title: Demonstrating bioequivalence using clinical endpoint studies.
abstract: For drug products not amenable to blood level studies, clinical endpoint studies have been used as an indirect measure of formulation difference in bioavailability between test and reference products. However, clinical endpoint studies are not as sensitive in detecting formulation differences as blood level studies and offer numerous challenges to both regulatory authorities and sponsors. The objective of this article is not to suggest new regulatory policies, but to explore new methodologies and alternative solutions to clinical endpoint bioequivalence (BE) studies, which are used when a blood level study is not considered to be appropriate. To achieve this objective, this article identifies situations where a clinical endpoint study might be appropriate, lists the advantages and disadvantages of this type of study design, and discusses possible alternative solutions. It is concluded that future evidence-based research is needed to explore new methodologies such as clinical trial simulations of various study designs, new statistical methods, and new in vitro methods to demonstrate BE.
authors.affiliation: Division of Therapeutic Drugs for Non-Food Animals, FDA Center of Veterinary Medicine, Rockville, MD, USA. eden.bermingham@fda.hhs.gov
authors.forename: E
authors.initials: E
authors.lastname: Bermingham
authors.forename: J R E
authors.initials: JR
authors.lastname: Del Castillo
authors.forename: C
authors.initials: C
authors.lastname: Lainesse
authors.forename: K
authors.initials: K
authors.lastname: Pasloske
authors.forename: S
authors.initials: S
authors.lastname: Radecki
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods / Q000662:veterinary*; D003198:Computer Simulation; D012107:Research Design / Q000592:standards* / Q000639:trends; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D019155:Veterinary Drugs / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019155:Veterinary Drugs