Cost-effectiveness assessment of interferon alfa-2b as adjuvant therapy of high-risk resected cutaneous melanoma Hillner B E

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1 Cost-effectiveness assessment of interferon alfa-2b as adjuvant therapy of high-risk resected cutaneous melanoma Hillner B E 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-2b (IFN-alfa2b) as adjuvant therapy for high risk resected cutaneous melanoma was compared to no IFN-alfa2b. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population The study population comprised a hypothetical cohort of 50-year-old, newly diagnosed patients with resectable, primary cutaneous melanoma. The data for the patients was projected from the results of the Eastern Cooperative Oncology (ECOG) trial 1684 (E1684). The E1684 trial evaluated 287 melanoma patients with histologically proven primary cutaneous melanoma without prior systematic adjuvant therapy and without evidence of distant metastatic disease. Setting The setting was secondary care. The economic study was conducted in the USA. Dates to which data relate The effectiveness data correspond to patients admitted to The Eastern Oncology Group (ECOG) trial 1684 (E1684) published in The cost data were published in The price year was Source of effectiveness data The effectiveness data were taken from a review of the literature. Modelling A decision-analytic model was used to estimate the costs and health benefits of IFN-alpha2b therapy. The time frame of the model was 35 years. Outcomes assessed in the review The outcomes used as input parameters to the model were: the disease free survival and overall survival (years) of patients receiving IFN-alpha2b compared to the observation group (6.9 year follow up period); Page: 1 / 6

2 the recurrence-free survival and hazard rate (risk of recurrence per year) of stage III melanoma at 5 years and beyond; and the utility assignments for patients outcomes (reflecting a patients utility for a specific level of functional and psychological health). Study designs and other criteria for inclusion in the review The authors did not report any designs or inclusion or exclusion criteria for studies included in the review. The review used data from a randomised trial carried out by the Eastern Oncology Group (ECOG) and two large databases of patients. No details on the method of randomisation used in the trial were reported. The duration of follow up in the trial was 6.9 years. Sources searched to identify primary studies The author did not report the search strategy or sources searched to identify primary studies. Criteria used to ensure the validity of primary studies The author did not report the criteria used to ensure the validity of primary studies. Methods used to judge relevance and validity, and for extracting data The author did not report the criteria used to judge the relevance or validity of the data or the methods used to extract data. Number of primary studies included Six primary data sources were used to derive the effectiveness data. Methods of combining primary studies The primary data sources used were not combined to produce individual estimates of the input parameters. Investigation of differences between primary studies The difference between primary data sources was not investigated or explained by the authors. Results of the review The overall survival rate of patients receiving IFN-alpha2bn, after a median follow up period of 6.9 years, was 46%; with increased survival duration of 3.8 years. The relapse-free survival rate was 37%; with increased relapse-free survival duration of 1.7 years. The recurrence-free survival rate of stage III melanoma at 5 years and beyond was: 50% at 5 years; 38.5% at 7 years; 32.9% at 10 years; and 29.3% at 15 years. The hazard rate (risk of recurrence) of stage III melanoma at 5 years and beyond was: 15% at 5-6 years; 5.4% at 7-9 years; and 2.5% at years. The utility assignments for patient outcomes were as follows: disease free, no treatment - utility value = 1.0; disease-free maintenance IFN-alpha2b - utility value = 0.8; Page: 2 / 6

3 disease-free, induction IFN-alpha2b - utility value = 0.7; and alive with recurrence - utility value = 0.5. Measure of benefits used in the economic analysis The author used quality adjusted life years (QALY's) as the measure of benefit for the economic analysis. The utility values were derived from 2 published studies. The method used to elicit utility values was not reported. Direct costs The only direct costs included in the analysis were medical costs, which were divided into 2 main categories: adjuvant treatment costs, including the cost of drug therapy and treatment of toxicity, and the costs of recurrence. IFN-alpha2b costs were based on an average wholesale unit cost of $10.98/MU and were calculated by multiplying the median dosage of administered E1684 by the median body surface area (1.9m^2) of patients in the trial. Other costs associated with treatment were estimated based on clinical experience. Administration and monitoring costs were estimated to be $4,000 during the initial 4-week induction and $200 per month during the maintenance period. No published costs of recurrent melanoma treatment costs were available, and thus a consensus of experts estimated a cost of $5,000 per month to treat recurrences, with an increase to $10,000 for the terminal month. No discounting was reported despite the fact that the published data follow-up period was 6.9 years and the timeframe of the model was 35 years. The date to which the cost data refer was not reported. Statistical analysis of costs No statistical analysis of costs was conducted. Indirect Costs No indirect costs were included in the analysis. Currency US dollars ($). A conversion rate of $1.00 = was reported, but no conversion date was reported. Sensitivity analysis The author conducted a one way sensitivity analysis to determine whether changes in the cost of recurrent disease and the quality of life utility values for IFN-alpha2b therapy and melanoma recurrence affected the results of the model. Estimated benefits used in the economic analysis The survival rate of patients receiving IFN-alpha2b were estimated at: 43% over the 5-year model follow up period; 35.8% (3.99 years) over the 7-year follow up period; and 5.4% (8.96 years) over the 35-year follow up period. The adjustment of survival for quality of life showed that, at 7 years, patients receiving IFN-alpha2b had 3.66 QALY's, increasing to 6.06 QALY's when the life expectancy of patients was projected to 35 years. The relapse-free survival rate of patients receiving IFN-alpha2b were estimated at: 36.8% over the 5-year model follow up period; Page: 3 / 6

