Linking Knowledge to Care: Knowledge Graph-Augmented Medical Follow-Up Question Generation

Large language models (LLMs) are increasingly used for diagnostic tasks in medicine. In clinical practice, the correct diagnosis can rarely be immediately inferred from the initial patient presentation alone. Rather, reaching a diagnosis often involves systematic history taking, during which clinicians reason over multiple potential conditions through iterative questioning to resolve uncertainty. This process requires considering differential diagnoses and actively excluding emergencies that demand immediate intervention. Yet, the ability of medical LLMs to generate informative follow-up questions and thus reason over differential diagnoses remains underexplored. Here, we introduce MedClarify, an AI agent for information-seeking that can generate follow-up questions for iterative reasoning to support diagnostic decision-making. Specifically, MedClarify computes a list of candidate diagnoses analogous to a differential diagnosis, and then proactively generates follow-up questions aimed at reducing diagnostic uncertainty. By selecting the question with the highest expected information gain, MedClarify enables targeted, uncertainty-aware reasoning to improve diagnostic performance. In our experiments, we first demonstrate the limitations of current LLMs in medical reasoning, which often yield multiple, similarly likely diagnoses, especially when patient cases are incomplete or relevant information for diagnosis is missing. We then show that our information-theoretic reasoning approach can generate effective follow-up questioning and thereby reduces diagnostic errors by ~27 percentage points (p.p.) compared to a standard single-shot LLM baseline. Altogether, MedClarify offers a path to improve medical LLMs through agentic information-seeking and to thus promote effective dialogues with medical LLMs that reflect the iterative and uncertain nature of real-world clinical reasoning.

Large language models (LLMs) have made substantial progress on medical question-answering, yet effective medical dialogue also requires learning to ask questions that uncover relevant patient information. To train such dialogue policies, a common pipeline combines supervised fine-tuning with reinforcement learning (RL) based on final diagnostic correctness. However, this outcome-based supervision does not directly distinguish the contributions of individual questions and provides no question-level feedback for unexecuted alternatives. To address this gap, we introduce PCQC (Privileged Counterfactual Question Credit), which uses privileged patient information during training to learn from questions never asked. During training, PCQC makes alternative questions directly comparable at the same dialogue state by using privileged patient facts to construct their answers. A frozen diagnostic scorer evaluates the diagnostic utility of each resulting question-answer pair by how strongly it supports the correct diagnosis. PCQC turns these comparisons into relative question credit that teaches the policy which questions to favor, directly supervising both executed and unexecuted questions alongside outcome-based RL without requiring complete rollouts for the unexecuted alternatives. Extensive experiments across four medical benchmarks demonstrate that PCQC achieves 63.10% mean diagnostic accuracy, outperforming GRPO and ATPO by 4.38 and 4.21 percentage points, respectively. These gains are achieved with 33.1% fewer inquiry turns than GRPO.

Large language models (LLMs) are increasingly used for health-related decision support. Yet most evaluations treat diagnosis as a single-shot task with complete information provided upfront, often as a multiple-choice selection. This diverges from clinical practice, where diagnosis is interactive and open-ended, involving sequential hypothesis refinement through targeted questioning. We address this gap. We build MeDxBench, a large-scale benchmark of 4,421 clinical cases across 20 specialties. We further propose MeDxAgent, a multi-agent consultation system for interactive diagnosis, and systematically study its prompt-, flow- and agent-level design choices. MeDxAgent achieves a 10.3% accuracy gain over the baseline on MeDxBench, closing 52.3% of the gap to a full-information oracle. We find that specific design choices: collecting demographics first, passing summarized dialogue for diagnosis, and feeding candidate diagnoses for targeted questioning, improve accuracy, mirroring how physicians reason, though their effect emerges fully only in combination. Code and dataset will be released upon publication.