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March 24, 2020

Treating COVID-19—Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics

Author Affiliations
  • 1Division of Infectious Diseases, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
JAMA. 2020;323(19):1897-1898. doi:10.1001/jama.2020.4742

In the 2014 Ebola outbreak, close to 30 000 individuals developed Ebola viral disease (EVD), and numerous therapies were tested against this virus, including chloroquine, hydroxychloroquine, favipiravir, brincidofovir, monoclonal antibodies, antisense RNA, and convalescent plasma, among many others. With such a large number of therapeutic interventions given to affected patients, the goal was to determine which was efficacious against Ebola. Ultimately, none proved to be efficacious or safe.

Why were new therapies not discovered? One reason is because virtually all studies were single-group interventions without concurrent controls, which led to no definitive conclusion related to efficacy or safety. Despite much resistance and controversy regarding asking patients with EVD to participate in a randomized clinical trial (RCT),1 the National Institutes of Health (NIH) conducted the first and only RCT during that outbreak. It took several months to design the trial, but it was implemented and successfully launched during the outbreak; however, it was too late for the RCT to be completed.2 This tragedy of not discovering new therapies during an outbreak cannot be repeated.