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A pragmatic and cost-effective strategy of a combination therapy of interferon alpha-2b and ribavirin for the treatment of chronic hepatitis C |
Sagmeister M, Wong J B, Mullhaupt B, Renner E L |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The health technologies studied were five strategies for the treatment of patients with chronic hepatitis C:
no treatment;
interferon (IFN) for 48 weeks (if at 12 weeks hepatitis C virus (HCV) RNA was undetectable);
IFN and ribavirin for 24 weeks (Comb I);
IFN and ribavirin for 48 weeks (Comb II); and
IFN and ribavirin for 48 weeks (if at 24 weeks HCV RNA was undetectable) (Comb III).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised treatment-naive, non-cirrhotic patients with mild to moderate hepatitis C (including bridging fibrosis). Patient characteristics were taken from a data set of 1,445 patients with a mean age of 42.2 years. 34.9% were female, 66.3% had moderate hepatitis, 64.6% were infected with G1, and 32.0% were infected with genotype G2 or G3.
Setting The setting was a hospital and the economic analysis was carried out in Switzerland.
Dates to which data relate Effectiveness data were collected from studies previously published in 1998. Cost and resource use data were collected from sources previously published between 1984 and 1998. The price year was 1999.
Source of effectiveness data Effectiveness estimates were taken from a review or synthesis of previously completed studies, expert opinion and, although not stated in this paper, probably also the authors' assumptions in designing the Markov model.
Modelling A validated lifetime Markov simulation model of the natural history of hepatitis C was used to determine the cost-effectiveness of the five treatment strategies (see Other Publications of Related Interest below).
Outcomes assessed in the review The review assessed the probability of sustained viral response.
Study designs and other criteria for inclusion in the review Effectiveness data were taken from two randomised controlled trials. Morbidity and mortality from hepatitis C and from other causes were based on the rates observed in the Swiss population.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Two primary studies were included.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The overall probability of sustained viral response was 15% with IFN, 33.8% with Comb I, 40.7% with Comb II, and 41.6% with Comb III. The probability of sustained viral response for genotype non-1 was 27.5% with IFN, 62.1% with Comb I, 61.2% with Comb II, and 62.4% with Comb III. The probability of sustained viral response for genotype 1 was 8.3% with IFN, 18.0% with Comb I, 29.6% with Comb II, and 30.2% with Comb III.
Methods used to derive estimates of effectiveness The quality of life estimates were based on the opinions of two gastroenterologists and three hepatologists, and were derived using a time trade-off technique.
Estimates of effectiveness and key assumptions Utility weights ranged from 0.9 with chronic hepatitis to 0.2 with refractory ascites, encephalopathy, or hepatocellular carcinoma.
Measure of benefits used in the economic analysis Quality-adjusted life years (QALYs) were used as the measure of benefits. Utility weights were based on expert opinion using a time trade-off technique. Benefits were discounted at an annual rate of 3%.
Direct costs Direct costs were discounted at an annual rate of 3%. Resource quantities and unit costs were not reported separately. Direct costs were given by costs of treatment and included the cost of complications, GP surgery visits and laboratory tests, drugs, and liver transplantation. The quantity/cost boundary adopted was that of the hospital. The costs of complications from HCV were estimated by two gastroenterologists and three hepatologists. Costs for GP surgery visits and laboratory tests were based on reimbursement tariffs. Drug costs were based on current retail prices. The length of stay per complication was based on the database of the Swiss Hospital Association. The cost of a liver transplantation was based on an analysis of the Swiss Hospital Institute. The costs of treatment reflected current recommendations for Switzerland. The price year was 1999.
Statistical analysis of costs No statistical analysis of costs was reported, costs being treated deterministically.
Indirect Costs Indirect costs were not included.
Currency Costs were calculated in Euros, with Euro 1.067 = $1.
Sensitivity analysis Sensitivity analyses were conducted to test the sensitivity of incremental cost-effectiveness to "Poynard's favourable response factors" (genotype, baseline viral load, presence of portal fibrosis, gender, and age), as well as discount rate (0 - 5%), progression rate to cirrhosis (-33%), and costs (+/- 25%).
Estimated benefits used in the economic analysis For genotype 1 patients, the number of QALYs gained was 15.32 without treatment, 15.62 with IFN, 15.95 with Comb I, 16.44 with Comb II, and 16.39 with Comb III.
For genotype non-1 patients, the number of QALYs gained was 17.99 with Comb I, 16.48 with IFN, 15.32 without treatment, 17.87 with Comb II, and 17.88 with Comb III.
Cost results For genotype 1 patients, lifetime direct costs were Euro 15,143 without treatment, Euro 16,631 with IFN, Euro 21,074 with Comb I, Euro 22,467 with Comb II, and Euro 26,268 with Comb III.
For genotype non-1 patients, lifetime direct costs were Euro 14,427 with Comb I, Euro 14,665 with IFN, Euro 15,143 without treatment, Euro 19,620 with Comb II, and Euro 21,533 with Comb III.
