In the base case simulation, the costs of pneumococcal disease that were avoided by vaccination were greater than the cost of a vaccination program, thus indicating that PPV23 vaccination was cost saving. The results of our analyses are consistent with other analyses performed on pneumococcal polysaccharide vaccines, which demonstrated that a pneumococcal vaccination program is likely to be cost effective if not cost saving.11,14–18
Pneumococcal vaccination has previously been reported to be cost-effective across 10 western European countries, including the prevention of bacteremia alone.19
However, pneumococcal vaccines were found to be greatly underused in the elderly population.17,18
In addition, a cost-effectiveness analysis for IPD in the elderly in England and Wales showed that routine vaccination of all elderly appeared to be cost effective, although the results were dependent on the uncertainties around vaccine effectiveness estimates and the number of hospitalizations and deaths attributable to IPD.11
Moreover, when also a small proportion of NBPP cases are prevented, the cost-effectiveness of pneumococcal vaccination increased markedly compared with preventing BPP alone.14
The present study does have limitations including the large standard deviation associated with the costing data. In the retrospective study during 2006, the inpatient costs were unexpectedly high compared with other years, which would have impacted the mean costs calculated. This could have been due to the intensive-care unit being used more in 2006 than in previous years, the fact that 100% of patients included in the 2006 data were high risk (compared to 87%, 97% and 92% in 2002, 2003 and 2004, and 2005 respectively), and the low sample size. Nevertheless, data found in patient's file were more precise in 2006 than previous year following hospital recommendations which can explain the higher cost but also increase the robustness of these costs. In comparison of IPD costs of several western European countries,15,20
the costs of illness found in our retrospective study are higher. However, they are similar to US cost data.18
2006 costs have been discussed with local hospitalization team and they validated the reliability of them. Therefore they were included in the base case analysis and the mean cost used should accurately represent the situation in clinical practice as they were obtained from resources consumed over 6 years. Univariate sensitivity analyses were performed using the costs excluding 2006 data from the retrospective study to evaluate the impact of cost data on the cost-effectiveness results. With much more lower costs for NBPP and BPP, a PPV23 program was not found to be cost-saving, however it was determined to be a very cost-effective strategy.
A second limitation is that costs of pneumococcal infections were retrieved from a university hospital where the population might not be representative of the general population in this country. However, since this hospital is located in one of the 3 biggest cities in Turkey and most of the complicated cases are referred to this hospital from other cities close to and far from Ankara, this population should be quite representative of the general Turkish population.
Costs are likely to be higher in a teaching hospital than in a public hospital due to the availability of a greater number of procedures and more advanced technology. According to principle of reimbursement system in Turkey, less severely ill patients should go to public hospital. Thus, this study should be repeated in state hospital. However, in such a setting it may be more difficult to obtain reliable and detailed records of costs.
Comprehensive meta-analyses of studies assessing the PPV23 vaccine efficacy have shown a protective effect against IPD and all-cause pneumonia in the elderly population.21,22
At the opposite, the Cochrane meta-analysis concluded that there was not sufficient evidence to support the routine use of PPV23 to prevent pneumonia.21
The lack of a sensitive and specific method for the diagnosis of pneumococcal pneumonia has limited the study of PPV23 and the conclusions of this meta-analysis can be considered a cause for debate.23
Furthermore, an extensive literature review strongly suggested that the published meta-analyses did not contain a sufficient number of person-years of observation to reach a reliable conclusion as to the efficacy of PPV23 in the prevention of pneumonia or death.24
Recently, a matched case-control study demonstrated that the vaccine was effective against IPD, and also prevented non-bacteremic pneumococcal pneumonia.25
In the present cost-effectiveness analysis only NBPP and BPP were considered. As S. pneumoniae can be also responsible for other conditions such as meningitis, which have an important social and economic burden, this calculation would produce a conservative estimate of the cost of pneumococcal infection. Furthermore, outpatient costs after hospitalization were only available for BPP. Inclusion of NBPP's costs would probably have increased the overall cost of pneumococcal infection, and thus, the benefits of vaccination.
