1、李文欽醫師實證醫學中心主任2013/11/08實證醫學與個案討論實證醫學與個案討論簡報大綱l簡述實證醫學五大步驟l如何問問題及形成PICO的內容l資料搜尋的策略、使用資料庫及 搜尋結果l對資料的評讀l如何落實實證醫學於個案討論過去過去 現在現在 未來未來當一個醫生該具備的的能力三日不讀書，面目可憎三日不讀書，面目可憎醫病照護教學研究 2000年Sackett將實證醫學定義為“整合最佳研究證據、臨床經驗以及病患價值以達成病患最佳治療的過程”實證醫學的實行是一種終身的、自發的、以問題為導向的學習過程實證醫學的重要性臨床經驗臨床經驗病患價值病患價值最佳研究證據最佳研究證據實證醫療實證醫療Sacket
2、t et al 2000實證醫學的五個步驟1.Asking an answerable question (提出可回答的臨床問題提出可回答的臨床問題)2.Tracking down the best evidence (搜尋最佳實證文獻資料搜尋最佳實證文獻資料)3.Critical appraisal (嚴謹的文獻評讀嚴謹的文獻評讀)4.Integrating the appraisal with clinical expertise and patients preference (將臨床專業與病人價值觀相結合將臨床專業與病人價值觀相結合)5.Evaluation the effective
3、ness and efficiency in executing steps 1-4 (評估改善評估改善)A stroke patient who has long term gouty arthritis Does gout cause a higher risk of stoke?痛風會增加中風的風險嗎？找資料來回答問題找資料來回答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAskingEBM的步驟Sir Austin Bradford Hill(1897-1991),English
4、epidemiologist and statisticianHe described the clinical trial as being a CAREFULLY,and ETHICALLY,described experiment with the aim of answering some PRECISELY FRAMED QUESTIONGreater precision is required in the objectives.We need to haveA defined populationDefined endpointsRelatively few question t
5、o be answered.問題要怎麼問？1.形成問題(Clinical Question)Does gout cause a higher risk of stoke?痛風會增加中風的風險嗎？臨床的問題模型(PICO)P:Patient,Population 指此病人或族群的年齡層指此病人或族群的年齡層、體質體質、疾病史疾病史、過去史等過去史等 I:Intervention 指治療指治療、診斷診斷、預後預後、成本效益分析等成本效益分析等，為研究的主題為研究的主題 C:Comparison 指做與不做或不同處置間的比較指做與不做或不同處置間的比較 O:Outcome 指預後或與目前問題有關的比
6、較基準指預後或與目前問題有關的比較基準找資料來回答問題找資料來回答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAskingEBM的步驟PICO 1 Does gout cause a higher risk of stoke?PICO type:TherapyPatient:老年人老年人Intervention:痛風痛風Comparison:無痛風無痛風Outcome:中風的風險中風的風險問題要怎麼問？2.Tracking down the best evidence 直接使用實證醫學資料
7、庫直接使用實證醫學資料庫(secondary databases)如如ACP journal club,Cochrane Library,UpToDate,MD Consult,Practice Guideline 找初步篩選的資料庫找初步篩選的資料庫(primary databases)PubMed,OVID,Proquest 未經篩選的資料庫未經篩選的資料庫如如Google可搜尋實證醫學的資料庫可搜尋實證醫學的資料庫如何尋找與EBM相關的館藏資源？主題切入主題切入本院一般綜合性資料庫本院一般綜合性資料庫 1.PudMed：可查出：可查出abstract 2.Ovid：可查出：可查出abst
8、ract、Fulltext 3.Proquest：可查出：可查出abstract、Fulltext 4.Clinicalkey：可查出：可查出abstract、Fulltext 找實證醫學資料時可加上找實證醫學資料時可加上 Systemic Review(系統性評論系統性評論)、Meta-analysis(整合分析整合分析)、Randomized Controlled Trial(隨機對照臨床試驗研究隨機對照臨床試驗研究)、Controlled Trials 利用資料庫功能鍵利用資料庫功能鍵MeSH to identify every term for example找資料來回答問題找資料來回
9、答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAskingSearching Strategy Finding out The Correct Keywords原始關鍵字原始關鍵字Primary Term 或或MeSH Term 同義字同義字1同義字同義字2P(oror)andI(Goutor Hyperuricemia or)andC(oror)andO(strokeoror)找資料來回答問題找資料來回答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否
10、可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAskingSearching Strategy Finding out The Correct KeywordsKeywords from PICO item:(“gout”OR“hyperuricemia”)AND“stroke”MeSH to identify every term for example找資料來回答問題找資料來回答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAsking善用搜尋 Systematic
11、review關鍵字:(“gout”OR“hyperuricemia”)AND(“stroke”OR“cardiovascular disease”)找資料來回答問題找資料來回答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAskingThe Evidence PyramidV.Animal researchV.In vitro(test tube)researchIV.Case series/ReportsV.Ideas,Editorials,OpinionsIII.Case Control
