August 27 - 30, 2012 Guideline and Systematic review Workshop

1. Dr. ElieAkl Dr. Holger Schünemann Dr. Ruth Kalda Dr. Alar Irs August 27 - 30, 2012Guideline and Systematic review Workshop

2. Dr. Holger Schünemann August 27, 2012Introduction to Guideline Development in the context of Evidence Based Medicine

3. The Department of Clinical Epidemiology & Biostatistics at McMaster History - 1967 – Founded by David Sackett - 6 chairs since - Instrumental in specialty of Clinical Epidemiology, origin of “Evidence-Based Medicine” People 45 full time and joint faculty ~ 120 associate & part time faculty; 19 emeritus ~ 180 staff ~ 200 PhD and Master students

4. Why EBM?Thrombolysis in Myocardial infarction Antman et al., JAMA, 1992; 268: 240-248

6. What is a guideline? • "Guidelines are recommendations intended to assist providers and recipients of health care and other stakeholders to make informed decisions. Recommendations may relate to clinical interventions, public health activities, or government policies." WHO 2003, 2007

7. When do we need guidelines? • Knowledge gap? • Is a guideline the right approach? • Diagnosis? • Too many cases? Too few? Variation? • Treatment? • Under? Over? Variation? Something new? • Screening? • Quality of care? Integration of care? • Other?

8. What healthcare workers want… • A guideline is not a textbook or a cookbook • To KNOW that the guideline is evidence based • But not necessarily all of the evidence… • To have it easy to use and accessible • Clear recommendations (more on that later)

10. Guideline development Process

11. Working with evidence • For key recommendations: • Search for and retrieve all available evidence • Identify relevant SRs • Formally assess quality of evidence • GRADE (systematic and transparent approach)

12. Institute of Medicine Report on Trustworthy guidelines • Be based on a systematic review of the existing evidence; • Be developed by a knowledgeable, multidisciplinary panel of experts and representatives from key affected groups; • Consider important patient subgroups and patient preferences as appropriate; • Be based on an explicit and transparent process that minimizes distortions, biases, and conflicts of interest; • Provide a clear explanation of the logical relationships between alternative care options and health outcomes, and provide ratings of both the quality of evidence and the strength of recommendations; and • Be reconsidered and revised as appropriate when important new evidence warrants modifications of recommendations.

13. Guideline International Network

14. Institute of Medicine Report on Trustworthy guidelines 2011 • Be based on a systematic review of the existing evidence; • Be developed by a knowledgeable, multidisciplinary panel of experts and representatives from key affected groups; • Consider important patient subgroups and patient preferences as appropriate; • Be based on an explicit and transparent process that minimizes distortions, biases, and conflicts of interest; • Provide a clear explanation of the logical relationships between alternative care options and health outcomes, and provide ratings of both the quality of evidence and the strength of recommendations; and • Be reconsidered and revised as appropriate when important new evidence warrants modifications of recommendations.

15. The origin of evidence appraisal systems Canadian Task Force on the Periodic Health Examination, CMAJ, 1979

16. Oxford Centre for Evidence Based Medicine

17. USPSTF - Grade Definitions After May 2007: Certainty The USPSTF defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct."

19. Recommendations for prognosis • Use prognostic information to determine baseline risk for healthcare decisions

22. Center for Disease Control and Prevention (CDC)

23. Your patient…as an internist • 68 year old man with hypertension and non-valvularatrial fibrillation > 3 months

24. Atrial Fibrillation - Stroke

25. The clinically sensible question Population: Does in patients with atrial fibrillation Intervention: oral anticoagulation Comparison: compared with no therapy Outcomes: reduce the risk for embolic stroke, increase the risk for bleeding, increase burden…? PICO

26. Evidence Recommendation B Class I A 1 IV C Organization AHA ACCP SIGN Which approach? Recommendation for use of oral anticoagulation in patients with atrial fibrillation and rheumatic mitral valve disease

27. What to do?

28. Hierarchy of evidencebased on quality BIAS • STUDY DESIGN • Randomized Controlled Trials • Cohort Studies and Case Control Studies • Case Reports and Case Series, Non-systematic observations • Expert Opinion

29. Issues with evidence hierarchies • Does one size fit all? • Should RCTs be on top? • What are the special strength of observational studies?

