Updating the evidence base on the operational costs of supplementary immunization activities for current and future accelerated disease control, elimination and eradication efforts

Over the past three decades, several global health initiatives have brought together public and private stakeholders to focus efforts on achieving globally or regionally defined goals of accelerated disease control^a, elimination and eradication (ADC/E/E) of several vaccine-preventable diseases—notably poliomyelitis (polio), measles/rubella, maternal and neonatal tetanus (MNT), yellow fever, and Neisseria meningitis serogroup A (menA) [1–8]. These initiatives have combined strategic focus, global coordination, expertise, and capacity to assist country governments mainly in low income countries (LICs) and middle income countries (MICs), complementing national routine immunization activities with intensive, time-limited, and targeted vaccination campaigns – Supplementary Immunization Activities (SIAs) [9–11]. At best, well-funded SIAs represent an important delivery strategy to improve population immunity, reduce inequities in access to vaccination, and help achieve ambitious public health goals.

Prices of the vaccines used in ADC/E/E initiatives have reached maturity in that they are relatively affordable (i.e. roughly $0.50 per dose or less) and in most cases supply and prices are quite stable [12]. From a funding standpoint, the cost of these vaccines have historically been covered by global financers of immunization such as the GAVI Alliance (formerly the ‘Global Alliance for Vaccines and Immunizations’); or vaccine costs have been covered by the resources mobilized by the partnerships that have coalesced around ADC/E/E efforts like the Global Polio Eradication Initiative (GPEI) and the Measles-Rubella Initiative (MRI). However, since the late 1990s, the increasing number of ADC/E/E as well as other health priorities has increased competition for resources. Funding from both national and global sources has often been insufficient to cover vaccine and non-vaccine SIA costs, but particularly the operational costs of SIAs. Along with a variety of other factors, funding shortfalls have led to delays in implementation or forced SIA efforts to be scaled back (i.e. to target narrower age groups) resulting in campaigns not reaching the necessary coverage rates nor the levels of population immunity necessary for disease control, in some cases resulting in large disease outbreaks after re-introduction of virus [13–16].

SIA funding shortfalls are likely to have been precipitated by a number of factors: ADC/E/E programs essentially deliver a ‘global good’ whose benefit may be underestimated on a national basis leading to underinvestment by national payers. The somewhat unpredictable nature of disease dynamics associated with many of the viruses targeted by ADC/E/E efforts may make longer term planning and budgeting for SIAs difficult at the national level. The broad age ranges targeted particularly with catch-up SIAs, and to a lesser extent follow-up SIAs, is likely to stretch national health budgets particularly where external partner funding (e.g. from GAVI Alliance or MRI) is not available. While weak governance within many of the countries that are worst affected by these diseases almost certainly limits the effectiveness of monies earmarked for SIAs.

Combining the above factors with the lack of information about the real operational costs of SIAs, how these costs differ by disease, delivery strategy, and setting, and how they may be changing over time, may have hampered the ability of payers at both country- and global levels to allocate adequate funds to cover SIA costs.

Looking ahead and beyond the existing ADC/E/E initiatives, it is clear that over the coming decade SIAs will continue to be an integral part of vaccination delivery strategies in combination with routine vaccine delivery (through outreach and fixed site –based approaches). Several underutilized and new vaccines that seem likely to be adopted across LICs and MICs in the coming years will include an SIA delivery component: either a one-time catch up campaign at the time of introduction to accelerate disease control (i.e. Japanese Encephalitis (JE) vaccines, typhoid conjugate vaccines), or periodic campaigns to maintain herd immunity (i.e. cholera vaccines) [17]. For these newer or still underutilized vaccines, all of which are components of the global immunization agenda set out in the Decade of Vaccines (DoV) Global Vaccine Action Plan (GVAP), there is limited evidence on the costs of campaign-based delivery making it more difficult to predict the necessary resource requirements to achieve the DoV goals [18–22]. Until such tailored evidence can be generated, the most up-to-date analogous evidence from existing ADC/E/E initiatives will be critical for long range financial planning.

The research was divided into two parts – (I) A literature review; and (II) An analysis of data from country-specific and global immunization plans and budgets.

