Timely Clinical Diagnosis through Active Test Selection

There is growing interest in using machine learning (ML) to support clinical diag- nosis, but most approaches rely on static, fully observed datasets and fail to reflect the sequential, resource-aware reasoning clinicians use in practice. Diagnosis remains complex and error prone, especially in high-pressure or resource-limited settings, underscoring the need for frameworks that help clinicians make timely and cost-effective decisions. We propose ACTMED (Adaptive Clinical Test selection via Model-based Experimental Design), a diagnostic framework that integrates Bayesian Experimental Design (BED) with large language models (LLMs) to better emulate real-world diagnostic reasoning. At each step, ACTMED selects the test expected to yield the greatest reduction in diagnostic uncertainty for a given patient. LLMs act as flexible simulators, generating plausible patient state distributions and supporting belief updates without requiring structured, task-specific training data. Clinicians can remain in the loop; reviewing test suggestions, interpreting intermediate outputs, and applying clinical judgment throughout. We evaluate ACTMED on real-world datasets and show it can optimize test selection to improve diagnostic accuracy, interpretability, and resource use. This represents a step to- ward transparent, adaptive, and clinician-aligned diagnostic systems that generalize across settings with reduced reliance on domain-specific data.

Learning a Dense Reasoning Reward Model from Expert Demonstration via Inverse Reinforcement Learning

We reframe and operationalise adversarial inverse reinforcement learning (IRL) to large language model reasoning, learning a dense, token-level reward model for process supervision directly from expert demonstrations rather than imitating style via supervised fine-tuning. The learned reasoning reward serves two complementary roles: (i) it provides step-level feedback to optimise a reasoning policy during training; and (ii) it functions at inference as a critic to rerank sampled traces under fixed compute budgets. We demonstrate that our approach prioritises correctness over surface form, yielding scores that correlate with eventual answer validity and enabling interpretable localisation of errors within a trace. Empirically, on GSM8K with Llama3 and Qwen2.5 backbones, we demonstrate: (i) dense reasoning rewards can be used as a learning signal to elicit reasoning, and (ii) predictive performance is improved from reward-guided reranking (notably for Llama-based policies). By unifying training signals, inference-time selection, and token-level diagnostics into a single reasoning reward, this work suggests reusable process-level rewards with broad potential to enhance multi-step reasoning in language models.

Inverse Reinforcement Learning Meets Large Language Model Post-Training: Basics, Advances, and Opportunities

In the era of Large Language Models (LLMs), alignment has emerged as a fundamental yet challenging problem in the pursuit of more reliable, controllable, and capable machine intelligence. The recent success of reasoning models and conversational AI systems has underscored the critical role of reinforcement learning (RL) in enhancing these systems, driving increased research interest at the intersection of RL and LLM alignment. This paper provides a comprehensive review of recent advances in LLM alignment through the lens of inverse reinforcement learning (IRL), emphasizing the distinctions between RL techniques employed in LLM alignment and those in conventional RL tasks. In particular, we highlight the necessity of constructing neural reward models from human data and discuss the formal and practical implications of this paradigm shift. We begin by introducing fundamental concepts in RL to provide a foundation for readers unfamiliar with the field. We then examine recent advances in this research agenda, discussing key challenges and opportunities in conducting IRL for LLM alignment. Beyond methodological considerations, we explore practical aspects, including datasets, benchmarks, evaluation metrics, infrastructure, and computationally efficient training and inference techniques. Finally, we draw insights from the literature on sparse-reward RL to identify open questions and potential research directions. By synthesizing findings from diverse studies, we aim to provide a structured and critical overview of the field, highlight unresolved challenges, and outline promising future directions for improving LLM alignment through RL and IRL techniques.

Beyond the ATE: Interpretable Modelling of Treatment Effects over Dose and Time

The Average Treatment Effect (ATE) is a foundational metric in causal inference, widely used to assess intervention efficacy in randomized controlled trials (RCTs). However, in many applications -- particularly in healthcare -- this static summary fails to capture the nuanced dynamics of treatment effects that vary with both dose and time. We propose a framework for modelling treatment effect trajectories as smooth surfaces over dose and time, enabling the extraction of clinically actionable insights such as onset time, peak effect, and duration of benefit. To ensure interpretability, robustness, and verifiability -- key requirements in high-stakes domains -- we adapt SemanticODE, a recent framework for interpretable trajectory modelling, to the causal setting where treatment effects are never directly observed. Our approach decouples the estimation of trajectory shape from the specification of clinically relevant properties (e.g., maxima, inflection points), supporting domain-informed priors, post-hoc editing, and transparent analysis. We show that our method yields accurate, interpretable, and editable models of treatment dynamics, facilitating both rigorous causal analysis and practical decision-making.

