Clinical Drug Development in Epilepsy Revisited: A Proposal for a New Paradigm Streamlined Using Extrapolation.
Data from clinical trials in adults, extrapolated to predict benefits in paediatric patients, could result in fewer or smaller trials being required to obtain a new drug licence for paediatrics. This article outlines the place of such extrapolation in the development of drugs for use in paediatric epilepsies. Based on consensus expert opinion, a proposal is presented for a new paradigm for the clinical development of drugs for focal epilepsies. Phase I data should continue to be collected in adults, and phase II and III trials should simultaneously recruit adults and paediatric patients aged above 2 years. Drugs would be provisionally licensed for children subject to phase IV collection of neurodevelopmental safety data in this age group. A single programme of trials would suffice to license the drug for use as either adjunctive therapy or monotherapy. Patients, clinicians and sponsors would all benefit from this new structure through cost reduction and earlier access to novel treatments. Further work is needed to elicit the views of patients, their parents and guardians as appropriate, regulatory authorities and bodies such as the National Institute for Health and Care Excellence (UK).
MRC North-West Hub for Trials Methodology Research, Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster, LA1 4YF, UK.
Ian
I
Wadsworth
MRC North-West Hub for Trials Methodology Research, Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster, LA1 4YF, UK.
Thomas
T
Jaki
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Graeme J
GJ
Sills
The Roald Dahl EEG Unit, Paediatric Neurosciences Foundation, Alder Hey Children's Hospital, Liverpool, UK.
Richard
R
Appleton
University College London-Institute of Child Health, Great Ormond Street Hospital for Children, London, UK.
J Helen
JH
Cross
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.|The Walton Centre NHS Foundation Trust, Liverpool, UK.
Anthony G
AG
Marson
Department of Paediatric Neurology, Royal Manchester Children's Hospital, Manchester, UK.
Tim
T
Martland
Department of Paediatric Neurosciences, Royal Hospital for Sick Children, Edinburgh, UK.
Ailsa
A
McLellan
Department of Neurology, University Hospital of Wales, Cardiff, UK.
Philip E M
PE
Smith
Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA.
John M
JM
Pellock
MRC North-West Hub for Trials Methodology Research, Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster, LA1 4YF, UK. l.v.hampson@lancaster.ac.uk.
Lisa V
LV
Hampson
D000927:Anticonvulsants / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans
D000927:Anticonvulsants