A natural language interface can be used to make cancer genomics databases easier to use, but even if a question is perfectly fluent, its scientific meaning can be ambiguous. We propose CLARA, a framework that represents a question as a typed scientific query specification, considers a few possible interpretations, executes them, and asks for clarification when the estimates diverge. CLARA was assessed on mutation-prevalence contrasts among eight TCGA PanCancer Atlas cohorts and a 30-gene panel. This benchmark consisted of 330 unique executable contrasts varying in mutation scope, assay denominator, and sample context; 115 contrasts were result-sensitive and 215 were result-stable, per the preregistered definition of relative divergence greater than 0.10 or absolute divergence greater than 5 percentage points. An independently implemented pandas execution engine perfectly replicated all 660 results from the SQLite engine. In a separate 120-question LLM-generated, manually vetted language stress test, CLARA recognized all 60 result-sensitive contrasts and needlessly clarified 13 of 60 stable contrasts (accuracy 89.2%, sensitivity/recall 100%, specificity 78.3%). Standalone machine learning had superior overall accuracy (97.5%) but missed one critical contrast. This demonstrates that downstream execution can distinguish consequential from inconsequential ambiguity and reveal an explicit trade-off between safety and burden.
Medical large language model (LLM) evaluations rely on simplified, exam-style benchmarks that rarely reflect the ambiguity of real-world medical inquiries. We introduce the CLinical Evaluation of Ambiguity and Reliability (CLEAR) framework, which assesses how decision-space presentation, ambiguity, and uncertainty affect LLMs' reasoning on medical benchmarks. CLEAR systematically perturbs (1) the number of plausible answer options, (2) the presence of a ground truth or abstention option, and (3) the semantic framing of answer options. Applying CLEAR on three benchmarks evaluated across 17 LLMs reveals three notable limitations of existing evaluation methods. First, increasing the number of plausible answers degrades a model's ability to identify the correct answer and abstain against incorrect ones. Second, this lack of caution intensifies as the framing of abstention shifts from assertive rejection like "None of the Above" to uncertainty admission like "I don't know" (IDK). Notably, just including IDK in the answer space increases incorrect answer selections. Lastly, we formalize the performance gap between identifying the correct answer and abstaining from incorrect ones as the humility deficit, which worsens with model scale. Our findings reveal limitations in standard medical benchmarks and underscore that scaling alone does not resolve LLM reliability issues.
Frontier language models are increasingly evaluated on biomedical benchmarks, but two problems undermine most published evaluations: legacy benchmarks are near-saturated, and open-ended responses are graded by other language models. We evaluate Claude Fable 5, Anthropic's most capable publicly available model, across eight biomedical benchmarks, four text and four multimodal, using deterministic scoring against fixed answer keys throughout. We include two Claude predecessors and GPT-5 as baselines. Refusal is tracked as a distinct outcome in every result table. That decision produces the paper's central finding. Fable 5 refuses between 8.0% and 99.4% of questions depending on the benchmark, a pattern absent in both predecessors and in GPT-5. Once refused items are excluded from the denominator, Fable 5's accuracy exceeds or meets every other model on every benchmark in this study. We identify two distinguishable refusal patterns: one concentrating in basic-science and mechanism content across MedQA and MedXpertQA MM, confirmed independently on two benchmarks using each benchmark's own category labels; and a separate disease-domain pattern on RareBench, where inborn metabolic disease presentations are refused near-universally while adult-onset autoimmune presentations are not. The primary constraint on Fable 5's biomedical usefulness is willingness to engage, not capability once it does.
Dominic Okonkwo, Magnus Hodgson, Temitope I. David +1
Clinicians exploring oncology trial repositories often need ad-hoc, multi-constraint queries over biomarkers, endpoints, interventions, and time, yet writing SQL requires schema expertise. We demo FD-NL2SQL, a feedback-driven clinical NL2SQL assistant for SQLite-based oncology databases. Given a natural-language question, a schema-aware LLM decomposes it into predicate-level sub-questions, retrieves semantically similar expert-verified NL2SQL exemplars via sentence embeddings, and synthesizes executable SQL conditioned on the decomposition, retrieved exemplars, and schema, with post-processing validity checks. To improve with use, FD-NL2SQL incorporates two update signals: (i) clinician edits of generated SQL are approved and added to the exemplar bank; and (ii) lightweight logic-based SQL augmentation applies a single atomic mutation (e.g., operator or column change), retaining variants only if they return non-empty results. A second LLM generates the corresponding natural-language question and predicate decomposition for accepted variants, automatically expanding the exemplar bank without additional annotation. The demo interface exposes decomposition, retrieval, synthesis, and execution results to support interactive refinement and continuous improvement.
Suparno Roy Chowdhury, Tejas Anvekar, Manan Roy Choudhury +5