Department of Obstetrics and Gynecology University of Washington, School of Medicine Seattle, WA; Department of Global Health, University of Washington School of Medicine, Seattle, WA.
Faculty of Medicine and Institute for Life Sciences, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Vaccine. 2020 Jun 15;38(29):4542-4547. doi: 10.1016/j.vaccine.2020.05.022. Epub 2020 May 11.
Vaccines designed for use in pregnancy and vaccine trials specifically involving pregnant women are rapidly expanding. One of the key challenges in designing maternal immunization trials is that developing exclusion criteria requires understanding and quantifying the background risk for adverse pregnancy outcomes in the pregnancy being studied, which can occur independent of any intervention and be unrelated to vaccine administration. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project has developed and published case definitions and guidelines for data collection, analysis, and evaluation of maternal immunization safety in trials involving pregnant women. Complementing this work, we sought to understand how to best assess obstetric risk of adverse outcomes and differentiate it from the assessment of vaccine safety. Quantification of obstetric risk is based on prior and current obstetric, and maternal medical history. We developed a step-wise approach to evaluate and quantify obstetric and maternal risk factors in pregnancy based on review of published literature and guidelines, and critically assessed these factors in the context of designing inclusion and exclusion criteria for maternal vaccine studies. We anticipate this risk assessment evaluation may assist clinical trialists with study design decisions, including selection of exclusion criteria for vaccine trials involving pregnant women, consideration of sub-group classification, such as high or low risk subjects, or schedule considerations, such as preferred trimester of gestation for an intervention during pregnancy. Additionally, this tool may be utilized in data stratification at time of study analyses.
旨在用于妊娠的疫苗和专门针对孕妇的疫苗试验正在迅速扩大。在设计母体免疫接种试验时,面临的一个关键挑战是,制定排除标准需要了解和量化正在研究的妊娠中不良妊娠结局的背景风险,这种风险可能独立于任何干预措施发生,并且与疫苗接种无关。全球妊娠免疫安全评估一致性(GAIA)项目已经制定并发布了针对涉及孕妇的试验中母体免疫安全性数据收集、分析和评估的病例定义和指南。为了补充这项工作,我们试图了解如何最好地评估产科不良结局的风险,并将其与疫苗安全性评估区分开来。产科风险的量化基于既往和当前的产科和产妇病史。我们根据已发表的文献和指南,开发了一种逐步评估和量化妊娠中产科和产妇风险因素的方法,并在设计母体疫苗研究的纳入和排除标准的背景下对这些因素进行了批判性评估。我们预计,这种风险评估评估可能有助于临床试验设计者做出研究设计决策,包括选择涉及孕妇的疫苗试验的排除标准,考虑亚组分类,如高风险或低风险受试者,或考虑妊娠期间干预措施的首选妊娠阶段。此外,该工具可在研究分析时用于数据分层。