02 Cost-Effectiveness of Influenza Vaccination for People Aged 50 to 64 - An International Model

8/3/2019 02 Cost-Effectiveness of Influenza Vaccination for People Aged 50 to 64 - An International Model

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Volume 10 Number 2 2007V A L U E I N H E A L T H

98 2007, International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 1098-3015/07/98 9811

10.1111/j.1524-4733.2006.00157.x

Blackwell Publishing IncMalden, USAVHEValue in Health1098-30152006, International Society for Pharmacoeconomics and Outcomes Research (ISPOR)200710298116Original ArticlesCEA of Inuenza Vaccination for 50- to 64-Year-OldsAballa et al.

Address correspondence to: Jeremy Chancellor, Director, i3 Inno-vus, 3rd oor, Beaufort House, Cricket Field Road, Uxbridge,Middlesex, UB8 1QG, UK. E-mail: [email protected]

The Cost-Effectiveness of Influenza Vaccination for People Aged50 to 64 Years: An International Model

Samuel Aballa, MSc,1 Jeremy Chancellor, MSc,1 Monique Martin, MSc,1 Peter Wutzler, MD,2

Fabrice Carrat, MD, PhD,3

Roberto Gasparini, MD,4

Joao Toniolo-Neto, MD,5

Michael Drummond, DPhil,1,6

Milton Weinstein, PhD7,81i3 Innovus, Uxbridge, UK;2Institute of Virology and Antiviral Therapy, University of Jena, Jena, Germany;3INSERM U444, Paris, France;4Department of Health Sciences, University of Genoa, Genoa, Italy;5Regional Inuenza Surveillance Group, Federal University of So Paulo, SoPaulo, Brazil;6Centre for Health Economics, University of York, York, UK;7i3 Innovus, Medford, MA, USA;8Harvard School of Public Health,Boston, MA, USA

ABSTRACT

Objectives: Routine inuenza vaccination is currently rec-ommended in several countries for people aged more than 60or 65 years or with high risk of complications. A lower age

threshold of 50 years has been recommended in the UnitedStates since 1999. To help policymakers consider whethersuch a policy should be adopted more widely, we conductedan economic evaluation of lowering the age limit for routineinuenza vaccination to 50 years in Brazil, France, Germany,and Italy.Methods: The probabilistic model was designed to comparein a single season the costs and clinical outcomes associatedwith two alternative vaccination policies for persons aged 50to 64 years: reimbursement only for people at high risk of complications (current policy), and reimbursement for allindividuals in this age group (proposed policy). Two perspec-tives were considered: third-party payer (TPP) and societal.

Model inputs were obtained primarily from the published lit-erature and validated through expert opinion. The historicaldistribution of annual inuenza-like illness (ILI) incidencewas used to simulate the uncertain incidence in any given sea-son. We estimated gains in unadjusted and quality-adjustedlife expectancy, and the cost per quality-adjusted life-year

(QALY) gained. Deterministic and probabilistic sensitivityanalyses were conducted.Results: Comparing the proposed to the current policy, the

estimated mean costs per QALY gained were R$4,100, 13,200, 31,400 and 15,700 for Brazil, France, Germany,and Italy, respectively, from a TPP perspective. From the soci-etal perspective, the age-based policy is predicted to yield netcost savings in Germany and Italy, whereas the cost perQALY decreased to R$2800 for Brazil and 8000 for France.The results were particularly sensitive to the ILI incidencerate, vaccine uptake, inuenza fatality rate, and the costs of administering vaccination. Assuming a cost-effectivenessthreshold ratio of 50,000 per QALY gained, the probabili-ties of the new policy being cost-effective were 94% and95% for France, 72% and near 100% for Germany, and89% and 99% for Italy, from the TPP and societal perspec-

tives, respectively.Conclusions: Extending routine inuenza vaccination topeople more than 50 years of age is likely to be cost-effectivein all four countries studied. Keywords: cost-effectiveness analysis, inuenza, model, vac-cination, vaccines.

Background and Objective

Inuenza epidemics are associated with an increase inacute respiratory infections, hospital admissions andmortality [14], imposing a signicant burden of ill-ness and placing an acute strain on health-careresources. This has led to a widespread policy of pro-viding routine annual vaccination for the elderly, whoare at high risk of potentially life-threatening com-plications. In many countries (including France andItaly), vaccination is recommended for people morethan 65 years old and for younger people with risk fac-

tors for inuenza complications. In other countries,such as Germany and Brazil, the policy is to vaccinateall people aged more than 60 years, as well as youngerpeople at increased risk. The range of risk factors gov-erning policy varies between countries, but generally

includes diabetes, chronic respiratory diseases (e.g.,asthma, chronic obstructive pulmonary disease), car-diovascular disease (e.g., ischemic heart disease, con-gestive heart failure, stroke), immunodeciencies (e.g.,HIV), and cystic brosis.

Implementing a risk-dened vaccination policydepends upon primary care providers taking concertedaction to identify and reach patients meeting the crite-ria. As risk is a function of increasing age as well ascomorbidity [5], possibly a more practical means of achieving coverage of at-risk patients would be simplyto lower the age threshold for routine eligibility.


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Aballa et al.100

literature on epidemiological surveillance and health-care resource utilization is based on ILI, so it was morepractical to estimate model parameters using this casedenition. According to the International Classica-tion of Health Problems in Primary Care [21], a diag-nosis of ILI should be made when at least one of the

three following conditions is veried:1. Inuenza virus culture positive or serological evi-

dence of inuenza virus infection;2. Context of inuenza epidemic and four of the cri-

teria in (3) below;3. Six of the following criteria: sudden onset (within

12 hours), cough, fever, chills, prostration andweakness, myalgia or general pain, rhinitis, phar-yngitis, and contact with a case.

European surveillance networks, however, use var-iable denitions [22], and the model inputs for eachcountry are driven by available data.

The use of ILI as the case denition is supported bythe availability of appropriate efcacy data for eachmodeled event: occurrence of ILI, work absence, minorcomplications, hospitalizations, and deaths. Themodel takes account of the fact that complications areless likely to occur in vaccinated than nonvaccinatedILI cases. Vaccine efcacy was considered similaracross all patient groups, as there is little evidence

for an association with age or presence of chronicconditions.

The pathways of events considered in the model areshown as a decision tree in Figure 1. Under each pol-icy, the target population consists of HRs and LRs,who may or may not be vaccinated and, as a conse-

quence, face differing probabilities of remaininghealthy or contracting ILI in the winter inuenza sea-son after vaccination. Patients with ILI choose whetheror not to seek medical help, and if so they may receivesymptomatic antiviral medication. The model includesthe effect of these drugs in reducing work absence andrisk of complications. Self-medication is not modeled,because of the difculty in estimating ILI-related over-the-counter drug use. Patients may remain free of com-plications and recover normally, incur a minor com-plication, suffer a complication requiring hospitaladmission, or die. For minor complications, such asacute bronchitis, the costs of additional consultations,

tests, and antibiotics are taken into account, but nolonger-term health decit is assumed to occur. Hospi-talizations are treated in three categories: pneumoniaand inuenza, other respiratory complications, andnonrespiratory complications, including circulatoryand diabetic problems. In the tree (Fig. 1), patients notattending for ILI may survive or die, although it wasassumed for the countries studied here that deaths

Figure 1 Decision tree for inuenza vaccination policies and consequences. Note: Repeating parts of the tree, or subtrees are omitted for clarity. Athe nodes marked Clone 1: Vaccination status subtree, the omitted subtrees are identical to the entire subtree that emanates from the right of the boldbranch and node labeled 1. At the node marked Clone 2: ILI subtree, the omitted subtree is identical to the entire subtree that emanates from thright of the bold branch and node labeled 2. A&E, accident and emergency; GP, general physician; ILI, inuenza-like illness.

