1、Medical Education in the New Century醫(yī)學(xué)人文教育BioinformaticsPatient-centered careProblem-based learningEvidence-based medicineMedical Education in the New C實(shí)證醫(yī)學(xué) (EBM, Evidence-based Medicine)以流行病學(xué)和統(tǒng)計(jì)學(xué)的方法，從龐大的醫(yī)學(xué)資料庫中嚴(yán)格評(píng)讀、綜合分析並找出值得信賴的部分，並將所能獲得的最佳文獻(xiàn)證據(jù)，應(yīng)用於臨床工作中，使病人得到最佳的照顧。實(shí)證醫(yī)學(xué) (EBM, Evidence-based Med實(shí)證醫(yī)學(xué)沿革1

2、972年英國臨床流行病學(xué)者Archie Cochrane提出實(shí)證醫(yī)學(xué)的概念。 所有醫(yī)療行為都應(yīng)有嚴(yán)謹(jǐn)研究且證實(shí)為有效的根據(jù)，才能將醫(yī)療資源做最有效的運(yùn)用，並強(qiáng)調(diào) Randomized controlled trials 的重要性。1992英國國家衛(wèi)生部成立實(shí)證醫(yī)學(xué)中心，並以Archie Cochrane之名命名，進(jìn)而促使1993年Cochrane Collaboration的設(shè)立。(Iain Chalmers, David Sackett)Lancet 曾把Cochrane Collaboration比作臨床醫(yī)學(xué)的人類基因組計(jì)劃實(shí)證醫(yī)學(xué)沿革1972年英國臨床流行病學(xué)者Archie CocDr.

3、 Sydney Burwell, Dean of Harvard Medical SchoolHalf of what you are taught as medical students will in ten years have been shown to be wrong. And the trouble is, none of your teachers knows which half.Dr. Sydney Burwell, Dean of H Use of current best evidence in making decisions about the care of in

4、dividual patients Not only a skill but also an attitude change Conscientious, explicit, and judicious use of current best evidence in making decisions about individual patients. Archie Cochrane 1972E B M Use of current best evidence實(shí)證醫(yī)學(xué)的實(shí)施醫(yī)師在處置病人所面臨的問題時(shí)有許多不確定性，這種不確定性常以機(jī)率來表示。機(jī)率的估計(jì)，可以來自個(gè)人的經(jīng)驗(yàn)，但是免不了有某種程

5、度的偏差，因此我們必須借重客觀可信的臨床研究結(jié)果，來作為照顧病人的主要依據(jù)。實(shí)證醫(yī)學(xué)是兼具科學(xué)方法，及人文特質(zhì)的診療模式，且以病人為中心，以問題為導(dǎo)向的精神，正確的應(yīng)用可以提昇整體的醫(yī)療品質(zhì)。隨著資訊科技的發(fā)展，醫(yī)師與病人可以很容易的從公正、可靠的資訊中獲得以實(shí)證為基礎(chǔ)的相關(guān)訊息。為了要跟得上醫(yī)學(xué)最新的腳步及病人被告知的權(quán)利，提供高品質(zhì)的醫(yī)療照護(hù)，實(shí)證醫(yī)學(xué)應(yīng)為醫(yī)學(xué)教育的核心原則。實(shí)證醫(yī)學(xué)的實(shí)施醫(yī)師在處置病人所面臨的問題時(shí)有許多不確定性，這進(jìn)階學(xué)習(xí)目前國外推動(dòng)實(shí)證醫(yī)學(xué)著名的單位加拿大McMaster University的HIRU（Health Information Research Unit

6、）是Cochrane Collaboration的重鎮(zhèn) http:/hiru.mcmaster.ca/ 英國Oxford University的 Centre for Evidence-Based Medicinehttp:/cemb.jr2.ox.ac.uk 美國American College of Physician（ACP），在全球資訊網(wǎng)出版 ACP Journal Club Online 進(jìn)階學(xué)習(xí)目前國外推動(dòng)實(shí)證醫(yī)學(xué)著名的單位加拿大McMastStep 1. Converting the need for information (about prevention, diagnosi

7、s, prognosis, therapy, causation, etc.) into an answerable question.Step 2. Searching the best evidence with which to answer that question.Step 3. Critically appraising the evidence for its validity (closeness to the truth), impact (size of the effect), and applicability (usefulness in our clinical

