Farmeco 2016;17(1)7-12.html

Farmeconomia. Health economics and therapeutic pathways 2016; 17(1): 7-12

http://dx.doi.org/10.7175/fe.v17i1.1225

Original research

Budget impact analysis of the use of daclatasvir in Italy for the treatment of Hepatitis C Virus (HCV) genotype 3 patients

Umberto Restelli 1,2, Alfredo Alberti 3, Adriano Lazzarin 4,5, Marzia Bonfanti 1, Carmela Nappi 6, Davide Croce 1,2

1 Centre for Research on Health Economics, Social and Health Care Management (CREMS) – LIUC – Carlo Cattaneo University, Castellanza (VA), Italy

2 School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

3 Department of Molecular Medicine, University of Padua, Padua, Italy

4 Department of Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy

5 Università Vita-Salute San Raffaele, Milan, Italy

6 Health Economic&Outocome Research Bristol Myers Squibb S.r.l., Rome, Italy

Abstract

BACKGROUND: Hepatitis C Virus (HCV) infection represents a global health problem, leading to chronic cirrhosis, hepatocellular carcinoma (HCC), hepatic decompensation and liver transplant. The aim of the study was the evaluation of the impact on the budget of the Italian National Health Service (INHS) of the use of Daclatasvir (DCV) for the treatment of HCV genotype 3 in patients with advanced fibrosis.

METHODS: An analytical decision model with a five year time horizon was implemented. Two scenarios were considered: a. 100% of market share for Interferon (INF-α)+Ribavirin (RBV)+Sofosbuvir (SOF) for 12 weeks; b. SOF+DCV+RBV for 24 weeks with annual market shares of 50% in 2015 and 2016, 55% in 2017 and 2018, 60% in 2019, and INF-α+RBV+SOF for 12 weeks with the remaining market shares. Every annual cycle a percentage of patients equal to the effectiveness of the antiviral treatment reach a sustained virologic response and during the first year of treatment patients may experience treatment related adverse events. The costs considered (2015) are those of the antiviral therapy, and direct medical costs for health state and adverse events management. Univariate and multivariate sensitivity analyses were performed.

RESULTS: DCV would lead to an increase of the costs for the INHS (year 1 +21.31 millions, year 2 +21.35 millions, year 3 + 23.37 millions, year 4 + 23.26 millions and year 5 +16.37 millions). The sensitivity analysis confirmed the robustness of the results.

CONCLUSIONS: The use of DCV is likely to have a short term impact on the INHS budget increasing resources use compared to the sole use of INF-α+RBV+SOF. However, a trend of reduction of the costs increase is observed due to the management of health states and adverse events which may lead to the possibility to reduce costs in the long term.

Keywords

Hepatitis C Virus; Daclatasvir; Budget Impact Analysis; Genotype 3

Corresponding author

Umberto Restelli

urestelli@gmail.com

Disclosure

This study was supported by Bristol-Myers Squibb

Background

Infections due to Hepatitis C Virus (HCV) represent a global health problem, affecting patients worldwide [1] with different prevalence and incidence among countries [2-4]. They may progress to chronic cirrhosis, hepatocellular carcinoma (HCC), hepatic decompensation and may lead to liver transplant [5].

The economic and social impact of the disease was investigated in different contexts, showing the cost increase for health services to manage HCV positive patients, leading to the conclusion that a lack of treatment of the pathology would lead to an increase of the disease burden due to HCV induced pathologies and the related worsening of the health condition of HCV positive patients [6-9].

Among HCV genotypes, genotype 3 is associated with higher HCC incidence and with accelerated fibrosis progression [10,11], and only two treatments are recommended by the Guidelines of the European Association for the Study of Liver for the treatment of HCV genotype 3 infected patients with compensated cirrhosis [12]: sofosbuvir (SOF) + daclatasvir (DCV) + ribavirine (RBV) for 24 weeks and peg interferon α (INF-α) + RBV + SOF for 12 weeks.

