非临床毒性研究中的虚拟控制组:对毒理学临床病理学的影响 数据解释
Adeyemi O Adedeji1, Adi Wasserkrug Naor2
1Genentech Inc., South San Francisco, California, USA.
Toxicologic pathology
|November 30, 2024
概括
虚拟对照组 (VCGs) 显示出减少毒理学研究中动物使用的前景. 然而,VCG和并发对照组 (CCG) 之间的临床病理学数据不一致,引发了关于可重现性和解释性的担忧.
科学领域:
- 毒理学 毒理学 毒理学
- 药物开发 药物开发
- 动物福利 动物福利
背景情况:
- 虚拟控制组 (VCG) 的使用是减少在非临床毒理学研究中使用动物的一种新兴策略.
- VCGs从历史数据集中生成控制数据以匹配特定的研究设计,旨在取代并发控制组 (CCG).
研究的目的:
- 本综述批判性地检查了两项关于大鼠毒理学模型中VCGs的概念验证研究.
- 识别和讨论与VCG实施相关的挑战,特别是关于数据可重现性的问题.
主要方法:
- 专注于最近的两项概念验证研究,在老鼠模型中使用VCG.
- 对定量终点的分析,特别强调临床病理学参数.
主要成果:
- 定量终点的不可重复性是一个一致的问题,尤其是临床病理学参数.
- 在审查的研究中观察到VCG和CCG数据之间的不一致性.
结论:
- 在临床病理学中观察到的不一致性可能导致对生物标志物的准确性和影响安全监测的误解.
- 挑战包括难以识别器官功能障碍,干扰证据权重的方法,并导致数据解释问题.
- 其他替代方法,如血液微量采样和合理使用恢复动物,也被认为可以减少动物使用.
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