Real-World Evidence in Cost-Effectiveness Analysis of Enhanced Influenza Vaccines in Adults ≥ 65 Years of Age: Literature Review and Expert Opinion

Abstract

Influenza vaccination can benefit most populations, including adults ≥ 65 years of age, who are at greater risk of influenza-related complications. In many countries, enhanced vaccines, such as adjuvanted, high-dose, and recombinant trivalent/quadrivalent influenza vaccines (aTIV/aQIV, HD-TIV/HD-QIV, and QIVr, respectively), are recommended in older populations to provide higher immunogenicity and increased relative vaccine efficacy/effectiveness (rVE) than standard-dose vaccines. This review explores how efficacy and effectiveness data from randomized controlled trials and real-world evidence (RWE) are used in economic evaluations. Findings from published cost-effectiveness analyses (CEA) on enhanced influenza vaccines for older adults are summarized, and the assumptions and approaches used in these CEA are assessed alongside discussion of the importance of RWE in CEA. Results from many CEA showed that adjuvanted and high-dose enhanced vaccines were cost-effective compared with standard vaccines, and that differences in rVE estimates and acquisition price may drive differences in cost-effectiveness estimates between enhanced vaccines. Overall, RWE and CEA provide clinical and economic rationale for enhanced vaccine use in people ≥ 65 years of age, an at-risk population with substantial burden of disease. Countries that consider RWE when making vaccine recommendations have preferentially recommended aTIV/aQIV, as well as HD-TIV/HD-QIV and QIVr, to protect older individuals.

Keywords: adjuvanted; cost-effectiveness analysis; enhanced vaccine; influenza.

Figure 1

rVE as used in base-case analyses of aTIV/aQIV compared with TIV/QIV and/or HD-TIV/HD-QIV [51,52,53,54,55,56,57,58,59,60,61,62,63,64]. aQIV, adjuvanted quadrivalent influenza vaccine; aTIV, adjuvanted trivalent influenza vaccine; CEA, cost-effectiveness analysis; HD-QIV, high-dose quadrivalent influenza vaccine; HD-TIV, high-dose trivalent influenza vaccine; QIV, quadrivalent influenza vaccine; RCT, randomized controlled trial; rVE, relative vaccine effectiveness; RWE, real-world evidence; TIV, trivalent influenza vaccine.

Figure 2

rVE as used in base-case analyses of HD-TIV/HD-QIV compared with TIV/QIV or aTIV/aQIV [65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81]. Note: no value indicates that a comparison was not evaluated. 0 indicates a rVE of 0% in base-case analysis. Note: rVE aTIV/aQIV versus TIV/QIV is captured as reported in studies that use a common comparator of TIV/QIV to indirectly compare rVE of HD-TIV/HD-QIV versus aTIV/aQIV. aQIV, adjuvanted quadrivalent influenza vaccine; aTIV, adjuvanted trivalent influenza vaccine; CEA, cost-effectiveness analysis; HD-QIV, high-dose quadrivalent influenza vaccine; HD-TIV, high-dose trivalent influenza vaccine; QIV, quadrivalent influenza vaccine; RCT, randomized controlled trial; rVE, relative vaccine effectiveness; RWE, real-world evidence; TIV, trivalent influenza vaccine.