A Comparative Study of Some Statistical Procedures in Establishing Therapeutic Equivalence of Nonsystemic Drugs with Binary Endpoints

Abstract

Traditionally, the bioequivalence of a generic drug with the innovator's product is assessed by comparing their pharmacokinetic profiles determined from the blood or plasma concentration-time curves. This method may only be applicable to formulations where blood drug or metabolite levels adequately characterize absorption and metabolism, not to the nonsystematic drugs categorized by the lack of systemic presence. When pharmacologic effects of the drugs can be easily measured, pharmacodynamic effect studies can be used to assess the therapeutic equivalence of nonsystemic drugs. When analytical methods or other tests cannot be developed to permit the use of the pharmacodynamic method, therapeutic equivalence clinical trials to compare one or several clinical endpoints may be the only suitable method of establishing therapeutic equivalence. This paper evaluates by Monte-Carlo simulations the fixed sample performances of some two one-sided tests procedures when the endpoints of the therapeutic equivalence trials are binary.

Keywords

Binary endpoints Hauck-Anderson corrections Monte-Carlo simulations Therapeutic equivalence Two one-sided tests procedure

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