Synthesis of costs and benefits For genotype 1 patients, the incremental cost-effectiveness of IFN compared to no antiviral treatment was Euro 4,886 per QALY gained. The incremental cost-effectiveness of Comb II compared to IFN was Euro 7,135 per QALY gained. Comb III was dominated by Comb II.
For genotype non-1 patients, Comb I dominated all other strategies by reducing costs and by extending quality-adjusted life expectancy. Consideration of Poynard's favourable response factors, other than genotype, was stated not to change the results. Some results were shown, but unfortunately they were given undiscounted. When the discount rate, histological progression rate to cirrhosis, and long-term disease costs were changed, the cost-effectiveness of treatment strategies was stated to remain below Euro 24,960 per QALY gained. Changing the discount rate from 3% to 0% showed that Comb I continued to dominate for genotype non-1 patients. For genotype 1 patients, Comb I and Comb III would continue to be dominated. No other results were shown.
Authors' conclusions For patients with genotype non-1 infection 24 weeks of combination therapy was found to dominate all other strategies. For genotype 1 infection 48 weeks of combination therapy for week-24 responders only was found to extend life expectancy at a favourable cost-effectiveness ratio per QALY.
CRD COMMENTARY - Selection of comparators The justification for the choice of IFN for 48 weeks was that, until recently, it represented the only available treatment. You, as a user of the database, should decide if these health technologies are relevant to your setting.
Validity of estimate of measure of effectiveness The authors did not state that a systematic review of the literature had been undertaken. More details about the sources searched and search strategies employed could have been provided. Effectiveness estimates were taken from two large randomised controlled trials. Additional effectiveness estimates (quality of life) were based on the opinion of experts, which would be appropriate, although access to the opinions of patients or the general public might be more appropriate.
Validity of estimate of measure of benefit The estimation of benefits was modelled. The instrument used to derive a measure of health benefit, the time trade-off technique, was appropriate.
Validity of estimate of costs Good features of the cost analysis were that all relevant cost categories appear to have been included, the price year was reported, and sensitivity analyses were performed. This assists in the replication of the results in other settings and improves the generalisability of the results. However, resource quantities and unit costs were not given, and drug costs were based on retail prices and, thus, a breakdown into resource quantities and unit costs was not possible. Cost estimates were derived from local sources and reflected current recommendations for Switzerland. Hence, they may not apply to other settin
Other issues The authors made appropriate comparisons of their findings with those from other studies, but did not address the issue of generalisability to other settings. The authors presented their results selectively with regard to the sensitivity analysis. The study considered patients with chronic hepatitis C and this was reflected in the authors' conclusions. The authors stated that cirrhotic patients were excluded as the antiviral treatment of cirrhotic patients is still under clinical evaluation.
Implications of the study The authors argued that "treating non-cirrhotic patients with chronic hepatitis C according to genotype only is most cost-effective, independent of the number of other known response factors". It would have been more transparent had the results of the sensitivity analysis been more completely reported. Also, although the authors emphasised 48 week combination therapy for 24 week responders because it was the most effective, monotherapy had a better incremental cost-effectiveness ratio. The decision about which technology to adopt will actually depend on the willingness to pay for any increase in effectiveness, which, in turn, depends on the cost-effectiveness of all other technologies within a given budget.
Source of funding Supported in part by unrestricted grants from Essex Chemie AG Lucerne, Switzerland and Roche Pharma (Schweiz) AG, Reinach, Switzerland.
Bibliographic details Sagmeister M, Wong J B, Mullhaupt B, Renner E L. A pragmatic and cost-effective strategy of a combination therapy of interferon alpha-2b and ribavirin for the treatment of chronic hepatitis C. European Journal of Gastroenterology and Hepatology 2001; 13(5): 483-488 Other publications of related interest Bennett W G, Inoue Y, Beck J R, Wong J B, Pauker S G, Davis G L. Estimates of the cost-effectiveness of a single course of interferon-alfa2b in patients with histologically mild chronic hepatitis C. Annals of Internal Medicine 1997;127:855-865.
Wong J B, Bennett W B, Koff R S, Pauker S G. Pretreatment evaluation of hepatitis C: risks benefits and costs. JAMA 1998;280:2088-2093.
Sagmeister M, Renner E L, Mulhaupt B, Wong J B. Modeling of hepatitis C in Switzerland: prevalence, future epidemic and costs. Schweizerische Medizinische Wochenschrift 2000;121(Suppl):9.
Comment in: European Journal of Gastroenterology and Hepatology 2001;13(5):473-476.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Antiviral Agents /economics /therapeutic use; Computer Simulation; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Hepatitis C, Chronic /drug therapy /economics; Humans; Interferon-alpha /economics /therapeutic use; Male; Markov Chains; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin /economics /therapeutic use; Switzerland; Treatment Outcome AccessionNumber 22001001199 Date bibliographic record published 30/09/2002 Date abstract record published 30/09/2002 |
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