Key points
GRADE requires a clear specification of the relevant setting, population, intervention, comparator(s), and outcomes.
Outcomes of interest should be those important to patients: if patient-important outcomes are represented by a surrogate, they will frequently require rating down the quality of evidence for indirectness.
Questions must be sufficiently specific: across the range of populations, interventions, and outcomes, a more or less similar effect must be plausible.
For a guideline, an initial rating of the importance of outcomes should precede the review of the evidence, and this rating should be confirmed or revised following the evidence review.