Objectives: To identify local resource use such as pharmaceutical treatment, medical follow-up, and patient hospitalization and estimate the budget impact of simeprevir (SMV) plus pegylated interferon (P)/ribavirin (R) as a treatment option in the early stages of the disease in Greece. Methods: A budget impact tool was developed with a two-year time horizon, which estimated the impact on the Social Insurance Funds (SIFs) of introducing SMV + PR in the management of the early disease stages. Total direct and indirect costs were estimated for each of the following health states: non-cirrhotic chronic Hepatitis C (and within that by fibrosis stage), compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma. Data gaps on treatment algorithms, resource use and productivity losses were covered via an expert panel of eight leading hepatologists. Epidemiology data were taken from the published literature. Unit costs were obtained from the Ministry of Health and SIFs. The perspective was that of the SIF and the cost base year was 2015. Results: The total (direct and indirect) cost per patient per year (excluding cost of antiviral treatment) was estimated at �47, �03, �,753, �6,313 and �7,237 for non-cirrhotic CHC, compensated cirrhosis, decompensated cirrhosis, HCC and liver transplantation, respectively. The budget impact analysis showed that adding SMV to PR in the early stages of the disease would lead to an increase in the cost of antiviral treatment by �.03 million. Conclusions: Costs of managing CHC increase dramatically with disease severity. SMV + PR for naive patients at early disease stages has a significant but manageable budget impact, and could prevent high costs in advanced stages.
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer [
HCV-specific burden of disease data for Europe are scarce [
The burden associated with the management of chronic Hepatitis C (CHC) is significant [
Simeprevir (Olysio®) is an HCV NS3/4A protease inhibitor that received a marketing authorization from the European Medicines Agency (EMA) in May 2014. It is indicated either in combination with pegylated-interferon and ribavirin (triple regimen) or in IFN free regimens for the treatment of CHC in adult patients.
In Greece, chronic patients, including those suffering from HCV, are fully covered by the work-related Social Insurance Funds (SIFs). In particular, the National Organization for Health Care Services Provision (EOPYY), which is the Reimbursement Agency of all SIFs, is responsible for reimbursing health care goods and services received by chronic patients, while SIFs are responsible for providing disability pensions to chronically ill patients that can no longer work.
Economic evaluation is becoming increasingly important in Greece, as the recently established Negotiation Committee which contributes to reimbursement decision making, requires an estimate of the budget impact to be included in the reimbursement dossier submitted by pharmaceutical companies. In this context, the aim of this study was to identify local resource use (health care resources associated with pharmaceutical treatment, medical follow-up, and hospitalization) and estimate the budget impact of simeprevir triple regimen as a treatment option in the early stages of the disease in Greece.
In order to estimate the budget impact on Social Insurance Funds (SIFs) of introducing simeprevir in combination with pegylated interferon and ribavirin (SMV + PR) in the management of the early stages of the disease, a budget impact analysis (BIA) was undertaken. A simplistic tool in Excel, a cost calculator with a 2-year time horizon, was developed in order to estimate the budget impact of the introduction of a new drug over the first two years into the Greek market.
In the health economics and HTA field budget impact analysis as well as other economic evaluation analyses are usually taking place in order to explore potential/future costs and related benefits depending on the analysis chosen. The study focused on genotype 1 patients. Total direct and indirect costs associated with the disease management were estimated for each of the following health states: non-cirrhotic chronic Hepatitis C (CHC) (and within that by fibrosis stage), compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). A comprehensive search of the international and local literature was performed to identify data on patient demographics, disease epidemiology (prevalence, incidence), resource use associated with medical, pharmaceutical and hospital care and productivity losses associated with the disease in Greece.
