrapolation of adult efficacy data to children and from one age group of children to another. The extrapolation concept is based on three foundational requirements that need to be satisfied before implementing such an approach. If these three conditions can be satisfied, it may be possible to extrapolate the efficacy data generated in adults (and/or older children) without having to conduct powered (Phase III) efficacy studies in pediatric patients:

1. The disease or condition in adults and children is essentially the same.
2. The response to treatment is anticipated to be comparable in children and adults.
3. An exposure-response (PK/PD relationship) can be established that will permit the use of pharmacokinetic extrapolation (i.e. dose adjusted exposure-matching) between adults and children of different ages.