KMGen: A Skill-based Approach for Synthetic Individual Patient Data Generation

Individual patient data (IPD) from clinical trials is the substrate for survival modeling, meta-analysis, and safety research, yet IPD is rarely released. Prior work has addressed only half of this gap: reconstructing Kaplan-Meier (KM) curves from published plots -- typically requiring manual digitization or human-in-the-loop correction -- while offering no mechanism for generating the adverse-event (AE) streams that constitute the other half of a patient record. We introduce KMGen, the first end-to-end framework that (i) fully automates KM curve extraction at accuracy competitive with human-guided tools, and (ii) generates synthetic per-patient AE trajectories from public trial registry records. The extraction stage is a fully automated agentic pipeline -- an agent generates code to extract each step in the KM curve -- achieving a mean Integrated Absolute Error (IAE) of 0.0151 on a 32-plot benchmark spanning clean, edge-case, and adversarial conditions. The IPD generation stage decouples patient archetype extraction from statistical sampling: an LLM distills the trial record into arm-specific statistics, adverse events, patient demographics, and risk multipliers. A mechanistic sampler generates patient events via clinical archetypes, bootstrap rank-correlation coupling to the empirical KM curve (preserving the marginal survival distribution exactly), and cycle-based AE scheduling with an induction/maintenance split. Across three held-out oncology trials spanning an order of magnitude in cohort size and 30 independent regenerations per trial, KMGen achieves mean integrated KM absolute difference $Δ_{\text{KM}}\,{\leq}\,0.051$, sex/ECOG JSD ${\leq}\,0.013$ on 5 of 6 demographic slots, and recovers ${\geq}\,71\%$ of the top-15 AEs by exact MedDRA term under a single fixed parameter set. The pipeline is released as open source at https://github.com/chufangao/kmgen.

Authoring and Management of Transparent Research Integrity Assessments of Randomised Clinical Trial Publications Using LLM-assisted Tools and Provenance Knowledge Graphs

Systematic reviews of Randomised Controlled Trials (RCTs) are routinely used as evidence for clinical care guidelines. Such evidence has to meet high research integrity standards to prevent low quality or false research outputs influencing the clinical care. However, assessing research integrity of published RCTs is a complex process requiring manual effort, and potentially resulting in diverse opinions of the human assessors. This paper describes INSPECT-AI, an LLM-based interactive tool that assists human reviewers with research integrity assessments of published RCTs based on the community approved INSPECT-SR framework, and the Research Integrity Provenance and Evidence ontology (RIPE-O) for documenting the provenance of the assessment process. In addition, we present the Research Integrity Provenance and Evidence knowledge graph (RIPE-KG), an initial set of 140 expert research integrity assessments of 95 RCT publications generated by INSPECT-AI and described using RIPE-O.

Research Assistant: AstraZeneca's Agentic System for R&D

We describe Research Assistant, an internal LLM-based system developed at AstraZeneca to help scientists and clinicians explore biomedical questions across a broad range of data sources. The system provides a chat-style interface that brings together evidence from scientific literature, knowledge graphs, chemistry, clinical trials, safety resources, expression data, and internal experimental systems. It supports both a fast mode for direct question answering and a multi-step mode for more complex research tasks. Responses are grounded in retrieved evidence and linked back to the original sources, allowing users to review and further explore the underlying data. In this technical note, we outline the system architecture, the main design choices behind the product, and lessons learned from deploying it at scale to support day-to-day R&D workflows across AstraZeneca.

Learning Clinical-Trial Strategy: Offline Policy Training for Decision Agents

Clinical development is sequential decision-making under uncertainty, where a sponsor must plan a portfolio of experiments from heterogeneous evidence. We study this setting by framing oncology clinical development as an offline decision-making problem in which an agent predicts the next six-month trial portfolio of an oncology drug program from information available at the decision date. To support this, we construct a temporal dataset that combines 31.7k heterogeneous public data records, including trial registries, regulatory reviews, sponsor filings, utilization data, and epidemiology, into 881 offline decision episodes across 45 historical programs. We compare four offline objectives: behavioral cloning, reward-weighted behavioral cloning, learned-reward training, and value-based implicit Q-learning against four frontier LLM agents that share a common date-gated retrieval scaffold across held-out drug, sponsor, drug-class, and temporal splits. Models trained offline outperform the non-fine-tuned baselines, particularly in the post-August 2025 contamination-clean holdout. Reward-weighted behavioral cloning performs the best, obtaining 46.2% indication F1 and 14.2% strict F1 against 25.0% and 2.1%, respectively, for the best-performing tool agent on each metric. These results suggest that structured offline learning can teach agents to plan clinical experiments.

