Emulating a Target Trial in Perinatal Pharmacoepidemiology: Challenges and Methodological Approaches

Abstract

The objective of this review is to examine the application of target trial emulation in perinatal pharmacoepidemiology research. Given that randomized clinical trials—the gold standard for causal inference—are often not feasible or ethical for studying medication safety during pregnancy, alternative methodologies are critically needed. This paper delves into the challenges and potential mitigation strategies of using target trial emulation in the specific context of perinatal pharmacoepidemiology research. Our review of identified studies (n = 9) reveals several unique considerations when leveraging target trial emulation for perinatal pharmacoepidemiology research. These include the alignment of the research question with the clinically relevant outcomes, identification of etiologically relevant time windows, defining relevant treatment strategies, and anchoring of exposure, eligibility criteria, and the start of follow-up. Despite these challenges, the methodology shows promise in bridging the gap between randomized clinical trials and observational research through the employment of a transparent and well-defined approach. Target trial emulation serves as a valuable tool in perinatal pharmacoepidemiology, allowing researchers to generate more reliable evidence concerning medication safety during pregnancy. Although the approach comes with specific challenges, strategies can be implemented to mitigate these difficulties. Overall, the adoption of target trial emulation has the potential to substantially enhance evidence quality, inform clinical decisions, and ultimately improve health outcomes for birthing people and their infants.