These have to be conducted to scientifically prove a vaccine, treatment, or medical device is safe and effective before it can be used by the population. There are three phases and sometimes four before the regulatory authority of a country gives its approval for a rollout of the vaccine, treatment, or device.
This entry refers to a vaccine to illustrate the phases of clinical trials but is also applicable to treatments and dvices.
Preclinical phase: The vaccine is tested in animal studies first to see if it safe (for serious adverse events) and to see if there is an immune response. If it’s successful, it will move on to human trials.
The full clinical evaluation of the vaccine in humans requires that the vaccine candidate completes each phase before moving onto the next stage along the vaccine development pathway, from Phase 1-4.
Phase I: The candidate vaccine is given to a small number, under 100 adults, to primarily evaluate its safety and to see if it generates an immune response (immunogenicity). Studies can also be done to determine the dosage.
Phase II: The vaccine is given to more volunteers usually between 200 to 400 people. With COVID-19, some trials have enrolled up to 2000 people for this phase. The vaccine is given to people with characteristics (such as the elderly, health workers, and people with comorbidities) similar to those for whom the vaccine is initially intended. Safety and immunogenicity continue to be evaluated and the optimal dose is tried on a larger group. Different populations can be enrolled in different countries to reduce costs, save time, and still collect meaningful data to be able to proceed to the next phase. Phase IIb or “proof of concept” trials are when efficacy is evaluated for the first time. This tells the researchers whether or not the vaccine has a good chance of working and is the make or break stage for many candidates with only a select, promising few moving on to the next stage.
Phase III: The vaccine is tested on several thousand people and also looks at safety and variations in, for example, ethnicity, sex, age, and those with chronic diseases. Efficacy is key at this stage. With a COVID-19 vaccine, the US regulatory authority is willing to accept an efficacy rate of 50% meaning that a vaccine will need to prevent or decrease the severity of the disease by at least 50%. The threshold is usually much higher to over 90%.
Volunteers are randomly assigned to receive either the vaccine or the placebo (a dummy such as saltwater which does not contain the actual vaccine). The group who got the vaccine is then compared to the control arm (placebo), or to normal rates of infection. The trials are double-blinded meaning that neither the volunteers nor the researchers know who got the real vaccine, so as to eliminate bias. These trials are multi-centered and happen across several countries. This phase is usually the last step before a manufacturer can apply to the country’s regulatory authority for a licence to produce and market its vaccine.
After approval vaccines mostly undergo Phase IV in an initial rollout of the vaccine and post-marketing surveillance to monitor for any unexpected, rare adverse events that may occur in the broader population.