The Dogma that Children are Therapeutic Orphans Challenged

Background: In 1963, Shirkey described children as "therapeutic orphans" (TOs), claiming they were denied the use of many new drugs. The American Academy of Pediatrics (AAP) took this up; resulting in US pediatric legislation (USPL) and eventually EU pediatric legislation (EUPL). Since 2007, new drugs cannot be EU-registered without pediatric investigation plan (PIP).

Objective: To verify/challenge Shirkey`s, AAP`s, USPL`s and EUPL`s assumptions

Methods: Shirkey`s original publication, AAP guidelines on pediatric studies & off-label, and the 1962 US law were analyzed. Key assumptions and the rationale for demanding separate pediatric safety & efficacy (S&E) studies were examined against the history of medicine & pediatric sub-disciplines.

Results: Shirkey incorrectly used "children" for underage persons as both a legal and physiological term. He misinterpreted some unintended consequences of the US law. Drug label warning clauses "not to be used in children" were not legally binding; they protected companies against lawsuits. In 1995, the AAP alarmingly "proved" that differences from adults in "kinetics, end organ responses, and toxicities" of drugs in children of all ages by citing two papers on preterm newborns. Children profit(ed) even more from modern drugs than adults. Pediatric oncology, pediatric cardiology, neonatology evolved successfully using drugs off-label. Children usually need assessment of appropriate dosing, not separate S&E studies. Children are not another species. Young children differ considerably from adults, but not adolescents in whom adult doses are appropriate as demonstrated by 2016 FDA labels for antiepileptic/ anticancer drugs.

Conclusion: The TO concept and demands for separate pediatric S&E studies are based on misinterpretation/confusion at the interface of law and medicine. Use of drugs in adolescents needs legal fixing, not S&E studies. Younger children need dose confirmation after modeling & simulation. The EAP needs an independent position on drug development and off-label use and should distance itself from the PIP system.