Gelperin Kate, Hammad Hoda, Leishear Kira, Bird Steven T, Taylor Lockwood, Hampp Christian, Sahin Leyla
U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER), Office of Surveillance and Epidemiology, Silver Spring, MD, USA.
FDA CDER, Office of New Drugs, Silver Spring, MD, USA.
Pharmacoepidemiol Drug Saf. 2017 Feb;26(2):208-214. doi: 10.1002/pds.4150. Epub 2016 Dec 27.
Our study sought to systematically evaluate protocol-specified study methodology in prospective pregnancy exposure registries including pre-specified pregnancy outcomes, power calculations for sample size, and comparator group selection.
U.S. pregnancy exposure registries designed to evaluate safety of drugs or biologics were identified from www.clinicaltrials.gov, the FDA's Office of Women's Health website, and the FDA's list of postmarketing studies. Protocols or similar documentation were obtained.
We identified 35 U.S. registries for drugs or biologic use during pregnancy. All registries assessed risk for overall major congenital malformations. Pre-specified target enrollment was stated for 18 (51%) registries, and ranged from 150 to 500 exposed pregnancies (median 300). Thirty-two (91%) registries identified at least one comparison group, but only nine (26%) planned to use an internal comparator. The most common external comparator group (n = 24, 69%) was the Metropolitan Atlanta Congenital Defects Program (MACDP).
No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
我们的研究旨在系统评估前瞻性妊娠暴露登记处中方案规定的研究方法，包括预先规定的妊娠结局、样本量的功效计算以及比较组的选择。
从美国国立医学图书馆临床试验数据库（www.clinicaltrials.gov）、美国食品药品监督管理局（FDA）妇女健康办公室网站以及FDA的上市后研究列表中识别旨在评估药物或生物制品安全性的美国妊娠暴露登记处。获取了方案或类似文件。
我们识别出35个美国妊娠期间药物或生物制品使用登记处。所有登记处均评估了总体主要先天性畸形的风险。18个（51%）登记处声明了预先规定的目标入组人数，范围为150至500例暴露妊娠（中位数为300）。32个（91%）登记处识别出至少一个比较组，但只有9个（26%）计划使用内部比较组。最常见的外部比较组（n = 24，69%）是亚特兰大大都会先天性缺陷项目（MACDP）。
尽管大多数致畸物可能导致特定缺陷，但没有一个登记处设计有足够的功效来评估特定畸形。只有一半的登记处进行了功效分析。尽管外部比较组（包括MACDP）被广泛使用，但存在重要局限性。在缺乏孕妇随机对照试验数据的情况下，妊娠登记处作为综合妊娠监测计划的一部分仍然是一个重要工具；然而，仅靠妊娠登记处可能不足以获得关于特定畸形风险的充分数据。2016年发表。本文为美国政府作品，在美国属于公共领域。
