Large Language Models forecast Patient Health Trajectories enabling Digital Twins

BackgroundGenerative artificial intelligence (AI) accelerates the development of digital twins, which enable virtual representations of real patients to explore, predict and simulate patient health trajectories, ultimately aiding treatment selection and clinical trial design. Recent advances in forecasting utilizing generative AI, in particular large language models (LLMs), highlights untapped potential to overcome real-world data (RWD) challenges such as missingness, noise and limited sample sizes, thus empowering the next generation of AI algorithms in healthcare. MethodsWe developed the Digital Twin - Generative Pretrained Transformer (DT-GPT) model, which utilizes biomedical LLMs using rich electronic health record (EHR) data. Our method eliminates the need for data imputation and normalization, enables forecasting of clinical variables, and preliminary explainability through a human-interpretable interface. We benchmarked DT-GPT on RWD including long-term US nationwide non-small cell lung cancer (NSCLC) and short-term Intensive Care Unit (ICU) datasets. FindingsDT-GPT surpassed state-of-the-art machine learning methods in patient trajectory forecasting on mean absolute error (MAE) for both the long-term (3.4% MAE improvement) and the short-term (1.3% MAE improvement) dataset. Additionally, DT-GPT was capable of preserving cross-correlations of clinical variables (average R2 of 0.98), handling data missingness and noise. Finally, we discovered the ability of DT-GPT to provide insights into a forecasts rationale and to perform zero-shot forecasting on variables not used during fine-tuning, outperforming even fully trained task-specific machine learning models on 13 clinical variables. InterpretationDT-GPT demonstrates that LLMs can serve as a robust medical forecasting platform, empowering digital twins which virtually replicate patient characteristics beyond their training data. We envision that LLM-based digital twins will enable a variety of use cases, including clinical trial simulations, treatment selection and adverse event mitigation.