Trends in AI and Human-AI Interaction in Clinical Trials -- A Hybrid Human-AI Exploration

Clinical trials are essential for advancing cancer care and drug development, but many fail because of insufficient patient enrollment. While there is growing interest in using AI to support patient recruitment, existing systems largely perform eligibility assessment alone and have rarely been evaluated in real-world oncology workflows. Here we present TrialGPT 2.0, an AI-assisted clinical trial recommendation system designed for real-world deployment. Rather than asking only whether a patient may qualify, the system also assesses which trials warrant further consideration given the patient's current clinical needs and local workflow priorities, and provides structured, inspectable explanations for expert review. Importantly, we evaluated TrialGPT 2.0 retrospectively and prospectively across multiple oncology-focused settings, spanning government, academic cancer-center, patient-advocacy, and NIH referral workflows. In retrospective multicenter cohorts comprising 288 cases, TrialGPT 2.0 retrieved at least one clinician-recommended trial in its top 10 recommendations for approximately 91% of cases while reducing clinician screening time by 55.0%. In a six-month prospective evaluation embedded in an active precision oncology tumor board, TrialGPT 2.0 contributed additional trial opportunities missed by the routine workflow, expanding patient access to clinical trial participation by 90.9%. To support scientific reproducibility, we also introduce NIH-TrialBench, a clinician-authored dataset comprising 126 diverse synthetic patient vignettes and matching scenarios from 11 NIH Institutes and Centers. Together, these results support the value of AI to assist clinical trial matching by improving clinician efficiency and identifying frequently overlooked trial opportunities, ultimately helping to expand and accelerate accrual to cancer trials.

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

Scientists have long sought to accurately predict outcomes of real-world events before they happen. Can AI systems do so more reliably? We study this question through clinical trial outcome prediction, a high-stakes open challenge even for domain experts. We introduce CT Open, an open-access, live platform that will run four challenge every year. Anyone can submit predictions for each challenge. CT Open evaluates those submissions on trials whose outcomes were not yet public at the time of submission but were made public afterwards. Determining if a trial's outcome is public on the internet before a certain date is surprisingly difficult. Outcomes posted on official registries may lag behind by years, while the first mention may appear in obscure articles. To address this, we propose a novel, fully automated decontamination pipeline that uses iterative LLM-powered web search to identify the earliest mention of trial outcomes. We validate the pipeline's quality and accuracy by human expert's annotations. Since CT Open's pipeline ensures that every evaluated trial had no publicly reported outcome when the prediction was made, it allows participants to use any methodology and any data source. In this paper, we release a training set and two time-stamped test benchmarks, Winter 2025 and Summer 2025. We believe CT Open can serve as a central hub for advancing AI research on forecasting real-world outcomes before they occur, while also informing biomedical research and improving clinical trial design. CT Open Platform is hosted at $\href{https://ct-open.net/}{https://ct-open.net/}$