OncoSynth: Synthetic data generation for treatment effect estimation in oncology

In oncology, access to patient-level data is often restricted. Synthetic data provides an alternative for analyzing treatment effectiveness, but existing methods for synthetic data generation fail to preserve the causal relationships between covariates, treatments, and outcomes, thereby leading to biased estimates of treatment effects. Here, we introduce OncoSynth, a generative, causally-aware machine learning framework designed to produce synthetic cohorts that enable accurate estimation of population- and patient-level treatment effects. OncoSynth uses a diffusion-based sequential approach to model how covariates influence treatment assignment and how treatment affects survival. We evaluate OncoSynth using large lung (N = 37,128) and breast cancer (N = 17,046) cohorts. Our results show that OncoSynth generates high-fidelity synthetic patient cohorts that preserve real-world patient, treatment, and outcome distributions. Notably, OncoSynth improves treatment effect estimation over existing approaches, by reducing population-level treatment effect error by up to 66%, and patient-level treatment effect error by up to 58%. Thereby, OncoSynth supports reliable evidence generation for precision oncology in settings where data sharing is restricted.

$\text{DT}^2$: Decision-Targeted Digital Twins

A digital twin (DT) is a virtual model of a real-world system that can assist decision-making by simulating scenarios induced by different policies. However, typical machine learning-based DTs do not optimise for this use case. We prove that, when model capacity is limited, training DTs to minimise one-step transition errors can produce suboptimal models for ranking sets of policies according to a reward function. We further show that this holds empirically, even with expressive model classes. To address this, we introduce $\text{DT}^2$, a decision-targeted DT training paradigm. Firstly, $\text{DT}^2$ uses fitted Q-evaluation to estimate values of candidate policies from offline data. A DT is then trained to generate rollouts that preserve pairwise policy rankings derived from these proxy ground-truth values with an architecture-agnostic loss function. We empirically demonstrate the efficacy of our method across a range of settings and architectures. $\text{DT}^2$ consistently improves policy ranking and reduces decision regret during policy selection relative to conventional DT training, both for policies used during training and for unseen policies, while maintaining a good level of raw simulation fidelity.

Hyperparameter Trajectory Inference with Conditional Lagrangian Optimal Transport

Neural networks (NNs) often have critical behavioural trade-offs that are set at design time with hyperparameters-such as reward weights in reinforcement learning or quantile targets in regression. Post-deployment, however, user preferences can evolve, making initial settings undesirable, necessitating potentially expensive retraining. To circumvent this, we introduce the task of Hyperparameter Trajectory Inference (HTI): to learn, from observed data, how a NN's conditional output distribution changes with its hyperparameters, and construct a surrogate model that approximates the NN at unobserved hyperparameter settings. HTI requires extending existing trajectory inference approaches to incorporate conditions, exacerbating the challenge of ensuring inferred paths are feasible. We propose an approach based on conditional Lagrangian optimal transport, jointly learning the Lagrangian function governing hyperparameter-induced dynamics along with the associated optimal transport maps and geodesics between observed marginals, which form the surrogate model. We incorporate inductive biases based on the manifold hypothesis and least-action principles into the learned Lagrangian, improving surrogate model feasibility. We empirically demonstrate that our approach reconstructs NN outputs across various hyperparameter spectra better than other alternatives.

Continuously Updating Digital Twins using Large Language Models

Digital twins are models of real-world systems that can simulate their dynamics in response to potential actions. In complex settings, the state and action variables, and available data and knowledge relevant to a system can constantly change, requiring digital twins to continuously update with these changes to remain relevant. Current approaches struggle in this regard, as they require fixed, well-defined modelling environments, and they cannot adapt to novel variables without re-designs, or incorporate new information without re-training. To address this, we frame digital twinning as an in-context learning problem using large language models, enabling seamless updates to the twin at inference time. We develop CALM-DT, a Context-Adaptive Language Model-based Digital Twin that can accurately simulate across diverse state-action spaces using in-context learning alone by utilising fine-tuned encoders for sample retrieval. We empirically demonstrate CALM-DT's competitive performance with existing digital twin approaches, and its unique ability to adapt to changes in its modelling environment without parameter updates.

Revolutionizing Clinical Trials: A Manifesto for AI-Driven Transformation

This manifesto represents a collaborative vision forged by leaders in pharmaceuticals, consulting firms, clinical research, and AI. It outlines a roadmap for two AI technologies - causal inference and digital twins - to transform clinical trials, delivering faster, safer, and more personalized outcomes for patients. By focusing on actionable integration within existing regulatory frameworks, we propose a way forward to revolutionize clinical research and redefine the gold standard for clinical trials using AI.