Evidence-Based Medicine

1. Evidence-Based Medicine 台北醫學大學附設醫院 實証醫學中心 主任 粟發滿 醫師

2. What is Evidence-Based Medicine? The conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.

3. What is EBM? The practice of evidence-based medicine means integrating individual clinical expertise and patient preference with the best available external clinical evidence from systematic research

4. 實證醫學的3”E” Evidence Experience Expectation Decision Analysis

5. Expertise • Evidence • Expectation (Preference)

6. A paradigm shift in expertise

7. A paradigm shift in expertise

8. A paradigm shift in expertise

9. A paradigm shift in expertise

10. Expertise • Evidence • Expectation (Preference)

11. The publication of research findings All research activity Published research Published in prestigious journals

12. A continuum of evidence

13. Evidence level Description Ia: evidence from meta-analysis of randomised controlled trials Ib: evidence from at least one randomised controlled trial IIa: evidence from at least one controlled study without randomisation IIb: evidence from at least one other type of quasi-experimental study III: evidence from non-experimental descriptive studies, such as comparative studies, correlation studies and case-control studies IV: evidence from expert committee reports or opinions and/or clinical experience of respected authorities Classification of evidence

14. A directly based on category I evidence, or assigned this grading by the developers, for explicit and documented reasons B directly based on category II evidence, or assigned this grading by the developers, for explicit and documented reasons C directly based on category III evidence, or assigned this grading by the developers, for explicit and documented reasons D directly based on category IV evidence, or assigned this grading by the developers, for explicit and documented reasons Grading of recommendations

15. Randomized controlled Double blind studies Randomized controlled studies Meta-analysis Cohort studies Case-control studies Case series Case reports Ideals, Editorials, Opinions Animal research In vitro (“test tube”) research Pyramid of Evidence

16. Diagnosis: prospective cohort study with good quality validation against “gold standard” • Prognosis: prospective cohort study • Therapy or prevention: prospective, randomized controlled clinical trial (RCT) • Harm / Etiology: RCT, cohort or case-control study (probably retrospective) • Economic: analysis of sensible costs against evidence-based outcomes

17. Case report or case series may be enough to answer question • Phocomedia in children born to women who took thalidomide • Troglitazone was removed from the U.S. market because 94 cases of liver failure were reported

18. Expertise • Evidence • Expectation (Preference)

19. Patient’s preference Utility a quantitative measure of the strength of a patient’s preference for a particular state of health or outcome

20. How do we actually practice EBM? Step 1: Converting the need for information (about prevention, diagnosis, prognosis, therapy, causation, etc) into an answerable question Step 2: Tracking down the best evidence with which to answer that question Step 3: Critically appraising that evidence for its validity (closeness to the truth), impact (size of the effect), and applicability (usefulness in our clinical practice) Step 4: Integrating the critical appraisal with our clinical expertise and with our patient’s 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

21. Clinical scenario A junior medical resident working in a teaching hospital admits a 43 year old previously well man who experienced a witnessed grand mal seizure. He had never had a seizure before and had not had any recent head trauma. Physical examination is negative. The patient is given an loading dose of phenytoin intravenously and the drug is continued orally. A computed tomographic head scan is completely normal and an electroencephalogram shows only nonspecific findings. The patient is very concerned about his risk of seizure recurrence

22. The way of the past The resident was told by her senior resident (who was supported in his view by the attending physician) that the risk is high and that was the information that should be conveyed to the patient. She now follows this path, emphasizing to the patient the need not to drive, to continue his medication, and to see his family physician in follow-up.

23. The way of the EBM 1. The resident asks herself whether she knows the prognosis of a first seizure. 2. She uses the Medical Subject Headings (MeSH) terms "epilepsy" and "prognosis" and "recurrence" and finds 25 citations. 3. She reviews the paper, finds that one meets criteria she has previously learned for a valid investigation of prognosis, and that the results are applicable to her patient. The results of the relevant study show that the patients risk of recurrence at one year is between 30% and 43%, and at three years is between 51% and 60%. After a seizure-free period of 18 months his risk of recurrence would likely be under 20%. 4. She conveys this information to the patient, along with a recommendation that he take his medication, see his family doctor regularly, and have a review of his need for medication if he remains seizure-free for 18 months.

24. Asking answerable clinical questions

25. 1. Clinical findings 2. Etiology 3. Clinical manifestations of disease 4. Differential diagnosis 5. Diagnostic tests 6. Prognosis. 7. Therapy 8. Prevention 9. Experience and meaning 10. Self-improvement Where and how clinical questions arise

26. Which question is most important to the patient's well being? • Which question is most feasible to answer in the time you have available • Which question are you most likely to encounter repeatedly in your practice? • Which question is most interesting to you?

