According to WHO Handbook for Guidelines, we used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to assess the quality of a body of evidence, develop and report recommendations. GRADE methods are used by WHO because these represent internationally agreed standards for making transparent recommendations. Detailed GRADE information is available on the following site:
https://www.gradeworkinggroup.org/
Table 1 Quality and Significance of the four levels of evidence in GRADE:
|
Quality |
Definition
|
Implications |
|
High |
The guideline development group is very confident that the true effect lies close to that of the estimate of the effect. |
Further research is very unlikely to change confidence in the estimate of effect |
|
Moderate |
The guideline development group is moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different |
Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate |
|
Low |
Confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the true effect |
Further research is very likely to have an important impact on confidence in the estimate of effect and is unlikely to change the estimate |
|
Very Low |
The group has very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of the effect. |
Any estimate of effect is very uncertain |
Table 2: Factors that determine How to upgrade or downgrade the quality of evidence:
|
Downgrade in presence of |
Upgrade in presence of |
|
Study limitations -1 Serious limitations -2 Very serious limitations
Consistency -1 Important inconsistency
Directness -1 Some uncertainty -2 Major uncertainty
Precision -1 Imprecise data Reporting bias -1 High probability of reporting bias |
Dose-response gradient +1 Evidence of a dose-response gradient
Direction of plausible bias +1 All plausible confounders would have reduced the effect
Magnitude of the effect +1 Strong, no plausible confounders, consistent and direct evidence
+2 Very strong, no major threats to validity and direct evidence |
The strength of recommendations:
The strength of a recommendation communicates the importance of adherence to the recommendation.
Strong recommendations
With strong recommendations, the guideline communicates the message that the desirable effects of adherence to the recommendation outweigh the undesirable effects. This means that in most situations the recommendation can be adopted as policy.
Conditional recommendations
These are made when there is greater uncertainty about the four factors above or if local adaptation has to account for a greater variety in values and preferences, or when resource use makes the intervention suitable for some, but not for other locations. This means that there is a need for substantial debate and involvement of stakeholders before this recommendation can be adopted as policy.
Good practice recommendations:
Clinical opinion suggests this advice is well established or supported. No robust underpinning research evidence exists. Good practice points are primarily based on extrapolation from research on related topics and/or clinical consensus, expert opinion and precedent, and not on research appropriate for rating the certainty or quality of the evidence
When not to make recommendations:
When there is lack of evidence on the effectiveness of an intervention, it may be appropriate not to make a recommendation.