Safety and accuracy follow different scaling laws in clinical large language models
Authors: Sebastian Wind, Tri-Thien Nguyen, Jeta Sopa, Mahshad Lotfinia, Sebastian Bickelhaup, Michael Uder, Harald Köstler, Gerhard Wellein, +4 more
Organizations: Pattern Recognition Lab, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany · Institute of Radiology, University Hospital Erlangen, Erlangen, Germany · Lab for AI in Medicine, RWTH Aachen University, Aachen, Germany · Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany · Erlangen National High Performance Computing Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany · Chair of Computer Science 10, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Abstract
Clinical LLMs are often scaled by increasing model size, context length, retrieval complexity, or inference-time compute, with the implicit expectation that higher accuracy implies safer behavior. This assumption is incomplete in medicine, where a few confident, high-risk, or evidence-contradicting errors can matter more than average benchmark performance. We introduce SaFE-Scale, a framework for measuring how clinical LLM safety changes across model scale, evidence quality, retrieval strategy, context exposure, and inference-time compute. To instantiate this framework, we introduce RadSaFE-200, a Radiology Safety-Focused Evaluation benchmark of 200 multiple-choice questions with clinician-defined clean evidence, conflict evidence, and option-level labels for high-risk error, unsafe answer, and evidence contradiction. We evaluated 34 locally deployed LLMs across six deployment conditions: closed-book prompting (zero-shot), clean evidence, conflict evidence, standard RAG, agentic RAG, and max-context prompting. Clean evidence produced the strongest improvement, increasing mean accuracy from 73.5% to 94.1%, while reducing high-risk error from 12.0% to 2.6%, contradiction from 12.7% to 2.3%, and dangerous overconfidence from 8.0% to 1.6%. Standard RAG and agentic RAG did not reproduce this safety profile: agentic RAG improved accuracy over standard RAG and reduced contradiction, but high-risk error and dangerous overconfidence remained elevated. Max-context prompting increased latency without closing the safety gap, and additional inference-time compute produced only limited gains. Worst-case analysis showed that clinically consequential errors concentrated in a small subset of questions. Clinical LLM safety is therefore not a passive consequence of scaling, but a deployment property shaped by evidence quality, retrieval design, context construction, and collective failure behavior.
Large language models (LLMs) are increasingly used for medical and health-related questions, yet their safety in high-risk medical scenarios remains poorly understood. We introduce \textsc{MedHarm}\footnote{Code and data will be released upon acceptance. Due to the sensitive nature of high-risk medical queries, data access will be available to qualified researchers upon request.}, a high-risk medical safety benchmark with 1,100 medically grounded queries across 10 safety-critical categories, including toxicology, pharmacology, covert poisoning, anesthesia, and fetal harm. Unlike broad medical QA benchmarks, \textsc{MedHarm} targets realistic clinical, educational, and technical prompts that require refusal, caution, or safe redirection rather than direct helpfulness. We evaluate 15 LLMs spanning general-purpose, medical-purpose, closed-source, and downstream SFT models, together with 4 representative guardrail models. Results reveal a substantial gap between apparent alignment and medical safety: aligned models can still produce unsafe or actionable responses, medical fine-tuning can amplify harmful specificity, and external guardrails reduce some failures while introducing brittle blocking and weak safe helpfulness. These findings show that medical safety cannot be inferred from general alignment or medical capability alone, highlighting the need for domain-specific stress testing before deploying LLMs in safety-critical medical applications.
Background: LLM judges increasingly score whether clinical language models give overconfident answers under incomplete evidence, yet whether a measured "safety gain" reflects real behavior change or the judge's calibration is unresolved. Using a structured evidence-sufficiency prompt as a test case, we asked whether it reduces unsafe overconfident answers, how far that effect depends on the scoring judge, and what it costs in helpfulness. Methods: In a retrospective public-data benchmark (Real-POCQi, HealthBench, MedRBench), four models (GPT-5.5, Claude Opus 4.8, Gemini 3.5 Flash, Grok 4.3) answered a fully paired common panel (1,200 cells) with a standard prompt and the wrapper. The pre-specified endpoint was the paired reduction in unsafe overconfidence scored by the primary judge (GPT-5.4-nano); secondary analyses added a different-family judge (Claude Sonnet 5), a correctness judge, matched scaffold controls, and a blinded three-clinician review. Results: Unsafe overconfidence fell from 49.3% to 24.7%, a paired reduction of 24.7 points (95% CI 21.8-27.7; p<0.001), robust in direction across models and paraphrases. Magnitude was judge-dependent: Sonnet agreed on direction but nearly halved the effect (+13.1 points), with one-directional disagreement. Blinded clinicians characterized the primary judge as a high-sensitivity (1.00), low-specificity (0.55) screen, not a calibrated rate. The gain carried a model-specific helpfulness cost (correct diagnosis 80.3% to 50.3%): near-free for GPT-5.5, near-total for Gemini (-58 points). Matched scaffold controls showed genuine behavior change, not judge circularity. Conclusions: LLM-judged clinical safety effects should be reported as directional and relative, anchored to human review and evaluated jointly with helpfulness, not as calibrated absolute rates. This does not establish clinical deployment readiness.
Large language models(LLMs) increasingly match expert performance on licensing examinations, yet routine clinical use remains limited because governance requires auditable reasoning, safety and ethics alignment, and resilience to adversarial misuse. Here we present SafeMed-R1, trained with a traceable Clinical Trust Signals(CTS) pipeline that links each reasoning instance to clinician rubric scores and edit histories, and aligned through safety and ethics supervision and red team stress testing. SafeMed-R1 attains a macro-averaged accuracy of 79.6% across clinical benchmarks. Under adversarial safety testing, it shows the lowest aggregated risk and reduces unsafe outputs by about 3 to 5% relative to its baseline. In a paired expert study of 30 medication safety vignettes, SafeMed-R1 matches PGY1 and PGY2 residents on medical correctness and scores higher for medication safety, guideline consistency, and clinical usefulness. Collectively, these results suggest that clinician-audited supervision provenance, together with domain-tailored safety and ethics alignment, can strengthen governance-relevant evidence without relying on inference-time retrieval or citation grounding.