php159
ISPOR 16 Annual European Congress
th
Dublin 2 - 6 November 2013
Workshop in Pharmacoeconomics:
an Italian experience of
multi-stakeholder HTA consensus
Americo Cicchetti , Antonio Gasbarrini , Matteo Ruggeri , Dario Sacchini , Elena Paola Lanati ,
on behalf of WEF study group
1
2
1
2
3
Faculty of Economics, Catholic University of Sacred Heart, Rome, Italy
2
Faculty of Medicine, Catholic University of Sacred Heart, Rome, Italy
3
3P Solution S.r.l., Milan, Italy
1
BACKGROUND
HTA is a very challenging issue in many countries, including Italy, where it has been officially mentioned for the first time in the
National Healthcare Plan 2006-2008. In Italy only few groups are recognized at international level, some pertaining to central
and regional Institutions, some being small independent working groups. The Technology Assessment Unit (UVT), situated at
the Policlinico Gemelli – Cattolica University in Rome, was the first HTA group and can be considered a pioneer in Italy.
Digestive and Liver Disease 2012 (5)
86
Institute of Internal Medicine, Catholic University
Medical School, Rome, Italy
The working method consists of a series of meetings (at least 4 per year) of the Scientific board (composed by high-profile
experts covering all HTA domains: clinicians, pharmacoeconomists, experts in organizational aspects, bioethicists, patients,
Institutions) that carries out a nationwide analysis of the topic under examination and focuses on the main clinical, economic,
organizational, social, and ethical features. Questionnaire-based surveys and Delphi panel are the main operational tools. WEF
adopts standard HTA procedures according to the EUnetHTA Core Model and to avoid any conflict of interests, no fee is paid to
any member.
∗ Corresponding author at: Institute of Internal
Medicine, Catholic University of Rome, 8 Largo A.
Gemelli, 00168 Rome, Italy. Tel.: +39 0630155451;
fax: +39 0635502775.
E-mail address: [email protected] (M. Biolato)
Reference
[1] Böhm G, Mossdorf A, Klink C, et al. Treatment algorithm for postoperative upper
gastrointestinal fistulas and leaks using combined Vicryl plug and fibrin glue.
Endoscopy 2010;42:599–602.
Angelo Caruso ∗
Raffaele Manta
Gianluigi Melotti
Rita Conigliaro
Nuovo Ospedale Civile S. Agostino Estense, Modena,
Italy
∗ Corresponding
Methods
author at: Nuovo Ospedale Civile
S. Agostino Estense Via Giardini, 1355 41126
Modena, Italy. Fax: +39 059 3961216;
mobile: +39 3494986810.
E-mail address: [email protected]
(A. Caruso)
doi:10.1016/j.dld.2011.07.004
Comment on “The role of endoscopic ultrasound in the
evaluation of chronic mesenteric ischaemia”
Sir,
We read with great interest the article by Almansa et al. published in Digestive and Liver Disease regarding the role of Doppler
endoscopic ultrasound as a comprehensive test to evaluate patients
with chronic upper abdominal pain in order to exclude chronic
mesenteric ischaemia [1]. In this study, authors employed, both
in Doppler endoscopic ultrasound and Dopper transabdominal
ultrasound, measurement of Peak Systolic Velocity (PSV) in celiac
artery and superior mesenteric artery as single parameter for the
detection of chronic mesenteric ischaemia. We would add that,
beside PSV, another Doppler parameter could be considered: EndDiastolic Velocity (EDV) appears comparable or superior to PSV
in identify significant arteriography-detected stenosis, and is not
influenced by an hyperdynamic circulation as for PSV [2–5]. In the
study of Almansa et al., Doppler endoscopic ultrasound (assessed by
means of PSV) presented a specificity of 84% in detecting chronic
mesenteric ischaemia; this figure could be even more appealing
employing EDV.
Conflict of interest statement
None declared.
Reference
[1] Almansa C, Bertani H, Noh KW, et al. The role of endoscopic ultrasound in the
evaluation of chronic mesenteric ischaemia. Dig Liver Dis 2011;43:470–4.
[2] Moneta GL, Yeager RA, Dalman R, et al. Duplex ultrasound criteria for diagnosis
of splanchnic artery stenosis or occlusion. J Vasc Surg 1991;14:511–8.
[3] Bowersox JC, Zwolak RM, Walsh DB, et al. Duplex ultrasonography in the diagnosis of celiac and mesenteric artery occlusive disease. J Vasc Surg 1991;14:780–6.
