William J Bolton
Publications
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.
Adversarial Fast-Moving Real-World Domains as Test Beds for Benchmarking AI Scientist Capabilities
Benchmarking the ability of AI scientists to generate novel ideas is notoriously difficult. Existing benchmarks in this field have made progress in evaluating scientific reasoning and research replication, but often rely on synthetic tasks or retrospective targets, which may be confounded by prior exposure. We hypothesize that complex, adversarial, fast-moving real-world domains where expert practitioners independently generate observable outputs can provide a practical solution to fill this gap and evaluate the capabilities needed for AI scientists, including reasoning, novelty, and hypothesis formulation. We instantiate this framework in two structurally different domains, Formula 1 (F1), where models ideate around car design concepts for the 2026 season, and real pre-season innovations provide a ground truth, and Magic: The Gathering (MTG), where models propose decks from a recently updated card pool and are evaluated against 19 Pro Tour (PT) decklists. Across both domains, models produce plausible outputs, but few align with real-world expert solutions. In F1, the best model, GPT-5.2 matched 10 of 40 real innovations with 166 ideas proposed across runs. In MTG, the best deck from Gemini 3 Flash recovered 5 of 7 new-set cards from the third-place PT deck, and across all 108 decks, the cards models selected most often were also the cards most widely adopted by PT decks (Spearman $ρ= 0.74$, $p = 0.0003$). These results suggest that a key capability gap for AI scientists is not idea generation, but filtering, prioritization, and coherent novelty.