Pharmacoepidemiologic Approaches to Studying Drug-Drug Interactions

1. Course Aim
The course will cover the foundations of pharmacoepidemiologic research on the health effects of drug-drug interactions (DDI) in populations. We will introduce the main sources of bias in DDI studies, cover main study designs and techniques to address bias, and walk the audience through several case studies.

2. Requisites Statement
This is an intermediate level course. Attendees should have basic knowledge of epidemiology or pharmacoepidemiology. The following papers are recommended for preparation for the course, but are not required:

Hennessy S et al. Pharmacoepidemiologic methods for studying the health effects of drug-drug interactions. Clin Pharmacol Ther 2016;99(1):92-100.
Dimakos J, Douros A. Methodological considerations on the use of cohort designs in drug-drug interaction studies in pharmacoepidemiology. Curr Epidemiol Rep. 2024 Mar 8 [Epub ahead of print]
Knol MJ, VanderWeele TJ. Recommendations for presenting analyses of effect modification and interaction. Int J Epidemiol. 2012 Apr;41(2):514-20

3. Course Objectives
- To describe the role of pharmacoepidemiology in generating real-world evidence on the population health effects of DDIs
- To describe main sources of bias in DDI research
- To describe the application of a cohort design to study the population health effects of DDIs
- To present new and advanced topics in DDI research, including but not limited to causal inference and alternative approaches to addressing bias.
- To facilitate discussion of challenges and solutions in DDI research

4. Syllabus Outline

Introduction, format, and objectives of the course | Presenter: Katsiaryna Bykov, PharmD, ScD (Brigham and Women’s Hospital and Harvard Medical School) | Duration: 5 minutes

Lecture 1: Core concepts in drug-drug interactions research and new-user, active-comparator cohort design | Presenter: Katsiaryna Bykov, PharmD, ScD (Brigham and Women’s Hospital and Harvard Medical School) | Duration: 55 minutes

This lecture will provide an overview of terminology and core concepts in DDI pharmacoepidemiology. Further, it will introduce key source of bias in DDI research and how bias can be mitigated via restriction and an active-comparator, new-user cohort design. An empirical case study will be presented to describe the decision-making process.

Lecture 2: When an active comparator is not available: time-varying exposure and prevalent new-use design | Presenter: Antonios Douros, MD (Charité – Universitätsmedizin Berlin) | Duration: 60 minutes

This lecture will focus on settings where an active comparator, i.e., that is the concomitant use of the object drug and a control precipitant drug, is not available. Then, the concomitant use of the object and the precipitant needs to be compared to the use of the object alone. We will discuss which biases may arise in these settings, and how time-varying exposures and the prevalent new-user design could address them.

Lecture 3: Special considerations for studying pharmacodynamic DDIs and drug-drug-disease interactions | Presenter: Todd Miano, PharmD, PhD, FCCM (University of Pennsylvania) | Duration: 60 minutes

Standard DDI study designs are often insufficient to examine questions pertaining to pharmacodynamic DDIs and higher-order drug-drug-disease interactions. This lecture will review key considerations for designing studies to address these challenges. In particular, the lecture will describe the distinction between causal interaction and effect modification and explain how this distinction guides study design choices.

Concluding remarks and Q&A session | Presenters: All faculty | Duration: 15 minutes