Mastering Evidence-Based Medicine: A Comprehensive Introduction

1. Evidence Based Medicine: An Introduction FarhadHosseinpanah, M.D. Obesity Research Center Research Institute for Endocrine sciences ShahidBeheshtiUniversityof Medical Sciences

2. Workshop objectives • Problems of conventional medicine • Definition and philosophy of EBM/IM • Different concepts such as • answerable question, systematic review, NNT,NNH,… • Search methods • Most popular EBM data bases • Critical appraisal skills

3. Agenda • Definitions: Science and EBM • Dimensions of the problem • Information management (mastery) • Limitations of current clinical practice • Heuristic and errors • Problems of communication • EBM

4. Definition: • Science is devoted to formulating and testing naturalistic explanations for natural phenomena. It is a process for systematicallycollecting and recording data about the physical world, then categorizing and studying the collected data in an effort to infer the principles of nature that best explain the observed phenomena.72 Nobel laureates. (From the Amicus Curiae presented in the US Supreme Court Case of Edwards vs Agullard, 1986)

5. Trace back to the development of EBM. • 1972:Archie Cochrane told about the role of randomized control trial in scientific medicine. • 1980's: Dave Sackett • 1990s :The term was generated by Gordon Guyatt from McMaster University

6. What evidence-based medicine is • “The conscientious (careful), explicit (clear, unambiguous) and judicious (sensible) , use of current best evidence in making clinical decisions about the care of individual patients.” Sackett et al, 2000

7. What evidence-based medicine is: The practice of EBM is the integration of • Individual clinical expertise with the • Best available external clinical evidence from systematic research. and • Patient’s values and expectations Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS: Evidence based medicine: what it is and what it isn’t. BMJ 1996;312:71-2.

8. I.Individual Clinical Expertise: • Experience: Relates to what we’ve done and to knowledge. • “An expert is a person who has made all the mistakes that can be made in a very narrow field” (Niels Bohr) • Clinical skills • Clinical judgment • Vital for determining whether the evidence applies to the individual patient at all and, if so, how

9. Patient seen in practice Matches research result to specific patients Hypothesis generating ? Clinical judgment Outcomes research Confirms or denies hypothesis

10. II. Best External Evidence: • From real clinical research amongintact patients. • Has a short doubling-time (10 years). • Replaces currently accepted diagnostic tests and treatments with new ones that are more powerful, more accurate, more efficacious, and safer.

11. III. Patients’ Values & Expectations • Have always played a central role in determining whether and which interventions take place

12. clinical expertise Current best evidence Patient preferences A model for evidence-based clinical decisions Sackett et al, 2000 Bayesian approach: background knowledge + evidence= decision making

13. Conventional medicine Expertise (intuition…) Pathophysiology, references, tradition… Patient value

14. Agenda • Definitions: Science and EBM • Dimensions of the problem • Information management (mastery) • Limitations of current clinical practice • Heuristic and errors • Problems of communication • EBM

15. Why Is It So Hard to BeUp-to-date? • The database of the National Library of Medicine MEDLINEhas approximately 6 million references from 4.000 journals with about 400.000 new entries added each year. • Doubling time of biomedical science is about 20 months in 2001

16. Increasing Knowledge

17. How many original articles should a specialist read each week to remain up to date in his/her own field only ? • 5 • 10 • 20 • 40 • 100 Dr.S.Naserimoghaddam

18. How many original articles should a specialist read each week to remain up to date in his/her own field only ? • 5 • 10 • 20 • 40 • 100 The story is different for a generalist: 17 /day! Dr.S.Naserimoghaddam

19. Thrombolytic Therapy & MI mortality RCT23 Patients 1960 Odds Ratio 2 0.5 1  Treatment Control Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC: A comparison of results of meta-analyses of randomised control trials and recommendations of clinical experts. JAMA 1992;268:240-8

20. Thrombolytic Therapy & MI mortality Cumulative Year RCTs Pts 1960 1965 Odds Ratio 2 0.5 1 1 23 2 65 3 149 4 316 7 1793      Treatment Control Antman JAMA 92

21. Thrombolytic Therapy & MI mortality Cumulative Year RCTs Pts 1960 1965 1970 1975 1980 1985 1990 Odds Ratio 2 0.5 1 1 23 2 65 3 149 4 316 7 1793 10 2544 11 2651 15 3311 17 3929 22 5452 23 5767 27 6125 33 6571 65 47185 70 48154       p < 0.01       p < 0.001    p < 0.00001  Treatment Control Antman JAMA 92

22. Thrombolytic Therapy & MI mortality Cumulative Year RCTs Pts 1960 1965 1970 1975 1980 1985 1990 Textbook Recommendations Rout Specif Exp NOT Odds Ratio 2 0.5 1 1 23 2 65 3 149 4 316 7 1793 10 2544 11 2651 15 3311 17 3929 22 5452 23 5767 27 6125 33 6571 65 47185 70 48154  21 5 10 2 8 7 8 12 4 3 1 1    1 1 2 8 7 2   p < 0.01    1 1 1 2 8 1    p < 0.001  5 15 6   p < 0.00001  Treatment Control Antman JAMA 92

23. Some parts of textbooks are out-of-date • Fail to recommend Rx up to ten years after it’s been shown to be efficacious. • Continue to recommend therapy up to tenyears after it’s been shown to be useless. • Different textbooks, different recommendations. • Textbooks are fact or opinion? • Textbooks are appraisable? Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC: A comparison of results of meta-analyses of randomised control trials and recommendations of clinical experts. JAMA 1992;268:240-8

