| dc.description.abstract | 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. |
| dc.contributor.authoraffiliation | [Dodd CN] Erasmus Medical Center, Rotterdam, The Netherlands. Julius Center Global Health, University Medical Center Utrecht, Utrecht, The Netherlands. [Ridder M, Weibel D] Erasmus Medical Center, Rotterdam, The Netherlands. [Huang WT] Taiwan Centers for Disease Control, Taipei, Taiwan. [Giner-Soriano M, Morros R] Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain. [Perez-Vilar S] Erasmus Medical Center, Rotterdam, The Netherlands. Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat (FISABIO), Vaccine Research, Valencia, Spain. [Diez-Domingo J] Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat (FISABIO), Vaccine Research, Valencia, Spain. [Svenson LW] University of Alberta, Division of Preventative Medicine, Alberta, Canada. [Mahmud SM] University of Manitoba, Rady Faculty of Health Sciences, Winnipeg, Manitoba, Canada. [Carleton B, Naus M] University of British Columbia, Faculty of Medicine, Vancouver, British Columbia, Canada. [Kwong JC] Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. Public Health Ontario, Toronto, Ontario, Canada. Department of Family & Community Medicine, University of Toronto, Toronto, Ontario, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. University Health Network, Toronto, Ontario, Canada. [Murray BJ] Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada. [Arnheim-Dahlstrom L] Karolinska Institut, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden. [Pedersen L] Aarhus University, Department of Clinical Epidemiology, Aarhus, Denmark. [Puertas FJ] Sleep Unit, Neurophysiology Department, La Ribera University Hospital, Valencia, Spain. Physiology Department, University of Valencia, Valencia, Spain. [Black S] Cincinnati Children’s Hospital, Center for Global Health, Cincinnati, Ohio, United States of America. [Sturkenboom M] Julius Center Global Health, University Medical Center Utrecht, Utrecht, The Netherlands |
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