Medical Causal Hypothesis Verification with Large Language Models

The growing use of large language models (LLMs) for search and information retrieval underscores the need to evaluate their reliability in high-stakes domains such as healthcare. Although LLMs can effectively answer questions about diseases, symptoms, and treatments, their ability to accurately assess causal relationships and ground their conclusions in verified scientific evidence remains unclear. Here, we present a preliminary, small-scale study that investigates the accuracy of LLMs in evaluating causal medical claims and supporting them with peer-reviewed research. We propose an evaluation framework for causal hypothesis verification that can be used to systematically track the performance of existing and future LLMs. We assess the performance of eight LLMs on 17 medical causal hypotheses to evaluate whether they can reliably verify these hypotheses using scientific evidence from the literature. We systematically annotate the scientific evidence they provide according to six criteria (a total of 1,067 annotation points) and assess them with nine evaluation metrics. Our analysis shows that while LLMs exhibit strong recall, they often perform poorly at providing valid scientific articles and evidence for support and at rejecting unsupported hypotheses. These findings highlight a critical limitation of current LLMs, as they cannot yet be trusted fully to verify causal relationships from the biomedical literature. This work underscores the need for rigorous evaluation before using LLMs for search and retrieval in healthcare settings.

Framework for Grounding Healthcare LLMs in a Causal Knowledge Graph: A Cardiovascular Example Pilot

Large language models (LLMs) are increasingly proposed for healthcare decision support, but their evaluations still reward single-answer accuracy rather than reasoning about interventions, mechanisms, harms, evidence, and uncertainty. We propose a reproducible, graph-centered evaluation framework for intervention-oriented LLM behavior in healthcare and stress-test it in a cardiovascular pilot. The framework has four components: (i) a domain causal knowledge graph in which assertions are first-class, provenance-preserving nodes with stable identifiers; (ii) a scenario-conditioned subgraph extraction step that, given any clinical scenario, retrieves the relevant reified-assertion subgraph; (iii) four controlled grounding conditions that vary how the retrieved subgraph is composed into the model's context (ungrounded C1, knowledge-graph C2, causal-graph C3, integrated C4); and (iv) an automated scoring pipeline, anchored on assertion identifiers, that computes intervention accuracy, and other evaluation measures on a single pass. To test the framework, we built a category-balanced scenario generator across eight reasoning failure modes and instantiated it on a cardiovascular graph. The metric panel discriminates conditions along interpretable, non-redundant axes: C4 obtains the strongest causal edge F1 (0.838), adverse-effect F1 (0.833), evidence accuracy (0.738), and unsupported claim rate (0.114), while C1 obtains the highest raw intervention accuracy (0.948) with no measurable causal or evidential grounding.

Causal-Adversarial Probing of Clinical Covariates for Prostate MRI Grading

Deep learning models for prostate MRI-based cancer grading may encode clinical covariates that either reflect useful disease-related signal or non-generalising shortcut information, but their role is usually assumed. We propose a causal-reasoning framework for probing covariate dependence in MRI-based International Society of Urological Pathology (ISUP) Grade Group prediction. Rather than treating mpMRI as a direct cause of grade, we model MRI appearance and ISUP grade as observations of latent tumour pathology, and test whether candidate clinical variables act as nuisance correlates, disease-related proxies, or irrelevant covariates in the learned representation. We implement this using an adversarial framework that suppresses the decodability of individual clinical covariate at a time while preserving MRI-based grade prediction. The approach is developed and evaluated on 2,903 prostate MRI examinations, with external validation on 576 patients. We report a set of interesting and previously under-explored imaging-to-clinical-variable interactions in the context of deep learning generalisation. For examples, in binary ISUP Grade Group $\geq2$ classification, suppressing age, BMI, and alcohol use improved AUC by 1.23%, 0.84%, and 1.42%, respectively (all p < 0.05), suggesting reduced non-generalising covariate information; In contrast, suppressing PSA and prostate volume degraded AUC by 1.91% and 7.61% (all p < 0.001), indicating that these variables carried task-relevant signal. These findings show that adversarial covariate suppression can provide a practical representation-level analysis for distinguishing potentially harmful dependence from informative signal in prostate MRI grading models.