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GRADE Methodology

The evidence grading system behind every SilverCancer synthesis.

Contents

What is GRADE?Certainty levelsRating domainsRecommendation strengthHow SilverCancer uses GRADEGRADE and ESMO

Also

ESMO guidelinesEU trial registriesDocumentation

What is GRADE?

GRADE (Grading of Recommendations Assessment, Development and Evaluation) is the internationally accepted framework for evaluating the quality of evidence and the strength of recommendations. Used by WHO, ESMO, EAN, Cochrane and most major oncology guideline bodies, it makes the basis of recommendations explicit and auditable.

GRADE addresses two distinct questions separately: how certain are we about the evidence? and how strong should the recommendation be? Conflating them is common and consequential.

Why it matters: Oncology decisions involve complex trade-offs between uncertain evidence, significant toxicity and patient values. GRADE makes certainty explicit — which is essential when AI synthesises the evidence.

Certainty levels

LevelSymbolMeaningTypical sources
HIGH⊕⊕⊕⊕Very confident the true effect is close to the estimate.Well-conducted RCTs with consistent results
MODERATE⊕⊕⊕◯Moderately confident. A substantially different effect is possible.RCTs with some limitations; upgraded observational studies
LOW⊕⊕◯◯Limited confidence. The true effect may be substantially different.Observational studies; RCTs with serious limitations
VERY LOW⊕◯◯◯Very little confidence. True effect likely substantially different.Case series, expert opinion, very indirect evidence

Rating domains

Factors that lower certainty (from RCTs)

  • Risk of bias — poor allocation concealment, lack of blinding, high dropout
  • Inconsistency — unexplained heterogeneity (high I²)
  • Indirectness — different populations, interventions or outcomes
  • Imprecision — wide confidence intervals, few events
  • Publication bias

Factors that can raise certainty (observational studies)

  • Large effect size — RR >2 or <0.5, no plausible confounding
  • Dose-response gradient with clear biological plausibility

Recommendation strength

GRADE distinguishes strong recommendations from conditional recommendations. Strength reflects the balance of benefits versus harms, patient values and resource use — not just evidence certainty. A conditional recommendation with high-certainty evidence means the trade-offs are context-dependent, not that the evidence is weak.

How SilverCancer uses GRADE

Every synthesis includes an explicit GRADE certainty rating with the reasoning behind it. We do not hide uncertainty.

Limitation: SilverCancer's GRADE assessments are AI-generated to support clinical reasoning — not produced by a formal guideline panel. For definitive assessments refer to the relevant ESMO CPG or Cochrane review directly.

GRADE and ESMO guidelines

ESMO CPGs use evidence levels I–V and recommendation grades A–E. SilverCancer maps both to GRADE certainty categories and displays them together. Where they diverge, this is noted. Further reading: gradeworkinggroup.org · ESMO Clinical Practice Guidelines