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Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate |
Dranitsaris G, Leung P, Mather J, Oza 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 two aromatase inhibitors, letrozole (LET, 2.5 mg/day) and anastrozole (ANA, 1 mg/day), as second-line therapy for women with breast cancer who did not respond to tamoxifen.
Type of intervention Treatment and palliative care.
Study population The study population comprised a hypothetical cohort of women with advanced breast cancer who were oestrogen receptor positive, anthracycline naive and who failed first-line hormonal therapy with tamoxifen.
Setting The setting was not stated. The economic study was carried out in Canada.
Dates to which data relate The effectiveness data were derived from studies published from 1983 to 1999. Resource consumption was estimated from 1997 to 1999. The price year appears to have been 1999.
Source of effectiveness data The effectiveness evidence was derived from a systematic review of published studies.
Modelling A tree-based decision model was constructed to model the costs and survival of the hypothetical patients considered in the study. Two oncologists involved in the treatment of breast cancer validated the model structure. According to the model, patients who responded to the second-line therapy continued treatment until disease progression, while those who did not respond after 3 months were offered standard chemotherapy (5-fluorouracil plus doxorubicin plus cyclophosphamide, FAC). After three cycles of FAC, nonresponding patients were offered best supportive care, while responders were offered three more cycles of FAC. An alternative scenario for nonresponding patients was considered. This comprised single-agent paclitaxel (PAC) or docetaxel (DOC).
Outcomes assessed in the review The health outcomes evaluated in the review were the response rate and the median progression-free survival with ANA, LET, MA, FAC, DOC and PAC.
Study designs and other criteria for inclusion in the review The authors carried out a systematic review of the literature to identify studies involving the study interventions. The inclusion criteria were randomised design and patient eligibility, as reported in the present study.
Sources searched to identify primary studies MEDLINE and Cancerlit were searched from 1984 to 1998.
Criteria used to ensure the validity of primary studies The validity of the primary studies was ensured by fulfilling the inclusion criterion for random allocation of the patients to the treatment groups.
Methods used to judge relevance and validity, and for extracting data Studies were included in the review on the basis of the inclusion criteria, and were agreed upon by two evaluators.
Number of primary studies included Thirteen randomised controlled trials and 7 comparative studies were included in the review.
Methods of combining primary studies The Bayesian approach was used to combine the data coming from the primary studies. In the case of progression-free survival, equal weighting was used with studies of similar sample size.
Investigation of differences between primary studies Results of the review The mean response rate was 10.3% (95% confidence interval, CI: 6.6 - 13.9) with ANA, 18.4% (95% CI: 11.4 - 25.4) with LET, 11% (95% CI: 7 - 14.9) with MA, 52.1% (95% CI: 46.7 - 57.5) with FAC, 30% (95% CI: 23.7 - 36.4) with DOC, and 26% (95% CI: 12 - 40) with PAC.
The median progression-free survival was 147 days with ANA, 135 days with LET, 135 days with MA, 236.5 days with FAC, 133 days with DOC, and 126 days with PAC.
Measure of benefits used in the economic analysis The benefit measure was the quality-adjusted progression-free benefit (QAPFB). This was calculated by combining survival data and quality of life data. Survival data were obtained from the literature review. Quality of life data were derived from a sample of 25 women from the general public, who were randomly selected. The time-trade-off technique was used. Women were asked to estimate the utility value associated with nine health states used in the decision model. The benefits were not discounted due to the short survival of the women considered in the analysis.
Direct costs The costs were not discounted due to the short time horizon of the study. The health services included in the economic evaluation were for hospital resource consumption. This covered hospitalisation, outpatient clinic visits, anti-emetics, chemotherapy, laboratory tests, patient monitoring, adverse effect treatment, physician fees, and monitoring during the progression-free period. The cost/resource boundary adopted was that of the Canadian health care system. The unit costs were reported separately from the quantities of resources used only for the hospitalisation cost. Resource use was estimated on the basis of a retrospective chart review carried out from 1997 to 1999 on a sample of 87 patients who met the inclusion criteria. The unit costs were derived from current pharmacy ordering catalogues, pharmacy and nursing workload measurement statistics, the outpatient pharmacy, the department of biochemistry, and the schedule of benefits for oncologist's fees. The price year appears to have been 1999.
Statistical analysis of costs The costs were reported as averages along with 95% CIs. No further statistical tests were conducted.
Indirect Costs The indirect costs were not included in the economic evaluation.
Currency Canadian dollars (Can$). The exchange rate at December 1999 was Can$1 = US$0.68.
