Inclusion of Safety-Related Issues in Economic Evaluations for Seasonal Influenza Vaccines: A Systematic Review

Abstract

(1) Background: Vaccines for seasonal influenza are a good preventive and cost-effective strategy. However, it is unknown if and how these economic evaluations include the adverse events following immunization (AEFI), and what the impact of such inclusion is on the health economic outcomes. (2) Methods: We searched the literature, up to January 2020, to identify economic evaluations of seasonal influenza vaccines that considered AEFIs. The review protocol was published in PROSPERO (CDR42017058523). (3) Results: A total of 52 economic evaluations considered AEFI-related parameters in their analyses, reflecting 16% of the economic evaluations on seasonal influenza vaccines in the initial study selection. Most studies used the societal perspective (64%) and evaluated vaccination of children (37%). Where considered, studies included direct medical costs of AEFIs (90%), indirect costs (27%), and disutilities/quality-adjusted life years loss due to AEFIs (37%). The majority of these studies accounted for the effects of the costs of AEFI on cost-effectiveness for Guillain-Barré syndrome. In those papers allowing cost share estimation, direct medical cost of AFEIs was less than 2% of total direct costs. (4) Conclusions: Although the overall impact of AEFIs on the cost-effectiveness outcomes was found to be low, we urge their inclusion in economic evaluations of seasonal influenza vaccines to reflect comprehensive reports for the decision makers and end-users of the vaccination strategies.

Keywords: adverse events following immunization; economic evaluations; seasonal influenza vaccines.

Figure A1

AEFI-related costs. All costs are presented in USD, and 2020 was taken as a reference price year. The cost values under 1 USD are displayed as 0 (Meltzer et al., 2005 [67]: anaphylaxis, unit cost per vaccine= 0.01; Lee et al., 2009 Vaccine (adjuvated) [39]: treatment, systemic AEFI = 0.35; Wang et al., 2005 [53]: other direct costs, travel fee = 0.02; Wang et al., 2005 [53]: other direct costs, outpatient treatment × rate of AEFI × outpatient treatment = 0.15; Meeyai et al., 2015 [47]: other direct costs, direct non-medical − transport and meals = 0.18; Meeyai et al., 2015 [47]: other direct costs, direct medical = 0.02; Wang et al., 2005 [53]: other indirect costs, AEFI rate × persons to accompany × outpatient visiting × time lost × production value per hour = 0.15).

Figure A2

Review of authors’ judgments about quality assessment items in Consensus Health Economic Criteria (CHEC) extended list presented as percentages across all included studies.

Figure A3

Risk of bias for each individual study, displaying the 20 questions from the Consensus Health Economic Criteria (CHEC) extended list for quality assessment of economic evaluations.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. NHS EED—National Institute for Health Research Economic Evaluation Database; HEED CEA—Health Economic Evaluations Database and Cost-Effectiveness Analysis registry; CEA—cost-effectiveness analysis; CUA—cost–utility analysis; CMA—cost-minimization analysis; CBA—cost–benefit analysis; EE—economic evaluation; AEFI—adverse event following immunization. This diagram shows the study selection process in steps, starting from database search, then removing duplicates, selecting by abstract screening, and full-text screening. The listed criteria for eliminating the full-text articles concern the following questions: (1) Is the article a full economic evaluation study (designs to be considered: CMA, CEA, CBA, or CUA)? (2) Is the intervention a vaccination? (3) Is the vaccine used for seasonal influenza? (4) Are the outcome measures economic parameters? (5) Does this EE discuses AEFI? Bold: 31+21 = 52, the total number of reviewed studies.

Figure 2

A four-step structure for inclusion of AEFI within economic evaluation on seasonal influenza vaccines. AEFI—adverse event following immunization; QALYs—quality-adjusted life years.