Do the European Medicines Agency Decisions Hurt Pediatric Melanoma Patients?
US pediatric legislation was introduced in 1997 and was followed by European Union pediatric legislation that, since 2007, requires a European Medicines Agency (EMA)-approved pediatric investigation plan (PIP) for registration of new medicines unless they are PIP exempted. In 2008, the EMA decided that enough adolescent patients with melanoma existed and removed melanoma from the list of PIP-exempted diseases (class waiver list). We examined the logic and the results of this decision.



We analyzed the EMA class waiver decision, the melanoma PIP decisions, the wording of the European Union pediatric legislation, and melanoma trials listed in www.clinicaltrials.gov and www.clinicaltrialsregister.eu that recruit adults and minors or only minors.



There are 12 melanoma PIP decisions. Two apparently PIP-triggered melanoma trials were terminated in 2016 because of slow recruitment, and 4 are ongoing. Numerous non-PIP-driven trials are recruiting both adults and minors with melanoma worldwide, thus competing with PIP-triggered melanoma trials.



Revoking the melanoma class waiver was not based on science but on flawed logic. It resulted in PIP-demanded pediatric trials that do not make medical sense, fail to recruit adequately, and prevent participants from more promising off-label treatment or treatment in clinically, scientifically, and ethically superior non-PIP-triggered studies. Institutional review boards and ethics committees should consult both www.clinicaltrials.gov and www.clinicaltrialsregister.eu for competing trials in the same population and reject or withdraw approval for questionable trials. A major revision or replacement of the European Union pediatric legislation is needed to prevent children from being enrolled in unnecessary, unfeasible, or scientifically invalid trials.
klausrose Consulting: Pediatric Drug Development & More, Riehen, Switzerland. Electronic address: klaus.rose@klausrose.net.
Klaus
K
Rose
Department of Clinical Pharmacology, University Medical School, Goettingen, Germany.
Philip D
PD
Walson
D000293:Adolescent; D000328:Adult; D002648:Child; D002986:Clinical Trials as Topic / Q000331:legislation & jurisprudence*; D005062:European Union; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*
European Medicines Agenca (EMA); melanoma; pediatric clinical pharmacology; pediatric drug development; pediatric investigation plan (PIP); pediatric legislation