Among all domestic COVID-19 vaccines, Sinopharm and Sinovac should have the largest number of vaccinations and the largest number of authorized use countries. Regarding the effectiveness of these two vaccines, safety is the most concerned about everyone - after all, Chinese people are most likely to receive these two vaccines. In contrast, Sinopharm has done the best confidentiality work. In addition to the media having announced the overall protective effect of 793 and the protective effect of medium and severe diseases in 995, there is no news of the third phase clinical trial. However, on April 29, who spent a day specifically evaluating whether Sinopharm and Sinovac vaccine meet the emergency authorization standards of the new crown vaccine. Now the effectiveness and safety data displayed by Sinopharm at the conference have also been published on the Who website. We might as well uncover the veil for this most mysterious COVID-19 vaccine.

Don't confuse the experimental results of different purposes

Making a vaccine is not easy, and completing the effectiveness and safety verification of the vaccine is also a big project. The results of clinical trials will involve different "categories". In tracking the development of the new crown vaccine, some information content unfortunately did not explain the results of different categories clearly. The most common example is to misunderstand the positive rate of antibodies as validity. Such misunderstandings are easy to confuse the public. Who's Sinopharm Evaluation Report did a good job in this regard. The first data summary is to display the tests of different purposes and the corresponding data volumes in categories.

Look at the above figure, the three categories of clinical trial data, safety, immunogenicity and effectiveness, are clearly classified, and the corresponding number is also clearly written by young people under 60 years old and elderly people over 60 years old. Note that these are all vaccinated people, and those who receive placebo are not counted in it.

Let’s talk about immunogenicity first, which is the result of the antibody conversion rate and neutralizing antibody titer that we often see. This is to examine whether the vaccine causes an immune response in the human body and how strong the immune response is. It should be noted that for a vaccine, good immunogenicity, such as 100 antibody conversion rate and high antibody titer inducing high antibody titers, are necessary conditions for the effectiveness of the vaccine, rather than sufficient conditions. That is to say, a vaccine that cannot even activate an immune response will definitely be out of the way. But based on the immune response alone, we cannot directly infer that the vaccine must be effective. In addition, it should be noted that immunogenicity is generally measured in the laboratory using blood samples of healthy volunteers. Therefore, people involved are relatively small and often do not have underlying diseases. For example, Sinopharm has only immunogenic data of 2,890 people in total, and 289 people over 60 years old.

If the immunogenicity is the smallest, then the largest number of people is generally safety. Even from the same Phase III clinical trial, the number of safety data involved will be higher than the effectiveness. Why? Because the effectiveness of the vaccine mainly starts from two weeks after the second dose, and safety starts after the injection. There are orders of volunteers who come in the group and come late, and may not be placed in the group that calculates effectiveness when analyzing the data, which naturally leads to more safety data than validity.

But this is also beneficial. After all, the most basic thing for a vaccine is to be safe, and more data in this regard is better. How many people have the safety data of Sinopharm? 16,671 people, the total number of people is OK. After all, for Oderna's Phase III clinical trial, half of which are vaccinated, and only about 15,000 data. But unfortunately, there are only 546 elderly people, which is very small.

How many people are used to analyze the effectiveness? There are 13,765 people, and there are only 209 elderly people over 60 years old. Note that the effectiveness of the analysis here refers to how much the risk of infection the vaccine really reduces. This is the effectiveness we care about. Don’t be confused by data such as the rate of positive conversion of antibodies to some people.

How effective is Sinopharm?

Sinopharm actually has two different vaccines, one is Sinopharm Beijing and the other is Sinopharm Wuhan. The effectiveness and safety of different vaccines must be evaluated separately. The effectiveness reported in the media before is 793 in Sinopharm Beijing and 725 in Sinopharm Wuhan. Then the protective efficacy of medium and severe diseases is 995 and 100 respectively.

Who evaluated this time only Sinopharm Beijing. The effectiveness data came from the Phase III clinical trial with clinical trial registration number viv-02nct04510207. The trial points include the UAE, Bahrain, Egypt and Jordan. The total enrollment is 45,000. But it should be noted that this trial includes Sinopharm Beijing and Sinopharm Wuhan. Who should only evaluate Sinopharm Beijing data.

