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The Intellectual
Tracking the safety of vaccines is not only the job of pharmaceutical companies, but also the responsibility of government regulators | Source: pixabay.com
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Recently, the issue of adverse events from COVID-19 vaccination has attracted great attention. Although the inactivated vaccine widely used in China has not reported serious adverse reactions, the mRNA vaccine myocarditis used abroad and the rare thrombotic adverse reactions of the adenovirus vaccine have been discovered through post-marketing pharmacovigilance and independent vaccine safety tracking systems. , the incidence data of relevant serious adverse reactions were also obtained in subsequent studies.
How to confirm the causal relationship between health problems after vaccination and vaccination is the key. In past experience, most serious adverse reactions to vaccines and -coupled events can be confirmed through incidence and pathological analysis. Even if serious adverse reactions are detected, it does not mean that we should discard the vaccine due to choking. This article reviews the cases of adverse reactions of the new crown vaccine that have been launched, and sorts out the safety tracking of the current vaccine before clinical trials, human clinical trials and post-marketing. The method, combined with landmark events in the history of vaccines, attempts to illustrate that the risks of vaccination are controllable and that the monitoring system for serious adverse reactions is sufficient to ensure the safety of the vaccine. Vaccines are the most advantageous tool known to mankind against infectious diseases, and vaccine hesitancy is an important threat to public health security.
Written by Zhou Yebin
Editor | Liu Chu
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Since the launch of the new coronavirus vaccine, in addition to effectiveness, safety is also a topic of great concern to the public. For example, there are multiple vaccines with different development routes on the market. Some people will ask whether a certain vaccine has fewer side effects? And when an article forwarded by a circle of friends says that someone developed a certain disease or even died after receiving a certain vaccine, many people will also ask whether this means that the vaccine is unsafe and can induce diseases?
For vaccines, an invasive disease prevention method, how do authoritative drug regulatory authorities determine the adverse reactions of vaccines? Why do diseases appear that people think are adverse reactions, but scientists say they are just couplings? And when faced with various adverse reactions, how should vaccinators, medical institutions, governments and other parties deal with them?
1
How to study vaccine safety in clinical trials?
The safety of a vaccine is as important as its effectiveness, and even meeting safety standards before confirming its effectiveness is a basic guarantee. In the current authoritative drug regulatory system, analysis and research on vaccine safety are required throughout the entire research and development process.
Generally speaking, before a vaccine enters human clinical trials, researchers will use animal models to observe the degree of tolerance of the vaccine in animals to provide a basic guarantee for the safety of human trials. In the later stages of human clinical trials, researchers are also collecting and improving vaccine safety data at different levels.
For example, the COVID-19 vaccine is like other new drugs. The entire clinical trial is carried out in stages from the first phase clinical trial to the third phase clinical trial. Each stage has a different design to correspond to the safety information that needs to be collected most at that stage. Among them, the first phase of clinical trials is the first time that the vaccine has been applied to humans. Although there are safety data from previous animal experiments, after all, there are considerable physiological differences between humans and experimental animals such as mice and rhesus monkeys . Researchers have to consider whether the human body can tolerate the vaccine, so phase one clinical trials often need to be designed with multiple doses, from low doses to high doses, and gradually confirm that the low dose can be tolerated before starting the next dose test.
Taking the Phase I/II clinical trial of the Sinovac COVID-19 inactivated vaccine as an example, two doses of 3 micrograms and 6 micrograms were designed and tested. The researchers found that from the perspective of immune response, the antibody titer of in the 6 microgram group was higher than that of . 3 microgram group; in terms of adverse reactions, the 3 microgram group was less than the 6 microgram group [1]. Finally, based on the data on immune response and adverse reactions, the Sinovac vaccine entered phase III clinical trials at a dose of 3 micrograms and was subsequently put on the market.
