/ Zhang Tiankan (columnist)
editor / Ji Jingjing New media editor / Nie Shufang
photo / Visual China
As the season enters the hot summer, children have more diseases. Children's illness is not only difficult to hang up, but also to parents and medical staff with medication after diagnosis. How to divide a tablet into 1/3 or even smaller? Over the years, the situation of "dosage depends on guessing, medicine distribution depends on breaking, and lack of special medicines" for children's medicine has not been greatly improved, which has also become a major hidden danger to children's life and health.
In fact, most children's drugs , including vaccine , are used at half or reduced doses of adults, which will inevitably lead to a large number of adverse drug reactions and poor efficacy. Because children are not miniature adults, and their organs and tissues are immature, even if the dosage of adults is halved or one-third of the dosage used for adults, it involves problems such as pharmacokinetics and liver decomposition, which may cause harm to children. .
Now, this problem has also occurred with the use of vaccines in children, especially the new coronary pneumonia vaccine. At present, more than 1.9 billion people worldwide have been vaccinated against the new crown vaccine , and China has the most vaccinations, which exceeded 660 million on June 1. But these vaccinated people are all people over 18 years old, and the number of people 17 years old and younger receiving the new crown vaccine is almost zero. The reason is that at present, there is no scientific evidence whether any new crown vaccine is suitable for children and teenagers to be vaccinated.
▲my country divides vaccines into two categories: first-class vaccines are provided by the government free of charge to citizens, that is, "immunization planning vaccines"; second-class vaccines are other vaccines vaccinated by citizens at their own expense and knowingly and voluntarily. At present, school-age children in my country can receive 11 types of vaccines for free, and more vaccines are trying to be included in the free range.
The lack of scientific basis for children's medicines and vaccines is due to the fact that there are no or very few children and adolescentsvolunteersparticipationclinical trials for medicines and vaccines. Human trials are required for drug and vaccine development, but recruits volunteers for research, most of them are adults, and it is even more difficult to recruit children. Even if it has undergone strict ethical and safety audits, and has a certain therapeutic effect on children with corresponding diseases, no parents are willing to let their children participate in the experiment.
On the other hand, even if there is some evidence of clinical trials of children's drugs and vaccines, pharmaceutical companies lack the incentive to produce. Because the number of users of children's medicines is small, the batch production is less than that of adult medicines. On the other hand, the dosage of children's medicines is small, and the profit of producing children's medicines is obviously much lower than that of adult medicines, so pharmaceutical companies are reluctant to produce them. In contrast, pharmaceutical companies are more willing to produce drugs that are suitable for a wider population and have larger market sales, that is, generic drugs for adults.
Now, the emergence of the new crown epidemic has brought an opportunity to develop vaccines for children and adolescents. Considering that obtaining global herd immunity through vaccines can prevent or even defeat the new coronary pneumonia, some research institutions and pharmaceutical companies have proposed that the scope of adaptation of vaccination needs to be expanded to children and teenagers aged 12-15, and later It has to be extended to children under 12 years old in order to build an effective shield against universal immunization. The current immunization is only for people over 18 years old, and the world's new coronary pneumonia immunity chain lacks children and teenagers under 18 years old.
However, vaccination of children and adolescents is not just about reducing the dose of adults. Therefore, recently, Pfizer (Pfizer) and partner BioNTech (BioNTech) jointly announced that its new coronary pneumonia mRNA vaccine Comirnaty (BNT162b2) ) Conditional marketing authorisation and use in the EU is extended to children and adolescents aged 12-15 years and applies to all 27 EU member states.
Forbitex is the first Covid-19 vaccine to be authorized in the EU and the first to be expanded to children and adolescents. On May 10th, the Food and Drug Administration (FDA) of the United States approved the use of Fubitai in the United States for children and adolescents aged 12-15 years, a little earlier than the European Union. Previously, the FDA has granted Fubitai for active immunization in people over 16 years old.
