title: Post-Marketing Benefit-Risk Assessment of Rotavirus Vaccination in Japan: A Simulation and Modelling Analysis.
abstract: BACKGROUND
  Rotarix™, GSK's live attenuated rotavirus vaccine, was introduced in Japan in 2011. A recent trend in reduction of rotavirus gastroenteritis (RVGE) due to this vaccine was described. However, an observed/expected analysis showed a temporal association with intussusception within 7 days post dose 1.
  
  
  OBJECTIVE
  In this paper, we compare the benefit and risk of vaccination side-by-side in a benefit-risk analysis.
  
  
  METHODS
  The number of vaccine-preventable RVGE-associated hospitalizations and deaths (benefit) and intussusception-associated hospitalizations and deaths (risk) following two doses of Rotarix™ in Japan was compared using simulations. Source data included peer-reviewed clinical and epidemiological publications, Japanese governmental statistics (Statistics Bureau, Ministry of Internal Affairs and Communications), and market survey data.
  
  
  RESULTS
  For a birth cohort of 1 million vaccinated Japanese children followed for 5 years, the benefit-risk analysis suggested that the vaccine would prevent ~17,900 hospitalizations and ~6.3 deaths associated with RVGE. At the same time, vaccination would be associated with about ~50 intussusception hospitalizations and ~0.017 intussusception deaths. Therefore, for every intussusception hospitalization caused by vaccination and for one intussusception-associated death, 350 (95 % CI 69-2510) RVGE-associated hospitalizations and 366 (95 % CI 59-3271) RVGE-associated deaths are prevented, respectively, by vaccination.
  
  
  CONCLUSIONS
  The benefit-risk balance for Rotarix™ is favorable in Japan. From a public health perspective, the benefits in terms of prevented RVGE hospitalizations and deaths for the vaccinated population far exceed the estimated risks due to intussusception.
authors.affiliation: Clinical Statistics, GSK Vaccines, Rixensart, Belgium. edouard.y.ledent@gsk.com.
authors.forename: Edouard
authors.initials: E
authors.lastname: Ledent
authors.affiliation: Chief Medical Office, GSK UK Ltd, Uxbridge, UK.
authors.forename: Alfons
authors.initials: A
authors.lastname: Lieftucht
authors.affiliation: Safety Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Hubert
authors.initials: H
authors.lastname: Buyse
authors.affiliation: Japan Vaccine Co., Ltd., Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Safety Department, GSK Vaccines, Wavre, Belgium.|Otsuka Europe Development and Commercialisation Ltd, Wexham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Mckenna
authors.affiliation: Health Economics Department, GSK Vaccines, Wavre, Belgium.
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Holl
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D003198:Computer Simulation; D005260:Female; D006760:Hospitalization / Q000639:trends; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D018570:Risk Assessment / Q000379:methods; D012401:Rotavirus / Q000187:drug effects; D012400:Rotavirus Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated