title: Reporting guidelines for population pharmacokinetic analyses.
abstract: The purpose of this work was to develop a consolidated set of guiding principles for the 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 (in which population PK frequently serves as preparatory analysis for exposure-response modeling) are the main areas of influence for population PK analysis. The proposed guidelines consider 2 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 2 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 6 questions that need to be addressed throughout the report. We recommend 8 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 toward industrialization of the field of pharmacometrics such that a nontechnical audience also understands the role of pharmacometric 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 pharmacokinetics/pharmacodynamics and simulation reports.
authors.affiliation: qPharmetra LLC, Andover, MA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dykstra
authors.affiliation: Division of Pharmacometrics, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mehrotra
authors.affiliation: Clinical Reporting, Novo Nordisk, Copenhagen, Denmark.
authors.forename: Christoffer Wenzel
authors.initials: CW
authors.lastname: Tornøe
authors.affiliation: Pharsight Consulting Services, Certara, St. Louis, MO, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Kastrissios
authors.affiliation: Clinical Pharmacology, Quantitative Sciences, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Bela
authors.initials: B
authors.lastname: Patel
authors.affiliation: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, MA, USA.
authors.forename: Nidal
authors.initials: N
authors.lastname: Al-Huniti
authors.affiliation: Quantitative Pharmacology and Pharmacometrics, Merck and Co., Whitehouse Station, NJ, USA.
authors.forename: Pravin
authors.initials: P
authors.lastname: Jadhav
authors.affiliation: Division of Pharmacometrics, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Global Innovative Pharma Business Clinical Pharmacology, Pfizer Inc., Groton, CT, USA.
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Byon
mesh_terms: D003142:Communication; D017408:Guidelines as Topic; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D011795:Surveys and Questionnaires
keywords: Best practices; PK reporting; Population pharmacokinetics; Regulatory submission