For another example, Pfizer/BioNTech's new coronavirus mRNA vaccine actually designed two vaccines in the early stage [2], one is bnt162b2 with the full-length spike protein as the antigen, and the other is with the spike protein. The receptor binding domain is the antigen bnt162b1. Both vaccines have entered Phase I clinical trials. Bnt162b1, which entered human clinical trials earlier, was tested at four doses of 10 micrograms, 20 micrograms, 30 micrograms and 100 micrograms. It was found that more subjects in the 100 microgram dose group experienced adverse reactions such as high fever after the first injection, so the trial at this dose was discontinued. On this basis, another vaccine, bnt162b2, only used 10 micrograms, 20 micrograms and 30 micrograms for phase one clinical trials. After comparing the test results, it was found that the immune responses of the two vaccines bnt162b1 and bnt162b2 were similar, while bnt162b2 had fewer adverse reactions.
Based on such immune response and safety data, Pfizer/BioNTech finally selected 30 micrograms of bnt162b2 for subsequent phase III clinical trials. This is the vaccine currently being used in China, Hong Kong, Macao and Taiwan.
Observing the phase I clinical trials of Sinovac and Pfizer/BioNTech vaccines, we will find that the number of subjects in each dose group is often only a dozen or dozens, so the safety data collection at this stage is more focused on Compare different doses to confirm the approximate maximum dose that the human body can tolerate. More detailed safety data, such as the types and incidence of common adverse reactions, need to be determined through larger phase III clinical trials with more people.
Most of the Phase III clinical trials of the new coronavirus vaccine currently on the market have recruited a large number of subjects, not only to clarify the effectiveness by comparing the new coronavirus infection rate between the vaccination group and the placebo group, but also to obtain sufficient amount of safety data.
For example, Sinopharm Group’s two inactivated vaccines, Beijing Biotech and Wuhan Biotech, both conducted phase III clinical trials in the United Arab Emirates. A total of more than 46,000 volunteers were recruited, and the number of participants in both vaccine groups exceeded 13,000. In the end, The safety data collected for each vaccine also exceeds 13,400 people [3] :
Figure 1 The number and grouping of Sinopharm inactivated vaccine Phase III clinical trials in the United Arab Emirates | Picture source [3]
It is precisely because Only with enough volunteers participating can we have a complete understanding of the common adverse effects of vaccines. For example, judging from the safety data of phase III clinical trials, most of the adverse reactions classified by the two Sinopharm inactivated vaccines are relatively mild. In fact, the incidence rate is similar to that of the placebo group using only aluminum adjuvant:
Figure 2 Sinopharm The incidence of adverse reactions in phase III clinical trials of vaccines | Picture source [3]
In fact, it is not just about simply recruiting more people and gradually selecting doses. In order to better clarify the safety of the vaccine, clinical trials The tracking analysis of adverse reactions also considers many of the following aspects.
For example, from the perspective of vaccine principles, adverse reactions such as fever are natural reactions that are foreseeable after the human immune system is stimulated. In contrast to immunogenicity such as antibody titers, which reflect the strength of the immune response, this type of Adverse reactions are "reactogenic".Therefore, during research and development, adverse reactions such as fever that are foreseeable or worthy of special attention will be directly asked to subjects through questionnaires and other forms, which is called "solicited adverse reactions" (solicited adverse reactions). This kind of proactive inquiry can more accurately record the specific circumstances of adverse reactions.
Another question that many people are concerned about is, what is the time dimension for tracking vaccine safety? Should the follow-up be one month or one year after vaccination?
From the perspective of the principle of vaccines, vaccination stimulates the body's immune response, and the time for the body to form an immune response is regular. For example, we can observe antibody formation one to two weeks after vaccination.
Therefore, if the vaccine causes an abnormal immune response, it will follow the same timing pattern, that is, symptoms will appear some time after vaccination rather than many years later. According to the accumulated research and development experience of various vaccines, adverse reactions mainly occur within two months after vaccination.
Therefore, like the emergency use authorization of the new crown vaccine, the safety data standard of the U.S. Food and Drug Administration (FDA) is that the median follow-up time of phase III clinical trials is at least two months, which is half a year longer than the half year it takes for a general vaccine to be officially authorized. The tracking time is shorter, but it still provides more than two months of tracking guarantee in terms of security. [4].
2
The safety of the vaccine will be tracked after it is launched.
Although the clinical trials of vaccines have provided a large amount of safety data, even in large-scale phase III clinical trials, only 10,000 to 20,000 volunteers are actually vaccinated.
html The clinical trial safety data of 10,000 people is very sufficient for monitoring common adverse reactions, and it can be used to observe rare adverse reactions of drugs - those adverse reactions with an incidence rate of less than 1 in 1,000 [5], but it will be stretched.