[4] Zwolak RM, Fillinger MF, Walsh DB, et al. Mesenteric and celiac duplex scanning:
a validation study. J Vasc Surg 1998;27:1078–87.
[5] Perko MJ, Just S, Schroeder TV. Importance of diastolic velocities in the detection of celiac and mesenteric artery disease by duplex ultrasound. J Vasc Surg
1997;26:288–93.
Marco Biolato ∗
Antonio Grieco
WEF E 2011 (1)
LETTERS TO THE EDITOR
Nationwide prediction of future expenditure for protease
inhibitors in chronic hepatitis C
Effect of discounting on estimation of benefits determined
by hepatitis C treatment
Dear Editor,
Peginterferon plus ribavirin is the current standard of care
for chronic hepatitis C, which determines sustained virological
response (SVR) in 30–50% of patients. Protease inhibitors (namely
boceprevir and telaprevir) are a further advancement that could
increase SVR to approximately 60% [1]. Boceprevir and telaprevir
have already been approved by the Food and Drug Administration (FDA) and are about to be marketed in Europe (boceprevir is
available in France where its cost per patient is around D 22,000
according to the website http://viralmatters.blogspot.com). The
globalization of pharmaceutical markets has much increased the
international homogeneity of drug prices; hence, transferring the
cost of innovative drugs from one country to another is likely to
imply a reasonable approximation.
Predicting the economic impact of adding a protease inhibitor
to patients treated for hepatitis C is a crucial point in terms of pharmaceutical governance, especially in countries like Italy where the
national health system provides full economic coverage of all essential treatments. The first step in evaluating an innovative treatment
is to determine its cost-effectiveness; if the pharmacoeconomic
profile is acceptable and the drug is therefore likely to be used,
the next step is to estimate the budget impact.
Since preliminary studies [2] indicate that the cost-effectiveness
of these protease inhibitors is favourable, a budget impact analysis
focused on these agents is worthwhile. The national expenditure
for ribavirin in Italy has been D 33 million in 2009; assuming that
each patient receives 840 capsules for a whole treatment (considering a cost of D 4.2 per capsule, and including adjustments for
treatment interruptions and suboptimal compliance [3]), this figure of national expenditure indicates that 9300 Italian patients/year
receive treatment for hepatitis C regardless of their genotype. Given
that genotype 1 accounts for 60% of all patients [4], this translates
into a prediction of 5500 Italian patients with genotype 1 to be
treated yearly with a protease inhibitor.
To estimate the economic impact of adding a protease inhibitor
to these patients, we used a prediction model described previously
[5]. According to this model, the yearly expenditure for the drug
is directly proportional to the yearly number of treated patients
(where the proportionality factor is the yearly cost per patient). The
model is not drug-specific because the mathematical function simply handles an initial phase where expenditure increases as more
and more patients of the eligible yearly population are being treated
over time.
Fig. 1 shows the results of our budget impact analysis for protease inhibitors based on this model. In our base-case prediction,
after projecting the expenditure for up to 5500 patients/year from
mid-2012 until 2017, the overall budget impact is estimated to be
D 115 million per year at steady state (solid line).
Two factors affect the above budget impact analysis by acting in
opposite directions. The first is that the patients actually receiving
Andrea Messori, Sabrina Trippoli, Laboratorio SIFO di Farmacoeconomia, Area Vasta Centro Toscana, 59100 Prato, Italy
Valeria Fadda, Dario Maratea, Department of Pharmaceutical
Sciences, University of Firenze, 50019 Sesto Fiorentino, Italy
Author contributions: All authors were involved in data collection, study design, data analysis and interpretation and all
authors were involved in writing of the manuscript.
Correspondence to: Dr. Andrea Messori, PhD, Laboratorio
SIFO di Farmacoeconomia, c/o Area Vasta Centro Toscana, Regional Health System, Via Guimaraes 9-11, 59100 Prato,
Italy. [email protected]
Telephone: +39-347-6053933 Fax: +39-574-701319
Received: December 23, 2011 Revised: February 27, 2012
Accepted: March 20, 2012
Published online: June 21, 2012
con il patrocinio di:
© 2012 Baishideng. All rights reserved.
Key words: Boceprevir; Telaprevir; Cost-effectiveness;
Markov model; Hepatitis C
Peer reviewers: Chao-Hung Hung, Kaohsiung Chang Gung
Memorial Hospital, 123 Ta Pei Road, Niao Sung, Kaohsiung
833, Taiwan, China; Faisal M Sanai, Hepatobiliary Sciences,
King Abdulaziz Medical City, King Abdulaziz Medical City,
Riyadh 11462, Saudi Arabia
Abstract
Messori A, Fadda V, Maratea D, Trippoli S. Effect of discounting
on estimation of benefits determined by hepatitis C treatment.
