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Prolonged treatment with interferon in patients with histologically mild chronic hepatitis C: a decision analysis |
Davis G L, Beck J R, Farrell G, Poynard T |
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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 Prolonged treatment (18 or 24 months) with interferon (IFN) in patients with histologically mild chronic hepatitis C. The dose of IFN was 3 million units (MU) three times a week.
Economic study type Cost-effectiveness analysis; cost-utility analysis.
Study population 35-year-old patient presenting with histologically mild chronic hepatitis C, as defined by a Knodell periportal inflammation score of 0 or 1 without fibrosis or cirrhosis.
Setting The study setting was hospital. The economic study was carried out in the USA.
Dates to which data relate Effectiveness data were collected from studies published in 1995 and studies used in a 1997 publication describing the decision model. Cost data were based on data collected from a 1995 source and a study published in 1997. The price year was 1995.
Source of effectiveness data Effectiveness data were derived by pooling results from two large multi-centre trials with the parameters for long term consequences from a model published elsewhere, which used other literature and was stated to have been validated by an expert panel.
Modelling A Markov decision analytic model was used to determine the cost-effectiveness of the treatment strategies.
Outcomes assessed in the review The review assessed response to IFN treatment as the sustained viral-negative response rate. Sustained was defined by a persistently normal serum alanine aminotransferase (ALT) level at the end of treatment and for at least 6 months after discontinuation of therapy. It was assumed that approximately 14% of sustained ALT responders would not be viral negative and therefore the percentage of sustained responders was reduced by 14%.
Study designs and other criteria for inclusion in the review The effectiveness estimates were derived from two multi-centre trials, which used the 6, 18 and 24 month treatment regimes.
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 Summary statistics from individual studies were used in the review.
Number of primary studies included Two studies were cited, but the number used in the original paper was not stated.
Methods of combining primary studies Estimates from the two multi-centre trials were pooled and combined with the results from other studies.
Investigation of differences between primary studies Results of the review Sustained response was achieved in 42.3% of those with mild hepatitis without fibrosis treated for 18-24 months and 17.8% in those treated for 6 months.
After reduction by 14%, the sustained viral-negative response rate for mild chronic hepatitis was 36.4% for 18-24 months of treatment and 15.3% for a 6-month course.
Estimates of effectiveness and key assumptions The authors made the following assumptions based on a published study. An 18-month treatment course was assumed. Sustained response was the only favourable response considered. Non-responders after the first 12 weeks of treatment stopped IFN. Relapse was not retreated in the model. The presence of hepatitis C virus (HCV) was assumed to be an essential requirement for disease progression. The effect of age on the rate of liver disease progression was not included. The effects of viral factors and serial liver biopsies were not considered.
Measure of benefits used in the economic analysis Quality adjusted life years (QALYs) and number of life years (LYs) saved were used as the measures of benefit. Benefits were discounted at an annual discount rate of 3%.
Direct costs Direct costs were discounted at an annual rate of 3%. Quantities and costs were reported separately for IFN only. Direct costs were for outpatient medications, an 18-24 month or 6-month course of interferon treatment, counselling and follow up blood tests and visits. The price year was 1995. Hospital costs or charges reduced to account for profit were used, and were collected from hospital records, a published study or from the 1995 Red Book, depending on which was the lowest in order to bias against the longer treatment duration. The price year was 1995.
Statistical analysis of costs No statistical analysis was reported.
Indirect Costs Indirect costs were not included.
Sensitivity analysis One way sensitivity analyses were conducted on all cost and progression rates.
Estimated benefits used in the economic analysis In the base case, for a 35 year old:
6 month versus no treatment:
Increase in LYs (undiscounted), 0.93;
Increase in LYs (discounted), 0.32;
Increase in QALYs (undiscounted), 2.13;
Increase in QALYs (discounted), 0.98.
18 months versus 6 months:
Increase in LYs (undiscounted), 1.17;
Increase in LYs (discounted), 0.4;
Increase in QALYs (undiscounted), 2.81;
Increase in QALYs (discounted), 1.28.
Cost results Cost results (in 1995 US dollars) were as follows:
6 months versus no treatment:
Increase in cost (undiscounted), -$1,107;
Increase in cost (discounted), $609.