Due to the high cost of new HCV antiviral treatments and in absence of scientific evidence about their economic impact on the Italian National Health Service (NHS), the study presented aimed at evaluating the impact on the budget of the Italian NHS of the use of daclatasvir for the treatment of HCV genotype 3 infected patients compared with the sole use of INF-α + RBV + SOF.

Materials and methods

An analytical decision model was implemented to forecast the impact on the budget of the Italian NHS of the use of DCV in a five year time horizon for the treatment of HCV positive patients [13].

The patients eligible to antiviral treatment were those with a fibrosis rate of 3 and 4 (F3 and F4), as recommended by the Italian NHS. The number of eligible patients was estimated using published prevalence and incidence data, as reported in Table I.

Pts (n.)

% of the previous category

Source

Italian population (1st January 2014)

60,782,668

[14]

HCV prevalence

2,725,359

4.5

[15]

HCV positive patients

300,000

11.0

[16]

HCV positive patients eligible to treatment (F3 – F4)

24,600

8.2

[16]

HCV genotipe 3 infected patients

2,706

11.0

[17]

Table I. Epidemiological data and number of HCV genotype 3 infected patients eligible to treatment

Health states transition

Rate

Source

F3 F4

0.112

[18]

F4 Decompensated cirrhosis

0.039

[19]

F4 HCC

0.014

Decompensated cirrhosis HCC

0.014

Decompensated cirrhosis Transplant

0.030

Decompensated cirrhosis Death

0.130

HCC Transplant

0.030

HCC Death

0.430

Transplant (Year 1) Death

0.210

Transplant (Year 2+) Death

0.057

Table II. Model’s health states transition rates

Two scenarios were structured based on the recommendations of the guidelines of the European Association for the Study of Liver [12]. In details the only two treatments recommended for cirrhotic genotype 3 HCV infected patients were considered in two scenarios, one not considering the use of DCV, therefore having a 100% market share of INF-α + RBV + SOF for 12 weeks from 2015 to 2019 (scenario 1); the second one introducing in the base case scenario SOF + DCV + RBV for 24 weeks with the following annual market shares: 50% in 2015 and 2016, 55% in 2017 and 2018, and 60% in 2019 (scenario 2). The market shares were based on experts’ opinions.

Patients enter the model in one of the following health states [15]: F3 (60%), F4 (16%), decompensated cirrhosis (3%), HCC (19%), liver transplant (2%). Each year patients may change their health states with probabilities based on previously published works [18,19], as presented in Table II.

Every annual cycle a percentage of patients, equal to the effectiveness of the antiviral treatment, reach a sustained virologic response (SVR). During the first year of treatment patients may experience treatment related adverse events (anemia and rash) with rates derived from literature. The effectiveness (SVR at 12 weeks after the end of the treatment) and adverse events rates are reported in Table III. Due to lack of data concerning the effectiveness and the efficacy of the treatments among patients affected with decompensated cirrhosis, HCC and eligible for liver transplant, the same effectiveness observed in patients with fibrosis stages 3 and 4 was considered.

The costs considered within the model are those of the antiviral therapy, direct medical costs for the management of the health state and direct medical costs for the management of the therapies’ adverse events.

Antiviral treatment

SVR at 12 weeks (%)

Anemia (%)

Rash (%)

SOF + DCV + RBV – 24 weeks

100 [20]

10.3 [21]

6.9 [21]

INF-α + RBV + SOF – 12 weeks

92.1 [22-24]

12.0 [22]

12.0 [22]

Table III. Effectiveness and adverse events rates of the two treatments

All costs refer to 2015, those derived from published articles were converted using the Italian yearly average inflation rates as reported by the International Monetary Fund [25]. The cost of the antiviral therapies considered were based on the price published in the Official Gazette of the Italian Medicines Agency [26-29]. The costs of the management of adverse events were calculated using an activity based costing approach, through interviews with clinical experts and are therefore based on the Italian real clinical practice. The cost of death was calculated by multiplying by 12.5 the average cost of 3 months in health states F3 and F4 [30]. The costs considered are reported in Table IV.

