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ppt - Slide 1

  1. 1. Rating quality of evidence and Strength of recommendations in GI using the GRADE Framework<br />AGA Clinical Practice & Quality Management Committee Teleconference<br /> 17 Oct 2008<br />Yngve Falck-Ytter, M.D.<br />Assistant Professor of Medicine<br />Case Western Reserve University, Cleveland<br />Division of Gastroenterology, Case and VA Medical Center <br />
  2. 2. Disclosure<br />In the past 4 years, Dr. Falck-Ytter received no personal payments for services from industry. His research group received research grants from Valeant and Roche that were deposited into non-profit research accounts. He is a member of the GRADE working group which has received funding from various governmental entities in the US and Europe. Some of the GRADE work he has done is supported in part by grant # 1 R13 HS016880-01 from the Agency for Healthcare Research and Quality.<br />
  3. 3. Content<br />Background and rationale for revisiting guideline methodology<br />The GRADE approach <br />Grading the quality of evidence and strength of recommendations in GI<br />
  4. 4. Hierarchy of evidence<br />STUDY DESIGN<br /><ul><li>Randomized Controlled Trials
  5. 5. Cohort Studies and Case Control Studies
  6. 6. Case Reports and Case Series, Non-systematic observations</li></ul>BIAS<br />Expert Opinion<br />Expert Opinion<br />Expert Opinion<br />
  7. 7. Reasons for grading evidence?<br />People draw conclusions about the<br />quality of evidence and strength of recommendations<br />Systematic and explicit approaches can help<br />protect against errors, resolve disagreements<br />communicate information and fulfill needs<br />Change practitioner behavior<br />However, wide variation in approaches<br />GRADE working group. BMJ. 2004 & 2008 <br />
  8. 8. 6<br />Grading used in GI CPGs<br />AGA<br />AASLD<br />ACG<br />ASGE<br />I Syst. review of RCTs<br />I RCTs<br />A. Prospect. controlled trials<br />I RCTs, well designed, n↑ for suff. stat. power<br />II-1 Controlled trials(no randomization)<br />II 1+ properly desig. RCT, n↑, clinical setting<br />B. Obser-vational studies<br />II 1 large well-designed clinical trial (+/- rand.), cohort or case-control studies or well designed meta-analysis<br />II-2 Cohort or case-control analytical studies<br />III Publ., well-desig. trials, pre-post, cohort, time series, case-control studies<br />II-3 Multiple time series, dramatic uncontr. experiments<br />IV Non-exp. studies >1 center/group, opinion respected authorities, clinical evidence, descr. studies, expert consensus comm.<br />C. Expert opinion<br />III Clinical experience, descr. studies, expert comm.<br />III Opinion of respected authorities, descrip. epidemiology<br />IV Not rated<br />
  9. 9. Limitations of existing systems<br />Confuse quality of evidence with strength of recommendations<br />Lack well-articulated conceptual framework<br />Criteria not comprehensive or transparent<br />GRADE unique<br />breadth, intensity of development process<br />wide endorsement and use<br />conceptual framework<br />comprehensive, transparent criteria<br />Focus on all important outcomes related to a specific question and overall quality<br />
  10. 10.
