循证医学医学知识讲座课件

循循证证医学医学知医学医学知识讲识讲座座循证医学医学知识讲座1MisguideMediaCelloranimalmodelOnlyintheLABNotestinhumanMisguideMediaCelloranimalm2MisguideAd.1997年上海医科大学中西医结合研究所完成的“中华灵芝宝”动物实验证实：该药物具有抑瘤作用、保护免疫功能和放化疗减毒增效作用。中国科学院上海药物研究所完成“中华灵芝宝对多种培养人癌细胞生长的作用”。课题，结论证实该药物对多种白血病和人体实体癌细胞具有明显的抑制作用，并呈现较好的量效关系。1999年中国科学院上海生物研究所丁健研究员等实验表明，中华灵芝宝（现名：双灵固本散）能抑制拓扑异构酶I和拓扑异构酶II，造成癌细胞DNA单链或双链断裂，阻断癌细胞的无限制繁殖，导致癌细胞破裂凋亡。2001年上海预防医学研究院以Ames试验和骨髓微核试验作了研究，结果表明中华灵芝宝具有抗突变作用。2002年国家药品监督管理局（SDA）批准中华灵芝宝转为“国药准字”B20020428，并更名为“双灵固本散”。2007年国食药监注2007253号 注销西安绿谷制药有限公司“双灵固本散”批准文号Cell or animal study apply to humanMisguideAd.1997年Celloranima3BackgroundLongerlifeChronicdiseasesormalignancyIncreasingmedicalcostsThepatientknowsmore,andquestionsmore!BackgroundLongerlife4BackgroundTokeepuptodateinInternalMedicine,Ineedtoread17articlesaday,365daysayearMorestudies,morearticles,muchmoreinformation20,000RCTspublishedannually，6000articlesenterMedlinemonthly1studyreportpublishedeveryhourMorediasgnostictools,moredrugs,moretreatmentmethods“Halfofwhatyouaretaughtasmedicalstudentswillin10yearshavebeenshowntobewrong.Andthetroubleis,nonofyourteachersknowswhichhalf.”BackgroundTokeepuptodatei5Background-FalseevidenceAnesthesiaandAnalgesia2007IF2.2142007TotalCites15960Background-FalseevidenceAne6Background-InadequatetoolsBackground-Inadequatetools7Background-Journals&PapersWereceivedinputfrom23scientists(headsoflaboratories)andcollecteddatafrom67projects,mostofthem(47)fromthefieldofoncology.Thisanalysisrevealedthatonlyin2025%oftheprojectsweretherelevantpublisheddatacompletelyinlinewithourin-housefindings(Fig.1c).-NatureReviewsDrugDiscovery10,712(September2011)Background-Journals&PapersWe8BackgroundTraditionalpracticeModelCliniciansareuseconvenientsourcesFactorsthatinfluencedecisionmaking.SeniordoctorsPatientrequestPharmaceuticalrepresentativesrecommendationLocalexpert-basedCMEOutdate!BackgroundTraditionalpractice9DefinitionEvidenceBasedMedicineistheconscientious(自觉),explicit(明确),andjudicious(审慎)useofcurrentbestevidenceinmakingdecisionsaboutthecareofindividualpatients.Sackett,D.L.BMJ1996Evidence-basedmedicineistheintegrationofbestresearchevidencewithclinicalexpertiseandpatientvaluesSackett,D.L.2001DefinitionEvidenceBasedMedic10DefinitionEBM:APracticalDefinitionWhenthereisevidenceofbenefitandvalue,doit.Whenthereisevidenceofnobenefit,harmorpoorvalue,dontdoit.Whenthereisinsufficientevidencetoknowforsure,beconservative.Andwhateverwedo,doitright!DavidEddyDefinitionEBM:APracticalDef11Definition Clinical expertise临床技能临床技能外部证据外部证据External evidencesPatient Values and Preferences病人价值病人价值DefinitionClinicalexpertise外部12CliniciansIndividualclinicalexpertisetheincreasingproficiencyandjudgementthatindividualcliniciansacquirethroughclinicalexperienceandclinicalpractice.CliniciansIndividualclinical13CliniciansEBM is a Lifelong learning modellifelong,self-directed,problem-basedlearningEBMproposemethodstofindandevaluateevidence.EBMconvertstheabstractexerciseofreadingandappraisingtheliteratureintothepragmaticprocessofusingtheliteraturetobenefitindividualpatientswhilesimultaneouslyexpandingthecliniciansknowledgebase.Bordley,D.RCliniciansEBMisaLifelongle14CliniciansThe basic for EBMThe basic for