Organizations: Department of Computer Science and Engineering, College of Engineering, Qatar University, Doha, Qatar · College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Doha, Qatar · Primary Health Care Corporation (PHCC), Doha, Qatar · Birmingham City University, Birmingham, United Kingdom.
Abstract
Large Language Models (LLMs) are increasingly used in clinical applications. However, their behavior remains highly sensitive to subtle linguistic variations, such as rephrasing or syntactic variation. This sensitivity poses risks in safety-critical healthcare settings, where semantically equivalent inputs should produce consistent predictions. However, a key challenge is to ensure that prompt variations truly preserve clinical meaning, as embedding-based similarity metrics often fail to capture distinctions involving negation, temporality, or severity. To address this limitation, we propose a semantic verification framework based on Natural Language Inference (NLI) to filter meaning-preserving prompt variations, which are further refined using an LLM-as-a-judge and audited by a clinical expert. In addition, we introduce three metrics to quantify model sensitivity: MeaningPreserving Variation Sensitivity (MVS), confidence variation (ΔC), and Worst-Case Instability (WCI). We evaluate 16 open-source general-purpose (GP) and medical LLMs within the same model families and parameter scales, using reformulated prompts derived from the DiagnosisQA and MedQA datasets. Our results demonstrate that robustness differences between domain-specific (DS) models are mixed and highly model-dependent, i.e., domain specialization does not consistently improve or reduce robustness to meaning-preserving prompt reformulations. Several DS models rank among the most robust (when compared with GP counterparts), and strong GP baselines remain competitive as well.
Large Language Models (LLMs) are increasingly used in healthcare for tasks such as clinical question answering, diagnosis support, and report summarization. Despite their promise, these models remain highly sensitive to subtle prompt perturbations, both lexical and syntactic, posing serious risks in safety-critical clinical applications. In this study, we conduct a systematic sensitivity analysis to evaluate the robustness of both general-purpose (e.g., GPT-3.5, Llama3) and medical-specific LLMs (e.g., ClinicalBERT, BioLlama3, BioBERT) using the MedMCQA benchmark. We categorize perturbations into natural and adversarial types and examine their effect on model consistency, accuracy, and reliability in clinical reasoning tasks. Our findings reveal that medical LLMs are not intrinsically safe. Even minor variations in phrasing can alter clinical advice, and targeted adversarial prompts can provoke harmful outputs. In high-stakes settings like healthcare, such unpredictability is unacceptable-models that change diagnoses due to reworded inputs or hallucinate medications when slightly rephrased cannot be reliably trusted by clinicians. While models tend to show resilience to simple lexical substitutions or paraphrasing, they often break down under syntactic reordering or misleading contextual cues. This fragility is evident across both general-purpose and domain-specific LLMs. Notably, adversarial manipulations can lead to clinically dangerous outputs, such as recommending incorrect dosages or omitting critical findings.
Despite strong medical benchmark accuracy, LLMs can exhibit severe multi-turn sycophancy in clinical dialogue, abandoning initial correct diagnosis under escalating pressure. We propose \textbf{\textsc{Med-Stress}}, a targeted stress test framework that evaluates belief stability under escalating pressure. Across nine frontier large language models (LLMs), we find a clear dissociation between medical knowledge and robustness: high initial diagnostic capability does not imply high belief stability, yielding large knowledge-robustness gaps for several LLMs. To mitigate this failure mode, we propose a lightweight inference-time defense, \textbf{\texttt{RBED}} (\textbf{R}ole-\textbf{B}ased \textbf{E}pistemic \textbf{D}efense), and \textbf{\texttt{R-FT}} (\textbf{R}esilience-oriented \textbf{F}ine-\textbf{T}uning), a training-time approach that internalizes evidence-based resistance to pressure. Experiments show that \textbf{\texttt{R-FT}} nearly eliminates belief change and substantially improves robustness.
Large language models (LLMs) are increasingly explored for clinical decision support, yet most evaluations are conducted in English, leaving their reliability in other languages uncertain. Here we evaluate the impact of prompting language on diagnostic reasoning and final diagnosis accuracy by comparing English and French performance across five LLMs (o3, DeepSeek-R1, GPT-4-Turbo, Llama-3.1-405B-Instruct, and BioMistral-7B). A total of 180 clinical vignettes covering 16 medical specialties were assessed by two physicians using an 18-point scale evaluating both diagnosis accuracy and reasoning quality. Four of the five models performed better in English (mean difference 0.37-0.91, adjusted p < 0.05), with the gap spanning multiple aspects of reasoning, including differential diagnosis, logical structure, and internal validity. o3 was the only model showing no overall language effect. These findings demonstrate that prompting language remains a critical determinant of LLM clinical performance, with implications for equitable linguistico-cultural deployment worldwide.