實用文檔ICH三方協調指導原則E6ICHGCP指導原則INTRODUCTION前言GoodClinicalPractice(GCP)isaninternationalethicalandscientificqualitystandardfordesigning,conducting,recordingandreportingtrialsthatinvolvetheparticipationofhumansubjects.Compliancewiththisstandardprovidespublicassurancethattherights,safetyandwell-beingoftrialsubjectsareprotected,consistentwiththeprinciplesthathavetheiroriginintheDeclarationofHelsinki,andthattheclinicaltrialdataarecredible.臨床試驗管理規范(GCP)是設計、實施、記錄和報告設計人類對象參加的試驗國際性倫理和科學質量標準。遵循這一標準為保護對象的權利、安全性和健康,為與源于赫爾辛基宣言的原則保持一致以及臨床試驗數據的可信性提供了公眾保證。TheobjectiveofthisICHGCPGuidelineistoprovideaunifiedstandardfortheEuropeanUnion(EU),JapanandtheUnitedStatestofacilitatethemutualacceptanceofclinicaldatabytheregulatoryauthoritiesinthesejurisdictions.ICH-GCP指導原則的目的是為歐盟、日本和美國提供統一的標準,以促進這些管理當局在其權限內相互接受臨床數據。TheguidelinewasdevelopedwithconsiderationofthecurrentgoodclinicalpracticesoftheEuropeanUnion,Japan,andtheUnitedStates,aswellasthoseofAustralia,Canada,theNordiccountriesandtheWorldHealthOrganization(WHO).本指導原則的發展考慮了歐盟、日本、美國,以及澳大利亞、加拿大、北歐國家和世界衛生組織(WHO)的現行GCP。Thisguidelineshouldbefollowedwhengeneratingclinicaltrialdatathatareintendedtobesubmittedtoregulatoryauthorities.在產生打算提交給管理當局的臨床數據時應當遵循本指導原則。Theprinciplesestablishedinthisguidelinemayalsobeappliedtootherclinicalinvestigationsthatmayhaveanimpactonthesafetyandwell-beingofhumansubjects.本指導原則中確立的原則也可應用于可能影響人類對象安全和健康的其他臨床研究。1.GLOSSARY1.術語1.1AdverseDrugReaction(ADR)藥品不良反應(ADR)Inthepre-approvalclinicalexperiencewithanewmedicinalproductoritsnewusages,particularlyasthetherapeuticdose(s)maynotbeestablished:allnoxiousandunintendedresponsestoamedicinalproductrelatedtoanydoseshouldbeconsideredadversedrugreactions.Thephraseresponsestoamedicinalproductmeansthatacausalrelationshipbetweenamedicinalproductandanadverseeventisatleastareasonablepossibility,i.e.therelationshipcannotberuledout.在一個新的藥品或藥品的新用途在批準之前的臨床實踐,尤其是治療劑量尚未確定前,ADR是指與藥物任何劑量有關的所有有害的和非意求的反應都應被考慮為藥物不良反應。該術語用于藥品是指在藥品與不良反應之間的因果關系至少有一個合理的可能性,即不能排除這種關系。Regardingmarketedmedicinalproducts:aresponsetoadrugwhichisnoxiousandunintendedandwhichoccursatdosesnormallyusedinmanforprophylaxis,diagnosis,ortherapyofdiseasesorformodificationofphysiologicalfunction(seetheICHGuidelineforClinicalSafetyDataManagement:DefinitionsandStandardsforExpeditedReporting).對已上市藥品,ADR指人對用于預防、診斷或治療疾病或改善生理功能的藥物在常用劑量出現的有害和非意求反應(參見ICH臨床安全性數據管理指導原則:快速報告的定義和標準)。1.2AdverseEvent(AE)不良事件(AE)Anyuntowardmedicaloccurrenceinapatientorclinicalinvestigationsubjectadministeredapharmaceuticalproductandwhichdoesnotnecessarilyhaveacausalrelationshipwiththistreatment.Anadverseevent(AE)canthereforebeanyunfavourableandunintendedsign(includinganabnormallaboratoryfinding),symptom,ordiseasetemporallyassociatedwiththeuseofamedicinal(investigational)product,whetherornotrelatedtothemedicinal(investigational)product(seetheICHGuidelineforClinicalSafetyDataManagement:DefinitionsandStandardsforExpeditedReporting).在用藥病人或臨床研究對象中發生的任何不幸醫療事件,他不一定要與治療有因果關系。因此,一個不良事件(AE)可以是與使用(研究)藥物在時間上相關的任何不利的和非意求的征兆(包括異常的實驗室發現)、癥狀或疾病,而不管其是否與藥物有關(參見ICH臨床安全性數據管理指導原則:快速報告的定義和標準)。