Remain healthy

Minor complication

Hospitalization

Death

Disease complication

No complication

Antiviral

Minor complication

Hospitalization

Death

Disease complication

No complication

No antiviral

Consult GP / A&E

Alive

DeadNo medical attendance

2

ILI

Vaccinated

Remain healthy

ILIClone 2: ILI subtree

Unvaccinated

1

High risk

Low riskClone 1: Vaccination status subtree

New policy

High riskClone 1: Vaccination status subtree

Low riskClone 1: Vaccination status subtree

Current policy

Vaccinationcandidatepopulation


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CEA of Inuenza Vaccination for 50- to 64-Year-Olds 101

occur only in patients who have received medicalattention.

An episode of ILI was assumed to result in a givennumber of lost workdays specic to each country,which did not vary according to vaccination status,but did vary according to whether or not the patient

consulted his or her general practitioner (GP). Treat-ment with antivirals was assumed to reduce the lengthof absence.

Model OutcomesThe following categories of costs were considered fromthe third-party payer (TPP) perspective:

Cost of vaccination, including vaccine acquisitionand administration;

Primary care costs for ILI patients: GP visits,prescription drugs, diagnostic tests, and possiblereferrals to a specialist in case of complication;

Hospitalizations because of pneumonia, otherrespiratory complications, or cardiovascularcomplications;

Sick-leave payments for countries where a singleagency funds both health care and sick leave, andwhere payments are given even for short absences(e.g., France).

The TPP perspective included only the share of totalhealth-care costs borne by third-party payers. It didnot include patient copayments. From the societal per-spective, patient copayments were included, alongwith the cost of absenteeism to employers. For France,Germany, and Italy, costs are reported in Euros ( ), for

the reference year 2003. For Brazil, costs are reportedin reals (R$). The mean nominal exchange rate in 2003was R$3.07 per US dollar and R$3.52 per euro. Allcosts were incurred within a single year, so the need fordiscounting did not arise.

The model is designed to calculate several out-comes: averted ILI cases, hospital admissions anddeaths, life expectancy in unadjusted life-years (LYs),and quality-adjusted life-years (QALYs). QALYs werecalculated by applying weighting factors representingthe quality of life for each year of survival and sum-ming over the number of years of life expectancy. Inthe absence of age-specic norms for the countries

studied, we used proxy weights from the Health Sur-vey for England 1996 for the base case [23] and fromthe Canadian National Population Health Survey(1996 for sensitivity analysis (see Table A1). Transientreductions in quality of life because of inuenza epi-sodes were not considered, as these are short incomparison with a lifetime. Any difference betweenpolicies in the calculated number of QALYs wouldtherefore be attributable only to differences in inu-enza mortality rates and the resulting impact on lifeexpectancy. LYs and QALYs were discounted topresent values at 3% per annum [24]. Principal model

inputs are shown in Table 1. Most data were obtainedfrom the literature, national, or general statisticalsources (e.g., Organisation for Economic Co-operationand Development, Eurostat), epidemiological surveil-lance Web sites, and country-specic tariffs.

Sources of Data: Noncountry-Specic We assumed that vaccine effectiveness does not differbetween countries and considered studies from anycountry. Where parameters were thought to be coun-try-specic, we sought local data but relied on datafrom other countries as needed. The clinician authors(JT-N, FC, PW, RG) validated inputs for their respec-tive countries. All epidemiological data (ILI incidence,hospitalization rates, case fatality rates) were specicto people aged 50 to 60 or 64 years old.

A number of clinical effectiveness parameters wererequired. The reduction in the number of ILI casesbecause of vaccination was taken from a systematic

Cochrane review by Demicheli et al. [25]. The reviewidentied 10 trials published between 1966 and 1997and reported that vaccination reduced the number of clinical cases by 29% (95% condence interval (CI)1242%). The ndings of more recent vaccine trials innonelderly adults (Campbell et al. (1997) [26], Nicholet al. (1999) [27], Bridges et al. (2000) [10], and Villari(2004) ) [28] are consistent with the systematic review.

A similar reduction of 29% was applied to theprobability of seeking medical attention for ILI, to theuse of antivirals and other medications (e.g., antibiot-ics, analgesics), and to lost workdays (Table A2). Thiswas broadly consistent with the results of trials by

Nichol et al. (1995) [8], Nichol et al. (1999) [27], andBridges et al. (2000) [10]. We assumed that the per-centage reduction in utilization of antivirals and othermedications (e.g., antibiotics, analgesics) is similar tothe percentage reduction in physician visits, whichwould be true if vaccinated patients were treated in thesame way as nonvaccinated patients. Although intui-tively the latter seem likelier to be treated as havingtrue inuenza, results from Nichol et al. [27] andBridges et al. [10] suggest the assumption is accepta-ble. For minor complications, we used the 28.1%(95% CI 16.038.4) reduction reported by Nicholet al. [27].

There have been relatively few studies [25,29] of theeffectiveness of inuenza vaccines in preventing hospi-talizations and deaths in nonelderly adults. We usedresults of a meta-analysis of 20 cohort studies of theeffectiveness of the inuenza vaccine in elderly persons[30], which reported a reduction in hospital admis-sions of 50% (95% CI 2865%) and a reduction inmortality of 68% (95% CI 5676%).

Antiviral effectiveness parameters are shown inTable A3. The reduction in lost workdays because of antivirals was obtained from a large, multinationaltrial of zanamivir versus placebo [31]. The reduction in


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antibiotic use was obtained from a systematic reviewon zanamivir in the treatment of inuenza in adults[32]. Reductions in complication rates were obtainedfrom a systematic review of zanamivir and oseltamivir[33]. As the prescribed proportions of the two antivi-rals vary between countries, we used market share datato calculate a weighted overall antiviral efcacy ratefor each country.

Sources of Data: Country-Specic Country-specic data included population size, lifeexpectancy, the proportion of HRs aged 50 to 59 or

64 years, the proportion currently eligible for vaccina-tion, vaccination uptake under the current policy, theinuenza attack rate, propensity to seek medical atten-tion for ILI, antiviral usage, probabilities of minorcomplications and of requiring hospital admission,and the case fatality rate. The base case inputs for eachcountry are shown in Tables A4A11. Our approachto gathering these inputs was to use published localdata as far as possible. To this end, the clinicianauthors (JT-N, FC, PW, RG) completed a detailed,structured questionnaire, identifying published sourcesof country-specic information as far as possible.

Where country-specic data were not available, judg-ments were made as to whether data from other coun-tries was likely to be generalizable, or whether expertopinion would be preferable. Sensitivity analyses wereperformed where parameter inputs were uncertain.Demographic data were taken from national sources.Unit costs for each resource item were collected foreach country, along with the proportions of costs facedby third-party payers compared with society as awhole, to allow analyses from TPP and societalperspectives.

