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Treatment of chronic type B and C hepatitis with interferon alfa: an economic appraisal |
Dusheiko G M, Roberts J A |
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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 Interferon alfa in the treatment of hepatitis B and C for patients starting treatment in young adulthood and who are followed until late middle age.
Type of intervention Treatment and secondary prevention.
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population Patients with hepatitis B (hepatitis B virus (HBV) DNA-positive) or C (hepatitis C virus (HCV) RNA-positive), between 25 and 35 years of age with a male to female ratio of 2:1 and with an overall ethnic distribution reflecting the composition of patients referred to liver disease clinics in North America or Europe. Both groups of patients were assumed to have the same demographic characteristics. Patients with dual infections were excluded.
Setting Tertiary care centre. The economic study was carried out in London, UK.
Dates to which data relate The data for the effectiveness analysis were based on studies published between 1988 and 1994, and on the advice of an international panel of hepatologists attending a consensus conference in London in April 1993. No dates were explicitly specified for the resource use data. The price year was 1993/1994.
Source of effectiveness data Effectiveness data were derived from a review of previously published studies and expert opinion (the advice of an international panel of hepatologists).
Modelling A transitional probability model was used to estimate the costs and benefits associated with each strategy .
Outcomes assessed in the review The main outcomes assessed in the review were the per annum rate of progression to cirrhosis for a cohort of heterogeneous patients with chronic hepatitis B or C, response rates, relapse rates, and the incidence of death for patients with decompensated cirrhosis.
Study designs and other criteria for inclusion in the review Prospective published studies and prospective studies in progress, and a meta-analysis (for obtaining response and relapse rates) were included in the review.
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 Not reported. Summary statistics from some studies were reported.
Number of primary studies included Twenty studies were included in the review.
Methods of combining primary studies A narrative method was used in most parts to report the results of individual studies. The studies were not combined, but were used as the basis for assigning parameter values to the model used in the final analysis.
Investigation of differences between primary studies The investigation of differences was not reported extensively. It was only reported that the patient populations in the primary studies used as sources of effectiveness data were heterogeneous and that the data on the rate of decompensation for hepatitis C were conflicting.
Results of the review The per annum rate of progression to cirrhosis for a cohort of heterogeneous patients with chronic hepatitis B or C was 0.0105 (lower rate) and 0.0221 (higher rate). The response rate for the intervention in patients with HBV infection was 40%, with a subsequent relapse rate of 12.5%, leading to a final response rate of 35%. For patients with chronic hepatitis C, the initial response rate was 50% with a relapse rate of 50%, leading to a final response rate of 25%. The annual incidence of death for patients with decompensated cirrhosis was given a value of 5% in one scenario and 13% in another.
Methods used to derive estimates of effectiveness Estimates of effectiveness were also based on assumptions made by the authors, based on the advice of an international panel of hepatologists.
Estimates of effectiveness and key assumptions The rate of transplantation for patients with decompensated liver disease was assumed to be 20%. Of these patients 80% would be alive at 2 years. The incidence of decompensated cirrhosis caused by hepatitis C and B was assumed to be the same for both types of diseases (0.05). With regard to the conflicting data for the rate of decompensation for hepatitis C, the authors assumed the same rate for hepatitis B and C.
Measure of benefits used in the economic analysis The benefit measures were life years saved, and quality-adjusted years of life saved (QALYs). A transition probability model was used to deal with the high degree of uncertainty in long-term follow up of treated patients and to avoid the high expense that a more rigorous study would imply. The basic method of valuation of health states was not clearly reported except for the scale of 0 to 1 used in quality of life adjustments. The authors reported that the weights used were somewhat arbitrarily chosen.
Direct costs The costs were discounted. Some quantities were reported separately from prices at a somewhat aggregated level. The costs measured were costs of drug therapy, follow-up costs, costs of disease episodes likely to be experienced by patients with decompensated cirrhosis, and costs of transplantation and subsequent follow-up plus time and travel costs to patients. The boundaries adopted were the hospital and the patient. The cost components were reported as packages of care for the different stages of disease. The cost estimates were based on data for the Liver Unit at the Royal Free Hospital in London for the period 1993 and 1994. The prices used were also, apparently, from that period, although this was not clearly reported. Time and travel costs to patients were based on assumptions made by the authors. The costs excluded from analysis were the general practice (non-hospital-based service costs), other costs to the patient's family or third parties caring for the ill patient, or costs due to adverse effects of treatment.