1.3Amendment(totheprotocol)修改(試驗方案)SeeProtocolAmendment.見試驗方案修改1.4ApplicableRegulatoryRequirement(s)適用的管理要求Anylaw(s)andregulation(s)addressingtheconductofclinicaltrialsofinvestigationalproducts.有關實施試驗用藥品臨床試驗的任何法律和法規。1.5Approval(inrelationtoInstitutionalReviewBoards)批準(機構審評委員會)TheaffirmativedecisionoftheIRBthattheclinicaltrialhasbeenreviewedandmaybeconductedattheinstitutionsitewithintheconstraintssetforthbytheIRB,theinstitution,GoodClinicalPractice(GCP),andtheapplicableregulatoryrequirements.IRB表示贊成的決定:指對一項臨床試驗已經進行審評,并可在IRB、研究機構、GCP和適用管理要求的約束下由研究機構方實施。1.6Audit稽查Asystematicandindependentexaminationoftrialrelatedactivitiesanddocumentstodeterminewhethertheevaluatedtrialrelatedactivitieswereconducted,andthedatawererecorded,analyzedandaccuratelyreportedaccordingtotheprotocol,sponsor'sstandardoperatingprocedures(SOPs),GoodClinicalPractice(GCP),andtheapplicableregulatoryrequirement(s).對試驗相關活動和文件進行系統和獨立的監察,以判定試驗的實施和數據的記錄、分析與報告是否符合試驗方案、申辦者的標準操作程序(SOP)、臨床試驗管理規范(GCP)以及適用的管理要求。1.7AuditCertificate稽查證書Adeclarationofconfirmationbytheauditorthatanaudithastakenplace.稽查員確認已進行稽查的聲明。1.8AuditReport稽查報告Awrittenevaluationbythesponsor'sauditoroftheresultsoftheaudit.申辦者方稽查關于稽查結果的書面評價1.9AuditTrail稽查軌跡Documentationthatallowsreconstructionofthecourseofevents.允許重復出現事件過程的文件。1.10Blinding/Masking設盲Aprocedureinwhichoneormorepartiestothetrialarekeptunawareofthetreatmentassignment(s).Single-blindingusuallyreferstothesubject(s)beingunaware,anddouble-blindingusuallyreferstothesubject(s),investigator(s),monitor,and,insomecases,dataanalyst(s)beingunawareofthetreatmentassignment(s).一種使試驗的一個或幾個部分的人員不知道治療分配的程序。單盲通常指對象不知道;雙盲通常指對象、研究人員、監察員以及在某些情況下數據分析人員也不知道治療分配。1.11CaseReportForm(CRF)病例報告表(CRF)Aprinted,optical,orelectronicdocumentdesignedtorecordalloftheprotocolrequiredinformationtobereportedtothesponsoroneachtrialsubject.設計用來記錄試驗方案要求向申辦者報告的有關每一例對象的全部信息的印刷的、光學的或電子的文件。1.12ClinicalTrial/Study臨床試驗/研究Anyinvestigationinhumansubjectsintendedtodiscoverorverifytheclinical,pharmacologicaland/orotherpharmacodynamiceffectsofaninvestigationalproduct(s),and/ortoidentifyanyadversereactionstoaninvestigationalproduct(s),and/ortostudyabsorption,distribution,metabolism,andexcretionofaninvestigationalproduct(s)withtheobjectofascertainingitssafetyand/orefficacy.Thetermsclinicaltrialandclinicalstudyaresynonymous.在人類對象進行的任何意在發現或證實一種試驗用藥品的臨床、藥理學和/或其他藥效學作用;和/或確定一種試驗用藥品的任何不良反應;和/或研究一種試驗用藥品的吸收、分布、代謝和排泄,以確定藥物的安全性和/或有效性的研究。術語臨床試驗和臨床研究同義。1.13ClinicalTrial/StudyReport臨床試驗/研究報告Awrittendescriptionofatrial/studyofanytherapeutic,prophylactic,ordiagnosticagentconductedinhumansubjects,inwhichtheclinicalandstatisticaldescription,presentations,andanalysesarefullyintegratedintoasinglereport(seetheICHGuidelineforStructureandContentofClinicalStudyReports).在人類對象進行的任何治療、預防或診斷劑的試驗/研究的書面描述。臨床和統計描述、陳述和分析全部列入該單份報告(見ICH臨床研究報告的結構和內容指導原則)。1.14Comparator(Product)對照(藥物)Aninvestigationalormarketedproduct(i.e.,activecontrol),orplacebo,usedasareferenceinaclinicaltrial.