Comparability of Pharmacodynamics Profiles with an Application to a Biosimilar Study

Abstract

It is often interest of comparing two pharmacodynamics (PD) profiles in drug development. Currently the common practice is borrowing the bioequivalence (BE) rule in pharmacokinetics analysis for pharmacodynamics comparison in terms of the area under the effect curve (AUEC) of the pharmacodynamics profile. However, this may not be a feasible and sensitive enough approach since the bioequivalence approach is based on the summarized parameter of the pharmacodynamics profile rather than on directly comparison of the whole pharmacodynamics profile. In this paper, a simple but efficient and pragmatic pharmacodynamics comparability index is proposed to evaluate the comparability of pharmacodynamics profiles by comparing the whole pharmacodynamics profiles directly. Different biological products have different variability and the CV% can be in a very large range. The PD comparability index can take account of the reference knowledge into consideration in assessment but the AUEC BE type approach ignores the reference variability. The good properties of the proposed approach are illustrated through simulated data and a real dataset.