GRADE system classification scheme

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was developed to determine the strength of recommendations as strong (1) or weak (2) and to guide assessment of quality of evidence from high (A) to very low (D).[1]

Strength of Recommendations

The GRADE system classifies recommendations as strong (grade 1) or weak (grade 2). Factors influencing this determination are as follows:

What Should be Considered Recommended Process
High or moderate evidence (Is there high or moderate quality evidence?) The higher the quality of evidence, the more likely a strong recommendation.
Certainty about the balance of benefits vs. harms and burdens (Is there certainty?) The larger the difference between the desirable and undesirable consequences and the certainty around that difference, the more likely a strong recommendation. The smaller the net benefit and the lower the certainty for that benefit, the more likely a weak recommendation.
Certainty in or similar values (Is there certainty or similarity?) The more certainty or similarity in values and preferences, the more likely a strong recommendation.
Resource implications (Are resources worth expected benefits?) The lower the cost of an intervention compared to the alternative and other costs related to the decision–ie, fewer resources consumed–the more likely a strong recommendation.

Quality of Evidence

The GRADE system classifies quality of evidence as high (grade A), moderate (grade B), low (grade C), or very low (grade D). Determinants of the quality of evidence are as follows:

Underlying methodology
  • A (high) — RCTs
  • B (moderate) — Downgraded RCTs or upgraded observational studies
  • C (low) — Well-done observational studies with control randomized controlled trials
  • D (very low) — Downgraded controlled studies or expert opinion based on other evidence
Factors that may decrease the strength of evidence
  • Poor quality of planning and implementation of available RCTs, suggesting high likelihood of bias
  • Inconsistency of results, including problems with subgroup analyses
  • Indirectness of evidence (differing population, intervention, control, outcomes, comparison)
  • Imprecision of results
  • High likelihood of reporting bias
Main factors that may increase the strength of evidence
  • Large magnitude of effect (direct evidence, relative risk > 2 with no plausible confounders)
  • Very large magnitude of effect with relative risk > 5 and no threats to validity (by two levels)
  • Dose-response gradient

References

  1. Guyatt, Gordon H.; Oxman, Andrew D.; Vist, Gunn E.; Kunz, Regina; Falck-Ytter, Yngve; Alonso-Coello, Pablo; Schünemann, Holger J.; GRADE Working Group (2008-04-26). "GRADE: an emerging consensus on rating quality of evidence and strength of recommendations". BMJ (Clinical research ed.). 336 (7650): 924–926. doi:10.1136/bmj.39489.470347.AD. ISSN 1756-1833. PMC 2335261. PMID 18436948.

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