Table 4

Description of methods for grading of overall evidence

Study designQuality of evidence*Lower certainty score ifHigher certainty score if
Randomised trialHighRisk of bias
  • 1 Serious

  • 2 Very serious


Inconsistency
  • 1 Serious

  • 2 Very serious


Indirectness
  • 1 Serious

  • 2 Very serious


Imprecision
  • 1 Serious

  • 2 Very serious


Publication bias
  • 1 Likely

  • 2 Very likely

Large effect
+1 Large
+2 Very large


Dose–response
+1 evidence of a gradient


All plausible confounding would:
+1 Reduce a demonstrated effect


+1 Suggest a spurious effect when results show no effect
Moderate
Observational studyLow
Very low
  • *In the GRADE approach, randomised controlled trials (RCTs) start as high-quality evidence and observational studies as low-quality evidence supporting estimates of intervention effects. Five factors may lead to rating down the quality of evidence, and three factors may lead to rating up. Ultimately, the quality of evidence for each outcome falls into one of four categories, from high to very low. GRADE is ‘outcome centric’: rating is made for each outcome, and quality may differ indeed, is likely to differ from one outcome to another within a single study and across a body of evidence.21