Vaccination is the key to immunization planning, and it is also a sharp weapon for China to deal with a series of infectious diseases such as COVID-19.
According to the "Immunization Agenda 2030" announced by 26 institutions including the World Health Organization (WHO), the goal is to achieve 90% coverage of basic vaccines for children and adolescents by 2030, and to reduce the number of children who have not been vaccinated at all by half. The "Healthy China 2030" Planning Outline clearly stated that "the expanded national immunization program should be continued, and the vaccination rate of school-age children in the national immunization program should be maintained at a high level".
At present, 14 kinds of vaccines under China’s immunization program can prevent 15 kinds of infectious diseases, including hepatitis A, meningitis and rubella, and the coverage population is mainly children aged 0 to 6. However, there are still four kinds of vaccines recommended by WHO that are internationally recognized as cost-effective and have not been included in China’s immunization program.
What is the urgency and cost-effectiveness of these four vaccines for patients? How to set relevant evaluation standards? On the occasion of "World Immunization Week", CBN interviewed a number of clinical and immunization planning experts and gave their answers.
The dilemma of high price of PCV vaccine
The vaccines recommended by WHO but not included in China’s immunization program mainly include Hib vaccine (Haemophilus influenzae type B vaccine), HPV vaccine (human papillomavirus vaccine), PCV vaccine (streptococcus pneumoniae conjugate vaccine) and RV vaccine (rotavirus vaccine).
"Streptococcus pneumoniae (SPN) is the main pathogen of community-acquired pneumonia and invasive infection among children in China." Zeng Mei, chief physician of the Pediatric Hospital affiliated to Fudan University, said that according to multi-center research, nearly 80% of patients with invasive pneumococcal diseases are children under 5 years old. "It is urgent to vaccinate this population with streptococcus pneumoniae vaccine."
As a pediatric clinician, Zeng Mei has been concerned about the impact of Streptococcus pneumoniae on children and the related immunization planning process for many years. For example, a multi-center clinical study covering 1138 cases of invasive Streptococcus pneumoniae in children from 2012 to 2017 showed that the mortality rate of these invasive Streptococcus pneumoniae diseases was as high as 16.2%, and the proportions of meningitis, bacteremia and bacteremia caused by these diseases were 22.9%, 9.1% and 7.8 respectively.
In terms of vaccine supply, at present, there are two kinds of PCV13-valent vaccines available in China. Among them, imported vaccines are suitable for infants aged 6 weeks to 15 months, and domestic vaccines are suitable for infants and children aged 6 weeks to 5 years. PPV23(23-valent pneumococcal polysaccharide vaccine) is used for people over 2 years old who are infected with SPN and have an increased risk of IPD (invasive pneumococcal disease).
"In China, there are obvious regional differences in deaths caused by Streptococcus pneumoniae, and about 49% of deaths caused by Streptococcus pneumoniae occurred in the western region. In terms of mortality, the mortality rate in the western region is 17 per 100,000, which is about twice as high as that in other regions. " Wang Weibing, director and professor of the Department of Epidemiology, School of Public Health, Fudan University, said that the vaccination rate of PCV13 vaccine in Shanghai has reached almost 50% in recent years, and the risk of pneumonia can be reduced by about 82% after vaccination, but the vaccination rate in the western region is less than 1%.
Wang Weibing further said that from the perspective of economic burden, the price of PCV vaccine in most countries covered by Gavi (Global Alliance for Vaccine Immunization) is about US$ 3.3 per dose. The price of imported PCV13 vaccine in China is about 700 yuan per dose, which still has a certain gap. "The current price also leads to the vaccine not being cost-effective in health economics." .
It is necessary to comprehensively consider many factors such as disease, vaccine, vaccination ability and so on when vaccines are included in the immunization program. Wang Weibing told reporters that on the one hand, epidemiological evidence such as the disease burden of influenza and pneumococcal diseases in China is still insufficient. Because pneumonia, influenza and other respiratory diseases usually have similar symptoms, there are many kinds of pathogens that can cause the same disease, which makes it difficult to estimate the disease burden of vaccine-preventable diseases, and it is difficult to observe the effect after vaccination.
