Avant Debbie, Baer Gerri, Moore Jason, Zheng Panli, Sorbello Alfred, Ariagno Ron, Yao Lynne, Burckart Gilbert J, Wang Jian
Office of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, USA.
Office of Clinical Pharmacology, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD, USA.
Ther Innov Regul Sci. 2017;2017:1-9. doi: 10.1177/2168479017716713. Epub 2017 Jun 28.
Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015.
FDA databases were searched for BPCA and/or PREA studies that enrolled neonates. Studies that enrolled a minimum of 3 neonates were analyzed for the presence and content of neonatal safety data.
The analysis identified 40 drugs that were studied in 3 or more neonates. Of the 40 drugs, 36 drugs received a pediatric labeling change as a result of studies between 1998 and 2015, that included information from studies including neonates. Fourteen drugs were approved for use in neonates. Clinical trials for 20 of the drugs reported serious adverse events (SAEs) in neonates. The SAEs primarily involved cardiovascular events such as bradycardia and/or hypotension or laboratory abnormalities such as anemia, neutropenia, and electrolyte disturbances. Deaths were reported during studies of 9 drugs.
Our analysis revealed that SAEs were reported in studies involving 20 of the 40 drugs evaluated in neonates, with deaths identified in 9 of those studies. Patients enrolled in studies were often critically ill, which complicated determination of whether an adverse event was drug-related. We conclude that the traditional means for collecting safety information in drug development trials needs to be adjusted for neonates and will require the collaboration of regulators, industry, and the clinical and research communities to establish appropriate definitions and reporting strategies for the neonatal population.
开展的新生儿药物研发研究相对较少，但随着《美国食品药品监督管理局安全与创新法案》（FDASIA）的颁布，预计此类研究将会增加。由于新生儿群体的独特性质以及疾病程度，了解在新生儿中所研究药物的安全性变得复杂。本研究的目的是审查1998年至2015年间依据《儿童最佳药物法案》（BPCA）和《儿科研究公平法案》（PREA）向美国食品药品监督管理局提交的新生儿安全性数据。
在食品药品监督管理局数据库中搜索纳入了新生儿的BPCA和/或PREA研究。对纳入至少3名新生儿的研究分析其新生儿安全性数据的存在情况和内容。
分析确定了40种在3名或更多新生儿中进行研究的药物。在这40种药物中，有36种药物因1998年至2015年间的研究而在儿科标签上发生了变化，这些研究包括来自纳入新生儿的研究的信息。14种药物被批准用于新生儿。20种药物的临床试验报告了新生儿严重不良事件（SAE）。严重不良事件主要涉及心血管事件，如心动过缓和/或低血压，或实验室异常，如贫血、中性粒细胞减少和电解质紊乱。9种药物的研究报告了死亡情况。
我们的分析显示，在对40种评估的新生儿药物中的20种进行的研究中报告了严重不良事件，其中9项研究发现了死亡情况。参与研究的患者通常病情危重，这使得确定不良事件是否与药物相关变得复杂。我们得出结论，药物研发试验中收集安全信息的传统方法需要针对新生儿进行调整，并且需要监管机构、行业以及临床和研究界的合作，为新生儿群体建立适当的定义和报告策略。
