Aarhus University Seal / Aarhus Universitets segl

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Caitlin N Dodd, Julius Center Global Health, University Medical Center Utrecht, Utrecht, The Netherlands.
  • ,
  • Maria de Ridder, ThoraxCentre, Erasmus Medical Center, Rotterdam, the Netherlands; Academic Medical Center, Amsterdam, the Netherlands.
  • ,
  • Wan-Ting Huang, Taiwan Centers for Disease Control, Taipei, Taiwan.
  • ,
  • Daniel Weibel, ThoraxCentre, Erasmus Medical Center, Rotterdam, the Netherlands; Academic Medical Center, Amsterdam, the Netherlands.
  • ,
  • Maria Giner-Soriano, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
  • ,
  • Silvia Perez-Vilar, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat (FISABIO), Vaccine Research, Valencia, Spain.
  • ,
  • Javier Diez-Domingo, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat (FISABIO), Vaccine Research, Valencia, Spain.
  • ,
  • Lawrence W Svenson, University of Alberta, Division of Preventative Medicine, Alberta, Canada.
  • ,
  • Salahddin M Mahmud, Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
  • ,
  • Bruce Carleton, Animal Welfare Program, Faculty of Land and Food Systems, University of British Columbia, 2357 Main Mall, Vancouver, British Columbia, V6T 1Z4, Canada; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus 43210.
  • ,
  • Monika Naus, Animal Welfare Program, Faculty of Land and Food Systems, University of British Columbia, 2357 Main Mall, Vancouver, British Columbia, V6T 1Z4, Canada; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus 43210.
  • ,
  • Jeffrey C Kwong, Department of Psychiatry, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
  • ,
  • Brian J Murray, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada.
  • ,
  • Lisen Arnheim-Dahlstrom, Karolinska Institut, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
  • ,
  • Lars Pedersen
  • Rosa Morros, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
  • ,
  • Francisco Javier Puertas, Physiology Department, University of Valencia, Valencia, Spain.
  • ,
  • Steven Black, Cincinnati Children's Hospital, Center for Global Health, Cincinnati, Ohio, United States of America.
  • ,
  • Miriam Sturkenboom, Julius Center Global Health, University Medical Center Utrecht, Utrecht, The Netherlands.

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
JournalPLOS ONE
Volume13
Issue10
Pages (from-to)e0204799
ISSN1932-6203
DOIs
Publication statusPublished - 2018

See relations at Aarhus University Citationformats

ID: 142682837