Introduction of a quadrivalent influenza vaccine in Italy: a budget impact analysis

A. PITRELLI

Access to Medicine, GlaxoSmithKline Italia, Verona, Italy


Keywords


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Influenza • Budget Impact Analysis • QIV


Summary


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Every year in Italy, the Ministry of Health (MoH) offers influenza vaccination free of charge to all subjects at risk and to all subjects aged 65 year old. Until 2014-2015 immunization campaign against Trivalent Influenza Vaccine (TIVs) were the only vaccines used in Italy.

Traditional TIVs contain antigens from three viral strains: A(H1N1), A(H3N2), and one of the two B lineages: B(Victoria) or B(Yamagata). Each year, the World Health Organization (WHO) decides which viral strains should be included in the next sea- sonal influenza vaccine. However, accurately predicting which B-lineage strain will predominate in the upcoming season has proved to be a challenging task, owing to the co-circulation of both lineages.

To address the issue of B-mismatch, a new Quadrivalent Influenza Vaccine (QIV) containing both B-lineage strains

has been developed, in order to achieve broader protection against influenza. The new QIV was approved in Italy in 2015 and included by the MoH in the national recommendations for the seasonal immunization campaign against influenza 2015-2016.

Recently, a Health Technology Assessment (HTA) Report has shown that, in comparison with TIVs, the new QIV is cost-effec- tive (Incremental Cost-Effectiveness Ratio (ICER) = 18,883/

(QALY) Quality-Adjusted Life-Year) from the Italian National Health Service (NHS) perspective. The present Budget Impact Analysis (BIA) showed that the introduction of the QIV with a 9% market share in the vaccine mix for the 2015-2016 flu

campaign would yield an annual saving of 674,089, mainly

owing to the broader protection offered by QIV vs TIVs with an estimated 49.12% B-mismatch.


Introduction


Every year the Italian Ministry of Health (MoH) offers an Influenza Immunization Program for all subjects at higher risk of flu complications on the basis of age (65 years old) or clinical and professional condition. Until 2014-2015 immunization campaign against influ- enza, Trivalent Inactivated influenza Vaccines (TIVs) were the only vaccines used in Italy.

Traditional TIVs contain antigens from three viral strains: A(H1N1), A(H3N2), and one of two B lin- eages: B(Victoria) or B(Yamagata). Each year, the World Health Organization (WHO) decides which viral strains should be included in the next seasonal influ- enza vaccine. However, accurately predicting which B- lineage strain will predominate in the upcoming season has proved to be a challenging task, resulting in fre- quent mismatches with the vaccine strain [1], owing to the co-circulation of both lineages or the predominant circulation of the non-vaccine B-lineage. During mis- match seasons, efficacy and effectiveness against the opposite B lineage are lower [2-8]. To address the issue of B-mismatch, a new Quadrivalent Inactivated influ- enza Vaccine (QIV) containing both B-lineage strains has been developed, in order to provide broader pro- tection against influenza. The new QIV was available in Italy [9] and included by the MoH in the national


recommendations for the seasonal immunization cam- paign against influenza 2015-2016 [10].

Recently, a Health Technology Assessment (HTA) Re- port has shown that, in comparison with TIVs, the new QIV is cost-effective (Incremental Cost-Effectiveness Ratio (ICER) = 18,883/(QALY) Quality-Adjusted Life-Year) from the Italian National Health Service (NHS) perspective [11].

The objective of the present analysis was to estimate the budget impact of the new QIV after its introduction into the national flu immunization campaign in Italy.


Methods


A budget impact analysis (BIA) was made from the NHS perspective, in order to estimate the financial im- pact due to the introduction of the QIV into the vaccine mix included by the MoH in the influenza immunization campaign for the 2015-2016 flu season.

The BIA included the following input data:

The analysis considered a single-year time horizon and focused on the first year of QIV introduction by the MoH in the 2015-2016 flu immunization cam- paign.

The results are shown as the net budget impact of the scenario of QIV in the flu vaccine mix (new scenario) versus the scenario in which only TIVs are used in the influenza immunization program (current scenario).


Target Population

The population targeted by the national Influenza Im- munization Program was calculated on the basis of the Italian population in 2014 [12].

Every year in Italy, the MoH offers free influenza vac- cination to all subjects at risk (for clinical/professional reasons) and to all subjects aged 65 year old, regard- less of other risk factors.

The prevalence of at-risk subjects eligible for influenza vaccination was calculated from the data collected in 25 EU countries (including Italy) by Ryan et al. [13]. The influenza vaccine coverage data in 2014 were then applied to the Italian general population, in order to es- timate the annual number of subjects undergoing influ- enza vaccination within the national Immunization Pro- gram [14, 15].

