Is a 9B Decision Foundation Model Needed for Symptom-to-Disease Classification? Fine-Tuning Clef-Flash Against TF-IDF Baselines

Clinical care, health-system operations and biomedical discovery depend on extracting reliable answers from patient records, yet applying diverse clinical questions across entire populations remains computationally expensive. Here we present Clinical System One (CS1), a 4-billion-parameter decision model for fast, typed judgments from clinical records, along with two agentic harnesses in which CS1 works together with a generalist language model. CS1-4B is trained on 12.4 million questions and answers from 3.6 million patients across a multi-hospital health system, combining structured-data keys, observed outcomes and language-model supervision across clinical notes, diagnostic reports and patient timelines. It answers multiple typed questions in a single forward pass without task-specific retraining, and each answer carries a probability that can route uncertain cases to human review. On 963,408 held-out patients, CS1-4B outperformed open decision models up to 27 billion parameters on 13 of 14 tasks scored independently of its training teacher. Across 21 external data sets, its aggregate performance approached that of the strongest tested 27-billion-parameter model, with 6.4-fold faster inference in a matched workload. Integrating CS1-4B with a language model agent produced cited answers over complete multi-year patient histories and screened a patient population against the eligibility criteria of 17 registered clinical trials, placing four times as many judged-eligible patients among its top 20 candidates as keyword search while using 690-fold fewer language-model tokens than a language model reading every record. These findings support a division of labour in clinical AI, with small decision models performing repeated record reading and generative models formulating questions and synthesizing evidence.

Clinical text classification requires choosing between specialized fine-tuned models (BERT variants) and general-purpose large language models (LLMs), yet neither dominates across all instances. We introduce Learning to Defer for clinical text (L2D-Clinical), a framework that learns when a BERT classifier should defer to an LLM based on uncertainty signals and text characteristics. Unlike prior L2D work that defers to human experts assumed universally superior, our approach enables adaptive deferral-improving accuracy when the LLM complements BERT. We evaluate on two English clinical tasks: (1) ADE detection (ADE Corpus V2), where BioBERT (F1=0.911) outperforms the LLM (F1=0.765), and (2) treatment outcome classification (MIMIC-IV with multi-LLM consensus ground truth), where GPT-5-nano (F1=0.967) outperforms ClinicalBERT (F1=0.887). On ADE, L2D-Clinical achieves F1=0.928 (+1.7 points over BERT) by selectively deferring 7% of instances where the LLM's high recall compensates for BERT's misses. On MIMIC, L2D-Clinical achieves F1=0.980 (+9.3 points over BERT) by deferring only 16.8% of cases to the LLM. The key insight is that L2D-Clinical learns to selectively leverage LLM strengths while minimizing API costs.

Current machine learning approaches to medical diagnosis often rely on correlational patterns between symptoms and diseases, risking misdiagnoses when symptoms are ambiguous or common across multiple conditions. In this work, we move beyond correlation to investigate the causal influence of key symptoms-specifically "chest pain" on diagnostic predictions. Leveraging the CausaLM framework, we generate counterfactual text representations in which target concepts are effectively "forgotten" enabling a principled estimation of the causal effect of that concept on a model's predicted disease distribution. By employing Textual Representation-based Average Treatment Effect (TReATE), we quantify how the presence or absence of a symptom shapes the model's diagnostic outcomes, and contrast these findings against correlation-based baselines such as CONEXP. Our results offer deeper insight into the decision-making behavior of clinical NLP models and have the potential to inform more trustworthy, interpretable, and causally-grounded decision support tools in medical practice.