Dykstra Kevin, Mehrotra Nitin, Tornøe Christoffer Wenzel, Kastrissios Helen, Patel Bela, Al-Huniti Nidal, Jadhav Pravin, Wang Yaning, Byon Wonkyung
qPharmetra LLC, Andover, MA, USA,
J Pharmacokinet Pharmacodyn. 2015 Jun;42(3):301-14. doi: 10.1007/s10928-015-9417-1. Epub 2015 Apr 30.
The purpose of this work was to develop a consolidated set of guiding principles for reporting of population pharmacokinetic (PK) analyses based on input from a survey of practitioners as well as discussions between industry, consulting and regulatory scientists. The survey found that identification of population covariate effects on drug exposure and support for dose selection (where population PK frequently serves as preparatory analysis to exposure-response modeling) are the main areas of influence for population PK analysis. The proposed guidelines consider two main purposes of population PK reports (1) to present key analysis findings and their impact on drug development decisions, and (2) as documentation of the analysis methods for the dual purpose of enabling review of the analysis and facilitating future use of the models. This work also identified two main audiences for the reports: (1) a technically competent group responsible for in-depth review of the data, methodology, and results, and (2) a scientifically literate, but not technically adept group, whose main interest is in the implications of the analysis for the broader drug development program. We recommend a generalized question-based approach with six questions that need to be addressed throughout the report. We recommend eight sections (Synopsis, Introduction, Data, Methods, Results, Discussion, Conclusions, Appendix) with suggestions for the target audience and level of detail for each section. A section providing general expectations regarding population PK reporting from a regulatory perspective is also included. We consider this an important step towards industrialization of the field of pharmacometrics such that non-technical audience also understands the role of pharmacometrics analyses in decision making. Population PK reports were chosen as representative reports to derive these recommendations; however, the guiding principles presented here are applicable for all pharmacometric reports including PKPD and simulation reports.
这项工作的目的是根据从业者调查的反馈以及行业、咨询和监管科学家之间的讨论，制定一套综合的群体药代动力学（PK）分析报告指导原则。调查发现，确定群体协变量对药物暴露的影响以及支持剂量选择（群体PK常作为暴露-反应建模的前期分析）是群体PK分析的主要影响领域。拟议的指导原则考虑了群体PK报告的两个主要目的：（1）呈现关键分析结果及其对药物研发决策的影响；（2）作为分析方法的文档，用于双重目的，即便于对分析进行审查并促进模型的未来使用。这项工作还确定了报告的两个主要受众：（1）负责深入审查数据、方法和结果的技术能力较强的群体；（2）具有一定科学素养但技术不太熟练的群体，他们主要关注分析对更广泛药物研发计划的影响。我们建议采用一种基于问题的通用方法，提出六个贯穿报告需要解决的问题。我们建议报告分为八个部分（概述、引言、数据、方法、结果、讨论、结论、附录），并针对每个部分的目标受众和详细程度提出建议。还包括一个从监管角度提供关于群体PK报告一般期望的部分。我们认为这是迈向药物计量学领域工业化的重要一步，以便非技术受众也能理解药物计量学分析在决策中的作用。选择群体PK报告作为具有代表性的报告来得出这些建议；然而，这里提出的指导原则适用于所有药物计量学报告，包括PKPD和模拟报告。
