Workshop in pharmacoeconomics:an italian experience of

multi-stakeholder hta consensus americo cicchetti1, antonio Gasbarrini2, matteo ruggeri1, dario sacchini2, elena Paola lanati3,

on behalf of WeF study group1 Faculty of Economics, Catholic University of Sacred Heart, Rome, Italy2 Faculty of Medicine, Catholic University of Sacred Heart, Rome, Italy

3 3P Solution S.r.l., Milan, Italy

BackGroundHTA 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.

objectivesThe 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.

methodsThe 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.

resultsSince 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.

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).

Digestive and Liver Disease 2012 (5) World Journal of Gastroenterology 2012 (6)

conclusionsThis 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.

ispor 16th annual european congressdublin 2 - 6 november 2013

3P SOLUTION s.r.l. MILAN - ITALYwww.3psolution.it - info@3psolution.it

+390236631574

pHp159

86 Correspondence / Digestive and Liver Disease 44 (2012) 85–87

Conflict of interest statementNo conflict of interest.

Reference

[1] Böhm G, Mossdorf A, Klink C, et al. Treatment algorithm for postoperative uppergastrointestinal fistulas and leaks using combined Vicryl plug and fibrin glue.Endoscopy 2010;42:599–602.

Angelo Caruso ∗

Raffaele MantaGianluigi Melotti

Rita ConigliaroNuovo Ospedale Civile S. Agostino Estense, Modena,

Italy

∗ Corresponding author at: Nuovo Ospedale CivileS. Agostino Estense Via Giardini, 1355 41126

Modena, Italy. Fax: +39 059 3961216;mobile: +39 3494986810.

E-mail address: angelocaruso@hotmail.it(A. Caruso)

doi:10.1016/j.dld.2011.07.004

Comment on “The role of endoscopic ultrasound in theevaluation of chronic mesenteric ischaemia”

Sir,

We read with great interest the article by Almansa et al. pub-lished in Digestive and Liver Disease regarding the role of Dopplerendoscopic ultrasound as a comprehensive test to evaluate patientswith chronic upper abdominal pain in order to exclude chronicmesenteric ischaemia [1]. In this study, authors employed, bothin Doppler endoscopic ultrasound and Dopper transabdominalultrasound, measurement of Peak Systolic Velocity (PSV) in celiacartery and superior mesenteric artery as single parameter for thedetection of chronic mesenteric ischaemia. We would add that,beside PSV, another Doppler parameter could be considered: End-Diastolic Velocity (EDV) appears comparable or superior to PSVin identify significant arteriography-detected stenosis, and is notinfluenced by an hyperdynamic circulation as for PSV [2–5]. In thestudy of Almansa et al., Doppler endoscopic ultrasound (assessed bymeans of PSV) presented a specificity of 84% in detecting chronicmesenteric ischaemia; this figure could be even more appealingemploying EDV.

Conflict of interest statementNone declared.

Reference

[1] Almansa C, Bertani H, Noh KW, et al. The role of endoscopic ultrasound in theevaluation of chronic mesenteric ischaemia. Dig Liver Dis 2011;43:470–4.

[2] Moneta GL, Yeager RA, Dalman R, et al. Duplex ultrasound criteria for diagnosisof 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 diagno-sis 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 detec-tion of celiac and mesenteric artery disease by duplex ultrasound. J Vasc Surg1997;26:288–93.

Marco Biolato ∗

Antonio Grieco

Institute of Internal Medicine, Catholic UniversityMedical School, Rome, Italy

∗ Corresponding author at: Institute of InternalMedicine, Catholic University of Rome, 8 Largo A.

Gemelli, 00168 Rome, Italy. Tel.: +39 0630155451;fax: +39 0635502775.

