实证医学之经验谈

1、Evidence-Based Medicine (EBM)實證醫學之經驗談顏鴻章Institute of Emergency and Critical Care MedicineDepartment of Emergency MedicineTaipei-Veterans General HospitalNational Yang-Ming UniversityWhat is Evidence-Based Medicine (EBM) ? nEvidence-based medicine (EBM) requires the integration of the best research e

2、vidence with our clinical expertise and our patients unique values and circumstances. By best research evidence By clinical expertise By patient values By patient circumstancesEvidence-Based Medicine (EBM)n是整合目前臨床上最好的研究結果與配合醫師專業能力，針對病患問題在各種不同的臨床環境與個人價值下， 做最適當的診治模式。How do We Actually Practice EBM?nSt

3、ep 1: converting the need for information (about prevention, diagnosis, prognosis, therapy, causation, etc.) into an answerable question.nStep 2: tracking down the best evidence with which to answer that question.nStep 3: critically appraising that evidence for its validity (closeness to the truth),

4、 impact (size of the effect), and applicability (usefulness in our clinical practice).nStep 4: integrating the critical appraisal with our clinical expertise and with our patients unique biology, values, and circumstances.nStep 5: evaluating our effectiveness and efficiency in executing steps 14 and

5、 seeking ways to improve them both for next time.Incorporating EBM into Inpatient RoundsnAdmission rounds (after every period on call, all over the hospital, by post-call team and consultantnMorning report (every day, sitting down, by entire medical service)nWork rounds (every day, on one or several

6、 wards, by trainees)nConsultant walking rounds (1-3 times a week, one or several wards, by trainees and consultantIncorporating EBM into Inpatient RoundsnReview rounds (or “card-flip”) (every day, sitting down and at the bedside, by trainees and consultants)nSocial issues rounds (periodically, by tr

7、ainees and a host of other professionals)nPreceptor rounds (“pure education”) (1-2 times a week, by learners (often stratified) and teacher)n“Down-time” or “dead space” during any roundIncorporating EBM into Inpatient RoundsIncorporating EBM into Inpatient RoundsCan Synopses of Evidence Really Get T

8、here That Fast?nSeveral formats including Structured synopses on paper in a binder (“big red book”, “medicine consult notebook”) Notebook computer carried by cart Portable text book format (e.g. Clinical Evidence or Evidence Based Acute Medicine), PDA with concise summariesnInstant electronic access

9、 PubMed, Cochrane Reviews, ACP Journal Club Online, Evidence-Based On Call, and Clinical Evidence, for both PCs and PDAs. 實證醫學教學三種方式n臨床個案模式的實證演練n以證據模式來教導臨床醫學n教導特定實證醫學的技巧臨床個案模式的實證演練 n使用臨床證據於病患照顧上。n以實際照顧病患個案來教學。n如何整合證據作為臨床判斷的過程。n舉例： 一位住院病患有上肢深度靜脈曲張；問題：你知道這樣的病人具有哪些潛在性疾病？比例為何？診斷流程表為何？ 以證據模式來教導臨床醫學 n使用臨床

10、證據於病患照顧上的學習模式。n將實證醫學觀念與其他的臨床知識結合，用於教學上。n整合實證醫學與其他臨床醫學知識後用於病患身上結果的評核。n舉例： (1) 當你聽到病患的心音有S3 gallop時，你診斷他具有心臟衰竭的正確性為何？(2) 一位下腹疼痛的病患到急診就診後，你的診斷懷疑是急性闌尾炎；問題：你知道這樣的疾病常發生在年輕或老年人？比例為何？你知道有Alvarado score嗎？如何使用？可以不開刀僅使用抗生素就可以？ 教導特定實證醫學的技巧 n如何簡潔的瞭解與使用證據。n以教練的方式來教學。n實際演練實證醫學五大步驟 (如何詢問問題？如何尋找資料？如何評核證據？如何應用證據？如何評估

11、應用這些資料於臨床執業過程的正確性、實用性與可行性。n舉例：當我們在學習照顧一位新診斷卵巢癌的病患時，你在臨床上應該如何結合臨床知識佐以實證醫學觀念去面對她？Asking QuestionsnExercise: study designs What is the question (PICO) of the study? What is the purpose of the study? Intervention Frequency (incidence or prevalence) Diagnostic accuracy Prognosis (or natural history) Aeti

12、ology and risk factors Which study type would give the highest quality evidence to answer the question? (level of evidence) Which is the best study type that is also feasible? What is the study type used?Formulate an Answerable QuestionnExampleStockings for long flights?A 43 year old male asked for