Univariate and multivariate sensitivity analyses were performed to test the robustness of the results. The parameters changed were the cost of DCV (±10%); the effectiveness of DCV (-5%) and the number of patients eligible for antiviral treatment (±10%).

Cost category

Cost yearly / per event / per treatment cycle (€)

Source

F3

302.0

[8]

F4

426.8

[8]

Decompensated cirrhosis

6,720.2

[8]

HCC

7,470.0

[8]

Transplant (year 1)

84,093.8

[8]

Transplant (year 2+)

4,958.7

[8]

Death

1,138.7

Reprocessed from [8,30]

Anemia

38.7

Expert opinion

Rash

34.6

Expert opinion

SOF + DCV + RBV – 24 weeks1

55,560.0

[26-29]

INF-α + RBV + SOF – 12 weeks1

39,809.0

[26-29]

Table IV. Costs considered in the model

1 Ex-factory negotiated net price considering confidential agreements

Results

The results of the analysis are reported in Table V.

Scenario

Cost category

Costs (€)

Year 2015

Year 2016

Year 2017

Year 2018

Year 2019

Total

Without DCV

Treatment

107,723,154

107,723,154

107,723,154

107,723,154

107,723,154

538.615.770

HS and AE

9,705,386

14,603,436

14,835,723

15,056,818

24,168,852

78,370,216

Total

117,428,540

122,326,590

122,558,877

122,779,972

131,892,006

616,985,986

With DCV

Treatment

129,034,257

129,034,257

131,165,367

131,165,367

133,296,478

653.695.726

HS and AE

9,702,128

14,646,651

14,762,469

14,877,664

14,965,146

68.954.059

Total

138,736,385

143,680,908

145,927,836

146,043,031

148,261,623

722.649.785

Budget impact

Treatment

21,311,103

21,311,103

23,442,213

23,442,213

25,573,324

115,079,956

HS and AE

- 3,258

43,215

- 73,254

- 179,154

- 9,203,706

- 9,416,157

Total

21,307,845

21,354,318

23,368,959

23,263,059

16,369,618

105,663,799

Table V. Impact on the budget of the Italian NHS of the use of DCV for the treatment of HCV genotype 3 infected patients

The use of DCV would lead to an increase of the costs for the Italian NHS in the five years considered in the analysis. In details, the costs increase is due to the cost of treatment, while the costs related to the management of patients conditions in terms of health state and to the management of the adverse events decrease in the first year (- 3,258 €), increase in year 2 (+ 43,215 €) and exponentially decrease in the last three years of the analysis (-73,254 €, -179,154 € and -9,203,706 €, respectively). The total impact on the budget of the Italian NHS increase, compared to the previous year in the second and third year (+ 0.22% and + 9.43%) and decrease in the last two years (- 0.45% and -29.63%).

The sensitivity analysis results are reported in Table VI.

All scenarios show the same trends of the base case analysis and show a budget impact with yearly variations lower than 6 million euros.

img_02_01.jpg

Figure 1. Impact on the budget of the Italian NHS of the use of DCV for the treatment of HCV genotype 3 infected patients

Scenario

Costs (€)

Year 2015

Year 2016

Year 2017

Year 2018

Year 2019

Base case

21,307,845

21,354,318

23,368,959

23,263,059

16,369,618

DCV cost -10%

19,007,745

19,054,218

20,838,849

20,732,949

13,609,498

DCV cost +10%

23,607,945

23,654,418

25,899,069

25,793,169

19,129,738

DCV effectiveness -5%

21,307,845

21,325,040

23,419,717

23,384,465

16,570,992

Number of patients eligible to antiviral treatments -10%

19,177,060

19,218,887

21,032,063

20,936,753

14,732,656

Number of patients eligible to antiviral treatments +10%

23,438,629

23,489,750

25,705,855

25,589,365

18,006,579

DCV cost -10% and DCV effectiveness -5%

19,007,745

19,024,940

20,889,607

20,854,355

13,810,872

DCV cost +10% and DCV effectiveness -5%

23,607,945

23,625,140

25,949,827

25,914,575

19,331,112

DCV cost -10%, DCV effectiveness -5% and number of patients eligible to antiviral treatments +10%

