ATHENA: Knowledge-guided agentic neural architecture search for AutoFormer-based electronic health record modeling

Abstract

Transformer-based models are widely used for clinical prediction from electronic health records (EHRs), yet their architectures require manual tuning, and the optimal configuration may vary across tasks and hospitals. Neural architecture search (NAS) automates architecture design, but conventional methods are computationally costly for Transformer-based EHR models. Recent large language model (LLM)-guided NAS methods reduce manual search design but conduct each search independently, without reusing architecture knowledge across hospitals. In this study, we propose ATHENA (Agentic Transfer across Hospitals for EHR Neural Architecture Search), a knowledge-guided agentic NAS framework for Transformer-based EHR modeling. ATHENA uses a weight-sharing supernet that is pretrained once per hospital, allowing candidate architectures to be instantiated as inherited subnetworks and evaluated through fine-tuning rather than independent pretraining. It incorporates a two-layer cross-hospital architecture prior. The first layer retrieves high-performing architecture examples from source sites based on task descriptors, while the second estimates the effects of architectural components using SHapley Additive exPlanations (SHAP)-based meta-regression. These priors guide a multi-agent LLM search using validation feedback from the target hospital. Across six clinical prediction tasks evaluated at one held-out OneFlorida+ site and one external MIMIC-IV site, ATHENA significantly outperforms all four baselines in 9 of 12 site-task evaluations under a strict equal-compute comparison. Using a common pretrained AutoFormer supernet for candidate evaluation, ATHENA ranks first in 9 of 12 evaluations at a search budget of 30. It also shows more consistent architecture selection across repeated searches. ATHENA provides a practical approach for reducing manual architecture tuning in Transformer-based EHR modeling.