Grading of Recommendations Assessment, Development and

Evaluation (GRADE) Methodology

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

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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

ObservationalStudies

• Start with “low-quality” rating• Magnitude of effect is very large • Dose-response relation • All plausible biases would

decrease magnitude of apparent treatment effect

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

Factors That Influence Strength of Recommendation

What should be considered Recommended 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 implications The 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.