27. Asking answerable clinical questions The patient is a 77-year-old man admitted for dyspnea and fever. He fell ill 4 days ago with low-grade fever, chills, myalgias, rhinorrhoea and a non-productive cough. One day ago he developed dyspnea on exertion, purulent sputum, lateral chest wall pain with inspiration and a shaking chill. His general health is fairly good; he has had essential hypertension for 12 years, well controlled on diuretic therapy. He has not smoked. He is independent in his activities of daily living. He lives alone now, after his wife died 3 years ago. On examination, his respiratory rate is 28, his heart rate is 108 and his temperature is 39.2°C. He may have subtle cyanosis. His chest expands symmetrically, he has no prolongation of expiration and no wheezing. There is bronchophony and egophony in the left lower posterior lung field. Initial blood tests show leukocytosis and hyponatremia. The team suspects acute community-acquired pneumonia with hypoxemia, and plans chest radiographs, sputum studies, supplemental oxygen and antimicrobial therapy.

28. The first three questions asked by the team’s students were: (a) What microbial organisms can cause community-acquired pneumonia? (b) How does pneumonia cause egophony? (c) What is the causes of hyponatremia?

29. Types of questions • Background questions • Foreground questions

30. Types of questions Background questions · Ask for general knowledge about a disorder · Have two essential components: 1. A question root (who, what, where, when, how, why) with a verb 2. A disorder, or an aspect of a disorder Examples: “What causes pneumonia?” “When do complications of acute pancreatitis usually occur?”

31. Types of questions Foreground questions · Ask for specific knowledge about managing patients with a disorder · Have four (or three) essential components: 1. Patient and/or problem 2. Intervention 3. Comparison intervention (if relevant) 4. Clinical Outcomes

32. The first three questions asked by the house officers were: (a) In patients with suspected pneumonia, are any clinical findings sufficiently powerful to confirm or exclude pneumonia all by themselves, or is a chest radiograph necessary for the diagnosis? (b) In patients with community-acquired pneumonia, is the probability of Legionella infection sufficiently high to warrant considering covering this organism with the initial antibiotic choice? (c) In patients with community-acquired pneumonia, do clinical features predict outcome well enough that “low risk” patients can be treated safely at home?

33. Types of questions

35. Asking answerable clinical questions

36. Asking answerable clinical questions

37. Key issues of critical appraisal • Are the results of the study valid? • What are the results? • Are the results relevant?

38. Therapy

39. Are the results of this individual study valid? 1. Was the assignment of patients to treatment randomized? And was the randomization list concealed? 2. Was follow-up of patients sufficiently long and complete? 3. Were all patients analyzed in the groups to which they were randomized? 4. Were patients and clinicians kept blind to treatment? 5. Were groups treated equally, apart from the experimental therapy? 6. Were the groups similar at the start of the trial?

40. Are the valid results of this individual study important? 1. What is the magnitude of the treatment effect? 2. How precise is this estimate of the treatment effect?

41. What is the magnitude of the treatment effect? • Control event rate (CER) • Experimental event rate (EER) • Relative risk reduction (RRR) |CER - EER | /CER • Relative benefit increase (RBI) | CER - EER | /CER

42. What is the magnitude of the treatment effect? • CER=22/1005=2.19% • EER=11/1022=1.08% • RRR=(2.19-1.08)/2.19=0.506=51%

43. What is the magnitude of the treatment effect? • Absolute risk reduction (ARR) CER-EER=2.19-1.08=1.11% • There would be 1.11 fewer fractures in the group of 100 people compared to a similar group of 100 people who had not received any treatment

44. What is the magnitude of the treatment effect? How many people we would need to treat to prevent one fracture?

45. Numbers Needed to Treat (NNT) • NNT=1/ARR • ARR=1.11% 100 people needed to treat to reduce 1.11 fracture • NNT=1/1.11%=100/1.11=90 We nee to treat 90 people to prevent one fracture

46. What is the magnitude of the treatment effect?

47. 115-129 mmHG 90-109 mmHG Some useful NNTs

48. Numbers Needs to Harm (NNH) The number of patients needed to produce harmful side effect from treatment • Actual Risk Increase (ARI)= |Control Event Risk (CER) - Experimental Event Risk (EER)| • NNH=1/ ARI

49. Numbers Needs to Harm (NNH) The risk of developing a deep vein thrombosis (DVT) in the leg in woman taking newer oral contraceptive pill was two times more than that of woman taking traditional oral pill • The risk of developing DVT in women taking pill: Traditional pill: 1/200,000 per year Newer pill: 1/100,000 per year

50. Numbers Needs to Harm (NNH) • The relative risk of developing DVT on the newer pill: CER/EER= 1/100,000 1/200,000 = 0.00001/0.000005 = 2 • Conclusion: The newer pill doubles the annual risk of developing DVT