5.1. Introduction

GRADE specifies four quality categories (high, moderate, low, and very low) that are applied to a body of evidence, but not to individual studies. In the context of a systematic review, quality reflects our confidence that the effect estimates are correct. In the context of recommendations, quality reflects our confidence that the effect estimates are adequate to support a particular recommendation.

Guideline panels have to determine the overall quality of evidence across all the critical outcomes essential to a recommendation they make. Guideline panels usually provide a single grade of quality of evidence for every recommendation, but the strength of a recommendation usually depends on evidence regarding not just one, but a number of patient-important outcomes and on the quality of evidence for each of these outcomes.

When determining the overall quality of evidence across outcomes:

• Consider only those outcomes that are deemed critical;
• If the quality of evidence differs across critical outcomes and outcomes point in different directions — towards benefit and towards harm — the lowest quality of evidence for any of the critical outcomes determines the overall quality of evidence;
• If all outcomes point in the same direction — towards either benefit or harm — the highest quality of evidence for a critical outcome, that by itself would suffice to recommend an intervention, determines the overall quality of evidence. However, if the balance of the benefits and harms is uncertain, the grade of the critical outcome with the lowest quality grading should be assigned.