Understanding clinical reasoning variability in medical large language models: a mechanistic interpretability study
Medical large language models achieving high benchmark accuracy exhibit unexplained variability in clinical tasks, producing errors that clinicians cannot safeguard against. We evaluated clinical reasoning stability in GPT-5, MedGemma-27B-Text-IT, and OpenBioLLM-Llama3-70B using 3035 systematic perturbations from physician-validated oncology SOAP, brief vignette, and MIMIC cases. We trained sparse autoencoders on 1 billion tokens from 50,000 MIMIC-IV clinical notes to decompose their internal representation. We find models exhibit dramatic reasoning instability, shifting staging accuracy by over 50% based solely on prompt format, or generating definitive staging in clinically insufficient scenarios. Sparse autoencoder analysis revealed hierarchical encoding in MedGemma, where high-magnitude features encode lexical identity and low-magnitude features encode contextual meaning. OpenBioLLM distributes information uniformly. We demonstrate that these internal encoding structures differentially affect retrieval and reasoning interventions, suggesting interventions effective for one architecture may harm another. These results motivate architecture-specific safety validation as a component of pre-deployment evaluation for medical LLMs.
Authors
- Zihai Li (ORCID: https://orcid.org/0000-0003-4603-927X)
- Jordan Edward Krull (ORCID: https://orcid.org/0000-0001-6507-8085)
- Qin Ma (ORCID: https://orcid.org/0000-0002-3264-8392)
- Mirage Modi (ORCID: https://orcid.org/0000-0001-5998-2107)
- Timothy D. Gauntner (ORCID: https://orcid.org/0000-0002-4745-2130)
- Daniel G. Stover (ORCID: https://orcid.org/0000-0001-9003-8165)
- Ping Zhang (ORCID: https://orcid.org/0000-0002-4601-0779)
- Xiaoying Wang (ORCID: https://orcid.org/0009-0002-2276-9323)
- Anjun Ma (ORCID: https://orcid.org/0000-0001-6269-398X)
- Jing Zhao (ORCID: https://orcid.org/0000-0002-2378-6371)
- Donte Johnson
- Mingjia Li
- Hao Cheng
Institutions
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- The Ohio State University Wexner Medical Center (US)
- The Ohio State University (US)
Publication Details
- Journal
- npj Digital Medicine
- Published
- 2026-10-31
- DOI
- https://doi.org/10.1038/s41746-026-03423-6
- Primary Topic
- Artificial Intelligence in Healthcare and Education
- Type
- article
- Field-Weighted Citation Impact
- 0.00