Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children.
Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children.
复制标题
DOI：
10.1002/jcph.1053
复制
发表时间：
2018-10
影响因子：
2.9
通讯作者：
Cohen-Wolkowiez M
中科院分区：
文献类型：
--
作者：
Balevic SJ;Cohen-Wolkowiez M
最近近一半的儿科试验未能达到标签适应症，这在很大程度上是由于研究设计不当。因此，创新的研究方法对于优化试验设计同时减少药物研究固有的潜在危害至关重要。有几种方法可以优化从尽可能小的体积和最少的程序中收集的药代动力学 (PK) 数据量，包括使用机会性和稀疏采样、替代和非侵入性基质以及微量测定。此外，使用主协议的大型研究网络可以促进协作、减轻监管负担并提高早期和后期试验的试验效率。利用电子健康记录的大型实用试验可以利用中央管理策略来降低成本、大规模招募患有罕见疾病的患者并增强研究的普遍性。此外，可以通过贝叶斯自适应技术来优化试验效率和安全性，该技术允许根据对先前和累积数据的分析来计划改变方案。除了这些试验设计功能之外，建模和模拟方面的进步也为基于系统和生理学的模型铺平了道路，这些模型可以个性化儿科剂量建议并支持药物批准。最后，鉴于许多儿科疾病的患病率较低，大规模收集去识别的遗传和临床数据是增强儿童临床药理学研究的潜在变革方式。
Almost half of recent pediatric trials failed to achieve labeling indications, due in large part to inadequate study design. Therefore, innovative study methods are crucial to optimize trial design while also reducing the potential harms inherent with drug investigation. Several methods exist to optimize the amount of pharmacokinetic (PK) data collected from the smallest possible volume and with the fewest number of procedures, including the use of opportunistic and sparse sampling, alternative and non-invasive matrices, and micro-volume assays. In addition, large research networks using master protocols promote collaboration, reduce regulatory burden, and increase trial efficiency for both early- and late-phase trials. Large pragmatic trials that leverage electronic health records can capitalize on central management strategies to reduce costs, enroll patients with rare diseases on a large scale, and augment study generalizability. Further, trial efficiency and safety can be optimized through Bayesian adaptive techniques that permit planned protocol changes based on analyses of prior and accumulated data. In addition to these trial design features, advances in modeling and simulation have paved the way for systems-based and physiologically-based models that individualize pediatric dosing recommendations and support drug approval. Lastly, given the low prevalence of many pediatric diseases, collecting de-identified genetic and clinical data on a large scale is a potentially transformative way to augment clinical pharmacology research in children.
登录
查看更多内容
影响因子：
3.6
作者：
Bradley, John S.;Sauberan, Jason B.;Capparelli, Edmund V.
通讯作者：
Capparelli, Edmund V.
影响因子：
3
作者：
Baudouin, Veronique;Alberti, Corinne;Loirat, Chantal
通讯作者：
Loirat, Chantal
影响因子：
6.7
作者：
Berry, D. A.
通讯作者：
Berry, D. A.
影响因子：
2.9
作者：
Burris, James F.;Tortorici, Michael A.;Reed, Michael D.
通讯作者：
Reed, Michael D.
DOI：
10.1097/qai.0000000000000996
发表时间：
2016-08-15
影响因子：
3.6
作者：
Cottrell, Mackenzie L.;Prince, Heather M. A.;Kashuba, Angela D. M.
通讯作者：
Kashuba, Angela D. M.