Elizabeth Garrett Anderson Institute for Women's Health, University College London, 74 Huntley Street, London, UK.
NIHR UCLH Biomedical Research Centre, 149 Tottenham Court Road, London, UK.
Ther Innov Regul Sci. 2022 Nov;56(6):976-990. doi: 10.1007/s43441-022-00433-w. Epub 2022 Jul 25.
The exclusion of pregnant populations, women of reproductive age, and the fetus from clinical trials of therapeutics is a major global public health issue. It is also a problem of inequity in medicines development, as pregnancy is a protected characteristic. The current regulatory requirements for drugs in pregnancy are being analyzed by a number of agencies worldwide. There has been considerable investment in developing expertise in pregnancy clinical trials (for the pregnant person and the fetus) such as the Obstetric-Fetal Pharmacology Research Centers funded by the National Institute of Child Health and Human Development. Progress has also been made in how to define and grade clinical trial safety in pregnant women, the fetus, and neonate. Innovative methods to model human pregnancy physiology and pharmacology using computer simulations are also gaining interest. Novel ways to assess fetal well-being and placental function using magnetic resonance imaging, computerized cardiotocography, serum circulating fetoplacental proteins, and mRNA may permit better assessment of the safety and efficacy of interventions in the mother and fetus. The core outcomes in women's and newborn health initiative is facilitating the consistent reporting of data from pregnancy trials. Electronic medical records integrated with pharmacy services should improve the strength of pharmacoepidemiologic and pharmacovigilance studies. Incentives such as investigational plans and orphan disease designation have been taken up for obstetric, fetal, and neonatal diseases. This review describes the progress that is being made to better understand the extent of the problem and to develop applicable solutions.
将妊娠人群、育龄妇女和胎儿排除在治疗药物的临床试验之外，是一个全球性重大公共卫生问题。这也是药品开发不公平的问题，因为妊娠是一种受保护的特征。目前，全球许多机构都在分析妊娠期间药物的现行监管要求。在妊娠临床试验（针对孕妇和胎儿）方面，已经投入了相当大的精力来发展专业知识，例如美国国立儿童健康与人类发展研究所资助的产科-胎儿药理学研究中心。在如何定义和分级孕妇、胎儿和新生儿临床试验安全性方面也取得了进展。使用计算机模拟来模拟人类妊娠生理学和药理学的创新方法也越来越受到关注。使用磁共振成像、计算机化胎心监护、血清循环胎儿胎盘蛋白和 mRNA 评估胎儿健康和胎盘功能的新方法，可能会更好地评估干预措施对母亲和胎儿的安全性和疗效。妇女和新生儿健康倡议的核心成果是促进妊娠试验数据的一致报告。与药房服务相结合的电子病历应能加强药物流行病学和药物警戒研究的力度。针对产科、胎儿和新生儿疾病，已经采取了研究计划和孤儿病指定等激励措施。这篇综述描述了为更好地了解问题的严重程度并制定可行的解决方案而取得的进展。
