ABSTRACT
Under the Biologic Price, Competition, and Innovation (BPCI) Act passed by the United Congress in 2009, the development of biosimilar (test) products compared to an innovative biological (reference) product provides a more affordable alternative to general patient population. In practice, however, as more and more biosimilar products are available in the marketplace, it is a concern whether these biosimilar products can be used interchangeable with one another. Thus, it is of interest to evaluate the risk in terms of possible reduction in efficacy and increase in safety concern with and without switch(es) under a switching study in biosimilar product development. For this purpose, in its recent draft guidance on interchangeability, the FDA suggested using a 2 × 2 crossover design (RT, RR) for the evaluation of single switch, and (RTR, RRR) and (RTRT, RRRR) for the evaluation of multiple switches. In this chapter, statistical properties, analyses, and sample size requirement of these switching designs are examined. The relative efficiencies of these switching designs as compared to the commonly used n-of-1 trial design are also studied.
