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| Cost-effectiveness analysis of adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) for node-positive breast cancer: modeling the downstream effects |
| Au HJ, Golmohammadi K, Younis T, Verma S, Chia S, Fassbender K, Jacobs P |
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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. CRD summary This study evaluated the quality-adjusted survival and cost-effectiveness of adjuvant docetaxel, doxorubicin, and cyclophosphamide versus 5-fluorouracil, doxorubicin, and cyclophosphamide in women with node-positive breast cancer. The authors concluded that the docetaxel regimen was cost-effective. There were some limitations to the study, but the authors’ conclusions reflect the scope of their analysis. Type of economic evaluation Study objective The aim was to evaluate the quality-adjusted survival and cost-effectiveness of an adjuvant docetaxel regimen versus fluorouracil regimen, in women with node-positive breast cancer. Interventions The docetaxel regimen was docetaxel, doxorubicin, and cyclophosphamide and this was compared with the fluorouracil regimen, which was 5-fluorouracil, doxorubicin, and cyclophosphamide. Location/setting Canada/out-patient and in-patient care. Methods Analytical approach:A Markov model was used to compare the outcomes of the two initial chemotherapy regimens, over approximately 10 years. The authors reported that a third-party payer perspective was taken.
Effectiveness data:Most of the evidence of progression for the two regimens was from the BCIRG 001 trial (Martin, et al. 2005, see ‘Other Publications of Related Interest’ below for bibliographic details). Other studies were identified and used to inform other parameters, such as the survival of patients with local recurrence and metastatic recurrence.
Monetary benefit and utility valuations:The utilities, for the different health states, were from the literature and were determined using the time trade-off or the standard gamble method. The utilities for chemotherapy-related adverse events were from expert opinion.
Measure of benefit:The measure of benefit was quality-adjusted life-years (QALYs).
Cost data:The resource use during adjuvant therapy was from the BCIRG 001 trial (Martin, et al. 2005). The resource use during recurrent disease was from the literature. All future costs were discounted at 5% per annum. The currency was Canadian dollars (CAD) and the price year was 2002. Older costs were reflated to 2002 values using a Canadian general inflation factor. Some were converted at a rate of 1.07 Australian dollars to CAD 1 or one US dollar to CAD 1.52. The main source for costs was Alberta Health and Wellness operating costs. The main cost categories were adjuvant therapy, local recurrence, and best supportive care.
Analysis of uncertainty:A scenario with discounting of the benefits was evaluated. One-way sensitivity analysis was performed to assess the impact of variations in the key model inputs. Probabilistic sensitivity analysis was also performed, using the underlying parameter distributions from the trial data, and the results were presented as cost-effectiveness acceptability curves. Two alternate models were tested: one with prophylactic granulocyte-colony stimulating factor (G-CSF) given to all patients receiving the docetaxel regimen; and the other focused only on human epidermal growth factor receptor two (HER2)-negative patients. Results An incremental analysis was performed and in the base case, with a cohort of 1,000 women, the docetaxel regimen led to a gain of 313 QALYs, with an incremental cost of CAD 5.8 million, compared with the fluorouracil regimen. The incremental cost-effectiveness ratio (ICER) of the docetaxel regimen over the fluorouracil regimen was CAD 18,505 per QALY with discounted costs and undiscounted benefits or CAD 24,000 per QALY when both the costs and benefits were discounted.
The probabilistic sensitivity analysis demonstrated that the probability that the docetaxel regimen was cost-effective, with the base case assumptions, at a $50,000 per QALY willingness-to-pay threshold, was 70%. In the alternative models, the ICERs of the docetaxel regimen were increased; CAD 46,003 per QALY with universal G-CSF, and CAD 34,951 per QALY if only analysing HER2-negative patients. Authors' conclusions The authors concluded that, for women with node-positive breast cancer, the adjuvant docetaxel regimen was cost-effective. The recommendations at the time suggested prophylaxis, using G-CSF, against neutropenia or trastuzumab for HER2-positive patients, and the docetaxel regimen remained cost-effective in these scenarios. CRD commentary Interventions:The interventions were described and seem to have been relevant for the health problem. A reference for the clinical trial was provided. The authors stated that, at the time, this regimen was only available for HER2-negative patients.
Effectiveness/benefits:The main benefits were estimated using data from one clinical trial and it was not clear if there were other trials or evidence that could have informed the model. Whilst this clinical trial was likely to have been robust, the lack of discussion on the identification and existence of other evidence casts doubt on the validity of the results. The authors did not discount the future benefits, in the base case, and they justified this, but it should be remembered when comparing these results with those of other evaluations; the vast majority of studies that have a horizon of over two years discount the benefits. This might be extremely important as both the alternative models produced results close to the cost-effectiveness threshold. Discounting was addressed in the sensitivity analysis and the results with discounting of benefits, as well as costs, were presented.
Costs:Most of the relevant cost categories were included for the selected perspective. It is not clear why the costs for 2002 were not inflated to later values, given the publication date of 2009. Many of the resources were those of the clinical trial and these might differ from the resources used in a real clinical setting. The impact of this was not discussed.
Analysis and results:The structure of the model was well described and a diagram was presented. In general, the model inputs and the health states and their associated utilities were well reported. An incremental analysis was appropriately conducted, but the base-case results were only partly reported, with only the incremental benefits and costs. Other limitations, stated by the authors, related to not including hormonal therapy, nor a third or further line of chemotherapy, and a lack of societal utility data for the QALYs. Overall, the analysis was well reported.
Concluding remarks:There were some limitations to the study, but the authors’ conclusions reflect the scope of the analysis. Funding Supported by a grant from sanofi-aventis, Canada. Bibliographic details Au HJ, Golmohammadi K, Younis T, Verma S, Chia S, Fassbender K, Jacobs P. Cost-effectiveness analysis of adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) for node-positive breast cancer: modeling the downstream effects. Breast Cancer Research and Treatment 2009; 114(3): 579-587 Other publications of related interest Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. New England Journal of Medicine 2005; 352: 2302-2313. Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Combined Chemotherapy Protocols /economics /therapeutic use; Breast Neoplasms /drug therapy /economics; Chemotherapy, Adjuvant /economics; Cost-Benefit Analysis /economics; Cyclophosphamide /administration & Doxorubicin /administration & Female; Humans; Markov Chains; Medical Oncology /economics /methods; Monte Carlo Method; Quality-Adjusted Life Years; Recurrence; Taxoids /administration & Treatment Outcome; dosage; dosage; dosage AccessionNumber 22009101099 Date bibliographic record published 09/09/2009 Date abstract record published 17/11/2010 |
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