E-mail address: marcobiolato@alice.it (M. Biolato)

doi:10.1016/j.dld.2011.07.011

Nationwide prediction of future expenditure for proteaseinhibitors in chronic hepatitis C

Dear Editor,

Peginterferon plus ribavirin is the current standard of carefor chronic hepatitis C, which determines sustained virologicalresponse (SVR) in 30–50% of patients. Protease inhibitors (namelyboceprevir and telaprevir) are a further advancement that couldincrease SVR to approximately 60% [1]. Boceprevir and telaprevirhave already been approved by the Food and Drug Administra-tion (FDA) and are about to be marketed in Europe (boceprevir isavailable in France where its cost per patient is around D 22,000according to the website http://viralmatters.blogspot.com). Theglobalization of pharmaceutical markets has much increased theinternational homogeneity of drug prices; hence, transferring thecost of innovative drugs from one country to another is likely toimply a reasonable approximation.

Predicting the economic impact of adding a protease inhibitorto patients treated for hepatitis C is a crucial point in terms of phar-maceutical governance, especially in countries like Italy where thenational health system provides full economic coverage of all essen-tial treatments. The first step in evaluating an innovative treatmentis to determine its cost-effectiveness; if the pharmacoeconomicprofile 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-effectivenessof these protease inhibitors is favourable, a budget impact analysisfocused on these agents is worthwhile. The national expenditurefor ribavirin in Italy has been D 33 million in 2009; assuming thateach patient receives 840 capsules for a whole treatment (consid-ering a cost of D 4.2 per capsule, and including adjustments fortreatment interruptions and suboptimal compliance [3]), this fig-ure of national expenditure indicates that 9300 Italian patients/yearreceive treatment for hepatitis C regardless of their genotype. Giventhat genotype 1 accounts for 60% of all patients [4], this translatesinto a prediction of 5500 Italian patients with genotype 1 to betreated yearly with a protease inhibitor.

To estimate the economic impact of adding a protease inhibitorto these patients, we used a prediction model described previously[5]. According to this model, the yearly expenditure for the drugis directly proportional to the yearly number of treated patients(where the proportionality factor is the yearly cost per patient). Themodel is not drug-specific because the mathematical function sim-ply handles an initial phase where expenditure increases as moreand more patients of the eligible yearly population are being treatedover time.

Fig. 1 shows the results of our budget impact analysis for pro-tease inhibitors based on this model. In our base-case prediction,after projecting the expenditure for up to 5500 patients/year frommid-2012 until 2017, the overall budget impact is estimated to beD 115 million per year at steady state (solid line).

Two factors affect the above budget impact analysis by acting inopposite directions. The first is that the patients actually receiving

LETTERS TO THE EDITOR

Effect of discounting on estimation of benefits determined by hepatitis C treatment

Andrea Messori, Valeria Fadda, Dario Maratea, Sabrina Trippoli

Andrea Messori, Sabrina Trippoli, Laboratorio SIFO di Farma-coeconomia, Area Vasta Centro Toscana, 59100 Prato, Italy Valeria Fadda, Dario Maratea, Department of Pharmaceutical Sciences, University of Firenze, 50019 Sesto Fiorentino, ItalyAuthor contributions: All authors were involved in data col-lection, 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, Re-gional Health System, Via Guimaraes 9-11, 59100 Prato, Italy. andrea.messori.it@gmail.comTelephone: +39-347-6053933 Fax: +39-574-701319Received: December 23, 2011 Revised: February 27, 2012 Accepted: March 20, 2012Published online: June 21, 2012

Abstract 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 hepati-tis 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 ben-efits under different conditions on the basis of stan-dard 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 viro-logic 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 QA-LYs with a 0% discount rate to 0.22 QALYs with a 6% discount rate (ratio between the two values = 2.04).

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.

© 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

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

TO THE EDITORThe review by Tsubota et al[1] has examined the main op-tions 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 treat-ment 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 combina-tion with ribavirin + interferon. Considering that the combination of either boceprevor or telaprevir with ribavirin+interferon (triple therapy) has been shown

World J Gastroenterol 2012 June 21; 18(23): 3032-3034 ISSN 1007-9327 (print) ISSN 2219-2840 (online)

© 2012 Baishideng. All rights reserved.

