Post-authorization Regulatory Strategies to Evaluate Drug Safety in Pregnancy: How to Optimize the Design of Registries & Database Studies

Background: The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) may require pharmaceutical companies to conduct post-authorization observational studies to generate data on the safety of pharmaceuticals when used during pregnancy. The COVID-19 pandemic has highlighted the need for efficient strategies to generate valid evidence throughout the product life cycle. Thus far, pregnancy registries and cohort studies nested in healthcare utilization databases are the primary sources of evidence. This symposium aims to crystallize the opportunities of each approach, as well as hybrid approaches between the two methods.

Objectives: First, to review the main features, strengths and limitations specific to pregnancy studies based on registries, databases, and expanded pharmacovigilance. Second, to discuss the considerations involved in designing the optimal, feasible strategy for valid and efficient generation of evidence targeted to specific real-life scenarios. This session will benefit investigators from industry, consulting and academic teams involved in the decision-making process of "what to do" to generate evidence on pregnancy safety, as well as regulators involved in the assessment of proposed strategies and evaluation of the study results.

Description: We will begin with the current regulatory perspective. Next, we will delve into the key features of common pregnancy registry designs and healthcare utilization databases amenable to pregnancy research. Speakers will then present applications to different scenarios that emphasize specific challenges and benefits of each approach (e.g., COVID-19 vaccines, anticonvulsants). This will lead into a summary of the key aspects to consider when selecting the sources of data and study designs with the highest likelihood of generating meaningful evidence on pregnancy safety given the specific scenarios (e.g., prevalence of the indication among women of childbearing age). Interactive discussion with the audience will inform the development of decision models to optimize post-authorization safety surveillance strategies.

Moderators: Leyla Sahin & Corinne de Vries.

Presentations:
· Leyla Sahin. Introduction. FDA regulatory perspective (10 min)
· Tina Chambers. Registries: Key considerations and COVID-19 vaccines and treatments as an example. (10 min)
· Andrea Margulis. Databases: Not all created equal, key considerations. (10 min)
· Sonia Hernandez Diaz. Registries: Application to antiepileptic drugs. (10 min)
· Krista Huybrechts. Databases: Application to antiepileptic drugs. (10 min)
· Corinne De Vries. Considerations to inform strategies: EMA perspective (10 min)
· Discussion (30 min)