Predicting the outcomes of prospective clinical trials remains a major challenge for large language models. Prior work has shown that both traditional correlational predictors, such as random forests and logistic regression, and strong commercial LLMs achieve limited performance on this task. In this paper, we propose DeepImagine, a framework for teaching LLMs biomedical reasoning through successive counterfactual imagining. The central idea is to approximate hidden causal mechanisms of clinical trials by training models to infer how observed trial results would change under controlled perturbations of experimental conditions, such as dosage, outcome measures, study arms, geography, and other trial attributes. To support this objective, we construct both natural and approximate counterfactual pairs from real clinical trials with reported outcomes. For settings where strict counterfactual supervision is available, such as paired outcome measures or dose-ranging study arms within the same trial, we train models with supervised fine-tuning. For broader settings where only approximate counterfactual pairs can be retrieved, we optimize models with reinforcement learning using verifiable rewards based on downstream benchmark correctness. We further augment training with synthetic reasoning traces that provide causally plausible explanations for local counterfactual transitions. Using this pipeline, we train language models under 10B parameters, including Qwen3.5-9B, and evaluate them on clinical trial outcome prediction. We aim to show that DeepImagine consistently improves over untuned language models and traditional correlational baselines. Finally, we aim to show that the learned reasoning trajectories provide interpretable signals about how models represent trial-level mechanisms, suggesting a practical path toward more mechanistic and scientifically useful biomedical language models.
Counterfactual explanations (CFEs) provide human-centric interpretability by identifying the minimal, actionable changes required to alter a machine learning model's prediction. Therefore, CFs can be used as (i) interventions for abnormality prevention and (ii) augmented data for training robust models. We conduct a comprehensive evaluation of CF generation using large language models (LLMs), including GPT-4 (zero-shot and few-shot) and two open-source models-BioMistral-7B and LLaMA-3.1-8B, in both pretrained and fine-tuned configurations. Using the multimodal AI-READI clinical dataset, we assess CFs across three dimensions: intervention quality, feature diversity, and augmentation effectiveness. Fine-tuned LLMs, particularly LLaMA-3.1-8B, produce CFs with high plausibility (up to 99%), strong validity (up to 0.99), and realistic, behaviorally modifiable feature adjustments. When used for data augmentation under controlled label-scarcity settings, LLM-generated CFs substantially restore classifier performance, yielding an average 20% F1 recovery across three scarcity scenarios. Compared with optimization-based baselines such as DiCE, CFNOW, and NICE, LLMs offer a flexible, model-agnostic approach that generates more clinically actionable and semantically coherent counterfactuals. Overall, this work demonstrates the promise of LLM-driven counterfactuals for both interpretable intervention design and data-efficient model training in sensor-based digital health. Impact: SenseCF fine-tunes an LLM to generate valid, representative counterfactual explanations and supplement minority class in an imbalanced dataset for improving model training and boosting model robustness and predictive performance
Shovito Barua Soumma, Asiful Arefeen, Stephanie M. Carpenter +2
Deploying Large Language Models (LLMs) in healthcare requires robust performance across two complementary dimensions - diagnostic reasoning: the convergent, evidence-driven task of inferring a patient's condition from clinical data to produce a diagnosis, and clinical healthcare reasoning: the broader, navigational judgment required to communicate, plan, and adapt across multi-turn clinical interactions where a single correct answer may not exist. Recent benchmarks such as HealthBench and MedXpertQA reveal persistent weaknesses in both areas, exposing failures in complex diagnostic scenarios and limitations in contextual, patient-centered dialogue. We introduce a sequential training framework that targets these facets using synthetic data and rubric-based reinforcement learning. First, we improve diagnostic reasoning using MedBullets-derived questions with rule- and rubric-guided Reinforcement Learning (RL). We then shift to clinical reasoning by generating 5.3k synthetic multi-turn scenarios, each paired with multi-dimensional rubrics to comprehensively assess the response. This approach yields over 10% improvement on MedXpertQA, and our 30B model achieves 50.1% accuracy on HealthBench-Hard, surpassing proprietary baselines including GPT-5 (thinking). Our results show that targeted synthetic datasets and rubric-based training can systematically improve both diagnostic and interactive clinical reasoning in medical LLMs.
Natural language understanding often depends on meanings that are implied rather than explicitly stated, requiring pragmatic reasoning. Despite strong performance on math and logical reasoning, large language models (LLMs) still struggle with making pragmatic inferences, often choosing literal interpretations. To improve LLM pragmatic reasoning, we introduce PragReST, a self-supervised framework that constructs pragmatic QA data, generates counterfactual reasoning traces, and trains models to internalize them through supervised fine-tuning and reinforcement learning, without human-labeled training data or distillation from a stronger teacher. Across four pragmatic benchmarks (PragMega, Ludwig, MetoQA, and AltPrag), PragReST improves over backbone models, task-specific pragmatic tuning baselines, and non-counterfactual variants of the same pipeline. On accuracy-based benchmarks, PragReST improves over the instruct backbone by 5.37 and 5.50% (absolute) for Qwen3-8B and Qwen3-14B, respectively. Our error analysis and ablations underscore the importance of counterfactual reasoning: PragReST primarily reduces errors caused by failures to contrast observed utterances with plausible alternatives, and removing counterfactual reasoning substantially reduces performance. Moreover, our training preserves out-of-domain performance on general-knowledge and mathematical reasoning benchmarks.