1、循证医学医学知识讲循证医学医学知识讲座座Misguide MediaCell or animal modelOnly in the LAB No test in human2循证医学医学知识讲座Misguide Ad.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
2、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 human3循证医学医学知识讲座Background Longer life Chronic diseases or malignancy
3、Increasing medical costs The patient knows more,and questions more!4循证医学医学知识讲座Background To keep up to date in Internal Medicine,I need to read 17 articles a day,365 days a year More studies,more articles,much more information 20,000 RCTs published annually，6000 articles enter Medline monthly 1 stud
4、y report published every hour More 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 your teachers knows which half.”5循证医学医学知识讲座Background-False evidenceAnesthesia and Analgesia 2
5、007 IF 2.2142007 Total Cites 159606循证医学医学知识讲座Background-Inadequate tools7循证医学医学知识讲座Background-Journals&PapersWe received input 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 proje
6、cts were the relevant published data completely in line with our in-house findings(Fig.1c).-Nature Reviews Drug Discovery 10,712(September 2011)8循证医学医学知识讲座Background Traditional practice Model Clinicians are use convenient sources Factors that influence decision making.Senior doctors Patient request
7、 Pharmaceutical representatives recommendation Local expert-based CMEOutdate!9循证医学医学知识讲座Definition Evidence Based Medicine is the conscientious(自觉),explicit(明确),and judicious(审慎)use of current best evidence in making decisions about the care of individual patients.Sackett,D.L.BMJ 1996 Evidence-based
8、 medicine is the integration of best research evidence with clinical expertise and patient values Sackett,D.L.200110循证医学医学知识讲座Definition EBM:A Practical Definition When 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 insuf
9、ficient evidence to know for sure,be conservative.And whatever we do,do it right!David Eddy11循证医学医学知识讲座Definition 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12循证医学医学知识讲座Clinicians Individual clinical expertise the increasing proficiency and judgement th
10、at individual clinicians acquire through clinical experience and clinical practice.13循证医学医学知识讲座Clinicians EBM is a Lifelong learning model lifelong,self-directed,problem-based learning EBM propose methods to find and evaluate evidence.EBM converts the abstract exercise of reading and appraising the
11、literature into the pragmatic process of using the literature to benefit individual patients while simultaneously expanding the clinicians knowledge base.Bordley,D.R14循证医学医学知识讲座Clinicians The basic for EBMThe basic for EBMAuthors证据提供者Users证据应用者Define clinical questions确定医疗问题+Task任务收集/评价/写作论文提供最佳证据Us
12、e evidence正确地应用证据KnowhowClinical training医疗实践+临床流行病学（DME）+Statistics医学统计学+Medical economics卫生经济学+Literature Search+RoleGroup团队Individual个人15循证医学医学知识讲座External evidences Best available external clinical evidence:clinically relevant research basic sciences of medicine patient-centred research External
13、 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 efficacious,and safer16循证医学医学知识讲座External evidences Is All Evidence Created Equal?Oxford Centre for Evidence
14、-based Medicine Levels of Evidence17循证医学医学知识讲座18循证医学医学知识讲座The Evidence PyramidHierarchy of evidence:arranges study designs by their susceptibility to biasPrimary Research Experimental observationalSecondaryResearchFor quantitative studiesFor qualitative studies No consensus about the relative rigour
15、 of different methodsSystematic review双灵固本散19循证医学医学知识讲座 Clinical trial and real world 临床试验中认为是有效可能在真实世界中无效20循证医学医学知识讲座Not all the evidences are the same importanceHollingworth&Jarvik,Radiology 2007;244:31-3821循证医学医学知识讲座GRADE（Grading of recommendations assessment,development and evaluation)推荐分级的评价、制定
16、与评估CodeQuality of EvidenceDefinitionAHighFurther 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
