Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill.
Food and Drug Administration, Rockville, Maryland.
JAMA Pediatr. 2014 Feb;168(2):130-6. doi: 10.1001/jamapediatrics.2013.4208.
Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end-point development is lagging and studies are more challenging.
To quantify progress made in neonatal studies and neonatal information in product labeling as a result of recent legislation.
DESIGN, SETTING, AND PARTICIPANTS: We identified a cohort of drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. We then examined the use of these drugs in a cohort of neonates admitted to 290 neonatal intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States from 2005 to 2010.
Infants exposed to a drug studied in neonates as identified by the FDA website.
Number of drug studies with neonates and rate of exposure per 1000 admissions among infants admitted to an NICU.
In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in fewer than 60 neonates. Of the drugs studied, ranitidine was used most often (15,627 neonates, 35 exposures per 1000 admissions).
Few drug labeling changes made under pediatric legislation include neonates. Most drugs studied are either not used or rarely used in US NICUs. Strategies to increase the study of safe and effective drugs for neonates are needed.
联邦立法导致向美国食品和药物管理局 (FDA) 提交的儿科研究显著增加，从而在产品标签中增加了新的儿科信息。然而，大约 50%的药品标签在安全性、有效性或儿童剂量方面的信息仍然不足。标签中新生儿的信息更加稀缺，因为新生儿是一个脆弱的亚人群，其终点发育滞后，研究更具挑战性。
定量评估最近立法在新生儿研究和产品标签中新生儿信息方面取得的进展。
设计、环境和参与者：我们利用 FDA 网站上的信息，确定了 1997 年至 2010 年间因儿科立法而纳入新生儿的药物研究队列。我们确定了哪些研究在医学文献中发表，哪些立法导致了这些研究，以及由此产生的新生儿标签变化。然后，我们在美国 290 个新生儿重症监护病房 (NICU)（Pediatrix Data Warehouse）中检查了 2005 年至 2010 年期间收治的新生儿队列中使用这些药物的情况。
在 FDA 网站上确定的接受研究中新生儿的药物暴露。
在 NICU 收治的婴儿中，每 1000 例入院接受药物治疗的新生儿研究数量和暴露率。
在对 FDA 数据库的审查中，我们确定了 28 种在新生儿中研究的药物和 24 种相关的标签变化。这 28 种药物涵盖了 41 项研究，其中 31 项（76%）已发表。24 项新生儿标签变化中的 11 项（46%）确定了安全性和有效性。在对 446335 名住院婴儿的队列研究中，我们确定了 399 种使用的药物和 28 天内的 1525739 次药物暴露。在新生儿中研究的 28 种药物中，有 13 种（46%）未在 NICU 使用；8 种（29%）在不到 60 名新生儿中使用。在所研究的药物中，雷尼替丁使用最频繁（15627 名新生儿，每 1000 名入院者 35 次暴露）。
儿科立法下的药物标签变化很少包括新生儿。大多数研究的药物在美国 NICU 中要么未使用，要么很少使用。需要制定策略来增加对安全有效的新生儿药物的研究。
