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, and the evidence of safety does not yet exist.
Abstract
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.
A narrative review of the available evidence presents a narrative review of the available evidence on the effect of LLMs on diagnostic reasoning, the optimal design of clinician-LLM interaction, the appropriate timing of consultation during the clinical encounter, the safest models of clinical-AI integration, and the main risks associated with their use.
L. Corral-Gudino, M. Ramos-Casals, M. Marcos et al.· Medicina clínica (Ed. impres...· 0 citations
Uncommon and off-guideline cases are difficult for clinical decision support, because physicians must make a series of management decisions under diagnostic uncertainty and rarely see the full case at once. Most large language model (LLM) benchmarks for medicine score only the final diagnosis, yet much of clinical care turns on the next appropriate action: the next test to order, the imaging study to obtain, the specialist to involve, or the differential to pursue. We introduce MedUPSQA, a dataset of 21,874 mid-stream clinical decision points built from 5,535 real case reports, and MedUPS, an alignment framework that supervises models on these intermediate decisions as they unfold along a patient's trajectory. We segment free-text case presentations into chronologically ordered, accumulating clinical chunks and align models to predict the next step with reinforcement learning (GRPO), using an external LLM-as-a-Judge reward. This objective mirrors how clinicians actually meet patients, reasoning forward from accumulating evidence toward the next decision, rather than committing to a final label. Across three backbones, mid-stream alignment raises next-step accuracy from 55.2 to 66.7 for Qwen3.6-27B, from 47.2 to 57.8 for Qwen3.5-9B, and from 37.8 to 44.4 for HuatuoGPT-3-8B, with 95% CI. In several model scales we test the objective improves accuracy more than scale, with smaller models surpassing larger, frontier models we evaluate. We further train supervised fine-tuning (SFT) baselines on the mid-stream task, SFT improves all backbones above base, indicating the target framwork carries signal independently of the optimizer. We release the dataset, code, and aligned checkpoints.
Ofir Ben Shoham, O. Perets, Nir Grinberg et al.· 0 citations
It is concluded that AI tools have matured to the extent that they can improve diagnostic decision-making of clinicians and can assist institutions in increasing diagnostic safety.
Although promising, LLM-based systems are not yet reliable enough for autonomous medical diagnosis, and multiple recommendations for future research are contained to ensure a high level of safety, transparency, and clinical applicability for LLMs and other AI/ML-related technologies and devices.
M. U. K. Gunawardhna, Pirunthavi Wijikumar, D. Weerasinghe· Sri Lankan Journal of Applie...· 0 citations
Large language models achieve high scores on medical knowledge assessments, yet clinical reasoning requires actively deciding what to investigate under uncertainty. We developed an agentic evaluation framework in hematologic oncology in which models must proactively request clinical data across three sequential rounds before committing to a diagnosis and treatment plan. Across 32 frontier models, the best achieved only 68% overall accuracy. Information utilization, the fraction of available data actually requested, was the strongest predictor of diagnostic accuracy (R = 0.69, P<0.001), yet utilization collapsed from 57% to 26% in the final round, leaving molecular and cytogenetic data critical for treatment selection unexamined. Reasoning traces scored high on a clinical reasoning rubric (91% above threshold) but decorrelated from accuracy, revealing a gap between locally coherent rationales and globally correct conclusions. Error analysis identified search satisficing, anchoring and premature closure as the dominant failure modes, the same cognitive biases that characterize novice clinicians under dual-process models of diagnostic reasoning. These findings demonstrate that the primary limitation of current models in clinical oncology is not insufficient medical knowledge but a systematic failure of information-seeking under uncertainty.
K. Braitsch, L. Schmalbrock, Theresa Weltermann et al.· 1 citation