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Cost-effectiveness analysis of interferon-alpha therapy in the treatment of chronic hepatitis B in Taiwan |
Pwu R F, Chan K 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 The use of recombinant interferon-alpha (IFN-a) for the treatment of chronic hepatitis B.
Study population The hypothetical study population comprised 35-year-old chronic hepatitis B patients with detectable serum levels of hepatitis B early antigen (HBeAg), no liver cirrhosis, and a serum alanine aminotransferase concentration greater than twice the normal upper limit.
Setting The setting was community care. The economic study was carried out in Taiwan.
Dates to which data relate The effectiveness data related to 1984 to 2000. The resource use and cost data related to 1994 to 2001. The price year was not reported.
Source of effectiveness data The effectiveness data were derived from a review of published studies.
Modelling A Markov model was used to estimate the lifetime costs and quality-adjusted life-years (QALYs). The model had nine health states. These related to the presence or absence of chronic hepatitis B, hepatitis B surface antigen (HBsAg), HBeAg, compensated cirrhosis of the liver, decompensated cirrhosis, hepatocellular carcinoma (HCC) and death. The cycle length was 1 year and the model was run for 65 cycles. The model was built using DATA TreeAge software.
Outcomes assessed in the review The outcomes assessed included:
the annual probability of loss of HBeAg;
the annual probability of loss of HBsAg;
the annual probability of HBeAg reversion;
the annual probability of progression from chronic hepatitis to compensated cirrhosis;
the annual probability of progression from compensated cirrhosis to decompensated cirrhosis;
the annual probability of developing HCC; and
excess mortality due to decompensated cirrhosis and HCC.
Study designs and other criteria for inclusion in the review The review included original research, review articles, conference proceedings, unpublished theses and books. The types of study design included were not specified. No other inclusion or exclusion criteria were reported.
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 The review included approximately 28 studies.
Methods of combining primary studies Where multiple studies reported estimates of the same parameter, the median or mode was used in the base-case model. The largest and smallest values were used to define the range to be explored in the sensitivity analysis.
Investigation of differences between primary studies Results of the review The annual probability of progressing from chronic hepatitis B to compensated cirrhosis was 3.2 (range: 2.4 - 3.9) with HBeAg+/HBsAg+, 0.8 (range: 0.5 - 1.3) with HBeAg-/HBsAg+ and 0.008 (range: 0.04 - 0.016) with HBeAg-/HBsAg-.
The annual probability of progressing from compensated to decompensated cirrhosis was 2.3 (range: 2.3 - 5.6).
The annual probability of developing HCC from chronic hepatitis was 0.014 (range: 0.007 - 0.028) with HBeAg-/HBsAg- and 1.4 (range: 0.8 - 1.5) with HBeAg+ or HBsAg+.
The annual probability of developing HCC from cirrhosis was 5 (range: 3 - 7.7).
The annual excess mortality rate from decompensated cirrhosis was 23.5 (range: 10 - 39).
The annual excess mortality rate from HCC was 37.2 (range: 30 - 56).
Measure of benefits used in the economic analysis The measure of benefits used was the QALYs. Utility values for each health state of the model were directly measured using the time trade-off method. The estimates were obtained through interviews with 12 clinicians and 53 patients.
Direct costs The study included direct costs to the hospital. These included the annual inpatient and outpatient costs of treating chronic hepatitis B and compensated cirrhosis according to HBsAg and HBeAg status, the annual cost of treating decompensated cirrhosis and HCC, and the cost of IFN-a. The resource use estimates were based on expert opinion. The resource use quantities were reported separately from the costs. A model was used to extrapolate the cost per health state per year to lifetime treatment costs. The prices were based on standard prices and on hospital reimbursement rates. The average cost of hospitalisation for liver conditions was derived from actual data. The costs were discounted at a rate of 3% per annum. The study reported the average costs. The price year was not stated.
Statistical analysis of costs Patient-level data were available for the costs of hospitalisations for liver conditions, but these were not statistically tested. The study reported median costs and a range used for the sensitivity analysis, which might be the minimum and maximum values. Limited data on the observational cohort used to estimate the costs of hospitalisation for liver conditions were provided.
Indirect Costs The indirect costs were not included in the analysis. If the study had been conducted from a societal perspective, as the authors stated, then the indirect costs should have been considered.
Currency Taiwanese dollars (NT$). The study also provided cost estimates in US dollars ($).
Sensitivity analysis Several one-way sensitivity analyses were conducted to investigate variability in the data. It appears that the majority of cost and health outcome parameters have been explored in sensitivity analyses. A full probabilistic analysis, in which all parameters were varied simultaneously, was also undertaken.