This decision in the European Union and the United States is backed by scientific research, namely the recruitment of volunteers of the same age group for clinical trials. In the past, vaccine studies were conducted with adult volunteers, but for fobex, researchers in the European Union and the United States conducted a multi-country, placebo-controlled, double-blind trial, and it was a Phase 3 clinical trial. A total of 2,260 teenagers aged 12-15 volunteered, with parental consent of course. These subjects were randomly assigned in a 1:1 ratio to receive either fubipate (n=1131, 2 doses, 30 μg, 21 days apart) or placebo (n=1129, 2 doses, 21 days apart) . The results of the
trial were published in the international medical journal "New England Journal of Medicine" on May 27, 2021. The main results of this study showed that the vaccine was 100% effective in subjects with or without prior SARS-CoV-2 infection and generated robust antibody responses. At the same time, the children and adolescents tested also showed good tolerance to the vaccine. Following the second dose of the vaccine, these subjects will continue to receive long-term protection and safety monitoring for an additional 2 years.
In addition, in order to include Fubitux in the vaccination of children aged 6 months to 11 years old, researchers are now conducting clinical trials in this age group, and the results are expected to be confirmed in September this year. Based on the data generated, scientific evidence for 2 age groups, children 2-5 and 5-11, will be submitted for health regulators to decide whether to approve use. In addition, trial results in children aged 6 months to 2 years are expected to be submitted in the fourth quarter of 2021 for approval by health authorities.
Once these studies are approved, the COVID-19 vaccine Fubitux can be expanded to children and adolescents aged 2-15, and the scope of herd immunity can be expanded to almost all groups of people. This is the biggest strategic layout and hope for defeating the new crown pneumonia.
On the other hand, for the difficulty that children cannot obtain effective scientific evidence for the use of vaccines and drugs, corresponding measures have also been proposed at home and abroad, that is, real-world research is used to obtain clinical data.
Real-world research refers to the non-random selection of treatment measures according to the actual condition and wishes of patients in the process of real medical treatment, long-term evaluation, focusing on meaningful outcome treatment, and evaluation of medical measures (drugs) in a wide range of real medical processes. efficacy and safety of all medical procedures, including surgery and instruments). The clinical randomized double-blind controlled trial is a well-designed type of trial, and both have their own strengths. However, there are now more of my professionals who believe that real-world studies have better data than well-designed clinical randomized double-blind controlled studies.
▲In 2020, the Center for Drug Evaluation of the State Food and Drug Administration of my country issued a notice on the "Technical Guidelines for Real-World Research Supporting the Development and Evaluation of Children's Drugs (Trial)"
Due to the small number of child volunteers participating in clinical trials, real-world research It has become a better way to test medicines, vaccines and other medical treatments for children.In August 2017, the International Council for Harmonization of Technical Requirements for Medicinal Products for Human Use (ICH) issued the Supplementary Document for Clinical Research of Medical Products for Use in the Pediatric Human Population (E11(R1)), which proposes a new approach to the administration of pediatric drugs in the real world. The understanding of drug behavior and the management of corresponding risks will help in the development of safe drugs. In January 2020, the State Food and Drug Administration issued the "Guidelines for Real-World Evidence Supporting Drug Development and Review", which clearly pointed out that the use of real-world evidence is a strategy for children's drug development.
The real-world research data on children's medicines and vaccines comes from several aspects, mainly in traditional medicines and vaccines, according to the indications of the disease, the adult medicines and vaccines are calculated for the statistics of real cases in children. Therefore, it is possible to collect medicines and vaccines that are actually used by children in clinical practice, and obtain clinical evidence, including efficacy and safety, to evaluate children's conditions of a certain medicine and vaccine, so as to formulate guidelines for safe and standardized medication and vaccination.
Obviously, in order to solve the problem of "dosage depends on guessing, drug distribution depends on breaking, and lack of special drugs", children and adolescents must first participate in clinical trials to obtain scientific evidence of drug use, in order to fundamentally solve the problem of children's drug use and the lack of special drugs. The conundrum of vaccinations. In the future, by recruiting volunteers and conducting real-world research, the shortage of special medicines and vaccines for children can be gradually changed.
References
1. Dosage depends on guessing, medicine distribution depends on breaking! How to protect the child's medication dose for difficult parents? 2021-05-31, Beijing Daily client
https://news.bjd.com.cn/deep/2021/05/31/98239t115.html
2.Pfizer and BioNTech Receive First Authorization in European Union for COVID-19 Vaccine in Adolescents , May 28, 2021
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-receive-first-authorization-european
3.Robert W.Frenck et al.Safety,Immunogenicity , and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents, NEJM, May 27, 2021 To reprint
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