Modern Pregnancy Pharmacoepidemiology: Emulating Target Trials

Course Aim
In this course, faculty will present and discuss considerations related to designing studies on the safety of medical products in pregnancy within the framework of target trial emulation. The course will consist of presentations by four faculty (general overview on evaluating the safety of medical products in pregnancy; target trial emulation framework; concrete applications to pregnancy pharmacoepidemiology). Talks will be followed by a practical component in which course registrants will apply the core course concepts in groups. In case of a virtual/remote delivery of this course, the practical session may be omitted.

We aim to cover new topics each year, while still providing a general overview for participants who are newer to the field. In 2015, the course provided an overview of issues that are particular to research on the safety of medical products in pregnancy. In 2016 the course focused on challenges related to exposure measurement, in 2017 the focus was on maternal and neonatal outcomes, and in 2018 the course presented pros and cons of various study designs. In 2019, the course discussed significance testing and analytical approaches to address biases. The content of the 2020 edition covered some of the main themes discussed in previous years. In 2021, we discussed to maternal and immediate and long-term offspring outcomes. In 2022, the course will discuss considerations when conducting pregnancy pharmacoepidemiologic research within the framework of target trial emulation, an approach which is gaining popularity.

Requisites Statement
This is an intermediate-level pharmacoepidemiology course.

Course Objectives
1. To be better equipped to critically assess the validity of studies on the safety of medical products in pregnancy
2. To understand key considerations related to the target trial emulation framework
3. To understand specific challenges and workarounds when applying this framework to research on the safety of medical products in pregnancy

Syllabus Outline
Overview of design and analytic issues in drug safety studies in pregnancy

Description: Focusing on the use of healthcare utilization data to study the safety of medications in pregnancy, an overview of key design and analytic considerations analysis will be provided. Topics considered will include defining exposure (including the etiologically relevant exposure window), outcomes, and confounders. Analytic approaches to address limitations inherent to claims data 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

Principles of target trial emulation

Description: Target trial emulation is an approach that has gained popularity in pharmacoepidemiology in recent years. During this session we will discuss the core principles behind the target trial emulation framework, with a particular focus on how it helps to conceptualize study design and analyses to address causal questions using observational data, and how it helps to avoid common methodological pitfalls. We will also dispel some of the myths surrounding this approach. After this session, participants should be well prepared to delve into the details of using the target trial emulation in pregnancy.
Instructor: Krista Huybrechts, Brigham and Women's Hospital, Harvard Medical School

Target trial emulation in pregnancy: example 1

Description: Observational studies are often the only option to estimate effects of interventions during pregnancy. Causal inference from observational data can be conceptualized as an attempt to emulate a hypothetical pragmatic randomized trial: the target trial. As an example, we provide a step-by-step description of how to specify and emulate a target trial of COVID-19 vaccination during pregnancy.
We identify challenges that affect i) the target trial and thus its observational emulation (censoring and competing events), and ii) mostly the observational emulation (confounding, immortal time and measurement biases). Explicitly emulating target trials at different gestational ages can help reduce bias and improve the interpretability of effect estimates for interventions during pregnancy.
Instructor: Sonia Hernandez-Diaz, Harvard T.H. Chan School of Public Health

Target trial emulation in pregnancy: example 2

Description: The second example will explore a practical application of this framework to a multi-database study assessing the safety of a short oral COVID-19 treatment in pregnant women in Europe. The presentation will discuss various aspects of the study design and how thinking within the target trial emulation framework favors particular study design choices.
Instructor: Andrea Margulis, RTI Health Solutions

Practical session

Description: During the final session, participants will have the opportunity in small groups to explicitly describe and emulate the target trial that would answer the causal question related to drug safety in pregnancy that they will be asked to address using observational data. Experiences will be shared and discussed with the entire group.