Signal detection in VAERS and EudraVigilance using disproportionality and time to onset method and their combination

Caitlin Dodd, Lionel van Holle, Maria de Ridder, Daniel Weibel, Miriam Sturkenboom

Research output: Contribution to journalMeeting AbstractAcademic

Abstract

Background: Adverse events following immunization (AEFIs) may be monitored in spontaneous reporting systems using signal detection algorithms which compare the frequency with which a vaccine‐AEFI combination is reported as compared with all reports in the database. Alternatively, a recently developed method uses distribution test of reported time‐to‐onset (TTO) to detect vaccine safety signals with unexpected reported temporal relationship. Objectives: To compare performance of the Empirical Bayes Geometric Mean (EBGM), the TTO method, and their combination in pediatric vaccine reports in the databases (DBs) of the US Vaccine Adverse Event Reporting System (VAERS) and EU EudraVigilance (EV) as part of the Global Research in Pediatrics project. Methods: Following DB conversion to a common data model, EBGM and TTO methods were applied to all pediatric vaccine reports and in subgroups of infants (age < 2 yr), children (2‐11 yr), and adolescents (12‐17 yr) in VAERS, EV, and their combination. Performance of each method was assessed using a previously published vaccine reference set comprising 18 true positive and 113 true negative associations to calculate area under the receiver operating characteristic curve (AUC). The method of Pepe & Thompson (2000) was used to determine the linear combination of EBGM and TTO which maximized the AUC in the VAERS database. Results: VAERS contained 1.85 million pediatric vaccine reports, in which TTO data was missing in 8%, with highest missing percentage in adolescents (10%). EV contained 251 770 pediatric vaccine reports, 57% of which were missing TTO data (74% missing in adolescents). In VAERS, the TTO method AUCs in the full pediatric population, infants, children, and adolescents were 0.89, 0.88, 0.89, and 0.73 while EBGM AUCs for the same age groups were 0.73, 0.67, 0.72, and 0.69. Performance in EV was similar with the exception that EBGM performed better (AUC = 0.80) than TTO (AUC = 0.70) in adolescents. The combination of TTO and EBGM in pediatrics in VAERS increased AUC to 0.91 from AUCs of 0.89 and 0.73 for the TTO and EBGM components, respectively. Conclusions: The TTO method performed better than EBGM in both VAERS and EV in pediatric age groups with the exception of adolescents in EV. Lower performance of the TTO method in adolescents could be related to a higher percentage of missing values in that age group. The combination of EBGM and TTO methods only marginally improved performance compared with TTO method alone.
Original languageEnglish
Pages (from-to)251-252
Number of pages2
JournalPharmacoepidemiology and Drug Safety
Volume27
Issue numberS2
Publication statusPublished - Aug 2018

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