  11. 11. GRADE Working Group<br />a) Agency for Healthcare Research and Quality, USA<br />b) Children's National Medical Center, USA<br />c) Centers for Disease Control and Prevention, USA<br />d) University of Newcastle upon Tyne, UK<br />e) German Cochrane Centre, Germany<br />f) Norwegian Centre for Health Services, Norway<br />g) McMaster University, Canada<br />h) Scottish Intercollegiate Guidelines Network, UK<br />i) Fédération Nationale des Centres de Lutte Contre le Cancer, France<br />j) University of Newcastle, Australia<br />k) McMaster University, Canada<br />l) National Institute for Clinical Excellence, UK<br />m) Università di Modena e Reggio Emilia, Italy<br />n) Centro per la Valutazione della Efficacia della Assistenza Sanitaria, Italy<br />o) Australasian Cochrane Centre, Australia <br />p) Polish Institute for Evidence Based Medicine, Poland<br />q) The Cancer Council, Australia<br />r) Centre for Evidence-based Medicine, UK<br />s) National Cancer Institute, Italy<br />t) World Health Organisation, Switzerland <br />u) Finnish Medical Society Duodecim, Finland <br />v) Duke University Medical Center, USA <br />w) Centers for Disease Control and Prevention, USA<br />x) University of London, UK<br />Y) BMJ Clinical Evidence, UK<br />David Atkins, chief medical officera<br />Dana Best, assistant professorb<br />Martin Eccles, professord<br />Francoise Cluzeau, lecturerx<br />Yngve Falck-Ytter, associate directore<br />Signe Flottorp, researcherf<br />Gordon H Guyatt, professorg<br />Robin T Harbour, quality and information director h<br />Margaret C Haugh, methodologisti<br />David Henry, professorj<br />Suzanne Hill, senior lecturerj<br />Roman Jaeschke, clinical professork<br />Regina Kunx, Associate Professor<br />Gillian Leng, guidelines programme directorl<br />Alessandro Liberati, professorm<br />Nicola Magrini, directorn<br />James Mason, professord<br />Philippa Middleton, honorary research fellowo<br />Jacek Mrukowicz, executive directorp<br />Dianne O’Connell, senior epidemiologistq<br />Andrew D Oxman, directorf<br />Bob Phillips, associate fellowr<br />Holger J Schünemann, professorg,s<br />Tessa Tan-Torres Edejer, medical officert<br />David Tovey, Editory<br />Jane Thomas, Lecturer, UK<br />Helena Varonen, associate editoru<br />Gunn E Vist, researcherf<br />John W Williams Jr, professorv<br />Stephanie Zaza, project directorw<br />
  12. 12. GRADE uptake<br />
  13. 13. 11<br />GRADE: Quality of evidence<br />The extent to which our confidence in an estimate of the treatment effect is adequate to support particular recommendation. <br />Although the degree of confidence is a continuum, we suggest using four categories: <br /><ul><li>High
  14. 14. Moderate
  15. 15. Low
  16. 16. Very low</li></li></ul><li>Quality of evidence across studies<br />Outcome #1<br />Quality: High<br />Outcome #2<br />Quality: Moderate<br />Outcome #3<br />Quality: Low<br />I B<br />II<br />V<br />III<br />
  17. 17. Determinants of quality<br />RCTs start high<br />Observational studies start low <br />What lowers quality of evidence? 5 factors:<br />Detailed design and execution<br />Inconsistency of results<br />Indirectness of evidence<br />Imprecision<br />Publication bias<br />
  18. 18. 14<br />What is the study design?<br />
  19. 19. 1. Design and execution<br />Study limitations (risk of bias)<br />Lack of allocation concealment<br />No true intention to treat principle<br />Inadequate blinding<br />Loss to follow-up<br />Early stopping for benefit<br />
  20. 20. 2. Consistency of results<br />Look for explanation for inconsistency<br />patients, intervention, comparator, outcome, methods<br />Judgment<br />variation in size of effect<br />overlap in confidence intervals<br />statistical significance of heterogeneity<br />I2<br />
  21. 21. Pagliaro L et al. Ann Intern Med 1992;117:59-70<br />17<br />Heterogeneity<br />
  22. 22. 3. Directness of Evidence<br />Indirect comparisons<br />Interested in head-to-head comparison<br />Drug A versus drug B<br />Infliximab versus adalimumab in Crohn’s disease<br />Differences in<br />patients (early cirrhosis vs end-stage cirrhosis)<br />interventions (CRC screening: flex. sig. vs colonoscopy)<br />outcomes (non-steroidal safety: ulcer on endoscopy vs symptomatic ulcer complications)<br />
  23. 23. 4. Imprecision<br />Small sample size<br />small number of events<br />wide confidence intervals<br />uncertainty about magnitude of effect<br />
  24. 24. 5. Reporting Bias (Publication Bias)<br />Reporting of studies<br />publication bias<br />number of small studies<br />Reporting of outcomes<br />
  25. 25. Quality assessment criteria<br />Lower if…<br />Study design<br />Higher if…<br />Quality of evidence<br />Study limitations<br />(design and execution)<br />Randomized trial<br />High (4)<br />Moderate (3)<br />Inconsistency<br />What can raise the quality of evidence?<br />Observational study<br />Low (2)<br />Indirectness<br />Very low (1)<br />Imprecision<br />Publication bias<br />21<br />
  26. 26. BMJ 2003;327:1459–61<br />22<br />