(I)→Analysis of data from country-specific plans – See Additional file 1

Analysis description

A previous unpublished analysis of costed country immunization plans assessed the operational costs per person for many of the vaccines noted above (P. Lydon and G. Gandhi: Introduction of New Vaccines: Analysis of non-vaccine routine and campaign costs for the GAVI Alliance. Unpublished). The previous analysis was based on a heterogeneous dataset that included actual costs and expenditures as well as projected costs. Since projections often rely on out of date benchmarks or historic expenditures, the unpublished study may have underestimated the true operational costs of SIAs. In this paper, we update the analysis restricting to a more homogenous and valid dataset (discussed in more detail below in the Analytic approach), and extend the analysis to illustrate how per person operational costs varied in aggregate by:

1. (i)

   Temporal characteristics – to assess how costs have changed over time.

    

• Comparing estimates identified in the literature with those generated from comprehensive multi-year plans (cMYPs) data.

• Comparing older estimates (from 2004–2008) from cMYPs versus more recent estimates (from 2009–2011) in aggregate across the dataset, as well as on a country-by-country basis where a country has conducted two SIAs against the same vaccine-preventable in the two time periods.

1. (ii)

   Vaccine delivery characteristics – to assess the effects on costs of different target populations and methods of administration.

    

• Comparing Oral Polio vaccines (OPV) and measles vaccines both targeting mainly under-five populations or slightly older children (in the case of measles vaccines), and tetanus-containing vaccines (e.g. tetanus toxoid—TT, tetanus-diphtheria—Td vaccines) targeting at-risk women of child bearing age (WCBA) populations^c.

• Comparing interventions administered orally^d versus injectable vaccination.

1. (iii)

   Country characteristics – to assess the effects of population size, region, and program strength.

    

• Comparing two country groupings by population size: Midsize/Large Countries with total population ≥ 10 million, and Small Countries with total population <10 million)^e.

• Comparing geographic regions as defined by the World Health Organization (WHO) regional groupings [26].

• Comparing the underlying strength of the routine immunization program, using estimated levels of vaccination coverage at the time the SIA was conducted, as a proxy (Grouping countries with coverage ≤ 70%, countries with coverage between 71% and 89%, and countries with coverage≥ 90%)^f.

We also analyzed the operational costs across the portfolio of vaccines that have a campaign-based delivery component (i.e. JE, measles, measles-rubella (MR), menA, typhoid, and yellow fever vaccines) and that the GAVI Alliance supports or has committed to support [27]. In particular, we sought to assess how the actual operational cost expenditures compare to the levels of support that GAVI offers to countries conducting SIAs; namely US$0.30 per targeted person for SIAs conducted between 2004 and 2012, and US$0.65 per targeted person thereafter [28].

Data sources

The primary source for this analysis was country-specific data from cMYPs submitted to the WHO and the United Nations Children’s Fund (UNICEF) in 2009 and 2011 [29]. cMYPs are used mainly by immunization program managers in LICs and MICs to articulate a long-term costed plan for a national immunization program. For the reference-style data underlying the analysis (e.g., country population size data, GDP deflators), we employed datasets validated by third-party multilateral agencies [30, 31].

Analytic approach

Each cMYP records actual cost data for a ‘baseline year’, followed by a five-year projection period in which future costs of the program are estimated. We extracted and aggregated operational cost data and total target population data per SIA conducted from the cMYP baseline years alone in order to focus on the best quality and most homogeneous actual information^g. The cost data were consolidated and inflation-adjusted into 2010 dollars [23]. The inflation-adjusted operational costs per SIA were then combined with data on relevant target populations specified in the cMYP in order to control for the different target populations of campaigns and to generate standardized operational costs metrics on a population-weighted per person basis.

Sample descriptive statistics

The extracted baseline cMYP data constitutes 142 SIA country observations of SIA operational costs from 70 cMYPs produced by 40 countries; i.e. several countries developed more than one cMYP, and several countries conducted more than one SIA over the analytical period. Of the 142 observations, 75 are from the period 2004–2007 while 67 are from the period 2008–2011. The distribution of the data by vaccine is illustrated in Figure 1.

