1、循證醫(yī)學(xué)醫(yī)學(xué)知識講座循證醫(yī)學(xué)醫(yī)學(xué)知識講座Misguide MediaCell or animal modelOnly in the LAB No test in human2循證醫(yī)學(xué)醫(yī)學(xué)知識講座Misguide MediaCell or animal mMisguide Ad.1997年上海醫(yī)科大學(xué)中西醫(yī)結(jié)合研究所完成的“中華靈芝寶”動物實(shí)驗(yàn)證實(shí)：該藥物具有抑瘤作用、保護(hù)免疫功能和放化療減毒增效作用。中國科學(xué)院上海藥物研究所完成“中華靈芝寶對多種培養(yǎng)人癌細(xì)胞生長的作用”。課題，結(jié)論證實(shí)該藥物對多種白血病和人體實(shí)體癌細(xì)胞具有明顯的抑制作用，并呈現(xiàn)較好的量效關(guān)系。1999年中國科學(xué)院上海生物研究所

2、丁健研究員等實(shí)驗(yàn)表明，中華靈芝寶（現(xiàn)名：雙靈固本散）能抑制拓?fù)洚悩?gòu)酶I和拓?fù)洚悩?gòu)酶II，造成癌細(xì)胞DNA單鏈或雙鏈斷裂，阻斷癌細(xì)胞的無限制繁殖，導(dǎo)致癌細(xì)胞破裂凋亡。2001年上海預(yù)防醫(yī)學(xué)研究院以Ames試驗(yàn)和骨髓微核試驗(yàn)作了研究，結(jié)果表明中華靈芝寶具有抗突變作用。2002年國家藥品監(jiān)督管理局（SDA）批準(zhǔn)中華靈芝寶轉(zhuǎn)為“國藥準(zhǔn)字”B20020428，并更名為“雙靈固本散”。2007年國食藥監(jiān)注2007253號 注銷西安綠谷制藥有限公司 “雙靈固本散”批準(zhǔn)文號Cell or animal study apply to human3循證醫(yī)學(xué)醫(yī)學(xué)知識講座Misguide Ad.1997年Cell o

3、r animaBackgroundLonger lifeChronic diseases or malignancyIncreasing medical costsThe patient knows more, and questions more!4循證醫(yī)學(xué)醫(yī)學(xué)知識講座BackgroundLonger life4循證醫(yī)學(xué)醫(yī)學(xué)知識BackgroundTo keep up to date in Internal Medicine, I need to read 17 articles a day, 365 days a yearMore studies, more articles, much

4、more information20,000 RCTs published annually，6000 articles enter Medline monthly 1 study report published every hourMore diasgnostic tools, more drugs, more treatment methods“Half of what you are taught as medical students will in 10 years have been shown to be wrong. And the trouble is, non of yo

5、ur teachers knows which half.”5循證醫(yī)學(xué)醫(yī)學(xué)知識講座BackgroundTo keep up to date iBackground-False evidenceAnesthesia and Analgesia 2007 IF 2.2142007 Total Cites 159606循證醫(yī)學(xué)醫(yī)學(xué)知識講座Background-False evidenceAneBackground-Inadequate tools7循證醫(yī)學(xué)醫(yī)學(xué)知識講座Background-Inadequate tools7Background-Journals&PapersWe received i

6、nput from 23 scientists (heads of laboratories) and collected data from 67 projects, most of them (47) from the field of oncology. This analysis revealed that only in 2025% of the projects were the relevant published data completely in line with our in-house findings (Fig. 1c). -Nature Reviews Drug

7、Discovery 10, 712 (September 2011)8循證醫(yī)學(xué)醫(yī)學(xué)知識講座Background-Journals&PapersWeBackgroundTraditional practice ModelClinicians are use convenient sourcesFactors that influence decision making.Senior doctorsPatient requestPharmaceutical representatives recommendationLocal expert-based CMEOutdate!9循證醫(yī)學(xué)醫(yī)學(xué)知識講座

8、BackgroundTraditional practiceDefinitionEvidence Based Medicine is the conscientious(自覺), explicit(明確), and judicious(審慎) use of current best evidence in making decisions about the care of individual patients.Sackett, D. L. BMJ 1996 Evidence-based medicine is the integration of best research evidenc

