Sample Size Calculations for the Development of Biosimilar Products

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

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.

Key Words:

• Equivalence trial
• Follow-on biologics
• Margin
• Power
• Sample size formula

FUNDING

This work was supported by the Basic Science Research Fund of the Department of Applied Statistics at Yonsei University.