臨床試驗中用做對照的試驗用藥品或市售藥物(即陽性對照)或安慰劑。1.15Compliance(inrelationtotrials)依從性(關于試驗的)Adherencetoallthetrial-relatedrequirements,GoodClinicalPractice(GCP)requirements,andtheapplicableregulatoryrequirements.遵循與試驗有關的所有要求、臨床試驗管理規范(GCP)要求和適用的管理要求。1.16Confidentiality保密性Preventionofdisclosure,tootherthanauthorizedindividuals,ofasponsor'sproprietaryinformationorofasubject'sidentity.不得向未經授權的個人泄漏申辦者所有的資料或對象的身份。1.17Contract合同Awritten,dated,andsignedagreementbetweentwoormoreinvolvedpartiesthatsetsoutanyarrangementsondelegationanddistributionoftasksandobligationsand,ifappropriate,onfinancialmatters.Theprotocolmayserveasthebasisofacontract.在兩個或幾個有關方之間的一份書面的、有日期和簽字的協議,其中陳述了關于工作和責任和分派的安排,以及關于財務問題的安排。試驗方案可以作為合同的基礎。1.18CoordinatingCommittee協調委員會Acommitteethatasponsormayorganizetocoordinatetheconductofamulticentretrial.申辦者組織的協調實施多中心試驗的委員會。1.19CoordinatingInvestigator協調研究者Aninvestigatorassignedtheresponsibilityforthecoordinationofinvestigatorsatdifferentcentresparticipatinginamulticentretrial.被指定負責協調參加一項多中心試驗的各中心研究者工作的一名研究者。1.20ContractResearchOrganization(CRO)合同研究組織Apersonoranorganization(commercial,academic,orother)contractedbythesponsortoperformoneormoreofasponsor'strial-relateddutiesandfunctions.與申辦者訂立契約完成一個或多個有關申辦者方的試驗任務和功能的個人或組織(商業性的,學術的或其他)。1.21DirectAccess直接訪問Permissiontoexamine,analyze,verify,andreproduceanyrecordsandreportsthatareimportanttoevaluationofaclinicaltrial.Anyparty(e.g.,domesticandforeignregulatoryauthorities,sponsor'smonitorsandauditors)withdirectaccessshouldtakeallreasonableprecautionswithintheconstraintsoftheapplicableregulatoryrequirement(s)tomaintaintheconfidentialityofsubjects'identitiesandsponsor’sproprietaryinformation.允許監察、分析、核對和復制任何對于評價臨床試驗有重要意義的記錄和報告。直接訪問的任何一方(如國內和國外的管理當局,申辦者方的監察員和稽查員)應當受適用管理要求的缺書,采取一切合理的預防措施維護對象身份和申辦者資料的保密性。1.22Documentation文件Allrecords,inanyform(including,butnotlimitedto,written,electronic,magnetic,andopticalrecords,andscans,x-rays,andelectrocardiograms)thatdescribeorrecordthemethods,conduct,and/orresultsofatrial,thefactorsaffectingatrial,andtheactionstaken.描述或記錄試驗的方法、實施和/或結果,影響試驗的因素,以及采取的措施等的任何形式的記錄(包括但不限于書面、電子、磁性和光學的記錄,以及掃描、X射線和心電圖)。1.23EssentialDocuments必需文件Documentswhichindividuallyandcollectivelypermitevaluationoftheconductofastudyandthequalityofthedataproduced(see8.EssentialDocumentsfortheConductofaClinicalTrial).指各自和合在一起允許評價一個研究的執行情況和所得數據的質量文件(見8.實施臨床試驗的必需文件)。1.24GoodClinicalPractice(GCP)臨床試驗管理規范(GCP)Astandardforthedesign,conduct,performance,monitoring,auditing,recording,analyses,andreportingofclinicaltrialsthatprovidesassurancethatthedataandreportedresultsarecredibleandaccurate,andthattherights,integrity,andconfidentialityoftrialsubjectsareprotected.是臨床試驗設計、實施、執行、監察、稽查、記錄、分析和報告的標準,它為數據和所報告結果的可信性和準確性提供了保證,并保護試驗對象的權利、完整性和機密性。1.25IndependentData-MonitoringCommittee(IDMC)(DataandSafetyMonitoringBoard,MonitoringCommittee,DataMonitoringCommittee)獨立的數據監察委員會(IDMC)(數據和安全監察委員會,監察委員會,數據監察委員會)Anindependentdata-monitoringcommitteethatmaybeestablishedbythesponsortoassessatintervalstheprogressofaclinicaltrial,thesafetydata,andthecriticalefficacyendpoints,andtorecommendtothesponsorwhethertocontinue,modify,orstopatrial.