AAPSAdvancesinthePharmaceuticalSciencesSeriesVolumeI:ClinicalTrialSimulations:ApplicationsandTrendsHollyH.C.KimkoandCarlC.PeckHollyH.C.KimkolCarlC.PeckEditorsClinicalTrialSimulationsApplicationsandTrendsEditorsHollyH.C.KimkoJohnson&JohnsonPharmaceuticalResearch&Development,LLCAdvancedModeling&SimulationRaritan,NJUSAhkimko@its.jnj.comCarlC.PeckCenterforDrugDevelopmentScienceDepartmentofBioengineeringandTherapeuticSciencesSchoolsofPharmacyandMedicineUniversityofCaliforniaSanFrancisco,CAUSAcarl@carlpeck.comISSN22107371eISSN2210738XISBN9781441974143eISBN9781441974150DOI10.1007/9781441974150SpringerNewYorkDordrechtHeidelbergLondon#AmericanAssociationofPharmaceuticalScientists2011Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewrittenpermissionofthepublisher(SpringerScience+BusinessMedia,LLC,233SpringStreet,NewYork,NY10013,USA),exceptforbriefexcerptsinconnectionwithreviewsorscholarlyanalysis.Useinconnectionwithanyformofinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodologynowknownorhereafterdevelopedisforbidden.Theuseinthispublicationoftradenames,trademarks,servicemarks,andsimilarterms,eveniftheyarenotidentifiedassuch,isnottobetakenasanexpressionofopinionastowhetherornottheyaresubjecttoproprietaryrights.PrintedonacidfreepaperSpringerispartofSpringerScienceþBusinessMedia(www.springer.com)PrefaceDuringthesevenyearsfollowingtheinauguralpublicationofSimulationforDesigningClinicalTrials:APharmacokinetic-PharmacodynamicModelingPer-spective,acceptanceandapplicationofclinicaltrialsmodelingandsimulation(M&S)indrugdevelopmentandregulationhavegreatlyexpanded.Biopharmaceu-ticalcompanieshaveemployedM&Sinallphasesofdrugdevelopmenttoachievegreaterefficiencyanddosageoptimization.ThefoodandDrugAdministration’s(FDA)visionary2004CriticalPathInitiativehighlightedclinicaltrialsimulations(CTS)in“modelbaseddrugdevelopment”tofacilitateefficientdevelopment.Inthemeantime,FDAandtheEuropeanMedicinesAgencyhaveencoura...