13、some repeat prescriptions and advice about preventing deep vein thrombosis on a 12 hour flight (his brother had had one last year). You suggest stockings as the most effective prevention.QuestionnPatient or Population: _In patients on long flights_nIntervention or Indicator: _do compression stocking

14、s_nComparator:_no compression stockings_nOutcome:_prevent deep vein thrombosis (DVT)_nQuestion sentence: In patients on long flights (P), do compression stockings (I) prevent DVT (O)?Library Searching SessionnUsing PubMed as an example: Go to and select Clinical Queries Select the app

15、ropriate Category (usually “therapy” which is the default) Type in the most crucial single element of your PICO search (usually the I or the P) If your search returns no articles then click the “Broad” scope If your search returns more than 30 articles then try adding more PICO elements, e.g, if you

16、 used only the “I” now try searching the I and P Select the best single article and record why you choose the article you did.Critical Appraisal of a Therapy StudynYou are seeing a 48 year old man who has just recovered from idiopathic pericarditis and he is asking about the chance of recurrence and

17、 whether he can do anything to prevent it. You recall hearing something about a new trial recently, but cant remember the details.Critical Appraisal of a Therapy StudynDecide what question (PICO) the study asked and answerednWhether the internal validity of the study is sufficient to allow firm conc

18、lusions (all studies have some flaws; but are these flaws sufficient to discard the study?)Critical Appraisal of a Therapy StudynIf the study is sufficiently valid, look at and interpret the resultswhat is the relevance or size of the effects of the intervention? What is the Relative Risk Reduction

19、(RRR) and Absolute Risk Reduction (ARR)?nDecide whether and how the results would apply to our patient above. Then role play explaining the condition and treatment to a patient using the following steps: The prognosis, ie. Chance of recurrence The impact of treatment on thisCritically Appraised Topi

20、c Presentation TemplatenGive a description of the clinical situation and the clinical question you need to answer.Question (PICO):nGive your search strategy including: (a) database used, (b) search terms used, and (c) number of papers identified, and (d) why did you choose the particular article? Cr

21、itically Appraised Topic Presentation TemplatenWhat was the question of the study? Appraise the validity of the study.nWhat were the results of the study?nState how the study applies to the patient you identified. CLINICAL SCENARIOnA 1-year-old boy is seen in our office due to cough with sputum and

22、mild short of breath (SOB) for 1 day. He was relative normal before. This time, he had the symptoms of cough and SOB with mild wheezs on occasion. Fever with up to 38.3 0C was noted. The physical examination revealed increase using of respiratory accessory muscle, and high-pitch wheez over bilateral

23、 basal lungs. The laboratory examination revealed mild leukocytosis and CXR showed increased infiltration over both basal lung field. Critically Appraised Topic Presentation Example1.The patient & clinical questionA 1 year old boy with first-time bronchiolitis visits our OPD. You may suggest that br

24、onchodilators can produce small short-term improvements in clinical score and oxygenation. Question (PICO): In infants with bronchiolitis (P), do bronchodilator (I) provide benefits in clinical improvement (O)?Critically Appraised Topic Presentation Example2.Search strategya)PubMed: Clinical queries

25、 (with therapy filters)b)Bronchiolitis AND bronchodilatorc)72 papers included 1 Cochrane Database Systemic Rev. 2006, Jul.d)A review article included 22 clinical trial and 1428 infants. Critically Appraised Topic Presentation Example3.The studythe question and appraisalStudy Question: In infants wit

26、h bronchiolitis, do bronchodilator provide more benefits in clinical improvement than placebo?Critically Appraised Topic Presentation Example3.The studythe question and appraisalRandomisation: All were randomized, double-blind, placebo control trials.Ascertainment: Multiple RCTs analyzed in this met

27、a-analysis review; this is adequate.Measurement: double-blind in treatment design through evaluation by clinical score, oxygenation, rate of hospital admission, duration of hospitalization.Critically Appraised Topic Presentation ExampleResults nTwenty-two clinical trials with 1428 infants with bronc

28、hiolitis were included in this review. nIn eight trials, with 468 infants, there was no improvement in clinical score for 43% of those treated with bronchodilators compared to 57% of those treated with placebo (odds ratio (OR) for no improvement 0.45, 95% confidence interval (CI) 0.15 to 1.29). nThe

29、re was a statistically significant but clinically modest improvement in the overall average clinical score (standardized mean difference (SMD) -0.48, 95% CI -0.62 to -0.33). Critically Appraised Topic Presentation ExampleResults nThere was no statistically significant improvement in oxygenation over