30. “Healthy people” “Rare disease” “Long term perspective” “Few RCTs” “Lots of other things” Healthcare problem recommendation

31. “Everything should be made as simple as possible but not simpler.” Explain the following? • Confounding, effect modification & ext. validity • Concealment of randomization • Blinding (who is blinded in a double blinded study?) • Intention to treat analysis and its correct application • P-values and confidence intervals

32. Relative risk reduction: • ….> 99.9 % (1/100,000) • U.S. Parachute Association reported 821 injuries and 18 deaths out of 2.2 million jumps in 2007 BMJ 2003 BMJ, 2003

33. Simple hierarchies are (too) simplistic • STUDY DESIGN • Randomized Controlled Trials • Cohort Studies and Case Control Studies • Case Reports and Case Series, Non-systematic observations BIAS Expert Opinion Expert Opinion Schünemann & Bone, 2003

34. GRADE Working Group • Aim: to develop a common, transparent and sensible system for grading the quality of evidence and the strength of recommendations (over 100 systems) • International group of guideline developers, methodologists & clinicians from around the world (>300 contributors) – since 2000 Grades of Recommendation Assessment, Development and Evaluation • International group: ACCP, AHRQ, Australian NMRC, BMJ Clinical Evidence, CC, CDC, McMaster Uni., NICE, Oxford CEBM, SIGN, UpToDate, USPSTF, WHO CMAJ 2003, BMJ 2004, BMC 2004, BMC 2005, AJRCCM 2006, Chest 2006, BMJ 2008

35. GRADE Uptake • World Health Organization • Allergic Rhinitis in Asthma Guidelines (ARIA) • American Thoracic Society • American College of Physicians • European Respiratory Society • European Society of Thoracic Surgeons • British Medical Journal • Infectious Disease Society of America • American College of Chest Physicians • UpToDate® • National Institutes of Health and Clinical Excellence (NICE) • Scottish Intercollegiate Guideline Network (SIGN) • Cochrane Collaboration • Infectious Disease Society of America • Clinical Evidence • Agency for Health Care Research and Quality (AHRQ) • Partner of GIN • Over 60 (major) organizations

36. Evidence based healthcare decisions Population/societal values and preferences (Clinical) state and circumstances Expertise Research evidence Haynes et al. 2002

37. Your patient…as an internist • 68 year old man with hypertension and non-valvularatrial fibrillation > 3 months • diabetes • large left atrium (→ cardioversion unlikely to be successful) • no history of strokes or transient ischemic attacks (TIAs) • Terrified of having a stroke

38. Risk factors for stroke with NVAF • CHADS2 score for assessment of stroke risk in patients with non-rheumatic AF

39. Risk factors for stroke with NVAF CHADS = 2 • CHADS2 score for assessment of stroke risk in patients with non-rheumatic AF

40. Evidence concerning NVAF and stroke* • Risk of stroke if untreated (CHADS =2): 45/1000 per year • Relative Risk Reduction for stroke • Warfarin: 0.64 (95%CI 0.51-0.77) • RRI for major bleeding • Warfarin: 2.58 (95%CI 1.12-5.97) Physician accuracy in estimating risk: no better than chance… * Pooled estimates of treatment effect in this evidence profile are from a meta-analysis conducted for these guidelines, including data from 6 RCTs of adjusted-dose vitamin K antagonist therapy versus no antithrombotic therapy (AFASAK I, BAATAF, CAFA, EAFT, SPAF I, SPINAF), You et al., in press.

41. Primum non nocere “Primum non netnocere”

42. Evidence based healthcare decisions Population/societal values and preferences (Clinical) state and circumstances Expertise Research evidence Haynes et al. 2002

43. Balancing desirable and undesirable consequences ↑ bleeding ↑ dietary restriction ↑ survival ↓ Morbidity ↑ resources ↑ burden ↓ stroke ↑ QoL Conditional Strong For Against

44. Balancing desirable and undesirable consequences ↑ bleeding ↑ dietary restriction ↑ survival ↓ Morbidity ↑ resources ↑ burden ↓ stroke ↑ QoL Conditional Strong For Against

45. Balancing desirable and undesirable consequences ↑ bleeding ↑ dietary restriction ↑ survival ↓ Morbidity ↑ resources ↑ burden ↓ stroke ↑ QoL Conditional Strong For Against

46. Balancing desirable and undesirable consequences ↑ bleeding ↑ dietary restriction ↑ survival ↓ Morbidity ↑ resources ↑ burden ↓ stroke ↑ QoL Conditional Strong For Against

47. Balancing desirable and undesirable consequences ↑ bleeding ↑ dietary restriction ↑ survival ↓ Morbidity ↑ resources ↑ burden ↓ stroke ↑ QoL Conditional Strong For Against

48. Balancing desirable and undesirable consequences ↑ bleeding ↑ dietary restriction ↑ survival ↓ Morbidity ↑ resources ↑ burden ↓ stroke ↑ QoL Conditional Strong For Against

49. Summary from the practitioner’s perspective for this patient • must anticoagulate 100 people with NVAF for 1 year to prevent 3 strokes per year (30 fewer per 1000 or NNT of 33) • for 100 anticoagulated patients in the community, this will cause 1additional people to have a major bleed per year (8 more per 1000 or NNT of 125)

50. Summary from this patient’s perspective • If you take anticoagulants • your risk of stroke in the coming year will decrease from 4.5% to 1.5% per year but • your risk of having a major bleed will increase from 0.5% to 1% per year