Table 4

The GRADE System for Grading Quality of Evidence and Strength of Recommendations[2,5]

Quality of evidence for each outcome (high, moderate, or low) – based on the following criteria:

• Study design– grade of high or low assigned based on design (RCT = high, observational study = low)

• Study quality– Detailed study methods and execution.

1) Limitations in quality can decrease grade one or two levels.

2) Evidence of reporting bias can also decrease grade one level.

3) Grade can be increased one level if all plausible confounders would have reduced the treatment effect.

• Consistency of results– The level of similarity of estimates of effects across studies.

1) Important inconsistency can decrease grade one level.

• Directness of evidence– the extent to which the people, interventions, and outcome measures are similar to those of interest.

1) Some or major uncertainty about directness lowers the grade one or two levels.

• Other considerations

1) Magnitude of effect can increase the grade of evidence. Strong evidence of association (significant relative risk of >2 or <0.5 based on consistent evidence from 2 or more observational studies with no plausible confounders) increases the grade by one level. Very strong evidence of association (significant relative risk of >5 or <0.2 based on direct evidence with no major threats to validity) increases the grade by two levels.

2) Evidence of a dose-response gradient increases the grade by one level.

3) Imprecise or sparse data can lower the grade by one level.

Relative importance of outcomes – included outcomes should be critical or important (but not critical) to a decision

Overall quality of evidence – judged across outcomes based on the lowest quality of evidence for any of the critical outcomes

Balance of benefits and harms – classified as net benefits, trade-offs, uncertain trade-offs, or no net benefits based on the important health benefits and harms

Balance of net benefits and costs – are incremental health benefits worth the costs?

Strength of recommendation – the extent to which one can be confident that adherence to a recommendation will do more good than harm

Treadwell et al. BMC Medical Research Methodology 2006 6:52   doi:10.1186/1471-2288-6-52