Current vaccination coverage rates were obtained

from TNS Sofres market research surveys in the threeEuropean countries [34] and from unpublished dataknown to JT-N in Brazil. The model required the inputof coverage rates by risk status, as vaccination isexpected to be higher in HRs. A Spanish study, usingdata from the 1997 National Health Survey, showedthat the uptake in HRs aged 50 to 64 years was 2.44times higher than the uptake in LRs in the same agegroup. Based on this information and the proportionof HRs, vaccine coverage rates were calculated forGermany and Italy. In France, the vaccination uptakein HRs (individuals younger than 65 but eligible for

Table 1 Model input values

Parameter Base case input value (SD) Alternative valuesType of

distribution Source

Discount rate (%) 3 0, 5, 8, 10 depending on countryIncidence of ILI consultations (%) Varies between countries

(approximately 5, SD 2.3)25 and 185 of base case Empirical [15;6062]

Probability of hospitalizations(Germany/France/Italy, %) HR: 11.3 (0.9)13.4 (1.0)LR: 1.4 (0.4)1.6 (0.5) HR: 044; LR: 0.04HR: 6.478.04; LR: 0.690.85HR: 10.69; LR: 2.38

Beta [63,64]

Probability of hospitalizations(Brazil, %)

HR: 3.05 (1.12); LR: 0.33 (0.12) HR: 0.44; LR: 0.04HR: 2.11; LR: 0.23HR: 3.11; LR: 0.34HR: 4.74; LR: 0.52HR: 10.69; LR: 2.38

Lognormal [64,65]

Probability of death (%) HR: 0.826 (0.222)1.023 (0.247)LR: 0.015 (0.029)0.017 (0.031)

HR: 0.241; LR: 0.081HR: 1.0051.249; LR: 0.0090.011HR: 1.0631.322; LR: 0.0090.012

[1,4,39,64]

Elasticity of labor to production (%) 100 80 Vaccine efcacy: reduction in

incidence of ILI consultations (%)29 (8) 1242 Lognormal [25]

Vaccine efcacy: reduction in excessincidence of hospitalizations (%)

50 (11) 2865 Lognormal [30]

Vaccine efcacy: reduction in excessmortality (%) 68 (5) 5676 Lognormal [30]Utilities Based on EQ-5D norms, Health

Survey for England, 1996Based on HUI3 norms, National Population

Health Survey, 1996 (Canada) [66]

Time off work for vaccination None 1 hour per vaccine in full-timeemployment

Vaccine administration, LRFrance(%)

Routine visit: 18.3 (7.9)Special visit: 73.2 (8.0)Occupational visit: 8.5 (1.4)

Routine visit: 40Special visit: 20Occupational visit: 40

Triangular [67,68]

Vaccine priceGermany ( ) 7.00 (0.55) 5.00, 9.00 Triangular [69]Vaccine priceItaly ( ) 6.57 (0.45) 5.00, 10.00 TriangularVaccine administration cost, societal

perspectiveBrazil (R$)3.58 (2.68) 0.50, 10.00 Gamma [15,70]

HR, patients at high risk of complications; HUI3, Health Utilities Index mark 3; ILI, inuenza-like illness; LR, patients at low risk of complications.


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free vaccination) was known from national insurancedata [35,36]. Coverage in LRs was calculated usingknown rates for HRs and the aggregate population. InBrazil, the VigiGripe study reported that the vaccina-tion coverage rates in the public sector were 12% inHRs and 2% in LRs [37].

Vaccination uptake under the proposed policy wasassumed be equal to current uptake in people morethan 65 years (more than 60 years in Germany andBrazil). Studies have suggested that when entire agegroups are targeted for routine vaccination, coverage isapproximately 30% higher in people with high-riskchronic conditions than in those without [3840]. Weused this assumption to apportion coverage betweenHRs and LRs across the 50 to 59 or 64 years agegroup. In Brazil, coverage rates of 75% and greaterhave been reported in people aged more than 65 years[41]. We considered that such high levels of coverageare unlikely to be reached in the 50 to 64 years age

group. Therefore, we based assumed coverage rates ona reported Brazilian government target of 70% [42].Unit costs of resource items, including vaccine andadministration, consultations for ILI, and clinicalconsequences and lost productivity, were obtainedfrom national sources (see Table A10 and Table A11).Analyses from the TPP perspective were based on thereimbursed portions only of unit costs.

Economic AnalysesExpected costs, outcomes and incremental cost-effectiveness ratios (ICERs) were calculated for each of the four countries and perspectives. ICERs were

reported as mean cost per QALY gained for the pro-posed versus current policy. Deterministic sensitivityanalyses were performed on key model inputs, subjectto scenario or parameter uncertainty, to determine theindividual impact of alternative assumptions. Base caseinputs and alternative values are shown in Table 1.

Probabilistic analyses were performed by MonteCarlo simulation to propagate the joint effects of parameter uncertainty through the model. Again, thesewere carried out for all four countries and both ana-lytic perspectives. For variables based on sample dis-tributions, such as the meta-analysis of efcacy rates,we applied the reported parameter values to an appro-

priate distributional form [43]. For some inputs, wewere obliged to specify distributions subjectively, inthe absence of empirical evidence. For example, wespecied the proportion of HRs as a triangular distri-bution around estimates of the extreme and mean val-ues. The model inputs specied as distributions, alongwith the distributional forms and parameters used, arelisted in Table A12. Mean incremental costs and incre-mental QALYs, along with 95% credible intervalsusing the 2.5th and 97.5th percentile values, werederived from the Monte Carlo simulations. The indi-vidual simulated pairs of incremental cost and QALY

values were used to generate cost-effectiveness accept-ability curves.

The underlying prevalence of inuenza viruses inthe winter months varies widely from year to year,with a relatively low number of true inuenza cases insome years and epidemics in others. To model this nat-

ural uctuation, we used an empirical distribution of historical ILI incidence as the best available data topredict future incidence. The INSERM surveillancenetwork in France provides estimates of the incidenceof ILI consultations for the years 1985 to 2002 amongpeople aged 50 to 59 years. These range from 1.2% to8.7%, with an average of 4.7% (compared with anaverage annual incidence of 6.1% in the overall pop-ulation). This distribution was used for the Frenchanalysis. Local surveillance data for the other threecountries were adjusted for age, and historical distri-butions were estimated using the INSERM data. It isnotable that average annual attack rates from surveil-

lance are much lower than those reported in clinicaltrials [25], and provide conservative estimates for thismodel.

These attack rate estimates could not be useddirectly, as they come from populations with a non-negligible proportion of vaccinated persons, and there-fore underestimate the probability of ILI in the unvac-cinated proportion. The incidence of ILI consultationsin the unvaccinated population was derived from theobserved incidence, the vaccination uptake during theobservation period, and vaccine efcacy. For example,in France, where the observed average incidence was4.69%, the overall vaccine uptake was 21.1%, and the

effectiveness on ILI was 29%, the incidence of ILI,I , inunvaccinated persons was calculated as:

Results

Base-Case AnalysesThe results of the incremental CEAs are shown inTable 2. The mean ICERs for Brazil, France, Germany,and Italy are approximately R$4100, 13,200, 31,400, and 15,700 per QALY gained, respectively,from a TPP perspective. From a societal perspective,

the new policy would cost R$2800 per QALY gainedin Brazil and 8000 per QALY gained in France,whereas it would dominate the current policy in Ger-many and Italy.

