| First step: quality of evidence and definitions |
| 4. High quality |
| Further research is very unlikely to change our confidence in the estimate of effect |
| 3. Moderate quality |
| Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate |
| 2. Low quality |
| Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate |
| 1. Very low quality |
| Any estimate of effect is very uncertain |
| Second step: criteria for assigning grade of evidence |
| Type of evidence |
| Randomised trial: high |
| Observational study: low |
| Any other evidence: very low |
| Decrease grade if: |
| Serious (-1) or very serious (-2) limitation to study quality |
| Important inconsistency (-1) |
| Some (-1) or major (-2) uncertainty about directness |
| Imprecise or sparse data (-1) |
| High probability of reporting bias (-1) |
| Increase grade if: |
| Strong evidence of association: significant relative risk of >2 (<0.5) based on consistent evidence from two or more observational studies, with no plausible confounders (+1) |
| Very strong evidence of association: significant relative risk of >5 (<0.2) based on direct evidence with no major threats to validity (+2) |
| Evidence of a dose–response gradient (+1) |
| All plausible confounders would have reduced the effect (+1) |
| Third step: strength of recommendation |
| Fs: strong recommendation for using an intervention |
| Fw: weak recommendation for using an intervention |
| Aw: weak recommendation against using an intervention |
| As: strong recommendation against using an intervention |
| Determinants of strength: balance between desirable and undesirable effects; quality of evidence; values and preferences; costs (resource allocation) |
Modified from [12] with permission from the publisher.