title: Adjustment for unbalanced sample size for analytical biosimilar equivalence assessment.
abstract: Large sample size imbalance is not uncommon in the biosimilar development. At the beginning of a product development, sample sizes of a biosimilar and a reference product may be limited. Thus, a sample size calculation may not be feasible. During the development stage, more batches of reference products may be added at a later stage to have a more reliable estimate of the reference variability. On the other hand, we also need a sufficient number of biosimilar batches in order to have a better understanding of the product. Those challenges lead to a potential sample size imbalance. In this paper, we show that large sample size imbalance may increase the power of the equivalence test in an unfavorable way, giving higher power for less similar products when the sample size of biosimilar is much smaller than that of the reference product. Thus, it is necessary to make some sample size imbalance adjustments to motivate sufficient sample size for biosimilar as well. This paper discusses two adjustment methods for the equivalence test in analytical biosimilarity studies. Please keep in mind that sufficient sample sizes for both biosimilar and reference products (if feasible) are desired during the planning stage.
authors.affiliation: a Global Biostatistical Science , Amgen Inc ., Washington , DC , USA.
authors.forename: Xiaoyu Cassie
authors.initials: XC
authors.lastname: Dong
authors.affiliation: b Office of Biostatistics/Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring , Maryland , USA.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Weng
authors.affiliation: b Office of Biostatistics/Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Silver Spring , Maryland , USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000592:standards*; D003627:Data Interpretation, Statistical; D006801:Humans; D012107:Research Design; D018401:Sample Size
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: Analytical biosimilarity; equivalence test; power; sample sizes imbalance; type I error rate