EBMAuthors证据提供者Users证据应用者Defineclinicalquestions确定医疗问题+Task任务收集/评价/写作论文提供最佳证据Useevidence正确地应用证据KnowhowClinicaltraining医疗实践+临床流行病学（DME）+Statistics医学统计学+Medicaleconomics卫生经济学+LiteratureSearch+RoleGroup团队Individual个人CliniciansThebasicforEBMAut15ExternalevidencesBestavailableexternalclinicalevidence:clinicallyrelevantresearchbasicsciencesofmedicinepatient-centredresearchExternalclinicalevidencehasashortdoubling-time,andbothinvalidatespreviouslyaccepteddiagnostictestsandtreatmentsandreplacesthemwithnewonesthataremorepowerful,moreaccurate,moreefficacious,andsaferExternalevidencesBestavailab16ExternalevidencesIsAllEvidenceCreatedEqual?Oxford Centre for Evidence-based Medicine Levels of EvidenceExternalevidencesIsAllEvide17循证医学医学知识讲座课件18TheEvidencePyramidHierarchyofevidence:arrangesstudydesignsbytheirsusceptibilitytobiasPrimary ResearchExperimentalobservationalSecondaryResearchFor quantitative studiesFor qualitative studies NoconsensusabouttherelativerigourofdifferentmethodsSystematicreview双灵固本散TheEvidencePyramidHierarchy19Clinicaltrialandrealworld临床试验中认为是有效可能在真实世界中无效Clinicaltrialandrealworld20NotalltheevidencesarethesameimportanceHollingworth&Jarvik,Radiology 2007;244:31-38Notalltheevidencesarethe21GRADE（Gradingofrecommendationsassessment,developmentandevaluation)推荐分级的评价、制定与评估CodeQualityofEvidenceDefinitionAHighFurtherresearchisveryunlikelytochangeourconfidenceintheestimateofeffect.Severalhigh-qualitystudieswithconsistentresultsInspecialcases:onelarge,high-qualitymulti-centretrialBModerateFurtherresearchislikelytohaveanimportantimpactonourconfidenceintheestimateofeffectandmaychangetheestimate.Onehigh-qualitystudySeveralstudieswithsomelimitationsCLowFurtherresearchisverylikelytohaveanimportantimpactonourconfidenceintheestimateofeffectandislikelytochangetheestimate.OneormorestudieswithseverelimitationsDVeryLowAnyestimateofeffectisveryuncertain.ExpertopinionNodirectresearchevidenceOneormorestudieswithveryseverelimitationsGRADE（Gradingofrecommendati22Right methods is crucialType of QuestionSuggested best type of StudyTherapyRCTcohort case control case seriesDiagnosisProspective,blind comparison to a gold standardEtiology/HarmRCT cohort case control case seriesPrognosisCohort study case control case seriesPreventionRCTcohort study case control case seriesClinical ExamProspective,blind comparison to gold standardCostEconomic analysisRightmethodsiscrucialTypeo23ExternalevidencesExternalevidences24 疗疗 效效的大小的大小疗效可信度估计疗效可信度估计I类类证据和/或达成一致意见认为某治疗/操作是有用/有效的。II类类对某治疗/操作的有用/有效性存在相互矛盾的证据或者分歧 III类无效类无效#或或III类有类有害害证据和/或达成一致意见认为某治疗/操作的无用/无效，在某些情况下可能有害IIa类类证据和共识赞同有用/有效IIb类类证据和共识对于有用/有效性不那么确定获益获益 风险风险治疗/操作应该应该执行获益获益 风险风险需要增加更多的证据应应用用某某治治疗疗/操操作作是是合合理的理的获益获益 风险风险需要更为广泛的证据，注册资料也是有益的可可考考虑虑应应用用某某治治疗疗/操操作作风险风险 获益获益不需要更加证据某某治治疗疗/操操作作不不应应使使用用，因为无益且可能有害因为无益且可能有害A级级已有大样本量研究数据来自多个RCT#或者meta分析认为治疗/操作有用/有效。已有足够证据，来自多个RCT或者meta分析支持治疗/操作有用/有效。来自多个RCT或者meta分析存在某些矛盾治疗/操作的有用/有效性不确定来自多个RCT或者meta分析存在较大的矛盾认为某治疗/操作无用/无效，某些情况下可能有害已有足够证据，来自多个RCT或者meta分析B级级较小样本量的研究数据来自单个RCT或者多个非RCT确认治疗/操作有用/有效。证据来自单个RCT或者多个非RCT支持治疗/操作有用/有效。来自单个RCT或者多个非RCT存在某些矛盾治疗/操作的有用/有效性不确定来自单个RCT或者多个非RCT存在较大的矛盾认为某治疗/操作无用/无效，某些情况下可能有害证据来自单个RCT或者多个非RCTC级级小样本量的研究仅有专家讨论共识，病例报告，或标准治疗确认治疗/操作有用/有效。证据来自专家讨论共识，病例报告，或标准治疗支持治疗/操作有用/有效。