Use of a two‐sided tolerance interval in the design and evaluation of biosimilarity in clinical studies

• Published in: Pharmaceutical statistics : the journal of the pharmaceutical industry Vol. 20; no. 1; pp. 175 - 184
• Main Authors: Chiang, Chieh, Chen, Chi‐Tian, Hsiao, Chin‐Fu
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01.01.2021; Wiley Subscription Services, Inc
• Subjects: Biological products; biosimilarity; Clinical trials; Clinical Trials as Topic; Humans; Research Design; Sample Size; sample size determination; Therapeutic Equivalency; Tolerance intervals; two‐sided tolerance interval; sample size determination; two-sided tolerance interval; biosimilarity
• ISSN: 1539-1604; 1539-1612
• DOI: 10.1002/pst.2065

Summary In assessing biosimilarity between two products, the question to ask is always “How similar is similar?” Traditionally, the equivalence of the means between products is the primary consideration in a clinical trial. This study suggests an alternative assessment for testing a certain percentage of the population of differences lying within a prespecified interval. In doing so, the accuracy and precision are assessed simultaneously by judging whether a two‐sided tolerance interval falls within a prespecified acceptance range. We further derive an asymptotic distribution of the tolerance limits to determine the sample size for achieving a targeted level of power. Our numerical study shows that the proposed two‐sided tolerance interval test controls the type I error rate and provides sufficient power. A real example is presented to illustrate our proposed approach.