CHAPTER1Introduction1.1AboutThisBookThisbookdescribesstatisticalmethodologyforthegroupsequentialdesignofstudiesinwhichinterimanalyseswillbeperformed.Theprincipalcontextinwhichweillustratethemethodswillbethatofclinicaltrials.However,applicationcanbefoundinalmostanyareawhereanexperimentorsurveycanbecarriedoutinphasesorwhereitsdurationislongenoughtopermitperiodicinterimanalyses.Inthemedicalfieldthisincludesanimalstudiesandalsoepidemiologicalstudies;inindustrialapplications,thereareestablishedsequentialandgroupsequentialdesignsforacceptancesamplinginqualitycontrolandforlifetestinginreliability.Clearly,interimanalysesmaybecalledforinanylong-termfollow-upstudy,beitafieldtestofproductreliability,aparoleerecidivismevaluationofcorrectionalprograms,orasurveillanceprogramformonitoringtheoccurrenceofchronicdiseaseinanoccupationalcohort.TheexamplesdescribedinSection1.4willillustratethebreadthofpossibleapplications.Sincemanyofourexampleswillbestatedintermsofclinicaltrials,weneedtoexplainalittleoftheterminologyforthoseunfamiliarwiththisfield.Anewtherapymaygothroughvariousstagesoftestinginhumansubjectsaftershowingpromiseinlaboratoryandanimalstudiesbeforeitisacceptedbythemedicalcommunity.PhaseItrialsareexploratoryandareconcernedwithaspectsofclinicalpharmacologyandtoxicity.Anobjectiveistofindasuitabledoselevelthatavoidsunacceptableadversesideeffects.Usuallythesampleconsistsofbetween20and80healthyvolunteers,oftenpharmaceuticalcompanyemployeesormedicalstudents.PhaseIIpilotstudiesareofmoderatesize,involving100to300diseasedpatients,andareconcernedwithevaluatingbothefficacyandsafetyaspects.APhaseIIItrialisthedefinitiveevaluationfortheproposednewtherapyinwhicheffectivenessisverifiedandthepresenceofanylong-termadversesideeffectsismonitored.Patientssufferingfromthediseaseinquestionarerandomlyassignedeithertothenewtreatmentortothecurrentstandard,orpossiblyplacebo,treatment.PhaseIIItrialsofteninvolvemorethan1000patientvolunteersandlastthreetofiveyears,ormaybelongerdependingonrecruitmentrate...
