1. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Methodology

2. Strength of Evidence A (high)RCT B (moderate)Downgraded RCT or upgraded observational studies C (low)Well-done observational or cohort studies with controls D (very low)Case series or expert opinion BMJ 2008;336:924

3. Downgrading and Upgrading Evidence RCT Poor quality of planning and implementation Inconsistency of results Indirectness of evidence Imprecision of results High likelihood of reporting bias Observational Studies Start with “low-quality” rating Magnitude of effect is very large Dose-response relation All plausible biases would decrease magnitude of apparent treatment effect

4. Strength of Recommendation Strong –Recommend –when virtually all informed patients would choose the same management strategy Weak (conditional) –Suggest –imply that choices will differ across the range of patient values and preferences

5. Factors That Influence Strength of Recommendation What should be consideredRecommended process High or moderate evidence The higher the quality of evidence, the more likely is a strong recommendation Certainty about the balance of benefits versus harms and burdens The larger the difference between the desirable and undesirable consequences and the certainty around that difference, the more likely a strong recommendation. The smaller the net benefit and the lower the certainty for that benefit, the more likely is a weak recommendation. Certainty in or similar values The more certainty or similarity in values and preferences, the more likely is a strong recommendation. Resource implicationsThe lower the cost of an intervention compared to the alternative and other costs related to the decision – that is, fewer resources consumed – the more likely is a strong recommendation.