Head Safety Science, Epidemiology GlaxoSmithKline Cary, United States
Background: The risks and benefits of medicine use during pregnancy are typically established through post-approval population-based observational studies. Currently, there is heterogeneity in the identification, selection and the definitions of key pregnancy and maternal outcomes of interest, exposures, risk factors, and confounders. There is also a large range of different study designs and statistical tools available for these studies.
Objectives: IMI-ConcePTION (https://www.imi-conception.eu/) identified the need to create recommendations for standardized key concepts and research methods.
Methods: The core evidence elements guide for population-based observational studies was compiled using expertise in pharmacovigilance, pharmacoepidemiology, perinatal epidemiology, statistics, perinatal clinical pharmacology, and health services research, both internal and external to IMI-ConcePTION. It also included reviews of the literature, best practices, and regulatory guidance documents.
Results: The recommendations cover core evidence elements including gestational age, exposures (dose/duration of medicine and etiological window); relevant confounders; pregnancy outcomes (live and non-live births), congenital anomalies, infant/childhood outcomes (including long-term outcomes), and maternal outcomes; research design considerations; analytical methods; statistical power/sample size considerations and study limitations. A list of “default” core evidence elements is also proposed as a minimal set of elements that should be considered in all pregnancy medicine safety surveillance studies. The recommendations also include guidance when assessing the quality of data sources.
Conclusions: This core evidence elements recommendations will facilitate setting standards with regards to the definitions used in medicine and pregnancy studies, the quality of the data and the suitability of data sources used for this work. It can also be tailored to address studies with specific research questions, particular medicines/disease areas or specific outcomes. It will promote the conduct of more standardized, high quality and clinically meaningful population-based studies among pregnant women. It will also help with alignment across different studies to improve evidence synthesis.
