3.3.6 Grading the quality of clinical evidence
After results were pooled, the overall quality of evidence for each outcome was considered. The following procedure was adopted when using GRADE:
1. A quality rating was assigned, based on the study design. RCTs start HIGH and observational studies as LOW, uncontrolled case series as LOW or VERY LOW.
2. The rating was then downgraded for the specified criteria: Study limitations, inconsistency, indirectness, imprecision and reporting bias. These criteria are detailed below. Observational studies were upgraded if there was: a large magnitude of effect, dose-response gradient, and if all plausible confounding would reduce a demonstrated effect or suggest a spurious effect when results showed no effect. Each quality element considered to have “serious” or “very serious” risk of bias was rated down -1 or -2 points respectively.
3. The downgraded/upgraded marks were then summed and the overall quality rating was revised. For example, all RCTs started as HIGH and the overall quality became MODERATE, LOW or VERY LOW if 1, 2 or 3 points were deducted respectively.
4. The reasons or criteria used for downgrading were specified in the footnotes.