Estimated benefits used in the economic analysis The measure of benefits used in the economic analysis was the QALYs. The total lifetime QALYs, discounted at a rate of 3% per annum, were 16.63 for a patient treated with IFN-a and 16.45 for a patient who received standard supportive care.
The model did not incorporate the side effects from treatment.
Cost results The total lifetime costs, discounted at a rate of 3% per annum, were NT$793,000 for a patient treated with IFN-a and NT$704,000 for a patient who received standard supportive care.
Synthesis of costs and benefits The costs and health outcomes were combined to estimate the cost per QALY. The incremental cost-effectiveness ratio (ICER) was NT$492,000 per QALY gained with IFN-a compared with no IFN-a.
The costs and benefits were both discounted at a rate of 3% per annum.
The median ICER value from the probabilistic sensitivity analysis was NT$188,000 per QALY gained with IFN-a compared with no IFN-a (95% confidence interval: 65,000 - 683,000).
Authors' conclusions Decision-analytic modelling is an important tool when assessing the cost-effectiveness of treatments for which there are little available data. The authors suggested that the incremental cost-effectiveness ratio (ICER) estimated in this study should be compared with ICERs for other treatments in Taiwan, to ascertain whether treatment of chronic hepatitis B with interferon-alpha (IFN-a) should be a priority for resource allocation.
CRD COMMENTARY - Selection of comparators The choice of the comparator was standard supportive care in Taiwan. It was chosen to reflect current practice. You should consider whether standard supportive care in Taiwan is representative of treatment patterns in your own setting.
Validity of estimate of measure of effectiveness The authors did not state that a systematic review of the literature had been undertaken. Instead, they specified that a comprehensive search was undertaken. It was therefore unclear whether the review was conducted in a systematic way to identify all relevant research and minimise bias. The effectiveness estimates from the primary studies were combined in a simplistic manner by using the median or mode as the base-case estimate, and the minimum and maximum values to provide the range. This approach treats any differences between primary studies as variability in a single parameter of interest, rather than as variations in the actual parameter estimated. This approach also implicitly gives all studies equal weight, regardless of size or quality.
Validity of estimate of measure of benefit The estimate of benefits was modelled with a Markov model. Each health state was valued using the time trade-off method with a mixture of clinicians and patients. The choice of benefit was appropriate for the study type, but it did not incorporate the impact of adverse events from treatment. However, the model did include a disutility associated with the discomfort of receiving treatment.
Validity of estimate of costs The authors stated that the study was performed from a societal perspective but, in fact, this was not the case. The costs included were the direct costs to the hospital and those of the study drug. The indirect costs were not included. The authors stated that, although patients are normally hospitalised for the first week of IFN-a therapy in Taiwan, this cost was not included in the model. This omission is likely to have biased the results in favour of treatment with IFN-a. The costs and the quantities were reported separately, which will aid reproducibility in other settings.
The resource use estimates were based on primary data and on expert opinion. No statistical analysis of the quantities was undertaken, although the authors explored variability in the sensitivity analyses. The prices were based on standard prices and on hospital reimbursement rates. The authors acknowledged that the use of hospital charges limits the generalisability of the study results. The prices were explored in the sensitivity analysis. The costs were discounted appropriately. The date to which the price data related was not reported, thus hindering any future reflation exercises.
Other issues The authors made appropriate comparisons of their findings with those from other studies. They were unable to compare the ICER with other studies relevant to Taiwan, owing to the lack of studies employing this methodology. The purpose of this study was to estimate an ICER for IFN-a treatment in Taiwan, as existing studies were based in other countries and were not considered suitable for generalisation to Taiwan. This may imply that the results of this study are, therefore, not generalisable to those other countries. The authors do not appear to have reported their results selectively and their conclusions reflected the scope of the analysis. The authors acknowledged that the use of expert opinion for some of the resource use estimates increases the uncertainty in the model results.
Implications of the study The authors suggested that more studies assessing health care in Taiwan using a decision-analytic approach are needed.
Bibliographic details Pwu R F, Chan K A. Cost-effectiveness analysis of interferon-alpha therapy in the treatment of chronic hepatitis B in Taiwan. Journal of the Formosan Medical Association 2002; 101(9): 632-641 Indexing Status Subject indexing assigned by NLM MeSH Adult; Antiviral Agents /economics /therapeutic use; Computer Simulation; Cost of Illness; Cost-Benefit Analysis /methods /statistics & Health Care Costs; Hepatitis B, Chronic /drug therapy /economics /mortality; Humans; Interferon-alpha /economics /therapeutic use; Markov Chains; Quality-Adjusted Life Years; Taiwan /epidemiology; numerical data AccessionNumber 22003000317 Date bibliographic record published 31/07/2005 Date abstract record published 31/07/2005 |
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