20,908,519

20,927,434

22,978,568

22,939,790

15,191,959

DCV cost +10%, DCV effectiveness -5% and number of patients eligible to antiviral treatments +10%

25,968,739

25,987,654

28,544,810

28,506,032

21,264,223

DCV cost -10%, DCV effectiveness -5% and number of patients eligible to antiviral treatments -10%

17,106,970

17,122,446

18,800,647

18,768,919

12,429,785

DCV cost +10%, DCV effectiveness -5% and number of patients eligible to antiviral treatments -10%

21,247,150

21,262,626

23,354,845

23,323,117

17,398,001

DCV cost +10%, and number of patients eligible to antiviral treatments +10%

25,968,739

26,019,860

28,488,976

28,372,486

21,042,711

DCV cost +10% and number of patients eligible to antiviral treatments -10%

21,247,150

21,288,977

23,309,162

23,213,852

17,216,764

DCV cost -10%, and number of patients eligible to antiviral treatments +10%

20,908,519

20,959,640

22,922,734

22,806,244

14,970,447

DCV cost -10% and number of patients eligible to antiviral treatments -10%

17,106,970

17,148,797

18,754,964

18,659,654

12,248,548

Table VI. Yearly budget impact resulting from the sensitivity analysis performed

Discussion

New HCV antiviral treatments, due to their high effectiveness compared with previously available treatments, give the opportunity to cure the infection and substantially reduce its prevalence. Few studies investigated the cost effectiveness of DCV for the treatment of HCV genotype 3 infection [31,32], however to our knowledge its impact on national budget was not investigated so far. These economic evaluation may provide information on the efficiency of the resource allocation, but not on the sustainability of the treatment strategy.

The analysis performed show an increase of costs for the treatment of HCV genotype 3 infected patients for the Italian NHS in the five years considered. The cost increase is due to the cost of the antiviral treatment, while the direct medical costs related to the management of the patients’ health state and of therapy related adverse events constantly decrease after the second year. The dynamics of cost reduction (-73,254 €, -179,154 € and -9,203,706 € in the last three years of the analysis) suggest the possibility to compensate over the years the higher cost of the treatment with the cost reduction for the management of patients improved health conditions.

The model is based on published data related to the Italian context. However, the number of HCV infected patients and the rate of genotype 3 infection are still discussed within the scientific community. Moreover, the effectiveness of therapies in genotype 3 HCV infected patients is based on studies with limited samples due to the lower prevalence of this genotype compared with other HCV genotypes.

The main limit of the analysis is related to the 5 year time horizon considered. The higher effectiveness of DCV+ SOF + RBV compared with INF-α + RBV + SOF, lead to a decrease in the number of patients infected with HCV. The direct medical costs of the management of HCV infection increase in the long period (due to decompensated cirrhosis, HCC and liver transplant), therefore the budget impact of the use of DCV+ SOF + RBV is likely to be overestimated in the analysis presented, not considering the therapy’s long term benefits.

Conclusion

The use of DCV for the treatment of HCV genotype 3 infected patients in the Italian context is likely to have a short term impact on the budget of the Italian NHS increasing the resources use compared to the sole use of INF-α + RBV + SOF. However, in the five years analysis there is a trend of reduction in the cost of the management of health states and adverse events with DCV+ SOF + RBV, compared with INF-α + RBV + SOF, which may lead to the possibility to reduce costs in the long term.

Acknowledgements

Professional medical writing and editorial assistance was provided by Lazzarin A, PhD, and Alfredo A, PhD, and was funded by Bristol-Myers Squibb.

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