  27. 27. Quality assessment criteria <br />Lower if…<br />Higher if…<br />Quality of evidence<br />Study design<br />Study limitations<br />Large effect (e.g., RR 0.5)<br />Very large effect (e.g., RR 0.2)<br />High (4)<br />Randomized trial<br />Moderate (3)<br />Inconsistency<br />Evidence of dose-response gradient<br />Observational study<br />Low (2)<br />Indirectness<br />All plausible confounding would reduce a demonstrated effect<br />Very low (1)<br />Imprecision<br />Publication bias<br />23<br />
  28. 28. 24<br />Categories of quality<br />Further research is very unlikely to change our confidence in the estimate of effect<br />High<br />Moderate<br />Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate<br />Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate<br />Low<br />Very low<br />Any estimate of effect is very uncertain<br />
  29. 29. 25<br />Judgments about the overall quality of evidence<br />Most systems not explicit<br />Options:<br />Benefits<br />Primary outcome<br />Highest <br />Lowest<br />Beyond the scope of a systematic review<br />GRADE: Based on lowest of all the critical outcomes<br />
  30. 30. GRADE evidence profile<br />
  31. 31. Strength of recommendation<br />“The strength of a recommendation reflects the extent to which we can, across the range of patients for whom the recommendations are intended, be confident that desirable effects of a management strategy outweigh undesirable effects.”<br />Although the strength of recommendation is a continuum, we suggest using two categories : <br /> “Strong” and “Weak”<br />
  32. 32. Desirable and undesirable effects<br />Desirable effects<br />Mortality reduction<br />Improvement in quality of life, fewer hospitalizations/infections<br />Reduction in the burden of treatment <br />Reduced resource expenditure <br />Undesirable effects<br />Deleterious impact on morbidity, mortality or quality of life, increased resource expenditure <br />
  33. 33. Determinants of the strength of recommendation<br />
  34. 34. Developing recommendations<br />
  35. 35. Implications of a strong recommendation<br /><ul><li>Patients: Most people in this situation would want the recommended course of action and only a small proportion would not
  36. 36. Clinicians: Most patients should receive the recommended course of action
  37. 37. Policy makers: The recommendation can be adapted as a policy in most situations</li></li></ul><li>Implications of a weak recommendation<br /><ul><li>Patients: The majority of people in this situation would want the recommended course of action, but many would not
  38. 38. Clinicians: Be prepared to help patients to make a decision that is consistent with their own values/decision aids and shared decision making
  39. 39. Policy makers: There is a need for substantial debate and involvement of stakeholders</li></li></ul><li>Where GRADE fits in<br />Prioritize problems, establish panel<br />Systematic review<br />Searches, selection of studies, data collection and analysis<br />Assess the relative importance of outcomes<br />Prepare evidence profile: Quality of evidence for each outcome and summary of findings<br />GRADE<br />Assess overall quality of evidence<br />Decide direction and strength of recommendation<br />Draft guideline<br />Consult with stakeholders and / or external peer reviewer<br />Disseminate guideline<br />Implement the guideline and evaluate<br />
  40. 40. Create <br />evidence profile with GRADEpro<br />Summary of findings & estimate of effect for each outcome<br />Guideline development<br />Rate <br />overall quality of evidence <br />across outcomes based on lowest quality <br />of critical outcomes<br />Rate quality of evidence for each outcome<br />Outcomes across studies<br />Formulate question<br />Rate importance<br />Select outcomes<br />RCT start high, <br />obs. data start low<br />Risk of bias<br />Inconsistency<br />Indirectness<br />Imprecision<br />Publication bias<br />P<br />I<br />C<br />O<br />Outcome<br />Critical<br />High<br />Outcome<br />Critical<br />Moderate<br />Grade down<br />Low<br />Outcome<br />Important<br />Very low<br />Outcome<br />Not<br />important<br />Large effect<br />Dose response<br />Confounders<br />Grade up<br />Panel<br />Formulate recommendations:<br /><ul><li>For or against (direction)
  41. 41. Strong or weak (strength)</li></ul>By considering:<br /><ul><li>Quality of evidence
  42. 42. Balance benefits/harms
  43. 43. Values and preferences</li></ul>Revise if necessary by considering:<br /><ul><li>Resource use (cost)</li></ul>Systematic review<br /><ul><li>“We recommend using…”
  44. 44. “We suggest using…”
  45. 45. “We recommend against using…”
  46. 46. “We suggest against using…”</li></li></ul><li>Conclusions<br />GRADE is gaining acceptance as international standard<br />Criteria for evidence assessment across questions and outcomes<br />Criteria for moving from evidence to recommendations<br />Simple, transparent, systematic<br />Transparency in decision making and judgments is key<br />

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