ADVANCE system testing: Can safety studies be conducted using electronic healthcare data? An example using pertussis vaccination.

Introduction: The Accelerated Development of Vaccine benefit-risk Collaboration in Europe (ADVANCE) public-private collaboration, aimed to develop and test a system for rapid benefit-risk monitoring of vaccines using healthcare databases in Europe. The objective of this proof-of-concept (POC) study was to test the feasibility of the ADVANCE system to generate incidence rates (IRs) per 1000 person-years and incidence rate ratios (IRRs) for risks associated with whole cell- (wP) and acellular- (aP) pertussis vaccines, occurring in event-specific risk windows in children prior to their pre-school-entry booster.
Methods: The study population comprised almost 5.1 million children aged 1 month to <6 years vaccinated with wP or aP vaccines during the study period from 1 January 1990 to 31 December 2015. Data from two Danish hospital (H) databases (AUH and SSI) and five primary care (PC) databases from, UK (THIN and RCGP RSC), Spain (SIDIAP and BIFAP) and Italy (Pedianet) were analysed. Database-specific IRRs between risk vs. non-risk periods were estimated in a self-controlled case series study and pooled using random-effects meta-analyses.
Results: The overall IRs were: fever, 58.2 (95% CI: 58.1; 58.3), 96.9 (96.7; 97.1) for PC DBs and 8.56 (8.5; 8.6) for H DBs; convulsions, 7.6 (95% CI: 7.6; 7.7), 3.55 (3.5; 3.6) for PC and 12.87 (12.8; 13) for H; persistent crying, 3.9 (95% CI: 3.8; 3.9) for PC, injection-site reactions, 2.2 (95% CI 2.1; 2.2) for PC, hypotonic hypo-responsive episode (HHE), 0.4 (95% CI: 0.4; 0.4), 0.6 (0.6; 0.6) for PC and 0.2 (0.2; 0.3) for H; and somnolence: 0.3 (95% CI: 0.3; 0.3) for PC. The pooled IRRs for persistent crying, fever, and ISR, adjusted for age and healthy vaccinee period were higher after wP vs. aP vaccination, and lower for convulsions, for all doses. The IRR for HHE was slightly lower for wP than aP, while wP was associated with somnolence only for dose 1 and dose 3 compared with aP.
Conclusions: The estimated IRs and IRRs were comparable with published data, therefore demonstrating that the ADVANCE system was able to combine several European healthcare databases to assess vaccine safety data for wP and aP vaccination.
Competing Interests: Declaration of Competing Interest Caitlin Dodd, Talita Duarte-Salles, Gino Picelli, Lara Tramontan, Giorgia Danieli, Ana Correa, Chris McGee, Elisa Martín-Merino, Consuelo Huerta, Hanne-Dorthe Emborg, Kaatje Bollaerts, Klara Berencsi declared no conflicts of interest. Daniel Weibel declared personal fees from GSK outside the submitted work. Olivia Mahaux, Francois Haguinet and Vincent Bauchau declared that they are employed by GSK and hold shares from GSK. Lina Titievsky declared that she is employed Pfizer and holds stocks from Pfizer. Miriam Sturkenboom declared that she has received grants from Novartis, CDC and the Bill & Melinda Gates Foundation outside the submitted work.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)