In terms of country size and geographic location, 64% of the SIA observations were for Midsize/Large countries, versus 36% for Small countries. Of the observations, 66% were for SIAs conducted in the African region (AFR), 21% in the Eastern Mediterranean (EMR), 11% in South East Asia (SEAR), and the remaining 2% in Western Pacific (WPR) and European (EUR) regions [26]. There were no SIA observations for the Americas region (AMR) because cMYPs are not produced in the same format for countries in this region. Given this regional distribution, only the average operational costs for AFR, EMR and SEAR are presented here since WPR/EUR observations were insufficient to draw out any meaningful results. In terms of immunization program capacity/performance as measured by vaccination coverage, 23% of all the country observations were from countries with DTP3 ≤ 70% at the time the SIA was conducted, 45% from countries with DTP3 between 71% and 89%, and 32% from countries with DTP3 ≥ 90%. By contrast, using MCV1 coverage, the distribution of countries is markedly different; 49% of countries had MCV1 ≤ 70% at the time the SIA was conducted, 32% from countries with MCV1 between 71% and 89%, and 19% from countries with MCV1 ≥ 90%. Finally, in terms of country wealth as measured by per capita income, the vast majority of countries (71%) were classified as Low Income Countries (LICs) by the World Bank at the time of conducting the SIAs, while the remainder of the sample was classified as Lower Middle Income Countries (LMICs).

Elimination and eradication of vaccine preventable disease represent the ultimate in addressing health inequities on a local and global scale respectively, while accelerated disease control represents the next best alternative. Achieving ADC/E/E goals is seen as a public health imperative but success since smallpox eradication has been elusive. Robust planning and budgeting, adequate financing, good governance, and effective implementation of SIAs building on strong routine immunization programs are critical to achieving these goals. Our analyses illustrate that existing evidence that often informs budgeting, planning and financing decisions, is out of date, and for many programs, operational costs may be higher than previously thought. Underestimation of costs and funding shortfalls can lead to SIA implementation delays, and can force implementers to target narrower age groups undermining efforts to reach program goals. Therefore, the results of the analysis presented here may provide national and global-level actors with newer SIA operational cost benchmarks to inform planning, budgeting, and financing decisions in absence of better information.

Our analyses also illustrate where program implementers might focus efforts to seek out efficiencies to manage the upward trends in SIA operational costs. For example, with a significant proportion of costs related to human resources, given that there is often criticism of the culture of per diems related to development assistance [53], new assessment of the most cost effective ways to implement SIAs may focus on this and other major cost drivers.

While the information presented here updates the evidence base, there is a need for continued monitoring and additional research into SIA operational costs and expenditures. These efforts might address the deficiencies and discrepancies in monitoring and reporting of operational costs that are highlighted in our review of the literature. Future research might build on the work presented here using more sophisticated multivariate analysis techniques to explore the extent to which each of the factors identified above (e.g. geographic region, population size, breadth of the target population, route of administration, and the strength of the routine immunization program as measured by vaccination coverage) explain and influence operational costs. Future research efforts might also seek to tie operational costs observed to intermediate outcomes such as coverage, or better still final outcomes like confirmed levels of population immunity so as to understand how different levels of investment in SIAs affect outcomes.

There are a number of areas that have yet to be fully explored where future research/monitoring efforts may focus – most notably to tease out the impact on SIA operational costs of routine system strengthening efforts embedded within SIAs. ADC/E/E program strategies are again pointing to the fact that the key to their success lies not just in high-quality and well-funded SIAs, but in effective routine immunization programs built of strong health systems [54]. Creating more robust routine systems requires its own investment increases (P. Lydon, G. Gandhi, J. Vandelaer, J-M Okwo-Bele: Health systems cost of delivering routine vaccination in low & middle-income countries: What is needed over the next decade?, Submitted), but where successful, these efforts should provide a broader platform for ADC/E/E programs to reach all communities – ultimately reducing the marginal costs of vaccinating each additional child as illustrated by our findings. By contrast however, there are also calls to exploit the visibility and resources of SIAs in order to strengthen routine immunization (e.g. through training routine health workers, procuring cold chain equipment, and improving injection safety and adverse events management), and there is evidence that such approaches are feasible and can have a positive impact [55–57]. While strengthening routine programs through SIAs could reduce the frequency with which these SIAs are needed, there is anecdotal evidence from measles SIAs (comparing follow-up SIAs – where system strengthening efforts are often embedded – to wide age range catch-up SIAs where no system strengthening is undertaken) that strengthening routine programs through SIAs will increase the per person costs of those campaigns (Robert Perry: Personal communication; 2013).

