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Statistical analysis of MMR vaccine adverse events on aseptic meningitis using the case cross-over design
Taesung Park1, Moran Ki, Sung-Gon Yi
1Department of Statistics, Seoul National University, San 56-1 Shin Lim-Dong, Kwanak-Gu, Seoul, Korea 151-742. tspark@stats.snu.ac.kr
Abstract:
Vaccination is quite effective in reducing the incidence of disease. However, it may cause some adverse events. For example, one of the adverse events of measles-mumps-rubella(MMR) vaccination is the occurrence of aseptic meningitis. Since the vaccination rate is usually quite high, it is not plausible to use popular study designs such as cohort or case-control studies. We considered a case cross-over design to investigate the association between MMR vaccination and aseptic meningitis in Korean children. We used the Cochran-Mantel-Haenszel(CMH) approach, and obtained a Mantel-Haenszel odds ratio estimator as a measure of association. However, the validity of case cross-over design or the CMH approach in vaccine adverse studies has not been fully investigated. In this paper, through Monte Carlo simulation studies, we show the appropriateness of the case cross-over design and the CMH approach. We also discuss alternative approaches such as Poisson regression using offset and a simple uniformity test. In conclusion, the case cross-over design seems useful to investigate the association between vaccination and occurrence of acute adverse events.
Insights
The case cross-over design is effective for studying adverse events like aseptic meningitis after measles-mumps-rubella (MMR) vaccination. This study validates the case cross-over design and Cochran-Mantel-Haenszel approach for vaccine safety research.
Area of Science:
- Epidemiology
- Biostatistics
- Vaccinology
Background:
- Vaccination significantly reduces disease incidence but can cause adverse events.
- Aseptic meningitis is a potential adverse event associated with measles-mumps-rubella (MMR) vaccination.
- High vaccination rates limit the feasibility of traditional cohort or case-control studies for vaccine adverse event research.
Purpose of the Study:
- To investigate the association between MMR vaccination and aseptic meningitis in Korean children.
- To evaluate the validity and appropriateness of the case cross-over design and Cochran-Mantel-Haenszel (CMH) approach for studying vaccine adverse events.
- To explore alternative statistical methods for vaccine safety analysis.
Main Methods:
- Utilized a case cross-over design to assess the relationship between MMR vaccination and aseptic meningitis.
- Employed the Cochran-Mantel-Haenszel (CMH) approach to obtain a Mantel-Haenszel odds ratio estimator.
- Conducted Monte Carlo simulation studies to demonstrate the appropriateness of the case cross-over design and CMH method.
- Discussed alternative approaches including Poisson regression with offset and uniformity tests.
Main Results:
- Monte Carlo simulations confirmed the appropriateness of the case cross-over design for investigating vaccine adverse events.
- The CMH approach, when applied within the case cross-over framework, proved suitable for estimating the association.
- The study provides evidence supporting the utility of these methods in vaccine safety surveillance.
Conclusions:
- The case cross-over design is a useful epidemiological tool for investigating the association between vaccinations and acute adverse events.
- The CMH approach is a valid statistical method for analyzing data from case cross-over studies in vaccine safety research.
- Further investigation into statistical methodologies for vaccine adverse event studies is warranted.
