Uncertainty-Guided Latent Diagnostic Trajectory Learning for Sequential Clinical Diagnosis

Most existing LLM diagnoses are evaluated on static, single-turn settings where complete patient information is provided upfront, an oversimplification of real clinical practice. We study active diagnosis: the real-life clinical process of starting from initial observation, ordering tests, interpreting results, and updating a differential diagnosis across multiple turns. Through systematic analysis, we identify three recurring failure modes in current LLMs: ungrounded test ordering, unreliable diagnostic update, and degraded multi-turn coherence. Together, these failures reveal a core deficit: existing medical training data teaches models to reason from complete information but not to act under evolving, partial evidence. To address this gap, we introduce MedAction, a tree-structured distillation pipeline that synthesizes diverse and high-quality multi-turn diagnostic trajectories via LLM-environment interaction. We propose two knowledge-graph-grounded metrics to filter trajectory quality: Disease Trajectory Consistency (DTC), which tracks whether the model's hypothesis converges toward the correct diagnosis, and Reasoning-Action Consistency (RAC), which verifies that belief updates are driven by gathered evidence. Using this pipeline, we construct MedAction-32K, a dataset of 32,681 trajectories from 2,896 PMC cases. Fine-tuning an 8B model on MedAction-32K achieves state-of-the-art performance among open-source models on both MedR-Bench and our curated MedAction-300-Hard benchmark, pushing the edge for open-source medical LLMs.

There is growing interest in using machine learning (ML) to support clinical diagnosis, but most approaches rely on static, fully observed datasets and fail to reflect the sequential, resource-aware reasoning clinicians use in practice. Diagnosis remains complex and error prone, especially in high-pressure or resource-limited settings, underscoring the need for frameworks that help clinicians make timely and cost-effective decisions. We propose ACTMED (Adaptive Clinical Test selection via Model-based Experimental Design), a diagnostic framework that integrates Bayesian Experimental Design (BED) with large language models (LLMs) to better emulate real-world diagnostic reasoning. At each step, ACTMED selects the test expected to yield the greatest reduction in diagnostic uncertainty for a given patient. LLMs act as flexible simulators, generating plausible patient state distributions and supporting belief updates without requiring structured, task-specific training data. Clinicians can remain in the loop; reviewing test suggestions, interpreting intermediate outputs, and applying clinical judgment throughout. We evaluate ACTMED on real-world datasets and show it can optimize test selection to improve diagnostic accuracy, interpretability, and resource use. This represents a step toward transparent, adaptive, and clinician-aligned diagnostic systems that generalize across settings with reduced reliance on domain-specific data.

Interactive medical diagnosis dynamically acquires patient information through multiple rounds of questioning, supporting accurate, efficient, and safe clinical decisions under incomplete evidence. Existing methods commonly guide information acquisition with predictive uncertainty or label ambiguity, but overlook the asymmetric clinical risk of missing severe diseases and lack unified long-horizon planning over whether to continue asking questions or commit to a diagnosis. To address these limitations, we propose Severity-Aware Conformal Clinical Planning, which formulates interactive diagnosis as a risk-sensitive sequential decision problem. The framework maintains complementary diagnostic, safety, and masked-evidence beliefs; calibrates turn-specific diagnostic prediction sets and severity-weighted differential-diagnosis risk on held-out diagnostic trajectories; and introduces the calibrated clinical risk into Monte Carlo Tree Search to jointly evaluate long-horizon Ask and Commit trajectories. Experiments on DDXPlus and MediQ show that our method achieves more accurate diagnoses with fewer questions across multiple large language models, while improving differential-diagnosis quality and reducing high-risk errors in severe cases. These findings validate the value of using clinical risk, rather than predictive uncertainty alone, as a planning signal and demonstrate the effectiveness of the proposed framework for information acquisition and risk-aware diagnostic decision making. They also motivate future work on clinical-risk-oriented interactive diagnosis and information-acquisition methods.