Giovanni Giuliani

Cost Effectiveness of Peginterferon α-2a Plus Ribavirin versus Interferon α-2b Plus Ribavirin as Initial Therapy for Treatment-Naive Chronic Hepatitis C

AbstractIntroduction: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon α-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon α-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon α-2a plus ribavirin is worth the incremental cost. Methods: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon α-2a plus ribavirin or interferon α-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon α-2a plus ribavirin and interferon α-2b plus ribavirin used to populate the model were 46% and 36% for patients infected with HCV genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs were in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service. Results: In patients infected with HCV genotype 1, peginterferon α-2a plus ribavirin increased life-years (LYs) by 0.78 years and QALYs by 0.67 years, compared with interferon α-2b and ribavirin. The incremental cost per LY and QALY gained was €9433 and €10 894, respectively. In patients infected with HCV non-1 genotypes, peginterferon α-2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with interferon α-2b plus ribavirin. The incremental cost per LY and QALY gained was €3261 and €3766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was €6811 per LY gained and €7865 per QALY gained. Conclusion: Our model suggests that peginterferon α-2a plus ribavirin is cost effective compared with conventional interferon α-2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.

Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheumatoid arthritis in Italy.

Abstract Objective: This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer’s perspective in Italy. Methods: An individual patient simulation model was used to project lifetime medical costs (payer’s perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis. Results: Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient’s lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY. Conclusion: The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.

Cost-effectiveness analysis of bevacizumab versus pemetrexed for advanced non-squamous NSCLC in Italy

INTRODUCTION The new targeted agent bevacizumab in combination with cisplatin and gemcitabine (BCG), and a third-generation chemotherapy pemetrexed in combination with cisplatin (PC), are approved as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC). METHODS An indirect comparison between BCG and PC showed that the bevacizumab triplet achieved a favourable hazard ratio in terms of progression-free survival among patients with advanced NSCLC. This analysis aimed to compare the detailed costs and benefits of these treatments for advanced non-squamous NSCLC in Italy. RESULTS The monthly cost of single-agent bevacizumab, including administration and supportive care costs, and costs for adverse events as a single agent was 4,007 euro/patient less than pemetrexed over the patients lifetime. BCG also achieved a mean gain of 0.12 life-years compared with PC over this period. The incremental cost-effectiveness ratio of BCG relative to PC was calculated to be 34,919 euro per additional life-year gained suggesting that BCG is cost-effective compared with PC as first-line treatment for advanced NSCLC in Italy. CONCLUSIONS In conclusion, bevacizumab-based therapy can be considered as a cost-effective option when compared to chemotherapy treatments such as pemetrexed for the treatment for advanced non-squamous NSCLC.

Cost-Effectiveness of Enfuvirtide for Treatment- Experienced Patients with HIV in Italy

Abstract Background: Enfuvirtide (ENF) plus an optimized background (OB) antiretroviral regimen delays virological failure (VF), reduces HIV-1 viral load, and increases CD4 count compared with OB only in pretreated patients. Purpose: To forecast long-term outcomes, costs, and cost-effectiveness of ENF+OB vs. OB in the Italian health care system. Method: A Markov model was developed and clinical trial results on viral suppression and CD4 count were linked with data from HAART-era studies of the risk of AIDS-defining events (ADEs) and death. Resource data were obtained from Italian sources on direct medical costs. Cost-effectiveness was computed as the incremental cost per quality-adjusted life year (QALY) saved. Results: Patients receiving ENF+OB were projected to experience a mean time to virological failure of 1.0 years vs. 0.5 years for OB and mean time to immunological failure of 3.1 years vs. 1.3 years for OB. Life expectancy and QALYs were greater for ENF+OB than OB by 1.8 and 1.5 years, respectively. Total lifetime medical cost was €126,487 for ENF+OB and €84,416 for OB, a difference of €42,071 due to the cost of ENF itself (€18,400) and the medical costs associated with additional life expectancy (€23,671). The incremental cost-effectiveness of ENF+OB was €23,721 per life year (€28,669 per QALY). Conclusion: ENF+OB is predicted to increase life expectancy at a cost per life year that is comparable to many well-accepted therapies in Europe.