World J Gastroenterol 2012; 18(23): 3032-3034 Available from:
URL: http://www.wjgnet.com/1007-9327/full/v18/i23/3032.htm
DOI: http://dx.doi.org/10.3748/wjg.v18.i23.3032
The combination of either boceprevir or telaprevir
with ribavirin and interferon (triple therapy) has been
shown to be more effective than ribavirin+interferon
(dual therapy) for the treatment of genotype 1 hepatitis C. Since the benefit of these treatments takes place
after years, simulation models are needed to predict
long-term outcomes. In simulation models, the choice
of different values of yearly discount rates (e.g., 6%,
3.5%, 2%, 1.5% or 0%) influences the results, but
no studies have specifically addressed this issue. We
examined this point by determining the long-term benefits under different conditions on the basis of standard modelling and using quality-adjusted life years
(QALYs) to quantify the benefits. In our base case
scenario, we compared the long-term benefit between
patients given a treatment with a 40% sustained virologic response (SVR) (dual therapy) and patients given
a treatment with a 70% SVR (triple therapy), and we
then examined how these specific yearly discount rates
influenced the incremental benefit. The gain between
a 70% SVR and a 40% SVR decreased from 0.45 QALYs with a 0% discount rate to 0.22 QALYs with a 6%
discount rate (ratio between the two values = 2.04).
T
he estimated global prevalence of hepatitis C
virus (HCV) infection is 2.2%, corresponding
to about 130 million HCV-positive persons
worldwide, most of whom are chronically infected.1 A
recent revision2 reported that the estimated prevalence
of HCV infection in Europe ranges from 0.6% to
5.6%. This is of increasing interest because HCV is a
leading cause of both cirrhosis and hepatocellular carcinoma (HCC) in Western countries. The prevalence
of HCV-related cirrhosis and its complications will
TO THE EDITOR
The review by Tsubota et al[1] has examined the main options available for the treatment of hepatitis C, including
two antiviral drugs that have recently been marketed
in many countries. Focusing more thoroughly on these
two innovative agents is worthwhile because boceprevir
and telaprevir, along with other innovative agents, are
thought to be an important advancement in the treatment of this disease[2], although at a high cost.
Hepatitis C virus (HCV) genotype 1, which accounts
for 60% of all HCV-infected patients[3-5], is the target at
which these two new agents are directed in combination with ribavirin + interferon. Considering that the
combination of either boceprevor or telaprevir with
ribavirin+interferon (triple therapy) has been shown
3032
continue to increase through the next decade, and will
mostly affect those above age 60.3
Considering the burden of HCV-related cirrhosis
and its complications, the achievement of a sustained
virologic response (SVR) is a very important surrogate
outcome in the management of chronic hepatitis C
(CHC) patients. In fact, viral eradication prevents the
development of cirrhosis4 and its complications, such
as esophageal varices5 and HCC,6 and leads to a
decrease in liver-related death.7
Abbreviations: BOC, boceprevir; CHC, chronic hepatitis C; DT, dual therapy; G1, genotype 1; ICER, incremental cost effectiveness ratio; PI, protease inhibitors;
PEG-IFN, pegylated interferon; RBV, ribavirin; TVR, telaprevir.
From the 1Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy; 2Dipartimento di Scienze Statistiche e Matematiche ‘‘S. Vianelli,’’ University of
Palermo, Palermo, Italy; 3Division of Infectious and Tropical Diseases, Foundation IRCCS San Matteo Hospital, University of Pavia, Italy; 4Universit
a Cattolica del
Sacro Cuore, Facolt
a di Economia, Roma, Italy; 5University of Pavia, School of Pharmacy, Italy; 6Universit
a Cattolica del Sacro Cuore, Facolt
a di Medicina e
Chirurgia, Gastroenterologia Roma, Italy.
Received December 20, 2011; accepted March 12, 2012.
This study was entirely funded by 3P Solution. The funding agency was not involved in the study design or its execution, data management or analysis, article
preparation or review, or the decision to submit the article for publication.
