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荷尔梅斯,生物可塑性,以及对临床试验研究的影响
Edward J Calabrese1, Peter Pressman2, A Wallace Hayes3
1Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA 01003, USA.
Ageing research reviews
|August 7, 2023
概括
这项研究确定了生物可塑性极限是药物试验中虚假阴性结果的原因. 一种依据证据权重的方法可以克服这些局限性,改善有益剂的检测.
科学领域:
- 药理学 药理学是指药理学的学科.
- 临床试验 临床试验
- 生物可塑性 生物可塑性
背景情况:
- 随机的人类药物试验可能会产生错误的负结果,无法检测出有益的药物.
- 人类性能提升受到生物可塑性的限制,通常在30-60%之间.
- 临床试验的高变异性往往需要大效果大小 (2-3x对照) 来获得统计学意义.
研究的目的:
- 确定导致人类药物试验中虚假阴性结果的关键因素.
- 解释生物可塑性限制如何影响试验结果.
- 提出一种新的方法来解决临床试验设计中的这些局限性.
主要方法:
- 测量剂量响应模型的分析,以确定生物可塑性的极限.
- 检查人类流行病学和临床试验中的变异性.
- 关于证据权重方法的建议.
主要成果:
- 生物可塑性对人类的表现施加了最大的增强限制.
- 临床试验的可变性可以掩盖在这些生物界限内的药物的疗效.
- 由于未能考虑可塑性,可能会错过潜在的有益剂.
结论:
- 霍尔梅斯-生物可塑性-临床试验相互作用是虚假阴性结果的重要来源.
- 与EPA的环境评估类似的证据权重方法可以成功解决这个难题.
- 这种方法可以改善药物开发中的有效药物的检测.
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