Sensitivity analysis One-way sensitivity analyses were conducted to evaluate the robustness of the estimated costs and QAPFB to variations in the response rates, costs for chemotherapy, and health state utilities. The ranges used were the 95% CIs found in the literature. A non-random sample of 25 female health care professionals was also interviewed to elicit utility data, as an alternative to data collected from the general public.
Estimated benefits used in the economic analysis When the utility values were estimated from the sample of women from the general public, the QAPFB was 0.40 years with MA, 0.41 years with LET, and 0.42 years with ANA. When the utility values were estimated from the sample of health care professionals, the QAPFB was 0.34 years with MA, 0.38 years with LET, and 0.39 years with ANA.
Cost results The estimated costs were Can$2,966 with MA, Can$2,949 with LET, and Can$3,149 with ANA.
Synthesis of costs and benefits An average cost-utility ratio was calculated to combine the costs and benefits of the evaluated alternative interventions. An incremental analysis was not conducted due to the similar costs and benefits obtained in the base-case analysis. The average cost-effectiveness ratio was Can$7,400 with MA, Can$7,200 with LET, and Can$7,500 with ANA. The results of the base-case analysis did not change under most of the scenarios evaluated in the sensitivity analyses,.
Authors' conclusions Letrozole (LET) had comparable costs and benefits to megestrol acetate (MA), despite its initial high acquisition costs. Anastrozole (ANA) was slightly more costly and similarly beneficial in comparison with MA. These conclusions were robust to a range of plausible variations considered in the sensitivity analyses.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparator was clear. The authors stated that MA represented the second-line agent of choice for women with breast cancer not responding to tamoxifen. The authors commented that other alternative therapies were available, but since they were not widely used as second-line treatments they were not considered. You should decide whether MA represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The analysis of effectiveness used a systematic review of the literature. The authors provided details of the specific inclusion criteria used, sources searched, methods employed and conduct of the review. The selection of randomised studies and the use of two reviewers ensured the validity of the primary studies. The estimates extracted from the primary studies were combined using Bayesian methods to obtain point estimates and CIs. The number of patients involved in the trials was reported, although details on individual studies were not given. In addition, it was unclear whether the authors considered any differences between the primary studies. Uncertainty in the estimates obtained from the review was investigated in sensitivity analyses. The estimates were varied within the CIs obtained when pooling the data.
Validity of estimate of measure of benefit Quality-adjusted survival was used as the summary benefit measure in the economic analysis. The authors made explicit the method used to obtain the utility weights required to calculate the quality-adjusted life-years. Details of the sample of women from which the utility values were obtained were reported, and an alternative source of data was also considered. Survival was obtained from a decision-tree model, which was represented graphically in the article. The use of quality-adjusted survival as a summary benefit measure facilitates comparisons with the benefits of other interventions.
Validity of estimate of costs The perspective adopted in the study was explicitly stated. It appears that all the relevant categories of costs have been included in the analysis. The indirect costs and productivity losses were not considered because they were not relevant to the perspective adopted in the study. The price year was given, thus making reflation exercises in other settings easy. The exchange rate from Canadian dollars into US dollars was also reported. The sources of the cost and resource use data were reported. Discounting was not relevant due to the short survival of the patients included in the study. However, the unit costs and the quantities of resources used were not analysed separately. The cost estimates were specific to the study setting and sensitivity analyses were carried out on one cost item only (chemotherapy). These factors limit the reproducibility of the results obtained.
Other issues The authors did not compare their findings with those from other studies. They also did not address the issue of the generalisability of the study results to other settings. Some sensitivity analyses were conducted. but only to evaluate the robustness of the results. Thus, the external validity of the analysis was low. The authors noted some limitations of their analysis. First, the need for modelling, due to the lack of direct comparison trials. Second, the high response rate observed with letrozole, although it was the one reported in the clinical trials. Third, the lack of third-line hormonal therapy for patients not responding to second-line treatment, although this was unlikely to have changed the conclusions of the study. Finally, the exclusion of the costs of side effects (this was a conservative choice because adverse events were more frequent with MA).
Implications of the study The study results suggested that LET may represent an effective and efficient alternative to MA for the treatment of women with advanced breast cancer who failed first-line hormonal therapy with tamoxifen.
Bibliographic details Dranitsaris G, Leung P, Mather J, Oza A. Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate. Anti-Cancer Drugs 2000; 11(7): 591-601 Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Agents /therapeutic use; Aromatase Inhibitors; Breast Neoplasms /drug therapy /economics; Canada; Costs and Cost Analysis; Decision Support Techniques; Female; Humans; Megestrol Acetate /therapeutic use; Nitriles /therapeutic use; Quality of Life; Randomized Controlled Trials as Topic; Triazoles /therapeutic use AccessionNumber 22000001551 Date bibliographic record published 29/02/2004 Date abstract record published 29/02/2004 |
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