The difficulty in monitoring rare adverse reactions in clinical trials is reflected in two aspects. The first aspect is that when the incidence of adverse reactions is too low, it may not be observed at all among 10,000 to 20,000 vaccinated people. For example, the new coronavirus mRNA vaccine can cause myocarditis in extremely rare cases. However, because the incidence rate is too low, neither Pfizer/BioNTech nor Moderna (Moderna) has been found in the clinical trials of the two vaccines. [6-7].
The second aspect is that even if rare adverse reactions are monitored in clinical trials, because there are so few cases, it is often impossible to judge whether they occur by chance or are actually caused by vaccination. For example, in the clinical trial of Johnson & Johnson's adenovirus COVID-19 vaccine, an adverse reaction [8] accompanied by decreased platelets thrombosis actually occurred. However, since there is only one reported case, it belongs to the general category of thrombosis. As for the adverse reactions of thrombosis, many cases occurred in both the vaccine group and the placebo group, and the overall incidence rate is also within the range of the natural background. Therefore, the researchers cannot clearly infer that this case of thrombotic adverse reactions accompanied by a decrease in platelets was caused by the vaccine.
But now, we have made it clear that the new coronavirus mRNA vaccine may cause myocarditis. Johnson & Johnson and Oxford University / AstraZeneca The two adenovirus new coronavirus vaccines may cause blood clots accompanied by a decrease in platelets.
There are also research data on the incidence rates of these two adverse reactions, myocarditis and severe thrombosis, in different age groups and genders, and these are all completed through safety tracking after the vaccine is launched.
The tracking of vaccine safety after marketing, including the monitoring of rare adverse reactions, is jointly completed by government regulatory authorities , vaccine developers and other parties. It includes multiple different monitoring systems that operate independently and assist each other.
From the perspective of vaccine developers, pharmaceutical companies need to do drug safety vigilance for marketed vaccines, just like other drugs, which means constantly collecting various reports related to drug safety. How to implement drug safety vigilance is not decided after the vaccine is launched, but is established in consultation with the drug regulatory structure during the marketing review process. For example, which adverse events require special attention, and how frequently relevant data should be reported to drug regulatory agencies, all of which need to be established before a vaccine is put on the market.
An example of the drug safety vigilance work carried out by pharmaceutical companies after the COVID-19 vaccine is launched: the "Pfizer document" that some anti-vaccine organizations loudly claimed some time ago. In fact, these documents are exactly the data collected by Pfizer during the drug safety vigilance work done by Pfizer/BioNTech’s mRNA COVID-19 vaccine after it was launched. The content includes a summary of various adverse events after vaccination, but does not show any adverse events beyond the natural background, which means that the vaccine is safe and no new rare adverse reactions have appeared after marketing. [9].
Tracking the safety of vaccines is not only the job of pharmaceutical companies, but also government regulators. Taking the United States as an example, the FDA will supervise the drug safety vigilance work of pharmaceutical companies. At the same time, the U.S. Centers for Disease Control and Prevention (CDC) also has multiple independent vaccine safety tracking systems.
The first type is a passive tracking system, represented by the Vaccine Adverse Reaction Reporting System (VAERS) established in cooperation with the FDA and CDC. The so-called passive tracking means that the system passively receives any adverse event reports related to the vaccine. Anyone can report any health problem that occurs after vaccination to VAERS [10]. The advantage of VAERS lies in its wide scope. Whether it is a reporter or an incident, the system itself has no restrictions, which is equivalent to casting a wide net. Of course, since it is completely unrestricted, VAERS data requires more sorting and verification before we can draw reliable conclusions.
The passive tracking system can easily achieve wide coverage, but due to limitations of human behavior, the reporting rate of adverse events may be low or high.