On the other hand, from the point of view of vaccine supply, because PCV vaccine contains many serotypes, the production process is complex and there are certain technical barriers, which leads to the vaccine supply can not meet the needs of being included in the national immunization plan. However, with the joining of Chinese manufacturers who independently research and develop PCV vaccine, it is believed that the current situation of insufficient supply will be expected to be improved.
Significance of free HPV vaccination
Since the first government-led HPV vaccine free vaccination project was launched in Erdos city three years ago, at present, Guangdong, Hainan, Jiangxi, Fujian, Tibet and Chongqing provinces have also started or announced that they will launch a global HPV vaccine free vaccination program.
According to other data, there are six kinds of HPV vaccines listed in the world, including two bivalent HPV vaccines independently developed by China (one from Wan Tai and one from watson biological). As of March 2023, 126 countries and regions have included HPV vaccine in the immunization program.
"In terms of HPV vaccination, people’s acceptance and participation enthusiasm are higher than expected. These explorations may provide important reference for the inclusion of HPV vaccine in national immunization planning decisions." Zhang Jun, deputy dean of the School of Public Health of Xiamen University and deputy director of the National Infectious Disease Diagnostic Reagents and Vaccine Engineering Technology Research Center of Xiamen University, said in an interview.
In Zhang Jun’s view, there is no doubt about the health damage caused by HPV infection in China. With the large and stable supply of high-quality domestic HPV vaccines and widely recognized by the public, the independent control of vaccine research and development and the long-term sustainability of supply have become a fact. "At present, HPV vaccines have not been included in the national immunization plan, and the main difficulty lies in the high cost and price of vaccines and the uncertainty of public acceptance."
Judging from the bidding price of Jiangsu Province’s previous procurement, the bivalent HPV vaccine in watson biological was 246 yuan/piece, and the bivalent HPV vaccine in Wan Tai was 329 yuan/piece, and three shots were inoculated in the whole process. In addition, the average price of HPV tetravalent vaccine ranges from 800 to 900 yuan per dose, and the total price of three doses of HPV nine-valent vaccine is about 4,000 yuan.
"Because the research and development cycle of HPV vaccine is generally more than 10 years, it requires high production facilities and quality control. In order to maintain a virtuous circle of market demand-R&D investment, the pricing of products should not be too low within several years of listing; This may put greater pressure on the country’s budget. " Zhang Jun analyzed the reporter.
Du Heng, senior project officer of the Beijing Representative Office of Bill and Melinda Gates Foundation, believes that enterprises will make production capacity layout and arrangement according to market demand, and naturally leave production capacity to the high-priced vaccine market and people with higher payment capacity. The key population that should be vaccinated with HPV vaccine first, that is, girls aged 9-15, can guide the production behavior of enterprises through strengthening the national immunization program and large-scale procurement.
Zhang Jun suggested that, on the one hand, a more flexible medical insurance payment mechanism could be considered. For example, formulate affordable medical insurance payment standards, where the expenses within the standards are reimbursed by medical insurance/finance, and the expenses beyond the standards are paid by individuals.
On the other hand, on the basis of bidding and purchasing with quantity, considering increasing the time factor, relatively high prices are allowed in the first few years, so that enterprises can recover their costs as soon as possible and obtain reasonable income, maintain their enthusiasm for innovation, and quickly switch to cost pricing or market competition after a certain number of years and more diversified manufacturers, so as to ensure the sustainability of immunization planning policies.
Implement a scientific and accurate evaluation standard path
Professor Tang Shenglan, co-director of the Global Health Research Center of Duke University in Kunshan and head of the Innovation Laboratory of Vaccine Delivery Research, told the reporter that there have been many mature research results on the key decision-making research and the selection of vaccine varieties for introducing immunization programs for new vaccines in the world, which generally involve three types of indicators.
