ABSTRACT
Under the Biologic Price, Competition, and Innovation (BPCI) Act passed by the United States Congress in 2009, the development of biosimilar (test) products comparing to an innovative biological (reference) product provides more affordable alternatives to general patient population. In practice, however, as more and more biosimilar products become available in the marketplace, it is a concern whether these biosimilar products can be used interchangeably with one another. Thus, it is of interest to evaluate the risk of drug interchangeability in terms of possible reduction of efficacy and increase of safety concern with and without switch(es) under a switching study in biosimilar product development. For this purpose, in its recent guidance on interchangeability, the United States Food and Drug Administration (FDA) suggested using a 2×2 crossover design (RT, RR) for evaluation of single switch and (RTR, RRR) and (RTRT, RRRR) for evaluation of multiple switches. In this chapter, statistical properties, analyses, and sample size requirements 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.
