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1、PAPERSP02@SASAPPLICATIONIN2*2CROSSOVERCLINICALTRIALWuweiWayneFeng,EliLilly&Company,Indianapolis,INDongDing,MedFocusInc.DesPlaines,ILABSTRACTCrossoverclinicaltrialdesignattractsalotofattentionintoday’sdrugdevelopmentenvironmentbecauseofitsuniquecharacteristics.Th
2、ispaperwillstartwithanintroductionofa2*2crossoverclinicaltrialdesign,thenareviewofadvantages@anddisadvantagesofcrossoverstudiescomparedwithparallelstudies.DifferenttypesofSASprocedure,suchasPROCTTEST,PROCGLMandPROCMIXEDwillbeusedasdemonstrationonhowtoanalyzethed
3、ataifresponsevariableiscontinuous.McNemartest,Mainland-Garttest,Prescotttestwillalsobereviewediftheoutcomemeasurementisabinaryvariable.Thepapercloseswithanexampleusingsimulateddata.INTRODUCTIONTOCROSSOVERDESIGNCrossoverstudydesignsareappliedinpharmaceuticalindus
4、tryasanalternativetoparalleldesignsoncertaindiseasetypes.Acrossovertrialisoneinwhichsubjectsaregivensequencesoftreatmentswiththeobjectiveofstudyingdifferencesbetweenindividualtreatments(Senn,2002).Incrossoverdesign,apatientreceivestreatmentssequentially,andhe/sh
5、ecanbeconsideredashis/herowncontrol.Comparedtoparalleldesign,crossoverdesigneliminatesthebetween-patientvariation,henceistheoreticallymorepowerfulthansimilarsizedparallelstudy.Toestimatethetreatmenteffectwithsimilarlevelofprecision,theoreticallycrossoverdesignre
6、quiresareducedsamplesize,henceismorecost-effective.However,crossoverdesignisonlysuitableforchronic,stablediseases,wherethetreatmentisnotbelievedto“correct”thecauseoftheillness,butisconsideredtoalleviatethesymptoms,suchasdiabetes,asthma,hypertension(Wood,etal.,19
7、89).Inappropriateapplicationofcrossoverdesignwillcomplicatethestatisticalanalysisandmaketheinterpretationoftheresultdifficult.Oneofthemajorproblemsincrossoverdesignistheperiodbytreatmentinteraction,thecarry-overeffect.Carry-overisthepersistence(whetherphysically
8、orintermsofeffect)ofatreatmentappliedinoneperiodinasubsequentperiodoftreatment(Senn,2002).Tominimizeanypossiblecarry-overeffect,usuallybetweenthetreatmentstherearewas
