Table 2

Criteria for downgrading the quality of outcomes using the grade approach (reproduced with permission)

	Reason to downgrade the level of evidence
Risk of bias	Majority of studies rated as being at unclear risk of bias. Outcome includes studies that have been rated as being at high risk of bias in two or more categories.
Inconsistency	Large heterogeneity based on the similarity of point estimates, statistical heterogeneity and I² ≥50%.
Imprecision	Large CIs when data are presented as standardised mean difference. Substantial heterogeneity (I² ≥50%) If a recommendation or clinical course of action would differ if the upper versus the lower boundary of the CI represented the truth. Sample size <400 within the meta-analysis for each variable.
Indirectness	Use of surrogate outcomes
Publication bias	Asymmetric funnel plot