Inclusion of Additional Unintended Consequences in Economic Evaluation: A Systematic Review of Immunization and Tuberculosis Cost-Effectiveness Analyses.

Objective: Our objective was to review economic evaluations of immunization and tuberculosis to determine the extent to which additional unintended consequences were taken into account in the analysis and to describe the methodological approaches used to estimate these, where possible.

Methods: We sourced the vaccine economic evaluations from a previous systematic review by Nymark et al. (2009-2015) and searched PubMed/MEDLINE and Embase from 2015 to 2019 using the same search strategy. For tuberculosis economic evaluations, we extracted studies from 2009 to 2019 that were published in a previous review by Siapka et al. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Studies were classified according to the categories and subcategories (e.g., herd immunity, non-specific effects, and labor productivity) defined in a framework identifying additional unintended consequences by Nymark and Vassall. Where possible, methods for estimating the additional unintended consequences categories and subcategories were described. We evaluated the reporting quality of included studies according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) extraction guideline.

Results: We identified 177 vaccine cost-effectiveness analyses (CEAs) between 2009 and 2019 that met the inclusion criteria. Of these, 98 included unintended consequences. Of the total 98 CEAs, overall health consequence categories were included 73 times; biological categories: herd immunity 43 times; pathogen response: resistance 15 times; and cross-protection 15 times. For health consequences pertaining to the supply-side (health systems) categories, side effects were included five times. On the nonhealth demand side (intrahousehold), labor productivity was included 60 times. We identified 29 tuberculosis CEAs from 2009 to 2019 that met the inclusion criteria. Of these, six articles included labor productivity, four included indirect transmission effects, and one included resistance. Between 2009 and 2019, only 34% of tuberculosis CEAs included additional unintended consequences, compared with 55% of vaccine CEAs.

Conclusions: The inclusion of additional unintended consequences in economic evaluations of immunization and tuberculosis continues to be limited. Additional unintended consequences of economic benefits, such as those examined in this review and especially those that occur outside the health system, offer valuable information to analysts. Further work on appropriate ways to value these additional unintended consequences is still warranted.