30、all (weighted mean difference (WMD) -0.57, 95% CI -1.17 to 0.03).nSubgroup analyses showed a slightly greater effect size in outpatient studies, where there were shorter follow up durations, than in inpatient studies for both oximetry (outpatients WMD -0.84, 95% CI -1.59 to -0.10 versus inpatients W

31、MD -0.25, 95% CI -1.18 to 0.67) and average clinical score (outpatients SMD -0.68, 95% CI -0.87 to -0.49 versus inpatients SMD -0.23, 95% CI -0.44 to -0.01). Critically Appraised Topic Presentation ExampleResults nBronchodilator recipients showed no improvement in the rate of hospital admission afte

32、r treatment as outpatients (18% versus 26%, OR 0.70, 95% CI 0.36 to 1.35) or duration of hospitalization for inpatients (WMD 0.02, 95% CI -0.32 to 0.36). nThe inclusion of studies that enrolled infants with recurrent wheezing may have biased the results in favor of bronchodilators. Critically Apprai

33、sed Topic Presentation ExampleResults nAUTHORS CONCLUSIONS: Bronchodilators produce small short-term improvements in clinical scores. This small benefit must be weighed against the costs and adverse effects of these agents.Critically Appraised Topic Presentation ExampleImplication for PracticenBronc

34、hodilators produce small short-term improvements in clinical scores among infants with bronchiolitis and may slightly improve oxygenation in those treated as outpatients. nHowever, given the high costs, incidence of adverse effects and uncertain efficacy based on the findings of this meta-analysis,

35、bronchodilators cannot be recommended for routine management of first-time wheezers who present with the clinical findings of bronchiolitis. nBronchodilators should not be used in patients who are hospitalized with bronchiolitis.Critically Appraised Topic Presentation ExampleImplication for Practice

36、Critically Appraised Topic Presentation Example (2)1.The patient & clinical questionA 43 year old male asked for some repeat prescriptions and advice about preventing deep vein thrombosis on a 12 hour flight (his brother had had one last year). You suggest stockings as the most effective prevention.

37、Question (PICO): In patients on long flights (P), do compression stockings (I) prevent DVT (O)?Critically Appraised Topic Presentation Example (2)2.Search strategya)PubMed: Clinical queries (with therapy filters)b)Flight *AND stocking*AND DVTc)6 papers included 2 separate trialsd)The Scurr article w

38、as the larger trial, and quality appeared equalCritically Appraised Topic Presentation Example3.The studythe question and appraisalStudy Question: In patients on flights over 8 hours in economy class, do Grade-I below-knee compression stockings, compared to no stocking, prevent ultrasound-detected D

39、VT?Critically Appraised Topic Presentation Example3.The studythe question and appraisalRandomisation: was by sealed envelope (not ideal) but lead to reasonable balance through more female appeared to receive stockings than males.Ascertainment: there was an 86% followup and ultrasound in each arm; th

40、is is adequate.Measurement: through stockings were removed pre-ultrasound, the sonographer may have seen the stocking mark and hence been unblinded.The study has some flaws, but these are probably insufficient to explain the size of the resultsCritically Appraised Topic Presentation Example4.The res

41、ultsDVT occurred in 12% of the No stocking group and 0% of the Stocking group.Relative risk reduction of 100% and an absolute risk reduction of 12% (95% CI 69-100)The NNT (number needed to treat) is 9. However, there was a small increase in superficial thrombophlebitis.Critically Appraised Topic Pre

42、sentation Example5.How the results applyMy patient is a little younger than the average of 62 years seen in the trial, and hence probably at somewhat lower risk. Nevertheless, this is a simple cheap and effective prevention procedure, which I would recommend to him.Are the Results of This Single Pre

43、ventive or Therapeutic Trial Valid?Was the assignment of patients to treatments randomized?Yes. Refers to another article that describes the methods more fully. Note that in ACP Journal Club it mentioned that allocation was concealed.Was the randomization list concealed?Yes.Was follow-up of patients

44、 sufficiently long and complete?99% follow-up at a mean of 5 years.Were all patients analyzed in the groups to which they were randomized?An intention to treat analysis was completed.Were patients, clinicians and study personnel kept “blind” to treatment?Yes. Participants, clinicians, data collector

45、s and outcomes assessors were blinded.Were the groups treated equally, apart from the experimental treatment?Yes.Were the groups similar at the start of the trial apart from the experimental therapy?Yes.OUR CALCULATIONS 95% CI 721.4%25%4.3%5.7%1/ARRCER EERCER EERCEREERCERNumber needed to treat (NNT)

