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Updated: Sep 5, 2025

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
How to gain evidence for causation in disease and therapeutic intervention: from Koch's postulates to
1Centre of Precision Rehabilitation for Spinal Pain, School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, B15 2TT, Edgbaston, Birmingham, UK. dwe@backpainclinic.co.uk.
Abstract:
Researchers, clinicians, and patients have good reasons for wanting answers to causal questions of disease and therapeutic intervention. This paper uses microbiologist Robert Koch's pioneering work and famous postulates to extrapolate a logical sequence of evidence for confirming the causes of disease: association between individuals with and without a disease; isolation of causal agents; and the creation of a counterfactual (demonstrating that an agent is sufficient to reproduce the disease anew). This paper formally introduces counter-counterfactuals, which appear to have been used, perhaps intuitively, since the time of Koch and possibly earlier. An argument is presented that counter-counterfactuals (disease-preventers) are a useful tool for identifying necessary causes of disease, and sometimes must be used in place of isolation which is not always possible. In addition, a logical sequence of causal evidence for a therapeutic intervention is presented: creating a counterfactual (demonstrating that the intervention is sufficient to change the natural course of a disease), comparisons between subjects in receipt of treatment versus those who are not (typically within a randomised controlled trial, which can quantify effects of intervention), and counter-counterfactuals (treatment-preventers, which can identify the intervention's mechanisms of action).
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