由申辦者設立一個獨立的數據監察委員會,它定期對研究進展、安全性數據和有效性終點進行評估,向申辦者建議是否繼續、調整或停止試驗。1.26ImpartialWitness公平的見證人Aperson,whoisindependentofthetrial,whocannotbeunfairlyinfluencedbypeopleinvolvedwiththetrial,whoattendstheinformedconsentprocessifthesubjectorthesubject’slegallyacceptablerepresentativecannotread,andwhoreadstheinformedconsentformandanyotherwritteninformationsuppliedtothesubject.獨立與臨床試驗、不受與試驗有關人員的不公正影響的個人。如果對象或對象的合法接受代表人不能閱讀,他/她將參與知情同意過程,并向對象閱讀提供給她們的知情同意書和其他書面資料。1.27IndependentEthicsCommittee(IEC)獨立的倫理委員會(IEC)Anindependentbody(areviewboardoracommittee,institutional,regional,national,orsupranational),constitutedofmedicalprofessionalsandnon-medicalmembers,whoseresponsibilityitistoensuretheprotectionoftherights,safetyandwell-beingofhumansubjectsinvolvedinatrialandtoprovidepublicassuranceofthatprotection,by,amongotherthings,reviewingandapproving/providingfavourableopinionon,thetrialprotocol,thesuitabilityoftheinvestigator(s),facilities,andthemethodsandmaterialtobeusedinobtaininganddocumentinginformedconsentofthetrialsubjects.一個由醫學專業人員和非醫學專業人員組成的獨立機構(研究機構的、地區的、國家的或超國家的審評機構或委員會),其職責是保證參加試驗對象的權益、安全性和健康;并通過對試驗方案、研究人員、設施以及用于獲得和記錄試驗對象知情同意的方法和材料的合理性進行審評和批準/提供起促進作用的意見以對這種保護提供公眾保證Thelegalstatus,composition,function,operationsandregulatoryrequirementspertainingtoIndependentEthicsCommitteesmaydifferamongcountries,butshouldallowtheIndependentEthicsCommitteetoactinagreementwithGCPasdescribedinthisguideline.在不同的國家,獨立的倫理委員會的法律地位、組成、職責、操作和適用的管理要求可能不用,但是應當如本指導原則所述,允許獨立的倫理委員會按GCP進行工作。1.28InformedConsent知情同意Aprocessbywhichasubjectvoluntarilyconfirmshisorherwillingnesstoparticipateinaparticulartrial,afterhavingbeeninformedofallaspectsofthetrialthatarerelevanttothesubject'sdecisiontoparticipate.Informedconsentisdocumentedbymeansofawritten,signedanddatedinformedconsentform.一個對象在被告知與其作出決定有關的所有試驗信息后,資源確認他或她參加一個特定試驗的意愿過程。知情同意采用書面的、簽字并注明日期的知情同意書。1.29Inspection視察Theactbyaregulatoryauthority(ies)ofconductinganofficialreviewofdocuments,facilities,records,andanyotherresourcesthataredeemedbytheauthority(ies)toberelatedtotheclinicaltrialandthatmaybelocatedatthesiteofthetrial,atthesponsor'sand/orcontractresearchorganization’s(CRO’s)facilities,oratotherestablishmentsdeemedappropriatebytheregulatoryauthority(ies).管理當局在試驗單位、申辦者和/或合同研究組織或管理當局認為何時的其他機構對其認為與臨床試驗有關的文件、設備、記錄和其他資源進行的官方審查的活動。1.30Institution(medical)(醫學)研究機構Anypublicorprivateentityoragencyormedicalordentalfacilitywhereclinicaltrialsareconducted.實施臨床試驗任何或私人的實體、代理機構、醫學或齒科設施。1.31InstitutionalReviewBoard(IRB)機構審評委員會(IRB)Anindependentbodyconstitutedofmedical,scientific,andnon-scientificmembers,whoseresponsibilityistoensuretheprotectionoftherights,safetyandwell-beingofhumansubjectsinvolvedinatrialby,amongotherthings,reviewing,approving,andprovidingcontinuingreviewoftrialprotocolandamendmentsandofthemethodsandmaterialtobeusedinobtaininganddocumentinginformedconsentofthetrialsubjects.