850
June 21, 2012|Volume 18|Issue 23|
Journal of Hepatology 2013 (9)
Cost-Effectiveness of Boceprevir or Telaprevir for
Untreated Patients With Genotype
1 Chronic Hepatitis C
Value in Health 2013 (10)
Available online at www.sciencedirect.com
Cost-effectiveness of boceprevir or telaprevir for previously
treated patients with genotype 1 chronic hepatitis C
journal homepage: www.elsevier.com/locate/jval
Calogero Cammà1,⇑, Salvatore Petta1, Giuseppe Cabibbo1, Matteo Ruggeri2, Marco Enea3,
Raffaele Bruno4, Vincenza Capursi3, Antonio Gasbarrini5, Alfredo Alberti6, Antonio Craxì1,
on behalf of the WEF Study Group
Calogero Camma,1 Salvatore Petta,1 Marco Enea,2 Raffaele Bruno,3 Fabrizio Bronte,1 Vincenza Capursi,2
Americo Cicchetti,4 Giorgio L. Colombo,5 Vito Di Marco,1 Antonio Gasbarrini,6 and Antonio Craxı̀,1
on behalf of the WEF Study Group
he estimated global prevalence of hepatitis C
virus (HCV) infection is 2.2%, corresponding
to about 130 million HCV-positive persons
worldwide, most of whom are chronically infected.1 A
recent revision2 reported that the estimated prevalence
of HCV infection in Europe ranges from 0.6% to
5.6%. This is of increasing interest because HCV is a
leading cause of both cirrhosis and hepatocellular carcinoma (HCC) in Western countries. The prevalence
of HCV-related cirrhosis and its complications will
I QUADERNI DI MEDICINA
Testing the other discounting assumptions confirmed
that the discount rate has a marked impact on the
magnitude of the model-estimated incremental benefit.
In conclusion, the results of our analysis can be helpful
to better interpret cost-effectiveness studies evaluating
new treatment for hepatitis C.
Research Article
T
I QUADERNI DI MEDICINA
Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon
alpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assessed the cost-effectiveness of TT compared
to DT in the treatment of untreated patients with G1 CHC. We created a Markov Decision
Model to evaluate, in untreated Caucasian patients age 50 years, weight 70 kg, with G1
CHC and Metavir F2 liver fibrosis score, for a time horizon of 20 years, the cost-effectiveness
of the following five competing strategies: 1) boceprevir response-guided therapy (BOCRGT); 2) boceprevir IL28B genotype-guided strategy (BOC-IL28B); 3) boceprevir rapid
virologic response (RVR)-guided strategy (BOC-RVR); 4) telaprevir response-guided therapy
(TVR-RGT); 5) telaprevir IL28B genotype-guided strategy (TVR-IL28B). Outcomes
included life-years gained (LYG), costs (in 2011 euros) and incremental cost-effectiveness ratio (ICER). In the base-case analysis BOC-RVR and TVR-IL28B strategies were the most
effective and cost-effective of evaluated strategies. LYG was 4.04 with BOC-RVR and 4.42
with TVR-IL28B. ICER compared with DT was €8.304 per LYG for BOC-RVR and
€11.455 per LYG for TVR-IL28B. The model was highly sensitive to IL28B CC genotype,
likelihood of RVR and sustained virologic response, and BOC/TVR prices. Conclusion: In
untreated G1 CHC patients age 50 years, TT with first-generation protease inhibitors is costeffective compared with DT. Multiple strategies to reduce costs and improve effectiveness
include RVR or genotype-guided treatment. (HEPATOLOGY 2012;56:850-860)
VALUE IN HEALTH 16 (2013) 965–972
WEF E 2012 (2)
APRILE 2012
Calogero Camma,1 Salvatore Petta,1 Marco Enea,2 Raffaele Bruno,3 Fabrizio Bronte,1 Vincenza Capursi,2
Americo Cicchetti,4 Giorgio L. Colombo,5 Vito Di Marco,1 Antonio Gasbarrini,6 and Antonio Craxı̀,1
on behalf of the WEF Study Group
Andrea Messori, Valeria Fadda, Dario Maratea, Sabrina Trippoli
1
Economic Assessment of an Anti-HCV Screening Program in Italy
Matteo Ruggeri1,*, Silvia Coretti1, Antonio Gasbarrini2, Americo Cicchetti1
2
Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy; Institute of Policy and Economics, Graduate school of Health Economics
and Management, Università Cattolica del Sacro Cuore, Roma, Italy; 3Dipartimento di Scienze Statistiche e Matematiche ‘‘S. Vianelli’’,
University of Palermo, Palermo, Italy; 4Division of Infectious and Tropical Diseases, Foundation IRCCS San Matteo Hospital,
University of Pavia, Italy; 5Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia, GastroenteroLogia, e Economica,
Università Cattolica del Sacro Cuore, Roma, Italy; 6Department of Histology, Microbiology and Medical Biotechnologies,
Venetian Institute of Molecular Medicine, University of Padova, Italy
Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon
alpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assessed the cost-effectiveness of TT compared
to DT in the treatment of untreated patients with G1 CHC. We created a Markov Decision
Model to evaluate, in untreated Caucasian patients age 50 years, weight 70 kg, with G1
CHC and Metavir F2 liver fibrosis score, for a time horizon of 20 years, the cost-effectiveness
of the following five competing strategies: 1) boceprevir response-guided therapy (BOCRGT); 2) boceprevir IL28B genotype-guided strategy (BOC-IL28B); 3) boceprevir rapid
virologic response (RVR)-guided strategy (BOC-RVR); 4) telaprevir response-guided therapy
(TVR-RGT); 5) telaprevir IL28B genotype-guided strategy (TVR-IL28B). Outcomes
included life-years gained (LYG), costs (in 2011 euros) and incremental cost-effectiveness ratio (ICER). In the base-case analysis BOC-RVR and TVR-IL28B strategies were the most
effective and cost-effective of evaluated strategies. LYG was 4.04 with BOC-RVR and 4.42
with TVR-IL28B. ICER compared with DT was €8.304 per LYG for BOC-RVR and
€11.455 per LYG for TVR-IL28B. The model was highly sensitive to IL28B CC genotype,
likelihood of RVR and sustained virologic response, and BOC/TVR prices. Conclusion: In
untreated G1 CHC patients age 50 years, TT with first-generation protease inhibitors is costeffective compared with DT. Multiple strategies to reduce costs and improve effectiveness
include RVR or genotype-guided treatment. (HEPATOLOGY 2012;56:850-860)
GIUGNO 2011
© 2012 Baishideng. All rights reserved.
doi:10.1016/j.dld.2011.07.011
WJG|www.wjgnet.com
Since 2011, three HTA reports have been produced on hepatology, focusing in 2011 and 2012 respectively on HBV/HCV screening
strategies and HCV new Direct Antiviral Agents (DAA)-based therapies and extending in 2013 to hepatocellular carcinoma. In
2013 a second therapeutical area was assessed, dealing with gastroenterology and inflammatory bowel diseases (IBDs), in
particular with Crohn’s disease and its treatment with biological high-cost drugs. For 2014, a fourth edition on hepatology and
a second on IBDs are being developed. A first WEF edition on HIV is also coming up next year.
Cost-Effectiveness of Boceprevir or Telaprevir for
Untreated Patients With Genotype
1 Chronic Hepatitis C
World J Gastroenterol 2012 June 21; 18(23): 3032-3034
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
Online Submissions: http://www.wjgnet.com/1007-9327office
[email protected]
doi:10.3748/wjg.v18.i23.3032
Hepatology 2013 (8)
Results
Hepatology 2012 (7)
Correspondence / Digestive and Liver Disease 44 (2012) 85–87
Conflict of interest statement
No conflict of interest.
Objectives
The objective of the Italian Workshop in Pharmacoeconomics (WEF), born as a practical application of HTA, is to validate an
innovative experience that aims at being recognized by Institutions as a national and independent HTA assessor, thus supporting
both national and regional healthcare decision-makers. This experience consists of a multi-stakeholder working group that, in
the field of new technologies proposed for critical clinical areas, discusses and develops guide-lines and decision rules and
comparatively examines local real practice data, directly collected by the members of the Scientific Board.
World Journal of Gastroenterology 2012 (6)
Background & Aims: Randomised controlled trials (RCTs) show
that triple therapy (TT) with peginterferon alfa, ribavirin, and
boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype
1 (G1) chronic hepatitis C (CHC) patients with previous relapse
(RR), partial response (PAR), and null-response (NR). We assess
the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC.
Methods: The available published literature provided the data
source. The target population was made up of previously treated
Caucasian patients with G1 CHC and these were evaluated over a
lifetime horizon by Markov model. The study was carried out
from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro at 2012 value), life
years gained (LYG), quality adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER).The robustness of the
results was evaluated by one-way deterministic and multivariable probabilistic sensitivity analyses.
Results: In RR patients, ICER per LYG compared to no therapy was
€9555 for BOC-LEAD-IN-RR and €7910 for TVR-LEAD-IN-RR, being
BOC dominated by TVR. In PAR patients, ICER for LYG was
€11,947 for BOC-LEAD-IN-PAR and €14,931 for TVR-PAR, being
TVR cost-effective compared to BOC (ICER for QALY €22,258). In
NR patients, ICER for LYG was €26,499 for TVR-LEAD-IN-NR.