24. Interesting Example Dr Naserimoghaddam

25. 182 Health authorities selected • 2 Articles: 1 on cardiac rehabilitation 1 on breast Ca screening • Results of each presented in 4 ways: • RRR (Relative Risk Reduction) • ARR (Absolute Risk Reduction) • PEFP (Proportion of Event Free Patients) • NNT ( Number Needed to Treat) Evidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October) Dr Naserimoghaddam

26. They were told that these were the results of 4 articles on each topic • Question: According to which set of data you may choose to adopt the method as part of your regional practice policy? Evidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October) Dr Naserimoghaddam

27. Interesting Results ! Evidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October) Dr Naserimoghaddam

28. Only 3 noted that all 4 sets of data are the same! • None were clinicians! Evidence based purchasing: understanding results of clinical trials and systematic reviews T Fahey, S Griffiths, T J Peters. BMJ 1995;311:1056-1059 (21 October) Dr Naserimoghaddam

29. Scientific illiteracy is a major failing of medical education

30. A Useful Equation! • The goal of information mastery is to determine the information source with the highest usefulness score relevance validity Usefulness= ________________ work

31. Relevancyis based on the frequency that we are exposed to the clinical question in our practice and the type of evidence presented.  • We are looking for patient-oriented evidence • Not enough to find patient-oriented evidence, but we are truly seeking patient-oriented evidence that matters (POEM)

32. Information Mastery (Relevancy) • Articles • POEM: Patient-oriented evidence that Matters • mortality, morbidity, quality of life • DOE: Disease-oriented evidence • pathophysiology, pharmacology, etiology

33. DOE POEM Examples of Hypothetical DOE and POEM studies Drug A decreases overall mortality Drug A lowers cardiovascular mortality Drug A lowers cholesterol HRT increase cardiovascular mortality HRT do not decreases overall mortality!! HRT lowers cholesterol Fluoride increase osteoblastic activity Fluoride increase Fx!! Fluoride increase BMD Pathophysiologic reasoning

34. Agenda • Definitions • Dimensions of the problem • Information management (mastery) • Limitations of current clinical practice • Heuristic and errors • Problems of communication • EBM

35. Global judgment by experts • A pervasive problem for primary care physicians attempting to appraise clinical information is the conflicting recommendations by experts. Bloor M. Bishop Berkeley and the adenotonsillectomy enigma: an exploration of the social construction of medical disposals. Sociology 1976; 10: 43–61. EVIDENCE-BASED PRACTICE 2000

36. Variation in current practice

37. Defer to authority Resident : So , which statin would you recommend ? Attending : I prefer Atorvastatin , and the last time I sent someone over to the lipid clinic , that was Dr. x recommendation as well. (Translation : Does it work? It does if Dr. Expert says so.) Evidence Based Fallacy

38. In My Experience Resident : So , which statin would you recommend ? Attending : I don’t really like any of them. I have had good experience with diet and Cholestyramine, and I never prescribe 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Results cannot be reproduced or verified. Studies, if any, are always so vaguely described that one can't figure out what was done or how it was done. Evidence Based Fallacy

39. Pathophysiologic approach • Resident: Do you recommend HRT fore high LDL in postmenopausal patients? • Attending: YES because estrogen increase HDL and decrease LDL, Lpa,and ……….. Evidence Based Fallacy

41. WHI: Invasive Breast Cancer 3% 2% 1% years1 2 3 4 5 6 7

42. WHI: Coronary Heart Disease years1 2 3 4 5 6

43. Does CME Work? • Traditional CME in a nice place with pleasant after lecture diversions is, unfortunately, completely ineffective in changing our behavior. Davis DA, Thompson MA, Oxman AD, Haynes RB: Changing physician performance. A systematic review of the effect of continuing medical education strategies. JAMA 1995;274:700-5.

44. The Slippery Slope 100% r = -0.54 p<0.001 . .. . . .... . knowledge of current best care ... ... ... 50% ... .. .... .... 0% years since graduation • Choudhry,Fletcher and Soumerai, • Ann Intern Med 2005;142:260-73 • 94% of 62 studies found decreasing competence for at least some tasks, with increasing physician age.

45. Agenda • Definitions: Science and EBM • Dimensions of the problem • Information management (mastery) • Limitations of current clinical practice • Heuristic and errors • Problems of communication • EBM

46. A quick assessment Consider the following list of words: goiter ,weight loss, sweating, hair loss, proptosis, lid lag, dyspnea, wide pulse pressure, weakness, hyperphagia, staring, diarrhea ,anxiety Write down as many as you can remember…

47. A quick assessment: • Did you include tremor or palpitation in the list of words you thought you heard? • Results : based on nonrandom sampling (N=600), error proportion was 20% (unpublished!) • What is the validity of the estimation of frequency (or other measures) of the clinical findings?

48. Heuristical errors • Heuristic = rule of thumb; mental process used to learn, recall, or understand knowledge • Some examples: • Recency • Rarity • “burned” by missing a case • Regression towards the mean • … (Tversky& Kahneman, 1974)

49. Agenda • Definitions • Dimension of problems • Information management (mastery) • Limitations of current clinical practice • Heuristic and errors • Problems of communication • EBM

50. Probability estimates of various qualitative verbal expressions Certain Likely Possible Probable Low probability Suggests High probability Unlikely Moderate probability Pathognomonic classic 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Evidence-Based Medicine: A Framework for Clinical Practice by Friedland et. al