8、practice).Step 4. Integrating the evidence with our clinical expertise and patients unique biology, values and circumstances.Step 5. Evaluating our effectiveness and efficiency in executing steps 1-4 and seeking ways to improve them both for next time.實(shí)證醫(yī)學(xué)的五大進(jìn)行步驟Five Steps to Practice EBM Step 1. Co

9、nverting the need fThe Evidence PyramidAnimal researchIn vitro (test tube) researchCase series/ReportsIdeas, Editorials, OpinionsCase Control StudiesCohort studiesRandomized Controlled StudiesRandomized Controlled Double Blind Studies Meta - analysisThe Evidence PyramidAnimal res實(shí)證醫(yī)學(xué)的五個(gè)進(jìn)行步驟由個(gè)案的臨床資料尋

10、找能解答、且具體的臨床問題。asking an answerable question尋找相關(guān)的醫(yī)學(xué)證據(jù)包括各種文獻(xiàn)及醫(yī)學(xué)資料庫，發(fā)表及未發(fā)表的研究成果。searching the best evidence評(píng)估各種醫(yī)學(xué)報(bào)告的可信度及臨床相關(guān)性，並作成結(jié)論。critical appraisal the evidence將結(jié)論應(yīng)用於實(shí)際患者的治療。臨床應(yīng)用評(píng)估治療的效果。evaluation 實(shí)證醫(yī)學(xué)的五個(gè)進(jìn)行步驟由個(gè)案的臨床資料尋找能解答、且具體的臨Asking Answerable Clinical QuestionsWell-built clinical question“Backgrou

11、nd” questionAsk general knowledge about a disorderHave two essential components:A question root (who, what, why, when) with a verbA disorder, or an aspect of a disorder“Foreground” questionAsk for specific knowledge about managing patients with a disorderHave four (or three) essential components:1.

12、Patient and/or problem2. Intervention (treatment)3. Comparison intervention4. Clinical outcomes Asking Answerable Clinical QuePatient Who is the patient or what is the problem being addressed?Intervention What is the intervention?Comparison What are the alternatives?Outcome What are the outcomes?The

13、re are four elements of a well-formulated questionPatient Who is the patient oSearching The Best Evidence尋找最佳實(shí)證資料一是研究論文資料庫(primary journals or databases) 如 Medline, NEJM, Lancet或是直接使用實(shí)證醫(yī)學(xué)資料庫 (secondary journals or databases) ACP journal club, Cochrane.盡量搜尋與病人問題相同且證據(jù)等級(jí)(level of evidence) 較高之文獻(xiàn)，再謹(jǐn)慎的評(píng)讀

14、與評(píng)估其在此人問題的適用性。Searching The Best Evidence尋找實(shí)證醫(yī)學(xué)資料庫查詢的優(yōu)點(diǎn)文獻(xiàn)資料可經(jīng)由網(wǎng)路快速查詢，最新的醫(yī)學(xué)進(jìn)展可以立即見於網(wǎng)路，比傳統(tǒng)教科書更update。以實(shí)證醫(yī)學(xué)特有的文獻(xiàn)格式，表達(dá)資料取得方法及重要結(jié)果，醫(yī)師不須花很多時(shí)間便能了解其要旨，與長篇大論的傳統(tǒng)文獻(xiàn)不同。利用這些資源，醫(yī)師可以節(jié)省閱讀大量文獻(xiàn)的時(shí)間。實(shí)證醫(yī)學(xué)臨床流行病學(xué)醫(yī)學(xué)資訊學(xué)團(tuán)隊(duì)合作實(shí)證醫(yī)學(xué)資料庫查詢的優(yōu)點(diǎn)文獻(xiàn)資料可經(jīng)由網(wǎng)路快速查詢，最新的醫(yī)實(shí)證醫(yī)學(xué)主要的四個(gè)資料庫 ACP Journal Club: 含括ACP Journal Club（American College of Ph