Online Submissions: http://www.wjgnet.com/1007-9327officewjg@wjgnet.comdoi:10.3748/wjg.v18.i23.3032

3032 June 21, 2012|Volume 18|Issue 23|WJG|www.wjgnet.com

Cost-Effectiveness of Boceprevir or Telaprevir forUntreated Patients With Genotype

1 Chronic Hepatitis CCalogero Camm�a,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

Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferonalpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginter-feron-ribavirin dual therapy (DT) in the treatment of previously untreated patients with ge-notype 1 (G1) chronic hepatitis C (CHC). We assessed the cost-effectiveness of TT comparedto DT in the treatment of untreated patients with G1 CHC. We created a Markov DecisionModel 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-effectivenessof the following five competing strategies: 1) boceprevir response-guided therapy (BOC-RGT); 2) boceprevir IL28B genotype-guided strategy (BOC-IL28B); 3) boceprevir rapidvirologic response (RVR)-guided strategy (BOC-RVR); 4) telaprevir response-guided therapy(TVR-RGT); 5) telaprevir IL28B genotype-guided strategy (TVR-IL28B). Outcomesincluded life-years gained (LYG), costs (in 2011 euros) and incremental cost-effectiveness ra-tio (ICER). In the base-case analysis BOC-RVR and TVR-IL28B strategies were the mosteffective and cost-effective of evaluated strategies. LYG was 4.04 with BOC-RVR and 4.42with 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: Inuntreated G1 CHC patients age 50 years, TTwith first-generation protease inhibitors is cost-effective compared with DT. Multiple strategies to reduce costs and improve effectivenessinclude RVR or genotype-guided treatment. (HEPATOLOGY 2012;56:850-860)

The estimated global prevalence of hepatitis Cvirus (HCV) infection is 2.2%, correspondingto about 130 million HCV-positive persons

worldwide, most of whom are chronically infected.1 Arecent revision2 reported that the estimated prevalenceof HCV infection in Europe ranges from 0.6% to5.6%. This is of increasing interest because HCV is aleading cause of both cirrhosis and hepatocellular car-cinoma (HCC) in Western countries. The prevalenceof HCV-related cirrhosis and its complications will

continue to increase through the next decade, and willmostly affect those above age 60.3

Considering the burden of HCV-related cirrhosisand its complications, the achievement of a sustainedvirologic response (SVR) is a very important surrogateoutcome in the management of chronic hepatitis C(CHC) patients. In fact, viral eradication prevents thedevelopment of cirrhosis4 and its complications, suchas esophageal varices5 and HCC,6 and leads to adecrease 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 delSacro Cuore, Facolt�a di Economia, Roma, Italy; 5University of Pavia, School of Pharmacy, Italy; 6Universit�a Cattolica del Sacro Cuore, Facolt�a di Medicina eChirurgia, 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

WEF E 2011 (1) WEF E 2012 (2)

WEF E 2013 (3) WEF IBD 2013 (4)

I QUADERNI DI MEDICINA

APRILE 2012

secondo WorkshoP naZionale di economia e Farmaci in ePatoloGia

WeF-e 2012

il tratt amento delle epati ti virali in italia:la sostenibilità di un modello vincente per

il bene del pazienteroma, 2 febbraio 2012

Questo report è stato pubblicato grazie ad un unrestricted grant di:

con il patrocinio di:

I QUADERNI DI MEDICINA

GIUGNO 2011

Primo WorkshoP naZionale di economia e Farmaci in ePatoloGia

WeF-e 2011

dalle epati ti all’epatocarcinoma: epidemiologia e costi associati

roma, 27-28 aprile 2011Questo report è stato pubblicato grazie ad un unrestricted grant di

I QUADERNI DI MEDICINA

GIUGNO 2013

con il patrocinio di:

PRIMO WORKSHOP DI ECONOMIAE FARMACI PER LE MALATTIEINFIAMMATORIE CRONICHE

INTESTINALIWEF-IBD 2013

ROMA6 FEBBRAIO 2013

I QUADERNI DI MEDICINA

xxxxxxxxxxxx 2013

con il patrocinio di:

TERZO WORkshOp di EcOnOmiaE FaRmaci in EpaTOlOgia

WEF-E 2013

ROma7 - 8 FEBBRAIO 2013

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 20112) 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 20123) 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 20134) 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.

