Design and Analysis of Biosimilar Switching Studies.

Under the US Biologics Price Competition and Innovation Act of 2009 (BPCI), the development of biosimilar (test) products provides affordable alternatives to innovative biological (reference) products for the general patient population. However, in practice, as the number of biosimilar products available on the market increases, whether these biosimilars can be used interchangeably is a concern. Thus, using switching studies to evaluate the risk of reduced efficacy and increased safety concerns with and without switch(es) in the development of biosimilar products is of interest. For this purpose, the US FDA, in its recent draft guidance on interchangeability, suggested using a 2 × 2 crossover design (RT, RR) to evaluate a single switch and (RTR, RRR) and (RTRT, RRRR) to evaluate multiple switches. In this article, we examine the statistical properties, analyses, and sample size requirements of these switching study designs. We also investigate the relative efficiencies of these switching designs compared with the complete  n-of-1 trial design.