Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act
Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act
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DOI：
10.1001/jamapediatrics.2018.3416
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发表时间：
2019-01-01
期刊：
影响因子：
26.1
通讯作者：
Bourgeois, Florence T.
中科院分区：
文献类型：
--
作者：
Hwang, Thomas J.;Orenstein, Liat;Bourgeois, Florence T.
许多给儿童开的药物尚未被研究或正式批准用于儿童。2003年儿科研究公平法案授权美国食品和药物管理局（FDA）要求儿科临床研究。目的评估《儿科研究公平法》要求的强制性儿科上市后研究的特征、完成率和研究设计和结果的透明度。设计与背景：本研究对2007年1月1日至2014年12月31日FDA批准的新药和新适应症所需的儿科上市后研究进行了回顾性队列研究，随访至2017年12月1日。关于儿科研究的状态、设计和结果的信息来自于公开的FDA数据库和ClinicalTrials.gov，与FDA的直接沟通，以及MEDLINE、EMBASE和Web of Science的同行评审出版物的搜索。儿科研究的特点和透明度、结果报告（在ClinicalTrials.gov、同行评议文献或FDA文件中）以及药品标签中儿科信息的可获得性。使用Cox比例风险回归模型评估研究完成率和时间。结果：2007年至2014年间，FDA批准了114种符合《儿科研究公平法案》要求的新药和已批准药物的新适应症。这些药物与222项必需的儿科上市后临床研究相关。截至12月1日，共有75项儿科研究（33.8%）完成。2017. 疗效研究的完成率（132例中有38例[28.8%]）明显低于药代动力学研究（34例中有19例[55.9%]）；校正风险比为0.31；95% CI为0.12-0.82)。74项研究（33.3%）无法确定随机化、盲法、比较物、终点和研究规模的信息，42项停止研究中有29项（69.0%）没有提供停止研究的原因。在已完成的研究中，57例（76.0%）报告了结果。在批准时，114种药物中有18种（15.8%）在其标签中有任何儿科疗效、安全性或剂量信息。中位随访时间为6.8年（四分位数间距为4.7-9.1年），114份药品标签中有47份（41.2%）含有儿科信息。结论和相关性：经过中位6.8年的随访，只有33.8%的强制性儿科上市后研究完成，而且大多数药物标签不包括对儿科使用重要的信息。为了改善以证据为基础的儿童药物处方，需要更及时地完成儿科药物研究。
IMPORTANCE Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies.OBJECTIVE To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act.DESIGN AND SETTING A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov , direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications.MAIN OUTCOMES AND MEASURES Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov , peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models.RESULTS Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1. 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1years), 47 of 114 of drug labels (41.2%) had any pediatric information.CONCLUSIONS AND RELEVANCE Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.