STATISTI(ALASPKTSOFTHEDlSlGNANDANAlYSlSOf(lINI(A1TRIALSSTATISTICALASPECTSOFTHEDESIGNANDANAlYSlSOF(llNKA1TRlAlSIBrian5.EverittAndrewPickleilnrtituteofPiychiatry,LondonUnivetrityofMonchertetImperialCollegePressPublishedbyImperialCollegePress57SheltonStreetCoventGardenLondonWC2H9HEDistributedbyWorldScientificPublishingCo.Re.Ltd.P0Box128,FarrerRoad,Singapore912805USAofice:SuitelB,1060MainStreet,RiverEdge,NJ07661UKofJice:57SheltonStreet,CoventGarden,LondonWC2H9HEBritishLibraryCataloguing-in-PublicationDataAcataloguerecordforthisbookisavailablefromtheBritishLibrary.STATISTICALASPECTSOFTHEDESIGNANDANALYSISOFCLINICALTRIALSCopyright01999byImperialCollegePressAllrightsreserved.Thisbook,orpartsthereof;maynotbereproducedinanyformorbyanymeans,electronicormechanical,includingphotocopying,recordingoranyinformationstorageandretrievalsystemnowknownortobeinvented,withoutwrittenpermissionfromthePublisher.Forphotocopyingofmaterialinthisvolume,pleasepayacopyingfeethroughtheCopyrightClearanceCenter,Inc.,222RosewoodDrive,Danvers,MA01923,USA.Inthiscasepermissiontophotocopyisnotrequiredfromthepublisher.ISBN1-86094-153-2Thisbookisprintedonacid-freepaper.PrintedinSingaporebyRegalPress(S)Re.Ltd.PREFACEAccordingtoSirDavidCox,therandomisedcontrolledclinicaltrialisperhapstheoutstandingcontributionofstatisticsto20thcenturymedicalresearch.Nowadaysabout8000suchtrialsareundertakenannuallyinallareasofmedicinefromthetreatmentofacnetothepreventionofcancer.Althoughthevastmajorityofthesetrialstakeplaceawayfromtheglareofpublicinterest,somedealwithissuesthatarecontroversialenoughtomakeeventhepopularpress;anobviousexampleistheuseofAZTforthetreatmentofAIDS.Therearemanyexcellentbooksavailablewhichgivecomprehen-siveaccountsofhowclinicaltrialsshouldbecarriedoutandorgan-ised.Ouraimissomewhatdifferent;weattempttogiverelativelyconcisedescriptionsofthemorestatisticalaspectsofthedesignandanalysisofclinicaltrials,particularlythosemethodsdevelopedoverthelastdecadeorso.Topicsdiscussedinthistextincluderandomi-sation,i...