9、e with clinical expertise and patient values Sackett, D. L. 200110循證醫(yī)學(xué)醫(yī)學(xué)知識講座DefinitionEvidence Based MedicDefinitionEBM: A Practical DefinitionWhen there is evidence of benefit and value, do it.When there is evidence of no benefit, harm or poor value, dont do it.When there is insufficient evidence t

10、o know for sure, be conservative.And whatever we do, do it right!David Eddy11循證醫(yī)學(xué)醫(yī)學(xué)知識講座DefinitionEBM: A Practical DefDefinition Clinical expertise臨床技能外部證據(jù)External evidencesPatient Values and Preferences病人價值12循證醫(yī)學(xué)醫(yī)學(xué)知識講座DefinitionClinical expertise外部CliniciansIndividual clinical expertisethe increasin

11、g proficiency and judgement that individual clinicians acquire through clinical experience and clinical practice. 13循證醫(yī)學(xué)醫(yī)學(xué)知識講座CliniciansIndividual clinical CliniciansEBM is a Lifelong learning modellifelong, self-directed, problem-based learningEBM propose methods to find and evaluate evidence.EBM c

12、onverts the abstract exercise of reading and appraising the literature into the pragmatic process of using the literature to benefit individual patients while simultaneously expanding the clinicians knowledge base. Bordley, D.R14循證醫(yī)學(xué)醫(yī)學(xué)知識講座CliniciansEBM is a Lifelong leCliniciansThe basic for EBMAuth

13、ors證據(jù)提供者Users證據(jù)應(yīng)用者Define clinical questions確定醫(yī)療問題+Task任務(wù)收集/評價/寫作論文提供最佳證據(jù)Use evidence正確地應(yīng)用證據(jù)KnowhowClinical training醫(yī)療實(shí)踐+臨床流行病學(xué)（DME）+Statistics醫(yī)學(xué)統(tǒng)計(jì)學(xué)+Medical economics衛(wèi)生經(jīng)濟(jì)學(xué)+Literature Search+RoleGroup團(tuán)隊(duì)Individual個人15循證醫(yī)學(xué)醫(yī)學(xué)知識講座CliniciansThe basic for EBMAutExternal evidencesBest available external clin

14、ical evidence: clinically relevant researchbasic sciences of medicinepatient-centred researchExternal clinical evidence has a short doubling-time, and both invalidates previously accepted diagnostic tests and treatments and replaces them with new ones that are more powerful, more accurate, more effi

15、cacious, and safer16循證醫(yī)學(xué)醫(yī)學(xué)知識講座External evidencesBest availabExternal evidencesIs All Evidence Created Equal?Oxford Centre for Evidence-based Medicine Levels of Evidence17循證醫(yī)學(xué)醫(yī)學(xué)知識講座External evidencesIs All Evide18循證醫(yī)學(xué)醫(yī)學(xué)知識講座18循證醫(yī)學(xué)醫(yī)學(xué)知識講座The Evidence PyramidHierarchy of evidence: arranges study designs

16、by their susceptibility to biasPrimary ResearchExperimentalobservationalSecondaryResearchFor quantitative studiesFor qualitative studies No consensus about the relative rigour of different methodsSystematic review雙靈固本散19循證醫(yī)學(xué)醫(yī)學(xué)知識講座The Evidence PyramidHierarchy Clinical trial and real world 臨床試驗(yàn)中認(rèn)為是有效

17、可能在真實(shí)世界中無效20循證醫(yī)學(xué)醫(yī)學(xué)知識講座Clinical trial and real world Not all the evidences are the same importanceHollingworth & Jarvik, Radiology 2007;244:31-3821循證醫(yī)學(xué)醫(yī)學(xué)知識講座Not all the evidences are the GRADE（Grading of recommendations assessment, development and evaluation) 推薦分級的評價、制定與評估CodeQuality of EvidenceDefin

18、itionAHighFurther research is very unlikely to change our confidence in the estimate of effect.Several high-quality studies with consistent resultsIn special cases: one large, high-quality multi-centre trialBModerateFurther research is likely to have an important impact on our confidence in the esti

19、mate of effect and may change the estimate.One high-quality studySeveral studies with some limitationsCLowFurther research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.One or more studies with severe limitationsDVery LowA

