STATISTICSAPPLIEDTOCLINICALTRIALSFOURTHEDITIONStatisticsAppliedtoClinicalTrialsFourtheditionbyTONJ.CLEOPHAS,MD,PhD,ProfessorStatisticalConsultant,Circulation,Boston,USA,Co-ChairModuleStatisticsAppliedtoClinicalTrials,EuropeanInteruniversityCollegeofPharmaceuticalMedicine,Lyon,France,Internist-clinicalpharmacologist,DepartmentMedicine,AlbertSchweitzerHospital,Dordrecht,TheNetherlandsAEILKOH.ZWINDERMAN,MathD,PhD,ProfessorCo-ChairModuleStatisticsAppliedtoClinicalTrials,EuropeanInteruniversityCollegeofPharmaceuticalMedicine,Lyon,France,ProfessorofStatistics,DepartmentBiostatisticsandEpidemiology,AcademicMedicalCenter,Amsterdam,TheNetherlandsTOINEF.CLEOPHAS,BScDepartmentofResearch,DamenShipyards,Gorinchem,TheNetherlandsandEUGENEP.CLEOPHAS,BScTechnicalUniversity,Delft,TheNetherlandsNopartofthisworkmaybereproduced,storedinaretrievalsystem,ortransmittedinanyformorbyanymeans,electronic,mechanical,photocopying,microfilming,recordingorotherwise,withoutwrittenpermissionfromthePublisher,withtheexceptionofanymaterialsuppliedspecificallyforthepurposeofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Printedonacid-freepaper987654321springer.comISBN978-1-4020-9522-1e-ISBN978-1-4020-9523-8Prof.TonJ.CleophasAlbertSchweitzerHospitalProf.AeilkoH.ZwindermanToineF.CleophasDamenShipyardsGorinchemTheNetherlandsTheNetherlandsTheNetherlandsEugeneP.CleophasTechnicalUniversityDelftTheNetherlandsAcademicMedicalCenterAmsterdamDordrechtLibraryofCongressControlNumber:2008939866©SpringerScience+BusinessMediaB.V.2009vPREFACESxviiFOREWORDxxiCHAPTER1/HYPOTHESES,DATA,STRATIFICATION1.Generalconsiderations12.Twomainhypothesesindrugtrials:efficacyandsafety23.Differenttypesofdata:continuousdata34.Differenttypesofdata:proportions,percentagesandcontingencytables85.Differenttypesofdata:correlationcoefficient116.Stratificationissues137.Randomizedversushistoricalcontrols148.Factorialdesigns159.Conclusions10.ReferencesCHAPTER2/THEANALYSISOFEFFICACYDATA1.Overview172.Theprincipleo...