Longitudinal Adaptive Experimental Design for Learning Multiple Target Estimands with Semiparametric Efficient Inference

Adaptive designs are increasingly used in clinical trials and digital experiments to improve estimation efficiency by updating treatment randomization probabilities as data accumulate. While most existing work focuses on settings with a single-stage treatment, adaptive designs for longitudinal studies with multi-stage, time-varying treatments remain relatively underexplored. In this work, we develop a general semiparametric efficiency framework for designing longitudinal adaptive experiments to optimize the estimation efficiency of a broad class of target estimands of interest. An efficiency-oriented design criterion is proposed to accommodate both single-estimand targets and joint optimization across multiple estimands. We demonstrate that optimal randomization at earlier stages depends on later-stage allocations, yielding a backward-recursive strategy for deriving the oracle design, and propose a longitudinal adaptive design to sequentially learn and target the oracle design using accumulating data. We further develop an adaptive-design-likelihood-based longitudinal targeted maximum likelihood estimator (ADL-LTMLE) for asymptotically normal and semiparametric efficient estimation of statistical estimands from dependent data collected from adaptive experiments, without relying on parametric model assumptions. Applying the framework to time-to-treatment-initiation effects that compare initiating treatment at a given stage with delaying initiation until a subsequent stage, we show that designs optimized for a particular stage-specific effect can substantially compromise estimation efficiency for effects defined at other stages, highlighting the design trade-offs addressed by our framework. Simulation studies show the proposed design and estimation approaches achieve substantial variance reductions relative to non-adaptive designs, with performance close to that of the oracle design.

The MADRS Pipeline: Supporting Depression Assessment in Clinical Trials

Depression is a major mental disorder for which diagnosis relies primarily on clinical assessments. Automated methods to support its detection via the psychiatric MADRS scale are getting more and more attention. While existing solutions primarily focus on detecting the disorder from different text sources (e.g., online text, social media), there is still limited support for clinical trials, where clinical assessments are conducted through structured interviews based on standard guidelines such as SIGMA. In this work, we develop a LLM pipeline specifically designed to support clinicians in supporting the assessment of depression in patients enrolled in clinical trials. Our pipeline converts audio interviews into transcripts, maps them into the ten MADRS symptom items, estimates their severity, and identify problematic clinical ratings associated with them. Evaluation on real clinical interviews shows a strong overall correlation of 0.867 with expert ratings, providing interpretable support for future assessments in clinical trials.

Full Bayesian Reinforcement Learning via LF-IBIS

Reinforcement Learning (RL) is a sequential decision-making framework in which an agent learns optimal policies through interaction with an environment by maximizing cumulative rewards. Among RL methods, Bayesian Reinforcement Learning (BRL) addresses common practical challenges related to data scarcity by leveraging prior knowledge about the environment and sequential belief updates. However, most BRL approaches require an explicit likelihood function, which is frequently inaccessible or intractable in real-world settings. We propose Likelihood-Free Iterated Batch Importance Sampling (LF-IBIS), a novel algorithm for BRL that updates the agent's beliefs online as new interactions become available. By combining Approximate Bayesian Computation with Iterated Batch Importance Sampling, LF-IBIS enables full Bayesian inference in settings where the environment dynamics are not described by an explicit or tractable likelihood. The method yields approximate posterior distributions over both environment parameters and optimal policies, providing a quantification of policy uncertainty useful for a Bayesian treatment of the exploration-exploitation trade-off. We test the method on a simulation study in response-adaptive randomization in clinical trials, where closed-form posteriors enable validation. Additional experiments address settings where the posterior has no closed form and illustrate online policy updating based on the posterior distribution of the optimal policy.

