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The level of evidence (LOE) grading system for ESC Clinical Practice Guidelines classifies the quality of the evidence supporting a recommendation. However, the current taxonomy does not fully consider the optimal study design necessary to establish evidence for such recommendations. Therefore, two separate taskforces of clinical and methodological experts were appointed by the Clinical Practice Guidelines Committee, with the first tasked with updating the LOE grading system for therapy and prevention, and the second responsible for developing a LOE grading system for diagnosis and prediction. The updated system for therapy and prevention presented here maintains the three-level grading structure but uses revised definitions. Level of evidence A represents conclusive evidence usually from ≥2 adequately powered randomized controlled trials (RCTs) free from major bias, with substantial evidence against the play of chance when combined in a meta-analysis (e.g. P < .005 for superiority). Additional criteria are specified to define substantial evidence against the play of chance in case of non-inferiority, equivalence, and harm. Level of evidence B is now subdivided into B1 and B2. Level of evidence B1 represents suggestive evidence usually from ≥1 adequately powered RCT free from major bias, or a meta-analysis of such RCTs, with some evidence against the play of chance (e.g. P < .05 for superiority). Level of evidence B2 represents limited evidence from ≥2 adequately powered non-randomized studies with careful control of major sources of bias or from a meta-analysis of small, underpowered RCTs. Level of evidence C represents preliminary evidence from either non-randomized studies without careful control of major sources of bias, a single small, underpowered RCT, or expert consensus.

Original publication

DOI

10.1093/eurheartj/ehaf009

Type

Journal

Eur Heart J

Publication Date

21/03/2025

Keywords

Guidelines, Level of evidence, Meta-analysis, Randomized controlled trial