The unique features of GRADE include: (1) explicit, comprehensive criteria for downgrading and upgrading quality of evidence ratings; (2) explicit evaluation of the importance of outcomes and (3) clear separation of quality of evidence from the strength of recommendations.
The unique features of Grading of Recommendations Assessment, Development and Evaluation include: (1) explicit, comprehensive criteria for downgrading and upgrading quality of evidence ratings; (2) explicit evaluation of the importance of outcomes; and (3) clear separation of quality of evidence from the strength of care recommendations.
In another example, in following recommendations from GRADE, we defined the factor for upgrading the quality of evidence based on large magnitude of effect as associations with an RR > 2 (+1 upgrade to the evidence) or an RR > 5 (+2 upgrade to the evidence).
Then, the related outcomes would be considered together and reevaluated for properties that relate to downgrading and upgrading the body of evidence.
23 In case of non-randomised studies, the following three factors that may lead to upgrading the quality of evidence will be considered: (1) a strong or very strong association, (2) a dose effect relationship, and (3) all plausible confounding may be working to reduce the demonstrated effect or increase the effect if no effect was observed.
Similar to previous overviews, we will make judgments to downgrade or upgrade the quality of evidence based on the risk of bias using criteria specified by the GRADE working group.
The instructions to review authors also contained information on how to evaluate the human body of evidence for upgrading based on consideration of three factors (animal evidence was not eligible for upgrading because of its initial "high" rating); for details, see Supplemental Material, "Instructions for rating the quality and strength of human and nonhuman evidence".
Consistent with GRADE guidelines (Guyatt et al. 2011d), we did not upgrade or downgrade the body of evidence unless there was a compelling rationale to do so.
According to the GRADE approach, observational studies are usually rated as low-quality evidence but can be upgraded based on the quality of evidence under certain exceptional conditions [ 7].
Despite potential biases as well as heterogeneity, inconsistency, diversity, and overlapping prediction intervals, the overall quality of evidence was upgraded from low to moderate based on the magnitude of effect observed, trial sequential analysis results, and lack of adverse events.
