1. Course Aim In this course, faculty will present and discuss considerations related to designing studies on the safety of medical products in pregnancy focusing on non-live pregnancy outcomes: spontaneous abortions, stillbirths, elective terminations. Studying these outcomes is subject to a specific set of challenges and biases and requires special design considerations.
The course will consist of three presentations followed by a practical component in which course registrants will apply the core course concepts in groups focusing on a specific research question.
The overarching goal of the Modern Pregnancy Pharmacoepidemiology course is to keep up with advances in the field. We cover new topics each year, from overviews of issues that are particular to research on the safety of medical products in pregnancy (2015, 2020) to deeper dives into specific aspects, such as study design (2018), exposure measurement (2016), various maternal, neonatal and childhood outcomes (2017, 2021), and significance testing and analytical approaches to address biases (2019). In 2022, the course discussed pregnancy pharmacoepidemiologic research within the framework of target trial emulation. This year, the focus will be on non-live birth outcomes.
2. Requisites Statement This is an intermediate level pharmacoepidemiology course.
3. Course Objectives a. To be better equipped to critically assess the validity of studies on the safety of medical products in pregnancy b. To learn key clinical aspects of non-live birth outcomes c. To identify the structure of potential biases in the study of non-live birth outcomes d. To understand operational and logistic challenges in research on non-live birth outcomes 4. Syllabus Outline 1. The clinical presentation and pathophysiology of non-livebirth and the relation to drug exposures. In this portion of the course, we will review the clinical presentation and risk factors for non-livebirths with an eye to how these inform the design and interpretation of studies of medication safety. Topics considered include mechanisms by which medications cause spontaneous abortion or stillbirth and the etiologically relevant time window for exposures. Examples of medications associated with an increased risk of non-livebirth will be discussed. Instructor: Brian Bateman, Stanford University School of Medicine
2. On the roles of non-live births: outcome, competing event, and source of bias Fetal losses may be our outcome of interest, or they may occur before or after other outcomes of interest. These three scenarios present distinct challenges of left and right truncation that may lead to selection and misclassification biases. In addition, fetal losses compete with later outcomes, which may complicate the conceptualization of research questions and the corresponding data analysis. We provide a framework that may facilitate the discussion of solutions, interpretations and assumptions. We will discuss examples of selection (survivor) bias when the follow-up starts after conception and of immortal time bias when time between conception and exposure initiation is misclassified as exposed. Instructor: Sonia Hernandez-Diaz, Harvard T.H. Chan School of Public Health
3. Challenges when studying non-live birth outcomes in case-control, registry and database studies During this section, we will discuss some of the key operational and logistical challenges faced with when studying non-live birth outcomes in the context of different study designs and review potential solutions. Issues that will be covered include amongst others identification of non-live birth outcome and gestational age estimation (database studies), potential selection bias associated with prospective enrolment throughout pregnancy and lack of power (registries), potential recall bias and lack of generalizability (case-control studies). Instructor: Krista Huybrechts, Brigham and Women’s Hospital, Harvard Medical School
4. Practical session During the final session, participants will discuss in small teams a request to study the potential association between a medical product and non-live birth outcomes posed by a regulatory agency at the time of marketing authorization. Experiences will be shared and discussed with the entire group. Led by: Andrea Margulis, RTI Health Solutions