The target population included in the BIA is summa- rized in Table I.


Epidemiology of influenza in Italy

The probability of contracting influenza in an unvacci- nated population was derived from the study by Turner et al. and is reported in Table II [16].

The prevalence of A and B influenza viruses circulat- ing during a season was estimated as the average data (A virus = 74.12% and B virus = 25.88%) from ECDC Surveillance Reports from 2003 to 2012 (excluding the 2009-2010 pandemic season) [11].

The prevalence of B-lineage strains circulating during a season was estimated as the average data from ECDC Surveillance Reports from 2003 to 2012 (B-Yamaga- ta = 50.88% and B-Victoria = 49.12%) [11].

Tab. I. Target population included in the BIA.


Age- range


Population

Overall Vaccine Coverage (%)


Population at risk (%)

Population at risk vaccinated (%)

< 5

2,724.106

2.04

15.10

9.66

5-17

7,433.899

2.30

15.18

10.86

18-49

25,543.294

3.87

16.52

17.24

50-59

8,435.388

9.50

45.36

19.30

60-64

3,361.039

9.50

45.36

19.30

65-69

3,447.791

55.40

45.63

55.40

70-74

3,044.129

55.40

46.15

55.40

75-79

2,645.596

55.40

47.31

55.40

80-84

2,013.904

55.40

50.05

55.40

≥ 85

1,863.522

55.40

57.44

55.40

Total

60,782,688

16.33

28.66

31.02


Tab. II. Probability of contracting influenza in the population broken down age-range.

Age-range

Probability (%)

< 5

19.21

5-17

19.21

18-49

6.55

50-59

6.55

60-64

6.55

65-69

6.17

70-74

6.17

75-79

6.17

80-84

6.17

≥ 85

6.17

Average

8.58


Efficacy of QIV vs TIV

In the present BIA, we assumed that:



Tab. III. Efficacy of QIV vs TIVs in preventing influenza viruses.

Influenza A virus

Influenza B virus

Age-range

QIV efficacy

TIV efficacy

QIV efficacy

TIV efficacy in match

TIV in mismatch

Overall

TIV efficacy vs B virus

< 5

59%

59%

66%

66%

44%

55%

5-17

59%

59%

77%

77%

52%

64%

18-49

61%

61%

77%

77%

52%

64%

50-59

61%

61%

73%

73%

49%

61%

60-64

61%

61%

73%

73%

49%

61%

65-69

58%

58%

69%

69%

47%

58%

70-74

58%

58%

69%

69%

47%

58%

75-79

58%

58%

66%

66%

44%

55%

80-84

58%

58%

66%

66%

44%

55%

≥ 85

58%

58%

66%

66%

44%

55%

Total

59%

59%

66%

66%

44%

55%

Tab. IV. Unit prices and market shares of the vaccines in the BIA.

Vaccine

Current scenario

New scenario

Market share (MS)

Unit price

Market share (MS)

Unit price

Split

49%

2.55 €

52%

2.55 €

Intradermal

26%

5.36 €

25%

5.36 €

Adjuvanted

25%

5.33 €

14%

5.33 €

QIV

0

0

9%

6.00 €

Total

100%

100%



Tab. V. Cost of influenza: direct costs included in the BIA and probabilities that patients with influenza will generate these costs.

Health resource

Probability of generating the cost for patients with influenza (%)

Cost

Source

GP consultation

60%

20.66 €

[21]

Antibiotic therapy

47.3%

3.53 € (< 18 years)/

3.06 € (≥ 18years)

Final cost on multiplying the initial cost by the likelihood of receiving antibiotics [22, 23]

Antiviral therapy

0.17%

17.3 € (< 5years) /

38.5 € (≥ 5years)

[24, 25]


included in TIVs, (mismatching); these are reported in Table III. In both cases, the efficacy of QIV vs TIVs was derived from the meta-analysis by Tricco et al. [20];

Tab. VI. Costs of influenza complications: inpatient and outpatient settings.

Respiratory complications

Inpatient cost < 18 years

Inpatient cost ≥ 18 years

Outpatient

Bronchitis

1,538 €

1,832 €

90 €

Pneumonia

1,948 €

2,291 €

90 €

Upper Respiratory Tract Infections (URTI)

5,768 €

€4,422

€90

Other complications not related to respiratory tract

2,777 €

2,900 €

83 €


Table VI reports the costs of complications in inpatient (hospitalization) and outpatient settings, based on DRG tariffs.


Results


The objective of this analysis was to estimate the budget impact of the new QIV after its introduction into the Na- tional Immunization campaign in Italy.

In the base-case scenario, we assumed that, in the 2015- 2016 flu season:

Tab. VIII. Impact of the introduction of a QIV in Italy on direct influenza costs: base-case results.

