Evidence Based Medicine

1. Evidence Based Medicine October 21, 2008 Mount Royal College Jeffrey P Schaefer, MD

2. Objectives • After this session • describe EBM process • understand the role of Critical Appraisal dr.schaeferville.com

3. What’s Evidence Based Medicine?

4. “Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.” • DL Sackett BMJ 1996; 312:71-2 Best Available Evidence Patient, Provider, and System Values

5. Evidence Based Medicine Process • Formulate a Clinical Question • Search for Evidence • Critically Appraise the Evidence • Apply the Evidence • Store what was learned • Assess the effects of decisions

6. Clinical Process • patient presents a problem (chief complaint) • history • describe the problem • risk factors for diseases are considered • test diagnostic hypotheses • physical examination • investigations • diagnosis • therapy / prevention • prognosis • harm

7. Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

8. Five Clinical Questions • harm? • prevention? • diagnosis? • therapy? • prognosis?

9. hypertension

10. Question ID: 75 year old male CC: ‘get my blood pressure checked out’ HPI: was at the mall, BP was 195 / 80 mmHg no symptoms PMH: negative FH: negative PSH: non-smoker, non-drinker Med: none (including over the counter medication) Allergy: negative ROS: negative

11. Question Physical Examination general: well VS: 180 / 75 mmHg, 82 /min derm: normal HNEENT: normal Chest: normal CVS: normal Abdo: normal GU: normal Neuro: normal MSK normal

12. Question Diagnosis: primary isolated systolic hypertension Patient asks, “should I be on something?”

13. Five Clinical Questions • harm? • prevention? • diagnosis? • therapy? • prognosis? (hypertension is the disease in this case)

14. Question “should he be on something?”

16. Question • Making a good question better… • Include • patient • intervention (exposure) • outcome • alternative

17. Formulating the Clinical Question: case 1 • patient / problem: • elderly person with isolated systolic hypertension • intervention / exposure • anti-hypertensive therapy • alternative • no therapy (or placebo in clinical trials) • outcomes (desired / undesirable) • cardiovascular outcomes / adverse effects / cost

18. Formulating the Clinical Question: case 1 “What is the effect of anti-hypertensive therapy on cardiovascular outcomes among elderly patients with isolated systolic hypertension when compared to no treatment?”

19. Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

20. Gathering Evidence What’s your 411?

21. Gathering Evidence

22. Gathering Evidence • Browsing • Problem Solving

23. Gathering Evidence • Filtered • Unfiltered

24. Diagnosis --> Cross Sectional Design Harm --> Cohort or Case Control Prognosis --> Cohort Therapy - Prevention --> RCT or Systematic Review

25. Therapy / Prevention Heirarchy • N of 1 randomized controlled trial • Systematic reviews of RCTs • A single RCT • Systematic review of observational studies • Physiological studies • Unsystematic clinical observations

26. Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

27. Critical Appraisal www.cche.net validity results applicability

28. Critical Appraisal: Therapy / Prevention • Validity: • random allocation? • subject accounting? • follow-up complete? • intention to treat analysis? • concealment? • group similarity? • similar treatment except for intervention?

29. Population with Condition Experimental baseline Experimental post- intervention • Typical Controlled Clinical Trial Design time Eligible (entry and exclusion criteria) allocation Control baseline Control post- intervention time

30. Bias New Current stroke rate 5% 10% What if… % smoker 30 30 % smoker 50 30 % smoker 30 50

31. Heart Outcomes Prevention Evaluation TrialLancet 2000

32. Critical Appraisal: therapy / prevention • Were patients analyzed in the group to which they were randomized? • Intention to treat • Explanatory analysis

33. intention to treat analysis explanatory analysis Consider: adjuvant therapy for breast cancer 100 adjuvant ----> only 80 receive 200 patients --> 100 control-------> all 100 receive ITT: outcome/100 (adjuvant) VERSUS outcome/100 (control) Exp: outcome/80 (adjuvant) VERSUS outcome/120 (control) ITT preferred: not receiving adjuvant is a risk of adjuvant tx

34. Critical Appraisal: therapy / prevention • Results • Magnitude of effect? • how large is the effect • Precision of measurement? • confidence interval

35. Critical Appraisal: therapy / prevention • Applicability • apply to my patient(s)? • were all important outcomes considered? • treatment worth the risk / cost?

36. What Critical Appraisal is Not... • It’s not about trashing an article • something can be learned from every article, even if it’s how to design a better trial! • It’s not about black and white answers • most studies have strengths and weaknesses • some articles are highly edited • It’s not the only reason to embark on a course of action • other factors to consider (harm, cost, patient values)

37. Evidence Based Medicine Process • formulate a clinical question • gather evidence • appraise the evidence • apply the evidence

38. Applying the Evidence • EBM does not replace patient values • EBM enhances patient decision making

39. Applying the Evidence • Antibiotics in pneumonia • good evidence to support antibiotics • antibiotics for a palliative care patient may not be appropriate depending on the patient (or surrogate decision maker’s) preferences • Numerous difficult questions • feeding tube in the setting of stroke • palliative chemotherapy, radiation, surgery • treating serious disease in children

41. Why EBM? • Good Ole Days… • clinical trials were sparse • treatment based on ‘common sense’ • risks / benefits unknown

42. Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin's disease • Immunoblastic lymphadenopathy with mixed cryoglobulinemia. A detailed case study • Vinyl-chloride-induced liver disease. From idiopathic portal hypertension (Banti's syndrome) to Angiosarcomas • Hodgkin's Disease, tonsillectomy and family size • Reduction of ischemic injury by nitroglycerin during acute myocardial infarction (no abstract available) • Frederick Stohlman, Jr., M.D Volume 292 January 2, 1975 Number 1

44. Risk / Benefit • Trephination • Vaccination

45. Previous Paradigm... • Example • Premature Ventricular Complexes (PVCs) are a risk factor for Ventricular Fibrillation (V fib), • Suppressing PVC  Reduce V-fib

46. PVC’s (R on T) ---> V Tach --> V Fib

47. Previous Paradigm • CAST (cardiac arrhythmia suppression trial) found that the encainide and flecainide groups had a 3.6-fold increase in arrhythmic death compared with their placebo group. N Engl J Med 1989; 321: 406-412.

48. Examples of Disparity... • Atrial Fibrillation (AF) • Atrial fibrillation is a risk factor for stroke • Warfarin anticoagulation significantly reduces risk of stroke among those with atrial fibrillation • Q: Is warfarin prescribed for those with AF? • A: Lancet 1998;352:1167-1171 • Among 26 practices in the UK, 49% of those with AF missed out on therapy.

50. EBM Criticisms • EBM is cookbook medicine • EBM is the knife of the cost cutter • EBM is impractical for the front line • EBM cannot substitute for experience