COVID-19 Real-World Evidence Primer

Chapter 2: Methods in Real-World Evidence Generation — Study Design

Authors: Marie C. Bradley, PhD, MScPH, MPharm1; Nicolle M. Gatto, PhD, MPH2,3; Masao Iwagami, MD, MPH, MSc, PhD4,5; Catherine Lerro, PhD, MPH1; Jeremy A. Rassen, ScD2

Acknowledgments: NG and JR wish to thank Pattra Mattox, MS, CMPP for her editorial assistance.

1Division of Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration
2Aetion, Inc., New York, NY, USA
3Columbia Mailman School of Public Health, New York, NY, USA
4Department of Health Services Research, University of Tsukuba, Ibaraki, Japan
5Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK

Disclosures: NG is an employee and stockholder of Aetion, Inc. and stockholder of Pfizer, Inc. JR is an employee and stockholder of Aetion, Inc.

In this chapter, we discuss 4 different observational study design families commonly used with real-world data (RWD):

  1. Target trial paradigm, which typically uses cohort study designs to emulate randomized controlled clinical trials (RCTs)
  2. Between-person designs, including cohort and case-control studies
  3. Within-person designs, which compare different time windows (i.e., lengths of time) within the same person
  4. Descriptive designs, which examine disease or exposure patterns in the population, focusing on characteristics related to person, place, and time

The chapter begins with the target trial paradigm and the concept of a randomized controlled trial, therefore providing an intuitive introduction into core methodological considerations when generating real-world evidence (RWE). Studies that utilize the target trial paradigm most commonly employ cohort study designs with a between-person approach, which is further addressed in section two of this chapter. The third section of the chapter introduces within-person designs, in which different time periods within the same person are compared. Finally, the fourth section covers descriptive study designs.