Jian Li
Publications
RareAlert: Aligning heterogeneous large language model reasoning for early rare disease risk screening
Missed and delayed diagnosis remains a major challenge in rare disease care. At the initial clinical encounters, physicians assess rare disease risk using only limited information under high uncertainty. When high-risk patients are not recognised at this stage, targeted diagnostic testing is often not initiated, resulting in missed diagnosis. Existing primary care triage processes are structurally insufficient to reliably identify patients with rare diseases at initial clinical presentation and universal screening is needed to reduce diagnostic delay. Here we present RareAlert, an early screening system which predict patient-level rare disease risk from routinely available primary-visit information. RareAlert integrates reasoning generated by ten LLMs, calibrates and weights these signals using machine learning, and distils the aligned reasoning into a single locally deployable model. To develop and evaluate RareAlert, we curated RareBench, a real-world dataset of 158,666 cases covering 33 Orphanet disease categories and more than 7,000 rare conditions, including both rare and non-rare presentations. The results showed that rare disease identification can be reconceptualised as a universal uncertainty resolution process applied to the general patient population. On an independent test set, RareAlert, a Qwen3-4B based model trained with calibrated reasoning signals, achieved an AUC of 0.917, outperforming the best machine learning ensemble and all evaluated LLMs, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet, o3-mini, Gemini-2.5-Pro, and Qwen3-235B. These findings demonstrate the diversity in LLM medical reasoning and the effectiveness of aligning such reasoning in highly uncertain clinical tasks. By incorporating calibrated reasoning into a single model, RareAlert enables accurate, privacy-preserving, and scalable rare disease risk screening suitable for large-scale local deployment.
Evaluating the Diagnostic Classification Ability of Multimodal Large Language Models: Insights from the Osteoarthritis Initiative
Multimodal large language models (MLLMs) show promising performance on medical visual question answering (VQA) and report generation, but these generation and explanation abilities do not reliably transfer to disease-specific classification. We evaluated MLLM architectures on knee osteoarthritis (OA) radiograph classification, which remains underrepresented in existing medical MLLM benchmarks, even though knee OA affects an estimated 300 to 400 million people worldwide. Through systematic ablation studies manipulating the vision encoder, the connector, and the large language model (LLM) across diverse training strategies, we measured each component's contribution to diagnostic accuracy. In our classification task, a trained vision encoder alone could outperform full MLLM pipelines in classification accuracy and fine-tuning the LLM provided no meaningful improvement over prompt-based guidance. And LoRA fine-tuning on a small, class-balanced dataset (500 images) gave better results than training on a much larger but class-imbalanced set (5,778 images), indicating that data balance and quality can matter more than raw scale for this task. These findings suggest that for domain-specific medical classification, LLMs are more effective as interpreters and report generators rather than as primary classifiers. Therefore, the MLLM architecture appears less suitable for medical image diagnostic classification tasks that demand high certainty. We recommend prioritizing vision encoder optimization and careful dataset curation when developing clinically applicable systems.