20、ny estimate of effect is very uncertain.Expert opinionNo direct research evidenceOne or more studies with very severe limitations22循證醫(yī)學(xué)醫(yī)學(xué)知識講座GRADE（Grading of recommendatiRight methods is crucialType of QuestionSuggested best type of StudyTherapyRCTcohort case control case seriesDiagnosisProspective,

21、 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 analysis23循證醫(yī)學(xué)醫(yī)學(xué)知識講座Right methods is crucialType

22、 oExternal evidences24循證醫(yī)學(xué)醫(yī)學(xué)知識講座External evidences24循證醫(yī)學(xué)醫(yī)學(xué)知識講座 療效的大小療效可信度估計(jì)I類證據(jù)和/或達(dá)成一致意見認(rèn)為某治療/操作是有用/有效的。II類對某治療/操作的有用/有效性存在相互矛盾的證據(jù)或者分歧 III類無效#或III類有害證據(jù)和/或達(dá)成一致意見認(rèn)為某治療/操作的無用/無效，在某些情況下可能有害IIa類證據(jù)和共識贊同有用/有效IIb類證據(jù)和共識對于有用/有效性不那么確定獲益 風(fēng)險(xiǎn)治療/操作應(yīng)該執(zhí)行獲益 風(fēng)險(xiǎn)需要增加更多的證據(jù)應(yīng)用某治療/操作是合理的獲益 風(fēng)險(xiǎn)需要更為廣泛的證據(jù)，注冊資料也是有益的可考慮應(yīng)用某治療/操作風(fēng)險(xiǎn)

23、 獲益不需要更加證據(jù)某治療/操作不應(yīng)使用，因?yàn)闊o益且可能有害A級已有大樣本量研究數(shù)據(jù)來自多個RCT#或者meta分析認(rèn)為治療/操作有用/有效。已有足夠證據(jù)，來自多個RCT或者meta分析支持治療/操作有用/有效。來自多個RCT或者meta分析存在某些矛盾治療/操作的有用/有效性不確定來自多個RCT或者meta分析存在較大的矛盾認(rèn)為某治療/操作無用/無效，某些情況下可能有害已有足夠證據(jù)，來自多個RCT或者meta分析B級較小樣本量的研究數(shù)據(jù)來自單個RCT或者多個非RCT確認(rèn)治療/操作有用/有效。證據(jù)來自單個RCT或者多個非RCT支持治療/操作有用/有效。來自單個RCT或者多個非RCT存在某些矛盾

24、治療/操作的有用/有效性不確定來自單個RCT或者多個非RCT存在較大的矛盾認(rèn)為某治療/操作無用/無效，某些情況下可能有害證據(jù)來自單個RCT或者多個非RCTC級小樣本量的研究僅有專家討論共識，病例報(bào)告，或標(biāo)準(zhǔn)治療確認(rèn)治療/操作有用/有效。證據(jù)來自專家討論共識，病例報(bào)告，或標(biāo)準(zhǔn)治療支持治療/操作有用/有效。存在分歧的專家討論共識，病例報(bào)告，或標(biāo)準(zhǔn)治療治療/操作的有用/有效性不確定存在分歧的專家討論共識，病例報(bào)告，或標(biāo)準(zhǔn)治療認(rèn)為某治療/操作無用/無效，某些情況下可能有害證據(jù)來自專家討論共識，病例報(bào)告，或標(biāo)準(zhǔn)治療建議書寫推薦時使用的語句應(yīng)該/推薦/有指征 有用/有效/有益合理的可能是有用/有效/有益的

25、可能推薦或者有指征可以考慮也許是合理的有用和有效性未知/不明/不確定或者未很好地確認(rèn)III類無效不推薦/無指征/不應(yīng)使用無用/無效/無益/III類有害可能有害/有危害不應(yīng)使用可能增加并發(fā)癥/死亡有效性比較語句$治療/策略A較B更推薦/更有指征選擇治療/策略A優(yōu)于B治療/策略A可能較B更推薦/更有指征選擇治療/策略A可能優(yōu)于BACCF/AHA 指南推薦強(qiáng)度和證據(jù)級別的應(yīng)用25循證醫(yī)學(xué)醫(yī)學(xué)知識講座 療Adequate sample sizePhase III RCT head to head Compare survivalControlSurvival（%）Improved survival a

