Experimental design for mixed models with application to population pharmacokinetic studies [Elektronische Ressource] / von Thomas Schmelter

ExperimentalDesignforMixedModelswithApplicationtoPopulationPharmacokineticStudiesDissertationzurErlangungdesakademischenGradesdoctorrerumnaturalium(Dr.rer.nat.)von omasSchmeltergeb.am26.03.1977inMainzgenehmigtdurchdieFakultat¨ fur¨ MathematikderOtto-von-Guericke-Universitat¨ MagdeburgGutachter: Prof.Dr.RainerSchwabeDr.BarbaraBogackaeingereichtam: 22.12.2006Verteidigungam: 25.05.20072Acknowledgment isPhDthesiswouldnothavebeenpossiblewithoutthehelpofmanypeople,whomIwouldliketothank.IwouldliketoexpressmydeepgratitudetomyadvisorProf.Dr.RainerSchwabeforallhissupportthroughoutmyPhDproject. Iamverygratefulforhisencouragement,hishelpfulsuggestions,andthefruitfuldiscussionswehad.Iwouldliketothankthewhole“Institutfur¨ MathematischeStochastik”fortheniceatmosphereandforthecross-wordpuzzlesduringthecoeebreaks.SincethisPhDthesiswasajointprojecttogetherwithScheringAG,IhadthelucktohaveDr.NorbertBenda(nowworkingatNovartis)asanadditionaladvisor,whomIwouldreallyliketothankforhismotivation,enthusiam,andhelpfuldiscussions.SpecialthanksalsogotoMarcVandemeulebroecke.Icouldreallybene tfromtheexperienceshehadgatheredwithinhisown“project”.Wehadmanyenlighteningdiscussions.Furthermore,IwouldliketothankthewholeClinicalStatisticsEuropedepartmentatSchering¨AG,whereIwasimmediatelywarmlywelcomed.EspeciallyIwouldliketothankDr.JurgenDinger,Dr.HermannKulmann,andDr.ChristophGerlingerforgivingmeanysupportIneeded.