Adapted Targeted Literature Review (ATLR) for Landscaping Trends in Pregnancy Post Authorization Safety Studies (PASS)

OBJECTIVES: Pregnant women are often excluded from clinical trials, resulting in limited data on drug safety for this population. In 2019, the FDA and EMA updated guidelines for observational, post approval studies for drug safety in pregnancy. This adapted targeted literature review (ATLR) aimed to identify and describe characteristics of published pregnancy Post-Approval Safety Studies (PASS) and protocols, focusing on secondary data-based analytics.

METHODS: MEDLINE and CINAHL were searched for published reports of completed studies, and the Heads of Medicines Agency-European Medicines Agency (HMA-EMA) and clinicaltrials.gov (CTG) registries were searched for published protocols. The search algorithm used a combination of indexing terms and free-text keywords specific to pregnancy PASS using secondary data sources between January 2014 and June 2024. Results were ordered by recency, titles and abstracts were screened and data was extracted for publication date and data source(s) utilized.

RESULTS: 18 completed studies and 1645 protocols were identified, among which 45% (N = 746) were from CTG and 55% (N = 899) were from HMA-EMA. 6 completed studies were included of which 5 were published on or after 2020; among included studies 3 utilized administrative claims data, 2 utilized patient reported outcomes and 1 utilized multiple data sources. 41 protocols were included among which 35 were published on or after 2020; among included protocols 18 utilized registry data, 11 utilized administrative claims data, 8 utilized multiple data sources and 4 utilized electronic health records.

CONCLUSIONS: We identified few published completed reports of pregnancy PASS based in secondary data. However there are a number of published protocols and both the number of completed reports and protocols based in secondary data (particularly administrative claims and registries) increased after 2020. There is increasing recognition of the role that real-world secondary data can play in evaluating drug safety during pregnancy.