SC-17 - Pregnancy Pharmacoepidemiology: Evidence Generation and Interpretation for Decision- Making

1. Course Aim

In this course, faculty will present and discuss the unique challenges of designing and conducting studies on the safety of medical products in pregnancy. The first talk will provide an introduction on features that are specific to this very specialized area of research. The three subsequent talks will discuss selected aspects related to research using pregnancy registries and electronic health data, and will address challenges when integrating results across studies addressing the same question. A practical group exercise will allow deeper discussion and application of these concepts.

The overarching goal of the Modern Pregnancy Pharmacoepidemiology course is to keep up with advances in the field. We cover new topics each year. For example, in 2022, the course discussed pregnancy pharmacoepidemiologic research within the framework of target trial emulation. In 2023, the course focused on non-live birth outcomes; in 2024, the course dug into challenges and solutions related to study design per a standard protocol template.

2. Requisites Statement

This is an intermediate level pharmacoepidemiology course.

3. Course Objectives

1. To be better equipped to critically assess the validity of studies on the safety of medical products in pregnancy
2. To learn new developments in research using pregnancy registries and health care databases
3. To integrate the contributions of one new study into existing evidence, which is often scarce or conflicting, to inform decision making.
4. Syllabus Outline

1. Setting the stage: Overview of design and analytic issues in drug safety studies in pregnancy

Focusing on the use of pregnancy registries and electronic data sources to study the safety of medications in pregnancy, this section will set the stage for subsequent sections by providing an overview of key design and analytic considerations. Topics considered will include defining exposure (including the etiologically relevant exposure window), outcomes, and confounders. Analytic approaches to address limitations inherent to drug safety studies in pregnancy will be discussed. This overview is intended to provide context to the course and to be especially useful for first-time course attendees
Instructor: Brian Bateman, Stanford University School of Medicine

2. Key things you need to know about research in pregnancy registries

This section will discuss key aspects to consider when designing or evaluating pregnancy registries to assess risks and benefits of medications during pregnancy. Topics will include 1) their goals; 2) distinctive methodological aspects including study population, gestational age at enrolment, follow-up and competing events, ascertainment and definition of interventions and outcomes, reference groups and confounding, prenatal diagnosis, and statistical power, and 3) operational aspects such as recruitment and retention of participants, methods of data collection, or when to release findings.
Instructor: Sonia Hernandez-Diaz, Harvard T.H. Chan School of Public Health

3. Key things you need to know about pregnancy research in electronic health data sources
This section will focus on challenges that are specific to pregnancy research in these data sources. Topics for discussion will include finding the study population (identification of pregnancies and gestational age at birth, mother-infant linkage), challenges in using data sources with information from different settings (primary care, hospital care, both), identifying outcomes (eg, major congenital malformations; EUROCAT and MACDP coding systems), and others.
Instructor: Andrea Margulis, RTI Health Solutions

4. From study to synthesis: Incorporating new data into existing evidence

No single study stands alone, nor can it offer a definitive answer. In this session, we will discuss strategies for interpreting the results of an individual study in the context of its methodological strengths and limitations. We will also explore approaches for integrating findings from a given study into the broader body of evidence—often heterogeneous and conflicting—to support more comprehensive and balanced conclusions about a drug’s safety. Finally, we will consider how to effectively communicate this synthesized evidence to patients, healthcare providers, and regulatory stakeholders.
Instructor: Krista Huybrechts, Brigham and Women’s Hospital, Harvard Medical School

5. Practical session

During the final session, participants will discuss in small teams a study to assess the potential association between a medical product and pregnancy, fetal and/or infant outcomes, with a particular focus on some of the issues raised during the sessions. Experiences will be shared and discussed with the course attendees.