The models were sensitive to likelihood of sustained virological
response and to BOC/TVR prices.
continue to increase through the next decade, and will
mostly affect those above age 60.3
Considering the burden of HCV-related cirrhosis
and its complications, the achievement of a sustained
virologic response (SVR) is a very important surrogate
outcome in the management of chronic hepatitis C
(CHC) patients. In fact, viral eradication prevents the
development of cirrhosis4 and its complications, such
as esophageal varices5 and HCC,6 and leads to a
decrease in liver-related death.7
Keywords: Boceprevir; Telaprevir; Cost-effectiveness.
Received 25 December 2012; received in revised form 9 May 2013; accepted 14 May
2013; available online 23 May 2013
⇑ Corresponding author. Address: Sezione di Gastroenterologia, University of
Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy. Tel.: +39 091 655 2145;
fax: +39 091 655 2156.
E-mail address: [email protected] (C. Cammà).
Abbreviations: CHC, chronic hepatitis C; G1, genotype 1; DT, dual therapy; PegIFN,
pegylated interferon; RBV, ribavirin; PI, protease inhibitors; BOC, boceprevir; TVR,
telaprevir; ICER, incremental cost-effectiveness ratio; NR, non-response; PAR,
partial response; RR, relapse.
1
Faculty of Economics, Catholic University of Sacred Heart, Rome, Italy; 2Faculty of Medicine, Catholic University of Sacred Heart, Rome, Italy
AB STR A CT
Conclusions: 1st generation HCV PI is highly cost-effective compared to no therapy in RR and PAR G1 CHC patients. TVR dominated BOC in RR, and was cost-effective compared to BOC in
PAR patients. In NR patients an assessment of the response after
a lead-in period should be performed to improve safety and costeffectiveness.
2013 European Association for the Study of the Liver. Published
by Elsevier B.V. All rights reserved.
Introduction
Approximately 50% of all patients with genotype 1 chronic hepatitis C (G1 CHC) treated with dual therapy (DT) with peginterferon (PegIFN) plus ribavirin (RBV) experience treatment failure [1].
This means they represent a growing cohort of individuals at
higher risk of liver-related complications [2]. Considering the
high likelihood of disease progression of CHC patients failing
DT [3,4], and the burden of hepatitis C virus (HCV)-related cirrhosis and its related complications, the achievement of a sustained
virological response (SVR) is a very important surrogate outcome
in patient management. In fact, viral eradication prevents the
development of cirrhosis [5] and its related complications, such
as oesophageal varices [6] and hepatocellular carcinoma (HCC)
[7], and reduces liver-related death [8].
Two large randomized controlled trials (RCTs) [3,4], studying
long-term maintenance therapy with low-dose PegIFN in CHC
patients failing DT, showed no benefit in terms of progression
of liver disease. Several RCTs [9,10] and a recent meta-analysis
[11] showed that re-treatment of G1 non-responders with DT
favours SVR achievement in only 15% of patients. Guidelines of
the European Association for the Study of the Liver (EASL) [12]
and of the American Association for the Study of Liver Disease
(AASLD, 2011) [13] recommended that patients infected with
G1 HCV and who failed to eradicate HCV after prior DT should
not be re-treated with the same drug regimen. It was suggested
were discounted by 3.5%. Results were expressed as cost/qualityadjusted life-year (QALY) gained through the screening program compared with the treatment of symptomatic patients. Deterministic and
probabilistic sensitivity analysis was performed. Results: The incremental cost-effectiveness ratio of the ‘‘Test Strategy’’ is €5171/QALY, definitively below the cost/QALY of other approved treatments in Italy. Model
results turned out as sensitive to the age of the target population, the
prevalence of HCV infection, and the time horizon adopted. Conclusions: The anti-HCV screening program is a valid health-related investment improving patients’ quality of life and survival with an acceptable
expenditure increase for the National Health Service.
Keywords: cost-effectiveness, Italy, liver disease, Markov model.
Introduction
benefits to health many years later. A recent systematic review
[2] summarized the results of seven studies about hepatitis C
screening programs carried out in France, Great Britain, and the
United Kingdom on subgroups of patients. The incremental costeffectiveness ratio (ICER) of screening compared with treatment
of symptomatic patients was found to range between €3,900 and
€243,700 per life-year gained, or €18,000 and €1,151,000 per
quality-adjusted life-year (QALY) gained. The authors concluded
that screening was cost-effective in populations with a high
prevalence of HCV infection but excessively costly in populations
with a low prevalence.
