Federal legislation and the advancement of neonatal drug studies.
Federal legislation and the advancement of neonatal drug studies.
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联邦立法和新生儿药物研究的进步。
DOI：
10.1016/j.jpeds.2012.08.034
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Akinbi,Henry
中科院分区：
文献类型：
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作者：
Wiles,JasonR;Vinks,AlexanderA;Akinbi,Henry
美国国会通过法律法规要求制药商证明新药在目标人群中安全有效的指令已经实施了50年[1，2]。然而，儿童，特别是新生儿在大多数药物临床试验中的代表性仍然不成比例地不足。迄今为止，联邦立法对这方面的改进需求反应缓慢，只是在过去15年里才试图纠正这种不可接受的状况。儿童仍然是治疗孤儿，联邦政府动用了强大的力量才将他们纳入药物开发过程。从成人和年龄较大的儿童中进行的研究数据推断新生儿的常见做法是有问题的，即使药物的效果和疾病的过程是相似的。这些数据的适用性受到新生儿独特生理学、不断变化的身体组成、快速发育过程以及体重与药理学变量之间的非线性关系的限制。与氯霉素（灰婴综合征）、磺胺异恶唑和青霉素（核黄疸）、新生霉素（高胆红素血症）和维生素E（新生儿败血症和坏死性小肠结肠炎）使用相关的严重后果提醒人们，在没有足够的科学信息支持药物在相关人群中的安全性的情况下采用治疗是危险的[3-8]。本综述评估了政府机构为扩大联邦立法对婴儿和儿童用药的益处所做的努力，
The directive from the United States Congress, through laws and regulations mandating that manufacturers of pharmaceuticals demonstrate proof that new drugs are both safe and efficacious in target groups, has been in place for 50 years [1, 2]. However, children and, in particular, neonates remain disproportionately underrepresented in the majority of drug clinical trials. To date, federal legislation has been slow to respond to the need for improvement in this regard, and it has only been in the last one and a half decades that attempts have been made to rectify this unacceptable situation. Children remain therapeutic orphans, and it has taken the might of the federal government to include them in drug development processes.The common practice of extrapolating data from studies conducted in adults and older children to neonates is problematic, even if the effects of the drugs and course of the disease are similar. Applicability of such data is limited by the unique physiology in neonates, an ever-changing body composition, rapid developmental processes, and a non-linear relationship between body weight and pharmacologic variables. Dire consequences associated with the use of chloramphenicol (gray baby syndrome), sulfisoxazole and penicillin (kernicterus), novobiocin (hyperbilirubinemia), and vitamin E (neonatal sepsis and necrotizing enterocolitis) are some of the reminders of the danger of adopting therapies without adequate scientific information supporting the safety of the medications in the relevant populations [3–8]. This review assesses efforts by government agencies to extend the benefits of federal legislations pertaining to drugs administered to infants and children,