Current scenario (€)

New Scenario (€)

∆ (€)

Vaccination cost

37,924.500

37,669.800

-254,700

TIVs

37,924.500

32,518.570

QIV

0

5,151.230

Cost of influenza

3,559.199

3,536.906

-22,293

GP consultation

3,169.698

3,149.846

-19,852

Antibiotic therapy

372,881

370,543

-2,337

Antiviral therapy

16,620

16,516

-104

Cost of influenza with complications

63,844.008

63,446.912

-397,096

Inpatient cost

50,394.190

50,080.269

-313,920

Outpatient cost

13,449.818

13,366.643

-83,176

Total

105,327.707

104,653.618

-674,089


full B-mismatch:

Figures 1 and 2 summarize the results from these two additional scenarios versus the base-case.

image

In the No B-mismatch scenario, there was no impact of QIV introduction in preventing influenza cases ver- sus TIVs, owing to the complete match between the B- strain circulating and the B-strain contained in the TIVs. Nevertheless, the net budget impact in this scenario was favourable, because the incremental cost due to QIV in- troduction was fully offset by increased use of split vac-

cine (Market Share (MS) +3%) and the decreased use of intradermal vaccine and adjuvanted vaccine (MS -12%), produced a net saving of 254,700 in a year.

In the Full B-mismatch scenario, the influenza cases avoided through the introduction of QIV was 3,120. In this scenario, the broader protection offered by QIV vs TIVs was maximized by the 100% mismatch between the B-strain circulating and the B-strain contained in the TIVs. The net budget impact in this scenario was highly in favour of the introduction of QIV, with 1,087.382 saved in one year. The majority of this saving came from the reduction in influenza treatment costs produced by QIV versus TIVs, owing to the full B-mismatch (-832,692).


Discussion


The WHO and European Health Authorities encouraged the development of QIV in order to achieve broader protection against influenza by reducing the impact of


Fig. 1. Number of avoided cases of influenza due to QIV introduction in the 3 scenarios included in the BIA.

Fig. 1. Number of avoided cases of influenza due to QIV introduction in the 3 scenarios included in the BIA.


Fig. 2. Number of avoided costs due to QIV introduction in the 3 scenarios included in the BIA.

Fig. 2. Number of avoided costs due to QIV introduction in the 3 scenarios included in the BIA.


image

B-Mismatch. Until 2014-2015 immunization campaign against influenza, only TIVs were available for the Na- tional Influenza Immunization campaign in Italy. Tra- ditional TIVs contain antigens from three viral strains: A (H1N1), A (H3N2), and one of two co-circulating B lineages: B(Victoria) or B(Yamagata). Each year, the WHO decides which viral strains should be included in the next seasonal influenza vaccine.

However, accurately predicting which B-lineage strain will predominate in the upcoming season has proved to be a challenging task, resulting in frequent mismatches with the vaccine strain. During mismatch seasons, effi- cacy and effectiveness against the opposite B lineage are lower because of the lack of cross-protection of the B- strain contained in the TIVs vs the circulating B-strain, when they differ.

In 2015, the first QIV was approved by the Italian Drug Agency (AIFA), and was included in the National In- fluenza Immunization campaign by the MoH for the 2015/2016 flu season.

An HTA Report showed that this new QIV was more cost-effective than TIVs (ICER = 18,883/QALY) from the Italian NHS perspective.

In the present analysis, we estimated the BIA after the introduction of QIV as an alternative to TIVs. The BIA showed that, with a 9% MS in the vaccine mix for the 2015-2016 flu campaign, the introduction of the QIV yielded an annual saving of 674,089, mainly due to the broader protection offered by QIV vs TIVs with an estimated 49.12% B-mismatch.

QIV is an effective and safe alternative to TIVs, offering broader protection when B-mismatch occurs in the flu sea- son. From the NHS perspective, QIV is cost-effective in Italy; our budget impact analysis estimated that the intro- duction of QIV into the influenza immunization campaign in 2015/2016 would produce a net annual saving ranging

from 254,700 (0% B-mismatch, Incremental cost of QIV fully offset by the saving due to the increased MS of split vaccines and the decreased MS of intradermal and adju- vanted vaccines) to 1,087,392 (100% B-mismatch).


Acknowledgments


A.P. is an employee of GlaxoSmithKline SpA - Pharma- ceuticals.


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n Received on January 20, 2016. Accepted on February 27, 2016.


n Correspondence: Andrea Pitrelli, GlaxoSmithKline Italia SpA, via A. Fleming 2, 37135 Verona, Italy - Tel. +39 045 9218111 - E- mail: andrea.n.pitrelli@gsk.com