RCTs & Human Uplift Studies: Methodological Challenges and Practical Solutions for Frontier AI Evaluation

Human uplift studies - or studies that measure AI effects on human performance relative to a status quo, typically using randomized controlled trial (RCT) methodology - are increasingly used to inform deployment, governance, and safety decisions for frontier AI systems. While the methods underlying these studies are well-established, their interaction with the distinctive properties of frontier AI systems remains underexamined, particularly when results are used to inform high-stakes decisions. We present findings from interviews with 16 expert practitioners with experience conducting human uplift studies in domains including biosecurity, cybersecurity, education, and labor. Across interviews, experts described a recurring tension between standard causal inference assumptions and the object of study itself. Rapidly evolving AI systems, shifting baselines, heterogeneous and changing user proficiency, and porous real-world settings strain assumptions underlying internal, external, and construct validity, complicating the interpretation and appropriate use of uplift evidence. We synthesize these challenges across key stages of the human uplift research lifecycle and map them to practitioner-reported solutions, clarifying both the limits and the appropriate uses of evidence from human uplift studies in high-stakes decision-making.

Measuring Mid-2025 LLM-Assistance on Novice Performance in Biology

Large language models (LLMs) perform strongly on biological benchmarks, raising concerns that they may help novice actors acquire dual-use laboratory skills. Yet, whether this translates to improved human performance in the physical laboratory remains unclear. To address this, we conducted a pre-registered, investigator-blinded, randomized controlled trial (June-August 2025; n = 153) evaluating whether LLMs improve novice performance in tasks that collectively model a viral reverse genetics workflow. We observed no significant difference in the primary endpoint of workflow completion (5.2% LLM vs. 6.6% Internet; P = 0.759), nor in the success rate of individual tasks. However, the LLM arm had numerically higher success rates in four of the five tasks, most notably for the cell culture task (68.8% LLM vs. 55.3% Internet; P = 0.059). Post-hoc Bayesian modeling of pooled data estimates an approximate 1.4-fold increase (95% CrI 0.74-2.62) in success for a "typical" reverse genetics task under LLM assistance. Ordinal regression modelling suggests that participants in the LLM arm were more likely to progress through intermediate steps across all tasks (posterior probability of a positive effect: 81%-96%). Overall, mid-2025 LLMs did not substantially increase novice completion of complex laboratory procedures but were associated with a modest performance benefit. These results reveal a gap between in silico benchmarks and real-world utility, underscoring the need for physical-world validation of AI biosecurity assessments as model capabilities and user proficiency evolve.