Therefore, CDC has also established another type of active tracking system, represented by the Vaccine Safety Data Link (VSD) . VSD was established by multiple hospitals and medical systems in the United States in cooperation with the CDC. It uses electronic medical records to proactively analyze the safety of each vaccine [11]. For example, we want to know whether the risk of myocarditis increases after mRNA vaccination. VSD can capture vaccination and myocarditis diagnosis information based on the electronic medical files in the system to analyze whether there is a difference in the risk of myocarditis between vaccinated and unvaccinated people. , if so, in what time period after vaccination there is a difference.
Limited by the actual number of people served by the participating medical systems, the population base of active monitoring systems such as VSD cannot be compared with VAERS. However, since the data is based on electronic medical records rather than individual subjective reports, the data quality is higher and is also suitable for some "hypothetical" research. For example, if there are multiple vaccines from different manufacturers circulating at the same time, researchers can easily use VSD to compare whether there is any difference in the incidence of certain adverse events between the two.
VAERS and VSD focus more on serious adverse reactions. For relatively minor adverse reactions such as fever and headache, most people may not think of submitting a report to VAERS, and they will naturally not enter the VSD system without going to the hospital for medical treatment.
In order to more comprehensively monitor the safety of the new crown vaccine, CDC has also established a V-safe system [12].V-safe asks the vaccinator about his or her physical condition through mobile phone text messages after registration, such as whether there are any adverse reactions such as fever, their severity, whether they affect daily life, whether they need medical treatment, etc.
In the practice of tracking the safety of COVID-19 vaccines, the United States mainly collects common adverse reaction data through the V-safe system as a verification of the incidence of adverse reactions in clinical trials. The pharmaceutical company's own drug safety alert provides the safety of a single vaccine. Tracking, the latter, together with VAERS and VSD, serve as mutual references to jointly assist in the discovery and identification of rare serious adverse reactions.
The safety tracking of vaccines after they are launched is also internationally coordinated. Like the drug safety alert work of pharmaceutical companies, the data collected is not limited to a certain country and region, but covers all countries and regions where the vaccine is marketed and used. Vaccine safety tracking and monitoring in different countries will also exchange information.
Such international communication and collaboration are necessary. In tracking the safety of the COVID-19 vaccine, Europe was the first to discover that the AstraZeneca/Oxford University adenovirus vaccine may have a very rare thrombotic adverse reaction accompanied by a decrease in platelets due to its early widespread use of the AstraZeneca/Oxford University adenovirus vaccine. The timely announcement and sharing of this information prompted the United States to pay more attention to the Johnson & Johnson vaccine, which is also an adenovirus vaccine. It was relatively earlier confirmed that the Johnson & Johnson adenovirus vaccine also had similar rare adverse reactions [13] .
In addition, the safety tracking after the vaccine is launched not only aims to find rare adverse reactions that are difficult to confirm in the clinical trial stage, but also monitors the quality of vaccine production throughout the cycle. For example, in the drug safety alert of pharmaceutical companies, the focus is not only on whether adverse reactions occur after vaccination, but also on various production quality-related issues, such as packaging damage.
The most well-known vaccine production quality accident in history is the Cutter vaccine incident in the United States. (Cutter incident)[14]. In 1955, a batch of inactivated polio vaccines manufactured by the pharmaceutical company Cutter Laboratories failed to be inactivated due to production quality problems (that is, the vaccine actually contained live poliovirus). The incident eventually led to approximately 200 children suffered varying degrees of paralysis and 10 died. It was the Keter vaccine incident that prompted the establishment of a series of vaccine safety monitoring systems such as VAERS.
3
From adverse events to adverse reactions, how to identify coupling
As can be seen from the above, analysis and research on vaccine safety continues from clinical trials to continuous post-marketing tracking, and rare adverse reactions often rely more on post-marketing tracking to identify.
Unlike clinical trials that have an unvaccinated placebo group for control, post-marketing vaccine "side effect" reports are limited to vaccinated people. How can we confirm that an adverse reaction is due to vaccination and does not just happen to occur in the post-vaccination period?
Recently, some groups who contracted leukemia after receiving the new crown vaccine have continued to speak out, causing many people to suspect that leukemia is a very serious adverse reaction after vaccination. To this, the chief expert of the immunization program of the China Centers for Disease Control and Prevention gave the answer: , which requires a comprehensive and professional complex judgment process [15] . Why is this?
