ICH临床试验统计原则(E9中文版)

2281999;15(3):228235ChinJClinPharmacol1999;15(3):228235:,,?ICU,,:ICUHarmonisedTripartiteGuidelines:E9StatisticalPrinciplesforClinicalTrials(Havingreachedstep4oftheICHProcessattheICHCommitteemeetingon5February1998,thisguidelineisrecommendedforadoptiontothethreeregulatorypartiestoICH.)()112341(,,100034)2(,)3(,,200032)4(,,200025)1.1.1ICH199651(GoodClinicalPractice,GCP):ICH(E6)ICH,,,CPMP(CommitteeforPropri2etaryMedicalProducts)(Biostatisticalmethodologyinclinicaltrailsinapplicationsformarketingauthorizationsformedicinalproducts,199412),(19923),(FoodandDrugAdministration,FDA)(19887)ICH,E1:E2A::E2B::E2C::E3:E4:E5:E6::E7::E8:E10:M1:M3:1.2,,ICH,,ICHE6,(),,,229,,,,(),(),,,,,(bias)(precision),,,,,,,,(robustness)P(Frequentist),/,,,,Bayes2.2.12.1.1,(ICHE8),,,,(7.2),,,,,(metaanalysis,),,,()2.1.2(confirmatorytrial),,,,,,,,,;,,,,,,,,,/(,),2.1.3,,,,,,,,,,,2.22.2.1,,,,230,,,,,,,,2.2.2((targetvariable),(primaryendpoint)),,,(3.5),,,;,,(),,(),,,,,,,,,,,/,,2.2.3,,(),,,,,,,(),()2.2.4,()/,,,:;;,;,,,,,,,,,2.2.5,,(),,,,(),,I231(5.6),II,,I,,II2.2.6,(),,,,,,,,,,;,,,,,,,,(i),(ii),(iii),2.2.7,,,()()90mmHg,,,,2.3,,,,,,,2.3.12.3.2,,,2.3.1(blinding)(bias),,,,(endpoint),,(doubleblindtrial),,,,,(treatmentcode)(,),,,/,,(openlable),,,:,,;,,,,;,,(),,,,,(),,,(),,,,,,;,,,,,,,,,,232,,,()()2.3.2(randomization),,,,,,(),,,(),,,,,,,,,,;,,(,,,)(),,,,,(,,),,,()(,),(),,,,,,,,,,,,,,,,3.3.13.1.1(parallelgroupdesign),,,,/,,,,,,,,,()3.1.2(cross-overdesigns),,,,22,,(washoutperiod)n(2)n,n(2),,n(n2)(carryover),,22,,,,,,,,,,,,,,,,233ICHE422,,,,,3.1.3(factorialdesigns),22,,AB,A,B,AB,AB,AB,AB,,,CD,Cm(0,),Dnnm,CDCD(ICHE4),22,,AB,,AB,B,A,3.2(multicentertrial),;,,,;,,,(),,,,,,,,(),,,,,,,,,,,(,),,,,,,,,;(),,(5.1)(,),,ICHE6,,,,,,,,,,,,,,,,,,,,,,,,,,,,,()234,,,(),,,,,3.33.3.1,-,(activecontrol),-(superiority)(),,,,,,,3.3.2,,(),(),,,,,,,,,,,,;(),,(),(),,,,,,,,,(,,),,,,,,,,;(5.5),,,(),,,I(typeIerror)(),I(3.5),,(5.2.3)3.3.3--(ICHE4),:;;;;,,,,(),,,,()3.4(4.5),,,,(,4.5)()(4.6),,,,235,3.5,,,,(ICH-E1a),:()(I)(II),,,,(),,(sensitivity),,5%,;10%20%;,,,()(3.3.2),0,0,;0,,,,,,,,,3.6,,,,,,()(missingvalue)0GCP(ICH-E6,5),,,,4.4.1,(ICH-E6),,,(),,,,,,,(4.24.4),,,I(ICH-E6),,()()(),()4.54.64.2,,,,,,,,(19994)311199934.3,,,,,,4.4,,,,,,,,,I,,(3.5)4.5,,,(3.4),,,,(,),,,,(alphaspending),,(4.6),,I,,,,,,,,,;,,,,,,,,,(Independentdatamonitoringcommittee,IDMC),(Dataandsafetymonitor2ingboard),(Datamonitoringcommit2tee),,,1999;15(4):311317ChinJClinPharmacol1999;15(4):311317ICH()112341(,,100034)2()3(,,200032)4(,,200025)312(),,,,,,4.6(IDMC)(1.25ICHE65.52),,,,IDMC,,,IDMC,IDMC(Institutionalreviewboard-IRB)(Independentethicscommittee-IEC),,(),5.5.1,,,,(),(7.1)(7.1),,,,,(),,(ICH-E3)5.2(Analysissets),(,),,,,,,,,,,,,,,,,,(ICHE3),:1),2)I5.2.1(intention-to-treat,):,,,,,,,(),:)))()),,,,,,,,,313,,,;,(carryingforward)(,/),,,,5.2.2,,:))),,,;,,,,,,,5.2.3,,,,,,,()(,3.3.2)(),,,,5.3,,,,,,,,,,,,,,,,,5.4,,(,),,,,,,,,,2.2.25.5/(),;,,,,,,,314,,,(),,(5.7)()(),,,,5.6(multiplicity),I,(2.2.2),,/(4.6),,(),(),(),,,;,,5.7,,,,,,,,,,,,,,,,,(),,,,,,,;,,,,,,(),,5.8,(),,6.6.1,(),,,,,,,,,6.2,,,,(pharmacodynamic/pharmacokinetic),,,(vitalsigns)(,),,(ICHE2AICHE3),,,,,()),6.3315,,,,(ICHE2B),,,(ICHE7),,(ICHE3),,,,,(),,,,,,(),,,,,,,(,),(),,,6.4,,,,,,,,,,,,P,,,,,,,,,I,II,,,,,,,6.5,,,(7.2.2),,ICHE3127.7.1,ICHE3ICH,5,,,,,5,,;,;;,,,,,,,,,,,,,,,,,,,316,,,,P(P=0.034),,,,,,,,(5.7),,,,,,7.2,(EU,),:;(),;,,,,,/,,,,7.2.1,,,,,,,,,7.2.2,,,,,,,(),,/,1.(BayesianApproaches),()2.()(BiasStatistical&Opera2tional)3.(BlindReview)(),4.(ContentValidity)()5.(Double-Dummy),317A()B();A()B(),A()B()6.(Dropout)/7.(EquivalanceTrial)8.(FrequentistMethods),,9.(FullAnalysisSet)10.(Generalisability,Generalisation)11.(GlobalAssessmentVariable),12.(,,)(IndependentDataMonitoringCommit2tee-IDMC(DataandSaftyMonitoringBoard,MonitoringCommittee,DataMonitoringCommittee),13.(IntentionToTreatPrinciple)(),,,14.()(Interaction(Qualitative&Quantitative))()(),15.(Inter-RaterReliability)16.(Intra-RaterReliability)17.(InterimAnalysis)18.(MetaAnalysis),19.(MulticentreTrial),20.(Non-InferiorityTrial)()21.(PreferredandIncludedTermes),MedDRA,,,,,:,(Arthralgia)22.(,,)(PerProtocolSet(ValidCases,EfficacySample,EvaluableSub2jectsSample)),,23.(SafetyandTolerability),(),,(),(,)24.(StatisticalAnalysisPlan),25.(SuperiorityTrial)()26.(SurrogateVariable)27.(TreatmentEffect)()28.(TreatmentEmergent),29.(TrialStatistician)/,