Incidence rates of narcolepsy diagnoses in Taiwan, Canada, and Europe: The use of statistical simulation to evaluate methods for the rapid assessment of potential safety issues on a population level in the SOMNIA study

Caitlin N. Dodd, Maria De Ridder, Wan Ting Huang, Daniel Weibel, Maria Giner-Soriano, Silvia Perez-Vilar, Javier Diez-Domingo, Lawrence W. Svenson, Salahddin M. Mahmud, Bruce Carleton, Monika Naus, Jeffrey C. Kwong, Brian J. Murray, Lisen Arnheim-Dahlstrom, Lars Pedersen, Rosa Morros, Francisco Javier Puertas, Steven Black, Miriam Sturkenboom

Research output: Contribution to journalArticleResearch

7 Citations (Scopus)

Abstract

© 2018 Dodd et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background & objectives Vaccine safety signals require investigation, which may be done rapidly at the population level using ecological studies, before embarking on hypothesis-testing studies. Incidence rates were used to assess a signal of narcolepsy following AS03-adjuvanted monovalent pandemic H1N1 (pH1N1) influenza vaccination among children and adolescents in Sweden and Finland in 2010. We explored the utility of ecological data to assess incidence of narcolepsy following exposure to pandemic H1N1 virus or vaccination in 10 sites that used different vaccines, adjuvants, and had varying vaccine coverage. Methods We calculated incidence rates of diagnosed narcolepsy for periods defined by influenza virus circulation and vaccination campaign dates, and used Poisson regression to estimate incidence rate ratios (IRRs) comparing the periods during which wild-type virus circulated and after the start of vaccination campaigns vs. the period prior to pH1N1 virus circulation. We used electronic health care data from Sweden, Denmark, the United Kingdom, Canada (3 provinces), Taiwan, Netherlands, and Spain (2 regions) from 2003 to 2013. We investigated interactions between age group and adjuvant in European sites and conducted a simulation study to investigate how vaccine coverage, age, and the interval from onset to diagnosis may impact the ability to detect safety signals. Results Incidence rates of narcolepsy varied by age, continent, and period. Only in Taiwan and Sweden were significant time-period-by-age-group interactions observed. Associations were found for children in Taiwan (following pH1N1 virus circulation) and Sweden (following vaccination). Simulations showed that the individual-level relative risk of narcolepsy was underestimated using ecological methods comparing post- vs. pre-vaccination periods; this effect was attenuated with higher vaccine coverage and a shorter interval from disease onset to diagnosis. Conclusions Ecological methods can be useful for vaccine safety assessment but the results are influenced by diagnostic delay and vaccine coverage. Because ecological methods assess risk at the population level, these methods should be treated as signal-generating methods and drawing conclusions regarding individual-level risk should be avoided.
Original languageEnglish
Article numbere0204799
JournalPLoS ONE
Volume13
DOIs
Publication statusPublished - 1 Oct 2018

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