Innovative Design and Analysis for PK/PD Biosimilar Bridging Studies with Multiple References.

When there are multiple reference products, (e.g., EU-approved product and US-licensed product), a pharmacokinetic/pharmacodynamic (PK/PD) bridging study is often conducted in order to bridge the clinical data from the original region (e.g., Europe) to the new region (e.g., USA) in support of the biosimilar regulatory submission in the new region. The purpose is to avoid duplicated clinical trials for clinical similarity between a proposed biosimilar product and the reference product in the new region provided that there is no ethnic concern in the two regions. In this article, some innovative statistical designs for PK/PD biosimilar bridging studies are proposed. Statistical model and methods under the proposed statistical designs are studied. Power analysis for sample size requirement based on Schuirmann's two one-sided tests procedure is also derived and compared to pairwise testing using simulation.