由醫學、科學和非科學成員組成的一個獨立機構,其職責是通過對試驗方案及其修訂本,獲得受試對象知情同意所用的方法和資料進行審評、批準和繼續審評,確保一項試驗的受試對象的權利、安全和健康得到保護。1.32InterimClinicalTrial/StudyReport臨床試驗/研究中期報告Areportofintermediateresultsandtheirevaluationbasedonanalysesperformedduringthecourseofatrial.根據試驗進行過程中所做的分析寫出的中期結果和評價的報告1.33InvestigationalProduct試驗用藥品Apharmaceuticalformofanactiveingredientorplacebobeingtestedorusedasareferenceinaclinicaltrial,includingaproductwithamarketingauthorizationwhenusedorassembled(formulatedorpackaged)inawaydifferentfromtheapprovedform,orwhenusedforanunapprovedindication,orwhenusedtogainfurtherinformationaboutanapproveduse.一種在臨床試驗中供試驗的或作為對照的活性成分或安慰劑的藥物制劑。包括一個已上市藥品以不同于所批準的方式適用或組合(制劑或包裝),或用于一個未經批準的適應證,或用于收集一個已批準用法的更多資料。1.34Investigator研究者Apersonresponsiblefortheconductoftheclinicaltrialatatrialsite.Ifatrialisconductedbyateamofindividualsatatrialsite,theinvestigatoristheresponsibleleaderoftheteamandmaybecalledtheprincipalinvestigator.SeealsoSubinvestigator.負責在一個試驗單位實施臨床試驗的人。如果在一個試驗單位是由一組人員實施試驗,研究者指這個組的負責人,也稱為主要研究者。見次級研究人員。1.35Investigator/Institution研究者/研究機構Anexpressionmeaning"theinvestigatorand/orinstitution,whererequiredbytheapplicableregulatoryrequirements".表示“符合適用管理要求的研究者和/或研究機構”1.36Investigator'sBrochure研究者手冊Acompilationoftheclinicalandnonclinicaldataontheinvestigationalproduct(s)whichisrelevanttothestudyoftheinvestigationalproduct(s)inhumansubjects(see7.Investigator’sBrochure).與試驗藥品在人類對象中的研究有關的臨床和非臨床資料的匯編(見7.研究者手冊)1.37LegallyAcceptableRepresentative法律上可接受的代表Anindividualorjuridicalorotherbodyauthorizedunderapplicablelawtoconsent,onbehalfofaprospectivesubject,tothesubject'sparticipationintheclinicaltrial.在適用法律下被授權代表一位未來的對象同意參加臨床試驗的個人,或司法人員或其他機關。1.38Monitoring監察Theactofoverseeingtheprogressofaclinicaltrial,andofensuringthatitisconducted,recorded,andreportedinaccordancewiththeprotocol,StandardOperatingProcedures(SOPs),GoodClinicalPractice(GCP),andtheapplicableregulatoryrequirement(s).監督一個臨床試驗的進展,保證臨床試驗按照試驗方案、標準操作程序(SOP)、臨床試驗管理規范(GCP)和適用的管理要求實施、記錄和報告的活動。1.39MonitoringReport監察報告Awrittenreportfromthemonitortothesponsoraftereachsitevisitand/orothertrial-relatedcommunicationaccordingtothesponsor’sSOPs.監察員在每一次現場訪問和/或其他與試驗有關的交流后,根據申辦者的SOP寫給申辦者的書面報告。1.40MulticentreTrial多中心試驗Aclinicaltrialconductedaccordingtoasingleprotocolbutatmorethanonesite,andtherefore,carriedoutbymorethanoneinvestigator.按照一個試驗方案,在一個以上試驗單位實施,因此由一名以上研究者完成的臨床試驗。1.41NonclinicalStudy非臨床試驗Biomedicalstudiesnotperformedonhumansubjects.不是在人類對象進行的生物醫學研究。1.42Opinion(inrelationtoIndependentEthicsCommittee)意見(與獨立的倫理委員會相關)Thejudgementand/ortheadviceprovidedbyanIndependentEthicsCommittee(IEC).由獨立的倫理委員會(IEC)給出的評價和/或建議1.43OriginalMedicalRecord原始醫學記錄SeeSourceDocuments.見源文件1.44Protocol試驗方案Adocumentthatdescribestheobjective(s),design,methodology,statisticalconsiderations,andorganizationofatrial.Theprotocolusuallyalsogivesthebackgroundandrationaleforthetrial,butthesecouldbeprovidedinotherprotocolreferenceddocuments.ThroughouttheICHGCPGuidelinethetermprotocolreferstoprotocolandprotocolamendments.一個闡明試驗的目的、設計、方法學、統計學考慮和組織的文件。