Emulation of a Target Trial in Pregnancy: Learning from the Chronic Hypertension And Pregnancy (CHAP) Trial

Background: While clinicians routinely treat chronic hypertension in people who are not pregnant, there has been considerable debate about the best approach in pregnancy because of concerns about potential risks of medications to the fetus. In 2022, a pragmatic randomized trial in the United States (CHAP trial) examined outcomes of a more aggressive strategy targeting blood pressure of less than 140/90 mm Hg and found overall benefit, leading to a recommendation for widespread implementation of this approach. However, interpretation of results is complicated by design and analytic decisions that excluded key subgroups, combined distinct clinical questions, and ignored gestational timing of blood pressure control. Target trials in observational data may address these issues; however, an appreciation of the methodologic concerns arising from the trial design is necessary.

Objectives: The objective of this symposium is to critically evaluate replicating the CHAP trial through the emulation of a target trial during pregnancy. This symposium will benefit researchers interested in perinatal pharmacoepidemiology, target trials, and real world data, as these methodologic considerations have implications for a variety of trials in obstetrics.

Description: The symposium will holistically evaluate the CHAP study findings and discuss several methodologic considerations for emulating a target trial in real world data. Dr. Osmundson, a US maternal-fetal medicine specialist, will provide an overview of the motivation for the CHAP study, review current treatment guidelines, and discuss clinical considerations for treatment of mild to moderate chronic hypertension during pregnancy. Dr. Bandoli, a perinatal epidemiologist, will dissect the CHAP trial methods and results, discuss potential threats to causal assumptions resulting from the pragmatic design, and highlight unanswered questions that remain post-CHAP. Then, Drs. Delker (a perinatal epidemiologist) and Wood (a perinatal pharmacoepidemiologist) will discuss target trial design with a focus on key methodological challenges. These include identification of eligible subjects in real world data, evaluation of effect modification across population subgroups, inclusion of prevalent and new users, and analysis of gestational timing of hypertension control. Dr. Dublin, an internal medicine physician and epidemiologist, will contrast the use of administrative data and electronic medical records data, including examining how the use of blood pressure values to identify eligible people may affect the population and outcomes studied. Finally, we will conclude with a panel discussion focused on applicability to other research questions.