Cost comparison of second-line treatment options for late stage non-small-cell lung cancer: cost analysis for Italy

Background: Lung cancer is the leading cause of cancer deaths worldwide (1.38 million cancer deaths, 18.2% of the total) and of cancer morbidity (1.61 million new cases, 12.7% of all new cancers). Currently only three second-line non-small-cell lung cancer (NSCLC) pharmacotherapies are licensed in the European Union: the chemotherapies pemetrexed and docetaxel and the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. These therapy alternatives have shown a comparable efficacy (survival benefit). In the past, cost comparisons showed that erlotinib was less costly compared to docetaxel, which in turn is cheaper than pemetrexed. Nowadays erlotinib (and docetaxel) are still less expensive than pemetrexed; but docetaxel lost patent protection (basic compound patent) at the end of 2010, so docetaxel drug costs have decreased rapidly and the question remains whether erlotinib is still the least costly therapy alternative in second-line NSCLC. Material and methods: Italy was selected for base case analysis to compare the total therapy costs, estimated by combining country-specific drug costs, administration costs, and adverse event costs of erlotinib and generic docetaxel in second-line NSCLC therapy. Sensitivity analyses on central input parameters have been performed. Results: The total costs of treating one patient with erlotinib therapy of €5121 are lower than the docetaxel costs of €6699 for the Italian health care setting. Although the drug costs of erlotinib are higher than generic docetaxel (incremental €3770): the costs of intravenous chemotherapy administration (incremental −€4510), and the costs of adverse event therapy (incremental −€837) lead to higher total therapy costs for docetaxel compared to the epidermal growth factor receptor tyrosine kinase inhibitor therapy erlotinib. Conclusion: The cost comparison findings for Italy show that erlotinib is still the less costly therapy alternative in second-line NSCLC. These results were robust to changes of central input parameters and robust to further potential price decreases for docetaxel.

Rapporto costo-efficacia della terapia peginterferone α-2a + ribavirina in confronto a interferone α-2b + ribavirina in pazienti affetti da epatite cronica di tipo C precedentemente non trattati

SummaryIntroductionIn adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon α-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon α-2b plus ribavirin, but it is still unproven whether this increase is cost-effective. The objective of this study was to determine if the gain in SVR with peginterferon α-2a plus ribavirin is worth the incremental cost.MethodsWe constructed a Markov model of disease progression in which cohorts of patients received peginterferon α-2a plus ribavirin or interferon α-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon α-2a plus ribavirin, and interferon α-2b plus ribavirin, were 46% and 36% for patients infected with HCV genotype 1, and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service.ResultsIn patients infected with HCV genotype 1, peginterferon α-2a plus ribavirin increased life years (LY) by 0.78 years and quality-adjusted life years (QALY) by 0.67 years, compared with interferon α-2b and ribavirin. The incremental cost per LY and QALY gained was €9,433 and € 10,894, respectively. In patients infected with HCV non-1 genotypes, peginterferon ?-2a plus ribavirin increased LY by 1.17 and QALY by 1.01 years, compared with interferon α-2b plus ribavirin. The incremental cost per LY and QALY gained was €3,261 and €3,766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was €6,811 per LY gained and €7,865 per QALY gained.ConclusionOur model suggests that peginterferon α-2a plus ribavirin is cost-effective compared with conventional interferon α-2b plus ribavirin for treatment of naïve adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.

Valutazione di convenienza economica comparata tra un farmaco orale (capecitabina) e una chemioterapia parenterale a base di 5-FU (regime Mayo) nel trattamento del carcinoma del colon retto metastatizzato

SummaryObjectiveTo assess and compare the incremental healthcare resource consumption and costs in advanced colorectal cancer patients treated with oral capecitabine or intravenous chemotherapy with 5-fluorouracil plus leucovorin (5FU/LV; Mayo regimen).DesignA cost-minimization analysis was conducted on medical resource consumption data collected in the course of a prospective, randomised, phase III clinical trial in which 602 patients with advanced colorectal cancer were treated with capecitabine or 5FU/LV Mayo regimen. Collected data concerned hospital visits for drug administration and hospital admissions, drugs and unscheduled physicians’ consultations required for the treatment of adverse events. Italian National Health Service charges and market values were used to value resources. Time horizon was 6 months and the NHS perspective was assumed.ResultsThe use of capecitabine saved € 823 (17.4%) per patient over a 6-month period. In the capecitabine group the main cost driver was the drug cost (73% of total chemotherapy cost), while in the 5-FU/LV group the main cost driver was the cost of drug administration (95% of total chemotherapy cost). Treatment of adverse events accounted for 4.2% of total treatment costs in the capecitabine group and 6.8% in the 5-FU/LV group.ConclusionsCapecitabine treatment of colorectal cancer patients results in a substantial cost saving compared to the 5-FU/LV Mayo regimen, mainly because hospital visits for intravenous administration are avoided and fewer hospitalisations are required for the treatment of adverse events.

