1.5 Field tests

To determine if a vaccine is truly effective it has to protect people from the naturally occurring infection in a phase-3 trial. The incidence of infection in vaccinated and non-vaccinated people is compared, to see what level of protection is given by the vaccine.

The studies are designed to be double-blind, meaning that neither the clinician administering the vaccine nor the recipient, know whether they have received the real vaccine or a placebo. Data is then collected over several months or years to determine the incidence of infection in the two groups. Once sufficient data has accumulated (number of infections) the coding on the treatments (vaccine or placebo) is opened to see whether there is a difference between the groups and how large the difference is.

If the prevalence of infection is low in the community, then it takes longer to see whether the vaccine is effective, because it requires sufficient infections, to obtain robust data. Ironically, when public health measures reduced the incidence of infection, it could then delay data accumulation on a phase-3 vaccine trial.

All of the approved COVID-19 vaccines have been tested in real-world trials and found to be very effective. But notice that these trials are not exactly comparable, because different trials took place at different times and in different countries where the dominant strains of the SARS-CoV2 virus have been different. For this reason, a simple comparison of ‘vaccine effectiveness’ in these trials is not straightforward.

As an example, you can see the design and outcomes of the phase-3 trial of the recombinant Oxford/AstraZeneca COVID-19 vaccine (AZD1222) at the US National Library of Medicine.

Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults