The Critical Need for Pregnancy Registry Studies and Robust Safety Monitoring in COVID-19 Vaccines

To-date, clinical trials for COVID-19 vaccines have excluded pregnant and lactating women, as drug manufacturers have only tested these products in healthy and “at-risk” populations, including older adults. However, it is critical that we study this previously excluded population of women in order to facilitate policy decisions, inform clinical practice and assist women, their partners, and healthcare providers in making informed decisions about the risks and benefits of COVID-19 vaccination during pregnancy.  In this blog, Dr. Deborah Covington, senior research leader at Evidera, explores the need for these post-approval safety studies.

Data are currently limited around the safety of COVID-19 vaccines in pregnancy, and recommendations from health authorities are ambiguous. Currently, The Centers for Disease Control and Prevention (CDC) states the decision is a personal choice and recommends talking to a healthcare provider. While we have limited data on the prevalence and severity of COVID-19 in pregnant women, there is a growing body of evidence that pregnant women are at increased risk for severe COVID-19 disease, complications, and death.

This combination of limited data, uncertainties around current recommendations, and evidence suggesting COVID-19 can lead to severe complications in pregnant women is sure to cause confusion and concern in this patient population, heightening the need for the rapid implementation of pregnancy studies.

Advancing Pregnancy Immunization Research

In recent years, much progress has been made in advancing research on immunization during pregnancy including:

• Well-established immunization recommendations for influenza and pertussis from the Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG)
• The May 2019 Food and Drug Administration (FDA) draft guidance on post-marketing pregnancy safety studies and clinical lactation studies
• Current FDA guidance on COVID-19 vaccine development that encourages the inclusion of pregnant women and women of child-bearing potential in later phases of development

These advances provide valuable lessons learned and guidance to serve as a solid foundation for COVID-19 vaccine research in pregnant populations.

Prospective Pregnancy Registries for Active Data Collection

Active data collection is key in assessing the safety of a COVID-19 vaccine in pregnant populations given the unique nature of the development landscape and accelerated timelines with which these products were developed.

Prospective registries are preferable in this scenario as they offer active data collection versus retrospective surveillance techniques. Ideally, especially given the uncertainties around COVID-19, these studies would be launched at the time a vaccine is first marketed and provide valuable safety data soon after the data becomes available to the general public. In this model:

• Active data collection begins at the time of vaccination during pregnancy and continues through pregnancy outcome and the infant’s first year
• Detailed data are collected on the vaccine exposure, pregnancy complications, and infant outcome
• Data are reported to the registry by pregnant women, their healthcare providers, and their infants’ healthcare providers

Using this model, signal detection can be more robust than in spontaneous reporting systems, which are the default source of event reporting at initial marketing. Because the exposure clearly occurs before the outcome, this design also avoids the recall bias that retrospective designs may introduce and enables the registry to capture critical data directly from the source.

Recommendations for Vaccine Developers

Ideally, COVID-19 vaccine manufacturers should work together to develop a global vaccine pregnancy safety monitoring system with a nested lactation study to begin monitoring pregnancy and lactation exposure at the launch of each vaccine.

Using this multi-national approach presents a unique opportunity to standardize safety monitoring in this population and would enable current and future analyses of standardized data to detect safety signals and evaluate pregnancy and infant outcomes.

This system would provide the robust data needed to fill current knowledge gaps around COVID-19 vaccine safety in pregnant and lactating women and help inform and empower vulnerable patients.