12、 StudiesII.Cohort studiesI.Randomized Controlled Studies(RCT)I.Randomized Controlled Double Blind Studies Meta-analysis 圖示結果Forest plot*Hierarchy of evidence:arranges study designs by their susceptibility to bias.(Level IV)From:Oxford Center for EBM研究設計研究設計 與與 證據強度證據強度Level Therapy/Prevention,Aetiol
13、ogy/HarmPrognosisDiagnosisDifferential diagnosis/symptom prevalence studyEconomic and decision analyses1aSR(with homogeneity*)of RCTs SR(with homogeneity*)of inception cohort studies;CDR validated in different populationsSR(with homogeneity*)of Level 1 diagnostic studies;CDR with 1b studies from dif
14、ferent clinical centresSR(with homogeneity*)of prospective cohort studies SR(with homogeneity*)of Level 1 economic studies1bIndividual RCT(with narrow Confidence Interval)Individual inception cohort study with 80%follow-up;CDR validated in a single populationValidating*cohort study with good referen
15、ce standards;or CDR tested within one clinical centreProspective cohort study with good follow-up*Analysis based on clinically sensible costs or alternatives;systematic review(s)of the evidence;and including multi-way sensitivity analyses1cAll or noneAll or none case-seriesAbsolute SpPins and SnNout
16、sAll or none case-seriesAbsolute better-value or worse-value analyses 2aSR(with homogeneity*)of cohort studiesSR(with homogeneity*)of either retrospective cohort studies or untreated control groups in RCTsSR(with homogeneity*)of Level 2 diagnostic studiesSR(with homogeneity*)of 2b and better studies
17、SR(with homogeneity*)of Level 2 economic studies2bIndividual cohort study(including low quality RCT;e.g.,80%follow-up;CDR validated in a single populationValidating*cohort study with good reference standards;or CDR tested within one clinical centreProspective cohort study with good follow-up*Analysi
18、s based on clinically sensible costs or alternatives;systematic review(s)of the evidence;and including multi-way sensitivity analyses1cAll or noneAll or none case-seriesAbsolute SpPins and SnNoutsAll or none case-seriesAbsolute better-value or worse-value analyses 2aSR(with homogeneity*)of cohort st
19、udiesSR(with homogeneity*)of either retrospective cohort studies or untreated control groups in RCTsSR(with homogeneity*)of Level 2 diagnostic studiesSR(with homogeneity*)of 2b and better studiesSR(with homogeneity*)of Level 2 economic studies2bIndividual cohort study(including low quality RCT;e.g.,
20、80%follow-up)Retrospective cohort study or follow-up of untreated control patients in an RCT;Derivation of CDR or validated on split-sample onlyExploratory*cohort study with good reference standards;CDR after derivation,or validated only on split-sample or databasesRetrospective cohort study,or poor
21、 follow-upAnalysis based on clinically sensible costs or alternatives;limited review(s)of the evidence,or single studies;and including multi-way sensitivity analyses2cOutcomes Research;Ecological studiesOutcomes Research Ecological studiesAudit or outcomes research3aSR(with homogeneity*)of case-cont
