PRINCIPLES OF STATISTICAL EVALUATION OF BIOEQUIVALENCE STUDIES IN THE CONTEXT OF CURRENT REGULATORY REQUIREMENTS AND LEGAL ACTS

Abstract

The article analyses regulatory documents and requirements for statistical principles of planning and evaluation of results of bioequivalence studies. It describes current statistical approaches to bioequivalence evaluation and relevant recommendations for the planning of studies of conventional medicinal products, medicinal products with a narrow therapeutic range, and analogues of endogenous compounds. The article analyses such statistical approaches as average Bioequivalence (ABE), Average Bioequivalence with Expanding Limits (ABEL), Reference-Scaled Average Bioequivalence (RSABE). It describes specific aspects of statistical analysis of insufficiently studied medicinal products. The article also describes acceptable algorithms of planning and performing two-stage bioequivalence study designs, since such studies call for multiple testing of the bioequivalence hypothesis which leads to an increased probability of type i error (consumer risk). The article offers recommendations for the choice of statistical approaches and describes some aspects of statistical analysis methods depending on the design of the study and the type of generic medicines.