By Hannah Clapham*
With COVID-19 cases still rising globally, the race is on for a vaccine. Pressures are mounting to get one available for use as soon as possible. The pandemic has brought the world to a standstill, and so it is tempting to think that the faster a vaccine is made available the better. But it is important to ensure that vaccines are safe — and that they actually work.
Vaccine hesitancy is widespread and the risk of increasing vaccine hesitancy by rolling out a vaccine without adequate testing is not a risk worth taking. The concerning knock-on effects from the vaccine roll-out of the dengue vaccine Dengvaxia in the Philippines should be taken seriously as a mindful example when it comes to the testing and use of COVID-19 vaccines.
Many diseases are vaccine preventable and the road to getting a vaccine developed and available for use is well-trodden and clear. Firstly, there is a pre-clinical phase, followed by three clinical phases of vaccine testing. Phase one and two test immunogenicity and safety, and phase three tests efficacy and safety in a larger number of people. In phase three trials, there is a vaccinated and un-vaccinated (control) group. These trials aim to determine whether rates of infection are lower in the vaccinated group compared to the unvaccinated.
Normally these trials take 3–5 years to complete with a vaccine candidate that is already developed. But with COVID-19, we have seen development through phase one and two in a matter of months, and vaccines are rapidly moving onto phase three. So it is perhaps easy to think that the next phase can happen just as quickly. But the length of follow-up in phase three trials is vital and cannot be sped up in quite the same way.
The end of phase two reveals whether a vaccine produces an immune response. But just because an immune response is produced, does not mean that a vaccine will protect against infection or disease.
Examples in Russia and China highlight the possibility of widespread use of a vaccination before phase three trials. Phase one results have been published for the vaccine developed in China and phase one and two results for the vaccine developed in Russia. But neither have started phase three trials, though there are now reports of plans for phase three trials in Philippines and mixed reports from Brazil about the possibility of phase three trials there.
Widespread use of vaccines before phase three trials is problematic for two reasons. First, without larger group testing in phase three, there may be safety issues that are yet to be determined. Individuals in phase three trials are closely monitored and there is no guarantee of this happening outside the trial setting. A recent example of this process is the stopping and restarting of the trial with the AstraZeneca vaccine in the United Kingdom after a participant had a suspected adverse reaction.
Second, it is impossible to know if a vaccine works without the control group of a phase three trial. But even with a good phase three trial, efficacy can only be determined if infection exposures are occurring. It has been reported that Vietnam bought large numbers of the Russian vaccine, hopefully to be used in a well-designed phase three trial, however with low transmission here, it may not be possible to determine vaccine efficacy.
It is also important to consider who is included in all phases of trials. In the Chinese example, members of the army, a homogenous group in terms of age and gender, are reported to have been vaccinated. This set-up means vital information will be missing on how the vaccine works in certain groups. Another reason for collecting excellent efficacy data is the need to compare and choose between multiple vaccines.
This is not to say that we cannot expedite other areas of the process. Once a vaccine has been successful in phase three trials, it needs to be manufactured and available for the people who need it. Building factories to manufacture vaccines at scale before phase three trials are complete will speed up the process, as will building frameworks to make decisions about who will be vaccinated first and how to get vaccines to these groups efficiently.
Every country is currently debating the future of COVID-19 vaccination for their country. Many countries have engaged with COVAX, the WHO initiative to ensure global equitable access to vaccines when they become available. There are many decisions to be made for each country, and well-designed trials for all vaccines will mean each country can make the necessary decisions to improve the health and wellbeing of their population, with the best possible information available.
*About the author: Hannah Clapham is Assistant Professor at the Saw Swee Hock School of Public Health, National University of Singapore.
Source: This article is part of an EAF special feature series on the novel coronavirus crisis and its impact.