评估儿科药理动力学研究设计的新方法,重点是精确的剂量选择
Yuanxi Zou1, Jerry Nedelman2, Mats O Karlsson1
1Department of Pharmacy, Uppsala University, Uppsala, Sweden.
剂量选择准确性 (ADS) 方法为儿科药理动力学研究设计提供了一种实用方法,与传统的参数精度方法相比,确保准确的剂量选择和强大的试验功率.
科学领域:
- 药理动力学 药理动力学
- 儿科药物开发儿童药物开发
- 临床试验的设计
背景情况:
- 儿科试验设计需要最大限度地利用数据,尽量减少样本采集.
- 参数精度 (PP) 是FDA推的常见标准,用于证明儿科药物动力学研究的合理性.
- 为设计评估,建议采用另一种方法,即剂量选择准确性 (ADS).
研究的目的:
- 评估用于儿科药物动力学研究设计的剂量选择 (ADS) 方法的准确性.
- 将ADS方法与传统的参数精度 (PP) 方法进行比较.
- 用ADS评估可变性和剂量选择对研究功率的影响.
主要方法:
- 采用了一个模拟和重新估计框架.
- 该研究的重点是针对抗结核药物普雷托曼尼德 (pretomanid) 的实际情况.
- 在各种条件下使用ADS计算研究功率,并与PP进行比较.
主要成果:
- 在大多数体重组中,ADS显示精确的剂量选择,功率>80%.
- 在PP方法中,发现设计在清除方面没有足够的力量.
- 在较小的体重组中,ADS功率下降,变化很大,剂量水平选择对功率产生非单调的影响.
结论:
- ADS为儿科药理动力学研究提供了对剂量选择精度的实际评估.
- ADS 作为一个相关的决策标准,特别是当离散的片子大小用于剂量时.
- 在儿科药物开发中,ADS方法可以作为功率评估的替代方案.
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