Table 1. Recommendation and evidence rating (GRADE system).

Assessment of evidence level					Strength of recommendation
Study design	Initial quality of evidence	Factors that downgrade quality of evidence	Factors that upgrade quality of evidence	Quality of evidence
Randomized study	High ⇨	Risk of bias  Serious: −1  Very serious: −2	Effect size  Large: +1  Very large: +2	High: 4 Moderate: 3 Low: 2 Very low: 1	Strong: Benefits clearly outweigh harm, or vice versa Weak: All cases other than “strong” recommendation
		Inconsistency  Serious: −1  Very serious: −2	Positive relation  Present: +1
Observational study	Low ⇨	Indirectness  Serious: −1  Very serious: −2	Confounding variables  Increased confidence of effect estimation: +1
		Imprecision  Serious: −1  Very serious: −2
		Publication bias  Strongly suspected: −1