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在大鼠毒性研究中,用虚拟对照组取代并发对照
Alexander Gurjanov1, Carlos Vieira-Vieira1, Julia Vienenkoetter2
1Bayer Research & Development, Pharmaceuticals, Investigative Toxicology, Berlin, Germany.
Regulatory toxicology and pharmacology : RTP
|February 24, 2024
概括
虚拟控制组 (VCGs) 可以用历史数据取代在毒性研究中的并发控制. 虽然统计结果各不相同,但VCGs维持了整体研究结论,支持它们在监管毒理学中的潜在用途.
科学领域:
- 毒理学 毒理学 毒理学
- 药理学 药理学是指药理学的学科.
- 药物开发 药物开发
背景情况:
- 虚拟控制组 (VCGs) 提供了一种方法,通过使用历史控制数据,在非临床毒性测试中取代活体动物.
- 标准化的历史数据对于构建可靠的VCG和与传统研究对其性能进行基准测试至关重要.
研究的目的:
- 评估VCGs在复制遗留毒性研究结果方面的表现.
- 评估VCGs复制统计偏差的能力,试验物质的影响,以及研究总体结论,包括剂量值和位器官.
主要方法:
- 基于三项为期四周的老鼠口服毒性遗留研究,开发了一种VCG评估概念.
- 评估VCG在复制统计学上显著偏差,与试验物质相关的影响和关键毒理终点方面的表现.
主要成果:
- VCGs表现出低到中等的能力,以复制统计学上显著的结果.
- 尽管统计复制的变化,毒性研究的总结在使用VCGs时保持一致.
结论:
- 经过仔细选择的历史控制数据有可能取代并发控制,而不会损害一般研究结论的完整性.
- 开发的VCG评估框架为未来对毒理学虚拟控制的验证和监管接受提供了基础.
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