Systematic Review of Published Meta-Analyses of Vaccine Safety

Meta-analysis can be especially useful for evaluation of vaccine safety, since individual studies often have limited power to detect an increase in safety risk. In order to gain a perspective on the current state of utilization of the technique of meta-analysis for evaluation of vaccine safety and to assess the methodological characteristics of these meta-analyses, we conducted a systematic review of published meta-analyses. We identified 61 meta-analyses of vaccine safety. Safety outcomes for influenza and human papillomavirus (HPV) vaccines were most frequently meta-analysed. The most studied safety outcomes were local and systemic reactions, as well as Serious Adverse Events. Most meta-analyses were literature based. Differences in the definitions of safety outcomes across the different studies and the poor reporting of safety in the published literature were described as challenges when conducting a meta-analysis of vaccine safety. A way to overcome these challenges is through the implementation of standardized safety outcomes definitions and reporting. A prospectively conducted meta-analysis, i.e. a meta-analysis planned prior to the conduct of the trials, as well as implementation of subject-level meta-analysis techniques can also reduce or eliminate the impact of these difficulties.