22、rol studiesSR(with homogeneity*)of 3b and better studiesSR(with homogeneity*)of 3b and better studiesSR(with homogeneity*)of 3b and better studies3bIndividual Case-Control StudyNon-consecutive study;or without consistently applied reference standardsNon-consecutive cohort study,or very limited popul
23、ationAnalysis based on limited alternatives or costs,poor quality estimates of data,but including sensitivity analyses incorporating clinically sensible variations.4Case-series(and poor quality cohort and case-control studies)Case-series(and poor quality prognostic cohort studies*)Case-control study
24、,poor or non-independent reference standard Case-series or superseded reference standardsAnalysis with no sensitivity analysis5Expert opinion without explicit critical appraisal,or based on physiology,bench research or first principlesExpert opinion without explicit critical appraisal,or based on ph
25、ysiology,bench research or first principlesExpert opinion without explicit critical appraisal,or based on physiology,bench research or first principlesExpert opinion without explicit critical appraisal,or based on physiology,bench research or first principlesExpert opinion without explicit critical
26、appraisal,or based on economic theory or first principlesOxford Centre for Evidence-based Medicine-Levels of Evidence(March 2009)http:/ Title:-Hyperuricemia and risk of stroke:a systematic review and meta-analysis.(2009)Source:Arthritis Rheum.2009 Jul 15;61(7):885-92 Level:2aLarge epidemiologic stud
27、ies have shown that hyperuricemia is associated with an increased incidence of coronary heart disease(CHD)and increased mortality in those with and without preexisting CHD.Fang J,Alderman MH.Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study,1971-1992.National He
28、alth and Nutrition Examination Survey.JAMA 2000;283:2404.Freedman DS,Williamson DF,Gunter EW,Byers T.Relation of serum uric acid to mortality and ischemic heart disease.The NHANES I Epidemiologic Follow-up Study.Am J Epidemiol 1995;141:637.Brand FN,McGee DL,Kannel WB,et al.Hyperuricemia as a risk fa
29、ctor of coronary heart disease:The Framingham Study.Am J Epidemiol 1985;121:11.Niskanen LK,Laaksonen DE,Nyyssnen K,et al.Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men:a prospective cohort study.Arch Intern Med 2004;164:1546.Choi HK,Curhan G.Independen
30、t impact of gout on mortality and risk for coronary heart disease.Circulation 2007;116:894.Proposed mechanisms for such an increase in risk include the development of hypertension and oxidative stress.Johnson RJ,Segal MS,Srinivas T,et al.Essential hypertension,progressive renal disease,and uric acid
31、:a pathogenetic link?J Am Soc Nephrol 2005;16:1909.Baker JF,Krishnan E,Chen L,Schumacher HR.Serum uric acid and cardiovascular disease:recent developments,and where do they leave us?Am J Med 2005;118:816.It is unclear if hyperuricemia has a causal effect or,as has been more often suggested,is simply
32、 a marker for other risk factors,such as hypertension,dyslipidemia,and diabetes.Culleton BF,Larson MG,Kannel WB,Levy D.Serum uric acid and risk for cardiovascular disease and death:the Framingham Heart Study.Ann Intern Med 1999;131:7.Wannamethee SG,Shaper AG,Whincup PH.Serum urate and the risk of ma
