Title: 

Statistical Challenges in Assessing the Equivalence of Complex Generic Products 

Abstract: 

Under current drug marketing regulations, generic products are considered therapeutically equivalent to the innovator or brand-name drug product if they meet regulatory criteria of pharmaceutical equivalence and bioequivalence (BE). For determining BE, the FDA may accept evidence from various approaches, including in vivo pharmacokinetic (PK) studies, certain in vitro studies that are correlated with and predictive of human in vivo bioavailability, and well-controlled clinical trials. 

For most oral drug products, plasma PK studies provide useful information. Two-period crossover designs and Schuirmann’s two one-sided tests procedure have been used in the assessment of bioequivalence. As more complex drug products have entered the marketplace, however, more complicated designs and other sorts of studies are needed, raising statistical challenges. In this talk I will discuss the statistical design and analysis of studies for the determination of BE, including PK as well as comparative clinical endpoint studies. I will outline conventional approaches and describe some recent research and open questions.