Doctoral dissertation

Monitoring the safety of vaccines in the world’s largest population

China has a total population of over 1.3 billion people and an annual birth cohort of 16 million children. Because of increasing demand for vaccines and the development of new manufacturing techniques, China now ranks among the world’s largest vaccine manufacturers, producing over one billion vaccine doses annually. Some of these vaccines are also being introduced to children in countries across Asia. As more vaccines are being introduced in immunization programs worldwide, high quality safety surveillance is critical to maintain public confidence in vaccines.

The National Surveillance System for vaccine-related adverse events is currently the sole data source available for nation-wide monitoring of the safety of vaccines manufactured and used in China. The studies in the dissertation of Wendi Wu evaluated how well this system works and used these unique data source to research important vaccine safety topics.

The development of vaccines is among the most important public health achievements. Although modern vaccines generally are safe, a small risk of adverse events exists, as is the case with any medical technology.

Licensed vaccines are considered safe, but rare adverse reactions cannot be detected in pre-licensure clinical trials because of their limited size and duration. Once vaccines are in large-scale use in the population, the main way to evaluate their safety is by conducting post-licensure surveillance and related observational epidemiology studies. An adverse event following immunization (AEFI) is a reaction or an event occurring after vaccine administration that is suspected to be related to vaccination. Although all detected AEFIs are not caused by vaccines, the public may perceive them to be vaccine-related which may raise concern, reduce public confidence and hamper the implementation of immunization programs.

The first study described and evaluated China’s national adverse events monitoring system to understand how well it works. It was found that the National Adverse Event Surveillance System was functional and provided useful data on the safety of vaccines in the world’s largest population. This large database has the unique ability and statistical power to detect changes in reporting rates of known adverse events to help determine whether potential changes in observed rates may reflect uneven reporting.

Subsequent studies assessed specific safety issues related to three vaccines used in China (polio vaccine, Japanese encephalitis vaccine and Hepatitis B vaccine). The research determined how common was paralytic poliomyelitis associated with polio vaccine administration (VAPP) and what kind adverse events were associated with the Japanese encephalitis (JE) vaccines manufactured and used in China.

These studies suggested acceptable vaccine safety profiles and the data also supported the Chinese JE vaccine’s introduction in other endemic countries.

One study responded to media reports of deaths associated with Hepatitis B vaccine in Hunan province. These reports had raised concerns about safety of vaccines among parents and the public and resulted in marked decline in parental and public confidence in vaccines. Childhood deaths are very concerning but rare events, whereas vaccinations in childhood are common. Therefore, a temporal association of reported fatalities with hepatitis B vaccination may have occurred by chance, without a causal link to vaccination. The analysis provided reassuring information about the small risk of death following immunization. The reporting peak illustrated the sensitivity of passive reporting systems to public information. It also highlighted the caution that should be exercised in interpreting peaks in reports of serious adverse events. This finding addressed the public’s concerns and should bolster confidence in the vaccine program.

The dissertation illustrates the progress made with vaccine safety monitoring during recent years in China.

Taken together, the study findings identified vaccine-related safety concerns, assessed whether these concerns were associated with vaccines or coincidental and, found ways to strengthen surveillance and investigation capacity of the immunization services in China. However, also several challenges were identified, such as lack of standard international diseases and symptoms coding system and case definitions which should be introduced to reduce misclassification and strengthen the system. In addition, the causality assessment procedures should be standardized and made more rigorous.

Finally, new statistical methods should be introduced for safety signal detection and hypothesis generation in future studies. These scientific improvements in the world’ largest vaccine safety data source should continue building public confidence in vaccine programs in China, and perhaps serve as a model to surveillance system development in other countries.

Wendi Wu comes from Beijing, China. She earned a BSc. in Human Medicine at Hebei Medical University, China and a MSc. in Human Medicine at the Chinese Center for Disease Control and Prevention, China. She is a graduate of the International Doctoral Programme in Epidemiology and Public Health (IPPE) at Tampere University. She currently works at the Chinese National Immunization Program in Beijing. This research project was a collaborative effort of China’s National Immunization Program and Tampere University.   

The doctoral dissertation of Master of Science Wendi Wu in the field of epidemiology titled Immunization Safety Monitoring and Vaccine Safety Assessment in China will be publicly examined in the Faculty of Social Sciences of Tampere University on Friday, 13th September 2019 at 12:00. Venue: Arvo building, Room F217. The opponent will be Professor Walter Orenstein from Emory University, Atlanta, USA. The Custos is Professor Pekka Nuorti from the Health Sciences Unit, Faculty of Social Sciences, Tampere University.

The dissertation is available online at