Cost-effectiveness evaluations, such as the one described here, are necessary to define population strategies and help decision makers to choose the most relevant options in term of cost/benefit ratio of immunization programs.
In view of the variety of healthcare systems that exist throughout Brazil, the present analysis was performed from three different scenarios. From the cost study performed in Sao Paulo State, three different costs of hospitalization appeared: the lowest cost was that paid by SUS (R$462 for NBPP and R$830 for BPP), the intermediate cost was the amount actually paid by the public hospital (R$1,992 for NBPP and R$5,103 for BPP) and the highest was the cost of hospitalization in the private hospital (R$19,764 for NBPP and R$33,320 for BPP). Evaluation of cost-effectiveness ratios using the SUS and the public healthcare costs allowed coverage of the public perspective on the whole. In scenario 3, integrating larger costs (private hospitalization costs and absenteeism costs) allowed the inclusion of persons who used a private health care system, i.e., 46% of the total elderly population e.g., persons using a managed care organization.
In many developed countries, acceptable cost-effectiveness thresholds have been defined for planning healthcare policies. However, no such definition is available in Brazil, an emerging country facing limited healthcare resources. The World Health Organization (WHO) has suggested an acceptable cost-effectiveness threshold as one that is less than three times the yearly gross domestic product (GDP) per capita and an excellent cost-effectiveness threshold as one that is less than one times the yearly GDP per capita.13
In Brazil, where the yearly GDP per-capita was R$13,720 in 2007 14
at the time of the analysis, an intervention with a cost-effectiveness of up to R$41,160 may therefore be considered as cost-effective by WHO standards. Consequently, in the present analysis, PPV23 vaccination program from age 60 was either extremely cost-effective (inferior to R$13,720 for social security and public health care perspectives) or cost saving (for societal perspective), depending on the scenario considered. This evidence was in favor of a routine PPV23 vaccination program that would be offered by the government to all adults 60 years of age and older.
Using pessimistic values in deterministic sensitivity analyses, all ICER also were found to be below the WHO cost-effectiveness threshold of R$41,160 (3 times the GDP per capita). Specifically, the ratio with an effectiveness of PPV23 against NBPP at 0% was R$33,342 which is still under this limit. This means that even with no effectiveness against NBPP, a routine PPV23 vaccination program in elderly in Sao Paulo is a cost-effective option, which is in line with the other published studies in reference 15–17
. In addition, in the probabilistic sensitivity analyses, taking into account all uncertainties around parameters and the thresholds of R$41,160, there were a probability of 99.8%, 100% and 100% that the funding of PPV23 vaccination is cost-effective compared to the current situation with no vaccination for scenarios 1, 2 and 3 respectively. If we considered the threshold of R$13,720, the probability would decrease to 60.9%, 74.8% and 87% respectively.
Our results are consistent with those of numerous cost-effectiveness analyses performed in US and Europe. As Postma et al.18
concluded in their literature review published in 2003 on the basis of the international literature in the elderly, the cost-effectiveness for the prevention of invasive pneumococcal disease, considering only direct medical costs, varies from cost-saving to more than €30,000 per LYG or per QALY.15,19–23
These results would justify local implementation of a pneumococcal polysaccharide vaccination program from a pharmacoeconomic point of view. In studies concerning both invasive and non invasive pneumococcal diseases, vaccination with PPV23 is again more cost-effective or cost-saving compared to no vaccination strategy among the elderly, considering only direct medical costs.24–27
This economic benefit increases with age of elderly targeted and vaccination of all individuals above the age 65 years is comparable in terms of cost-effectiveness to many accepted health care interventions.27
The study's limitations were related to the various inputs used. Firstly, in absence of specific local data, incidence and case-fatality rates were derived from international data. It is likely that the disease epidemiology and health service utilization might be different between US/Europe and Brazil because of differences in prevalent strains, antibiotic resistance within the populations, quality of health care and financial architecture of their respective health-care systems. However, the chosen values were discussed and accepted by local experts to ensure their consistency with the local epidemiology. Moreover, to be sure to not overestimate the impact of S. pneumoniae
in Brazil, we used generally the most conservative value found. Epidemiological data related to pneumonia in Latin America was published just before the finalization of this manuscript.7
These local data were globally less conservative than those used in the base case and were all included in sensitivity analysis range. Using these data in the SUS base case scenario returned a cost-effectiveness ratio of R$9,709/LYG. The second limitation is related to the disease costs used in the present analysis. The sample size used to calculate the costs of hospitalization may be considered a limitation. It is enough large for NBPP cost calculation (N = 173 and N = 163 for public and private hospital respectively) but too small for BPP (N = 12 and N = 17 for public and private hospital respectively). Larger studies including larger numbers of patients with BPP will be necessary for confirmation. In addition, our analysis considered only the costs of hospitalization and not the outpatient costs and other costs related to pneumococcal infections such as transportation, diet, etc. Including these costs would increase the economic benefit of PPV23 vaccination. Thirdly, vaccination costs concerned only vaccine price and transportation. Promotion costs to ensure a high coverage rate also would have been estimated.
Over the last decade, the importance and benefit of pneumococcal polysaccharide vaccination in adults has been reviewed due to the decrease of pneumococcal incidence rate in countries with a high coverage rate of pneumococcal conjugate vaccines (PCV) in infants. Indeed, in the US, where the coverage rate of the 7-valent pneumococcal conjugate vaccine (PCV7) in children has achieved 80–90% over the last 6 years, herd immunity has globally led to a 38% decrease in the rate of IPD among elderly.28
However, an increase of the incidence of IPD in adults and elderly caused by non-PCV serotypes has been noted in many settings (“serotype replacement”); these increases range from minimal to substantial29
and could reduce the benefits of the PCV vaccination.30
Subsequently, PPV23 is the only protection available against these non-PCV7 serotypes at this time. Our analysis did not take into account the diminution of pneumococcal infections incidence in adults that could result thanks to the use of the 10-valent pneumococcal conjugate vaccine (PCV10), now routinely used in Brazil. The use of PCV10 in Brazil is recent and to date no herd immunity data are available. The future effect of a PCV10 program in Brazil will depend on coverage rates, serotype prevalence and serotype replacement inherent to PCV would not likely to be observed before the program is well established with a high vaccine coverage rate. However, even including an indirect effect of PCV, we can still expect cost-effectiveness results for PPV23 vaccination program regarding our univariate sensitivity analyses (with the most pessimistic incidence values for NBPP and BPP, ICER stayed cost-effective) and regarding a recent analysis performed in US that included this indirect effect.22
Within the Brazilian population aged more than 59 years, a large proportion is still economically active. Indeed 18.8% of people older than 60 years-old are still employed.31
For this reason, the analysis undertaken from the societal perspective was relevant in Brazil. Prevention strategies such as vaccination are extremely important to maintain the economic activity of adults aged 60 and older to maintain functional independence with advancing age. The aging of the population increases health costs and elderly people with acute diseases often require more complex health examinations and treatments. Elderly patients admitted for longer treatments are also much more susceptible to functionality loss. Therefore, a patient with pneumococcal disease can become economically inactive and incur high expenses with the initial disease and any subsequent sequelae.