4 32.8% over the 7-year follow up period; and 5.8% over the 35-year follow up period. The benefits were assessed over a 35-year follow-up period. The side effects of the treatment were not referred to in the analysis. Cost results The cost of starting IFN-alpha2b was $28,636, compared to a cost of $0 for observation. The total cost of care for patients receiving IFN-alpha2b was $91,656 over a 7 year period, compared to a total care cost of $76,580 for observation (difference = $15,076). Projections over a 35 year period estimated the total cost of care for patients receiving IFN-alpha2b to be $105,479, compared to $87,356 for patients receiving observation (difference = $18,123). Synthesis of costs and benefits Incremental cost-effectiveness ratios were calculated. The incremental cost per quality -adjusted life-year saved by IFNalpha2b therapy was $43,200 over a 7-year period, projected to $15,200 over a 35-year follow-up period. The results of sensitivity analysis were clearly reported. The recalculation of cost-effectiveness, assuming no costs of recurrent disease, resulted in the cost per life-year saved rising to $61,700 over a year period, and to $21,600 at the projected life expectancy of 35 years. The corresponding figures for the cost per quality-adjusted life-year saved were $81,600 at 7 years and $23,900 at the projected life expectancy of 35 years. The assumption that the quality of life associated with IFN-alpha2b therapy and melanoma recurrence is equal to death resulted in a decrease of 0.07 QALY's compared with observation at 7 years. The projection of the analysis to 35 years, however, produced an increase of 0.76 QALY's for those receiving IFN-alpha2b compared to those in the observation group (corresponding to a cost of $23,260 per QALY). Authors' conclusions The author concluded that the use of adjuvant IFN-alpha2b as a therapy of high-risk resected cutaneous melanoma significantly prolongs relapse-free and overall survival, even when adjusted for quality of life utilities. The treatment also has a cost-effective ratio at 7 years that is similar to other well established medical interventions, and which can be projected to decline further over time. CRD COMMENTARY - Selection of comparators The author compared the use of IFN-alpha2b as an adjuvant therapy for high-risk resected cutaneous melanoma against the use of no therapy; where patients receive only observation. This was explicitly justified on the basis that IFNalpha2b is the only adjuvant therapy proven to be effective in the treatment of high-risk resected cutaneous melanoma. Validity of estimate of measure of effectiveness The author did not report whether a systematic search and review of the literature had been undertaken. The author appeared to use data from the available sources selectively. The author did not consider the impact of differences between studies when estimating effectiveness. The choice of primary studies appears relevant, however the method used to combine the studies was not transparent. The estimates of effectiveness (life years gained) were estimated from a model. The model structure was not described. The model was validated empirically by comparing predicted values from a 5-year analysis to the actual values derived from a randomised-controlled trial. The author did not report whether other methods were used to assess the face validity of the model (e.g. the treatment path used). A sensitivity analysis was used to assess the impact of variability in the data on the results, but not the impact of changes in the structure of the model. Validity of estimate of measure of benefit The author used QALY's as the measure of benefit, which was appropriate. However, the author did not report the Page: 4 / 6

5 quality of the original sources used to provide utility estimates or how the utility weights were derived. Sensitivity analysis was used to test the impact of different utility values on the results. Validity of estimate of costs The author included only the medical costs of IFN-alpha2b as an adjuvant therapy and recurrence. The costs of IFNalpha2b were estimated from wholesale prices. The costs of administration and treatment of associated toxicity were estimated from clinical experience. Expert opinion was used to estimate the costs of recurrence. Resource use and prices were not reported separately. Discounting of future costs in the 7- and 35-year analyses was not reported. A sensitivity analysis to assess the impact of variability or uncertainty in the data was limited to the costs of recurrence. Other issues The author presented incremental cost effectiveness ratios for France, Germany and the UK. These were based on local prices of the drug. No other cost values were adjusted for differences in practice patterns, resource use or relative costs in these countries. The author did not discuss other issues of generalisability. The author compared the results of the study with economic studies of other interventions. Implications of the study The use of IFN-alpha2b as an adjuvant therapy of high-risk resected cutaneous melanoma results in significant improvements in relapse-free survival and overall survival. Furthermore the therapy also appears cost-effective in light of comparisons made with other well-established medical interventions. However the author did state that the results require confirmation in a prospective study. Source of funding None stated. Bibliographic details Hillner B E. Cost-effectiveness assessment of interferon alfa-2b as adjuvant therapy of high-risk resected cutaneous melanoma. European Journal of Cancer 1998; 34(Supplement 3): S18-S21 PubMedID Other publications of related interest Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST Journal of Clinical Oncology 1996;14:7-17. Hillner BE, Kirkwood JM, Atkins MB, Johnson ER, Smith TJ. Economic analysis of adjuvant interferon alfa-2b in highrisk melanoma based on projections from Eastern Cooperative Oncology Group Journal of Clinical Oncology 1997;15: Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Agents /economics /therapeutic use; Cohort Studies; Combined Modality Therapy /economics; Cost- Benefit Analysis; Disease-Free Survival; Health Care Costs; Humans; Interferon-alpha /economics /therapeutic use; Melanoma /therapy; Middle Aged; Recombinant Proteins; Skin Neoplasms /therapy; Survival Rate; Virginia Page: 5 / 6

6 Powered by TCPDF ( AccessionNumber Date bibliographic record published 28/02/2002 Date abstract record published 28/02/2002 Page: 6 / 6