Decide, Ask, or Defer: Clinical LLMs under Incomplete Evidence

Large language models (LLMs) are increasingly used for decision support in healthcare, but clinical evidence is often incomplete or evolving. When the available information is insufficient to support a reliable answer, models should request clarification or abstain rather than provide unsupported responses. Existing medical benchmarks, however, typically assume that complete information is available upfront. We introduce Safe-Psych, a sequential benchmark for evaluating how LLMs handle evolving diagnostic uncertainty in clinical psychiatry. Safe-Psych contains over 1,000 real-world psychiatric clinical notes segmented to simulate incremental evidence disclosure, with psychiatrist-derived action labels at each stage: DIAGNOSE, CLARIFY, or ABSTAIN. We evaluate multiple state-of-the-art LLMs in full-information and sequential settings. Our findings show that capability does not ensure calibration: even strong models struggle under incomplete clinical information, with under-abstention exceeding 60% for most models and safety-aware prompting reducing premature commitment only by shifting errors toward excessive abstention. In sequential evaluation, models frequently diagnose before sufficient evidence is available and rarely seek clarification unless explicitly prompted; these premature diagnoses are less accurate than on-time diagnoses. Overall, Safe-Psych reveals a limitation across the evaluated models: recognizing when clinical evidence is incomplete and additional information is needed. We release Safe-Psych to support research on improving LLM safety in healthcare.

LLM now pass medical licensing examinations and, in curated cases, can rival physicians at diagnostic reasoning. These developments have accelerated the use of LLMs for symptom assessment and clinical decision support in diagnostic and treatment guidance, administrative documentation, and rules-based alert enhancement. This Perspective concerns the most consequential of these applications: the autonomous triage of self-presenting, undifferentiated patients, with little or no clinician in the loop. For that task, the evidence of safety does not yet exist. The gap is not in medical knowledge but in the fidelity of clinical evaluation: a model optimized to continue the most probable text is not optimized to act safely when the safe answer is the improbable must-not-miss diagnosis. Safe triage is not the selection of the most likely diagnosis; it is a sequential decision under asymmetric cost, in which the single catastrophic miss outweighs many false alarms, and the decisive signal may be one the patient has not volunteered - and that the model has not been trained to seek. The core deficit is therefore one of information gathering under uncertainty. Under incomplete histories, LLM systems may fail to show the behaviors safe triage requires: broadening the differential; seeking the missing red flag; lowering the threshold for escalation; deferring judgement until sufficient information is obtained; and escalating concern where high-harm diagnoses remain unexcluded. These modes of failure for LLMs can be difficult to detect considering that evaluations to date often use complete, well-curated, confidence-gated simulations. The application of LLMs under these conditions may be amplified by assistant-like behaviors and positive bias, including credulity, agreeableness, and miscalibration - when these are not constrained by clinical triage logic.

Premature closure, or committing to a conclusion before sufficient information is available, is a recognized contributor to diagnostic error but remains underexamined in large language models (LLMs). We define LLM premature closure as inappropriate commitment under uncertainty: providing an answer, recommendation, or clinical guidance when the safer response would be clarification, abstention, escalation, or refusal. We evaluated five frontier LLMs across structured and open-ended medical tasks. In MedQA (n = 500) and AfriMed-QA (n = 490) questions where the correct choice had been removed, models still selected an answer at high rates, with baseline false-action rates of 55-81% and 53-82%, respectively. In open-ended evaluation, models gave inappropriate answers on an average of 30% of 861 HealthBench questions and 78% of 191 physician-authored adversarial queries. Safety-oriented prompting reduced premature closure across models, but residual failure persisted, highlighting the need to evaluate whether medical LLMs know when not to answer.