Abstract
While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do not include enough subjects to detect rare adverse events, and they generally exclude special populations such as pregnant women. It is therefore necessary to conduct postmarketing vaccine safety assessments using observational data sources. The study of rare events has been enabled in through large linked databases and distributed data networks, in combination with development of case-centred methods. Distributed data networks necessitate common protocols, definitions, data models and analytics and the processes of developing and employing these tools are rapidly evolving. Assessment of vaccine safety in pregnancy is complicated by physiological changes, the challenges of mother-child linkage and the need for long-term infant follow-up. Potential sources of bias including differential access to and utilisation of antenatal care, immortal time bias, seasonal timing of pregnancy and unmeasured determinants of pregnancy outcomes have yet to be fully explored. Available tools for assessment of evidence generated in postmarketing studies may downgrade evidence from observational data and prioritise evidence from randomised controlled trials. However, real-world evidence based on real-world data is increasingly being used for safety assessments, and new tools for evaluating real-world evidence have been developed. The future of vaccine safety surveillance, particularly for rare events and in special populations, comprises the use of big data in single countries as well as in collaborative networks. This move towards the use of real-world data requires continued development of methodologies to generate and assess real world evidence.