Pediatric investigation plans for specific immunotherapy: Questionable contributions to childhood health.
Allergen-specific immunotherapy (SIT) is the only disease-modifying treatment for children, adolescents, and adults with allergic diseases. The EU has a combined system of national and EU-wide marketing authorization for all medicines. Germany introduced a new therapy allergen ordinance in 2008. Allergen products manufacturers had to apply for marketing authorization application for the major allergen groups (grass group, birch group, mites group, bee/wasp venom). Due to the EU pediatric regulation, in force since 2007, manufacturers had also to submit a pediatric investigation plan (PIP) for each allergen product. We investigated the allergic rhinoconjunctivitis (ARC) standard PIP, developed jointly by the European Medicines Agency (EMA) and the German Paul Ehrlich Institut (PEI). We analyzed the 118 EMA PIP decisions, looked for SIT trials in children in www.clinicaltrials.gov, and further analyzed EMA/EU justifications. The PIPs request a 1-year dose-finding study in adults, a 5-year placebo-controlled (PC) efficacy & safety (E&S) study in adults, and a 5-year PC E&S study in children. Fifty-eight PIP development programs will have to be performed until 2031. But children benefit even more from SIT for ARC than adults. There is no convincing medical/scientific justification for PC E&S studies in children in the relevant EMA documents. The PIP requirement to withhold effective treatment to thousands of children in the placebo group over a 5-year period raises profound concerns. The EMA justifications are formalistic and lack scientific foundation. A critical academic review of the ARC PIPs and the entire PIP system is urgently needed.
['Rose|Klaus|K|', 'Kopp|Matthias Volkmar|MV|']
D000293:Adolescent D000328:Adult D000485:Allergens D001709:Biotechnology D002648:Child D002986:Clinical Trials as Topic D003231:Conjunctivitis D003888:Desensitization, Immunologic D005062:European Union D019317:Evidence-Based Medicine D005858:Germany D033161:Government Regulation D006801:Humans D065631:Rhinitis, Allergic
pediatric investigation plan children allergic rhinoconjunctivitis European Medicines Agency allergic asthma allergy better medicines for children pediatric committee sensitization specific allergen immunotherapy