Skip to main content

This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

ArXiv logoLink to ArXiv
[Preprint]. 2025 Dec 17:arXiv:2512.01241v2. [Version 2]

First, do NOHARM: towards clinically safe large language models

David Wu, Fateme Nateghi Haredasht, Saloni Kumar Maharaj, Priyank Jain, Jessica Tran, Matthew Gwiazdon, Arjun Rustagi, Jenelle Jindal, Jacob M Koshy, Vinay Kadiyala, Anup Agarwal, Bassman Tappuni, Brianna French, Sirus Jesudasen, Christopher V Cosgriff, Rebanta Chakraborty, Jillian Caldwell, Susan Ziolkowski, David J Iberri, Robert Diep, Rahul S Dalal, Kira L Newman, Kristin Galetta, J Carl Pallais, Nancy Wei, Kathleen M Buchheit, David I Hong, Ernest Y Lee, Allen Shih, Vartan Pahalyants, Tamara B Kaplan, Vishnu Ravi, Sarita Khemani, April S Liang, Daniel Shirvani, Advait Patil, Nicholas Marshall, Kanav Chopra, Joel Koh, Adi Badhwar, Liam G McCoy, David J H Wu, Yingjie Weng, Sumant Ranji, Kevin Schulman, Nigam H Shah, Jason Hom, Arnold Milstein, Adam Rodman, Jonathan H Chen, Ethan Goh
PMCID: PMC12794822  PMID: 41532042

Abstract

Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a benchmark using 100 real primary care-to-specialist consultation cases to measure frequency and severity of harm from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 31 LLMs, potential for severe harm from LLM recommendations occurs in up to 22.2% (95% CI 21.6-22.8%) of cases, with harm of omission accounting for 76.6% (95% CI 76.4-76.8%) of errors. Safety performance is only moderately correlated (r = 0.61-0.64) with existing AI and medical knowledge benchmarks. The best models outperform generalist physicians on safety (mean difference 9.7%, 95% CI 7.0-12.5%), and a diverse multi-agent approach improves safety compared to solo models (mean difference 8.0%, 95% CI 4.0-12.1%). Therefore, despite strong performance on existing evaluations, widely used AI models can produce severely harmful medical advice at nontrivial rates, underscoring clinical safety as a distinct performance dimension necessitating explicit measurement.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


Articles from ArXiv are provided here courtesy of arXiv

RESOURCES