Towards a Cascaded LLM Framework for Cost-effective Human-AI Decision-Making

Effective human-AI decision-making balances three key factors: the \textit{correctness} of predictions, the \textit{cost} of knowledge and reasoning complexity, and the confidence about whether to \textit{abstain} automated answers or involve human experts. In this work, we present a cascaded LLM decision framework that adaptively delegates tasks across multiple tiers of expertise -- a base model for initial candidate answers, a more capable and knowledgeable (but costlier) large model, and a human expert for when the model cascade abstains. Our method proceeds in two stages. First, a deferral policy determines whether to accept the base model's answer or regenerate it with the large model based on the confidence score. Second, an abstention policy decides whether the cascade model response is sufficiently certain or requires human intervention. Moreover, we incorporate an online learning mechanism in the framework that can leverage human feedback to improve decision quality over time. We demonstrate this approach to general question-answering (ARC-Easy and ARC-Challenge) and medical question-answering (MedQA and MedMCQA). Our results show that our cascaded strategy outperforms in most cases single-model baselines in accuracy while reducing cost and providing a principled way to handle abstentions.

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.

G-Sim: Generative Simulations with Large Language Models and Gradient-Free Calibration

Constructing robust simulators is essential for asking "what if?" questions and guiding policy in critical domains like healthcare and logistics. However, existing methods often struggle, either failing to generalize beyond historical data or, when using Large Language Models (LLMs), suffering from inaccuracies and poor empirical alignment. We introduce G-Sim, a hybrid framework that automates simulator construction by synergizing LLM-driven structural design with rigorous empirical calibration. G-Sim employs an LLM in an iterative loop to propose and refine a simulator's core components and causal relationships, guided by domain knowledge. This structure is then grounded in reality by estimating its parameters using flexible calibration techniques. Specifically, G-Sim can leverage methods that are both likelihood-free and gradient-free with respect to the simulator, such as gradient-free optimization for direct parameter estimation or simulation-based inference for obtaining a posterior distribution over parameters. This allows it to handle non-differentiable and stochastic simulators. By integrating domain priors with empirical evidence, G-Sim produces reliable, causally-informed simulators, mitigating data-inefficiency and enabling robust system-level interventions for complex decision-making.

Improving LLM Agent Planning with In-Context Learning via Atomic Fact Augmentation and Lookahead Search

Large Language Models (LLMs) are increasingly capable but often require significant guidance or extensive interaction history to perform effectively in complex, interactive environments. Existing methods may struggle with adapting to new information or efficiently utilizing past experiences for multi-step reasoning without fine-tuning. We introduce a novel LLM agent framework that enhances planning capabilities through in-context learning, facilitated by atomic fact augmentation and a recursive lookahead search. Our agent learns to extract task-critical ``atomic facts'' from its interaction trajectories. These facts dynamically augment the prompts provided to LLM-based components responsible for action proposal, latent world model simulation, and state-value estimation. Planning is performed via a depth-limited lookahead search, where the LLM simulates potential trajectories and evaluates their outcomes, guided by the accumulated facts and interaction history. This approach allows the agent to improve its understanding and decision-making online, leveraging its experience to refine its behavior without weight updates. We provide a theoretical motivation linking performance to the quality of fact-based abstraction and LLM simulation accuracy. Empirically, our agent demonstrates improved performance and adaptability on challenging interactive tasks, achieving more optimal behavior as it accumulates experience, showcased in tasks such as TextFrozenLake and ALFWorld.

Statistical Hypothesis Testing for Auditing Robustness in Language Models

Consider the problem of testing whether the outputs of a large language model (LLM) system change under an arbitrary intervention, such as an input perturbation or changing the model variant. We cannot simply compare two LLM outputs since they might differ due to the stochastic nature of the system, nor can we compare the entire output distribution due to computational intractability. While existing methods for analyzing text-based outputs exist, they focus on fundamentally different problems, such as measuring bias or fairness. To this end, we introduce distribution-based perturbation analysis, a framework that reformulates LLM perturbation analysis as a frequentist hypothesis testing problem. We construct empirical null and alternative output distributions within a low-dimensional semantic similarity space via Monte Carlo sampling, enabling tractable inference without restrictive distributional assumptions. The framework is (i) model-agnostic, (ii) supports the evaluation of arbitrary input perturbations on any black-box LLM, (iii) yields interpretable p-values; (iv) supports multiple perturbations via controlled error rates; and (v) provides scalar effect sizes. We demonstrate the usefulness of the framework across multiple case studies, showing how we can quantify response changes, measure true/false positive rates, and evaluate alignment with reference models. Above all, we see this as a reliable frequentist hypothesis testing framework for LLM auditing.