The purpose of this study was to evaluate the costeffectiveness of a screening strategy aimed at identifying HCVpositive patients in comparison with the treatment of patients
who have developed cirrhosis or HCC following undiagnosed
chronic hepatitis.
Viral hepatitis is a chronic condition with a latent, nonlinear
disease progression. Hepatitis C virus (HCV) disease can remain
asymptomatic for decades and resolves spontaneously only in
exceptional cases. The disease normally takes over a decade to
progress, although this may be accelerated by the presence of
various cofactors including alcohol use, diabetes mellitus (for
which HCV is a risk factor), the age at which the disease was
developed, and coinfection with HIV or other hepatotropic
viruses. Between 10% and 40% of patients with chronic HCV
infection will develop cirrhosis, depending on the occurrence of
these cofactors. The annual incidence of death due to cirrhosis
complications is around 4%, while the annual incidence of
hepatocarcinoma (HCC) among patients with chronic HCV infection is 1% to 5%. Patients with HCC have a 33% chance of
surviving beyond 1 year after its onset [1].
Early diagnosis following a screening test for chronic hepatitis
is an effective tool for the prompt treatment of HCV infection,
stopping the progression of any liver disease. Numerous studies
have been conducted in recent years to investigate the costeffectiveness ratio of screening for viral hepatitis. Many of these
studies have used decisional models because these tools are wellsuited to the design of early diagnosis programs, which usually
require considerable investment in the present but pay back their
Journal of Hepatology 2013 vol. 59 j 658–666
Abbreviations: BOC, boceprevir; CHC, chronic hepatitis C; DT, dual therapy; G1, genotype 1; ICER, incremental cost effectiveness ratio; PI, protease inhibitors;
PEG-IFN, pegylated interferon; RBV, ribavirin; TVR, telaprevir.
From the 1Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy; 2Dipartimento di Scienze Statistiche e Matematiche ‘‘S. Vianelli,’’ University of
Palermo, Palermo, Italy; 3Division of Infectious and Tropical Diseases, Foundation IRCCS San Matteo Hospital, University of Pavia, Italy; 4Universit
a Cattolica del
Sacro Cuore, Facolt
a di Economia, Roma, Italy; 5University of Pavia, School of Pharmacy, Italy; 6Universit
a Cattolica del Sacro Cuore, Facolt
a di Medicina e
Chirurgia, Gastroenterologia Roma, Italy.
Received December 20, 2011; accepted March 12, 2012.
This study was entirely funded by 3P Solution. The funding agency was not involved in the study design or its execution, data management or analysis, article
preparation or review, or the decision to submit the article for publication.
Background: The progression of hepatitis C virus (HCV) disease
usually occurs over a 10-year period. HCV-related complications as
well as the highly debilitating effects on patients represent a significant item of expenditure for the National Health Service. Early
detection of HCV infection is an excellent opportunity to improve
patients’ quality of life and to rationalize resource allocation. Objective: The aim of this study was to provide a cost-effectiveness
evaluation of an anti-HCV screening program in the Italian National
Health Service perspective. Methods: We built a Markov model made
up of two arms. The ‘‘Test Strategy’’ arm involves a screening program
based on the enzyme immunoassay for detection of antibodies as
first-level test and the research of HCV RNA as second-level detection;
patients with positive test results are treated with peg-interferon alfa
in combination with ribavirine. Parameters were derived from the
literature and validated through experts’ opinion. Costs and benefits
Copyright & 2013, International Society for Pharmacoeconomics and
Outcomes Research (ISPOR). Published by Elsevier Inc.
Methods
Model Structure
We studied HCV disease progression up to death, simulating the
observation of a cohort of 100,000 individuals from the general
* Address correspondence to: Matteo Ruggeri, Faculty of Economics, Catholic University of Sacred Heart, l.go F.Vito 1, Rome 00168, Italy.
E-mail: [email protected].
1098-3015/$36.00 – see front matter Copyright & 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
Published by Elsevier Inc.
