Executive Director, Research Science PPD a part of Thermo Fisher Scientific Raleigh, United States
Background: FDA-mandated post-marketing requirements (PMRs) for pregnancy and lactation studies have evolved following the release of FDA guidance, in May 2019, on post-approval pregnancy safety studies and clinical lactation studies. From May 2019 through December 2022, the FDA issued 21 pregnancy study PMRs with the broad description “worldwide descriptive study that collects prospective and retrospective data.” These studies are commonly referred to as descriptive pregnancy safety studies or pregnancy surveillance programs (PSPs). Prior to July 2021, PMR descriptions for PSPs indicated that these studies should collect data on individuals exposed to the product of interest during pregnancy only. Since July 2021, all PMR descriptions for PSPs have indicated that data should additionally be collected on individuals exposed during lactation.
Objectives: To explore key considerations for the design of expanded PSPs that collect post-approval safety data on both pregnant and lactating individuals.
Methods: We reviewed protocols for PSPs and expanded PSPs to identify key differences.
Results: Our review identified the following key considerations for the design of expanded PSPs: - Study population: beyond individuals exposed during pregnancy (with or without exposure during lactation), the study population must also include individuals exposed during lactation but not pregnancy - Exposure definition: beyond exposure during pregnancy (from date of conception to pregnancy outcome) or prior to pregnancy (within 5 half-lives of conception), the exposure definition must also include the period after pregnancy outcome up to 12 months of infant age (or weaning) - Prospective enrollment: individuals who enroll after pregnancy outcome but before the infant reaches 12 months of age (or weans) are considered retrospective for pregnancy portion and prospective for lactation portion of study - Data collection: must capture detailed breastfeeding information, including breastfeeding start/stop dates and maternal exposures to medicinal and recreational drugs during breastfeeding - Recruitment: both currently and recently pregnant individuals should be targeted
Conclusions: To meet the FDA’s recent PMRs for expanded PSPs that additionally assess the effects of medicinal product exposure during lactation, it is important to adapt study design. There are several key implications to study design related to the study population, exposure definition, recruitment strategy, prospective/retrospective enrollment, and data collection that must be considered.