What is the result of Sinopharm in Beijing? The following table is clear.

As mentioned earlier, there were 13,765 people vaccinated, corresponding to the same number of placebo groups. These people have been tracked for an average of 112 days. If you look at all confirmed cases of COVID-19, there were 21 cases in the vaccine group and 95 cases in the placebo group. The effectiveness was calculated to be 781, and the confidence interval was 649-863.

The confidence interval is mentioned slightly in previous articles. Since this is really important but overlooked by various vaccine effectiveness reports, I will say it again. Sinopharm conducted this trial this time with the effectiveness of 781. Is this effective performance repeated? Will it be this number if it is done again? The confidence interval can be understood as repeating countless such clinical trials, and most of the results will be within this range. For Sinopharm, it is 649 to 863. This data can tell us how reliable the effectiveness of Sinopharm 781 is.

These are all new coronavirus cases, so how effective is the protection of severe diseases? The trial was divided into two categories of severe diseases. One is hospitalized, and the other is more serious. The specific criteria are not stated. Personally, the difference is probably whether oxygen is needed. For hospitalized cases, 3 cases were given Sinopharm and 14 cases were given placebo, which corresponds to the effectiveness of 787 and the confidence interval is 26-939. From the range of the confidence interval, you can also see that the evaluation error range is very large in severe cases. For more serious cases, there are only two cases in the placebo group. It should be noted that since this is too few, the effectiveness cannot be evaluated separately, so it cannot be said that 100 protection is the most serious.

In general, the overall effectiveness of Sinopharm is still good. However, due to the trial itself, the amount of data on critical care is limited and we cannot draw too many conclusions. As for the overall effectiveness of 793 published in the media before and the effectiveness of 995 in critical care, perhaps because of the data at that time, it has been updated over time, or some people have other unique algorithms.

Is the effectiveness and safety of Sinopharm universal?

In addition to the overall effectiveness and the effectiveness of critical care, we should actually be more concerned about whether these effectiveness and safety data can be extended to all groups of people.

For example, if I have underlying diseases, is this vaccine still effective for me? Is it safe? If I am old, can this vaccine still be used?

This is also why many vaccines emphasize that the recruitment should be diverse in phase 3 clinical trials. You should know that the most dangerous thing after infection with the new crown is the elderly and people with underlying diseases. These people are involved in clinical trials and obtain relevant effectiveness and safety data are very important.

At this point, the results of the Phase III clinical trial released by Sinovac in Brazil have great flaws. There are only more than 400 elderly people over 60 years old and cannot judge the effectiveness and safety of this age group. Of course, this is the inevitable result of Sinovac's decision to recruit medical staff to conduct the trial.

Unfortunately, Sinopharm has not improved at this point. Only 209 people over the age of 60 were vaccinated, and corresponding to the placebo group of 206 people, there was no case of COVID-19 in these 415 people, so the effectiveness of these 415 people naturally cannot be evaluated.

In terms of underlying diseases, only hypertension, diabetes and obesity are classified. Except for obesity, more than 3,000 volunteers were vaccinated, which corresponds to the effectiveness of 807, the other two underlying diseases cannot be analyzed because of the small number of people.

Overall, the current clinical trial data cannot show that Sinopharm is safe and effective among the elderly and patients with underlying diseases. What is more surprising is that among the volunteers of Sinopharm enrollment, women account for only about 15. Although the customs in the Middle East may be a major resistance to recruiting female subjects, it is really necessary to consider other places to conduct trials to remedy this. We shouldn’t just develop vaccines for a group of young men, right?

Other data and unfinished events

In clinical trials, Sinopharm's safety is still good. Although who did not describe this list in detail, it also provides some summary. For example, common adverse reactions are relatively mild, mainly pain at the injection point, headache and fatigue. The total number of serious adverse reactions is not significantly different between the vaccine group and the placebo group.

However, after all, the number of people enrolled in Sinopharm is less elderly and patients with underlying diseases, and these shortcomings greatly limit the practical significance of the label of "good safety".

