Table 1.

Use of GRADE not considering ROBINS-I and similar tools: According to GRADE, certainty, quality, strength of the evidence or the confidence in the estimate of effect, is determined for each outcome based on a systematic review of the evidence for each outcome. For recommendations, the overall certainty is determined across outcomes based on the lowest quality outcome among those critical for decision-making for the specific context.

1. Establish initial level of certainty (as implemented in current GRADE)			2. Consider lowering or raising level of certainty			3. Final level of certainty rating
Study design	Initial certainty in the evidence		Reasons for considering lowering or raising certainty			Certainty in the evidence across those considerations
			↓ Lower if	↑ Higher if*
Randomized trials →	High certainty		Risk of Bias	Large effect		High ⊕⊕⊕⊕
			Inconsistency	Dose response
			Indirectness	All plausible confounding and bias would reduce a demonstrated effect or would suggest a spurious effect if no effect was observed		Moderate ⊕⊕⊕○
			Imprecision
Observational studies →	Low certainty		Publication bias			Low ⊕⊕○○
						Very low ⊕○○○

^*Criteria for upgrading the quality are usually only applicable to observational studies without any reason for rating down.