Structuring versus Problematizing: How LLM-based Agents Scaffold Learning in Diagnostic Reasoning

Clinical diagnosis is a complex reasoning process in which clinicians gather evidence, form hypotheses, and test them against alternative explanations. In medical training, this reasoning is explicitly developed through counterfactual questioning--e.g., asking how a diagnosis would change if a key symptom were absent or altered--to strengthen differential diagnosis skills. As large language model (LLM)-based systems are increasingly used for diagnostic support, ensuring the interpretability of their recommendations becomes critical. However, most existing LLM-based diagnostic agents reason over fixed clinical evidence without explicitly testing how individual findings support or weaken competing diagnoses. In this work, we propose a counterfactual multi-agent diagnostic framework inspired by clinician training that makes hypothesis testing explicit and evidence-grounded. Our framework introduces counterfactual case editing to modify clinical findings and evaluate how these changes affect competing diagnoses. We further define the Counterfactual Probability Gap, a method that quantifies how strongly individual findings support a diagnosis by measuring confidence shifts under these edits. These counterfactual signals guide multi-round specialist discussions, enabling agents to challenge unsupported hypotheses, refine differential diagnoses, and produce more interpretable reasoning trajectories. Across three diagnostic benchmarks and seven LLMs, our method consistently improves diagnostic accuracy over prompting and prior multi-agent baselines, with the largest gains observed in complex and ambiguous cases. Human evaluation further indicates that our framework produces more clinically useful, reliable, and coherent reasoning. These results suggest that incorporating counterfactual evidence verification is an important step toward building reliable AI systems for clinical decision support.

Deploying Large Language Models (LLMs) in healthcare requires robust performance across two complementary dimensions - diagnostic reasoning: the convergent, evidence-driven task of inferring a patient's condition from clinical data to produce a diagnosis, and clinical healthcare reasoning: the broader, navigational judgment required to communicate, plan, and adapt across multi-turn clinical interactions where a single correct answer may not exist. Recent benchmarks such as HealthBench and MedXpertQA reveal persistent weaknesses in both areas, exposing failures in complex diagnostic scenarios and limitations in contextual, patient-centered dialogue. We introduce a sequential training framework that targets these facets using synthetic data and rubric-based reinforcement learning. First, we improve diagnostic reasoning using MedBullets-derived questions with rule- and rubric-guided Reinforcement Learning (RL). We then shift to clinical reasoning by generating 5.3k synthetic multi-turn scenarios, each paired with multi-dimensional rubrics to comprehensively assess the response. This approach yields over 10% improvement on MedXpertQA, and our 30B model achieves 50.1% accuracy on HealthBench-Hard, surpassing proprietary baselines including GPT-5 (thinking). Our results show that targeted synthetic datasets and rubric-based training can systematically improve both diagnostic and interactive clinical reasoning in medical LLMs.

Clinical diagnosis is an active evidence-seeking process in which clinicians acquire evidence, update competing hypotheses, and decide when the available evidence is sufficient for diagnosis. Yet many medical diagnosis systems built around large language models (LLMs) still formulate diagnosis as static case-to-answer prediction, with limited support for evidence acquisition. Agentic LLMs offer a dynamic alternative through tool use and intermediate diagnostic trajectories, but existing systems often under-specify how patient evidence should be exposed, scaffolded, and controlled at runtime. We introduce EviDx, an evidence-aware active diagnosis framework that pairs patient-specific diagnostic environments with a clinical diagnostic scaffold and an observer-guided runtime harness. In EviDx, $\mathcal{E}$-Synthesis constructs interactive environments from raw clinical cases; the scaffold organizes role-specialized agents, evidence tools, and evolving evidence states; and the harness regulates diagnostic termination by tracking uncertainty and evidence coverage. A 3-level evaluation pyramid assesses execution robustness, reasoning dynamics, and diagnostic outcomes. Experiments show that EviDx improves diagnostic performance and process stability while revealing model-dependent capability boundaries.