試驗方案通常也給出試驗的背景和理論基礎,但者這可以寫在與方案有關的其他參考文件中。在ICH指導原則中,試驗方案這一術語指試驗方案和方案的修改。1.45ProtocolAmendment試驗方案的修改Awrittendescriptionofachange(s)toorformalclarificationofaprotocol.對試驗方案的改變或澄清的書面描述。1.46QualityAssurance(QA)質量保證(QA)Allthoseplannedandsystematicactionsthatareestablishedtoensurethatthetrialisperformedandthedataaregenerated,documented(recorded),andreportedincompliancewithGoodClinicalPractice(GCP)andtheapplicableregulatoryrequirement(s).為保證試驗的進行和數據產生、記錄以及報告都符合臨床試驗管理規范(GCP)和適用管理要求所建立的有計劃的系統活動。1.47QualityControl(QC)質量控制(QC)Theoperationaltechniquesandactivitiesundertakenwithinthequalityassurancesystemtoverifythattherequirementsforqualityofthetrial-relatedactivitieshavebeenfulfilled.在質量保證系統內所采取的操作技術和活動,以查證與試驗相關的活動都符合質量要求。1.48Randomization隨機化Theprocessofassigningtrialsubjectstotreatmentorcontrolgroupsusinganelementofchancetodeterminetheassignmentsinordertoreducebias.為了減少偏倚,采用機遇決定分配的原理將試驗對象分配倒治療組或對照組的過程。1.49RegulatoryAuthorities管理當局Bodieshavingthepowertoregulate.IntheICHGCPguidelinetheexpressionRegulatoryAuthoritiesincludestheauthoritiesthatreviewsubmittedclinicaldataandthosethatconductinspections(see1.29).Thesebodiesaresometimesreferredtoascompetentauthorities.有權進行管理的基構。在ICHGCP指導原則中,管理當局一詞包括審評所提交的臨床數據和實施視察的機構(見1.29)。這些機構有時指主管當局。1.50SeriousAdverseEvent(SAE)orSeriousAdverseDrugReaction(SeriousADR)嚴重不良事件(SAE)或嚴重藥品不良反應Anyuntowardmedicaloccurrencethatatanydose:發生在任何劑量的任何不幸醫學事件:●resultsindeath,●-導致死亡●islife-threatening,●-危及生命●requiresinpatienthospitalizationorprolongationofexistinghospitalization,●-需要住院治療或延長住院時間resultsinpersistentorsignificantdisability/incapacity,or●-導致永久或嚴重的殘疾/能力喪失,或●isacongenitalanomaly/birthdefect●-先天性異常/出生缺陷(seetheICHGuidelineforClinicalSafetyDataManagement:DefinitionsandStandardsforExpeditedReporting).(見ICH臨床安全性數據管理指導原則,快速報告的定義和標準)1.51SourceData源數據Allinformationinoriginalrecordsandcertifiedcopiesoforiginalrecordsofclinicalfindings,observations,orotheractivitiesinaclinicaltrialnecessaryforthereconstructionandevaluationofthetrial.Sourcedataarecontainedinsourcedocuments(originalrecordsorcertifiedcopies).臨床試驗中的臨床發現、觀察或其他活動的原始記錄及其可靠副本中的全部資料,他們對于重建和評價試驗是必要的。源數據包含在源文件中(原始記錄或可靠副本)。1.52SourceDocuments源文件Originaldocuments,data,andrecords(e.g.,hospitalrecords,clinicalandofficecharts,laboratorynotes,memoranda,subjects'diariesorevaluationchecklists,pharmacydispensingrecords,recordeddatafromautomatedinstruments,copiesortranscriptionscertifiedafterverificationasbeingaccuratecopies,microfiches,photographicnegatives,microfilmormagneticmedia,x-rays,subjectfiles,andrecordskeptatthepharmacy,atthelaboratoriesandatmedico-technicaldepartmentsinvolvedintheclinicaltrial).原始文件、數據和記錄(如醫院記錄,臨床和辦公室圖標,實驗室筆記,備忘錄,對象日記卡或評價表,藥房發藥記錄,自動儀器的記錄數據,在核對后做為準確副本的可靠復印件或抄件,顯微膠片,攝影負片,縮微膠卷或磁介質,X線,對象文件,以及保存在藥房、實驗室和與參與臨床試驗的醫學技術部門中的記錄。1.53Sponsor申辦者Anindividual,company,institution,ororganizationwhichtakesresponsibilityfortheinitiation,management,and/orfinancingofaclinicaltrial.對一個臨床試驗的發起、管理和/或財務負責的個人、公用、機構或組織。