Clinical trials of investigational antiepileptic drugs: monotherapy designs

Epilepsia. Sep-Oct 1991;32(5):716-21. doi: 10.1111/j.1528-1157.1991.tb04715.x.

Abstract

The standard designs for safety and efficacy trials of investigational antiepileptic drugs are placebo-controlled, add-on trials and active control equivalence studies. These designs, motivated by medical ethics, have serious evidential limitations. Add-on trials are frequently criticized as insensitive and difficult to interpret in the presence of drug interactions; active control equivalence studies are not probative of test drug activity. As an alternative, we describe two trial designs: a placebo-control design with inpatients who in undergoing a presurgery seizure evaluation have had all antiepileptic drugs discontinued; and an active-control design aimed at showing the test drug superior to the control treatment, thus avoiding the interpretational difficulties of no-difference outcomes. A critical feature of these new designs is the limitation of subject exposure to unacceptable treatments. This is accomplished through protocol criteria--corresponding to therapeutic failure--which both terminate a subject's trial participation and form the basis of efficacy comparisons.

MeSH terms

  • Anticonvulsants / therapeutic use*
  • Clinical Protocols / standards
  • Double-Blind Method
  • Drugs, Investigational / therapeutic use*
  • Electroencephalography
  • Epilepsy / drug therapy*
  • Ethics, Medical
  • Hospitalization
  • Humans
  • Placebos
  • Randomized Controlled Trials as Topic / methods*
  • Randomized Controlled Trials as Topic / standards
  • Research Design / standards

Substances

  • Anticonvulsants
  • Drugs, Investigational
  • Placebos