A biosimilar refers to a follow-on biologic intended to be approved for marketing based on biosimilarity to an existing patented biological product (i.e., the reference product). To develop a biosimilar product, it is essential to demonstrate biosimilarity between the follow-on biologic and the reference product, typically through two-arm randomization trials. We propose a Bayesian adaptive design for trials to evaluate biosimilar products. To take advantage of the abundant historical data on the efficacy of the reference product that is typically available at the time a biosimilar product is developed, we propose the calibrated power prior, which allows our design to adaptively borrow information from the historical data according to the congruence between the historical data and the new data collected from the current trial. We propose a new measure, the Bayesian biosimilarity index, to measure the similarity between the biosimilar and the reference product. During the trial, we evaluate the Bayesian biosimilarity index in a group sequential fashion based on the accumulating interim data, and stop the trial early once there is enough information to conclude or reject the similarity. Extensive simulation studies show that the proposed design has higher power than traditional designs. We applied the proposed design to a biosimilar trial for treating rheumatoid arthritis.
Keywords: Bayesian adaptive design; Biosimilarity index; Biosimilars; Borrow information; Calibrated power prior; Follow-up biologics; Historical data.