title: 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.
authors.affiliation: a Department of Biostatistics and Bioinformatics , Duke University School of Medicine , Durham , North Carolina , USA.
authors.forename: Shein-Chung
authors.initials: SC
authors.lastname: Chow
authors.affiliation: b Peking University Clinical Research Institute , Peking University , Beijing , China.
authors.forename: Fuyu
authors.initials: F
authors.lastname: Song
authors.affiliation: a Department of Biostatistics and Bioinformatics , Duke University School of Medicine , Durham , North Carolina , USA.
authors.forename: Can
authors.initials: C
authors.lastname: Cui
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000592:standards*; D018592:Cross-Over Studies; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: Alternation; N-of-1 trial design; by period analysis; by sequence analysis; switching