The first category is indicators related to disease prevalence and burden. "For example, malaria is highly prevalent and has a high disease burden in many African countries, so it is necessary to include malaria vaccines in the immunization programs of these countries. However, malaria has been effectively controlled in China. In 2021, WHO awarded China the certification for eliminating malaria. Obviously, malaria vaccine will not be considered in the expansion of immunization programs in China. " Tang Shenglan said.
The second kind of indicators mainly focus on the vaccine itself, including its effectiveness, safety, quality, supply capacity and health and economic benefits.
The third category of indicators involves financial resources, manpower and material resources. Tang Shenglan analyzed in detail for the reporter. Financial resources mainly refer to whether China’s health financing mechanism can support the expansion decision. Generally speaking, if the budget is abundant this year, it will vigorously expand vaccination, and if the budget is tight next year, it will reduce vaccination coverage (the baby born next year will not be able to enjoy the plan). This obviously violates the principle of fairness. Manpower, every time a new vaccine is added to the immunization program, it means that the workload of vaccination increases and the number of possible vaccine adverse reactions increases; Correspondingly, the inoculation technology of new vaccines needs training, and the results of disease surveillance also need to be reported. Material resources include whether the vaccine distribution has cold chain conditions, whether the monitoring system can "expand" synchronously, and whether the media and grassroots science popularization have enough resources for public science popularization.
In the next step, what specific measures and adjustments should be made in immunization planning in various places?
Tang Shenglan suggested that, first of all, from the national level, a scientific and dynamic adjustment mechanism of immunization program catalogue can be gradually established, and based on this mechanism, the adjustment plan of national immunization program in the next 5-10 years can be defined, and the market can be shaped through this plan. At the same time, guided by health and fairness, taking into account the local disease burden, financial level and residents’ ability to pay, we will explore and support the gradual inclusion of more cost-effective vaccines in the national immunization plan in different regions, batches and steps, and include high-risk groups such as teenagers, the elderly, chronically ill patients and medical workers in the vaccination scope, so as to accelerate the realization of life-cycle vaccination.
Secondly, it is to improve the sustainable financing mechanism of vaccines, which can establish the clear expectations of relevant enterprises for the market. "Practice in some places shows that medical insurance reimbursement or moderate subsidies can effectively incite individuals to share and improve the vaccination rate without significantly increasing the financial burden." For example, Tang Shenglan, Qinhuai District of Nanjing, for example, paid about 670,000 yuan to buy varicella vaccine through finance in 2019, accounting for only 1.10% of the basic public health service expenses in the district, but it increased the coverage rate of the first vaccination by 10 percentage points.
Thirdly, improve the research and development of key vaccines through policy guidance. These policy guidance can include: optimizing vaccine review and approval standards, accelerating industrial transformation and upgrading, supporting joint vaccine research and development and production, and leaving room for optimizing immunization strategies; Support the domestic substitution of key vaccines to ensure a stable and sufficient supply of vaccines included in the immunization program.
Finally, Tang Shenglan suggested that we can learn from some innovative international procurement mechanisms to balance the risks and benefits of enterprises while adjusting vaccine prices.
"For example, in the bidding process in the UK, manufacturers are allowed to give different quotations according to different purchase quantities (often the larger the purchase quantity, the lower the price), so that economies of scale can be effectively utilized and the risks of manufacturers can be reduced. The Canadian government will require provinces or regions to estimate their demand before awarding the contract to manufacturers, and require provinces or regions to purchase at least 75% of their estimated amount, thus forming a quantitative guarantee for manufacturers. " Tang Shenglan said that China can fully learn from the experience of developed countries, start with regional pilot projects, and explore a better procurement model. While reducing the price of non-immunization vaccines, it also enhances the R&D enthusiasm of enterprises and achieves the goal of multi-win.
