Supervised Fine-tuning with Synthetic Rationale Data Hurts Real-World Disease Prediction
Authors: Buxin Su, Bingxuan Li, Cheng Qian, Yiwei Wang, Jin Jin, Bingxin Zhao
Organizations: University of Pennsylvania · University of Illinois Urbana-Champaign · University of California, Merced
Abstract
Supervised fine-tuning with synthetic rationale data is widely assumed to improve language model performance on clinical prediction tasks by teaching models not just what to predict but why. We test this assumption on five-year Alzheimer's disease and related dementias (ADRD) prediction from longitudinal health histories. Across a large-scale controlled experiment of 504 configurations, we find that rationale-based SFT consistently and substantially hurts prediction performance relative to label-only fine-tuning. The degradation persists across model families and data scales, and is not resolved by using a reasoning-oriented base model. Crucially, the failure is not explained by poor rationale quality: human expert annotation confirms that the generated rationales are medically accurate and faithfully grounded in patient-specific evidence, and few-shot experiments show that the same rationales improve performance when used as inference-time demonstrations rather than training targets. We identify the root cause as a structural conflict between narrative plausibility and discriminative optimization. We hope our work paves the path toward a more precise understanding of when and how rationale-based supervision helps and when it does not, guiding the responsible development of language models for high-stakes clinical prediction.
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.
Supervised fine-tuning (SFT) on a small, high-quality set of long reasoning traces is an effective approach for eliciting strong reasoning capabilities in Large Language Models (LLMs). However, existing methods for curating high-quality SFT data rely heavily on strong reasoning models to filter examples based on diversity and difficulty, making the curation process costly while often yielding suboptimal data quality. In this work, we show that diverse and challenging reasoning examples can be identified using only the initial reasoning tokens. Specifically, we demonstrate that difficult problems can be reliably detected based on the loss of the first 100 reasoning tokens evaluated at a randomly perturbed checkpoint of the pretrained model. We further show that examples exhibiting similar loss patterns over their first 1k reasoning tokens across a small number of perturbed checkpoints extrapolating along the fine-tuning trajectory provably induce similar gradients. We validate our approach through extensive experiments on fine-tuning Qwen2.5-7B and Llama3.1-8B models on the M23K medical reasoning and OpenThoughts-Math datasets. Our method outperforms existing baselines by up to 1.7% while being 91% more token efficient.
Longitudinal clinical notes contain rich evidence of how patients evolve over time, but converting this signal into training supervision for clinical prediction remains challenging. We extend Foresight Learning to clinical prediction by converting time-ordered MIMIC-III notes into examples consisting of past patient context, a natural-language question about a possible future event, and a label resolved from later documentation. This process yields 6,900 prediction examples from 702 admissions across medications, procedures, organ support, microbiology, and mortality. A small LoRA adapter trained on these examples improves over the prompted base model, reducing expected calibration error from 0.1269 to 0.0398 and Brier score from 0.199 to 0.145, while slightly outperforming GPT-5 point estimates on held-out questions. The approach enables reusable clinical prediction supervision from longitudinal notes without hand-engineered structured features or endpoint-specific classifiers.