Tab. 5  Classification of levels of evidence according to SIGN.

Level	Description
1++	High-quality meta-analyses, systematic review of 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, or High-quality case-control or cohort studies with a very low risk of confounding, bias or “chance” and a high probability that the relationship is causal.
2+	Well-conducted case-control studies or cohort studies with a low risk of confounding, bias or “chance” and a moderate probability that the relationship is causal.
2−	Case-control studies or cohort studies with a high risk of confounding, bias or “chance” and a significant risk that the relationship is not causal.
3	Non-analytical studies, e.g., case reports, case series
4	Expert opinion