It should be noted that although the simulation was for a single dose of vaccine, which is commonly recommended, two doses are sometimes appropriate for some at-risk individuals. In addition, the simulation assumed that an age-based vaccination policy resulted in a higher VCR than one that was risk based. Indeed, an age-based strategy has been shown to be easier to implement than a risk-based strategy for the vaccination program.11,12
Our model did not take into account the protective effect that vaccinating infants with PCV7 has been demonstrated to have adults (i.e., herd immunity). In US, where the coverage rate in children was around 80–90% over the last 6 years, herd immunity has globally led to a 38% decrease in the rate of IPD among elderly.26
However, an increase of the incidence of serotypes not covered by PCV7 in adults and elderly people has been observed, and subsequently, PPV23 is the only protection available against these non-PCV serotypes.27
At present, Turkey has not undertaken universal immunization of infants with PCV7, although it is considering the implementation of such a program. The future effect of a PCV7 program in Turkey will depend on the VCR and serotype prevalence, and would not likely to be observed before the program is well established with a high VCR. However, in terms of the conclusions drawn on cost-effectiveness, PPV immunization should not changed, since its cost-effectiveness has recently been demonstrated by an analysis performed in the US.18
This study showed that vaccination remains economically attractive and cost-effective even if the incidence of pneumococcal disease has decreased among adults. Indeed, the lower IPD incidence in adults simply means that the Cost Effectiveness (CE) ratio must increase. Since the initial CE ratio was very low, even if doubled the cost-effectiveness of PPV23 for elderly and high risk adults would still be highly acceptable. Using the GDP threshold given by the WHO guidelines (strategy not cost-effective if superior to 3 times the GDP per capita i.e., superior to 47,400 YTL for Turkey), we evaluated the value of the IPD incidence where the public funding of PPV23 in elderly and at-risk people were not cost-effective. The IPD incidence should decrease by 60% (21 per 100,000) and 85% (7.9 per 100,000) from the base case values in elderly and in at-risk adults respectively in order to give an ICER not cost-effective that is higher than 47,400 YTL/QALYs.
The current VCR in Turkey of 2% of at-risk adults and elderly is very low despite the reimbursement of PPV23 in these groups since 2007. The reasons for this may implicate factors involving intervention by public health organizations or the perspective of physicians and the general public on pneumococcal vaccination. Low VCR can be explained by the lack of an effective vaccination program or absence of systems for delivering the vaccination, such as in the workplace, nursing homes or healthcare center.28,29
Indeed, in Turkey, every patient should visit pharmacy, buy the vaccine and then come to health care setting to receive prescribed vaccine, knowing that physicians can not offer PPV before the patient's discharge from their clinic. In addition, physicians have a low awareness of the risks of pneumococcal disease and the benefits of vaccination which affects their recommendation of PPV23, health care workers recommendation being the most important driver of the coverage rate's improvement.10
Lastly, other clinical priorities compete against vaccination programs and physicians delegate vaccination issues to the primary care settings. Offering vaccination in different places such as adult vaccination rooms or before discharging patient from hospital seems to increase such a low PPV23 vaccination rates in Turkey. Data from the active promotion of the benefits of pneumococcal vaccination were not included in this study since the results have been difficult to evaluate. However, costs saved by a pneumococcal vaccination program could be reinvested in the education of physicians and the public on the benefits of vaccination. In conclusion, this model suggests that a pneumococcal vaccination program in the elderly and at-risk populations in Turkey would be cost saving. These results are consistent with previous studies conducted with pneumococcal polysaccharide vaccines. Vaccination of the elderly with PPV23 is now publicly funded in Turkey. Nevertheless, the VCR in Turkey has been minimal, and its increase would improve public health. In addition, an awareness campaign to promote the benefits of pneumococcal vaccination in the elderly and at-risk adults should be undertaken in Turkey, targeting selected high-risk populations and the medical community. An appropriate use of the money saved as a result of pneumococcal vaccination would be to promote the benefits of vaccination and thereby raise the VCR.