Data gaps on treatment algorithms, resource use and productivity losses were covered via an expert panel of eight leading hepatologists, who have co-authored the local guidelines. The panel covered geographically the largest District Health Authorities and the Hospital Liver Units treating the majority of patients with HCV. For the purposes of the panel, a questionnaire was developed, structured by health state and validated by a clinical expert. The elicitation method used during the expert panel was the Delphi technique [
The direct medical costs considered in the analysis were hospitalization, lab and imaging tests, medical consultation and pharmaceutical care. The cost base year was 2015. Unit costs were retrieved from officially published sources. In particular, for non-antiviral pharmaceutical treatments, prices based on the positive reimbursement list were used [
Productivity losses for patients were estimated as absence from work due to illness (disease symptoms) and/or in order to receive treatment and medical consultation―these data were elicited from the panel. Costs associated with productivity losses were estimated based on per capita Gross Domestic Product (GDP) data in Greece [
All costs refer to first year of treatment at the specific disease stage (i.e. when patients are on treatment or when the procedure takes place, e.g. the liver transplant). Population data were taken from OECD [
Patients with non-cirrhotic disease were grouped into patients with F0 - F2 before initiation of treatment and patients with F2 - F3 after they have started treatment. Total lab and imaging test costs were weighted for frequency and percentage of patients undergoing each test and are presented by disease stage in
The results show that patients in stages prior to decompensated cirrhosis do not require hospitalization. All patients (100%) with decompensated cirrhosis are hospitalized on average 2 - 3 times per year. The expert panel provided data on the percentage of patients being hospitalized under each diagnosis-related group (DRG) relating to cirrhosis. The average per patient cost of hospitalization for decompensated cirrhosis was estimated at €2,670 (
HCC also requires hospitalization in 100% of the patient population (approx. 2 - 3 times per year). The average hospitalization cost per HCC patient was estimated at €6,751.13 (
With regards to medical consultation, the vast majority of patients (>95%) across all fibrosis stages visits hospital outpatient wards for medical follow up. This entails no cost to SIFs. In addition, pharmaceutical treatment (other than
Test | F0 - F2, from diagnosis to initiation of treatment | F2 - F3 while on treatment | F4 (compensated cirrhosis) | Decompensated cirrhosis | HCC |
---|---|---|---|---|---|
FBC | 2.88 | 28.80 | 8.64 | 11.52 | 8.64 |
SGOT, SGPT | 6.98 | 69.80 | 20.94 | 27.92 | 20.94 |
Τ3, Τ4, TSH | 11.02 | 11.02 | 11.02 | 11.02 | |
ALP, GGT, albumin, bilirubin, creatinine | 18.16 | 36.32 | 72.64 | 36.32 | |
Prothrombin time | 12.00 | 8.10 | 48.00 | 8.10 | |
AFP | 3.71 | 12.38 | |||
Hepatitis C antibody | 9.00 | ||||
Liver biopsy | 0.39 | ||||
Upper abdomen U/S | 15.68 | 33.44 | 33.44 | 7.32 | |
Upper abdomen CT | 6.68 | 20.03 | 133.52 | ||
Gastroscopy | 28.18 | ||||
MRI | 165.00 | ||||
Total cost | 65.09 | 109.62 | 128.85 | 265.13 | 390.86 |
AFP: alpha-fetoprotein; ALP: alkaline phosphatase; CT: computed tomography; F0, 1, 2, 3, 4: Fibrosis stage 0, 1, 2, 3, 4; FBC: full blood count; GGT: gamma-glutamyltransferase; HCC: hepatocellular carcinoma; MRI: Magnetic resonance imaging; SGOT: Serum glutamic oxaloacetic transaminase; SGPT: serum glutamic-pyruvic transaminase; TSH (T3, T4): thyroid-stimulating hormone (T3, T4); U/S: Ultrasound.
DRG code | Description | Unit cost (? | % of patients hospitalized under each DRG | Frequency (number of hospitalizations per year) | Weighted average cost (? |
---|---|---|---|---|---|
H40Μα | Cirrhosis with catastrophic (systematic) comorbidities/complications | 1700.00 | 40% | 2.5 | 1700.00 |
H40Μβ | Cirrhosis with moderate to severe comorbidities/complications | 717.00 | 50% | 2.5 | 896.25 |
H40Χ | Cirrhosis without comorbidities/complications | 296.00 | 10% | 2.5 | 74.00 |
Total cost | 2670.25 |
DRG: diagnosis-related group.
DRG code | Description | Unit cost (? | % of patients | Average cost per event (? |
---|---|---|---|---|
H41Μ | Malignancy of the hepatic system with catastrophic comorbidities/complications | 1754.00 | 70% | 3663.50* |
H41Χ | Malignancy of the hepatic system without catastrophic comorbidities/complications | 792.00 | 30% | |
H01Μ | Hepatic surgeries with catastrophic comorbidities/complications | 5296.00 | 7% | 370.72 |
Angiography with chemoembolization^ | 30% | 2048.78 | ||
RF ablation^ | 15% | 668.14 | ||
Total cost | 6751.13 |
DRG: diagnosis-related group; RF: Radiofrequency; *Based on input from the expert panel that HCC patients are hospitalized 2 - 3 times per year under H41M & H41X; ^Related cost not included in DRGs-estimated with input from the expert panel.
antiviral treatment) was sought for all fibrosis stages and disease states; however, the expert panel concluded that the only disease states that require additional pharmaceutical treatment are advanced disease stages (compensated cirrhosis and HCC).
Patients with decompensated cirrhosis require additional pharmaceutical treatment (on top of antiviral therapy) for the management of disease symptoms and infections. This mainly consists of beta blockers (€28.08), diuretics (€169.13) and antibiotics (€37.61), summing up to €234.82 per patient per year. Approxi-mately 10% of patient with HCC are also treated with sorafenib, 40% of whom receive full recommended by SPC dose and 60% receive half dose due to AEs, with an average cost (weighted with the probability of receiving sorafenib) of €1,136.41.
