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Cost-effectiveness of 6 and 12 months of interferon-alpha therapy for chronic hepatitis C |
Kim W R, Poterucha J J, Hermans J E, Therneau T M, Dickson E R, Evans R W, Gross J B |
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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 Six months versus 12 months of interferon-alpha therapy at standard doses (3 million U three times weekly by self injection) in the treatment of patients with chronic hepatitis C.
Type of intervention Treatment and secondary prevention.
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population Four hypothetical populations of patients with chronic hepatitis C, aged 30, 40, 50 and 60 years.
Setting Hospital and community. The economic study was carried out in the USA.
Dates to which data relate Effectiveness data were based on studies published between 1987 and 1997. Resource use data and their corresponding collection dates were not reported. The price year was not explicitly specified.
Source of effectiveness data Effectiveness data were derived from a review of the literature and assumptions made by the authors.
Modelling A Markov model was developed to represent the natural progression of the disease and to estimate costs and effects associated with each treatment strategy.
Outcomes assessed in the review The following outcomes were assessed:
The rate of progression from chronic hepatitis C to compensated cirrhosis; initial response to interferon-alpha and sustained response to interferon-alpha; transition probabilities for compensated cirrhosis to decompensated cirrhosis, decompensated cirrhosis to hepatocellular carcinoma, decompensated cirrhosis to death, hepatocellular carcinoma to death, and orthotopic liver transplantation to death.
Study designs and other criteria for inclusion in the review Age-specific estimates of the effectiveness and duration of protection among immunocompetent patients were reported to be based on a case control study. The sources of some other clinical probabilities seems to have been unpublished data from epidemiologic cohort studies.
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 A total of 7 studies were included.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The estimates for a cohort of 50% aggressive disease and 50% indolent disease and for the overall cohort, respectively, were as follows:
rate of progression from chronic hepatitis C to compensated cirrhosis, 10% (annually), 1% (annually), and 5.5%;
initial response to interferon-alpha, 30%, 70%, and 50%;
sustained response to interferon-alpha, 2%, 20%, and 11% for the 6 months of treatment and 3%, 30%, and 17% for the 12 months of treatment.
Transition probabilities were as follows:
compensated cirrhosis to decompensated cirrhosis, 4% (3 - 5%);
decompensated cirrhosis to hepatocellular carcinoma, 3% (1.5 - 5%);
decompensated cirrhosis to death, 10% (5 - 15%);
hepatocellular carcinoma to death, 80% (50 - 100%); and:
orthotopic liver transplantation to death, 6.9% (5 - 10%).
Methods used to derive estimates of effectiveness Assumptions around effectiveness were also made by the authors.
Estimates of effectiveness and key assumptions It was assumed that after the development of cirrhosis, both cohorts of patients with the aggressive and indolent disease had the same rate of occurrence of complications (such as hepatic decompensation, hepatocellular carcinoma, and liver-related death); patients with sustained remission had the same mortality rate as the general population.
Measure of benefits used in the economic analysis The benefit measures were the number of liver-related deaths, quality-adjusted life-years (QALYs) based on the utility weights produced by a panel of hepatologists and a nurse specialist using a generic instrument. A Markov model was used to estimate the benefits.
Direct costs Costs were discounted. Quantities were not reported separately from the costs. Cost items were reported separately. Cost analysis covered the costs of treating decompensated cirrhosis and hepatocellular liver transplantation, interferon-alpha, injection supplies, clinical and biochemical monitoring, and treatment of side effects. The perspective adopted in the cost analysis was that of society. The sources of cost data were literature published between 1994 and 1995 and institutional data. The cost of interferon alpha was based on the average wholesale price plus 20% for costs of injection supplies, clinical and biochemical monitoring, and treatment of side effects. The date of the price data was not explicitly specified. The non-medical costs of complications of chronic liver disease were not considered in the cost analysis.
