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Updated: Oct 10, 2025

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Reverse-Bayes methods for evidence assessment and research synthesis
Leonhard Held1, Robert Matthews2, Manuela Ott1,3
1Department of Biostatistics, University of Zurich, Zurich, Switzerland.
Abstract:
It is now widely accepted that the standard inferential toolkit used by the scientific research community-null-hypothesis significance testing (NHST)-is not fit for purpose. Yet despite the threat posed to the scientific enterprise, there is no agreement concerning alternative approaches for evidence assessment. This lack of consensus reflects long-standing issues concerning Bayesian methods, the principal alternative to NHST. We report on recent work that builds on an approach to inference put forward over 70 years ago to address the well-known "Problem of Priors" in Bayesian analysis, by reversing the conventional prior-likelihood-posterior ("forward") use of Bayes' theorem. Such Reverse-Bayes analysis allows priors to be deduced from the likelihood by requiring that the posterior achieve a specified level of credibility. We summarise the technical underpinning of this approach, and show how it opens up new approaches to common inferential challenges, such as assessing the credibility of scientific findings, setting them in appropriate context, estimating the probability of successful replications, and extracting more insight from NHST while reducing the risk of misinterpretation. We argue that Reverse-Bayes methods have a key role to play in making Bayesian methods more accessible and attractive for evidence assessment and research synthesis. As a running example we consider a recently published meta-analysis from several randomised controlled trials (RCTs) investigating the association between corticosteroids and mortality in hospitalised patients with COVID-19.
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