Using the assumed rates of population coverage, theproposed policy would avert approximately 80,000cases of ILI per year in Brazil, 116,000 cases in France,54,000 cases in Germany and 96,000 in Italy. Thiswould translate into approximately 210, 440, 120,and 230 deaths avoided annually in these four coun-tries, respectively. Detailed results on the outcomesexpressed as ILI cases, hospital admissions, deaths and

I = ( )

=4 69

1 21 1 295 00.

..

% %%


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the assumed overall increase in coverage, particularlyamong HRs, is less than that in the other countries,resulting in a correspondingly smaller gain in QALYs.Health gain is strongly related to the improvement of vaccination uptake in the HR group.

As noted earlier, the adoption of a societal ratherthan a TPP perspective enhances the cost-effectivenessof the new policy in all four countries. As Table 4shows, this is due to net reductions in incrementalcosts, although their magnitude and breakdown differsmarkedly between countries. The inclusion of theimpact on productivity losses contributes favorably to

cost-effectiveness in all four countries, but this effect ismodied in differing directions by national variationsin payment arrangements for additional vaccinecoverage.

In Brazil, there is a high degree of variability in thecost-to-charge ratio for vaccine administration. Thisintroduces uncertainty into the societal results, whichare based on costs rather than charges. In Germanyand Italy, the incremental societal cost of expandingvaccination is mitigated by the fact that under the cur-rent policy noneligible individuals purchase vaccine atprices much higher than contract prices that third-party payers could negotiate under the proposed pol-

icy. Furthermore, under the nancing assumptionsused in this analysis, although newly covered personsin France would receive the vaccine free of charge, theywould face a 30% copayment for the cost of an addi-tional primary care visit for vaccination. The smallproportion of Italians opting for vaccination in the pri-vate sector would face the full cost of vaccination andphysician visit, whereas patients covered in Germanywould bear none of the vaccination costs at all. The netimpact of these variations is to reverse the ordering of results between perspectives among the Europeancountries. From a TPP perspective, the new policy was

most cost-effective in France, then Italy, then Germany,but from a societal perspective the new policy wasclearly dominant in Germany, just dominant in Italy,and not dominant in France. The incremental societalcosts of the new policy would be lowest in Germanyand highest in France among the European countries.

Another variation between countries is the relativecost of vaccination between new and existing policies.In France, most current visits for vaccination areopportunistic, so the cost is lower than it would be forvaccination-specic visits under the new policy. In Ger-many and Italy, however, signicant numbers of non-

eligible persons currently choose to be vaccinated, inspite of facing a higher cost than public payers incuron behalf of eligible vaccinees.

Deterministic Sensitivity AnalysesDeterministic sensitivity analyses were carried out onall variables, subject to decision or parameter uncer-tainty. By far the most sensitive input was the attackrate, i.e., the incidence of ILI consultations, regardlessof country or perspective. As Figure 2 shows, the ICERfor all three of the European countries fell below 50,000 per QALY gained from a TPP perspective pro-vided the attack rate exceeded 3%, which was true in

13 of the 18 years of INSERM surveillance databetween 1985 and 2002. Greater proportions of thepopulation at high risk of complications from ILI andhigher death rates after consultation for ILI producedlower ICERs. These were the three most sensitiveinputs, regardless of country perspective. The resultswere moderately sensitive to the choice of discountrate, lower rates producing lower ICERs, and theuptake rate of the new policy, for which higher ratesresulted in lower ICERs.

From the societal perspective, assumptions concern-ing the numbers of workdays lost to ILI were moder-

Table 4 Total cost breakdown of current and proposed policies at population level, by country

Country Perspective PolicyVaccination Primary care Hospitalization Lost productivity Total

Absolute Difference Absolute Difference Absolute Difference Absolute Difference Absolute Difference

Brazil TPP Current 0.9 5.0 0.6 0 6.5Proposed 12.4 11.5 4.1 0.9 0.4 0.2 0 0 16.9 10.4

Societal Current 1.4 15.1 4.4 35.4 56.4Proposed 19.7 18.3 12.3 2.8 3.0 1.4 28.6 6.9 63.5 7.2

France TPP Current 7.3 13.8 62.7 5.9 90.6Proposed 97.8 90.5 11.9 1.8 45.7 17.0 6.8 0.9 161.4 70.8


Germany TPP Current 5.1 11.3 62.6 0 79.2Proposed 59.0 53.9 10.6 0.7 56.3 6.4 0 0 125.9 46.7


Italy TPP Current 13.5 13.7 68.9 0 96.0Proposed 69.9 56.5 12.4 1.3 57.7 11.1 0 0 140.0 44.0


Brazil data in R$ millions, France, Germany, and Italy in millions, rounded to nearest 0.1 million.TPP, third-party payer.


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cost-effective were 94% and 95% for France, 72%and near 100% for Germany, and 89% and 99% for

Italy from the TPP and societal perspectives, respec-tively. If the Brazilian GDP per capita in 2003 of R$8558 ( 2431) were taken as a possible ceiling value,the new policy would be cost-effective with a proba-bility of 83% from the TPP perspective, and 79% fromthe societal perspective in that country. Differencesamong countries were mainly driven by vaccinationuptake rates, vaccine administration costs, and nanc-ing arrangements. This analysis conrms the ndingsof previous published economic evaluations, whichhave established economic advantages of inuenzavaccination [7,9,33,44,47].

In this study, we used a reported rate of efcacy

from a meta-analysis [25] of clinical trials of inacti-vated vaccines, using ILI as the end point. At facevalue, the efcacy of 29% appears surprisingly low,but it must be remembered that in a majority of con-sultations for ILI, the infection is not true inuenza.The efcacy of vaccination against serologically con-rmed cases of inuenza was estimated at 68% in thesame review. As much of the literature informing thismodel necessarily uses a case denition of ILI, becauseof the infeasibility of laboratory conrmation of inu-enza in large, community-based studies, we wereobliged to use this end point also. Since our analysis

was conducted, an update of the Cochrane review onwhich the vaccine efcacy assumptions were based has

been published [48]. Although the data are not pooledin exactly the same manner, the updated study suggestsan efcacy of approximately 26% or 27% comparedwith 29% in the original review. In light of the sensi-tivity analyses performed on vaccine efcacy, theimpact of using the updated data would be a smallincrease in the estimated ICERs.

Most evaluations in nonelderly adults have concen-trated on healthy working persons. These studiesreported cost savings, largely related to avoided loss inworkdays, but used less conservative assumptions forthe efcacy of vaccination. Nichol [49] assumed anincidence of inuenza illness of 5% but a vaccine effec-

tiveness of 75%, and Lee et al. [44] assumed an inci-dence of inuenza illness of 15% and an effectivenessof 68%. Our ndings were similar when higher ef-cacy rates were used in sensitivity analyses.

