Extrapolation or controlled trials in paediatrics: the current dilemma

• Published in: Archives of disease in childhood Vol. 102; no. 10; pp. 949 - 951
• Main Authors: Ruperto, Nicolino, Brunner, Hermine I, Lovell, Daniel J, Martini, Alberto
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.10.2017; BMJ Publishing Group LTD
• Subjects: Adults; Analysis; Biological products; Child; Clinical trials; Clinical Trials as Topic; Collaboration; Dilemma; Disease; Drug dosages; Female; Humans; Immunoglobulins; Learning Activities; Legislation; Male; Marketing; Monoclonal antibodies; Narcotics; Networks; Pediatrics; Pharmaceutical industry; Placebos; Rheumatoid arthritis; Rheumatology; Safety and security measures; rheumatology; extrapolation; clinical trials; pediatrics
• ISSN: 0003-9888; 1468-2044; 1468-2044
• DOI: 10.1136/archdischild-2017-312994

Thanks to the Best Pharmaceuticals for Children Act in USA and to a dedicated legislation for paediatric medicines development (Paediatric Regulation) in the European Union, this dire situation is very much improved. 1 2 Undoubtedly, in some paediatric specialities, such as paediatric rheumatology, this legislation has been a great success. 3 At least to some extent, this success seems attributable to the existence of two large networks, namely the Pediatric Rheumatology Collaborative Study Group (PRCSG) ( www.prcsg.org) , covering North America, and the Paediatric Rheumatology International Trials Organisation (PRINTO) ( www.printo.it) , covering more than 60 countries worldwide. 4 Through coordinated and collaborative activities over the preceding two decades, these two networks have effectively worked in academia (over 35000 children enrolled in not-for-profit studies) and with various pharmaceutical companies and succeeded to help enrol more than 3000 children at over 250 centres from 39 countries in international clinical trials. 5-12 Indeed, all studies of biological medications by these two networks, with the exception of the infliximab trial (see later), 6 have led to a marketing authorisation for juvenile idiopathic arthritis (JIA). Paediatric trials can capitalise on robust data coming from large adult trials. [...]paediatric programmes typically commence with phase II dose finding studies rather than phase I studies of healthy children or very ill subjects, like for cancer trials. [...]not all drugs to be marketed for adults must necessarily be studied in children. [...]the current legislation does not foresee any obligation for pharmaceutical companies to obtain marketing authorisation for children, even if the 'reference medicine' has such authorisation.