First, we distinguish two concepts: vaccination adverse events and adverse reactions . Adverse events after vaccination refer to any health problems that occur after vaccination. Adverse events only need to have a temporal relationship with vaccination, and do not need to have a clear cause-and-effect relationship.
Vaccination adverse events are the basis for vaccine safety tracking. Whether it is drug safety alerts of pharmaceutical companies or government vaccine safety tracking systems such as VAERS, all adverse events are collected.
Since there is only one time sequence with vaccination, adverse events will include the following three categories: the first category is causally related to the vaccine, which is also called adverse reactions, that is, side effects; the second category is those that occur accidentally during vaccination Finally, there is no causal connection, which is the so-called coupling event; the last category is those events for which we cannot yet judge the causal connection and can neither confirm nor rule out.
It is not difficult to see that From adverse events to adverse reactions, the key is to determine the causal relationship. But how to analyze the possibility of causality without a placebo group to provide a control?
Taking the rare thrombotic adverse reactions of foreign new coronavirus adenovirus vaccines as an example, researchers generally analyze the causal relationship with vaccination from the two perspectives of the difference between the incidence of adverse events and the "natural background" and the mechanism of adverse events.
Abnormal thrombotic events that occurred after vaccination with the new coronavirus adenovirus vaccine. The initial reports focused on a case of cerebral thrombosis (cerebral venous sinus thrombosis, CVST). CVST itself is a relatively rare thrombosis, and more abnormal It is these cases that occur after vaccination that are accompanied by a decrease in platelets. Therefore, CVST accompanied by thrombocytopenia is very rare under normal circumstances.
Comparing the groups vaccinated by different routes, in April 2021, no such cases were reported after more than 97 million doses of Pfizer/BioNTech vaccine, and there were only 3 cases of CVST after more than 84 million doses of Moderna vaccine, none of which were reported. Platelets decreased, and only 6.86 million doses of the Johnson & Johnson adenovirus vaccine were administered, but 6 cases of CVST accompanied by platelet decreases occurred [16].
Such a huge difference in incidence rates obviously points to the fact that in extremely rare cases, adenovirus COVID-19 vaccination may cause thrombosis accompanied by a decrease in platelets, and the location of thrombosis is also specific, with CVST being the most common. Therefore, this type of blood clot is no longer just an adverse event with unknown causal link after vaccination, but an extremely rare adverse reaction.
Supporting this causal association is also the study of the pathogenic mechanism of this adverse reaction. Some studies [17] found that the mechanism of thrombosis accompanied by thrombocytopenia caused by adenovirus vaccine is similar to heparin-induced thrombocytopenia. Patients who develop this type of thrombosis have autoimmune antibodies against platelet factor IV, which causes platelets to be activated (thrombus formation) and at the same time cleared by immune cells (platelets decrease as a result).
That is, in extremely rare cases, about one in a million, adenovirus vaccine recipients induce an autoimmune reaction after vaccination, resulting in blood clots accompanied by a decrease in platelets. Combined with the above-normal incidence rate, the study further confirmed that blood clots accompanied by a decrease in platelets is indeed a rare adverse reaction of the new coronavirus adenovirus vaccine.
Through incidence and pathological analysis, we can also rule out the causal relationship between many adverse events and vaccines. For example, some news reports on death cases after vaccination with a certain vaccine. Such reports can easily mislead the public into thinking that the direct cause of death in this case is vaccination.
Take Hong Kong’s COVID-19 vaccine adverse event tracking as an example. From May 2 to May 15, 2022, a total of 3 adverse events occurred within 14 days after receiving the COVID-19 vaccine. However, compared with 2019 before the outbreak of the new coronavirus, during the same time period, there were 132 coronary heart disease deaths and 252 heart disease deaths [18] among adults over 30 years old in Hong Kong.After analysis, the Hong Kong Vaccine Expert Group concluded that in March 2022, there were 17 deaths after vaccination in Hong Kong (11 cases received the Sinovac vaccine and 6 cases received the Compitax vaccine), and there were no any There is evidence that the death cases are related to the vaccine, and 6 of them have been directly excluded from the vaccine based on clinical information and autopsy.