1.54Sponsor-Investigator申辦者-研究者Anindividualwhobothinitiatesandconducts,aloneorwithothers,aclinicaltrial,andunderwhoseimmediatedirectiontheinvestigationalproductisadministeredto,dispensedto,orusedbyasubject.Thetermdoesnotincludeanypersonotherthananindividual(e.g.,itdoesnotincludeacorporationoranagency).Theobligationsofasponsor-investigatorincludeboththoseofasponsorandthoseofaninvestigator.單獨與其他人一起,發起并實施一個臨床試驗的個人。在他(們)的直接指示下,給對象服用、發給對象或由對象使用試驗藥品。該術語并不包括除了個人以外的任何人(如不包括一個公司或一個機構)。一個申辦者-研究者的義務包括一個申辦者和一個研究者兩者的義務。1.55StandardOperatingProcedures(SOPs)標準操作程序(SOP)Detailed,writteninstructionstoachieveuniformityoftheperformanceofaspecificfunction.為達到均一性完成一個特定職責指定的詳細書面說明。1.56Subinvestigator次級研究人員Anyindividualmemberoftheclinicaltrialteamdesignatedandsupervisedbytheinvestigatoratatrialsitetoperformcriticaltrial-relatedproceduresand/ortomakeimportanttrial-relateddecisions(e.g.,associates,residents,researchfellows).SeealsoInvestigator.在一個試驗單位,在主要研究者指定和監督下的臨床試驗組中完成與試驗有關的重要程序和/或作出與有關試驗的重大決定的成員(如同事,住院醫生,特別是研究生)。見研究者。1.57Subject/TrialSubject對象/試驗對象Anindividualwhoparticipatesinaclinicaltrial,eitherasarecipientoftheinvestigationalproduct(s)orasacontrol.參加一個臨床試驗作為試驗藥品的接受者或作為對照的個人。1.58SubjectIdentificationCode對象識別編碼Auniqueidentifierassignedbytheinvestigatortoeachtrialsubjecttoprotectthesubject'sidentityandusedinlieuofthesubject'snamewhentheinvestigatorreportsadverseeventsand/orothertrialrelateddata.研究者為每一名受試對象指定的獨特識別號碼,以保護對象的身份并在研究者報告不良事件和/或其他與試驗有關數據時代替對象姓名。1.59TrialSite試驗單位Thelocation(s)wheretrial-relatedactivitiesareactuallyconducted.真正開展與臨床試驗有關活動的地方。1.60UnexpectedAdverseDrugReaction非預期的藥品不良反應Anadversereaction,thenatureorseverityofwhichisnotconsistentwiththeapplicableproductinformation(e.g.,Investigator'sBrochureforanunapprovedinvestigationalproductorpackageinsert/summaryofproductcharacteristicsforanapprovedproduct)(seetheICHGuidelineforClinicalSafetyDataManagement:DefinitionsandStandardsforExpeditedReporting).一種不良反應,其性質或嚴重程度與現有的產品資料(如一種未批準試驗用藥品的研究者手冊,或包裝插入頁/一個已經批準藥物的產品性能摘要)不符的不良反應(見ICH臨床安全性數據管理指導原則:快速報告的定義和標準)。1.61VulnerableSubjects弱勢對象Individualswhosewillingnesstovolunteerinaclinicaltrialmaybeundulyinfluencedbytheexpectation,whetherjustifiedornot,ofbenefitsassociatedwithparticipation,orofaretaliatoryresponsefromseniormembersofahierarchyincaseofrefusaltoparticipate.Examplesaremembersofagroupwithahierarchicalstructure,suchasmedical,pharmacy,dental,andnursingstudents,subordinatehospitalandlaboratorypersonnel,employeesofthepharmaceuticalindustry,membersofthearmedforces,andpersonskeptindetention.Othervulnerablesubjectsincludepatientswithincurablediseases,personsinnursinghomes,unemployedorimpoverishedpersons,patientsinemergencysituations,ethnicminoritygroups,homelesspersons,nomads,refugees,minors,andthoseincapableofgivingconsent.指受到不正當的影響而稱為一個臨床志愿者的人,他們可能由于期望(無論正當與否)參加試驗而伴隨的利益,或者拒絕參加會受到等級中資深成員的報復。有等級結構的團體的成員,如醫學、藥學、齒科或護理專業的學生,附屬醫院和實驗室人員,制藥公司的雇員,軍人,以及被監禁的人。其他弱勢對象包括無可救藥的患者,住在福利院利的人,失業者或窮人,處于危急狀況的病人,少數民族,無家可歸者,流浪者,未成年者,和那些無能力給出知情同意的人1.62Well-being(ofthetrialsubjects)健康(試驗對象的)Thephysicalandmentalintegrityofthesubjectsparticipatinginaclinicaltrial.