Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using electronic health record (eHR) databases in Europe. Proof-of-concept studies were designed to assess the proposed processes and system for generating the required evidence to perform B/R assessment and near-real time monitoring of vaccines. We aimed to test B/R methodologies for vaccines, using the comparison of the B/R profiles of whole-cell (wP) and acellular pertussis (aP) vaccine formulations in children as an example. Methods: We used multi-criteria decision analysis (MCDA) to structure the B/R assessment combined with individual-level state transition modelling to build the B/R effects table. In the state transition model, we simulated the number of events in two hypothetical cohorts of 1 million children followed from first pertussis dose till pre-school-entry booster (or six years of age, whichever occurred first), with one cohort receiving wP, and the other aP. The benefits were reductions in pertussis incidence and complications. The risks were increased incidences of febrile convulsions, fever, hypotonic-hyporesponsive episodes, injection-site reactions and persistent crying. Most model parameters were informed by estimates (coverage, background incidences, relative risks) from eHR databases from Denmark (SSI), Spain (BIFAP and SIDIAP), Italy (Pedianet) and the UK (RCGP-RSC and THIN). Preferences were elicited from clinical and epidemiological experts. Results: Using state transition modelling to build the B/R effects table facilitated the comparison of different vaccine effects (e.g. immediate vaccine risks vs long-term vaccine benefits). Estimates from eHR databases could be used to inform the simulation model. The model results could be easily combined with preference weights to obtain B/R scores. Conclusion: Existing B/R methodology, modelling and estimates from eHR databases can be successfully used for B/R assessment of vaccines.

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Keywords Benefit-risk assessment, Electronic health record databases, Europe, Methodological study, Pertussis vaccines
Persistent URL dx.doi.org/10.1016/j.vaccine.2019.09.034, hdl.handle.net/1765/120154
Journal Vaccine
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Citation
Bollaerts, K. (Kaatje), Ledent, E. (Edouard), de Smedt, T. (Tom), Weibel, D.M, Emborg, H.-D. (Hanne-Dorthe), Danieli, G. (Giorgia), … Bauchau, V. (Vincent). (2019). ADVANCE system testing: Benefit-risk analysis of a marketed vaccine using multi-criteria decision analysis and individual-level state transition modelling. Vaccine. doi:10.1016/j.vaccine.2019.09.034