17、on our confidence in the estimate 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
18、 severe limitationsDVery LowAny estimate of effect is very uncertain.Expert opinionNo direct research evidenceOne or more studies with very severe limitations22循证医学医学知识讲座Right methods is crucialType of QuestionSuggested best type of StudyTherapyRCTcohort case control case seriesDiagnosisProspective,
19、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循证医学医学知识讲座External evidences24循证医学医学知识讲座
20、 疗效疗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用某治疗应用某治疗/操作是合操作是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考虑应用某治疗可考虑应用某治疗/操操作作风险风险 获
21、益获益不需要更加证据某治疗某治疗/操作不应使用操作不应使用，因为无益且可能有，因为无益且可能有害害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。
22、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，或标准治疗建议书写推荐时使用的建议书写推荐时使用的语句语
23、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可能可能较B更推荐/更有指征选择治疗/策略A可能可能优于BACCF/AHA 指南推荐强度和证据级别的应用25循证医学医学知识讲座Adequate sample sizePhase III RCT head to head Comp
24、are survivalPhase III RCT head to head Compare survivalControlSurvival（%）Improved survival and sample sized5%10%15%101,290394134151,894544208202,444676328252,92678837426循证医学医学知识讲座科学引文索引Science Citation Index，SCI Impact factor This is the mean citation rate of all articles contained in the journal Pu
25、blished annually in the SCI Journal Citation reports a quantitative 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循证医学医学知识讲座Find Journa
26、ls查杂志28循证医学医学知识讲座Find a paper 查论文29循证医学医学知识讲座Find who cite the paper 查引用30循证医学医学知识讲座31循证医学医学知识讲座Cited and quality of study被引/他引与论文的质量32循证医学医学知识讲座33循证医学医学知识讲座34循证医学医学知识讲座35循证医学医学知识讲座Source of Medical Information Primary MEDLINE，CBM Secondary Guidelines，Cochrane Lib Much more likely(than personal sear
27、ch and critical appraisal)to be true Saves the clinicians time Textbook Others？Conference Institutional or personal experience36循证医学医学知识讲座Source of Medical Information Interest group or organization Commercial Companys News or Brief Google,Yahoo!Open Mind and Be Very Carefully37循证医学医学知识讲座Quick Infor
28、mation Guidelines Explicit evidence-based Evidence-based Research-based(highly referenced)Opinion-based“expert consensus”38循证医学医学知识讲座National Guideline Clearinghouse(http:/www.guideline.gov/)39循证医学医学知识讲座Quick Information Cochrane Library-The Cochrane Collaboration Systematic reviews The current reso
29、urce with the highest methodological rigor For each clinical question,all of the English literature meticulously searched for randomized trials Large systematic reviews with valid methods+collaborative effort Conclusions are based on all the evidence from valid randomized trials40循证医学医学知识讲座41循证医学医学知
30、识讲座Cochrane Library Advantage highest quality evidence well ever have on the effectiveness of health care Disadvantage not yet many systemic reviews necessarily omits the newest treatmentStep 242循证医学医学知识讲座PDQ(Physician Data Query)http:/www.cancer.gov/cancer_information/pdq/43循证医学医学知识讲座45循证医学医学知识讲座Pu
31、bMed/MEDLINE http:/www.ncbi.nlm.nih.gov/Pubmed46循证医学医学知识讲座Step 247循证医学医学知识讲座Step 248循证医学医学知识讲座Step 249循证医学医学知识讲座Step 250循证医学医学知识讲座Step 251循证医学医学知识讲座52循证医学医学知识讲座53循证医学医学知识讲座54循证医学医学知识讲座Medline-PubMedAdvantage exhaustiveness,flexibility of searching journal coverage,currency(on-line versions)widesprea
32、d availability and supportDisadvantage have to do your own quality filtering putting together good searches is difficult gaps in coverage(medical,geographical and linguistic)Step 255循证医学医学知识讲座The Patients Individualize 个体化；Compliance 依从性；Informed consent 知情同意 Value 56循证医学医学知识讲座Definition Clinical ex
33、pertise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 insurance57循证医学医学知识讲座Evidence-based Medicine Bases action on best evidence synthesis Good doctors use both individual clinical expertise and the best available external evidence,and neither alone is enough.EBM is not restricted to randomised trials58循证医学医学知识讲座
