Background: Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. Methods: The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. Results: We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. Conclusion: A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.

Adverse event following immunization (AEFI), Data mining, Pediatrics, Pharmacovigilance, Reference set, Vaccine,
This work was funded by the European Commission 7th Framework Programme; grant id fp7/261060 - Global Research in Paediatrics (GRIP)
Erasmus MC: University Medical Center Rotterdam

Brauchli Pernus, Y, Nan, C, Verstraeten, T, Pedenko, M, Osokogu, O.U, Weibel, D.M, … Bonhoeffer, J. (2016). Reference set for performance testing of pediatric vaccine safety signal detection methods and systems. Vaccine, 34(51), 6626–6633. doi:10.1016/j.vaccine.2015.10.013