A biosimilar is a biological product that is highly similar to an existing approved reference drug and has no clinically meaningful difference from it. Biosimilars are composed of or derived from living cells or organisms. Therefore, they are often sensitive to slight variations in the manufacturing process. Consequently, in demonstrating biosimilarity, it might be inappropriate to focus solely on the mean difference, or ratio of means, while ignoring the variabilities associated with the test and reference products. It is important to account for the entire population of clinical outcomes. Thus, we propose using the concept of tolerance intervals and related hypothesis testing for assessing biosimilarity. Our approach has the advantage of considering entire populations associated with both groups. A real example is used to illustrate our proposed method, and our approach is more stringent than those that employ confidence intervals. This is specifically the case when the mean difference of two drugs is not sufficiently large, but the biosimilar has a higher variability than that in the reference drug.

中文翻译：

---

使用公差区间评估生物相似性。

生物仿制药是一种与现有批准的参考药物高度相似且与之没有临床意义差异的生物产品。生物仿制药由活细胞或生物组成或衍生自活细胞或生物。因此，它们通常对制造过程中的细微变化敏感。因此，在证明生物相似性时，仅关注均值差或均值比，而忽略与测试和参考产品相关的变异性可能是不合适的。重要的是要考虑整个临床结果。因此，我们建议使用公差区间的概念和相关的假设检验来评估生物相似性。我们的方法的优势在于考虑了与这两个群体相关的全部人口。一个真实的例子用来说明我们提出的方法，并且比采用置信区间的方法更严格。当两种药物的平均差异不够大，但生物仿制药的可变性高于参考药物时，尤其是这种情况。