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Automated Hypothesis Validation with Agentic Sequential Falsifications

14 February 2025
Kexin Huang
Ying Jin
Ryan Li
Michael Y. Li
Emmanuel Candès
J. Leskovec
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Abstract

Hypotheses are central to information acquisition, decision-making, and discovery. However, many real-world hypotheses are abstract, high-level statements that are difficult to validate directly. This challenge is further intensified by the rise of hypothesis generation from Large Language Models (LLMs), which are prone to hallucination and produce hypotheses in volumes that make manual validation impractical. Here we propose Popper, an agentic framework for rigorous automated validation of free-form hypotheses. Guided by Karl Popper's principle of falsification, Popper validates a hypothesis using LLM agents that design and execute falsification experiments targeting its measurable implications. A novel sequential testing framework ensures strict Type-I error control while actively gathering evidence from diverse observations, whether drawn from existing data or newly conducted procedures. We demonstrate Popper on six domains including biology, economics, and sociology. Popper delivers robust error control, high power, and scalability. Furthermore, compared to human scientists, Popper achieved comparable performance in validating complex biological hypotheses while reducing time by 10 folds, providing a scalable, rigorous solution for hypothesis validation.

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@article{huang2025_2502.09858,
  title={ Automated Hypothesis Validation with Agentic Sequential Falsifications },
  author={ Kexin Huang and Ying Jin and Ryan Li and Michael Y. Li and Emmanuel Candès and Jure Leskovec },
  journal={arXiv preprint arXiv:2502.09858},
  year={ 2025 }
}
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