A feature of this study is its pragmatic view on thecoverage likely to be achieved under the new policy.Although all persons more than 50 years old would beeligible for vaccination, it seems unlikely that thiswould be achieved without a signicant increase inhealth promotion efforts. We assumed that uptakerates would be equivalent to the reported level of cov-erage achieved in people in the higher age groups who

Figure 3 Tornado chart of univariate sensitivity analyses: France, TPP perspective. Note: ranges of input values shown in parentheses correspond to order of ICER values represented by ends of bars. Asterisked values are base case inputs. HR, patients at high risk of complications; HUI3, Health UtIndex mark 3; LR, patients at low risk of complications.

0 20 40 60 80

Elasticity of production (100%* to 80%)

Less GP visits per case (1.2* to 1 visit)

Minor complication (LR 22.9/13.6*/0.9%, HR 29.0/17.3*/7.2%)

500,000 vaccination campaign vs. none*

Uptake under current policy (95% CI for TNS survey)

Greater antiviral use (LR 4* to10%, HR 6* to15%)

Workdays lost (5.9/4.0*/1.3 days)

HUI3 in lieu of EQ-5D*

Vaccine efficacy: ILI (95% CI: 42/29*/12%)

Vaccine efficacy: hospital admission (95% CI: 65/50*/28%)

Admission|ILI consultations (LR 1.54* vs 0.04%, HR 12.73* vs 0.44%)

Vaccine efficacy: mortality (95% CI: 76/68*/56%)

Proportion at high risk of complications (31/25*/21%)

Incremental use of routine visits, nurse-administered

Discount rate (0/3*/5%)

Lower uptake - new policy (LR 60* to 29%, HR 77* to 41%)

Death|ILI consultations (HR 1.17/0.96*/0.24%)

Incidence of ILI consultations (8.7/4.7*/1.2%)

Thousands

ICER ( per QALY gained)


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Aballa et al.108

Figure 4 Tornado chart of univariate sensitivity analyses: France, societal perspective. Note: ranges of input values shown in parentheses correspoto the order of ICER values represented by ends of bars. Asterisked values are base case inputs. HR, patients at high risk of complications; HUI3, HeUtilities Index mark 3; LR, patients at low risk of complications.

0 20 40 60 80

Less GP visits per case (1.2* to 1 visit)

500,000 vaccination campaign vs. none*

Minor complication (LR 22.9/13.6*/0.9%, HR 29.0/17.3*/7.2%)

Greater antiviral use (LR 4* to10%, HR 6* to15%)

Uptake under current policy (95% CI for TNS survey)

HUI3 in lieu of EQ-5D*

Elasticity of production (100%* to 80%)

Vaccine efficacy: mortality (95% CI: 76/68*/56%)

Vaccine efficacy: hospital admission (95% CI: 65/50*/28%)

Admission|ILI consultations (LR 1.54* vs 0.04%, HR 12.73* vs 0.44%)

Proportion at high risk of complications (31/25*/21%)

Discount rate (0/3*/5%)

Lower uptake - new policy (LR 60* to 29%, HR 77* to 41%)

Workdays lost (5.9/4.0*/1.3 days)

Vaccine efficacy: ILI (95% CI: 42/29*/12%)

Incremental use of routine visits, nurse-administered

Death|ILI consultations (HR 1.24/0.96*/0.24%)

Time off work for vaccination (0*/1 hour)

Incidence of ILI consultations (8.7/4.7*/1.2%)

Thousands

ICER ( per QALY gained)

Figure 5 Cost-effectiveness acceptability curves. ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year; TPP, third-party payer

0%

20%

40%

60%

80%

100%

0 10 20 30 40 50 60 70 80 90 100

Ceiling value for ICER (Currency units x 1 ,000 per QALY gained)

P r o

b a

b i l i t y c o s

t - e

f f e c

t i v

France - TPP

France - societal, no lost productivity at time of vaccination

Germany - TPP

Germany - societal

Italy - TPP

Italy - societal

Brazil - TPP

Brazil - societal

Europe: possible threshold of 50,000 Euro per QALY

Brazil: hypothetical threshold of R$8,558 per QALY


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are eligible under current policy. Higher uptake ratescould be modeled if evidence could be found for themarginal costs and impact of health promotion efforts.A recent study [50] concluded that comprehensivevaccination of the elderly is cost-effective, althoughless so than opportunistic vaccination. That study,

however, did not report the marginal cost-effectivenessbetween an opportunistic and a comprehensive strat-egy, which would seem to be the pertinent question fordecision-makers.

Although this study suggests inuenza vaccinationis likely to be cost-effective from the restricted perspec-tive of third-party payers, the case for the proposedpolicy is strengthened when a more comprehensivesocietal viewpoint is taken. It is well known that theopportunity cost of lost productivity due to ILI is sub-stantial, and we estimated this from two studies [8,10]that specically considered this question, as the 2001Cochrane review [25] included, along with one [8] of

these, two old studies that we did not consider repre-sentative. Productivity effects, however, apply not onlyto time saved due to averted illness but also to the timerequired for the vaccination itself. Workplace vaccina-tion can minimize time lost in travel and disruption tonormal working patterns. Delegating vaccine adminis-tration to staff whose time carries a lower opportunitycost can allow coverage to be expanded more ef-ciently; indeed it may be a practical necessity.

This study has a number of limitations, mainlybecause of lack of available data. Although there is avast literature on the epidemiology of inuenza, datawere not always available in the form required for the

model, and we were obliged to make judgments inadjusting data, for example in estimating coverageamong LRs and HRs from aggregate data. There arefew studies reporting the effectiveness of vaccines inaverting hospital admissions and deaths in nonelderlyadults, so we were obliged to use published evidencerelating to elderly persons for the relative risk reduc-tion. Since carrying out the analysis, however, a large,case-control study (PRISMA) [51] from The Nether-lands of adults aged 18 to 64 years has appeared,which suggests our assumptions are conservative.PRISMA found a 78% reduction in deaths and an87% reduction in hospital admissions, compared with

our base case assumptions of 68% and 50%, respec-tively. Although the model is sensitive to severalparameters including vaccine efcacy, by far the mostinuential factor is the annual attack rate. The uncer-tainty due to the natural variation in attack rate,among the other sources of sampling uncertainty, iscaptured in the cost-effectiveness acceptability curvesand the distributions of net monetary benets. Thispresentation provides an explicit basis for policymak-ers to consider the proposed policy according to theircriteria for cost-effectiveness and the degree of uncer-tainty they are prepared to accept.

A further improvement would be to account for theimpact of illness on health-related quality of life. In theCEA undertaken by Turner et al. [33], an episode of symptomatic inuenza caused a loss of 3.71 quality-adjusted life-days. Also, in that analysis, the gain inQALYs for healthy adults was caused by the impact of

vaccination on quality of life. The fact that patientswho die from inuenza complications may be lesshealthy than average, and therefore would have lowerutilities as well as lower life expectancy, was not mod-eled, as this effect was not possible to quantify. Age-specic utility values were only available from Englandand Canada and might be overestimates for Brazil,where life expectancy is lower and health is likely to beworse at a given age. Potential adverse effects of vac-cination are not represented in the model, as these aregenerally local reactions with no associated cost andlittle impact on quality of life. In a review of severalstudies by Turner et al. [33], there was no statistically

signicant difference in reported reactions betweenvaccine and control arms. We applied conventionalpractice [24] to the discounting of health effects. Analternative approach has recently been proposed forpreventive interventions [52] in which risk reduction isdiscounted from the time of intervention, which wouldlead to more favorable cost-effectiveness ratios.