Sinopharm is also trying to make up for it through other studies. For example, in China, elderly people over 60 have received 1.1 million doses of Sinopharm vaccine, and 45 cases are considered to be related to vaccines. According to this data, the safety of elderly people over 60 is still good. However, it should be noted that this kind of post-market tracking is greatly affected by the improvement of the local drug safety tracking system. If it is passively dependent on the method of reporting by the vaccinator, it is easy to miss the report. There are not many details in the who file. Out of the attitude of being responsible to the vaccinator, Sinopharm needs to disclose such research in more detail.

In addition, according to data collected from a post-market COVID-19 cases in Bahrain, Sinopharm has 91 validity at over 60 years old, similar to the value of 90 for all adults from the same data source. However, the number of people in this study is very small and there are not many details. It is only said that it is the PCR test result in the Bahrain National Health System in the same period. There are less than 8,000 adults, but more than 2,400 positive COVID-19 cases. Such a high positive test rate really makes people doubt its data screening process. There are less than 800 elderly people over 60 years old.

When calculating the effectiveness of a vaccine using such real-world test reports, it is necessary to consider whether there is a possibility that vaccinated people will have fewer tests. Even if a vaccinated person is infected and has symptoms, he may feel that he cannot get the new crown and will not do the test. Therefore, this type of research requires very detailed data selection criteria, and often requires a large amount of original data. Who only publishes this table, which can be said to be unconvincing.

In addition to the elderly and the lack of data on patients with underlying diseases, we do not know whether Sinopharm can still be effective for the emerging mutant virus strains. Who should have quoted the results of Sinopharm and Sinovac serum neutralization experiments in previous studies, and only said that the neutralization ability of mutant strains in South Africa has decreased. This aspect is definitely needed in the future.

Some obvious evidence is missing. Who specifically summarized a slide, including how protective Sinopharm is for critical illness, how long is the protection time, whether it is safe for pregnant women, and whether it is safe and effective for the elderly and those with underlying diseases. These are not difficult to see from our above analysis, and they are all very reasonable. In addition, it is also specifically mentioned that the current post-market safety tracking data is not enough.

Based on the existing validity and security data and the "failure" of this kind of evidence, who also gave several overall evaluations of validity and security, which is the table below.

Simply put, for people aged 18-59, there is currently sufficient evidence for the effectiveness of protecting the new crown, and the safety evidence is also OK. However, the confidence in the effectiveness of the elderly over 60 years old is relatively low. As for the safety of the elderly, the effectiveness and safety of the people with underlying diseases, it is very low. These evaluations can be said to be completely based on the existing evidence, and whether it is the place where the Chinese people feel comfortable or the uncomfortable part, they are all objective and fair.

The global COVID-19 epidemic is now severe. As a vaccine that can protect the COVID-19, Sinopharm, of course, can and should be used as an important tool for global fight against the epidemic.

However, looking back at the various publicity before this vaccine and the data that have only been barely disclosed now, it is inevitable that people will have mixed feelings. From saying that the high positive rate of 97 antibody is effective, to the emergency authorization of millions of people to be infected, so 100 people are effective, such absurd words come from the pharmaceutical company itself, which is really shameful. After it was launched, the data on the third phase of clinical trials has not been disclosed. Now, it is a serious shortage of recruitment for both the elderly and patients with underlying diseases. The 995 I mentioned earlier is also unaware of the severe protection effect.

Of course, no clinical trial can be covered in everything, and it is common for bad results to occur. But just like people can be poor but not short of ambition, pharmaceutical companies are the same. You can fail the experiment - this is also normal in the high-risk new drug research and development industry, but you cannot lose your ambition. The ambition of pharmaceutical companies is not only the courage to try, but also the courage to openly and transparently and the determination to make an objective narrative.

China's pharmaceutical industry is still very young, and there are still many areas to improve, but the premise for improvement is that we can raise the standards ourselves first. We cannot just see that we are our own children, and we can also give 100 points if we get 60 points. Fortunately, Sinopharm has arranged many follow-up trials and tracking, including Phase III clinical trials in Peru and Argentina. These may prove whether Sinopharm vaccines are effective for Brazilian mutant strains that are prevalent in South America. In addition, China has also set up safety tracking for the elderly and patients with underlying diseases - not only those who passively collect data, but also those who actively track vaccinated people, which should also solve some doubts about safety.
Chapter completed!