Sensitivity analysis A set of one-way and two-way sensitivity analyses was performed on all parameters of the model. An analysis of extremes was conducted based on constructing best-case and worst-case scenarios using the most influential parameters of the model.
Estimated benefits used in the economic analysis The 'no treatment' strategy was associated with a liver-related mortality rate of 26.5% versus 25% with 6 months of treatment and 24.3% with 12 months of treatment. The corresponding values in terms of cumulative QALYs were 18 years versus 18.25 and 18.37 years, respectively. The utility weights considered in the analysis were: 0.5 for decompensated cirrhosis, 0.95 for chronic hepatitis, 0.8 for compensated cirrhosis, 0.8 for time after liver transplantation, 0.25 for hepatocellular carcinoma, and 0 for death. The discount rate was 3%.
Cost results The discount rate was 3% in the base case. The 'no treatment' strategy was associated with a total cost of $24,600 versus $25,600 with 6 months of treatment and $26,500 with 12 months of interferon alpha treatment.
Synthesis of costs and benefits The incremental cost per QALY gained was the cost-utility measure adopted in the economic analysis, yielding values of $4,000 for the 6-month and $5,000 for the 12-month therapy compared to no treatment. The incremental cost per QALY and per liver-related death prevented were also reported for different cohorts of patients (ages 30, 40, 50, and 60 years). The sensitivity analyses considered the cost and efficacy of interferon-alpha, the cost of treatment for decompensated cirrhosis, and quality of life in patients with chronic hepatitis C, as the most sensitive parameters of the model. In the best-case scenario interferon alpha therapy resulted in cost-savings in all but the 60 year old cohort. In the worst-case scenario the cost per QALY gained increased dramatically compared with the base-case scenario, although the cost-effectiveness was still in a reasonable range for younger cohorts.
Authors' conclusions From the standpoint of cost-effectiveness, interferon alpha therapy for 6 or 12 months may be justified in patients with chronic hepatitis C. The possible exception is patients aged more than 60 years of age.
CRD COMMENTARY - Selection of comparators The reason for the choice of the comparator is clear.
Validity of estimate of measure of benefit The internal validity of the estimates of benefit measures can not be guaranteed due to the apparent absence of a systematic literature review, quality assessment of the primary studies included in the review, the inherent limitations of utility values being derived from expert opinions rather than patients' preferences, and the possibility of effectiveness data not reflecting the current standard of practice (as acknowledged by the authors).
Validity of estimate of costs Some details of methods of cost estimation were not given and the price year was not reported. Cost results may not be generalisable to other settings or countries.
Other issues The authors' conclusions seem to be justified given the extensive sensitivity analyses performed to address uncertainties surrounding the parameters of the model. Appropriate comparisons were made with other studies.
Implications of the study Quality of life data for patients with chronic viral hepatitis are limited. In light of the recent emphasis on assessing outcomes of medical interventions from the perspective of the patient, more investigation is urgently needed in this area.
Source of funding Supported in part by grant DK34238 from the National Institutes of Health.
Bibliographic details Kim W R, Poterucha J J, Hermans J E, Therneau T M, Dickson E R, Evans R W, Gross J B. Cost-effectiveness of 6 and 12 months of interferon-alpha therapy for chronic hepatitis C. Annals of Internal Medicine 1997; 127(10): 866-874 Other publications of related interest Comment in: Annals of Internal Medicine 1997;127(10):918-20.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Age Factors; Aged; Antiviral Agents /administration & Cost-Benefit Analysis; Disease Progression; Drug Administration Schedule; Hepatitis C, Chronic /drug therapy /economics; Humans; Interferon-alpha /administration & Markov Chains; Middle Aged; Quality-Adjusted Life Years; Sensitivity and Specificity; Treatment Outcome; dosage /economics; dosage /economics AccessionNumber 21997008353 Date bibliographic record published 31/10/2000 Date abstract record published 31/10/2000 |
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