15、ysicians， 美國內(nèi)科醫(yī)師學(xué)會(huì)出版）與Evidence-Based Medicine（ACP 與 British Medical Journal Group合作出版）兩種出版品，每月至少過濾50種以上之核心期刊，搜尋最佳之原始與評(píng)論性文章，結(jié)構(gòu)化整理摘要出其中重要實(shí)證所得。DARE: Database of Abstracts of Reviews of Effectiveness 收錄評(píng)論性文章的全文型資料庫，由 National Health Services Centre for Reviews and Dissemination（NHS CRD）組織出版， 此一組織針對(duì)部份經(jīng)過評(píng)

16、估、挑選有學(xué)術(shù)價(jià)值的醫(yī)學(xué)期刊中選出系統(tǒng)性評(píng)論的文章，並將之集合而成 DARE。CDSR：Cochrane Database of Systematic Reviews 為Cochrane 合作研究機(jī)構(gòu)（ Cochrane Collaboration）所出版， 其為一個(gè)人與機(jī)構(gòu)共同組成之國際性網(wǎng)路組織，有系統(tǒng)的研究上百種期刊文獻(xiàn)，專門從事有系統(tǒng)的評(píng)論儲(chǔ)備、維護(hù)和傳遞影響醫(yī)療保健相關(guān)之業(yè)務(wù)主題性評(píng)論。 CCTR：Cochrane Central Register of Controlled Trials 超過 300,000筆有關(guān)健康保健的控制實(shí)驗(yàn)樣品參考型書目資料，內(nèi)容包括 RCTRandomi

17、zed Controlled Trials及 CCT Clinical Controlled Trials 。由 Cochrane groups 及其單位組織將 Medline 及 EMBASE 檢索出來的隨機(jī)樣品文獻(xiàn)登記集中而成。 實(shí)證醫(yī)學(xué)主要的四個(gè)資料庫 本院EBM資料庫比較ACP Journal ClubDARECDSRCCTR出版者美國內(nèi)科醫(yī)師學(xué)會(huì)出版NHS CRDCochrane Cochrane資料來源每月至少過濾 50種以上之核心期刊，例：NEJM、JAMA、Lancet、Circulation.等經(jīng)過評(píng)估、挑選有學(xué)術(shù)價(jià)值的醫(yī)學(xué)期刊、Medline、CINAL、Biosis、ER

18、IC、PsycINFO、上百種期刊文獻(xiàn) Medline、EMBASE、其他電子資料庫資料庫類型全文型全文型全文型書目型本院EBM資料庫比較ACP Journal ClubDARE實(shí)證醫(yī)學(xué)的參考書籍實(shí)證醫(yī)學(xué)的參考書籍循證醫(yī)學(xué)EBM的過去現(xiàn)在與未來常用實(shí)證醫(yī)學(xué)網(wǎng)路連結(jié)CGMH長庚醫(yī)院圖書館資料庫 PubMed: /PubMed/1. ACP Journal Club: / (1-4, 7項(xiàng)需由圖書館進(jìn)入)2. Cochrane DARE (Database of Abstracts of Reviews of Effects)3.CDSR (Cochrane Database of Systema

19、tic Reviews) Collaborative Review Groups /cochrane/revabstr/crgindex.htm 4.CCTR (Cochrane Central Register of Controlled Trials): 5.Cochrane collaberation 介紹6.NGC (National Guideline Clearinghouse): 7.Micromedex (CCIS) 為毒物、藥學(xué)及急診醫(yī)學(xué)專業(yè)之全文資料庫，每季更新 8.Centre for Evidence-Based Medicine: / = http:/cemb.jr2

20、.ox.ac.uk 9.加拿大McMaster University的HIRU（Health Information Research Unit）是Cochrane Collaboration的重鎮(zhèn): http:/hiru.mcmaster.ca/10. 美國的 American College of Physician（ACP）: 11.Bandolier: = http:/www.jr2.ox.ac.uk/bandolier/12.AHRQ website: http/13.InfoPOEMs: 14.Other resources: .tw/ / /15.彰化基督教醫(yī)院證據(jù)醫(yī)學(xué)中心 16

21、.萬芳醫(yī)院實(shí)證醫(yī)學(xué)中心17.醫(yī)藥衛(wèi)生研究資訊網(wǎng) (HINT): .tw 以上建議由部門版面直接連結(jié)較快常用實(shí)證醫(yī)學(xué)網(wǎng)路連結(jié)CGMH長庚醫(yī)院圖書館資料庫 PubThe Evidence PyramidAnimal researchIn vitro (test tube) researchCase series/ReportsIdeas, Editorials, OpinionsCase Control StudiesCohort studiesRandomized Controlled StudiesRandomized Controlled Double Blind Studies Meta

