Posted May 16, 2022 | By
Sara Head, PhD, FDA Office of Women’s Health
The U.S. Food and Drug Administration (FDA) is working on ways to facilitate greater use of real-world data (RWD) to help understand the safety and effectiveness of drugs used during pregnancy and pregnancy. feeding with milk.
Despite the widespread use of prescription and over-the-counter medications by pregnant and breastfeeding women, there is often little or no information to guide decisions about starting and stopping medications or changing doses.
“Although the lack of scientific data prevents us from understanding the true risk of most medications during pregnancy, research suggests that women overestimate the risk of taking medications and decide against using them when their own research gives conflicting safety information,” Sara Head, PhD, of the FDA’s Office of Women’s Health, said at a public workshop hosted by the Johns Hopkins Center of Excellent in Regulatory Science and Innovation (JH-CERSI ) and the FDA’s Office of Women’s Health.
The workshop comes as the FDA signaled how it would use RWD to make regulatory decisions. In 2021, the agency published draft guidance documents on using RWD with clinical registries, using RWD with electronic health records and claims data, and how RWD could be incorporated into clinical study designs (RELATED: FDA releases draft guidelines on designing studies using real-world dataRegulatory guidance 09 December 2021; FDA proposes draft guidelines for registries as RWDRegulatory guidance November 29, 2021; FDA releases draft RWD guidance from EHRs and claims dataRegulatory guidance September 29, 2021).
Advice on pregnancy and breastfeeding
“It’s important to note that we’ve relied on RWD for a long time to educate about drug safety in pregnancy and lactation, long before it was called RWD. We can think of RWD as pharmacovigilance and observational studies,” said Leyla Sahin, MD, acting assistant director for safety in the Division of Pediatrics and Maternal Health in the Center for New Medicines Office. FDA Drug Review and Investigation (CDER).
The agency addressed many issues related to RWD during pregnancy and breastfeeding in two draft guidelines released in 2019, according to Sahin (RELATED: Studying drugs in pregnancy and breastfeeding women: FDA releases draft guidelinesRegulatory guidance May 08, 2019).
The draft pregnancy safety studies post-approval guidelines are currently being revised based on public feedback. The guidance includes a discussion of pharmacovigilance, pregnancy registries, electronic health record data, and surveillance programs. It also covers complementary studies, which can provide data to complement the information collected through pregnancy registries.
The draft guidelines address considerations for when exposure during pregnancy should be rare, but there is still a need to collect data on pregnancy safety, similar to a rare disease. In these situations, a sufficiently powerful pregnancy registry or database study may not be feasible, and the guidelines offer an alternative study method called a “pregnancy surveillance program”.
“Since these guidelines were released, we have encountered confusion related to this terminology,” Sahin said. “And so, the terminology is currently under discussion, and we’ve now moved to using the terminology ‘descriptive pregnancy safety study’.”
This study method involves systematic collection of pregnancy-specific data, includes prospective and retrospective data collection, and can be conducted as part of a disease registry.
The draft breastfeeding clinical study guide, released at the same time, is also being revised based on public feedback. It recommends conducting lactation studies for drugs intended to be used by breastfeeding individuals and discusses study design and analysis considerations. “Lactation studies, even those conducted as opportunistic studies, may not be considered RWD per se, but have a RWD component in that milk samples are taken from infants under real-life conditions” , Sahin said. “RWD, such as usage data and safety data, may be collected to support data generated from lactation studies.”
The FDA also participated in the National Working Group on Research Specific to Pregnant and Nursing Women (PRGLAC) to address knowledge and research gaps regarding safe and effective therapies for pregnant and breastfeeding women. The task force submitted two reports to Congress in 2018 and 2020.
RWD recommendations include:
- Increase the quantity, quality and timeliness of research into therapeutic products used by pregnant and breastfeeding women.
- Optimize pregnancy registries to move away from single-product, single-company pregnancy registries and expand the use of disease-based registries.
- Implement a proactive approach to protocol development and study design to systematically develop a plan for timely data collection, including pregnancy safety data.
- Design health record systems to link maternal and infant records and leverage large studies and databases.
“RWD plays an important role in bridging the data gap, as most safety data related to pregnancy and lactation is collected in the post-approval setting,” Sahin said. “We cannot rely on a single study to optimize safety assessment in pregnancy. We need multiple data streams.
PDUFA VII Commitments
Pregnancy safety is also among the FDA’s commitments in the proposed Prescription Drug User Fee Act (PDUFA VII) reauthorization for fiscal years 2023-2027. As part of this plan, the FDA would develop a framework outlining how data from different types of postmarketing pregnancy safety studies could best be used. By September 30, 2023, the agency would hold a public workshop on post-marketing safety studies in pregnant women and publish a report outlining the proposed framework by September 30, 2024.
Under the plan, the agency would conduct five demonstration projects evaluating various study designs, both when exposure during pregnancy is common and when it is rare. Engagement goals set September 30, 2027 as the deadline to update the proposed framework and develop guidance or policy to implement a standardized process for determining the need and type of post-marketing pregnancy studies .
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