S I G N

Levels of evidence and grades of recommendation

1⁺⁺

High quality meta analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias

1⁺

Well conducted meta analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1 ^-

Meta analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2⁺⁺

High quality systematic reviews of case-control or cohort or studies

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 or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal

2 ^-

Case control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal

3

Non-analytic studies, e.g. case reports, case series

4

Expert opinion

A

At least one meta analysis, systematic review, or RCT rated as 1⁺⁺, and directly applicable to the target population; or

A systematic review of RCTs 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⁺