22、- analysisThe Evidence PyramidAnimal resGrade of RecommendationLevel of EvidenceTherapyA1aSystemic review of RCTs1bSingle RCT1cAll-or-noneB2aSystemic review of cohort studies2bCohort study or poor RCT2cOutcomes research3aSystemic review of case-control studies3bCase-control studyC4Case seriesD5Exper

23、t opinion, physiology, bench researchGrade of RecommendationLevel o統(tǒng)計(jì)數(shù)字會(huì)說話評(píng)估時(shí)以具體的數(shù)字呈現(xiàn)結(jié)果敏感度（sensitivity）、特異度（specificity）、概似比（likelihood ratio）、檢測(cè)前機(jī)率（pre-test probability）、檢測(cè)後機(jī)率（post-test probability）ARR (Absolute risk reduction) = EER (Experimental Event Rate) - CER (Control Event Rate)、 Number need

24、ed to treat, NNT=1/ARR （增加一位病患得到某種處置好處所需的治療病人數(shù)）、相對(duì)危險(xiǎn)度減少百分比（relative risk reduction，RRR）絕對(duì)危險(xiǎn)度增加百分比（absolute risk increase，ARI）= EER (Experimental Event Rate) - CER (Control Event Rate)、Number needed to harm, NNH=1/ARI（增加一位受試者罹患某種醫(yī)源性傷害的治療病人數(shù)）相對(duì)危險(xiǎn) (Relative risk)、勝算 (Odds)、勝算比 (Odds ratio) 、信賴區(qū)間(confid

25、ence interval)統(tǒng)計(jì)數(shù)字會(huì)說話評(píng)估時(shí)以具體的數(shù)字呈現(xiàn)結(jié)果敏感度（sensDiagnosisDiagnostic test (ferritin)Disease (IDA)PresentAbsentPositive731 ab 270Negative 78 cd 1500Sensitivity = a/a+c = 731/809 = 90%Specificity= d/b+d = 1500/1770 = 85%Positive predictive value = a/a+b = 731/1001 = 73%Negative predictive value = d/c+d = 150

26、0/1578 = 95%LR+for a positive result = sens/(1- spec) = 90%/15% = 6LR- for a negative result = (1-sens)/spec = 10%/85% = 0.12Pre-test probability (prevalence)= a+c/a+b+c+d= 31%Pre-test odds = prevalence/(1-prevalence) = 31%/69% = 0.45Post-test odds = Pre-test odds Likelihood RatioPost-test probabili

27、ty= Post-test odds/(Post-test odds + 1)DiagnosisDiagnostic testDiseasCalculation of OR/RRTreatmentEventPositiveNegativeExposed (experimental)A = 1B = 29Not exposed(control)C = 9D = 21EER = a/a+b = 0.033CER = c/c+d = 0.30Relative risk= EER/CER = (a/a+b)/(c/c+d) = 0.11Experimental event Odds = a/b = 0

28、.034Control event Odds = c/d = 0.43Relative Odds = Odds ratio= (a/b)/(c/d) = ad/bc = 0.08Odd: a ratio of non-events to eventsCalculation of OR/RRTreatmentEAsking Answerable Clinical QuestionPatient/ProblemInsulin-dependent diabeticsInterventionIntensive insulin regimenComparisonRegular insulin regim

29、enOutcomesRetinopathySymptomatic hypoglycemiaAsking Answerable Clinical QueTreatment EffectsOccurrence of diabetic retinopathy at 5 years among insulin-dependent diabetic in the DCCT trialUsual insulin regimen (CER: control event rate): 38%Intensive insulin regimen (EER: experimental event rate): 13

30、% Risk Reduction (calculation)Absolute risk reduction (ARR) = CER-EER = 38%-13% = 25%Relative risk reduction (RRR) = CER-EER/CER = 25%/38% =66%Number needed to treat (NNT) = 1/ARR = 1/25% = 4 patientsThe number of patients that need to be treated to prevent one bad outcome or get one good outcome.Tr

