FDA Foundation’s COVID-19 RWE Primer Compiles Lessons for Researchers
The COVID-19 pandemic triggered an immediate global effort to develop vaccines and treatments in 2020. This accelerated the use of real-world data (RWD) in clinical studies on the safety and effectiveness of vaccines, diagnostics, drug repurposing, and novel therapies in near real time.
As variants of COVID-19 continue to spread around the world, and as the world better prepares for a future global viral pandemic, it is wise to apply the lessons learned about the benefits of RWD and real-world evidence (RWE) to clinical research and public health policy in order to help save lives.
To document these lessons and make them accessible, the Reagan-Udall Foundation for the Food and Drug Administration (The FDA Foundation), in collaboration with the International Society for Pharmacoepidemiology (ISPE), created The COVID-19 Real-World Evidence Primer. Consisting of seven chapters, the primer covers types of RWD, study design, sources of error in RWE generation, examples of RWE studies and initiatives, and strategies for communicating about RWE.
Verana Health senior medical director, Michael Mbagwu, MD, was given a unique opportunity by The FDA Foundation to co-author a chapter (4) for this important online resource on using RWD and RWE for clinical research.
The chapter reviews and assesses COVID-19 RWE studies, and was written in collaboration with Matthew Roe, MD, former chief medical officer at Verana Health and currently vice president and head of early clinical development (Cardiovascular, Renal, and Metabolic) at AstraZeneca, and Christina Mack, PhD, vice president of epidemiology and clinical evidence at IQVIA.
“Real-world evidence—as opposed to clinical trials alone—helped provide timely insights into COVID-19.”
“From an evidence-based perspective, we didn’t know much about COVID-19 for a long time,” says Dr. Mbagwu. “Real-world evidence—as opposed to clinical trials alone—helped provide timely insights into COVID-19. Plus, it was based on sizable study populations and cohorts, which helped guide the medical community’s decision making, including establishing standards of care to help patients.”
Dr. Mbagwu and his co-authors summarized a half-dozen types of COVID-19 studies that used RWD to generate RWE. These studies included:
- Target trial emulation
- Cohort study
- Case-control study
- Self-control case series
- Drug utilization study
- Diagnostic test evaluation study
For each type of study presented in their chapter, the co-authors discuss the study’s objective, data source, study period, outcomes, and how researchers handled key potential sources of error.
The cohort study, for example, “sought to understand the potential effectiveness of hydroxychloroquine in preventing COVID-19 mortality in the general population.” The data source for the study, conducted from March 1 to July 13, 2020, was the OpenSAFELY platform, an open-source software platform that enables analysis of de-identified electronic health record data and SARS-CoV-2 testing, hospitalization, and death records for approximately 40% of the population in England.
While the longitudinal data collected from routine clinical practices was rich with patient medication data, “it was limited by a lack of information on medications prescribed by specialists, such as biologic treatments for rheumatological disease,” Dr. Mbagwu and his co-authors wrote.
The study authors took a number of actions to mitigate the impact of potential errors. They calculated bias-adjusted effect estimates using quantitative bias analysis, conducted sensitivity analyses to assess the potential of exposure misclassification, and used multiple imputation to address missing ethnicity data for 23% of individuals. Further, the authors published an open-source protocol prior to analyzing the data. This reduced the chances that subjectivity would influence decision-making during analysis.
Documenting the steps taken to recognize and control for errors in studies using RWD and defining observational study designs makes the COVID-19 Real-World Evidence Primer an invaluable resource for drug and public health researchers. But, the FDA Foundation went even further, using the publication of the primer to introduce the COVID-19 Evidence Accelerator (“Accelerator”), an initiative launched by the Reagan-Udall Foundation for the FDA in collaboration with Friends of Cancer Research. Established during the pandemic to support RWD studies, the Accelerator is designed to “provide a unique venue for major data organizations, government and academic researchers, and health systems to share information about COVID-19 efforts, and to convene a community to urgently address questions about COVID-19.” (Chapter 6 of the primer is devoted to the Accelerator.)
It is this sort of collaborative effort that Dr. Mbagwu says excites and inspires him.
“As someone who works with real-world data and cares for patients, it was very powerful to me that researchers around the world were rolling up their sleeves to help.”
“When the COVID-19 pandemic began, we were building a ship as it was starting to sail and we really didn’t have many insights on the virus,” he says. “As someone who works with real-world data and cares for patients, it was very powerful to me that researchers around the world were rolling up their sleeves to help.”