46、Absolute risk reduction (ARR)Relative risk reduction (RRR)Can We Apply This Valid, Important Evidence About Therapy in Caring for Our Patient? Do these results apply to our patient?Is our patient so different from those in the study that its results cannot apply?No. Includes patients 4080 years old

47、with TIA, carotid endarterectomy and normal lipid profiles. Is the treatment feasible in our setting?Yes it is available but must explore with patient if he is willing to take it.What are our patients potential benefits and harms from the therapy?Method I: fRisk of the outcome in our patient, relati

48、ve to patients in the trial.Expressed as a decimal: _NNT/f=_/_=_(NNT for patients like ours)Method II: 1/(PEERRRR)Our patients expected event rate (PEER) if they received the control treatment:PEER=_1/(PEERRRR)=1/_=_(NNT for patients like ours)Study includes a subgroup analysis looking at the patien

49、ts aged 7580 years at study entry with outcomes of major vascular event. CER=32.3%, EER=23.1%. Therefore, RRR is 29% and NNT is 11.Are our patients values and preferences satisfied by the regimen and its consequences?Do we and our patient have a clear assessment of their values and preferences?Need

50、to explore with patient.Are they met by this regimen and its consequences?Need to explore with patient.Writing Structured Summaries of Evidence-based Learning, or CATs (critically appraised topics)nTitle: declarative sentence that states the clinical bottom line.nClinical question: four (or three) c

51、omponents of the foreground question that started it all.nClinical bottom line: concise statement of best available answer(s) to the question.nEvidence summary: description of methods and/or results in concise form (e.g. table).nComments: about evidence (e.g. limitations) or how to use it in your ow

52、n setting.nCitation(s): include evidence appraised and other resources, if appropriate.nAppraiser: so youll know who did the appraising when you return to it later.nDate CAT was “born”/expiration date: so folks will know when to look again.PresentationsnFor your brief presentation: Please hand a cop

53、y of your review and paper to the tutor before presenting. You will have about 7 minute to present and 3 minutes for discussion. This should require about 2-3 overheadse.g., one for the patients, one for the search and paper, and one for application to the individual patient.Diagnostic EssentialsCLI

54、NICAL SCENARIOn假如我們現在正在診治一位貧血病患，且目前已知造成他貧血的原因有50%機會是缺鐵性貧血，我們想要以一個有用的血清標記ferritin 作為偵測此病患確定為缺鐵性貧血的可能性。因此我們去尋求外在的證據，包括病患的血清ferrin值為60 mmol/L 。此時我們如何來評核與判讀此病患所有資料的意義？Diagnosis of Iron-deficiency Anemia in the ElderlyGuyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R. (Am J Med. 1990;8

55、8:205-9)nPURPOSE: To determine the value of serum ferritin, mean cell volume, transferrin saturation, and free erythrocyte protoporphyrin in the diagnosis of iron-deficiency anemia in the elderly. nPATIENTS AND METHODS: We prospectively studied consecutive eligible and consenting anemic patients ove

56、r the age of 65 years, who underwent blood tests and bone marrow aspiration. The study consisted of 259 inpatients and outpatients at two community hospitals in whom a complete blood count processed by the hospital laboratory demonstrated previously undiagnosed anemia (men: hemoglobin level less tha

57、n 12 g/dL; women: hemoglobin level less than 11.0 g/dL) 26Diagnosis of Iron-deficiency Anemia in the ElderlyGuyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R. (Am J Med. 1990;88:205-9)Diagnosis of Iron-deficiency Anemia in the ElderlyGuyatt GH, Patterson C, Ali M, Singer J, Levine

58、 M, Turpie I, Meyer R. (Am J Med. 1990;88:205-9)nRESULTS: Thirty-six percent of our patients had no demonstrable marrow iron and were classified as being iron-deficient. The likelihood ratios associated with the serum ferritin level were as follows: ferrtine 100 micrograms/L, 0.13 45 micrograms/L fe

59、rritin 100 micrograms/L, 0.46 18 micrograms/L ferritin 45 micrograms/L, 3.12 18 micrograms/L ferritine, 41.47. Diagnosis of Iron-deficiency Anemia in the ElderlyGuyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R. (Am J Med. 1990;88:205-9)nThese results indicate 72% of those who wer

60、e not iron-deficient had serum ferritin values greater than 100 micrograms/L In populations with a prevalence of iron deficiency of less than 40%, values of greater than 100 micrograms/L reduce the probability of iron deficiency to under 10% 55% of the iron-deficient patients had serum ferritin valu