Capabilities of Claude Fable 5 on Biomedical Challenge Problems

Frontier large language models are increasingly deployed as orchestration backbones for biological research workflows, yet no shared evidence base exists for comparing their refusal behaviour on legitimate research prompts. RefusalBench, introduced here, is a matched-triple benchmark of 141 prompts in 47 bundles that holds task framing constant while varying only biological risk tier (benign, borderline, dual-use), enabling tier-conditioned comparisons robust to subdomain confounding. A 15-prompt should-refuse positive-control module establishes per-model calibration floors; three models fail to refuse even these prompts. Across 19 frontier models in the May 2026 snapshot, strict refusal rates span 0.1% to 94.6% on identical prompts. Jurisdiction does not predict refusal in this snapshot (Mann-Whitney U, p = 0.393; EU n = 1, US bimodal); provider identity does, with Anthropic's API stack predicting refusal at OR = 21.03 (95% CI: 14.58-30.34 prompt-clustered; 5.70-77.55 under model-clustered GEE). This effect is best read as access-path-level rather than model-weight-level: 99.8% of Anthropic's strict refusals carry the same safety_policy adjudicated reason code, consistent with a small set of canonical refusal templates rather than case-by-case model reasoning. Strict refusal rate misranks safety calibration: Grok 4.20 achieves the highest tier discrimination (Youden's J = 0.787) while ranking only seventh by overall refusal rate, and Claude Opus 4.7's J dropped 65% from prior versions with no improvement in dual-use detection. Nine of 18 frontier models exhibit a hedge-but-help partial-compliance pattern at dual-use tier that binary refusal metrics cannot detect.

Biomedical question answering with large language models is commonly evaluated using answer accuracy, but answer accuracy alone does not indicate whether a model can produce parseable outputs, follow structured reliability instructions, recognize weak answer spaces, or avoid confident incorrect commitments. This paper presents HypothesisMed, an inference-time reliability pipeline for biomedical multiple-choice question answering. It combines direct, chain-of-thought, HypothesisMed-v3 prompting, and answer fusion. The final answer is selected by fusion, while HypothesisMed-v3 supplies SPACE labels and confidence information. SPACE labels mark the answer space as VALID, INCOMPLETE, or CONTRADICTED. We evaluate Qwen2.5-7B, Phi-4-mini, DeepSeek-R1-32B, and BioMistral-7B on MedQA, MedMCQA, and PubMedQA using 1,000 examples per dataset. The pipeline improves weighted accuracy over each model's best direct or chain-of-thought baseline while increasing parse and SPACE coverage. We also scale evaluation to Qwen2.5-7B and Phi-4-mini using 10,183 examples per model. Fusion improves Phi-4-mini accuracy from 0.4296 to 0.5192, while Qwen2.5-7B chain-of-thought remains slightly higher in answer accuracy. However, Qwen2.5-7B fusion achieves complete parse and SPACE coverage with much lower false commitment. A 12,000-example SPACE stress test shows answer-space diagnosis remains difficult, with SPACE accuracy of 0.3074 for Qwen2.5-7B and 0.4168 for Phi-4-mini. These results show that answer accuracy, parseability, structured reliability reporting, calibration behavior, and false-commitment behavior are separable capabilities. The main contribution is not a universal state-of-the-art claim, but a reproducible inference-time framework for evaluating biomedical question answering models as auditable workflow components under structured reliability constraints.

Safety alignment in Large Language Models is critical for healthcare; however, reliance on binary refusal boundaries often results in over-refusal of benign queries or unsafe compliance with harmful ones. While existing benchmarks measure these extremes, they fail to evaluate Safe Completion: the model's ability to maximise helpfulness on dual-use or borderline queries by providing safe, high-level guidance without crossing into actionable harm. We introduce Health-ORSC-Bench, the first large-scale benchmark designed to systematically measure Over-Refusal and Safe Completion quality in healthcare. Comprising 31,920 benign boundary prompts across seven health categories (e.g., self-harm, medical misinformation), our framework uses an automated pipeline with human validation to test models at varying levels of intent ambiguity. We evaluate 30 state-of-the-art LLMs, including GPT-5 and Claude-4, revealing a significant tension: safety-optimised models frequently refuse up to 80% of "Hard" benign prompts, while domain-specific models often sacrifice safety for utility. Our findings demonstrate that model family and size significantly influence calibration: larger frontier models (e.g., GPT-5, Llama-4) exhibit "safety-pessimism" and higher over-refusal than smaller or MoE-based counterparts (e.g., Qwen-3-Next), highlighting that current LLMs struggle to balance refusal and compliance. Health-ORSC-Bench provides a rigorous standard for calibrating the next generation of medical AI assistants toward nuanced, safe, and helpful completions. Furthermore, our benchmark facilitates reproducible evaluation, encourages safety calibration, and supports development of clinically reliable, context-aware, human-aligned medical AI systems. Our code and data are available at: https://github.com/ZhihaoZhang97/Health-ORSC-Bench. Warning: Some contents may include toxic or undesired contents.