Ethical Issues in Pediatric Regulatory Studies Involving Placebo Treatment

Abstract Separate pediatric studies for antiepileptic drugs (AEDs) emerged with general separate drug approval in children and were defined by the U.S. Food and Drug Administration (FDA) as <17 years and by the European Union (EU) as <18 years. These administrative age limits are necessary in pediatrics, but they correspond variably with the physiological maturity of young patients and are not helpful for therapeutic decisions or as study inclusion criteria. AEDs are often effective for partial onset seizures (POS) in 2 to 17-year-olds as well as in ≥18-year-olds, if dosed correctly. Separate pediatric AED studies assume no difference between the legal and the physiological meaning of the word “child.” While the FDA now accepts efficacy of AEDs in POS in children ≥2 years, the EU still requires separate “pediatric” studies. For retigabine it waived all pediatric studies after having required 20 such studies over several years. We feel the current regulation creates a situation where many studies in children are done unnecessarily; we question the ethics of such an approach, which in our view, is morally wrong. Critical publications contributed to the FDA's shift of opinion for AEDs in POS but did not address the blur of different meanings of the word “child.”