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Posted By: Lawrence Herman, PA-C, MPA
July 10, 2020
There are more than 160 COVID-19 vaccines currently in development, with the University of Oxford/AstraZeneca AZD1222 vaccine (an attenuated altered adenovirus) already in phase III trials and the Moderna mRNA-1273 vaccine (which holds the potential to become the first-ever licensed mRNA vaccine) expected to start phase III trials this month. The Inovio vaccine, INI-4800 (a DNA vaccine that is delivered through pores in the skin), is in phase I trials, while the Pfizer/BioNTech BNT162 vaccines (following Moderna with four different mRNA vaccines) are currently in a compressed phase I and II trial in Germany. Johnson and Johnson and Merck also have vaccines in preliminary trials.
To speed development of an effective vaccine, several contenders have been selected by the federal government to be developed in parallel as part of the accelerated program dubbed Operation Warp Speed. By design, each vaccine in this program utilizes a different mechanism of action.
Phase I vaccine trials typically involve 45 healthy volunteers receiving different doses to evaluate immune response (eg, antibody levels) and safety, while specifically looking for adverse events (AEs) over 52 weeks. Phase II trials typically enroll 400 to 800 healthy patients, again, commonly utilizing different doses. Phase III trials expand age groups; include patients with stable, chronic diseases; and usually study no more than two doses. Phase 3 trials also examine AEs and antibody response, but for the first time in the process they also examine the response to accidental, real-world exposure to the organism—in this case SARS-CoV-2.
Because of the time frames typically needed to complete phases 1 to 3, vaccine development historically has taken more than five years—a luxury we simply do not have with COVID-19. Each of the current vaccine trials has been compressed, in potentially significant ways, to allow for rapid development. Normally, data are examined in every conceivable way over a lengthy observation period prior to beginning the next phase of the trial. In the COVID-19 trials, the time allotted for evaluation of safety is being compressed, and while data are being studied, the next phase protocol has been designed and—at times—implemented on the heels of completion of the previous phase. Admittedly, this condensed methodology leaves open the possibility that we may administer large quantities of a vaccine before latent safety concerns are fully teased out.
Volunteers enrolling in a COVID-19 vaccine trial likely would not be able to enroll in multiple COVID-19 vaccine trials, but they would still be eligible for subsequent vaccination with an FDA-approved vaccine.
Now that volunteers are being recruited, would you volunteer for such a clinical trial? Knowing that healthcare workers will likely be the first to be offered the final FDA-approved vaccines, and perhaps even mandated to receive them, would this alter your thinking?
- Mullard A. COVID-19 vaccine development pipeline gears up. Lancet. 2020;395:1751-1752.