| Downgrades the evidence* | Upgrades the evidence |
| Study limitation | Large magnitude of effect |
| Inconsistency of results (unexplained heterogeneity, inconsistency of results) | All plausible confounding would reduce the demonstrated effect |
| Indirectness of evidence (indirect population, intervention, control, outcomes) | Dose‐response gradient |
| Imprecision (wide confidence intervals, single trial) | |
| Publication bias |