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Clinical Trials of Investigational Antiepileptic Drugs: Monotherapy Designs
Author(s) -
Pledger Gordon W.,
Kramer Lynn D.
Publication year - 1991
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1991.tb04715.x
Subject(s) - clinical trial , clinical study design , medicine , placebo , drug , antiepileptic drug , protocol (science) , drug trial , research design , intensive care medicine , medical physics , pharmacology , alternative medicine , epilepsy , psychiatry , social science , pathology , sociology
Summary: 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.