title: Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development.
abstract: There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development.
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia. michele.simonato@unife.it
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
authors.forename: Edward H
authors.initials: EH
authors.lastname: Bertram
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Collins
authors.forename: Merab
authors.initials: M
authors.lastname: Kokaia
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Henrik
authors.initials: H
authors.lastname: Klitgaard
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Staley
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vaudano
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
authors.forename: Michele
authors.initials: M
authors.lastname: Simonato
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic / Q000191:economics; D017322:Clinical Trials, Phase II as Topic / Q000191:economics; D017046:Cost Savings; D004353:Drug Evaluation, Preclinical / Q000191:economics; D004351:Drug Resistance; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D015337:Multicenter Studies as Topic / Q000191:economics; D012109:Research Support as Topic / Q000191:economics; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D015507:Drugs, Investigational
keywords: Antiepilepsy therapies; Multicenter; Preclinical development