26、nd sample sized5%10%15%101,290394134151,894544208202,444676328252,92678837426循證醫(yī)學(xué)醫(yī)學(xué)知識講座Adequate sample sizePhase III 科學(xué)引文索引Science Citation Index，SCIImpact factorThis is the mean citation rate of all articles contained in the journalPublished annually in the SCI Journal Citation reportsa quantitativ

27、e measure of the frequency with which the average article published in a given scholarly journal has been cited in a particular year or period; The impact factor is a measure of importance of scientific journals 27循證醫(yī)學(xué)醫(yī)學(xué)知識講座科學(xué)引文索引Science Citation IndeFind Journals查雜志28循證醫(yī)學(xué)醫(yī)學(xué)知識講座Find Journals查雜志28循證醫(yī)

28、學(xué)醫(yī)學(xué)知識講座Find a paper 查論文29循證醫(yī)學(xué)醫(yī)學(xué)知識講座Find a paper 查論文29循證醫(yī)學(xué)醫(yī)學(xué)知識講座Find who cite the paper 查引用30循證醫(yī)學(xué)醫(yī)學(xué)知識講座Find who cite the paper 查引用30循31循證醫(yī)學(xué)醫(yī)學(xué)知識講座31循證醫(yī)學(xué)醫(yī)學(xué)知識講座Cited and quality of study被引/他引與論文的質(zhì)量32循證醫(yī)學(xué)醫(yī)學(xué)知識講座Cited and quality of study被引/33循證醫(yī)學(xué)醫(yī)學(xué)知識講座33循證醫(yī)學(xué)醫(yī)學(xué)知識講座34循證醫(yī)學(xué)醫(yī)學(xué)知識講座34循證醫(yī)學(xué)醫(yī)學(xué)知識講座35循證醫(yī)學(xué)醫(yī)學(xué)知識講座35循證醫(yī)學(xué)

29、醫(yī)學(xué)知識講座Source of Medical InformationPrimaryMEDLINE，CBMSecondaryGuidelines，Cochrane LibMuch more likely (than personal search and critical appraisal) to be trueSaves the clinicians timeTextbookOthers？ConferenceInstitutional or personal experience36循證醫(yī)學(xué)醫(yī)學(xué)知識講座Source of Medical InformationPSource of Medi

30、cal InformationInterest group or organizationCommercial Companys News or BriefGoogle, Yahoo! Open Mind and Be Very Carefully37循證醫(yī)學(xué)醫(yī)學(xué)知識講座Source of Medical InformationIQuick InformationGuidelinesExplicit evidence-basedEvidence-basedResearch-based (highly referenced)Opinion-based“expert consensus”38循證醫(yī)

31、學(xué)醫(yī)學(xué)知識講座Quick InformationGuidelines38循National Guideline Clearinghouse(/)39循證醫(yī)學(xué)醫(yī)學(xué)知識講座National Guideline ClearinghouQuick InformationCochrane Library- The Cochrane CollaborationSystematic reviewsThe current resource with the highest methodological rigorFor each clinical question, all of the English li

32、terature meticulously searched for randomized trialsLarge systematic reviews with valid methods + collaborative effortConclusions are based on all the evidence from valid randomized trials40循證醫(yī)學(xué)醫(yī)學(xué)知識講座Quick InformationCochrane Libr41循證醫(yī)學(xué)醫(yī)學(xué)知識講座41循證醫(yī)學(xué)醫(yī)學(xué)知識講座Cochrane LibraryAdvantagehighest quality evide

33、nce well ever have on the effectiveness of health careDisadvantagenot yet many systemic reviews necessarily omits the newest treatmentStep 242循證醫(yī)學(xué)醫(yī)學(xué)知識講座Cochrane LibraryAdvantageStep PDQ (Physician Data Query)/cancer_information/pdq/43循證醫(yī)學(xué)醫(yī)學(xué)知識講座PDQ (Physician Data Query)43循證循證醫(yī)學(xué)醫(yī)學(xué)知識講座培訓(xùn)課件45循證醫(yī)學(xué)醫(yī)學(xué)知識講座45循證醫(yī)學(xué)醫(yī)學(xué)知識講座PubMed /MEDLINE/Pubmed46循證醫(yī)學(xué)醫(yī)學(xué)知識講座PubMed /MEDLINEhttp:/www.ncbiStep 247循證醫(yī)學(xué)醫(yī)學(xué)知識講座Step 247循證醫(yī)學(xué)醫(yī)學(xué)知識講座St