Indirect Costs The costs were discounted. Some quantities were reported separately from prices. The costs measured were those associated with lost productivity from inpatient admission, undergoing a transplantation, and lives lost due to death. The boundary adopted was the patient. The estimation of quantities was based on the authors' assumptions, whereas the unit costs (average wage) were based on data from the Department of Employment in a publication from 1993. A figure of 1.4 million was imputed to the value of lives lost, based on studies published between 1977 and 1989. The prices used were apparently from this reference year, although this was not explicitly stated.
Sensitivity analysis The incidence rates, costs of drugs and treatments, and the discount rate were the parameters reported to have been used in the analysis. A set of one-way and two-way simple sensitivity analyses was carried out.
Estimated benefits used in the economic analysis 164 years of life were saved for hepatitis B patients in the low progression scenario with low mortality, whereas for hepatitis C patients under the same scenario the figure was 117 years. The high progression-high mortality scenario yielded figures of 591 for patients with chronic hepatitis B and 422 for hepatitis C. The low progression-high mortality scenario resulted in figures of 31 (hepatitis B) and 22 (hepatitis C), whereas the high progression-low mortality scenario had values of 35 (chronic HBV) and 25 (chronic HCV). Quality-adjusted life years (QALYs) were not reported.
Cost results A 5% discount rate was used. The additional discounted direct medical costs associated with the treatment of hepatitis B and C in the low progression-low mortality scenario were 2,809,000 and 1,036,000, respectively. The total discounted net expected savings (direct medical costs, social costs, and value of life) with the low progression-low mortality scenario for treating the cohort of patients with hepatitis B was 6,351 compared to the untreated cohort, whereas for the HCV patient the corresponding figure was $5,405, both under the low-progression (0.0105 per annum) scenario and the low mortality (5% annually) scenario. The rest of the scenarios yielded higher savings, with the savings increasing both with the 'mortality' and 'progression' values.
Synthesis of costs and benefits The cost per year of life saved and cost per QALY saved were the main outcome measures used to report the results. The total discounted cost per year of life saved was 17,128 for chronic HBV patients and 8,855 for chronic HCV patients, under the assumption of low-progression/low mortality. The respective values in terms of cost per QALY saved were 1,103 and 506. The remainder of the scenarios yielded higher benefits, as can be noted from the costs results. In general, the sensitivity analysis was reported to provide robust results.
Authors' conclusions The authors concluded that: "The present analysis suggests that interferon alfa is a cost-effective treatment for patients with chronic viral hepatitis B (HBV )and C (HCV), and the potential usefulness of interferon alfa on the clinical and economic outcome of treatment is indicated from the model".
CRD COMMENTARY - Selection of comparators The reason for the choice of comparators is clear.
Validity of estimate of measure of benefit Despite a fairly comprehensive literature review, the internal validity of the study should be assessed bearing in mind the limited availability of the required data and the inherent limitations of the study designs of the primary studies included in the review. As acknowledged by the authors, the benefits that are likely to accrue from the reduction in infectious individuals were not incorporated in the model.
Validity of estimate of costs Some quantities were reported separately from prices and adequate details of the methods of cost estimation were given. Some costs were omitted but it is likely that this would make the results more conservative.
Other issues The authors' conclusions were justified, given the uncertainties in the data. The population assumed in the model was thought to represent a likely high-response group. In Europe, it was noted, that type 3 (the type with the highest response rate) is more common in patients under 40 years of age. Some brief comparisons with other studies were made. The results were not presented selectively, and a detailed report of the final results was included.
Implications of the study Research into wider effects of the disease is needed. Further research is needed to develop better measures to value health status at the various stages of acute liver disease. These findings, together with the benefits that are likely to accrue from the reduction in infectious individuals suggest that this therapy has a role to play in public health policy to contain the impact of hepatitis.
Bibliographic details Dusheiko G M, Roberts J A. Treatment of chronic type B and C hepatitis with interferon alfa: an economic appraisal. Hepatology 1995; 22(6): 1863-1873 Indexing Status Subject indexing assigned by NLM MeSH Adult; Chronic Disease; Cohort Studies; Cost-Benefit Analysis; Costs and Cost Analysis; Drug Costs; Drug Monitoring /economics; Hepatitis B /economics /mortality /therapy; Hepatitis C /economics /mortality /therapy; Humans; Interferon-alpha /economics /therapeutic use; Liver Cirrhosis /virology; Liver Transplantation /economics; Quality of Life AccessionNumber 21996000139 Date bibliographic record published 30/11/2000 Date abstract record published 30/11/2000 |
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