Evaluating statistical methods to establish clinical similarity of two biologics.

The design, endpoints, statistical methods, and equivalence boundary for studies seeking to demonstrate clinical similarity between biologics are not standardized by any regulatory agency. We describe our experience in conducting a phase III study of a biologic product before and after a manufacturing change, focusing on statistical considerations for claiming equivalence for the dosing endpoint. We discuss and evaluate traditional statistical methods like two one-sided testing and the Kolmogorov-Smirnov test, as well as the newly proposed overlap coefficient method. We conclude that establishing clinical similarity of biologics is complex and demands more thought from regulatory agencies and the biopharmaceutical industry.