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.

Hepatology 2012 (7)

Hepatology 2013 (8) Journal of Hepatology 2013 (9)

Cost-Effectiveness of Boceprevir or Telaprevir forUntreated Patients With Genotype

1 Chronic Hepatitis CCalogero Camm�a,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

Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferonalpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginter-feron-ribavirin dual therapy (DT) in the treatment of previously untreated patients with ge-notype 1 (G1) chronic hepatitis C (CHC). We assessed the cost-effectiveness of TT comparedto DT in the treatment of untreated patients with G1 CHC. We created a Markov DecisionModel 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-effectivenessof the following five competing strategies: 1) boceprevir response-guided therapy (BOC-RGT); 2) boceprevir IL28B genotype-guided strategy (BOC-IL28B); 3) boceprevir rapidvirologic response (RVR)-guided strategy (BOC-RVR); 4) telaprevir response-guided therapy(TVR-RGT); 5) telaprevir IL28B genotype-guided strategy (TVR-IL28B). Outcomesincluded life-years gained (LYG), costs (in 2011 euros) and incremental cost-effectiveness ra-tio (ICER). In the base-case analysis BOC-RVR and TVR-IL28B strategies were the mosteffective and cost-effective of evaluated strategies. LYG was 4.04 with BOC-RVR and 4.42with 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: Inuntreated G1 CHC patients age 50 years, TTwith first-generation protease inhibitors is cost-effective compared with DT. Multiple strategies to reduce costs and improve effectivenessinclude RVR or genotype-guided treatment. (HEPATOLOGY 2012;56:850-860)

The estimated global prevalence of hepatitis Cvirus (HCV) infection is 2.2%, correspondingto about 130 million HCV-positive persons

worldwide, most of whom are chronically infected.1 Arecent revision2 reported that the estimated prevalenceof HCV infection in Europe ranges from 0.6% to5.6%. This is of increasing interest because HCV is aleading cause of both cirrhosis and hepatocellular car-cinoma (HCC) in Western countries. The prevalenceof HCV-related cirrhosis and its complications will

continue to increase through the next decade, and willmostly affect those above age 60.3

Considering the burden of HCV-related cirrhosisand its complications, the achievement of a sustainedvirologic response (SVR) is a very important surrogateoutcome in the management of chronic hepatitis C(CHC) patients. In fact, viral eradication prevents thedevelopment of cirrhosis4 and its complications, suchas esophageal varices5 and HCC,6 and leads to adecrease 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 delSacro Cuore, Facolt�a di Economia, Roma, Italy; 5University of Pavia, School of Pharmacy, Italy; 6Universit�a Cattolica del Sacro Cuore, Facolt�a di Medicina eChirurgia, 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

Cost-effectiveness of boceprevir or telaprevir for previouslytreated patients with genotype 1 chronic hepatitis C

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 Group1Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy; 2Institute 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

Background & Aims: Randomised controlled trials (RCTs) showthat triple therapy (TT) with peginterferon alfa, ribavirin, andboceprevir (BOC) or telaprevir (TVR) is more effective than pegin-terferon-ribavirin dual therapy (DT) in the treatment of genotype1 (G1) chronic hepatitis C (CHC) patients with previous relapse(RR), partial response (PAR), and null-response (NR). We assessthe cost-effectiveness of TT compared to no therapy in the treat-ment of patients previously treated with G1 CHC.Methods: The available published literature provided the datasource. The target population was made up of previously treatedCaucasian patients with G1 CHC and these were evaluated over alifetime horizon by Markov model. The study was carried outfrom the perspective of the Italian National Health Service. Out-comes included discounted costs (in euro at 2012 value), lifeyears gained (LYG), quality adjusted life year (QALY), and incre-mental cost-effectiveness ratio (ICER).The robustness of theresults was evaluated by one-way deterministic and multivari-able 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, beingBOC dominated by TVR. In PAR patients, ICER for LYG was€11,947 for BOC-LEAD-IN-PAR and €14,931 for TVR-PAR, beingTVR cost-effective compared to BOC (ICER for QALY €22,258). InNR patients, ICER for LYG was €26,499 for TVR-LEAD-IN-NR.The models were sensitive to likelihood of sustained virologicalresponse and to BOC/TVR prices.

