Background Both FDA and EMA reward/demand pediatric oncology studies. Do they advance pediatric cancer care?
Methods We analysed publications of FDA representatives,1–3 FDA-triggered pediatric oncology studies in the literature and in www.clinicaltrials.gov,4 and FDA/EMA pediatric reports.5–6
Results FDA authors express two key assumptions: (1) children, defined as < 17y, need separate proof of efficacy;1–3 (2) with the exception of chronic myelogenous leukema, the biology of cancer in children is different from adult cancer.1 FDA-triggered studies investigated single cytoxics agents in heavily pretreated refractory/relapsed patients < 21y.2 4 In these days, combination treatment with up to 13 cytotoxic agents was standard of care.7 Another round of treatment with a single chemotherapy agent did not increase survival, but rewarded companies with patent extension, researchers with publications, the FDA with labeled information. The EU expanded the definition of children to < 18y and demands ‘pediatric investigation plans’ (PIPs) also for rare diseases. One FDA-triggered package investigated ipilimumab in ‘pediatric’ melanoma; 13 EMA PIPs demand ‘pediatric’ studies in solid tumors including melanoma; two ‘pediatric’ monotherapy studies with ipilimumab and vemurafenib, respectively, were terminated in 2016, five others continue recruiting.3 4 8
Discussion FDA/EMA-requested/demanded ‘paediatric’ oncology studies focus on labels in administratively defined ‘children’. FDA/EMA-used age limits are not physiological. FDA assumptions about different biology of ‘pediatric’ malignancies are incorrect.3 4 8 9 FDA/EMA reports list regulatory, not therapeutic achievements.5–6 Some EU researchers perform predominantly PIP-demanded oncology studies. In a cartel-like cooperation, the EMA demands such studies, threatening non-approval of life-saving drugs. Researchers and EMA representatives co-author lauding reports.10
Conclusion FDA representatives augmented the flawed ‘therapeutic orphans’ concept by additional wrong assumptions about ‘paediatric’ malignancies´ biology.1–4 The EMA further expanded the ‘Paediatric Imperative’. Also PIPs do not advance treatment. Ethics committees should be alerted to re-analyze ongoing ‘pediatric’ studies, suspend questionable ones, and reject new ones. US+EU pediatric laws need revision.
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EMA. 10-year Report to the European Commission. General report on the experience acquired as a result of the application of the Paediatric Regulation.
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Ruperto N et al. A European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA). Arch Dis Child. 2012 Mar;97(3):185–8.
Disclosure(s) The author has worked for more than 20 years in research & development/medical affairs in pharma¬ceutical industry and is now an independent consultant, advising pharmaceutical companies and academic institutions in all aspects of pediatric drug development, organizing scientific conferences, publishing, & more. The author´s elder daughter is severely handicapped with a rare syndrom, which has biased him against empty governmental promises.
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