title: Evaluation of serological trials submitted for annual re-licensure of influenza vaccines to regulatory authorities between 1992 and 2002.
abstract: BACKGROUND
  As part of the regulatory requirements, serological evaluation of trivalent inactivated influenza vaccines must be performed before annual re-licensure in the European Union. These studies are typically set up as uncontrolled, open label trials including 2 groups of at least 50 healthy adults and healthy elderly.
  
  
  METHODS
  The serological data submitted to the Dutch Medicines Evaluation Board (MEB) for annual re-licensure purposes between 1992 and 2002, were analysed with respect to their ability to assess the immunogenic properties of the vaccines. The trials in this meta-analysis were selected by strictly applying the inclusion and exclusion criteria described in the Committee of Human Medicinal Products (CHMP) Note for Guidance on harmonisation of requirements for influenza vaccines. To select the final dataset additional exclusion criteria were defined: age outside the inclusion criterion of the trial, incomplete demographics, co-morbid conditions, antibody determination by SRH assay, incomplete dataset and sample size smaller than 50 subjects.
  
  
  RESULTS
  Out of 51 trials retrieved from the archives, 48 age-defined trials including 2510 adults and 2008 elderly fulfilled all the in- and exclusion criteria. A large proportion of vaccinees already met the threshold for seroprotection at baseline. Post-vaccination, the serological response was shown to be age dependent. Previous influenza vaccinations significantly affected pre-vaccination but not post-vaccination titres.
  
  
  CONCLUSIONS
  The annual update trials performed for regulatory purposes have serious methodological limitations, which affect their ability to identify influenza vaccines with low immunogenicity. To establish clinical (protective) efficacy different trials and different assessment criteria are needed.
authors.affiliation: Pharmaco-epidemiology Unit, Departments of Internal Medicine and Epidemiology & Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands. ac.voordouw@cbg-meb.nl
authors.forename: A C G
authors.initials: AC
authors.lastname: Voordouw
authors.forename: W E P
authors.initials: WE
authors.lastname: Beyer
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
authors.forename: M C J M
authors.initials: MC
authors.lastname: Sturkenboom
authors.forename: B H Ch
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D000293:Adolescent; D000328:Adult; D002986:Clinical Trials as Topic; D006801:Humans; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D008875:Middle Aged; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated