Table 4.

Factors that may influence the quality level of a body of evidence.

Decrease Quality	Increase Quality
Within study, risk of bias causes the overall analysis to be biased Indirectness of evidence (i.e., considering each of the following 4 PICO letters — participant, intervention, control, and outcome, especially surrogates). If any of the PICO factors are not directly clinically relevant, the evidence might be judged appropriate for downgrading Unexplained heterogeneity or inconsistency of results (including problems with subgroup analyses, making it difficult to interpret the overall metaanalysis) Lack of precision of the overall effect estimates (wide CI), when the overall analysis does not confirm that the effect size is evident Risk of publication bias	A large magnitude of effect All plausible confounding would reduce a demonstrated effect or suggest a spurious effect when results show no effect Evidence of a dose-response gradient

Decrease Quality

Increase Quality

Within study, risk of bias causes the overall analysis to be biased
Indirectness of evidence (i.e., considering each of the following 4 PICO letters — participant, intervention, control, and outcome, especially surrogates). If any of the PICO factors are not directly clinically relevant, the evidence might be judged appropriate for downgrading
Unexplained heterogeneity or inconsistency of results (including problems with subgroup analyses, making it difficult to interpret the overall metaanalysis)
Lack of precision of the overall effect estimates (wide CI), when the overall analysis does not confirm that the effect size is evident
Risk of publication bias

A large magnitude of effect
All plausible confounding would reduce a demonstrated effect or suggest a spurious effect when results show no effect
Evidence of a dose-response gradient