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Antiepileptic drugs: evolution of our knowledge and changes in drug trials Volume 21, numéro 4, August 2019

TEST YOURSELF

(1) The first testing of phenytoin in animal models was conducted in 1936. How long did it take for phenytoin to reach the market, and how many randomized controlled trials led to its marketing?

(2) Do modern randomized adjunctive therapy placebo-controlled trials typically utilize a cross-over, or a parallel group design?

(3) Does the FDA require specific monotherapy studies to grant a license for monotherapy use of an AED?

 

 

 

 

 

 

 

 

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Answers

(1) Phenytoin reached the market within two years, and there were no randomized controlled trials completed by then.

 

(2) They utilize a parallel-group design, which minimizes trial duration and avoids the confounding influence of carry-over effects. Still, regulatory adjunctive therapy trials require a 12-week maintenance period, plus a titration phase of variable duration.

 

(3) No. The FDA may approve a monotherapy indication based solely on results from adjunctive therapy trials. To do so, the FDA must be satisfied that the efficacy demonstrated in adjunctive therapy trials is not related to drug interactions. Additionally, dosing recommendation for monotherapy is required to ensure that the level of plasma drug is equivalent to that which has been found to be efficacious based on adjunctive therapy trials.

 

 

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