Drug development at different stages may require assessment of similarity of pharmacokinetics (PK). The common approach for such assessment when the difference is drug formulation is bioequivalence (BE), which employs a hypothesis test based on the evaluation of a 90% confidence interval for the ratio of average pharmacokinetic (PK) parameters. The role of formulation effect in BE assessment is replaced by subject population in PK similarity assessment. The traditional approach for BE requires that the PK parameters, primarily AUC and Cmax, be obtained from every individual. Unfortunately in many clinical circumstances, some or even all of the individuals may be sparsely sampled, making the individual evaluation difficult. In such cases, using models, particularly population models, becomes appealing. However, conducting an appropriate statistical test based on population modeling in a form consistent, at least in principle, with traditional 90% confidence interval approach is not so straightforward as it may appear. This manuscript proposes one such approach that can be applied to sparse sampling situations. The approach aims to maintain, as much as possible, the appropriateness of the hypothesis test. It is applied to data from clinical studies to address a need in drug development for assessment of PK similarity in different populations.

中文翻译：

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使用稀疏采样的对象评估生物等效性或PK相似性的建模方法中的统计问题。

在不同阶段的药物开发可能需要评估药代动力学（PK）的相似性。当差异是药物配方时，这种评估的常用方法是生物等效性（BE），该方法基于90％置信区间对平均药代动力学（PK）参数比率的评估，采用了假设检验。配方效应在BE评估中的作用已被PK相似性评估中的受试者群体所取代。传统的BE方法要求从每个人获取PK参数，主要是AUC和Cmax。不幸的是，在许多临床情况下，可能会稀疏地采样一些甚至全部个体，从而使个体评估变得困难。在这种情况下，使用模型，尤其是人口模型变得很有吸引力。然而，至少在原则上与传统的90％置信区间方法相一致的形式基于总体模型进行适当的统计检验并不像看起来那样简单。该手稿提出了一种可用于稀疏采样情况的方法。该方法旨在尽可能保持假设检验的适当性。它可用于临床研究的数据，以解决药物开发中评估不同人群PK相似性的需求。假设检验的适当性。它可用于临床研究的数据，以满足药物开发中评估不同人群PK相似性的需求。假设检验的适当性。它可用于临床研究的数据，以满足药物开发中评估不同人群PK相似性的需求。