Methods for the assessment of selection bias in drug safety during pregnancy studies using electronic medical data.

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.