CaresAI at CT-DEB26: Detecting Dosing Errors In Clinical Trials Using Domain-Specific Transformer Embeddings and Classification Models

Medication errors, particularly dosing errors in clinical trials (CT), can lead to patient harm, adverse drug events and worse patient outcomes. Dosing errors are preventable, and early identification can improve trial integrity and mitigate subsequent clinical and financial burden. This study aims to detect dosing errors within CT protocols by evaluating text representations of trial information using transformer-based language models trained on biomedical corpora. CT textual data was encoded using several models, including ClinicalBERT, PubMedBERT, BioBERT, and MedCPT, and integrated with categorical features. These text embeddings were used as input to classical machine learning models and neural network architectures within an experimental framework. Performance was primarily assessed using ROC-AUC with respect to predicting dosage error. Under a logistic regression baseline, BioBERT consistently outperformed alternative encoders, achieving an ROC-AUC of 0.794, a 3.95% improvement over the ClinicalBERT baseline. Combining multiple embeddings did not yield improvements, indicating that domain alignment outweighs representational stacking. Gradient boosting models, support vector classifiers, logistic regression, and residual neural networks achieved the strongest performance for predicting dosage error, achieving ROC-AUCs: 0.821 to 0.853. Overall, the integration of domain-specific transformer embeddings with structured metadata enables discrimination of trials meeting a predefined elevated dosing error risk criterion, advancing safety monitoring and supporting informed regulatory decision-making.

On Response-Adaptive Targeting Strategies for Multi-Treatment Experiments

Response-adaptive randomization (RAR) in clinical trials aims to improve ethical and statistical efficiency by dynamically allocating patients to treatments based on observed outcomes. While RAR based on a target optimal allocation have been extensively studied for two-arms settings, their extension to multi-treatment experiments ($K \geq 2$) remains theoretically fragmented, with most existing methods focusing on specific algorithms or restricted target allocations. In this paper, we introduce a unified framework for response-adaptive targeting, the $α$-Rebalancing Targeting Strategies ($α$RTS), which generalize the ERADE two-armed strategy of Hu et al. [2009]. We prove that all designs in this family share fundamental asymptotic properties: strong consistency, asymptotic normality of allocation proportions and treatment effect estimators, and asymptotic efficiency. To address sparse target regimes (where some treatments are asymptotically eliminated), we further propose $α$RTS with Forced Exploration, a variant that guarantees infinite sampling for all treatments while preserving the asymptotic guarantees. Extensive simulations illustrate the finite-sample behavior of $α$RTS variants in a 3-armed context, highlighting in particular the critical role of forced exploration in sparse settings.

TrialCalibre: A Fully Automated Causal Engine for RCT Benchmarking and Observational Trial Calibration

Real-world evidence (RWE) studies that emulate target trials increasingly inform regulatory and clinical decisions, yet residual, hard-to-quantify biases still limit their credibility. The recently proposed BenchExCal framework addresses this challenge via a two-stage Benchmark, Expand, Calibrate process, which first compares an observational emulation against an existing randomized controlled trial (RCT), then uses observed divergence to calibrate a second emulation for a new indication causal effect estimation. While methodologically powerful, BenchExCal is resource intensive and difficult to scale. We introduce TrialCalibre, a conceptualized multiagent system designed to automate and scale the BenchExCal workflow. Our framework features specialized agents such as the Orchestrator, Protocol Design, Data Synthesis, Clinical Validation, and Quantitative Calibration Agents that coordi-nate the the overall process. TrialCalibre incorpo-rates agent learning (e.g., RLHF) and knowledge blackboards to support adaptive, auditable, and transparent causal effect estimation.

Diagnosis, Bad Planning & Reasoning. Treatment, SCOPE -- Planning for Hybrid Querying over Clinical Trial Data

We study clinical trial table reasoning, where answers are not directly stored in visible cells but must be reasoned from semantic understanding through normalization, classification, extraction, or lightweight domain reasoning. Motivated by the observation that current LLM approaches often suffer from "bad reasoning" under implicit planning assumptions, we focus on settings in which the model must recover implicit attributes such as therapy type, added agents, endpoint roles, or follow-up status from partially observed clinical-trial tables. We propose SCOPE (Structured Clinical hybrid Planning for Evidence retrieval in clinical trials), a multi-LLM planner-based framework that decomposes the task into row selection, structured planning, and execution. The planner makes the source field, reasoning rules, and output constraints explicit before answer generation, reducing ambiguity relative to direct prompting. We evaluate SCOPE on 1,500 hybrid reasoning questions over oncology clinical-trial tables against zero-shot, few-shot, chain-of-thought, TableGPT2, Blend-SQL, and EHRAgent. Results show that explicit multi-LLM planning improves accuracy for reasoning-based questions while offering a stronger accuracy-efficiency tradeoff than heavier agentic baselines. Our findings position clinical trial reasoning as a distinct table understanding problem and highlight hybrid planner-based decomposition as an effective solution