Conditional Agreements For Innovative Therapies In Italy: The Case Of Pirfenidone.

● In 2005, AIFA (Italian Drug Agency) implemented drug registries to ensure appropriate use of the treatment and enabling conditional agreements (i.e., risk-sharing) until the risk/benefit ratio of the drug is confirmed in clinical practice. ● Strong collaboration between AIFA, Clinicians, Hospital Pharmacists, Pharmacologists, Payers (Regional and Local) and pharmaceutical companies is needed through the Registries management (i.e., prescription, purchasing process, effectiveness evaluation) ● Registries permit to collect real world data to re-assess the clinical value in clinical practice (i.e., effectiveness) enabling a value-based pricing approach. ● For all stakeholders, registries represent an opportunity to work together in the light of partnership and sustainability. ● As an example of implementation of conditional agreement based on AIFA registries, we report the re-negotiation process of pirfenidone in the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF). ● Pirfenidone had its first reimbursement authorization in 2013 with a risk-sharing agreement (Success Fee) and drug inclusion in the AIFA Registry.

Costo-efficacia di capecitabina in combinazione con docetaxel versus docetaxel in monoterapia nel trattamento del carcinoma alla mammella metastatico in pazienti pretrattate con antracicline

SummaryIntroductionIn female adults with metastatic breast cancer, the combination of capecitabine plus docetaxel produces more life years and QALYs than docetaxel, but it is still unproved whether this gain is cost-effective. The objective of this study was to find an answer about such issue.MethodsWe used outcome results and resource consumption data from a randomized clinical trial in which two cohorts of patients were treated with capecitabine plus docetaxel (n = 255) or docetaxel (n = 256) for 36 months. The Utility associated to each health state was based on literature estimates. Costs were assessed in 2004 Euros and benefits were discounted at 3%. Sensitivity analyses were performed on key economic parameters. The analysis was conducted from the hospital perspective.ResultsIn patients with metastatic breast cancer, capecitabine plus docetaxel increased life years (LYs) by 0.22 years and quality-adjusted life years (QALYs) by 0.14 years, compared with docetaxel monotherapy. The incremental cost per LY and QALY gained was € 1,743.18 and € 2,736.25, respectively.ConclusionThis study suggests that, compared with docetaxel monotherapy, capecitabine plus docetaxel is cost-effective for the treatment of metastatic breast cancer.

PIN31: THE COST-EFFECTIVENESS OF PEGINTERFERON ALFA-2A (40KD) (PEGASYS) PLUS RIBAVIRIN (COPEGUS) VS. INTERFERON ALFA-2B PLUS RIBAVIRIN FOR CHRONIC HEPATITIS C (CHC)

nomic evaluation of drug therapy. OBJECTIVES: This was to assess the cost effectiveness of some antimicrobial agents used in the treatment of sexually transmitted diseases (STD). These include doxycycline versus tetracycline for chlamydial infection, benzathine penicillin versus procaine penicillin for syphilis, and ceftriaxone versus spectinomycin for gonorrhoea. The choices were based on standard treatment guidelines and observed prescriptions. METHODS: Cost Effectiveness Analysis was used. The prescribed/dispensed prescriptions in STD clinic between 1997 and 1999 were reviewed retrospectively. Relevant information such as diagnosis, prescribed/ dispensed drugs, dosage, duration of therapy, laboratory results, physician’s remarks among others were obtained from patient case-notes and dispensed prescriptions. In conjunction with these, time and motion studies and standard cost accounting technique were used. The cost per defined daily dose (DDD) and the cost of therapy for each agent were calculated. The cost components include overhead costs, and cost of drug/disposables acquisition. The literature was reviewed for positive and negative consequences of the considered therapeutic options. Improvements in signs and symptoms as well as eradication of the implicated organisms are the outcome measures. Decision table was used in the effectiveness rating. These were compared using chi square analysis. RESULTS: The results showed that doxycycline, benzathine penicillin and ceftriaxone were more effective than their respective counterparts in the treatment of stated infections. For example, doxycycline was N0.92 per unit effective while tetracycline was N1.82 per unit effective. Tetracycline is still widely used in the country. Alteration of some variables (cost and effectiveness rating) in favour of less cost effective option did not change the conclusion confirming that doxycycline is truly more cost effective. CONCLUSION: It is concluded that tetracycline should no longer be used except when doxycycline is not available. This equally applies to benzathine penicillin and ceftriaxone compared to their counterparts. However patients peculiarities and contraindications need to be considered at all times.