BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK, United Kingdom
Background: Assessing drug safety in pregnancy is challenging due to ethical constraints and observational study limitations. Prospective pregnancy registries, though widely requested by health authorities, are costly and are often terminated early due to low enrollment. Integrating multiple epidemiological approaches may improve evidence generation and risk assessment in exposed pregnancies, especially in the treatment of complex autoimmune conditions with disease activity and flares that can pose significant maternal and fetal risks.
Objectives: To share early learnings from the integration of three complementary epidemiological study designs—a retrospective multinational cohort study, a prospective pregnancy registry, and enhanced pharmacovigilance—to strengthen drug safety assessments in pregnancy.
Methods:
Design: This approach integrates three designs: (1) a retrospective cohort study using secondary data from Europe and the U.S., (2) a prospective U.S. pregnancy registry, and (3) an enhanced global pharmacovigilance pregnancy data collection strategy.
Setting: Secondary data spanning multiple years, while the registry (country specific) enrolls exposed and unexposed pregnancies across multiple years. Enhanced pharmacovigilance supplements routine reporting with active case follow-up up to 1-year after birth.
Exposure: Medication use in women of childbearing potential
Outcomes: Adverse pregnancy and birth outcomes.
Analysis: Propensity score matching for retrospective data, inverse probability of treatment weighting (IPTW)-adjusted models for the registry, and descriptive analysis for pharmacovigilance.
Results: Preliminary endeavors suggest that this multimodal approach could improve exposure assessment, enhance rare outcome detection, and strengthen drug safety evaluation. However, challenges persist, including data harmonization, standardization of outcome definitions, and residual confounding. Secondary databases may over-represent early adverse pregnancy outcomes, a potential limitation that could be mitigated by prospective registry follow-up. Additionally, double counting of adverse outcomes across study designs is a potential issue. Despite these challenges, integrating these methods offers a more comprehensive and robust framework for evaluating drug safety in pregnancy.
Conclusions: A multimodal epidemiological approach provides a more comprehensive evaluation of drug safety in pregnancy than any single method alone. Future efforts should focus on methodological refinements, cross-disciplinary collaboration, and regulatory harmonization to optimize maternal-fetal pharmacovigilance and improve public health outcomes.
