Identifiability is an important component of pharmacokinetic-pharmacodynamic (PKPD) model development. Structural identifiability is concerned with the uniqueness of the model parameters for a set of perfect input-output data and deterministic identifiability with the precision of parameter estimation given imperfect input-output data. We introduce two subcategories of deterministic identifiability, external and internal, and consider factors that distinguish between these forms. We define external deterministic identifiability as a function of externally controllable variables, i.e., the design, and internal deterministic identifiability as a function of the model and its parameter values. The concepts are explored using three common PK and PKPD models, and verified for their precision for the selected set of parameter values under optimal design.

译文

:可识别性是药代动力学-药效学(PKPD)模型开发的重要组成部分。结构可识别性涉及一组完美输入输出数据的模型参数的唯一性,以及在给定不完整输入输出数据的情况下参数估计精度的确定性可识别性。我们介绍了确定性可识别性的两个子类别,即外部和内部,并考虑了区分这些形式的因素。我们将外部确定性可识别性定义为外部可控制变量(即设计)的函数,并将内部确定性可识别性定义为模型及其参数值的函数。使用三种常见的PK和PKPD模型探索了这些概念,并在优化设计下针对选定的一组参数值验证了它们的精度。

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