Sinclair Susan, Cunnington Marianne, Messenheimer John, Weil John, Cragan Janet, Lowensohn Richard, Yerby Mark, Tennis Patricia
University of North Carolina Wilmington, Wilmington, NC, USA; INC Research LLC, Wilmington, NC, USA.
Pharmacoepidemiol Drug Saf. 2014 Aug;23(8):779-86. doi: 10.1002/pds.3659. Epub 2014 Jun 27.
The International Lamotrigine Pregnancy Registry monitored for a signal of a substantial increase in the frequency of major congenital malformations associated with lamotrigine exposures in pregnancy over an 18-year period. Key methodological lessons are discussed.
The strengths and weaknesses of the Registry were assessed using quantifiable methodological and operational parameters including enrollment, completeness of exposure and outcome data reporting, and lost to follow-up. The choice of comparator groups and stopping rules for registry closure were critically evaluated.
The reliance on voluntary reporting was associated with a clustered geographical distribution of registered pregnancies. The enrollment rate increased over time with new approvals and indications for lamotrigine and publication of interim data. Reporter burden was minimized through a streamlined data collection approach resulting in a high level of completeness of exposure and primary outcome data. Lost to follow-up rates were high (28.5% overall) representing a major limitation; incentives to increase the completeness of reporting failed to reduce rates. A lack of an internal comparator group complicated data interpretation; but external comparisons with multiple external groups allowed an assessment of consistency of outcome data across multiple data sources. A lack of a priori closure criteria prolonged the life of the Registry, and consideration of regulatory guidelines on this subject is encouraged at the time of conception of future registries.
A successful pregnancy exposure registry requires ongoing flexibility and continuous re-assessment of enrollment, recruitment, and retention methods and the availability of comparison data, throughout its lifecycle.
国际拉莫三嗪妊娠登记处监测了18年间与孕期暴露于拉莫三嗪相关的重大先天性畸形频率大幅增加的信号。讨论了关键的方法学经验教训。
使用可量化的方法学和操作参数评估登记处的优缺点，包括入组、暴露和结局数据报告的完整性以及失访情况。对比较组的选择和登记处关闭的停止规则进行了严格评估。
对自愿报告的依赖导致登记妊娠的地理分布呈聚集性。随着拉莫三嗪新的批准和适应症以及中期数据的公布，入组率随时间增加。通过简化数据收集方法将报告负担降至最低，从而使暴露和主要结局数据具有较高的完整性。失访率很高（总体为28.5%），这是一个主要限制；提高报告完整性的激励措施未能降低失访率。缺乏内部比较组使数据解释变得复杂；但与多个外部组的外部比较允许评估多个数据源的结局数据的一致性。缺乏先验的关闭标准延长了登记处的存续时间，鼓励在未来登记处设立时考虑关于这一主题的监管指南。
一个成功的妊娠暴露登记处需要在其整个生命周期内持续保持灵活性，并不断重新评估入组、招募和保留方法以及比较数据的可用性。