18 months versus 6 months:
Increase in cost (undiscounted), -$1,118;
Increase in cost (discounted), $1,123.
Synthesis of costs and benefits 6 months versus no treatment:
Cost/LY (discounted), $1,903;
Cost/QALY (discounted), $621.
18 months versus 6 months:
Cost/LY (discounted), $2,808;
Cost/QALY (discounted), $877.
Unfortunately, several of the results were expressed in terms of 18 months versus no treatment, and therefore the increments have been recalculated to show only 18 months versus 6 months. Please refer to the commentary for explanation.
According to the sensitivity analysis, cost-effectiveness decreases with age. Varying viral clearance probabilities showed a threshold such that 18 month versus 6 month was more cost-effective than 6 months versus no treatment up to probability (6 months) = 13% and then an increasing divergence in the opposite direction. The probabilities in the trials never actually exceeded 20%.
Authors' conclusions Longer treatment with interferon always showed a survival benefit, and the cost of longer treatment was reasonable compared with that for a 6-month course.
CRD COMMENTARY - Selection of comparators A justification was given for the comparator used, namely that it was a currently employed strategy. You, as a user of the database, should decide if these health technologies are relevant to your setting.
Validity of estimate of measure of benefit The authors did not state that a systematic review of the literature had been undertaken. More information about the design of the review and the method of combining primary effectiveness estimates could have been reported. Estimation of some benefits was obtained directly from the effectiveness analysis. The instrument used to derive utility values was not reported.
Validity of estimate of costs Good features of the cost analysis were that all relevant direct cost categories were included, sensitivity analyses were conducted on costs and quantities, quantities and costs were reported separately, and the price year was reported. As the authors stated, an attempt was made to avoid using charges (which are likely to include a non-market determined profit margin), in order to increase generalisability to other settings. However, it would have been preferable to see the actual adjustment made to some charges.
Other issues The authors did make appropriate comparisons of their findings with those from other studies and did address the issue of generalisability to other settings, particularly with regards to costs and also instances where decisions to treat asymptomatic patients rely on levels of decision making beyond those used in the model, e.g. the possibility of future new treatments and individual patient preferences. The study considered patients presenting with histologically mild chronic hepatitis C and this was reflected in the authors' conclusions. Although the authors acknowledged that relapse was not dealt with in the model, the effect of age on the rate of liver disease progression could not be determined, and the effect of viral factors, such as genotype and the pre-treatment level of viraemia, were not considered. Not all the results of the sensitivity analysis were presented and, as was stated earlier, results of incremental changes for 18 months versus no treatment were presented. This is misleading because it is the average of the incremental effect of 6 months versus no treatment and 18 months versus 6 months, the former generally being more cost-effective than the latter. You as the decision maker need to decide how much you are willing to pay for an increase in benefit.
Implications of the study Longer treatment with interferon showed a survival and QALY benefit. The cost per QALY or LY seems reasonable compared, for example, to the judgements of NICE, which seem to have a much higher threshold (about 30,000). As the authors stated, 'the results of this study provide some guidance as to the potential benefits of IFN treatment in patients with histologically mild disease.' They suggest that future models might include viral levels, presence of viral quasispecies and viral genotype when tests are available which provide better prediction of response.
Source of funding Supported in part by unrestricted grants from the Schering-Plough Corporation to the University of Florida and Baylor College of Medicine.
Bibliographic details Davis G L, Beck J R, Farrell G, Poynard T. Prolonged treatment with interferon in patients with histologically mild chronic hepatitis C: a decision analysis. Journal of Viral Hepatitis 1998; 5(5): 313-321 Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Antiviral Agents /economics /therapeutic use; Cohort Studies; Cost-Benefit Analysis; Decision Support Techniques; Female; Hepatitis C, Chronic /drug therapy /economics; Humans; Interferon-alpha /economics /therapeutic use; Male; Middle Aged; Recombinant Proteins; Sensitivity and Specificity; Time Factors AccessionNumber 21998001473 Date bibliographic record published 31/12/2001 Date abstract record published 31/12/2001 |
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