Return to the incident that attracted attention and was diagnosed with leukemia after receiving the new crown vaccine. Leukemia is a blood tumor . The pathogenic mechanism behind it involves genetic mutations in different white blood cells, causing the cells to become cancerous, and this process sometimes even takes several years. And vaccinations—including the various COVID-19 vaccines—do not alter genes. For example, inactivated vaccines do not enter the nucleus of human cells where genetic information is stored. From a mechanism point of view, leukemia is unlikely to be an adverse reaction caused by vaccination, and it is even less likely to cause genetic mutations within a short period of time after vaccination, forming cancer .
Looking at the incidence rate of leukemia, more than 80,000 new cases of various leukemias are diagnosed in China every year [19]. The vast majority of Chinese people have completed the COVID-19 vaccination in the past year and a half. With almost all the people vaccinated with the COVID-19 inactivated vaccine, there will not be a few confirmed cases of leukemia that appear shortly after vaccination.
Of course, if the disease control department can publish more data collected from vaccine adverse event tracking and respond more clearly to public concerns, it should help eliminate some unnecessary doubts.
4
How to weigh the pros and cons in the face of adverse reactions
Although we hope that the vaccine will be as safe as possible, and it is best that there will be no extremely rare adverse reactions, but for the extremely complex human body, the possibility of a vaccine having rare serious adverse reactions can be completely ruled out Not yet realistic. Considering that vaccination itself is to deal with various more serious diseases and is currently the most beneficial tool for mankind to maintain public health security, what we need to do should not be to stop eating due to choking, abandon vaccines to avoid rare adverse reactions, or Is it to give up more effective vaccines in pursuit of "more comfortable" vaccination? Instead, we should comprehensively analyze the pros and cons and find ways to improve the identification and treatment of adverse reactions.
Some rare and serious adverse reactions can be managed safely. For example: Soon after the new coronavirus mRNA vaccine was launched, there were cases of anaphylactic shock after vaccination. This was because these recipients were severely allergic to the components of the vaccine. Existing research data shows that the incidence of anaphylactic shock caused by the mRNA vaccine is about 5 per million, which is extremely rare [20]. We often hear about pollen allergy, dust mite allergy, seafood allergy, peanut allergy, etc. In fact, people may be allergic to anything, so we cannot guarantee that no one will be allergic to the ingredients of a drug. reaction, but some scientific solutions can be adopted.
Anaphylactic shock that occurs after mRNA vaccination can be safely dealt with through relatively simple precautions: allergic reactions after vaccination are often acute, most of which occur within 15 minutes after vaccination, and can be treated by injecting into the adrenal gland Element rescue. Therefore, by requiring the vaccinator to observe the vaccine at the vaccination site for 15-30 minutes after vaccination, and at the same time providing injectable epinephrine at the vaccination site, this serious adverse reaction can be effectively dealt with.
For other serious adverse reactions, the vaccination strategy can also be adjusted based on the pros and cons analysis to minimize the risk. For example, among the two types of new coronavirus vaccines currently used in European and American countries, the adenovirus vaccine has a rare adverse reaction of thrombosis, and the mRNA vaccine has a rare adverse reaction of myocarditis, but the risks of the two adverse reactions are different.
Among them, the adenovirus vaccine is associated with platelet decline and thrombosis. Although the incidence rate is about one in a million among all vaccine recipients, the incidence rate in women aged 30-50 is one in 100,000, and death after the occurrence is The rate is as high as 20% [21].
The risk of myocarditis from the mRNA vaccine is highest among men aged 18-24 after the second dose, reaching four cases per 100,000 shots. However, most of this type of myocarditis is mild and poses little threat to the health of the recipients. And by extending the interval between the first two shots, the risk can be further reduced [22] . Therefore, the new coronavirus vaccination in European and American countries is currently focusing on mRNA vaccines, and adenovirus vaccine is an alternative for people who cannot receive the mRNA vaccine (such as those who are severely allergic to the mRNA vaccine).
The adverse reaction tracking results of past vaccines will also promote future research on vaccine safety. In the process of tracking vaccine adverse events, if we do not focus on the key points and wait until the incidence rate of any adverse event is significantly higher than the natural background before analyzing whether it is causally related to the vaccine, it is likely to delay some rare adverse events. Reactions are detected, resulting in more affected vaccine recipients.