Conclusions: 1st generation HCV PI is highly cost-effective com-pared to no therapy in RR and PAR G1 CHC patients. TVR domi-nated BOC in RR, and was cost-effective compared to BOC inPAR patients. In NR patients an assessment of the response aftera lead-in period should be performed to improve safety and cost-effectiveness.� 2013 European Association for the Study of the Liver. Publishedby Elsevier B.V. All rights reserved.

Introduction

Approximately 50% of all patients with genotype 1 chronic hepa-titis C (G1 CHC) treated with dual therapy (DT) with peginterfer-on (PegIFN) plus ribavirin (RBV) experience treatment failure [1].This means they represent a growing cohort of individuals athigher risk of liver-related complications [2]. Considering thehigh likelihood of disease progression of CHC patients failingDT [3,4], and the burden of hepatitis C virus (HCV)-related cirrho-sis and its related complications, the achievement of a sustainedvirological response (SVR) is a very important surrogate outcomein patient management. In fact, viral eradication prevents thedevelopment of cirrhosis [5] and its related complications, suchas oesophageal varices [6] and hepatocellular carcinoma (HCC)[7], and reduces liver-related death [8].

Two large randomized controlled trials (RCTs) [3,4], studyinglong-term maintenance therapy with low-dose PegIFN in CHCpatients failing DT, showed no benefit in terms of progressionof liver disease. Several RCTs [9,10] and a recent meta-analysis[11] showed that re-treatment of G1 non-responders with DTfavours SVR achievement in only 15% of patients. Guidelines ofthe 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 withG1 HCV and who failed to eradicate HCV after prior DT shouldnot be re-treated with the same drug regimen. It was suggested

Journal of Hepatology 2013 vol. 59 j 658–666

Keywords: Boceprevir; Telaprevir; Cost-effectiveness.Received 25 December 2012; received in revised form 9 May 2013; accepted 14 May2013; available online 23 May 2013⇑ Corresponding author. Address: Sezione di Gastroenterologia, University ofPalermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy. Tel.: +39 091 655 2145;fax: +39 091 655 2156.E-mail address: calogero.camma@unipa.it (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.

Research Article Avai lable onl ine at www.sc iencedirect .com

journal homepage: www.elsevier .com/ locate / jva l

Economic Assessment of an Anti-HCV Screening Program in ItalyMatteo Ruggeri1,*, Silvia Coretti1, Antonio Gasbarrini2, Americo Cicchetti1

1Faculty of Economics, Catholic University of Sacred Heart, Rome, Italy; 2Faculty of Medicine, Catholic University of Sacred Heart, Rome, Italy

A B S T R A C T

Background: The progression of hepatitis C virus (HCV) diseaseusually occurs over a 10-year period. HCV-related complications aswell as the highly debilitating effects on patients represent a signifi-cant item of expenditure for the National Health Service. Earlydetection of HCV infection is an excellent opportunity to improvepatients’ quality of life and to rationalize resource allocation. Objec-tive: The aim of this study was to provide a cost-effectivenessevaluation of an anti-HCV screening program in the Italian NationalHealth Service perspective. Methods: We built a Markov model madeup of two arms. The ‘‘Test Strategy’’ arm involves a screening programbased on the enzyme immunoassay for detection of antibodies asfirst-level test and the research of HCV RNA as second-level detection;patients with positive test results are treated with peg-interferon alfain combination with ribavirine. Parameters were derived from theliterature and validated through experts’ opinion. Costs and benefits

