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Extrapolation in the development of paediatric medicines: examples from approvals for biological treatments for paediatric chronic immune-mediated inflammatory diseases
  1. Anna M Stefanska1,
  2. Dorota Distlerová2,
  3. Joachim Musaus1,
  4. Thorsten M Olski1,
  5. Kristina Dunder1,3,
  6. Tomas Salmonson1,3,
  7. Dirk Mentzer1,4,
  8. Jan Müller-Berghaus1,4,
  9. Robert Hemmings1,2,
  10. Richard Veselý1
  1. 1European Medicines Agency, London, UK
  2. 2Medicines and Healthcare Products Regulatory Agency, London, UK
  3. 3Läkemedelsverket, Medical Products Agency, Uppsala, Sweden
  4. 4Paul-Ehrlich Institut, Langen, Germany
  1. Correspondence to Dr Richard Veselý, European Medicines Agency, 30 Churchill Place, London E14 5EU, UK; richard.vesely{at}ema.europa.eu

Abstract

The European Union (EU) Paediatric Regulation requires that all new medicinal products applying for a marketing authorisation (MA) in the EU provide a paediatric investigation plan (PIP) covering a clinical and non-clinical trial programme relating to the use in the paediatric population, unless a waiver applies. Conducting trials in children is challenging on many levels, including ethical and practical issues, which may affect the availability of the clinical evidence. In scientifically justified cases, extrapolation of data from other populations can be an option to gather evidence supporting the benefit–risk assessment of the medicinal product for paediatric use. The European Medicines Agency (EMA) is working on providing a framework for extrapolation that is scientifically valid, reliable and adequate to support MA of medicines for children. It is expected that the extrapolation framework together with therapeutic area guidelines and individual case studies will support future PIPs. Extrapolation has already been employed in several paediatric development programmes including biological treatment for immune-mediated diseases. This article reviews extrapolation strategies from MA applications for products for the treatment of juvenile idiopathic arthritis, paediatric psoriasis and paediatric inflammatory bowel disease. It also provides a summary of extrapolation advice expressed in relevant EMA guidelines and initiatives supporting the use of alternative approaches in paediatric medicine development.

  • Clinical Trials
  • Paediatric
  • Extrapolation
  • Psoriasis
  • Juvenile Idiopathic Arthritis
  • Crohn’s Disease
  • Ulcerative Colitis

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Footnotes

  • Contributors RV conceived the idea for the study, AMS and DD extracted the data, and AMS and RV wrote the manuscript. RV, JM, TMO, KD, TS, DM, JM-B and RH critically reviewed and contributed to the text of the manuscript.

  • Competing interests The authors declare no conflicts of interest. AMS is currently employed by Novartis.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with 'BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.

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