title: Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial.
abstract: BACKGROUND
  Adults aged 65 years and older account for most seasonal influenza-related hospital admissions and deaths. Findings from the randomised controlled FIM12 study showed that high-dose inactivated influenza vaccine is more effective than standard-dose vaccine for prevention of laboratory-confirmed influenza in this age group. We aimed to assess the economic impact of high-dose versus standard-dose influenza vaccine in participants in the FIM12 study population.
  
  
  METHODS
  The FIM12 study was a head-to-head randomised controlled trial in which 31,989 participants aged 65 years and older were randomly assigned (1:1) to receive either high-dose or standard-dose trivalent inactivated influenza vaccine over two influenza seasons (2011-12 and 2012-13). Data for health-care resource consumption obtained in the FIM12 study were summarised across vaccine groups. Unit costs obtained from standard US cost sources were applied to each resource item, including to the vaccines (high dose US$31·82, standard dose $12·04). Clinical illness data were mapped to existing quality-of-life data. The time horizon was one influenza season; however, quality-adjusted life-years (QALYs) lost due to death during the study were calculated over a lifetime. We calculated incremental cost-effectiveness ratios (ICERs) for high-dose versus standard-dose vaccine and used QALYs as an outcome in the cost-utility analysis. We undertook a probabilistic sensitivity analysis using bootstrapping to explore the effect of statistical uncertainty on the study results.
  
  
  RESULTS
  Mean per-participant medical costs were lower in the high-dose vaccine group ($1376·72 [SD 6857·59]) than in the standard-dose group ($1492·64 [7447·14]; difference -$115·92 [95% CI -264·18 to 35·48]). Mean societal costs were likewise lower in the high-dose versus the standard-dose group ($1506·48 [SD 7305·19] vs $1634·50 [7952·99]; difference -$128·02 [95% CI -286·89 to 33·30]). Hospital admissions contributed 95% of the total health-care-payer cost and 87% of the total societal costs. The mean per-participant number of hospital admissions was 0·0937 (SD 0·3644) in the high-dose group and 0·1017 (0·3708) in the standard-dose group (difference -0·0080, 95% CI -0·0160 to -0·0003). The high-dose vaccine provided a gain in QALYs (mean 8·1502 QALYs gained per participant [SD 0·5693]) compared with the standard-dose vaccine (8·1499 QALYs [0·5697]) and, due to cost savings, dominated standard-dose vaccine in the cost-utility analysis. The probabilistic sensitivity analysis showed that the high-dose vaccine is 93% likely to be cost saving.
  
  
  CONCLUSIONS
  High-dose trivalent inactivated influenza vaccine is a less costly and more effective alternative to the standard-dose vaccine, driven by a reduction in the number of hospital admissions. These findings are relevant to US health-care beneficiaries, providers, payers, and recommending bodies, especially those seeking to improve outcomes while containing costs.
  
  
  BACKGROUND
  Sanofi Pasteur.
authors.affiliation: Sanofi Pasteur, Swiftwater, PA, USA; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada. Electronic address: ayman.chit@sanofipasteur.com.
authors.forename: Ayman
authors.initials: A
authors.lastname: Chit
authors.affiliation: Optum, Burlington, ON, Canada.
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Becker
authors.affiliation: Sanofi Pasteur, Swiftwater, PA, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: DiazGranados
authors.affiliation: Optum, Burlington, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Maschio
authors.affiliation: inVentiv Health Clinical, Burlington, ON, Canada.
authors.forename: Eddy
authors.initials: E
authors.lastname: Yau
authors.affiliation: University of York, York, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Drummond
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003362:Cost-Benefit Analysis; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007115:Immunization Schedule; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000191:economics*; D007251:Influenza, Human / Q000191:economics* / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008297:Male; D015233:Models, Statistical; D019057:Quality-Adjusted Life Years; D022223:Vaccines, Subunit
chemical_list: D007252:Influenza Vaccines; D022223:Vaccines, Subunit