The end of regulatory monotherapy trials?

Abstract

The ongoing debate about the value and the ethics of monotherapy trials of antiepileptic drugs (AEDs) is now invigorated by an elegant Personal View article by Scott Mintzer and colleagues in The Lancet Neurology. 1 Mintzer S French JA Perucca E et al. Is a separate monotherapy indication warranted for antiepileptic drugs?. Lancet Neurology. 2015; 14: 1229-1240 Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar Briefly, the authors recommend that the US Food and Drug Administration (FDA) approve adjunctive AEDs in a combined indication for the treatment of seizures or epilepsies, irrespective of concurrent medication use. Why should the traditional separation of monotherapy and adjunctive therapy indications be abandoned? Because, the authors argue, valuable new AEDs such as levetiracetam are not labelled for monotherapy in the USA because of regulatory issues. Many physicians see this restriction as harmful for patients. Is a separate monotherapy indication warranted for antiepileptic drugs?Antiepileptic drugs (AEDs) are the only neurotherapeutics for which regulatory approval is consistently separated into monotherapy or adjunctive-therapy indications. Because head-to-head comparisons of AEDs (used in the European Union to approve drugs for monotherapy) have not shown substantial differences in efficacy between drugs, FDA approval for use of an AED as monotherapy has typically been based on trials with novel designs that have been criticised for reasons of ethics and clinical relevance. Full-Text PDF