33、jor coronary heart disease events.Heart 1997;78:147.Wheeler JG,Juzwishin KD,Eiriksdottir G,et al.Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls:prospective study and meta-analysis.PLoS Med 2005;2:e76.Feig DI,Kang DH,Johnson RJ.Uric acid and cardiovascular ris
34、k.N Engl J Med 2008;359:1811.文獻評讀三部曲文獻評讀三部曲文獻評讀最主要的三個步驟，即是VIP V：Validity/Reliability;效度/信度我們能相信這篇文章嗎?I：Importance/Impact;重要性我們相信它，但這個結論重要嗎?P：Practice/Applicability;臨床適用性如果我們相信它，這個結論可以應用在我們所照護的病患嗎?找資料來回答問題找資料來回答問題Acquire嚴格評讀文獻嚴格評讀文獻Appraisal是否可應用到病人身上是否可應用到病人身上Apply將病人的問題寫成將病人的問題寫成PICOAskingAccording
35、 to“Sharon E.Straus et al,Evidence-based medicine:how to practice andteach EBM,Elsevier,2005:33-7.“ValidityImportanceApplicabilityResults fromsecondarydatabaseResults fromprimarydatabaseAppraised byexpertsNeeded tobeappraisedResults(NNT)ResultsConsiderpopulationand feasibilityConsiderpopulationand f
36、easibility效度效度(Validity)：可以用：可以用RAM-bo方式審視效度方式審視效度研究族群是否有隨機分配研究族群是否有隨機分配(Randomized)？隨機分配的方法是否適當隨機分配的方法是否適當(Accounted)？結果的衡量結果的衡量(Measurement)，即是否依照即是否依照 盲法盲法(blind)及客觀及客觀(objective)二要素操作二要素操作治療意圖分析治療意圖分析(Intention-to-treat analysis,ITT)隨機試驗的一種分析方法隨機試驗的一種分析方法所有被分配在治療組所有被分配在治療組/對照組的病人無論是否完成該項對照組的病人無論
37、是否完成該項 治療治療/安慰劑都應該被放進治療組安慰劑都應該被放進治療組/對照組對照組(原分派組別原分派組別)中做分析中做分析文獻評讀三部曲文獻評讀三部曲重要性重要性(Importance/Impact)：研究結果是什麼研究結果是什麼?研究結果如何被估計研究結果如何被估計?經過多久的時間經過多久的時間?文獻結果的評估方式：文獻結果的評估方式：勝算比勝算比(odds ratio)代表生物學上的影響。代表生物學上的影響。相對危險相對危險(relative risk)、絕對危險降低度絕對危險降低度(absolute risk reduction)、相對危險降低度相對危險降低度(relative ri
38、sk reduction)、益一需治數益一需治數(NNT,number needed to treat):為預防為預防一個不良結果或使一個病人達實驗所求之有益結果所一個不良結果或使一個病人達實驗所求之有益結果所需治療的病人數需治療的病人數NNT=1/ARR文獻評讀三部曲文獻評讀三部曲可行性可行性(Practical,Applicability?)：臨床實用性如何？：臨床實用性如何？1.應考量病患的生物因素應考量病患的生物因素(biological issues):-同樣的治療應用在不同的病患族群是否有不同反應同樣的治療應用在不同的病患族群是否有不同反應?-我們的病人與研究中的病人是否非常不同，
39、以致無法應用我們的病人與研究中的病人是否非常不同，以致無法應用 在研究結果？在研究結果？2.其他的社會經濟因素其他的社會經濟因素（social and economic issues）的考的考量量:-這個治療適用於我們的診療環境嗎？病患的配合度如何？這個治療適用於我們的診療環境嗎？病患的配合度如何？-醫療提供者的配合度及能力如何？醫療提供者的配合度及能力如何？3.3.流行病學因素流行病學因素(epidemiological issues）的考量）的考量:-我們的病人是否有其他共病狀況，可能改變治療的結果？我們的病人是否有其他共病狀況，可能改變治療的結果？影響有多大？影響有多大？-病人可能從治療
40、中得到什麼好處或壞處？病人可能從治療中得到什麼好處或壞處？-經由治療而減少的不良後果是否比不治療有明顯的差別？經由治療而減少的不良後果是否比不治療有明顯的差別？文獻評讀三部曲文獻評讀三部曲幫助文獻評讀的工具依所搜尋文獻類別依所搜尋文獻類別，評讀所問的問題評讀所問的問題4.將臨床專業與病人價值觀相結合您的病人是否與研究中的病人差別很大，以至於無法適用該研究結果？族群/地域/文化差異您期望您的病人從研究結果中獲得多大的好處？還有哪些替代方案？研究結果適用於您的病人嗎？5.評估執行效果及改善過程您是否開始使用實證手法搜尋最佳證據？您搜尋及評讀證據的速度有多快？您有能力將這些證據應用在適當的病人身上嗎
41、？您是否依循這些新證據來改變您的診療習慣？如何落實實證醫學於個案討論會如何落實實證醫學於個案討論會?如何落實實證醫學於個案討論會1.1.由討論的個案找尋問題由討論的個案找尋問題 (形成形成PICO)2.進行文獻搜尋進行文獻搜尋(PUB Med,Cochrane,Ovid)3.進行文獻評讀進行文獻評讀(Evidence level,Recommend grade)會議中報告文章重點與結論會議中報告文章重點與結論4.4.所搜尋的文獻值得應用到本病人身上嗎所搜尋的文獻值得應用到本病人身上嗎?實證醫學個案討論會順序實證醫學個案討論會順序1.Case report(個案報告個案報告)2.提出問題提出問題
42、，建立建立 PICO格式格式3.文獻搜尋文獻搜尋(所使用關鍵字所使用關鍵字、資料庫資料庫)4.所搜尋到文獻的題目所搜尋到文獻的題目、出處出處、及及文獻文獻 的證據等級的證據等級 5.報告文獻的重點與結論報告文獻的重點與結論6.是否可應用到我們的病人身上是否可應用到我們的病人身上 Clinical question:Does gout cause a higher risk of stoke?PICO type:TherapyPatient:Old patientIntervention:GoutComparison:Without goutOutcome:Risk of stroke Title:Hyperuricemia and risk of stroke:a systematic review and meta-analysis.(2009)Source:Arthritis Rheum.2009 Jul 15;61(7):885-92 Level:2a科別選定與討論頻率1.科別:內、外、婦、兒、皮膚科 藥劑、護理、(檢驗、放射)2.頻率:每月一次3.會議主題設定:實證醫學個案討論會實證醫學個案討論會4.請科部主任定期檢視結果與統計
