摘要
由于儿童处于生长发育过程中,不同年龄儿童对药物的处置能力不同,药物的疗效和安全性也与成人有所不同。一般来说,对于特定年龄段儿童的用药,应有相应儿科人群的临床试验数据予以支持。然而,相比于成人,儿童临床试验存在伦理限制、受试者入组困难等诸多挑战,导致儿童用药往往是未被药监部门正式批准的应用。目前,国际上的先进经验是将建模与仿真应用于临床试验,在药物临床使用前进行前瞻性研究,预测不同年龄儿童的最佳剂量方案。尤其是在根据最优设计理论确定临床试验最佳样本量、采用建模所得先验信息确定最适采样时间点、利用贝叶斯原理处理稀疏数据等方面,国际上已有成功案例。本文通过查阅国内外有关建模与仿真的儿童临床试验文献进行综合分析,概述建模与仿真在儿童临床试验中的作用。
Children′s ability to dispose of drugs and the efficacy/safety of drugs for children differ from those adults as children are in the process of growth and development.In general,medication for children in a certain age group should be supported by clinical trial data from the corresponding pediatric population.However,compared with clinical trials in adults,children′s clinical trials have many challenges such as the ethical limitation and the difficulty in enrolling subjects.As a result,the use of drugs for children is often not formally approved by the drug regulatory authorities.At present,researchers tend to apply modeling and simulation to clinical trials,and conduct prospective studies before the clinical use of drug to predict the optimal dosage regimen for children of different ages.In particular,there have been several successful cases in determining the optimal sample size for clinical trials based on the optimal design theory,optimizing sampling time point using the prior information from modeling,and processing sparse data by the Bayesian principle.This paper summarizes the role of modeling and simulation in pediatric clinical trials by reviewing previously reported clinical trial literature.
作者
袁劲杰
赵娣
陈西敬
赵立波
YUAN Jin-jie;ZHAO Di;CHEN Xi-jing;ZHAO Li-bo(Clinical Research Center,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Clinical Pharmacokinetics Laboratory,School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China)
出处
《国际药学研究杂志》
CAS
北大核心
2019年第10期745-754,共10页
Journal of International Pharmaceutical Research
关键词
临床试验
药代动力学
模型
仿真
临床试验设计
clinical trial
pharmacokinetics
modeling
simulation
clinical trial design
