1. Considerations in grading a recommendation methodological quality of evidencemethodological quality of evidence likelihood of biaslikelihood of bias trade-off between benefits and riskstrade-off between benefits and risks

2. Methodological quality specific to an outcome benefitsbenefits –often have RCTS risksrisks –often limited to observational studies

3. Possible levels of quality strongstrong intermediateintermediate weakweak very weakvery weak

4. Quality of evidence, Where to start? basic study designbasic study design randomized trialsrandomized trials –strong evidence observational studiesobservational studies –weak evidence

5. Downgrading quality, weak implementation detailed design and executiondetailed design and execution –concealment –balance in known prognostic factors –intention to treat principle observed –blinding –completeness of follow-up

6. Downgrading quality inconsistency evidence weaker if results differ from study to studyevidence weaker if results differ from study to study subjective judgementsubjective judgement –you will be told

7. Downgrading quality, indirectness indirect treatment comparisonsindirect treatment comparisons –interested in A versus B –have A versus C and B versus C different patient populationdifferent patient population different interventiondifferent intervention different outcomedifferent outcome

8. Downgrading quality, reporting bias, sparse data what if you have a biased sample of studies?what if you have a biased sample of studies? publication biaspublication bias what if one study with 10 people?what if one study with 10 people?

9. What can increase strength of evidence? large association can upgradelarge association can upgrade –very large, 2 levels –large with no plausible confounders, 1 level dose-response gradientdose-response gradient –can upgrade one level

10. Grade of Recommendations do it or don’t do itdo it or don’t do it –strong recommendation probably do it, or probably don’tprobably do it, or probably don’t –weaker recommendation

11. Risk/Benefit tradeoff seriousness of outcomeseriousness of outcome magnitude of effectmagnitude of effect precision of treatment effectprecision of treatment effect risk of target eventrisk of target event risk of adverse eventsrisk of adverse events cost of therapycost of therapy values and preferencesvalues and preferences