# Large language models as synthetic clinical experts to inform longitudinal rare-disease modeling

arXiv: https://arxiv.org/abs/2608.16507 · HTML: https://mlsanity.com/paper/2608.16507/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 31 references that are in the map.
- First posted on arXiv 17 Aug 2026.

## Builds on (most cited first, 13 of 13)

- [Distilling the Knowledge in a Neural Network](https://mlsanity.com/paper/1503.02531/) (2015)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [Deep reinforcement learning from human preferences](https://mlsanity.com/paper/1706.03741/) (2017)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [Distilling Step-by-Step! Outperforming Larger Language Models with Less Training Data and Smaller Model Sizes](https://mlsanity.com/paper/2305.02301/) (2023)
- [Adapted Large Language Models Can Outperform Medical Experts in Clinical Text Summarization](https://mlsanity.com/paper/2309.07430/) (2023)
- [Hidden Stratification Causes Clinically Meaningful Failures in Machine Learning for Medical Imaging](https://mlsanity.com/paper/1909.12475/) (2019)
- [Language Models in the Loop: Incorporating Prompting into Weak Supervision](https://mlsanity.com/paper/2205.02318/) (2022)
- [Prior knowledge elicitation: The past, present, and future](https://mlsanity.com/paper/2112.01380/) (2021)
- [Leveraging Large Language Models for Knowledge-free Weak Supervision in Clinical Natural Language Processing](https://mlsanity.com/paper/2406.06723/) (2024)
- [Latent mixed-effect models for high-dimensional longitudinal data](https://mlsanity.com/paper/2409.11008/) (2024)
- [Using latent representations to link disjoint longitudinal data for mixed-effects regression](https://mlsanity.com/paper/2510.25531/) (2025)

## Abstract (arXiv)

Due to the limited amount of information, modeling longitudinal rare-disease data can benefit from integrating clinical knowledge. Yet, elicitation of expert knowledge and formalization for model fitting is challenging, in particular due to limited time of clinical experts. To nevertheless make domain knowledge accessible during model fitting, we use large language models (LLMs) as synthetic clinical experts to supervise a variational-autoencoder-based approach that learns low-dimensional latent summaries of visit-level observations. Specifically, LLMs are queried offline on textual descriptions of patient observations to obtain judgments, e.g., the suspected clinical category. To improve the variational autoencoder fit, we train a differentiable surrogate model on these judgments and augment the loss function to encourage reconstructions that preserve the clinical-label distribution of their corresponding input profile. In an application to longitudinal motor-function assessments from children with spinal muscular atrophy, we map visit-level clinical profiles to low-dimensional representations that are linked by a multivariate mixed-effects model. The synthetic expert loss discourages reconstructions that remain numerically close in data space but alter the clinical interpretation of the reconstructed motor function profile, such as by crossing a disease-type boundary. We thus reduced disagreement between original and reconstructed SMA type labels from about 11 to 7 percent. Furthermore, informing the latent representation by the synthetic expert improved prediction of motor function milestones compared with unsupervised latent representations and a data-level baseline. These results suggest that incorporating LLMs into model fitting can make clinical knowledge available to representation learning and improve clinical faithfulness for longitudinal rare-disease data.