Patients with HCC and liver transplant go on full disability pension (>80% disability), which entails an average monthly per patient cost to SIFs of €650. Indirect costs for all other disease stages were based on the number of days lost from work due to illness or treatment, which were estimated via the expert panel at 10 days for non-cirrhotic CHC and compensated cirrhosis and 45 days for decompensated cirrhosis.
The average cost of managing patients in each of the CHC disease states is presented in
The budget impact analysis was based solely on the antiviral treatments and the number of eligible patients for treatment with SMV + PR in the early stages. The total number of eligible patients was estimated at 372 (
Resource category | Non-cirrhotic CHC (F0-F3) | Compensated cirrhosis (F4) | Decompensated cirrhosis | HCC | Liver transplant |
---|---|---|---|---|---|
Lab & imaging tests | 73.41 | 128.85 | 265.13 | 390.86 | 537.00 |
Other medication (non-CHC related) | 234.82 | 1371.23 | |||
Hospitalization (including procedures*) | - | - | 2670.25 | 6751.13 | 28900.00 |
Direct cost | 73.41 | 128.85 | 3170.20 | 8513.22 | 29437.00 |
Indirect costs | 573.89 | 573.89 | 2582.50 | 7800.00^ | 7800.00^ |
Total costs | 647.30 | 702.74 | 5752.70 | 16313.22 | 37237.00 |
CHC: chronic Hepatitis C; F0, 1, 2, 3, 4: Fibrosis stage 0, 1, 2, 3, 4; HCC: hepatocellular carcinoma; *Procedures: liver transplant, hepatectomy, chemoembolisation RF ablation etc.; ^Indirect costs for HCC and liver transplant refer to the average annual disability pension.
Under the assumptions that, the market share of SMV in the triple regimen could increase from 5% in 2015 to 50% in 2016, the average per patient cost would increase from €10,973 to €16,444 (
2015 | 2016 | Source | |
---|---|---|---|
Total population | 10858018 | 10855694 | Hellenic Statistical Authority [ |
Prevalence | 1.2% | 1.2% | Hatzakis et al. 2015 [ |
Prevalent cases | 126713 | 126686 | |
% of diagnosed patients | 20.0% | 20.0% | Papatheodoridis et al. 2015 [ |
Number of patients diagnosed | 25343 | 25337 | |
% of G1 patients | 33% | 33% | Manolakopoulos et al. 2013 [ |
G1 patients | 8363 | 8361 | |
% of Q80K patients | 2.3% | 2.3% | Expert panel data |
Number of patients after excluding Q80K | 8169 | 8167 | |
% of F0 - F2 patients | 70% | 70% | Expert panel data |
F0 - F2 patient population | 5718 | 5717 | |
% of treatment naïve patients at F0 - F2 | 65% | 65% | Expert panel data |
Treatment naïve F0 - F2 patient population | 3717 | 3716 | |
% of patients initiating treatment | 10.0% | 10.0% | Expert panel data^ |
Patient population | 372 | 372 |
F0, 1, 2: Fibrosis stage 0, 1, 2; G1: Genotype 1; *Data projected to year 2016 based on the MAGR of the time series 2002-2015; ^The percentage of patients initiating treatment refers only to IFN-containing regimens.
Cost per year (? | Difference (? | ||||
---|---|---|---|---|---|
Duration of treatment (weeks) | Cost per year (? | 2015 | 2016 | ||
PR | 48 | 7204.1 | 5763.3 | 3241.9 | |
TVR + PR | TVR (12) + PR (48)* | 27267.5 | 1363.4 | 0.0 | |
BOC + PR | BOC (24) + PR (48) | 17855.0 | 892.7 | 0.0 | |
SMV + PR | SMV (12) + PR (24) | 22774.8 | 1138.7 | 11387.4 | |
SOF + PR | 12 | 36288.8 | 1814.4 | 1814.4 | |
Average cost per patient | 10972.6 | 16443.7 | 5471.1 | ||
Patient population | 372 | 372 | |||
Total budget impact | 4078168 | 6110293 | 2032124 |
BOC: boceprevir; PR: pegylated interferon; SMV: simeprevir; SOF: sofosbuvir; TVR: telaprevir; *This is a conservative approach reflecting the longest treatment duration (and thus highest cost), as some patients under treatment with TVR + PR might receive PR for 24 weeks.
The present study showed that both direct and indirect costs of CHC increase with disease severity. The cost of managing CHC at the compensated cirrhosis stage is 75.5% higher than the cost in previous stages, while the cost of decompensated cirrhosis is 24.6 times higher than the compensated. Similarly, productivity losses are 3.5 times higher in the decompensated cirrhosis compared with respective costs in stages F0 - F4, and almost 13 times higher if the patient develops HCC or undergoes liver transplant. The major cost driver is hospitalization.
