Clinical epidemiology of vaccines and vaccine-preventable diseases using administrative healthcare data

Abstract

For centuries, infectious diseases have been among the top 10 leading causes of death. In 2015, they accounted for about 11% of 56.4 million deaths worldwide indicating a global public health relevance. Vaccines provide an opportunity to eliminate or even eradicate infectious diseases. In order to maximize the benefit of vaccines while minimizing their risks, it is important to investigate infectious disease etiology as well as to continuously monitor and evaluate direct vaccination effects as well as indirect vaccination effects through herd immunity. Since vaccines are usually administered to healthy people to prevent infectious diseases, the monitoring of the safety of vaccines is of high importance. For their evaluation, there is usually no trade-off between risk of disease and risk of its treatment as is usually the case for the treatment of severe diseases. Vaccine safety is also essential for the acceptance of vaccines in the population and thus for high vaccine uptake to enable herd immunity. Epidemiological observational studies are a powerful tool to investigate the burden of vaccine-preventable diseases, direct and indirect vaccination effects as well as the safety of vaccines in a real-world setting, meaning they provide important data as they includea often in contrast to randomized controlled trialsa older or immunocompromised people as well as children or pregnant women, which are most often the target population groups for vaccinations. Administrative data are a valuable data source for epidemiological observational studies and are increasingly used for studies on vaccines and vaccine-preventable diseases. However, a comprehensive knowledge of the healthcare system itself, including reimbursement policies, but also of the data source and the containing information depth is required. This thesis investigates different aspects of vaccines and vaccine-preventable diseases. Thus, in a first study, the burden of the vaccine-preventable disease of herpes zoster (HZ) and its complications is investigated and in a separate study, the risk of stroke complication after HZ infection. Vaccine uptake of the human papillomavirus (HPV) vaccine at the population level as well as its indirect impact after vaccine recommendation is assessed. Furthermore, this thesis discusses the nested case-control design with respect to its potential use for direct effectiveness and safety studies of vaccines. Relevant methodological challenges when using different observational study designs based on administrative healthcare data as well as methods to control confounding or to reduce bias are elucidated and discussed. Finally, this thesis gives outlook on potential challenges of future studies on vaccines and vaccine-preventable diseases, especially with regard to newly developed therapeutic vaccines for chronic diseases.