Statistics - Discovery/Development, Eli Lilly and Company , Indianapolis, Indiana, USA.
Bioproduct R&D - Bioassay, Eli Lilly and Company.
J Biopharm Stat. 2020 Jul 3;30(4):721-733. doi: 10.1080/10543406.2020.1730875. Epub 2020 Mar 12.
Potency determination via bioassay is a relative measure that requires an evaluation of parallelism between the dose-response relationships of a reference standard and a sample material. Typical approaches for assessing parallelism include difference ([Formula: see text]-value) and equivalence tests. These traditional methods rely on a statistical assessment of model parameters as opposed to direct evaluation of the similarity of the dose-response curves. We propose a simple curve similarity approach that tests the hypothesis that the sample material is a dilution or concentration of the reference standard. The test is achieved by quantifying and normalizing the total area between the two curves and provides a single composite measure of parallelism. Both a frequentist and a Bayesian approach to the test are provided. We show through a simulation study that the curve similarity approach overcomes the drawbacks of the traditional methods and is effective at detecting parallelism and non-parallelism for bioassays.
通过生物测定法进行效价测定是一种相对的测量方法，需要评估参考标准和样品材料的剂量-反应关系之间的平行性。评估平行性的典型方法包括差异 ([Formula: see text]-值）和等效性检验。这些传统方法依赖于对模型参数的统计评估，而不是直接评估剂量-反应曲线的相似性。我们提出了一种简单的曲线相似性方法，检验样本材料是参考标准的稀释或浓缩的假设。该测试通过量化和归一化两条曲线之间的总区域来实现，并提供了平行性的单一综合度量。该测试提供了一种频率主义和贝叶斯方法。我们通过模拟研究表明，曲线相似性方法克服了传统方法的缺点，对于生物测定法，它能够有效地检测平行性和非平行性。
