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. 2024 Dec 6:18:377-387.
doi: 10.2147/BTT.S470182. eCollection 2024.

Comparison of Innovative and Conventional Methods in Biosimilar Bridging Studies with Multiple References

Annpey Pong  1 , Susan S Chow  2 , Shein-Chung Chow  3
Affiliations

Comparison of Innovative and Conventional Methods in Biosimilar Bridging Studies with Multiple References

Annpey Pong et al. Biologics. .

Abstract

For assessment of biosimilar drug products, if there are multiple-reference products (eg, a US-licensed product and an EU-approved product), a biosimilar bridging study with a 3-way pairwise comparison is often conducted. In our paper, two innovative methods in biosimilar bridging study are compared with the conventional method of pairwise comparisons. For parallel study design, the simultaneous confidence interval (CI) method is compared to the convention method. For crossover study design, the multiplicity-adjusted Schuirmann's two one-sided tests (MATOST) is considered. This paper conclude that the simultaneous CI method achieves the similar statistical power to the conventional approach in biosimilarity assessment. However, the MATOST method using the conservative Holm and Bonferroni approaches is not favorable since it leads to a large sample size although it controls the type I error rate.

Keywords: MATOST; bioequivalence and biosimilarity; multiple references; multiplicity-adjusted two one-sided tests; simultaneous confidence interval approach.

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Conflict of interest statement

Pong A is the employees of Merck & Co., Inc., Rahway, NJ, USA, who own stock in Merck & Co., Inc.. The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Power analysis for comparing simultaneous CI method versus 3-way pairwise comparison in parallel design. Sub-figures (A–D) represent the 4 different assumptions on (μT, μR1, μR2) and (σT, σR1, σR2).
Figure 2
Figure 2
Power analysis for comparing Schuirmann’s TOST method versus 3-way pairwise comparison in crossover design. Sub-figures (A1–A4) represents CV from 0.1 to 0.4 when μT = μR1 = μR2 = 1; (B1–B4) represents CV from 0.1 to 0.4 when μT = μR1 = μR2 = 1.1; (C1–C4) represents CV from 0.1 to 0.4 when μT = μR1 = μR2 = 0.9.
See this image and copyright information in PMC

References

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