### Abstract

The most widely used design for a Phase III comparative study for demonstrating the biosimilarity between a biosimilar product and a renovator biological product is the equivalence trial, whose aim is to show that the difference between two population means of a primary endpoint is less than a prespecified equivalence margin. A well-known sample size formula for the equivalence trial is given by n_{1} = kn_{2} n_{2} = (zα + zβ/2)^{2} ω^{2} (δ |μT - μR|)^{2} (1 + 1k). Since this formula is obtained based on the approximate power rather than the exact power, we investigate in this article the accuracy of the sample size formula. We conclude that the sample size formula is very conservative. Specifically, we show that the exact power based on the sample size calculated from the formula to have power is actually under some conditions. Therefore, the use of the sample size formula may cause a huge extra cost to biotechnology companies. We propose that the sample size should be calculated based on the exact power precisely and numerically. The R code to calculate the sample size numerically is provided in this article.

Original language | English |
---|---|

Pages (from-to) | 1215-1224 |

Number of pages | 10 |

Journal | Journal of Biopharmaceutical Statistics |

Volume | 24 |

Issue number | 6 |

DOIs | |

Publication status | Published - 2014 Nov 2 |

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### All Science Journal Classification (ASJC) codes

- Statistics and Probability
- Pharmacology
- Pharmacology (medical)

### Cite this

*Journal of Biopharmaceutical Statistics*,

*24*(6), 1215-1224. https://doi.org/10.1080/10543406.2014.941984

}

*Journal of Biopharmaceutical Statistics*, vol. 24, no. 6, pp. 1215-1224. https://doi.org/10.1080/10543406.2014.941984

**Sample size calculations for the development of biosimilar products.** / Kang, Seung Ho; Kim, Yongjo.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Sample size calculations for the development of biosimilar products

AU - Kang, Seung Ho

AU - Kim, Yongjo

PY - 2014/11/2

Y1 - 2014/11/2

N2 - The most widely used design for a Phase III comparative study for demonstrating the biosimilarity between a biosimilar product and a renovator biological product is the equivalence trial, whose aim is to show that the difference between two population means of a primary endpoint is less than a prespecified equivalence margin. A well-known sample size formula for the equivalence trial is given by n1 = kn2 n2 = (zα + zβ/2)2 ω2 (δ |μT - μR|)2 (1 + 1k). Since this formula is obtained based on the approximate power rather than the exact power, we investigate in this article the accuracy of the sample size formula. We conclude that the sample size formula is very conservative. Specifically, we show that the exact power based on the sample size calculated from the formula to have power is actually under some conditions. Therefore, the use of the sample size formula may cause a huge extra cost to biotechnology companies. We propose that the sample size should be calculated based on the exact power precisely and numerically. The R code to calculate the sample size numerically is provided in this article.

AB - The most widely used design for a Phase III comparative study for demonstrating the biosimilarity between a biosimilar product and a renovator biological product is the equivalence trial, whose aim is to show that the difference between two population means of a primary endpoint is less than a prespecified equivalence margin. A well-known sample size formula for the equivalence trial is given by n1 = kn2 n2 = (zα + zβ/2)2 ω2 (δ |μT - μR|)2 (1 + 1k). Since this formula is obtained based on the approximate power rather than the exact power, we investigate in this article the accuracy of the sample size formula. We conclude that the sample size formula is very conservative. Specifically, we show that the exact power based on the sample size calculated from the formula to have power is actually under some conditions. Therefore, the use of the sample size formula may cause a huge extra cost to biotechnology companies. We propose that the sample size should be calculated based on the exact power precisely and numerically. The R code to calculate the sample size numerically is provided in this article.

UR - http://www.scopus.com/inward/record.url?scp=84910025405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84910025405&partnerID=8YFLogxK

U2 - 10.1080/10543406.2014.941984

DO - 10.1080/10543406.2014.941984

M3 - Article

C2 - 25032735

AN - SCOPUS:84910025405

VL - 24

SP - 1215

EP - 1224

JO - Journal of Biopharmaceutical Statistics

JF - Journal of Biopharmaceutical Statistics

SN - 1054-3406

IS - 6

ER -