Evaluation of Causal Reasoning for Large Language Models in Contextualized Clinical Scenarios of Laboratory Test Interpretation

This study evaluates causal reasoning in large language models (LLMs) using 99 clinically grounded laboratory test scenarios aligned with Pearl's Ladder of Causation: association, intervention, and counterfactual reasoning. We examined common laboratory tests such as hemoglobin A1c, creatinine, and vitamin D, and paired them with relevant causal factors including age, gender, obesity, and smoking. Two LLMs - GPT-o1 and Llama-3.2-8b-instruct - were tested, with responses evaluated by four medically trained human experts. GPT-o1 demonstrated stronger discriminative performance (AUROC overall = 0.80 +/- 0.12) compared to Llama-3.2-8b-instruct (0.73 +/- 0.15), with higher scores across association (0.75 vs 0.72), intervention (0.84 vs 0.70), and counterfactual reasoning (0.84 vs 0.69). Sensitivity (0.90 vs 0.84) and specificity (0.93 vs 0.80) were also greater for GPT-o1, with reasoning ratings showing similar trends. Both models performed best on intervention questions and worst on counterfactuals, particularly in altered outcome scenarios. These findings suggest GPT-o1 provides more consistent causal reasoning, but refinement is required before adoption in high-stakes clinical applications.