were discounted by 3.5%. Results were expressed as cost/quality-adjusted life-year (QALY) gained through the screening program com-pared with the treatment of symptomatic patients. Deterministic andprobabilistic sensitivity analysis was performed. Results: The incremen-tal cost-effectiveness ratio of the ‘‘Test Strategy’’ is €5171/QALY, defin-itively below the cost/QALY of other approved treatments in Italy. Modelresults turned out as sensitive to the age of the target population, theprevalence of HCV infection, and the time horizon adopted. Conclu-sions: The anti-HCV screening program is a valid health-related invest-ment improving patients’ quality of life and survival with an acceptableexpenditure increase for the National Health Service.Keywords: cost-effectiveness, Italy, liver disease, Markov model.

Copyright & 2013, International Society for Pharmacoeconomics andOutcomes Research (ISPOR). Published by Elsevier Inc.

Introduction

Viral hepatitis is a chronic condition with a latent, nonlineardisease progression. Hepatitis C virus (HCV) disease can remainasymptomatic for decades and resolves spontaneously only inexceptional cases. The disease normally takes over a decade toprogress, although this may be accelerated by the presence ofvarious cofactors including alcohol use, diabetes mellitus (forwhich HCV is a risk factor), the age at which the disease wasdeveloped, and coinfection with HIV or other hepatotropicviruses. Between 10% and 40% of patients with chronic HCVinfection will develop cirrhosis, depending on the occurrence ofthese cofactors. The annual incidence of death due to cirrhosiscomplications is around 4%, while the annual incidence ofhepatocarcinoma (HCC) among patients with chronic HCV infec-tion is 1% to 5%. Patients with HCC have a 33% chance ofsurviving beyond 1 year after its onset [1].

Early diagnosis following a screening test for chronic hepatitisis an effective tool for the prompt treatment of HCV infection,stopping the progression of any liver disease. Numerous studieshave been conducted in recent years to investigate the cost-effectiveness ratio of screening for viral hepatitis. Many of thesestudies have used decisional models because these tools are well-suited to the design of early diagnosis programs, which usuallyrequire considerable investment in the present but pay back their

benefits to health many years later. A recent systematic review[2] summarized the results of seven studies about hepatitis Cscreening programs carried out in France, Great Britain, and theUnited Kingdom on subgroups of patients. The incremental cost-effectiveness ratio (ICER) of screening compared with treatmentof symptomatic patients was found to range between €3,900 and€243,700 per life-year gained, or €18,000 and €1,151,000 perquality-adjusted life-year (QALY) gained. The authors concludedthat screening was cost-effective in populations with a highprevalence of HCV infection but excessively costly in populationswith a low prevalence.

The purpose of this study was to evaluate the cost-effectiveness of a screening strategy aimed at identifying HCV-positive patients in comparison with the treatment of patientswho have developed cirrhosis or HCC following undiagnosedchronic hepatitis.

Methods

Model Structure

We studied HCV disease progression up to death, simulating theobservation of a cohort of 100,000 individuals from the general

1098-3015/$36.00 – see front matter Copyright & 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Published by Elsevier Inc.

http://dx.doi.org/10.1016/j.jval.2013.07.005

E-mail: mruggeri@rm.unicatt.it.* Address correspondence to: Matteo Ruggeri, Faculty of Economics, Catholic University of Sacred Heart, l.go F.Vito 1, Rome 00168, Italy.

V A L U E I N H E A L T H 1 6 ( 2 0 1 3 ) 9 6 5 – 9 7 2

Value in Health 2013 (10)

0   50   100   150   200   250   300  

Emilia-­‐Romagna  Lazio  

Sardegna  Toscana  Umbria  Veneto  ITALY  

Days  from  na+onal  authoriza+on    

Reduc+on  in  +me-­‐to-­‐market  

Mean  

HCV  DAAs