How and when will we know that a COVID-19 vaccine is safe and effective ?

William Petri
Contd from previous issue
How is the FDA ensuring that a vaccine will be safe yet quickly produced ?
The FDA has issued guidance for industry on the steps required for developing and ultimately licensing vaccines to prevent COVID-19 – these are the same rigorous safety standards required for all vaccines.
There are, however, ways to speed the process of approval that are centred on “platform technology.” What this means is that if a vaccine is using an approach such as an adenovirus that has previously been shown to be safe, it may be possible for a company to use previously collected data on toxicity and pharmacokinetics to fast-track clinical trial approval.
While speed and safety may appear conflicting goals, it is also encouraging to note that the rival vaccine manufacturers have jointly pledged not to bow to any political pressures to rush vaccine approval, but to maintain the most rigorous safety standards.
How protective does a vaccine need be to receive FDA approval ?
The FDA has set the bar for the primary endpoint of a phase 3 trial of 50% protection for approval of a COVID-19 vaccine.
Protection is defined as protection from symptomatic COVID-19 infection, defined as laboratory-confirmed SARS-CoV-2 infection plus symptoms such as fever or chills, cough, shortness of breath, fatigue, muscle aches, loss of taste or smell, congestion or runny nose, diarrhoea, nausea or vomiting.
This means that an effective vaccine is considered one that will reduce the number of infections in vaccine recipients by half. This is the minimal protection that is anticipated to be clinically useful. That is, in part, because lower levels of efficacy could paradoxically increase COVID-19 infections if it leads vaccinated people to decrease mask wearing or social distancing because they think they are completely protected.
Since a vaccine might be more effective at preventing severe COVID-19, the FDA instructs that protection from severe COVID-19 should be a secondary endpoint.
How many people have to be vaccinated to know if a vaccine works in Phase 3 ? The current phase 3 trials are enrolling 30,000-40,000 subjects. Most of these participants will receive the vaccine and some a placebo.
When, exactly, the results of phase 3 studies will be released depends in large part on the rate of infection in the placebo recipients. The way that these vaccine studies work is that they test if naturally acquired new coronavirus infections are lower in the group that received the vaccine compared with the group receiving the placebo.
So while it is good news that COVID-19 infections have dropped recently in the US from 70,000 to 40,000 cases per day, this drop in new infections may slow the vaccine studies.
Will emergency use authorisation fast-track vaccine? In an emergency such as we are faced with the COVID-19 pandemic, with approximately 700 new deaths and 40,000 new cases per day right now, the FDA is authorised to allow the use of unapproved products for the diagnosis, treatment and prevention of disease. That includes a vaccine.
The standard approval process for vaccines can require more than one year of observation after vaccination. If the short-term safety is good and the vaccine works to prevent COVID-19, then the vaccine should be approved for use under an emergency use authorisation while it is still being studied.
Under emergency use Authorisation, the FDA will continue to collect information from the companies producing the vaccines for benefit and harm, including surveillance for vaccine-associated enhanced respiratory disease or other potentially rare complications that might be observed in only one in a million.
What should we expect in terms of approvals?
I expect that the FDA will approve several vaccines by the end of 2020 under its emergency use authorisation authority so that vaccination can begin immediately, starting with high-risk groups including first responders, health care personnel, and the elderly and those with preexisting medical conditions.
This will be followed rapidly with roll-out of vaccination to the population at large, while all of the time the FDA and vaccine manufacturers will continue to monitor for side effects and work to improve upon these first vaccines. This process is expected to take months.
It may not be life back to normal next year, but all signs point to a healthier 2021.
William Petri is a Professor of medicine at the University of Virginia.
Courtesy The Wire