Table 1 SIGN (Scottish Intercollegiate Guidelines Network) Annex B: key to evidence statements and grades of recommendations

Levels of evidence
1++	High-quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+	Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
1−	Meta-analyses, systematic reviews, or RCTs with a high risk of bias
2++	High-quality systematic reviews of case–control or cohort studies
	High-quality case–control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+	Well-conducted case–control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2−	Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3	Non-analytical studies (eg, case reports, case series)
4	Expert opinion

Grades of recommendations
A	At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population; or
	A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B	A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
	Extrapolated evidence from studies rated as 1++ or 1+
C	A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
	Extrapolated evidence from studies rated as 2++
D	Evidence level 3 or 4; or
	Extrapolated evidence from studies rated as 2+

Good practice points
√	Recommended best practice based on the clinical experience of the guideline development group

Note: the grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.