參加臨床試驗對象的體格和精神的完整性。2.THEPRINCIPLESOFICHGCPICH-GCP的原則2.1ClinicaltrialsshouldbeconductedinaccordancewiththeethicalprinciplesthathavetheiroriginintheDeclarationofHelsinki,andthatareconsistentwithGCPandtheapplicableregulatoryrequirement(s).2.1臨床試驗的實施應符合源自赫爾辛基宣言的倫理原則,與GCP和適用管理要求一致。2.2Beforeatrialisinitiated,foreseeablerisksandinconveniencesshouldbeweighedagainsttheanticipatedbenefitfortheindividualtrialsubjectandsociety.Atrialshouldbeinitiatedandcontinuedonlyiftheanticipatedbenefitsjustifytherisks.2.2在開始一個試驗之前,應當權衡個體試驗對象和社會的可預見風險、不方便和預期的受益。只有當預期的受益大于風險時,才開始和繼續一個臨床試驗。2.3Therights,safety,andwell-beingofthetrialsubjectsarethemostimportantconsiderationsandshouldprevailoverinterestsofscienceandsociety.2.3試驗對象的權利、安全和健康是最重要的考慮,應當勝過科學和社會的利益。2.4Theavailablenonclinicalandclinicalinformationonaninvestigationalproductshouldbeadequatetosupporttheproposedclinicaltrial.2.4關于試驗用藥品可得到的非臨床和臨床資料應足以支持所提議的臨床試驗。2.5Clinicaltrialsshouldbescientificallysound,anddescribedinaclear,detailedprotocol.2.5臨床試驗應當有堅實的科學基礎,有明確、詳細描述的試驗方案。2.6Atrialshouldbeconductedincompliancewiththeprotocolthathasreceivedpriorinstitutionalreviewboard(IRB)/independentethicscommittee(IEC)approval/favourableopinion.2.6臨床試驗的實施應當遵循事先已經得到研究機構審查委員會(IRB)/獨立的倫理委員會(IEC)批準/贊成的試驗方案。2.7Themedicalcaregivento,andmedicaldecisionsmadeonbehalfof,subjectsshouldalwaysbetheresponsibilityofaqualifiedphysicianor,whenappropriate,ofaqualifieddentist.2.7一名合格醫生或合格牙醫的職責永遠是給予對象醫療保健,代表對象作出醫學決定。2.8Eachindividualinvolvedinconductingatrialshouldbequalifiedbyeducation,training,andexperiencetoperformhisorherrespectivetask(s).2.8參與實施臨床試驗個每一個人應當在受教育、培訓和經驗方面都有資格完成他或她的預期任務。2.9Freelygiveninformedconsentshouldbeobtainedfromeverysubjectpriortoclinicaltrialparticipation.2.9應當在參加臨床試驗前每一個對象獲得自由給出的知情同意書。2.10Allclinicaltrialinformationshouldberecorded,handled,andstoredinawaythatallowsitsaccuratereporting,interpretationandverification.2.10所有臨床試驗資料被記錄、處理和儲存的方式應當允許資料的準確報告、解釋和核對。2.11Theconfidentialityofrecordsthatcouldidentifysubjectsshouldbeprotected,respectingtheprivacyandconfidentialityrulesinaccordancewiththeapplicableregulatoryrequirement(s).2.11可能鑒別對象身份的記錄的保密性應當得到保護,依照適用的管理要求尊重隱私和保密規定。2.12Investigationalproductsshouldbemanufactured,handled,andstoredinaccordancewithapplicablegoodmanufacturingpractice(GMP).Theyshouldbeusedinaccordancewiththeapprovedprotocol.2.12試驗用藥品應當按照適用的藥品生產質量管理規范(GMP)生產、處理和儲存。試驗用藥品應按照已批準的方案使用。2.13Systemswithproceduresthatassurethequalityofeveryaspectofthetrialshouldbeimplemented.2.13應當建立保證試驗各方面質量的程序系統。3.INSTITUTIONALREVIEWBOARD/INDEPENDENTETHICSCOMMITTEE(IRB/IEC)機構審查委員會/獨立的倫理委員會3.1Responsibilities職責3.1.1AnIRB/IECshouldsafeguardtherights,safety,andwell-beingofalltrialsubjects.Specialattentionshouldbepaidtotrialsthatmayincludevulnerablesubjects.3.1.1IRB/IEC應當保護所有試驗對象的權利、安全和健康。應當特別注意那些可能包括有弱勢對象的試驗。3.1.2TheIRB/IECshouldobtainthefollowingdocuments:3.1.2IRB/IEC應當得到以下文件:trialprotocol(s)/amendment(s),writteninformedconsentform(s)andconsentformupdatesthatthe