31、eatment EffectsOccurrence ofHarmThe proportion of patients with at least one episode of symptomatic hypoglycemia Usual insulin regimen (CER: control event rate): 23%Intensive insulin regimen (EER: experimental event rate): 57% Risk Increase (calculation)Absolute risk increase (ARI) = EER - CER = 57%

32、 - 23% = 34% Relative risk increase (RRI) = EERCER/CER = 57% - 23%/23% = 148%Number needed to harm (NNH)=1/ARI = 1/0.34= 3 patients (取整數(shù))The number of patients that need to be treated to cause one bad outcome (being harmed)HarmThe proportion of patientsTreatment of Class III-IV Lupus NephritisMeta-A

33、nalysisTreatment of diffuse proliferative lupus nephritis: A meta-analysis of randomized controlled trialsAm J Kidney Dis. 2004 Feb;43(2):197-208.Cochrane Renal Group Cochrane Database of Systematic Reviews. 1, 2004.Treatment of Class III-IV Lupu循證醫(yī)學(xué)EBM的過去現(xiàn)在與未來Values of RR less than 1 indicate a red

34、uction in risk for the outcome with the experimental treatment. Conversely, values of RR more than 1 indicate an increase in risk. The 95% CIs are a measure of variability in the precision of the RR estimate and its statistical significance. Heterogeneity of treatment effects between studies was inv

35、estigated by visual examination of graphic meta-analysis plots and from the Cochran Q (heterogeneity chi-square) and I2 statistic.This is a forest plot, with a vertical line at 1.0 representing equivalence in risk for an outcome with experimental and control treatment (null hypothesis). The RR for e

36、ach outcome and its 95% CI are indicated by a solid square and a line. The size of the solid square represents the contribution (weight) of the trial to the analysis. Diamond-shaped symbols represent the summary estimator of overall effect pooling the weighted effect of individual RCTs. Values of RR

37、 less than 1 indic循證醫(yī)學(xué)EBM的過去現(xiàn)在與未來循證醫(yī)學(xué)EBM的過去現(xiàn)在與未來實(shí)證醫(yī)學(xué)發(fā)展的重點(diǎn)實(shí)證醫(yī)學(xué)發(fā)展的重點(diǎn)，主要有四大範(fàn)疇： 增進(jìn)醫(yī)療決策技能 medical decision making technique 改善醫(yī)療資訊擷取技能 accessing medical information 嚴(yán)格評(píng)估醫(yī)療資訊及其臨床應(yīng)用 assessing the validity of medical information 促進(jìn)專家間之合作，以作隨機(jī)對(duì)照試驗(yàn) (RCT randomized controlled trials) 的研究 應(yīng)用最佳實(shí)證文獻(xiàn)，訂出臨床疾病診療的guid

38、eline，並促進(jìn)clinical pathway形成。實(shí)證醫(yī)學(xué)發(fā)展的重點(diǎn)實(shí)證醫(yī)學(xué)發(fā)展的重點(diǎn)，主要有四大範(fàn)疇：應(yīng)用最醫(yī)療資源有限，對(duì)醫(yī)療資源的合理運(yùn)用，必須利用現(xiàn)有的證據(jù)，及使用標(biāo)準(zhǔn)化的規(guī)範(fàn)及流程。大量的醫(yī)學(xué)知識(shí)文獻(xiàn)，使醫(yī)療提供者(health care-provider)無法消化這些知識(shí)。因此在實(shí)驗(yàn)室或臨床研究獲得的知識(shí)，與一般醫(yī)師真正日常行醫(yī)行為之應(yīng)用之間產(chǎn)生不一致的現(xiàn)象。透過各種疾病的臨床診療指引(clinical practice guideline)，使醫(yī)療不一致性減低，以提高醫(yī)療品質(zhì)。 Clinical Practice Guidelines醫(yī)院評(píng)鑑暨醫(yī)療品質(zhì)策進(jìn)會(huì) 中央健保局 實(shí)證醫(yī)學(xué)會(huì) 國家衛(wèi)生研究院醫(yī)療資源有限，對(duì)醫(yī)療資源的合理運(yùn)用，必須利用現(xiàn)有的證據(jù)，及使Resource Centers for GuidelinesNGC - National Guideline ClearinghouseAGREE - appraisal of guideline research & evaluation/Guidelines Intern