"Achievements" Claimed In The EMA Paediatric 10-Years-Report On The EU Pediatric Regulation Don`t Withstand Critical Examination

Background: The EMA 10-years-report claims that many medicines for the treatment of infectious diseases became available after completion of paediatric investigation plans (PIPs), giving peginterferon alpha (PEGα) for hepatitis C as an example.

Objective: To verify/challenge the EMA`s claims and the medical justifications given for requiring separate safety & efficacy (S&E) studies in minors.

Methods: PIPs listed on the EMA website and associated publications of pediatric PEGα trials were analyzed for medical validity considering basic principles of developmental pharmacology/physiology and commonsense.

Results: Three PIPs required pediatric hepatitis C S&E studies: two open-label studies PEGα + ribavirin in 3-17 year olds, and one double-blind placebo-controlled study in 5-17 year olds. The latter, performed in the USA (Schwarz K et al. 2011), confirmed superiority of PEGα + ribavirin over PEGα alone shown years before in adults. The belief that children need separate proof of S&E originates from the poorly supported dogma that "kinetics, end organ responses, and toxicities" of drugs in children of all ages differ fundamentally from adults, expressed in key documents of the American Academy of Pediatrics (AAP). This dogma wrongly uses "children" as both a legal and physiological term. Children are not another species. Physiology and pharmacology often differs in babies and young children but not in most, more mature minors.

The EMA`s claim that their PIPs made PEGα available for children with hepatitis C is misleading at best. PEGα was available off-label without PIPs. Medically, assessment of paediatric dosing is needed, but this can be better achieved by modeling & simulation and confirmation by opportunistic PK/PD studies rather than the medically and ethically questionable, PIP-demanded PEGα double-blind placebo-controlled S&E study.

Conclusion: The EAP should voice an independent position on what type of paediatric regulatory studies are needed based on science, developmental pharmacology/physiology, and commonsense; not on dogma.