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J Clin Epidemiol. 2011 Dec;64(12):1311-6. doi: 10.1016/j.jclinepi.2011.06.004. Epub 2011 Jul 30.

GRADE guidelines: 9. Rating up the quality of evidence.

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Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street, West Hamilton, Ontario L8N 3Z5, Canada.


The most common reason for rating up the quality of evidence is a large effect. GRADE suggests considering rating up quality of evidence one level when methodologically rigorous observational studies show at least a two-fold reduction or increase in risk, and rating up two levels for at least a five-fold reduction or increase in risk. Systematic review authors and guideline developers may also consider rating up quality of evidence when a dose-response gradient is present, and when all plausible confounders or biases would decrease an apparent treatment effect, or would create a spurious effect when results suggest no effect. Other considerations include the rapidity of the response, the underlying trajectory of the condition, and indirect evidence.

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