Therefore, when tracking actual vaccine safety, researchers will develop a list of key concerns based on the mechanism of action of the specific vaccine and potential adverse reactions encountered in previous vaccine development. Once these key adverse events are tracked, targeted case studies can be conducted immediately to analyze whether they are related to the vaccine and to identify safety issues as early as possible.
For example, during the development of the new coronavirus vaccine, the AstraZeneca/Oxford University vaccine was suspended due to a case of transverse myelitis that emerged in clinical trials. Why was the trial suspended due to this adverse event? The reason is that as an inflammation of the nervous system, transverse myelitis has a "record" in the safety tracking of some vaccines in the past.[25]. Therefore, transverse myelitis is an adverse event that requires special attention in terms of vaccine safety. When only one case occurs in a clinical trial involving tens of thousands of subjects, researchers need to focus on analysis and research to confirm that there is no problem with the vaccine.
A more open and honest analysis and response to vaccine adverse reactions will help us select better and more suitable vaccines. In fact, when applying for emergency use authorization of the new crown vaccine from the World Health Organization in 2021, China's inactivated vaccines, including Sinovac and Sinopharm, all proposed complete post-marketing safety tracking plans.
For example, the safety tracking plan proposed by Sinopharm to the World Health Organization in April 2021 mentioned that in addition to using China's adverse drug event reporting system, it will also establish active tracking and more than 100,000 cases of elderly people over 60 years old. Passive safety report of 1 million people [26] :
Figure 3 Vaccine tracking plan provided by Sinopharm to the World Health Organization
If these vaccine safety tracking data can be fed back to the public in a timely manner, vaccine hesitancy may be reduced and accelerated China's COVID-19 vaccination process protects more people from the impact of the COVID-19 epidemic.
Note: This article only represents my personal views and does not represent any company or organization.
"Intellectuals" columnist
has a Ph.D. from the University of Alabama at Birmingham. He is currently working in a pharmaceutical company engaged in the research and development of new drugs. He writes about popular science in his spare time. His WeChat public account is: a science popularization park for biological dogs.
Zhou Yebin
Reference:
(swipe up and down to browse)
1. https://www.thelancet.com/article/S1473-3099(20)30843-4/fulltext
2.https://www.nejm.org/doi /full/10.1056/NEJMoa2027906
3.https://jamanetwork.com/journals/jama/fullarticle/2780562
4.https://www.fda.gov/media/142749/download
5.https://www.imedpub.com/articles /rare-adverse-events-establishing-causality.php?aid=19174
6.https://www.nejm.org/doi/full/10.1056/nejmoa2034577
7.https://www.nejm.org/doi/full/10.1056 /nejmoa2035389
8. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04/02-COVID-Janssen-508.pdf
9. https://healthfeedback.org/claimreview/pfizers-confidential -document-shows-adverse-events-reported-following-vaccination-it-doesnt-demonstrate-vaccine-caused-events-or-is-unsafe/
10.https://www.cdc.gov/coronavirus/2019-ncov /vaccines/safety/vaers.html
11.https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/index.html
12.https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety /vsafe.html
13.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04/01-COVID-Bell-508.pdf
14.https://www.ncbi.nlm.nih .gov/pmc/articles/PMC1383764/
15.https://www.chinanews.com.cn/sh/2022/05-27/9765213.shtml
16.https://www.cdc.gov/vaccines/acip/meetings /downloads/slides-2021-04-23/03-COVID-Shimabukuro-508.pdf
17.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-04-23/02-COVID -Strieff-508.pdf
18.https://www.covidvaccine.gov.hk/en/dashboard/safety/aefi
19.https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact -sheets.pdf
20.https://jamanetwork.com/journals/jama/fullarticle/2776557
21.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-12-16/02-COVID -See-508.pdf
22.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/11-COVID-Moulia-508.pdf
23.https://www.ncbi .nlm.nih.gov/pmc/articles/PMC533948/
24.https://www.cdc.gov/vaccines/vpd/polio/public/index.html
25.https://www.imrpress.com/journal/FBL /9/2/10.2741/1351
26.https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/2_sage29apr2021_critical-evidence_sinopharm.pdf
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