850
http://dx.doi.org/10.1016/j.jval.2013.07.005
Primo WorkshoP naZionale
di economia e Farmaci in ePatoloGia
WeF-e 2011
dalle epatiti all’epatocarcinoma:
epidemiologia e costi associati
to pubblicato grazie ad un unrestricted grant di
Questo report è stato pubblicato grazie ad un unrestricted grant di:
roma, 27-28 aprile 2011
secondo WorkshoP naZionale
di economia e Farmaci in ePatoloGia
WeF-e 2012
il trattamento delle epatiti virali in italia:
la sostenibilità di un modello vincente per
il bene del paziente
roma, 2 febbraio 2012
Reduc+on in +me-­‐to-­‐market WEF E 2013 (3)
WEF IBD 2013 (4)
xxxxxxxxxxxx 2013
I QUADERNI DI MEDICINA
GIUGNO 2013
I QUADERNI DI MEDICINA
con il patrocinio di:
con il patrocinio di:
TERZO WORkshOp di EcOnOmia
E FaRmaci in EpaTOlOgia
WEF-E 2013
ROma
7 - 8 FEBBRAIO 2013
ITALY Veneto Umbria Toscana Sardegna Lazio Emilia-­‐Romagna Mean HCV DAAs 0 PRIMO WORKSHOP DI ECONOMIA
E FARMACI PER LE MALATTIE
INFIAMMATORIE CRONICHE
INTESTINALI
WEF-IBD 2013
50 100 150 200 250 300 Days from na+onal authoriza+on ROMA
6 FEBBRAIO 2013
Conclusions
Along with 6 publications in international journals (mean impact factor 7,1), there have also been auditions at the Italian Drug
Agency (AIFA) and at the Healthcare Commission in Parliament that have facilitated the approval of new HCV drugs. Furthermore,
the analysis of available data about delays in approvals by regional formularies have been reduced by about 55% (from 221 days
after national marketing authorization to 101 days; Farmindustria data).
1) Primo Workshop Nazionale di Economia e Farmaci in Epatologia WEF-E 2011 - Roma, 27-28 aprile 2011. I quaderni di medicina Il 24 ore Sanità. Giugno 2011
2) Secondo Workshop Nazionale di Economia e Farmaci in Epatologia WEF-E 2012 - Roma, 2 febbraio 2012. I quaderni di medicina Il 24 ore Sanità. Aprile 2012
3) Terzo Workshop Nazionale di Economia e Farmaci in Epatologia WEF-E 2013 - Roma, 7-8 febbraio 2013. I quaderni di medicina Il 24 ore Sanità. Luglio 2013
4) Primo Workshop Nazionale di Economia e Farmaci per le Malattie Infiammatorie Croniche Intestinali -WEF-IBD 2013 - Roma, 6 febbraio 2013. I quaderni
di medicina Il 24 ore Sanità. Giugno 2013
5) Maratea D, Messori A, Fadda V; WEF-E Study Group. Nationwide prediction of future expenditure for protease inhibitors in chronic hepatitis C. Dig Liver
Dis. 2012 Jan;44(1):86-7.
6) Messori A, Fadda V, Maratea D, Trippoli S. Effect of discounting on estimation of benefits determined by hepatitis C treatment. World J Gastroenterol.
2012 Jun 21;18(23):3032-4.
This new multidisciplinary and multistakeholder approach proved to be well-accepted, and the “WEF method” is already
recognized as a milestone in the Italian HTA landscape, by Institutions (e.g. AIFA and Italian MoH), Scientific Societies and
pharma industries, thus helping payers in making rational decisions based on HTA methods.
This is the proof that HTA, if well built and following a scientific evidence-based process, is a very useful tool that, considering
all aspects concerning the healthcare system, may pragmatically improve prescriptive appropriateness of drugs/technologies
and facilitate access to cures.
7) Cammà C, Petta S, Enea M, Bruno R, Bronte F, Capursi V, Cicchetti A, Colombo GL, Di Marco V, Gasbarrini A, Craxì A; WEF Study Group. Cost-effectiveness
of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C. Hepatology. 2012 Sep;56(3):850-60.
8) Cammà C, Cabibbo G, Petta S, Enea M, Iavarone M, Grieco A, Gasbarrini A, Villa E, Zavaglia C, Bruno R, Colombo M, Craxì A; WEF study group; SOFIA study
group. Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma. Hepatology. 2013 Mar;57(3):1046-54.
9) Cammà C, Petta S, Cabibbo G, Ruggeri M, Enea M, Bruno R, Capursi V, Gasbarrini A, Alberti A, Craxì A; WEF Study Group. Cost-effectiveness of boceprevir
or telaprevir for previously treated patients with genotype 1 chronic hepatitis C. J Hepatol. 2013 Oct;59(4):658-66.
10) Ruggeri M, Coretti S, Gasbarrini A, Cicchetti A. Economic assessment of an anti-HCV screening program in Italy. Value Health. 2013 Sep-Oct;16(6):965-72.
3P SOLUTION s.r.l. MILAN - ITALY
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