These findings are consistent with other studies conducted in Greece. In particular, Athanasakis et al. have estimated the costs per disease stage, and results support an increase in the economic burden in patients with advanced liver disease [
With respect to the international literature, our study findings are also consistent with the study by Solomon et al., which highlights the cost increase in the management of advanced liver disease, reaching €35,000 in the first year of liver transplant [
The present study also showed that treating half of the eligible patients with SMV + PR has a budget impact of €2.03 million on the SIF budget. It should be noted that this cost does not take into consideration additional discounts on drug prices, rebates and clawbacks, which significantly reduce the costs incurred by SIFs. In addition, given the reductions in prices overtime, this budget impact is expected to be reduced in the future, thus currently reflects the maximum possible budget impact under the specific assumptions of the analysis.
Furthermore, the budget impact of increasing the use of SMV + PR in 2016 is associated with long-term benefits for SIFs, as SMV + PR has a significantly improved effectiveness profile compared with PR alone. More specifically, the sustained virological response (SVR) of SMV + PR in this patient population (naïve, F0 - F2 patients) is 84% versus 52% in patients treated with PR [
The current study only focuses on the economic impact of treating patients at early disease stages with SMV + PR and does not take into consideration the treatment’s effectiveness, as it was out of scope. However, it was recently shown by Westerhout and colleagues that, within the UK health care setting, SMV + PR is cost-effective versus PR, for all fibrosis stages, with an incremental cost-effectiveness ratio of £9,725/QALY for treatment-naïve and £7,819/QALY for treatment-experienced patients [
This study has some limitations. First, resource use and associated costs are based on expert panel data rather than real world or registry evidence. Expert panels as a source of determining resource use is weaker than evidence from clinical trials or patient files, however, given the lack of such data for Greece, it was deemed as the most appropriate method to elicit such information. Delphi panels are widely recognized as valid evidence generation methods for eliciting resource use in health care, and have been widely accepted by health technology assessment agencies globally [
Another limitation of the study is that in the present analysis the cost of medical consultation has been set to zero, due to the fact that consultations in hospital outpatient wards (where 100% of the consultations for this disease take place) are covered by the hospital budget that are not incurred by SIFs. This however, does not mean that there is no cost to the health care system. Therefore, it could be argued that the total direct cost of the disease management is not fully reflected due to the perspective adopted in this analysis. In addition, it should be highlighted that prices reimbursed by EOPYY for lab and imaging tests and hospital care do not properly capture true costs, as most of these prices have not been updated for at least the past 5 - 6 years (for example, the cost of DRGs has not been updated since March 2012). Therefore, total cost estimated in this analysis could be underestimated.
Furthermore, there are certain aspects of the disease - related costs that have not been investigated in the present study, such as presenteeism (i.e. going to work despite illness), social care, patients’ shorter life-expectancy, time and productivity losses of non-paid care-givers (from patients family and friendly environment). Clinical and quality of life considerations have been excluded from the analysis as out of scope.
Despite limitations, the present study provides a view of the cost of managing CHC through all disease stages without pharmaceutical treatment, and the costs of curing patients―rather than just managing disease symptoms―in the early stages. Also, to the best of our knowledge, this is the first study to estimate indirect costs associated with the disease by stage.
The estimated budget impact of SMV + PR reflects the cost of complete patient cure, which can bring additional savings from allowing patients to exit the health care system and not seek treatment at later, more costly disease stages. Therefore, the results of the present study can provide valuable input to evidence based decision making in health care. Especially under current economic environment, decision makers in Greece need to seek treatment options that can provide future savings. Further research is required at the local level in order to determine the cost-effectiveness of SMV + PR in the management of CHC in Greece.
Costs of managing CHC increase dramatically with disease severity. SMV + PR as a treatment option for naive patients at early disease stages has a significant but manageable budget impact, and could prevent high costs at advanced stages.
Funding for this project was provided from Janssen Cilag to the University of Peloponnese. Publication of the study results was not contingent upon sponsor’s approval.
Geitona, M., Kousoulakou, H., Goulis, I., Manolakopoulos, S., Vasiliadis, T., Christodoulou, D., Gogos, C., Dourakis, S., Koskinas, I.G., Papadokostopoulou, A., Lathouris, A. and Papatheodoridis, G. (2017) Managing Hepatitis C Patients in Greece: A Budget Impact Analysis of Simeprevir plus Pegylated Interferon/Ribavirin Regimen at Early Stages of the Disease. Health, 9, 1482-1493. https://doi.org/10.4236/health.2017.911109