New research might also focus on the effect of growing security needs on operational costs. Recent attacks on vaccinators, particularly those conducting OPV SIAs in remote areas of the remaining polio endemic countries, are hampering ADC/E/E efforts [58, 59]. Additional costs of security for vaccinators in the likes of Northern Nigeria, Pakistan and Afghanistan may drive up SIA costs particularly for SIAs conducted in these areas. Documenting and factoring in these additional costs will be important to ensure SIA budgets are sufficient to overcome these challenges.

Finally, the focus of new studies may need to go beyond existing ADC/E/E programs discussed here. As aforementioned, several underutilized and new vaccines that seem likely to be introduced in the coming years have an SIA delivery component as one-time catch-up strategies, or to periodically maintain herd immunity. Better understanding of the costs of SIAs and how these are likely to change over time will enable more robust assessment of future ADC/E/E policies [60] and help inform the design of new financing strategies to facilitate the large but infrequent investments associated with catch up and follow up SIAs.

^aEncompassing epidemic prevention.

^bOperational costs are normally expressed on a “per person” basis. In some instances, these data are expressed on a “per dose” basis. Where there was insufficient information in the paper to express the information on a per person basis, we excluded the paper.

^cThese were the vaccines and programs for which we had sufficient data to draw out vaccine delivery -specific findings; i.e. for menA SIAs targeting the populations below 29 years of age, or yellow fever SIAs targeting those below 60 years of age, there were insufficient observations to assess how operational costs for these vaccines/age groups compared to OPV, measles and TT/Td vaccines.

^dSince Albendazole/Mebendazole for de-worming and Vitamin A (VitA) are often delivered in campaigns and because many countries have estimated the operational costs of delivering these interventions within their cMYPs, these were included in the per person average costs of orally administered interventions along with OPV.

^eThese population grouping cut-offs were determined based on the countries included in the analysis dataset, balancing a need to ensure sufficient observations in each grouping to explore meaningful differences in operational costs for small versus midsize/large country both by vaccine, route of administration, and overall while simultaneously grouping similar sized countries together (at least where we expect there to be fewest economies of scale—for small countries).

^fThese cut-offs were selected based on published policy/strategy targets associated with the third dose of Diphtheria-Tetanus-Pertussis (DTP3): The GAVI eligibility policy permits countries to apply for most of the routine new/underutilized vaccines so long as they have DTP3 coverage equal to, or greater than 70% [61]. Separately, one of the goals of Global Immunization Vision and Strategy (GIVS) defined in 2005 and reiterated in the DoV GVAP is to reach 90% DTP3 coverage in all national immunization programs [62, 63]. However, we also used the same cut-offs when using the first dose of measles-containing vaccine coverage (MCV1) as an alternative proxy for immunization program strength.

^gAs aforementioned, and unpublished analysis of a larger dataset including actual expenditures and projected operational cost data is presented elsewhere (P. Lydon and G. Gandhi: Introduction of New Vaccines: Analysis of non-vaccine routine and campaign costs for the GAVI Alliance. Unpublished). The larger dataset covered 257 SIAs and was extracted from 87 unique cMYPs produced by 55 countries – Comparing the results generated from the larger but more heterogeneous dataset of 257 observations with the data/results presented in this paper, the estimates for the former were mostly lower than from the latter.

^hAlthough investments to cover core costs are often reported and/or projected by the global coordinators of ADC/E/E programs as part of financial resource requirements (FRRs). [64], (Measles Rubella Initiative: Measles and Measles-Rubella SIA Forecast 2013–2018. Unpublished).