Our study was designed to inform a decisionbetween the current policy of providing selective vac-cination for persons aged 50 to 59 or 64 years and theproposed policy, which would cover all persons in thisage group, thus increasing the demand for vaccine. Thexed costs that vaccine manufacturers would incur in

stepping up capacity mean that a policy of selectingtarget groups on a year-by-year basis is not feasible.Therefore, the policy decision has to be a once andfor all consideration that takes into account thenatural annual variation in attack rate. Our cost-effectiveness estimates are based on an interpandemicperiod from 1985 to 2002. It is a certainty that at somepoint in the future, a pandemic will occur. Pandemicinuenza can result from a phenomenon known asantigenic shift, involving an abrupt change in thesurface glycoproteins in an emergent strain of inu-enza A virus to which the human population has noimmunity. This occurred from 1918 to 1919, causing

an estimated 40 million to 50 million deaths world-wide, and more recently in 1957 and 1968. Pandemicscan also result from viral strains, such as avian inu-enza, crossing the species barrier. With the entire pop-ulation lacking immunity and susceptible to infection,it would be imperative to expand vaccination, ideallyto achieve full coverage. Nevertheless, unless vaccinemanufacturing capacity was sufcient, it would not bepossible to cover the whole population and prioritiza-tion would be necessary. An important benet of theproposed policy to expand coverage to all personsaged more than 50 years is that it would entail an


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Aballa et al.110

increase in interpandemic vaccine use and encouragemanufacturers to step up capacity, thus enabling morepeople to be vaccinated during a pandemic. Thiswould probably not be sufcient, but at least would bea step in the right direction. The World Health Organ-ization (WHO) has developed a pandemic prepared-

ness plan, a key feature of which is to address theshortage of vaccine when ideally, sufcient vaccineshould be available for the whole population. TheWHO notes production and use of vaccines duringthe interpandemic period will inuence their availabil-ity during a pandemic, by improving the infrastructurefor vaccine production and administration, and byimproving public and professional familiarity withinuenza vaccine. History indicates that there is noregular pattern to pandemics and, in spite of surveil-lance programs, there is no reliable basis for predictingwhen a pandemic might occur.

The use of economic evaluation to inform decision-

making is steadily expanding from its traditional basein Europe, North America, and Australia. A recentstudy [53] reviewed the use of economic evaluation inLatin America, with Brazil the highest producer of published studies, including four concerned with vac-cination [15,5456]. Hence, it was timely to include aLatin American country within this internationalproject. This study should enable decision-makers toconsider the local and international economic consid-erations for a possible expanded vaccination policy,alongside the much-publicized public health issues of improving control of annual inuenza epidemics andpreparing for a pandemic [57,58].

Subject to decision-makers valuations of a QALY,we conclude that targeting all people aged 5064 yearsfor inuenza vaccination is likely to be cost-effective inthe four countries studied. This conclusion applieswhether a TPP or a societal perspective is taken, butespecially so from the latter. The new policy is pre-dicted to yield net cost savings to society in Germanyand Italy. Even from a narrower, TPP viewpoint, how-ever, the cost-effectiveness ratios reported here arewithin the range reported for other interventionsaccepted in European countries. For Brazil, the newpolicy would generate QALYs at a cost lower than theannual GDP per capita, arguably a conservative crite-

rion for cost-effectiveness of the proposed policy. Ourresults are consistent with the existing international lit-erature, reviews of which [7,59] have concluded thatinuenza vaccination is likely to be cost-effective orcost-saving in healthy, working adults.

Acknowledgments

The authors would particularly like to thank UrsulaKhnel, Valentine Delors, and Bertrand Verwee, mem-bers of the Inuenza Vaccine Supply (IVS) Interna-tional Task Force, for their valuable advice based on

their extensive knowledge of inuenza vaccination. Wewould also like to thank Dr. Srgio Kowalski and Dr.Marco Bosi Ferraz of the Federal University of SoPaulo for providing advice and data on costing health-care resources in Brazil.

Source of nancial support: This study was carried out inde-pendently by i3 Innovus under a grant from the IVS Inter-national Task Force. Each author approved the manuscriptbefore submission. Members of the Task Force commentedon a draft of the manuscript and the authors were free todecline publication.

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Appendices

Table A1 Utility values by age group

Age group(years)

Base case:Health Survey for England [66]

1996

Sensitivity analysis:Canadian NPHS*

1996

5054 0.85 0.895559 0.79 0.876064 0.79 0.876569 0.78 0.867074 0.78 0.837579 0.73 0.788084 0.73 0.7285+ 0.73 0.58

*Jean-Marie Berthelot, 2005, pers. comm.

Table A2 Model inputs: vaccine effectiveness

Efcacy parameter Reduction (%)

Incidence of ILI [25] 29Probability of GP visit* 29Probability of prescription of u treatment* 29Probability of prescription of other treatment* 29Probability of stopping work* 29Probability of minor complication* [27] 28Probability of hospitalization* [30] 50Probability of death* [30] 68

*Reductions are modeled as unconditional on presence of inuenza-like illness (ILI).GP, general physician.

Table A3 Model inputs: antiviral effectiveness

Reduction in:

Oseltamivir(%)

Zanamivir(%)

HR LR HR LR

Probability of absence from work [31] 13 13 13 13Probability of antibiotic use [32] 6 27 6 27Probability of minor complication [33] 34 58 44 26Probability of hospitalization [33] 25 84 33 64Probability of death [33] 29 74 29 64

HR, patients at high risk of complications; LR, patients at low risk of complications.

Table A4 Populations considered, by age subgroup, in 2003

Age (years) Brazil (So Paulo)* France Germany Italy

5054 1,899,953 4,254,104 5,428,591 3,815,4995559 1,475,451 3,704,782 4,453,475 3,529,0116064 NA 2,672,132 5,681,618 3,463,235

Total 3,375,404(5059) 10,631,018 9,882,066(5059) 10,807,745

*Estimates for Brazil are for 2002.NA, not applicable.

Table A5 Life expectancy in years by age, in 2000

Age (years) Brazil France Germany Italy

5054 25.6 29.8 29.6 31.35559 21.6 25.5 25.2 26.96064 17.9 21.4 20.9 22.6

Source: OECD Health Data, Paris: OECD/CREDES.

Table A6 Consultation, prescribing, and outcomes for ILI

Brazil(%)

France(%)

Germany(%)

Italy(%)

Probability of seekingmedical attention,given ILI symptoms

40 [15] 57 [71] 53 [71] 60 [72]

Average annualincidence of ILIconsultations inunvaccinatedpersons*

5.07 5.00 4.70 5.84

At ILI consultation,proportionprescribed antiviral

HRs 0 6 [71] 20 0LRs 0 4 [71] 15 0

After ILI consultation,proportion of cases resulting inMinor complication

[63,73]HRs 17.3 17.3 17.3 17.3LRs 13.6 13.6 13.6 13.6

Hospital admission[1,64]

HRs 3.01 13.2 14.1 11.4LRs 0.33 1.3 1.4 1.1

Death [39,64,74] HRs 0.950 0.963 1.028 0.826LRs 0.009 0.009 0.009 0.008

*France: INSERM, Rseau Sentinelles, average over period 19852002 for 5059 agegroup. Adjusted from total to unvaccinated population. Other countries based onsame source, adjusted for propensity to seek medical attention.IMS monthly MIDAS data, quoted with permission from IMS Health. Average costsof antivirals based on country-specic prices of oseltamivir and zanamivir weightedby market shares.HRs, patients at high risk of ILI complications; ILI, inuenza-like illness; LRs, patientsat low risk of ILI complications.

