Information-seeking failures of large language models in agentic clinical reasoning

Krischan Braitsch, Laura K. Schmalbrock, Theresa Weltermann, Andrew F. Berdel, Isabella Miller, Kai Tran, Michael Heider, Sabrina Kraus, Florian Bassermann, Jacqueline Lammert, Sebastian Ziegelmayer, Marcus Makowski, Lisa C. Adams, Keno K. Bressem

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.