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基本説明
Establishes techniques used in the assessment of bioequivalence and describes the use of statistics in clinical pharmacology studies of safety, ECG monitoring, efficacy, and population pharmacokinetics.
Full Description
Maintaining a practical perspective, Bioequivalence and Statistics in Clinical Pharmacology explores statistics used in day-to-day clinical pharmacology work. The book covers the methods needed to design, analyze, and interpret bioequivalence trials; explores when, how, and why these studies are performed as part of drug development; and demonstrates the proposed methods using real world examples. Drawing on knowledge gained directly from working in the pharmaceutical industry, the authors set the stage by describing the general role of statistics. Once the foundation of clinical pharmacology drug development, regulatory applications, and the design and analysis of bioequivalence trials are established, they move on to related topics in clinical pharmacology involving the use of cross-over designs. These include, but are not limited to, safety studies in Phase I, dose-response trials, drug interaction trials, food-effect and combination trials, QTc and other pharmacodynamic equivalence trials, and dose-proportionality trials. Purposefully designed to be instantly applicable, the book provides examples of SAS code so that the analysis described can be immediately implemented. The authors have made extensive use of the proc mixed procedures available in SAS.Each chapter includes a vignette based on co-author Scott Patterson's experience in the clinical pharmacology work place and all the data sets are taken from real trials. The authors delineate practical utility and objectives, provide real-world examples of the topic under discussion, and include statistical theory and applications. Technical theory, where extensive, is included in technical appendices at the end of the chapter. Each topic contains worked examples that illustrate the applications of the statistical techniques and their interpretation. The authors also develop statistical tools useful for other topics of clinical pharmacology - namely general safety testing, testing for proarrythmic potential, population pharmacokinetics, and dose-selection.
Contents
DRUG DEVELOPMENT AND CLINICAL PHARMACOLOGYAims of This BookDrug DevelopmentClinical PharmacologyStatistics in Clinical PharmacologyStructure of the BookWhen and How BE Studies Are PerformedWhy Are BE Studies Performed?Deciding When Formulations Are BioequivalentPotential Issues with TOST BioequivalenceCurrent International RegulationTESTING FOR AVERAGE BIOEQUIVALENCEBackgroundLinear Model for 2 x 2 DataApplying the TOST ProcedureCarry-over, Sequence, and Interaction EffectsChecking Assumptions Made about the Linear ModelPower and Sample Size for ABE in the 2 x 2 DesignExample Where Test and Reference Are Not ABENonparametric AnalysisSome Practical IssuesBE STUDIES WITH MORE THAN TWO PERIODSBackgroundThree-period DesignsWithin-subject VariabilityRobust Analyses for Three Period DesignsFour-Period DesignsDesigns with More than Two TreatmentsNonparametric Analyses of TmaxTechnical Appendix: EfficiencyTables of DataRestricted Maximum Likelihood ModellingFailing BE and the DER AssessmentSimulation Data-Based Simulation Carry-OverOptional DesignsDetermining Trial SizeWhat Outliers are and How to Handle Their DataBayesian BE AssessmentTechnical AppendixBrief History Individual and Population BE Scaled Average BE CLINICAL PHARMACOLOGY SAFETY STUDIESBackgroundFirst-time-in-humansSub-chronic Dosing StudiesFood-Effect Assessment and DDIsDose-ProportionalityTechnical AppendixQTC BackgroundModelling of QTc DataInterpreting the QTc Modelling FindingsDesign of a Thorough QTc Study in the FutureTechnical AppendixCLINICAL PHARMACOLOGY EFFICACY STUDIESBackgroundSub-chronic DosingPhase IIa and the Proof of Concept Methodology Studies POPULATION PHARMACOKINETICSPopulation and PharmacokineticsAbsolute and Relative BioavailabilityAge and Gender Pharmacokinetic StudiesEthnicity Liver Disease Kidney Disease Technical Appendix Epilogue Bibliography Index