Table A7 Numbers of missed workdays and workforce par-ticipation rates by country

Brazil France Germany Italy

Missed workdays [71,72,75]Consulting cases 3.8 3.7 3.8 4.8Nonconsulting cases 0.3 0.3 0.3 0.3

Workforce participationrates (%), by age (years)*5054 58.9 76.7 74.6 62.65559 52.4 57.4 58.8 39.46064 NA 15.6 22.8 18.8

*OECD, 2002 (France, Germany, Italy); IBGE, PNAD-2002 (Brazilian NationalHousehold Survey).

Table A8 Proportions of persons with high-risk conditionsand eligible for vaccination reimbursement

Brazil(%)

France(%)

Germany(%)

Italy(%)

Proportion of persons:At high risk of complications

(HRs)30 25 [39] 25 [39] 25 [39]

Currently eligible forvaccination reimbursement*

30 5 10 25

Vaccination uptakeCurrent uptake under current policy

Proportion of HRs vaccinated 12 27 39 42Proportion of LRs vaccinated 2 19 16 17

Forecast uptake under new policyProportion of HRs vaccinated 70 77 53 67Proportion of LRs vaccinated 70 60 41 51

*Assumed same proportion as HRs, expert opinion for France and Germany.CNAMTS,http://www.ameli.frTNS Sofres survey data for season 2002/3 for France, Germany, Italy. Brazil: Unpub-lished data from Dr. Toniolo-Neto, based on UNIFESP study.HRs, patients at high risk of ILI complications; LRs, patients at low risk of ILI com-plications.
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Table A9 Primary care and outpatient resource utilization

Brazil France Germany Italy

GP visits for ILINo. of visits 1 1.2 [71] 1 1% visits at home, HR 10 20.4 8 20% visits at home, LR 5 20.4 5 10

Minor complicationsPneumonia and inuenza

No. of GP visits (HR, LR) 4, 2 3, 2 5, 4.5 4, 4% home visits (HR, LR) 25, 50 50, 20 30, 20 70, 60Tests, HR Complete blood count,

chemistry panel, x-ray: 100%Chest x-ray: 80% ESR, leucocytes x-ray,

ECG, CRP: 80%Blood, urine, x-ray: 100%

Tests, LR Complete blood count, arterialblood gases, chest x-ray: 80%

Chest x-ray: 80% As above As above

Other respiratory illnessesNo. of GP visits (HR, LR) 3, 2 2, 2 3.5, 3 2, 2% home visits (HR, LR) 30, 0 40, 5 15, 10 60, 50Tests, HR Complete blood count, sinus

and chest x-ray: 100%X-ray: 10% ESR, leucocytes x-ray,

ECG: 30%Blood, urine, x-ray: 20%

Tests, LR As above X-ray: 10% As above Tests above: 10%Cardiovascular

No. of visits (HR, LR) 4, 3 3, 3 5, 5 4, 3% home visits (HR, LR) 25, 30 50, 20 70, 70 80, 70

Tests, HR Blood count, x-ray, ECG,echocardiography: 100% ECG: 100% ESR, leucocytes x-ray,ECG, CRP: 100% Blood, urine, ECG,echocardiogram: 50%Tests, LR Id.: 90% ECG: 80%, As above Tests above: 20%

Other minor complicationsNo. of GP visits 3, 2 2, 2 % home visits 30, 0 40, 5

Data are from questionnaires completed by clinician authors, except where publication is cited.CRP, C-reactive protein; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; GP, general physician; HR, patients at high risk of complications; ILI, inuenza-likeLR, patients at low risk of complications.

Table A10 Main unit costs and associated reimbursement rates, by country

CountryPerspectiveBrazil France Germany Italy

TPP Societal TPP Societal TPP Societal TPP Societal

Standard GP visit R$7.55 R$54 70% of 20

100% of 20

100% of 8.75

100% of 8.75

100% of 12.91

100% of 12.91 [76]

Home visit R$16.63 R$18.94 70% of 33.50

100% of 33.50

100% of 13.20

100% of 13.20

0% of 18.07*

100% of 18.07

Antibiotic R$0 R$2.29 65% of 7.55

100% of 7.55

19 less 5 co-pay

19 100% of 9.21

100% of 9.21[77]

HospitalizationPneumonia and

inuenzaR$498.11 R$3,653 80% of

3,669*100% of

3,669100% of

3,671100% of

3,671100% of

3,966100% of

3,966Other respiratory

complicationsR$177.59 R$1,270 80% of

4,362*100% of

4,362 3,327 less

90 3,327 100% of

3,774100% of

3,774Cardiovascular and

cerebrovascularcomplications

R$246.29 R$1,762 80% of 3,789*

100% of 3,789

7,279 less$90

7,279 100% of 3,270

100% of 3,270

Lost productivity,per workday [78] R$0 R$85.75

[79] 25.50 216.64 0 226.26 0 164.91[47,76,77]

*100% reimbursement rate applies to individuals eligible for vaccination because of chronic health conditions.Sources:Brazil: Tabelas de Procedimentos dos Sistemas de Informaes Ambulatorial e Hospitalar do Sistema nico de Sade (SIA and SIH/SUS), 2004; DATA SUS, Sao PaulIBGE,PNAD-2002 (National Household Survey).France: Drugs: Vidal, BIAM; Fee schedules for physician visits and tests: NGAP; Hospital costs: PMSI (data obtained from ATIH); Reimbursement rates: CNAMTS.Germany: Drugs: Rote Liste; Fee schedules for physician visits and tests: EBM; Hospital costs: DRG database, v1.0 (2003) available athttp://www.g-drg.de;Zahlenbericht, PKV;Diagnosedaten der Krankenhauspatienten 1999, Statistiches Bundesamt 2001.Italy: Drugs:http://www.giol.it;Tests: Prestazioni di Assistenza Specialistica Ambulatoriehttp://www.ministerosalute.it;Home visits: DPR270, Nomenclatore Tariffario (2000);Hospital costs: Schede di Dimissione Ospedaliere.GP, general physician; TPP, third-party payer.
http://www.g-drg.de/http://www.giofil.it/http://www.ministerosalute.it/http://www.ministerosalute.it/http://www.giofil.it/http://www.g-drg.de/


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Table A11 Vaccine acquisition and administration costs

Brazil [15] France Germany Italy [80]

Vaccinationsetting

Public hospital orvaccination center, bynurse: 100%

Current policy: 70% routinevisits, 20% special visits,10% occupational visits

New policy, high-risk:70% routine visits,

20% special visits,10% occupational visitsNew policy, low-risks:

20% routine visits,70% special visits,10% occupation visits

Physicians performall vaccinations.

