Application of a target trial framework to questions in reproductive and perinatal pharmacoepidemiology
Embargo Date
2024-05-11
OA Version
Citation
Abstract
The gold standard for evaluating questions of drug safety or efficacy is a well-designed randomized trial. However, randomized trials are often infeasible due to ethical or logistical reasons. When a randomized trial is not possible, we rely on observational studies. We can conceptualize the design and analysis of an observational study as an attempt to emulate a randomized trial. Becoming more intentional about this framework (i.e., “trial emulation”) allows investigators to identify and minimize common biases. This dissertation explores the feasibility of applying a trial emulation framework to three questions evaluating the safety of medications used before or during pregnancy. First, we evaluated the comparative effects of preconception use of various contraceptives on miscarriage. Second, we evaluated the effect of preconception vaccination against coronavirus disease 2019, compared with no preconception vaccination, on rate of miscarriage. Third, we evaluated the comparative safety of metformin plus insulin versus insulin alone during pregnancy for pregestational type 2 diabetes, in relation to perinatal outcomes. The findings of these studies advance our knowledge of medication safety in addition to our understanding of how to mitigate bias in pharmacoepidemiologic studies of pregnancy.