Two one-sided tests procedures in establishing therapeutic equivalence with binary clinical endpoints: fixed sample performances and sample size derformination

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 metabolites levels adequately characterize absorption and metabolism. For non-systematic drugs categorized by the lack of systemic presence, such as metered dose inhalers (MDI), anti-ulcer agents and topical antifungals and vaginal antifungals, new definition of therapeutic equivalency and criteria for acceptance should be used. When pharmacologic effects of the drugs can be easily measured, pharmacodynamic effect studies can be used to assess the therapeutic equivalence of non-systemic drugs. When analytical methods or other tests cannot be developed to permit use of the pharmacodynamic method, clinical trials to compare one or several clinical endpoints may be the only suitable method to establishing therapeutic equivalence. In this paper we evaluate by Monte-Carlo simulations the fixed sample performances of some two one-sided tests procedures which may be used to assess the therapeutic equivalence of non-systemic drugs with binary clinical endpoints. Formulae of sample size determination for therapeutic equivalence clinical trials are also given.