Abstract

Objective:Root causes of disease intuitively correspond to root vertices of a causal model that increase the likelihood of a diagnosis. This description of a root cause nevertheless lacks the rigorous mathematical formulation needed for the development of computer algorithms designed to automatically detect root causes from data. We seek a definition of patient-specific root causes of disease that models the intuitive procedure routinely utilized by physicians to uncover root causes in the clinic. Methods:We use structural equation models, interventional counterfactuals and the recently developed mathematical formalization of backtracking counterfactuals to propose a counterfactual formulation of patient-specific root causes of disease matching clinical intuition. Results:We introduce a definition of patient-specific root causes of disease that climbs to the third rung of Pearl’s Ladder of Causation and matches clinical intuition given factual patient data and a working causal model. We then show how to assign a root causal contribution score to each variable using Shapley values from explainable artificial intelligence. Conclusion:The proposed counterfactual formulation of patient-specific root causes of disease accounts for noisy labels, adapts to disease prevalence and admits fast computation without the need for counterfactual simulation.

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