使用元分析将药物对酒精使用障碍的影响翻译为临床前,人体实验室和临床试验结果
Steven J Nieto1,2, Suzanna Donato3, Han Du3
1Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA. snieto@psych.ucla.edu.
Translational psychiatry
|July 21, 2025
概括
酒精使用障碍 (AUD) 药物的临床前模型显示了一些人类试验的预测价值. 在动物模型中的早期疗效,特别是酒精偏好和恢复,与临床研究中饮酒回归的减少有关.
科学领域:
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
- 翻译医学是一种翻译医学.
背景情况:
- 动物模型对于潜在的酒精使用障碍 (AUD) 药物的初步测试至关重要.
- 在预测人类临床试验结果方面,临床前发现的可靠性仍然不确定.
- 现有的研究缺乏全面的分析,将动物模型的疗效与人类实验室和临床试验结果联系起来.
研究的目的:
- 调查临床前动物模型在人体试验中的酒精使用障碍 (AUD) 药物疗效的预测有效性.
- 确定动物模型中的早期疗效是否与人类实验室暗示反应性研究和随机临床试验 (RCT) 的结果相关.
- 为AUD药物开发中临床前发现的翻译潜力提供经验证据.
主要方法:
- 在临床前模型中测试的药物的系统文献搜索 (两瓶选择,操作者恢复),人类实验室暗示反应性研究,以及AUD的RCT.
- 对动物对酒精偏好和恢复的药物效应的元分析,人类的提示诱导的渴望,以及RCT中的临床终点 (恢复饮酒).
- 应用威廉森-约克双变量加权最小方程估计来分析临床前和临床结果之间的关联.
主要成果:
- 在临床前模型中,药物对两瓶选择酒精偏好和操作者恢复的影响与人类临床试验中任何饮酒回归的减少有关.
- 在临床前发现与其他RCT结果之间没有发现显著的关联,例如重返重度饮酒.
- 临床前药物发现与人类实验室研究中对提示诱导的渴望的影响没有相关性.
结论:
- 临床前模型,特别是那些评估酒精偏好和恢复酒精的模型,在人类临床试验中证明了药物对回归饮酒可能性的影响的部分预测有效性.
- 这些发现支持了跨物种和实验模型观察到的药物效应可以与临床结果相关的前提.
- 该研究强调了在开发用于治疗酒精使用障碍的新药时,仔细选择和解释临床前数据的重要性.
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