On hybrid parallel–crossover designs for assessing drug interchangeability of biosimilar products

ABSTRACT

In recent years, a specific hybrid parallel–crossover design that consists of two sequences of treatments, namely R–R–R–R and R–T–R–T, where T and R is a proposed biosimilar product and an innovative biological product, respectively, have been proposed and received much attention for assessing drug interchangeability between T and R, where R could be either a US-licensed product or an EU-reference product. In practice, there are three types of hybrid parallel–crossover designs that are commonly employed in assessing drug interchangeability of biosimilar products. These three types of parallel–crossover hybrid designs include (1) a parallel + 2 × 2 crossover design, (2) a parallel + 2 × 3 crossover design, and (3) a parallel + 2 × 4 crossover design. This article provides a comprehensive review of these study designs including a complete N-of-1 randomized trial design. A specific hybrid parallel–crossover design, that is, (RRRR, RTRT) for addressing drug interchangeability in terms of switching and the relative risk between with/without alternation is discussed.

KEYWORDS:

• Alternation
• by period analysis
• by sequence analysis
• N-of-1 trial design
• switching