Human uplift studies, or studies that measure the effects of AI access on human performance via randomized controlled trials (RCT) or similar methodologies, increasingly inform frontier AI governance and deployment decisions. While RCT methods are robust in other fields, 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 the standard causal inference assumptions upon which human uplift studies rely 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 contribute (1) a synthesis of methodological challenges in human uplift studies, mapped to risks to study validity and classified by their degree of specificity to large language model (LLM) systems, and (2) a mapping from challenges to proposed solutions. By collating expert-identified challenges and solutions, we seek to clarify the interpretive limits and appropriate uses of human uplift evidence, to align evaluation practice with the decisions it informs, and to support more coordinated methodological foundations for AI governance.

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