Harmonized pregnancy studies to enhance external and internal validity of drug safety studies evaluating real-world evidence: An expert consensus on definitions and methods

Drug safety during pregnancy is an area of continued importance as substantial uncertainty persists regarding the safety of many medications, and the use of medications during pregnancy and lactation continues to increase. Real-world evidence (RWE) generation for pregnancy-related outcomes relies mostly on the use of existing data sources and primary data collection in post-marketing settings, however the conduct of reliable studies requires rigorous methods including comprehensive and transparent measures to deal with key challenges and outcome-specific considerations.

Several guidance documents have been published over the past two decades, but are challenged by misalignment in, or lack of, recommended definitions of key variables, and insufficient guidance on handling of challenges and considerations. Furthermore, country and data source specific adaptations of definitions and guidance is still a challenge in evidence generation for real-world pregnancy studies.

The lack of consensus for assessment windows and outcome definitions impedes the optimal use of perinatal research in regulatory and clinical decision-making.

This research topic aims to collate and present clear guidance on best practice methods and aligned definitions needed to enable informed decision making and improve public health. The challenges, considerations, and recommendations should be based on expert consensus of interpretation of existing guidelines, as well as filling in the gaps for future perinatal research.

The International Society for Pharmacoepidemiology (ISPE) special interest group for Medication in Pregnancy and Lactation (MiPAL) established a consensus task force group consisting of members from regulators, academia, consulting research organizations, and industry partners was established within MiPAL to create a global alignment of pregnancy definitions and best practice methods to improve research quality and inform decision-making. The task force group has already considered pregnancy anchors, spontaneous abortions, congenital malformations, and neurodevelopment disorders, but would like to call for contributions to cover further topics (i.e., additional outcomes, or methods) and to simulate the potential impact of recommended definitions.

We would welcome original research (including simulation studies), review articles, and method article types. Authors will be expected to lead their proposed topic but can request support from the existing task force. Each contribution will require review of existing guidance and literature to identify parameters for alignment, key challenges and considerations, and recommendations where applicable.

Topic Editor DL is currently employed by PHARMO, part of Lumanity, UK and is Director of PEPI Consultancy Limited and has received funds from AstraZeneca Ltd., Ariello SRO and Annexon Biosciences for consultancy. The other Topic Editor declares no competing interests with regard to the Research Topic.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Drug safety in pregnancy, Real-world evidence, Pharmacovigilance, Congenital malformations, Spontaneous abortion, Neurodevelopmental disorders, Pregnancy anchors, Perinatal pharmacoepidemiology, Simulation studies, Pregnancy cohort studies

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.