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Updated: Nov 2, 2025

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
When applying GRADE, how do we decide the target of certainty of evidence rating?
Linan Zeng1,2, Romina Brignardello-Petersen3, Gordon Guyatt3
1Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada zengl15@mcmaster.ca.
Abstract:
The Grades of Recommendation, Assessment, Development and Evaluation' (GRADE) offers a widely adopted, transparent and structured process for developing and presenting summaries of evidence, including the certainty of evidence, for systematic reviews and recommendations in healthcare. GRADE defined certainty of evidence as 'the extent of our confidence that the estimates of the effect are correct (in the context of systematic review), or are adequate to support a particular decision or recommendation (in the context of guideline)'. Realising the incoherence in the conceptualisation, the GRADE working group re-clarified the certainty of evidence as 'the certainty that a true effect lies on one side of a specified threshold, or within a chosen range'. Following the new concept, in the context of both systematic reviews and health technology assessments, it is desirable for GRADE users to specify the thresholds and clarify of which effect they are certain. To help GRADE users apply GRADE in accordance with the new conceptualisation, GRADE defines three levels of contextualisation: minimally, partially and fully contextualised approaches, and provides possible thresholds for each level of contextualisation. In this article, we will use a hypothetic systematic review to illustrate the application of the minimally and partially contextualised approaches, and discuss the application of a fully contextualised approach in deciding how we are rating our certainty (i.e.target of the rating of certainty of evidence).
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