This review shows that several broader categories of economic benefits associated with vaccination in LMICs are being captured in primary studies and quantified in economic evaluations. Our search identified 26 studies which assessed at least one broader benefit of an immunization program.
The first category involves productivity gains because of reduced disease risk. Of these, productivity gains related to care and to short-term outcomes are more commonly captured in economic evaluations. Productivity gains related to long-term outcomes and to household behavior are not commonly estimated or incorporated in economic evaluations [4
]. There may be a number of reasons for this. Firstly, evidence for many of the proposed benefits of vaccination is still limited. Vaccine trials do not routinely incorporate cognitive, educational and behavioral outcomes. Furthermore, the final endpoint in such an analysis is the productivity of an adult of working age who either was or was not vaccinated as a child. Such an endpoint may occur too long after the vaccination event to be feasibly collected. There are also ethical problems in keeping trial participants unvaccinated once a vaccine has been shown to be safe and effective. Hence existing evidence is largely based around retrospective observational cohorts, which may be biased since they rely on controls with unvaccinated individuals.
Secondly, the economic modeling framework within which such benefits can be incorporated is still unclear. While many of the reviewed studies were able to quantify the productivity-related benefits of vaccination, apart from care-related and short-term outcome-related productivity effects this was not routinely incorporated into summary statistics such as cost-effectiveness or cost-benefit ratios. The most common means of incorporating productivity gains was the human capital approach, which values the remaining years of productive employment a person can have up to retirement based on national average incomes [43
]. However, this method only captures productivity loss due to death or disability, and not due to cognitive or educational deficits as a result of childhood illness. Furthermore, the method has been criticized in its own right, since it assumes that the work a sick or deceased worker does cannot be replaced by someone currently unemployed or by simply reassigning it to other workers [44
]. Possibly for this reason, lost income as a result of premature death was rarely incorporated in the reviewed studies, even when economic evaluations used the human capital approach to value productivity loss. Other methods (such as the friction cost approach) are less likely to overestimate productivity loss due to illness, but are equally difficult to use to capture the effects of long-term outcomes [44
None of the studies accounted for behavior related productivity gains such as potential reductions in fertility as a result of improved child survival. In principle, lifetime benefit models (such as by Connolly and Constenla [27
] and Bloom et al.
]) are able to quantify the effect of demographic changes such as dependency ratio improvements or productivity changes from increased female workforce participation. However, primary studies are still needed to explore the link between vaccination and household decisions such as childbearing and investment spending.
Value of statistical life methodology, used by Ozawa et al.
], offers a different approach by valuing lives based on individuals’ willingness to pay to reduce the risk of death rather than the economic output accrued to a year of life. This method often produces estimates of monetary value of prevented deaths that are far greater than those estimated using other methods (see for example Molinari et al.
]). While this does not mean it is wrong, it does raise issues of comparability with existing economic evaluations and burden estimates conducted using more conservative methods. Another challenge in applying this methodology on a global level is the difficulty in knowing the extent to which to apply normative values on life (which mostly originate from high income countries) across national borders. Traditional cost-effectiveness analyses sidestep this problem by valuing health equally across the world in non-monetary terms; differences in decision making across countries hence stem from differences in thresholds representing societal willingness to pay for health (which reflect differences in budgets and national priorities) and in the direct economic impact of disease.
Ecological externalities, particularly herd immunity, were the most common broader benefit to be incorporated into economic evaluations. This is likely to be because the techniques for such analyses (such as the use of “transmission dynamic models”) are already well-established in the epidemiological and health economics fields [13
]. However, many LMICs lack the capacity and/or surveillance systems to perform and parameterize these sophisticated analyses [46
]. For example, infection transmission models capturing the indirect effects of vaccination may require data on behavioral and contact patterns which are not readily available in many LMICs. Besides herd immunity, negative ecological externalities may also occur such as replacement of strains of pathogens eliminated by vaccination with other strains unaffected by vaccination [13
Equity, affordability and financial sustainability are often important considerations for vaccine introduction in LMICs. However, trials do not to routinely collect economic information by socioeconomic strata. Such data would enable analyses of the impact of vaccines on equity or financial sustainability of other interventions, as well as elucidate any methodological difficulties with incorporating them into standard cost-effectiveness frameworks. This is evident in the case of certain spill over effects of immunization programs. Reuse of immunization infrastructure, better surveillance, human resource gains, and improved drug procurement systems, are some potential benefits of immunization programs which are rarely incorporated into cost effectiveness studies [47
]. Other frameworks such as return on investment analyses or optimization modeling may be able to address some of these issues more effectively, and provide more comprehensive representation of the societal value of vaccination.
None of the identified studies took a macroeconomic approach to evaluating the impact of vaccination, as proposed by a recent World Health Organization guidance document [9
]. Such an approach has been used to evaluate the impact of vaccination during an influenza pandemic in several European countries, using computable general equilibrium models [48
], but an LMIC application or an application to situations beyond pandemics (such as an endemic disease) has yet to be published.
This review has limitations, because it was designed to give a broad qualitative overview of existing literature rather than to enable detailed quantitative synthesis. Only one person was responsible for study selection, and the studies were not weighted by quality scores. However, the permissive inclusion criteria ensured that a variety of study types and measurement techniques were reviewed, including those employing unconventional tools and techniques. Also, our study was restricted to methods applied to LMICs only, since it was motivated by decision making in these settings, where stakeholders often require information not provided by conventional economic evaluation methods. As a result, it may not have captured novel approaches being developed or applied in high income settings.
Most (22/26) of the reviewed studies included only a single category of broader economic impact. There may be several reasons for this. Most (16/26) studies were observational, willingness to pay, return on investment or cost of illness studies rather than full economic evaluations (cost-effectiveness or cost-benefit analyses) attempting to capture all important costs and outcomes of an intervention. However, even the full economic evaluations presented a limited number of broader categories of impact, even though a comprehensive range of traditional (narrow) measures were presented, such as direct medical costs, cases avoided or lives saved. This may be due to the current novelty of these measures, as well as the lack of comprehensive guidelines for economic evaluations about which of these broader measures should be reported and in what way. A further difficulty is the complexity of the relationships between vaccination, health and broader economic outcomes, which require a range of types of evidence and techniques to quantify. Given the difficulty with both measurement and interpretation, it may be impractical to develop a single composite measure capturing all relevant economic benefits of vaccination. Instead, several evaluation techniques may need to be implemented to obtain a representative set of outcome measures. However, there is little guidance about the way several categories of benefits estimated using different techniques can be combined in the same evaluation.