When Will the New Coronavirus Vaccine be Assured? What is Phase III Clinical Trials?

It is impossible to plan when the Phase III clinical trial will end, but to look at the control group in the phase 3 clinical trial, that is, among the people who were injected with placebo but not vaccinated, whether anyone became ill due to the new coronavirus.


Why is the Phase III clinical trial important for the new crown vaccine? It is important for all vaccines, because they can be marketed only after Phase III clinical trials.
 

But listing is not the goal, it is to provide safe and effective protection for human beings. A vivid analogy : If you have only met a person for a few days, can you believe that you have a fateful relationship with him? The same is true for vaccines. They have only been developed not long ago. If you don’t use the 'trio', how can you believe that it can really be guaranteed to learn from the experience?
 

Phase III is important because its mission is to use rigorous and detailed scientific data to prove whether the vaccine is safe and effective. Phase III clinical trials are mainly to evaluate the protective efficacy of vaccines. Its 'trio' is to use the real epidemic area, large sample size (tens of thousands), and 2 epidemic seasons to test the vaccine.
 

In order to ensure a long-term test, the verification time of Phase III clinical trials is relatively rigid. Generally speaking, it takes 2-5 years. For infectious diseases, it takes at least two epidemic seasons. After the test, many candidate vaccines will fail : human clinical trials of AIDS vaccine have failed more than 200 times, and some vaccines for respiratory infectious diseases have not been successful (such as herpes simplex vaccine, respiratory syncytial vaccine etc.).
 

Due to the urgency of the epidemic prevention and control of the third phase of the new coronavirus vaccine, it is currently believed that the subjects will need to last for at least 2 months after the full course of immunization, and the prevailing statement at the end of December mainly refers to the time required to obtain preliminary results (if done). Only by this way, the interaction between the vaccine and the human body, and the choice of clinical research methods, which may appear to be flawed, we can then have the vaccine to be discovered and then continuously revised, in order to avoid accidents before the large-scale use on the market.
 

If the preliminary effective verification of Phase III preclinical vaccines is 'warm-up', then it is the real 'actual combat' in Phase III clinical trials, which is to obtain key clinical data. Why is it said that it was 'warm-up' before? For example, in the preliminary validity verification of Phase II clinical trials, the effectiveness is indirectly proved by testing the concentration of neutralizing antibodies. In preclinical tests, animal tests are used to prove the possible protection of the vaccine.

The main observation of the phase III clinical trial is to observe the incidence of the included study population to evaluate the efficacy of the vaccine. Only by comparing the occurrence of new coronary pneumonia cases in the vaccinated population and the unvaccinated population can the protective efficacy of the new coronavirus vaccine be evaluated.
 

In the real 'actual combat', someone will inevitably be infected to prove that someone is not infected because of the vaccination, so as to prove the protective power of the vaccine.
 

This is reflected in the end point of the Phase III clinical trial. Internationally, it is believed that 14 days after the full vaccination of the new coronavirus vaccine, someone in the control group needs to have new coronary pneumonia due to infection with the new coronavirus to reach the end of the test, and the specific number of infected people is required. For example, the plan announced by Moderna in the United States shows that it needs 30,000 subjects. The end point is when 151 people in the control group are infected with new coronary pneumonia, and AstraZeneca is similar. The end point is 30,000 subjects and 150 people are infected.
 

It can be seen that when the Phase III clinical trial will end is not planned, but to look at the control group in the Phase III clinical trial, that is, among the people who were injected with placebo but not vaccinated, whether anyone became ill due to the new coronavirus .
 

What is the protective efficacy of the vaccine? This is the answer that only Phase III clinical can give.
 

For most virus vaccines, the protective effect is required to be above 75%. For the new coronavirus vaccine, WHO guidelines stipulate that in a randomized controlled trial, the vaccine efficacy must reach at least 50% (the lower limit of the confidence interval is at least 30%).
 

Perhaps for a person, the difference between protection and non-protection is 0 and 100%, but this number accumulated from the overall population is related to the probability of each person being protected. The amount and proportion of neutralizing antibodies produced in the Phase II clinical trials are only indirect evidence, and it does not answer whether the antibodies have the ability to protect the human body from virus attacks.
 

There are also questions that require long-term observation to be answered. For example, what is the acute toxicity of the vaccine, and what is the immunopathological response of the vaccine?
 

The former is familiar to everyone, that is, redness, swelling, fever, etc. that occur after injection, but as long as these are within a certain acceptable range, these often do not hinder the approval of the vaccine. Only serious adverse reactions and specific vaccine-related adverse reactions, severe cases still occur after vaccination, etc., which will influence the fate of vaccines.
 

The immune pathological response of the vaccine requires more people to be vaccinated and followed up for a longer period of time to appear, because the body's immune response is a very complicated process in the body.
 

Another vivid analogy to help understand the immune pathological response : a unit is of a number of good soldiers and strong generals (the functional components in the vaccine are very immunogenic), but they do nothing and stand and watch. It’s hard to guarantee that these people will make trouble for a long time. The composition of vaccine products is more complicated. In history, Even if it is approved for clinical use, there are cases of delisting due to safety issues.
 

The research and development of the new coronavirus vaccine is still in the first stage of solving the 'whether or not'. How its true protection will inevitably require a large population of Phase III clinical trials and a long period of 'test' before people can obtain scientific and objective answers. Therefore, the development of the new coronavirus vaccine will continue for a long time.

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