Evaluating Patient Safety Risks in Generative AI: Development and Validation of a FMECA Framework for Generated Clinical Content

Large language models are increasingly used to summarize clinical trial results for healthcare providers, patients, and payers, but their tendency to hallucinate poses significant risks in this high-stakes context. This study introduces a benchmark evaluation framework for measuring the faithfulness of LLM-generated clinical trial summaries across three stakeholder audiences. The framework consists of 200 stratified trials drawn from the Aggregate Analysis of ClinicalTrials.gov database, evaluated using audience-specific prompt templates and a six-dimension faithfulness annotation schema. Baseline measurements were established for GPT-4o, Claude Sonnet 4.6, and Gemini 2.5 Flash across 1,800 generated summaries scored using a cross-encoder natural language inference (NLI) model. Unsupported Claims was identified as the dominant failure mode across all three models, with a mean annotation score of 1.55 out of three. A knowledge-graph-augmented retrieval system was developed and evaluated against the baseline, producing statistically significant improvements in NLI-based faithfulness scores (entailment +0.0125, faithfulness +0.0130, p < 0.0001). Improvement pathways were model-dependent, with GPT-4o improving primarily through contradiction reduction while Claude Sonnet 4.6 and Gemini 2.5 Flash improved through increased entailment.

Large language models (LLMs) are increasingly used for medical summarization, but their outputs can omit medically important information and introduce unsupported claims. Existing error-detection methods produce heuristic or uncalibrated scores, providing no formal control over missed errors and no principled way to trade off safety against clinician review burden. We introduce Conformal Assessment for Risk Evaluation (CARE), a post-hoc, model-agnostic safety layer that uses conformal risk control to overlay calibrated omission and hallucination flags onto summaries from any LLM without retraining. CARE provides finite-sample, distribution-free guarantees through two controllers: a hallucination controller that bounds the probability of a document containing any unflagged hallucinated sentence, and an omission controller that bounds the expected fraction of important omissions not surfaced for review. Unlike hallucination detection, omissions depend jointly on whether a source sentence is important and whether it is covered by the summary. We show that calibrating only one dimension can violate the target risk bound, while marginal decompositions remain valid but overly conservative. By jointly calibrating over the full $(τ,γ)$ threshold space, CARE preserves formal guarantees while surfacing up to 5$\times$ fewer sentences than alternative calibrated baselines. Across five medical summarization tasks, CARE satisfies the target risk bound at $α= 0.15$ with 95% confidence across 100 calibration/test resplits, using only ~100 labeled documents per domain. In a preliminary clinician study (75 document reviews), calibrated flags improved omission detection by 28.6 percentage points on average. These results show that sentence-level safety guarantees are feasible for LLM-assisted medical summarization and offer a tunable mechanism for balancing residual risk and review effort.

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.