Human organ-on-a-chip (Organ-Chip) technology has the potential to disrupt preclinical drug discovery and improve success in drug development pipelines as it can recapitulate organ-level pathophysiology and clinical responses. The Innovation and Quality (IQ) consortium formed by multiple pharmaceutical and biotechnology companies to confront this challenge has published guidelines that define criteria for qualifying preclinical models, however, systematic and quantitative evaluation of the predictive value of Organ-Chips has not yet been reported. Here, 870 Liver-Chips were analyzed to determine their ability to predict drug-induced liver injury (DILI) caused by small molecules identified as benchmarks by the IQ consortium. The Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 87% and a specificity of 100%. A computational economic value analysis suggests that with this performance the Liver-Chip could generate $3 billion annually for the pharmaceutical industry due to increased R&D productivity.

中文翻译：

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对人类肝脏芯片进行预测毒理学鉴定：性能评估和经济影响

人体器官芯片 (Organ-Chip) 技术有可能破坏临床前药物发现并提高药物开发管道的成功率，因为​​它可以概括器官水平的病理生理学和临床反应。由多家制药和生物技术公司组成的创新与质量 (IQ) 联盟为应对这一挑战，已发布了定义临床前模型合格标准的指南，但尚未报告对器官芯片预测价值的系统和定量评估。在这里，对 870 个肝芯片进行了分析，以确定它们预测由 IQ 联盟确定为基准的小分子引起的药物性肝损伤 (DILI) 的能力。Liver-Chip 符合 27 种已知肝毒性和无毒药物的盲法鉴定指南，敏感性为 87%，特异性为 100%。一项计算经济价值分析表明，凭借这一性能，由于研发生产力的提高，肝脏芯片每年可为制药行业创造 30 亿美元的收入。