# Evolving Interactive Diagnostic Agents in a Virtual Clinical Environment

arXiv: https://arxiv.org/abs/2510.24654 · HTML: https://mlsanity.com/paper/2510.24654/

## Key facts

- Cited by 9 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 21 of its 55 references that are in the map.
- First posted on arXiv 28 Oct 2025.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 21 of 21)

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [Llama 2: Open Foundation and Fine-Tuned Chat Models](https://mlsanity.com/paper/2307.09288/) (2023)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [OpenAI o1 System Card](https://mlsanity.com/paper/2412.16720/) (2024)
- [DeepSeek-V3 Technical Report](https://mlsanity.com/paper/2412.19437/) (2024)
- [MedGemma Technical Report](https://mlsanity.com/paper/2507.05201/) (2025)
- [HealthBench: Evaluating Large Language Models Towards Improved Human Health](https://mlsanity.com/paper/2505.08775/) (2025)
- [Towards Expert-Level Medical Question Answering with Large Language Models](https://mlsanity.com/paper/2305.09617/) (2023)
- [MedAgents: Large Language Models as Collaborators for Zero-shot Medical Reasoning](https://mlsanity.com/paper/2311.10537/) (2023)
- [MEDITRON-70B: Scaling Medical Pretraining for Large Language Models](https://mlsanity.com/paper/2311.16079/) (2023)
- [AgentClinic: a multimodal agent benchmark to evaluate AI in simulated clinical environments](https://mlsanity.com/paper/2405.07960/) (2024)
- [Agent Hospital: A Simulacrum of Hospital with Evolvable Medical Agents](https://mlsanity.com/paper/2405.02957/) (2024)
- [MDAgents: An Adaptive Collaboration of LLMs for Medical Decision-Making](https://mlsanity.com/paper/2404.15155/) (2024)
- [Sequential Diagnosis with Language Models](https://mlsanity.com/paper/2506.22405/) (2025)
- [Baichuan-M1: Pushing the Medical Capability of Large Language Models](https://mlsanity.com/paper/2502.12671/) (2025)
- [Self-Evolving Multi-Agent Simulations for Realistic Clinical Interactions](https://mlsanity.com/paper/2503.22678/) (2025)
- [Automatic Interactive Evaluation for Large Language Models with State Aware Patient Simulator](https://mlsanity.com/paper/2403.08495/) (2024)
- [Quantifying the Reasoning Abilities of LLMs on Real-world Clinical Cases](https://mlsanity.com/paper/2503.04691/) (2025)
- [Real-World Doctor Agent with Proactive Consultation through Multi-Agent Reinforcement Learning](https://mlsanity.com/paper/2505.19630/) (2025)
- [Foundation Model of Electronic Medical Records for Adaptive Risk Estimation](https://mlsanity.com/paper/2502.06124/) (2025)

## Built on by (most cited first, 9 of 9)

- [LongMedBench: Benchmarking Medical Agents for Long-Horizon Clinical Decision-Making](https://mlsanity.com/paper/2607.09322/) (2026)
- [Joint Optimization of Reasoning and Dual-Memory for Self-Learning Diagnostic Agent](https://mlsanity.com/paper/2604.07269/) (2026)
- [ResidencyRL: Reinforcement Learning in Simulated Clinical Environments](https://mlsanity.com/paper/2608.07418/) (2026)
- [Aligning Clinical Needs and AI Capabilities: A Survey on LLMs for Medical Reasoning](https://mlsanity.com/paper/2607.07761/) (2026)
- [PhenoLIP: Integrating Phenotype Ontology Knowledge into Medical Vision-Language Pretraining](https://mlsanity.com/paper/2602.06184/) (2026)
- [Reinforcement Learning for Evidence-Seeking Diagnostic Reasoning with Large Language Models](https://mlsanity.com/paper/2607.02983/) (2026)
- [CDEG: Learning Decision-Critical Evidence for Long-Horizon Diagnostic Agents](https://mlsanity.com/paper/2608.22899/) (2026)
- [SCOPE-AD: Sequential cost-aware ordinal-belief planning with energy-based models for diagnostic agents](https://mlsanity.com/paper/2610.01278/) (2026)
- [Reinforcement Learning In Partially Verifiable Environments for Colon Cancer Treatment Planning](https://mlsanity.com/paper/2610.17426/) (2026)

## Abstract (arXiv)

We present a framework for training large language models (LLMs) as diagnostic agents with reinforcement learning, enabling them to manage multi-turn interactive diagnostic processes, adaptively select examinations, and commit to final diagnoses. Unlike instruction-tuned models trained on static data, our method acquires diagnostic strategies through dynamic exploration and outcome-based feedback, mapping evolving patient states to the next optimal examination and subsequent diagnosis. Our contributions include: (i) DiagGym, a diagnostics world model trained with electronic health records, serving as a virtual clinical environment to support closed-loop in-silico training and evaluation for interactive diagnosis; (ii) DiagAgent, trained via end-to-end multi-turn RL to learn dynamic diagnostic policies that optimize both interactive effectiveness and final accuracy; (iii) DiagBench, a multi-center diagnostic benchmark designed to evaluate multi-turn diagnostic interaction trajectories. The benchmark comprises 2.2K physician-validated cases sourced from 4 distinct distributions, alongside 3.3K physician-written rubrics for granular process-oriented evaluation. (iv) Extensive evaluations demonstrate DiagAgent's superior performance across both in-domain and out-of-domain (OOD) settings. DiagAgent significantly outperforms 11 SOTA LLMs and 2 prompt-engineered agents. In the end-to-end setting, it delivers a 11.20% increase in diagnostic accuracy and a 17.58% boost in examination recommendation F1 score, while consistently maintaining SOTA performance across all three external centers. Furthermore, in rubric-based evaluations, it surpasses the next-best model by 7.1% in weighted rubric score. These findings indicate that learning policies in interactive clinical environments confers long-term diagnostic management abilities unattainable through passive training.