存在分歧的专家讨论共识，病例报告，或标准治疗治疗/操作的有用/有效性不确定存在分歧的专家讨论共识，病例报告，或标准治疗认为某治疗/操作无用/无效，某些情况下可能有害证据来自专家讨论共识，病例报告，或标准治疗建建议议书书写写推推荐荐时时使使用用的的语句语句应该/推荐/有指征 有用/有效/有益合理的可能是有用/有效/有益的可能推荐或者有指征可以考虑也许是合理的有用和有效性未知/不明/不确定或者未很好地确认III类无效类无效不推荐/无指征/不应使用无用/无效/无益/III类有害类有害可能有害/有危害不应使用可能增加并发症/死亡有效性比较语句有效性比较语句$治疗/策略A较B更推荐/更有指征选择治疗/策略A优于B治疗/策略A可可能能较B更推荐/更有指征选择治疗/策略A可可能能优于BACCF/AHA指南推荐强度和证据级别的应用疗25Adequate sample sizePhase III RCT head to head Compare survivalPhase III RCT head to head Compare survivalControlSurvival（%）Improved survival and sample sized5%10%15%101,290394134151,894544208202,444676328252,926788374AdequatesamplesizePhaseIII26科学引文索引ScienceCitationIndex，SCIImpactfactorThisisthemeancitationrateofallarticlescontainedinthejournalPublishedannuallyintheSCIJournalCitationreportsaquantitativemeasureofthefrequencywithwhichtheaveragearticlepublishedinagivenscholarlyjournalhasbeencitedinaparticularyearorperiod;Theimpactfactorisameasureofimportanceofscientificjournals科学引文索引ScienceCitationInde27FindJournals查杂志FindJournals查杂志28Findapaper查论文Findapaper查论文29Findwhocitethepaper查引用Findwhocitethepaper查引用30循证医学医学知识讲座课件31Citedandqualityofstudy被引/他引与论文的质量Citedandqualityofstudy被引/32循证医学医学知识讲座课件33循证医学医学知识讲座课件34循证医学医学知识讲座课件35SourceofMedicalInformationPrimaryMEDLINE，CBMSecondaryGuidelines，Cochrane LibMuchmorelikely(thanpersonalsearchandcriticalappraisal)tobetrueSavestheclinicianstimeTextbookOthers？ConferenceInstitutional or personal experienceSourceofMedicalInformationP36SourceofMedicalInformationInterest group or organizationCommercial Companys News or BriefGoogle,Yahoo!Open Mind and Be Very CarefullySourceofMedicalInformationI37QuickInformationGuidelinesExplicitevidence-basedEvidence-basedResearch-based(highlyreferenced)Opinion-based“expertconsensus”QuickInformationGuidelines38National Guideline Clearinghouse(http:/www.guideline.gov/)NationalGuidelineClearinghou39QuickInformationCochraneLibrary-TheCochraneCollaborationSystematicreviewsThecurrentresourcewiththehighestmethodologicalrigorForeachclinicalquestion,alloftheEnglishliteraturemeticulouslysearchedforrandomizedtrialsLargesystematicreviewswithvalidmethods+collaborativeeffortConclusionsarebasedonalltheevidencefromvalidrandomizedtrialsQuickInformationCochraneLibr40循证医学医学知识讲座课件41CochraneLibraryAdvantagehighestqualityevidencewelleverhaveontheeffectivenessofhealthcareDisadvantagenotyetmanysystemicreviewsnecessarilyomitsthenewesttreatmentStep 2CochraneLibraryAdvantageStep42PDQ(Physician Data Query)http:/www.cancer.gov/cancer_information/pdq/PDQ(PhysicianDataQuery)43ClinicalTrialDatabaseCurrent Controlled Trialshttp:/www.controlled-NIH ClinicalTrials.gov ClinicalTrialDatabaseCurrent44循证医学医学知识讲座课件45PubMed/MEDLINEhttp:/www.ncbi.nlm.nih.gov/PubmedPubMed/MEDLINEhttp:/www.ncbi46Step 2Step247Step 2Step248Step 2Step249Step 2Step250Step 2Step251循证医学医学知识讲座课件52循证医学医学知识讲座课件53循证医学医学知识讲座课件54Medline-PubMedAdvantageexhaustiveness,flexibilityofsearchingjournalcoverage,currency(on-lineversions)widespreadavailabilityandsupportDisadvantagehavetodoyourownqualityfilteringputtingtogethergoodsearchesisdifficultgapsincoverage(medical,geographicalandlinguistic)Step 2Medline-PubMedAdvantageStep255The PatientsIndividualize个体化；Compliance依从性；Informedconsent知情同意ValueThePatientsIndividualize个体化；56Definition Clinical expertise临床技能临床技能Patient Values and Preferences病人价值病人价值外部证据外部证据External evidencesOther factorsOther factors 1.Regulations1.Regulations 2.Medical insurance 2.Medical insuranceDefinitionClinicalexpertisePa57Evidence-basedMedicineBasesactiononbestevidencesynthesisGooddoctorsusebothindividualclinicalexpertiseandthebestavailableexternalevidence,andneitheraloneisenough.EBMisnotrestrictedtorandomisedtrialsEvidence-basedMedicineBasesa58