Why is the new crown vaccine phase III clinical trial important?
Ask about the new crown vaccine
Our reporter Zhang Jiaxing
Why is the Phase III clinical trial important for the new crown vaccine?
Some people may think: I still need to ask this question?
!
It is important for all vaccines because they can only be marketed after phase III clinical trials.
But listing is not the goal, it is to provide safe and effective protection for human beings.
"If you know a talent for a few days, can you believe that you have a fateful relationship with him?" Recently, Zhu Fengcai, deputy director of the Jiangsu Provincial Center for Disease Control and Prevention, accepted an exclusive interview with a reporter from Science and Technology Daily. He made a vivid analogy, vaccine It's the same, it's not long after it was developed, how can you make it out without using the "Sanmai Real Fire", so as to "guarantee you to learn the sutras"?
Phase III clinical is important because its mission is to use rigorous and detailed scientific data to prove whether the vaccine is safe and effective.
A common saying can more vividly summarize the mission of Phase III clinical practice-"Lu Yao knows the strength of Miao, and sees the heart of Miao over time"!
Phase III clinical trials such as "Sanmei Real Fire"
Phase III clinical trials are mainly to evaluate the protective efficacy of vaccines.
Its "sanmai real fire" is to test vaccines with real epidemic areas, large sample sizes (tens of thousands), and two epidemic seasons.
In order to ensure a long-term test, the verification time of phase III clinical trials is relatively rigid. Generally speaking, it takes 2 to 5 years. For infectious diseases, it takes at least two epidemic seasons.
After the test of "Sanmei Real Fire", 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). Virus vaccines, etc.).
"Due to the urgency of the epidemic prevention and control of the new crown vaccine phase III, it is currently believed that the subjects will need to last for at least two months after the full immunization process. However, it is said that the current epidemic will be clear at the end of December, mainly referring to the initial results (such as It takes half of the data) time." Zhu Feng said, only in this way, the vaccine itself, the interaction between the vaccine and the human body, and the choice of clinical research methods, etc., can be found and continuously revised. , To avoid accidents in the large-scale use on the market.
The prerequisite for phase III clinical trials to be effective is "human infection"
If the preliminary effective verification of phase III preclinical vaccines is "wenxi", then it is the real "real combat" in phase III clinical trials, which is to obtain key clinical data.
Why is it said that it was "literary opera" before?
For example, in the preliminary effectiveness verification of phase II clinical trials, the effectiveness was indirectly proved by testing the concentration of neutralizing antibodies.
In preclinical tests, animal tests are used to prove the possible protection of the vaccine.
"Phase III clinical observation mainly observes the incidence of the included study population before assessing the efficacy of the vaccine." Zhu Feng explained, "Only by comparing the vaccinated population and the unvaccinated population with cases of new coronary pneumonia, can the protective efficacy of the new crown vaccine be evaluated. ."
In 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.
The phase III clinical trial endpoints reflect this.
Internationally, it is believed that 14 days after the full vaccination of the new crown vaccine, it is necessary for someone in the control group to suffer from new crown pneumonia due to the new crown virus in order 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, and the control group is 151 people infected with new coronary pneumonia as the end point; AstraZeneca is similar with the end point being 30,000 subjects and 150 people infected.
It can be seen that it is impossible to plan when the phase III clinical trial will end. It depends on the control group in the phase III clinical trial, that is, among the people who have been injected with placebo but not vaccinated, whether anyone has contracted the new coronavirus. disease.
These answers can only be given in Phase III clinical trials!
What is the protective effect of the vaccine?
This is the answer that only Phase III clinical can give.
For most virus vaccines, the protective efficacy is required to be above 75%.
For the new crown vaccine, the World Health Organization (WHO) guidelines stipulate that in randomized controlled trials, the efficacy of the vaccine 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 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?
What is the immunopathological response of the vaccine?
"Everyone is familiar with the former, that is, redness, swelling, fever, etc. that occur after injection, but as long as they are within a certain acceptable range, these often do not hinder the approval of the vaccine." Zhu Feng said that 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.
Zhu Fengcai gave a very vivid analogy to help understand the immune pathological response-"For example, a unit has a number of good soldiers and strong generals (the functional components in the vaccine are very immunogenic), but they stand and watch nothing. There are even a lot of mess (other proteins except functional ingredients). You can hardly guarantee that these people will not mess up for a long time." Zhu Fengcai said that the composition of vaccine products is more complicated. In history, even if approved Clinically, there are also cases of delisting due to safety issues.
"The research and development of the new crown vaccine is still in the first stage of solving the "whether or not". 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." Zhu Fengcai said, therefore, the development of the new crown vaccine will continue for a long time.