An introduction to Evidence-Based Medicine part- 1

1. An introduction toEvidence-Based Medicinepart-1 Akbar Soltani, MD Tehran University of Medical Sciences Endocrine and Metabolism Research Center Evidence-Based Medicine Working Team Shariati Hospital www.soltaniebm.com www.ebm.ir www.avicennact.ir

2. Some assumptions • You, the audience, between you know much more than I do about this • Lao Tzu said: “Those who know do not speak/Those who speak do not know.” • Kafka: What a silence had been established in the world if every person talk correlated with his/her knowledge

3. What is the best way of walking? What is the best way of thinking? What is Critical Thinking? fshahrtash@gmail.com>

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

6. 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)

8. Reference based medicine

9. Trace back to the development of EBM. • 1972:Archie Cochrane published an book, and told about the important role of RCTs. • 1980's: Dave Sackett at McMasterUniversity in Canada. • 1990s :The term was generated and coined by Gordon Guyatt and his colleagues from McMaster University

10. Trace back to the development of EBM

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

12. I.Individual Clinical Expertise: • Experience: Relates to what we’ve done and to knowledge. • Clinical skills • Clinical judgment • Vital for determining whether the evidence applies to the individual patient at all and, if so, how

14. II. Best External Evidence: • From real clinical research amongintact patients. • Has a short doubling-time (10 years).

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

16. 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

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

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

19. Why Is It So Hard to Be Up-to-date? • 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

20. Increasing Knowledge

21. 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

22. 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

23. 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

24. 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

25. Antman JAMA 92

26. 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 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

27. Expert component • Professor Paul Knipschild has described how Nobel prize winning biochemist Linus Pauling used selective quotes from the medical literature to "prove" his theory that vitamin C helps you live longer and feel better. • When Knipschild and his colleagues searched the literature systematically for evidence They found that

28. Expert component • One or two trials did strongly suggest that vitamin C could prevent the onset of the common cold • There were far more studies which did not show any beneficial effect.

30. Interesting Example Dr Naserimoghaddam

31. 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

32. 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

33. 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

34. 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

35. Hypothesis? Sample size estimation None!

36. Failure to detect a difference = Equivalence?

37. Assume non-inferiority if the lower limit of 95% CI is less than –5%, N=904 per group!

38. Percent correct answers for knowledge questions

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

40. Global judgment by experts • A pervasive problem for primary care physicians attempting to appraise clinical information is the conflicting recommendations by experts. Vote counting!

41. Variation in prostatectomy

42. 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

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

45. 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.

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

47. 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)

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

49. 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

50. West Vs East – Language American ways-A guide for foreigner Eloquent=expressive