[Bioequivalence and generic drugs. I. Studies of bioequivalence, considering the theoretical basis, design and use].

OBJECTIVES

To describe the studies done before a generic drug is marketed.

DEVELOPMENT

We reflect on the concept of bioequivalence and its limitations, then describe the parameters on which a study of bioequivalence is based and explain the statistical hypothesis of bioequivalence. Finally, we explain the process of a clinical trial of bioequivalence and how the results are analyzed, using a clinical trial as an example. We show how 'carry-over', formulation and period effects are analyzed; and also how bioequivalence may be evaluated by using different approximations: construction of the confidence interval, confidence hypothesis and nonparametric approximations. Finally, we mention the methods used to estimate the size of the sample required in a study of this kind.

CONCLUSIONS

Studies of bioequivalence, even the simplest, have peculiarities of design and statistical basis which are markedly different from other clinical trials. When generic drugs are marketed it is important to know about the peculiarities and characteristics of the studies on which affirmation of the bioequivalence of these products is based.