Fixed item-of-service fee(independent of setting)

Current policy, HR: 90% inpublic sector (LHA/familydoctor), 10% in private sector

Current policy, LR: 100% inprivate sector

New policy: 90% in publicsector, 10% in private sector

Unit costs Vaccine: R$4.74Vaccination by nurse:

TPP: R$ 0.50 Societal: R$ 3.58

Vaccine: 6.28GP visit: 20 (routine visit: 0)Vaccination in occupational

setting: 2.90

Vaccine: Eligible person: 7.00 Noneligible: 17.28

Physician fee: 6.50

Vaccine: Pharmacy: 12.77* Under contract: 4.98 [80]

Family doctor incentive/LHAadministration fee: 8.00

Private doctor: 15.49Reimbursement 100% of all costs (TPP)

for all vaccinatedpersons

Vaccine: For eligible persons: 100% For noneligible persons: 0%

Administration: 70% if by GP,0% if by nurse at occupational visit

Eligible persons: 100%Noneligible persons: 0%

Family doctor/LHA: 100%Private doctor: 0%

Sources:Brazil: SIA and SIH/SUS, 2004.France: NGAP.Germany: Regional physicians associations: Wezel, Liebold. Handkommentar: BM, E-GO und GO, IGEL.Italy: *http://www.giol.it/ofine/SOuauett.htm(accessed January 15, 2004).HR, patients at high risk of complications; LHA, Local Health Authority; LR, patients at low risk of complications.

Table A12 Distributions and parameters for probabilistic analyses

Model inputs France Germany Italy Brazil

Proportion of 5064 year-olds eligiblefor vaccination reimbursementunder existing policy

Triangular (min= 3.76%,mode= 4.70%,max= 5.64%)

Beta( = 20, = 180) Assumed equal toproportion atincreased risk (see below)

Assumed equal toproportion at increasedrisk (see below)

Proportion of u patients aged5064 years at increased risk of complication (HR group)

Triangular (min= 20%;mode= 25%; max= 30%)

Triangular (min= 20%,mode= 25%,max= 30%)

Triangular (min= 20%,mode= 25%,max= 30%)

Lognormal (mean 0.3,SD 0.03)

Proportion of individuals seekingmedical care for u/ILI in oneseason

Empirical distribution of incidences from 1985 to2002

French distributionrescaled, equatingmean to base caseconsultation rate



Proportion of individuals with ILIseeking medical care

Beta( = 178, = 135) (4.4%/4.69%)Beta(178, 135).

Beta( = 180, = 120) Triangular20%40%60%

Vaccination uptakeExisting policy Ratio eligible/noneligibleadjusted for age: triangular(min= 2.5; mode= 3.22;max= 4)

Ratio (more than 50 : lessthan 50 years) amongeligibles: triangular(min= 1; mode= 2;max= 3)

Overall coverage:Beta( = 198, = 646)

Ratio HR/LR:Beta( = 112, = 162)/Beta( = 176, = 880)

Overall coverage: = 557.72)

Ratio HR/LR:Beta( = 112, = 162)/Beta( = 176, = 880)

Overall coverage:Beta( = 161.28,

HR: Triangular (min= 8%,mode= 10%,max= 18%)

LR: Triangular (min= 1%,mode= 1%, max= 4%)Beta( = 189, = 606)

Probability of any hospitalization |ILI medically attended,unvaccinated

HR: Beta( = 148, = 1011)LR: Beta( = 9, = 553)

HR:Beta( = 144.48; = 930.38)

LR:Beta( = 8.47; = 516.94)

HR:Beta( = 154.75; = 1219.86)

LR:Beta( = 9.23; = 671.23)

HR: Lognormal(mean 0.0305,SD 0.0012)

LR: Lognormal(mean= 0.0033,SD= 0.0112)

Probability of death | ILI medicallyattended, unvaccinated

HR: Beta( = 15.89; = 1,638.85)

LR: Beta ( = 0.29; = 1748.52)

HR: Beta( = 16.98, = 1642.76)

LR: Beta( = 0.30, = 1748.52)

HR: Beta( = 13.69, = 1642.18)

LR: Beta( = 0.26, = 1735.71)

HR: Beta( = 15.79, = 1638.95)

LR: Beta( = 0.30, = 1748.52)

Number of workdays lost forcases seeking medical attention

Normal (Mean 4.00;SD 0.15)

LogNormal (3.78; 0.82) Normal (4.55; 0.71) Lognormal (mean 3.98,SD 1.17)

Note. As sources of data and types of evidence were country-specic for some inputs, the appropriate statistical distributions were also subject to variability.GP, general physician; HR, patients at high risk of complications; ILI, inuenza-like illness; LR, patients at low risk of complications; OR, odds ratio; TPP, third-party pay
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Number of workdays lost for othercases

Prob. absence:Beta( = 29, = 36)

Mean # days | absence:Lognormal (mean 0.68,SD 0.15)


Mean # days | absence:Lognormal (Mean0.68, SD 0.15)


Mean # days | absence:Lognormal (Mean0.68, SD 0.15)


Mean # days | absence:Lognormal (mean 0.68,SD 0.15)

Vaccine effectiveness: reduction inrisk of ILI Normal (mean0.34, SD0.11) on log(OR)

Vaccine effectiveness: Reduction inminor complications

Normal (mean0.33, SD0.08) on log(OR)

Vaccine effectiveness: reduction inhospitalizations

Normal (mean0.69, SD0.21) on log (OR)

Vaccine effectiveness: reduction indeaths

Normal (mean1.14, SD0.15) on log(OR)

Vaccine administration, existing policy Occupational: Triangular(min= 5, mode= 8.5,max= 12%)

Special visit | vacc. byGP: Uniform (min= 10%,max= 35%)

Prob. private visit, HR:Triangular (0%10%20%)

Vaccine administration, new policy Occupational:Triangular (min= 5%,

mode= 8.5%, max= 12%)Special visit | GP, HR:Uniform (min= 10%,max= 35%)

Special visit | GP, LR:Uniform (min= 65%,max= 95%)

Prob. private visit, HR:Equal to prob. under

existing policy (seeabove)

Vaccine acquisition cost (if paid byTPP)

Triangular (min= 6,mode= 6.50,max= 8.50)

Triangular (min= 4.5,mode= 4.98,max= 5.5)

Vaccine administration cost Triangular: (min= 5.5,mode= 6.50,max= 7.70)

Family doctor / LocalHealth Authority:Triangular (min= 6,mode= 8,max= 10)

By nurse:Gamma distribution

(Location= 0.5,Shape= 2.37,Scale= 1.30)

Hospitalization cost, societalperspective

Gamma distribution(Location= 331,

Shape= 1.84,Scale= 1,105.11)

Model inputs France Germany Italy Brazil

Note. As sources of data and types of evidence were country-specic for some inputs, the appropriate statistical distributions were also subject to variability.GP, general physician; HR, patients at high risk of complications; ILI, inuenza-like illness; LR, patients at low risk of complications; OR, odds ratio; TPP, third-party pay

Table A12 continued

02 Cost-Effectiveness of Influenza Vaccination for People Aged 50 to 64 - An International Model

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