APPENDIX 1:
SIGN grading
| Levels of evidence | |
| 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, 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 recommendation | |
| 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 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 2++ | |
| D | Evidence rated 3 or 4, or |
| Extrapolated evidence from studies rated 2+ |
