1、循证医学医学知识讲座循证医学医学知识讲座Misguide MediaCell or animal modelOnly in the LAB No test in humanMisguide 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）能抑制拓扑异构酶I和拓扑异构酶
2、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 humanBackground Longer life Chronic diseases or malignancy Increasing medical cos
3、ts The patient knows more,and questions more!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 study report published every hour Mor
4、e 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.”Background-False evidenceAnesthesia and Analgesia 2007 IF 2.2142007 Total Cites 15960Background
5、-Inadequate toolsBackground-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 projects were the relevant published data completely in line with our i
6、n-house findings(Fig.1c).-Nature Reviews Drug Discovery 10,712(September 2011)Background Traditional practice Model Clinicians are use convenient sources Factors that influence decision making.Senior doctors Patient request Pharmaceutical representatives recommendation Local expert-based CMEOutdate!
7、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 medicine is the integration of best research evidence with clinical expertise and patie
8、nt values Sackett,D.L.2001Definition 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 insufficient evidence to know for sure,be conservative.And whatever we do,do it right!David EddyDefinitio
9、n 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Clinicians Individual clinical expertise the increasing proficiency and judgement that individual clinicians acquire through clinical experience and clinical practice.Clinicians EBM is a Lifelong learning mod
10、el lifelong,self-directed,problem-based learning EBM propose methods to find and evaluate evidence.EBM converts 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 clinicia
11、ns knowledge base.Bordley,D.RClinicians 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Use 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External e
12、vidences Best available external clinical evidence:clinically relevant research basic sciences of medicine patient-centred research External clinical evidence has a short doubling-time,and both invalidates previously accepted diagnostic tests and treatments and replaces them with new ones that are m
13、ore powerful,more accurate,more efficacious,and saferExternal evidences Is All Evidence Created Equal?Oxford Centre for Evidence-based Medicine Levels of EvidenceThe Evidence PyramidHierarchy of evidence:arranges study designs by their susceptibility to biasPrimary Research Experimental observationa
14、lSecondaryResearchFor quantitative studiesFor qualitative studies No consensus about the relative rigour of different methodsSystematic review双灵固本散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Not all the evidences are the same importanceHollingworth&Jarvik,Radiology 2007;244:31-38GRADE（Grading
15、of recommendations assessment,development and evaluation)推荐分级的评价、制定与评估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 tr
16、ialBModerateFurther research is likely to have an important impact 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 e
17、ffect and is likely to change the estimate.One or more studies with severe limitationsDVery LowAny estimate of effect is very uncertain.Expert opinionNo direct research evidenceOne or more studies with very severe limitationsRight methods is crucialType of QuestionSuggested best type of StudyTherapy
18、RCTcohort 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 standardCostEcon
19、omic analysisExternal evidences 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
20、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
21、。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
22、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Adequate sample sizePhase III RC
23、T head to head Compare survivalPhase III RCT head to head Compare survivalControlSurvival（%）Improved survival and sample sized5%10%15%101,290394134151,894544208202,444676328252,926788374科学引文索引Science Citation Index，SCI Impact factor This is the mean citation rate of all articles contained in the jou
24、rnal Published 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 Find Journals查杂志
25、Find a paper 查论文Find who cite the paper 查引用Cited and quality of study被引/他引与论文的质量Source of Medical Information Primary MEDLINE，CBM Secondary Guidelines，Cochrane Lib Much more likely(than personal search and critical appraisal)to be true Saves the clinicians time Textbook Others？Conference Institution
26、al or personal experienceSource of Medical Information Interest group or organization Commercial Companys News or Brief Google,Yahoo!Open Mind and Be Very CarefullyQuick Information Guidelines Explicit evidence-based Evidence-based Research-based(highly referenced)Opinion-based“expert consensus”Nati
27、onal Guideline Clearinghouse(http:/www.guideline.gov/)Quick Information Cochrane Library-The Cochrane Collaboration Systematic reviews The current resource with the highest methodological rigor For each clinical question,all of the English literature meticulously searched for randomized trials Large
28、 systematic reviews with valid methods+collaborative effort Conclusions are based on all the evidence from valid randomized trialsCochrane Library Advantage highest quality evidence well ever have on the effectiveness of health care Disadvantage not yet many systemic reviews necessarily omits the ne
29、west treatmentStep 2PDQ(Physician Data Query)http:/www.cancer.gov/cancer_information/pdq/Clinical Trial Database Current Controlled Trialshttp:/www.controlled- NIH ClinicalTrials.gov PubMed/MEDLINE http:/www.ncbi.nlm.nih.gov/PubmedStep 2Step 2Step 2Step 2Step 2Medline-PubMedAdvantage exhaustiveness,
30、flexibility of searching journal coverage,currency(on-line versions)widespread availability and supportDisadvantage have to do your own quality filtering putting together good searches is difficult gaps in coverage(medical,geographical and linguistic)Step 2The Patients Individualize 个体化；Compliance 依
31、从性；Informed consent 知情同意 Value Definition 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 insuranceEvidence-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 trials
