Faculté de pharmacie Université de Montréal Montreal Canada.
Hôpital du Sacré Cœur de Montréal Centre intégré universitaire de santé et de services sociaux du Nord-de-l'île-de-Montréal Montreal Canada.
Pharmacol Res Perspect. 2018 Sep 21;6(5):e00426. doi: 10.1002/prp2.426. eCollection 2018 Oct.
Electronic health data are routinely used for population drug studies. Due to the ethical dilemma in carrying out experimental drug studies on pregnant women, the effects of medication usage during pregnancy on fetal and maternal outcomes are largely evaluated using this data collection medium. One major limitation in this type of study is the delayed inclusion of pregnancies in the cohort. For example, in the province of Quebec, Canada, a major pregnancy cohort only captured pregnancies after 20 weeks gestation. The purpose of this study was to demonstrate three methods that can be used to assess the extent of selection bias due to the delayed inclusion of pregnancies. We use causal directed acyclic graphs to explain the source of this selection bias. In an example involving a cohort of pregnant asthmatic women reconstructed from the linkage of administrative health databases from the province of Quebec, we use numerical derivations, a simulation study and a sensitivity analysis to investigate the potential for bias and loss of power due to the delayed inclusion. We find that this selection bias can be partially mitigated by controlling for variables related to (spontaneous or therapeutic) abortion and the outcome of interest. The three proposed methods allow for the pre and post hoc ascertainment of the bias. While delayed pregnancy inclusion selection bias (which includes "live birth bias") can produce substantial bias in pregnancy drug studies, all three methods are effective at producing estimates of the size of the bias.
电子健康数据通常用于人群药物研究。由于在孕妇中进行实验性药物研究存在伦理困境，因此，药物在怀孕期间使用对胎儿和产妇结局的影响主要通过这种数据收集媒介进行评估。这种类型的研究存在一个主要限制，即妊娠的延迟纳入。例如，在加拿大魁北克省，一个主要的妊娠队列仅捕获妊娠 20 周后的妊娠。本研究旨在展示三种可用于评估因妊娠延迟纳入而导致选择偏倚程度的方法。我们使用有向无环图来解释这种选择偏倚的来源。在一个涉及从魁北克省的行政健康数据库中链接重建的妊娠哮喘妇女队列的例子中，我们使用数值推导、模拟研究和敏感性分析来研究由于延迟纳入而导致的偏倚和效能损失的可能性。我们发现，通过控制与（自发性或治疗性）流产和感兴趣的结局相关的变量，可以部分减轻这种选择偏倚。这三种方法都可以在研究前和研究后确定偏倚的大小。虽然妊娠延迟纳入选择偏倚（包括“活产偏倚”）可能会对妊娠药物研究产生实质性的偏倚，但这三种方法都能有效地估计偏倚的大小。
