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| Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan |
| Kondo M, Hoshi SL, Toi M |
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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 The objective was to evaluate the cost-effectiveness of chemoprevention of breast cancer with tamoxifen or raloxifene among high-risk women in Japan. The authors concluded that that the introduction of chemoprevention for extremely high-risk women could be cost-effective. The methods were adequate, but only limited details were reported on how the effectiveness and clinical data were identified. The results were provided in detail and, given the scope of the analysis, the authors’ conclusions appear to be valid. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective The objective was to evaluate the cost-effectiveness of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan. Interventions Prophylaxis with tamoxifen and raloxifene was compared against no preventive therapy. Methods Analytical approach:A Markov model was used to evaluate the treatments throughout the course of high-risk women's lives. Different ages for starting prophylaxis were modelled. The time horizon was age 100 years or the lifetime of the patient, if shorter. The authors reported that the perspective adopted was that of Japan’s health system and, in a sensitivity analysis, it was societal.
Effectiveness data:The clinical and effectiveness parameters were derived from published studies. The risk profiles of patients were from clinical trials and other sources. The main effectiveness parameter was the five-year predicted breast cancer risk, which was derived from two clinical trials (Vogel, et al. 2006 and Fisher, et al. 2005, see 'Other Publications of Related Interest' below for bibliographic details).
Monetary benefit and utility valuations:An expert panel of doctors was used to review the available published studies from other countries and to obtain the best estimates for Japan by consensus.
Measure of benefit:Quality-adjusted life-years (QALYs) gained and life-years gained were the measures of benefit. As they could be generated over the lifetime of the patient, future benefits were discounted at an annual rate of 3%.
Cost data:The authors divided the costs into two main categories: those for healthy states and those for cancer states. For each of these two categories the costs were obtained for the following: ages 35 to 49, 50 to 64, 65 to 79, and over 80 years, and terminal care. Also included were the costs of non-invasive breast cancer surgery; endometrial cancer; pulmonary embolism; cataract; hip fractures; and chemoprevention drugs. The annual treatment costs by age group were estimated from the annual health care expenditure per woman, which was derived from data from the Ministry of Health. The costs for cancer states were derived from insurance claim reviews from a Tokyo cancer hospital. The costs of chemoprevention were from drug price lists. Other costs, such as those of hip fracture, endometrial cancer, and cataract, were from published studies. The price year was not reported. As costs could be incurred over the lifetime of the patient, future costs were discounted at an annual rate of 3%. All costs were reported in Japanese yen (JPY).
Analysis of uncertainty:A series of one-way sensitivity analyses assessed the impact of uncertainty in the model parameters on the model outputs. The authors varied the transitional probabilities, using 95% confidence intervals reported in the literature; the utility weights, by ±20%; the costs, by ±50%; and the discount rates, between 0 and 6%. The risk reduction effect of tamoxifen was also prolonged from five to 10 and 15 years. Results The results were presented for three five-year predicted risk levels (1.66% or more; 3.01 to 5.00%; and 5.01% or more) and for different starting ages (35, 50 and 60 years for Tamoxifen; and 50 and 60 years for raloxifene). A summary of the main results is presented here.
Tamoxifen was less effective (i.e. generated less QALYs) than no prophylaxis for women with five-year cancer risks of less than 5.00%. For this subgroup, tamoxifen prophylaxis was more costly than no treatment and, therefore, tamoxifen was dominated, which means it was more costly and less effective.
For women with cancer risks of more than 5.00%, tamoxifen was associated with QALY gains, when compared with no prophylaxis. For this risk group, tamoxifen generated cost savings, except for women aged 60 years, in whom an incremental cost of JPY 99,857 was incurred. In these women aged 60 years, the incremental cost-utility ratio (ICUR) or the additional cost per QALY gained was JPY 26,648,821. For women aged under 60 years, tamoxifen was dominant.
Raloxifene was less effective than no prophylaxis for women with five-year cancer risks of less than 5.00%. For this subgroup, raloxifene prophylaxis was more costly than no treatment and, therefore, raloxifene was dominated.
For women with cancer risks of more than 5.00%, raloxifene was associated with QALY gains, when compared with no prophylaxis, of 0.039 for women aged 50 years and 0.019 for those aged 60 years. The incremental costs for this risk group were JPY 44,053 for women aged 50 and JPY 203,455 for women aged 60 years. Raloxifene was associated with an ICUR of JPY 1,123,880 for women aged 50 and JPY 10,664,954 for women aged 60 years.
The authors reported that these results were most sensitive to changes in the utility values, particularly for healthy states, and the discount rates. Authors' conclusions The authors concluded that the introduction of chemoprevention targeting extremely high-risk women, with a five-year risk of 5% or more, could be cost-effective. CRD commentary Interventions:The interventions were appropriately reported and an explicit justification was given for using no prophylaxis as the comparator, which was that it was the status quo in Japan.
Effectiveness/benefits:The authors provided very few details of how the studies that supplied the clinical and effectiveness data were identified. They presented no details of a search, inclusion criteria, selection, etc. and it is not possible to determine if all the available evidence was included. The authors did report that the main clinical parameters were derived from two trials, both of which were published in high-impact journals and these estimates should be valid. More details on the review methods would have enhanced the overall validity of the clinical inputs.
Costs:The perspective was explicitly reported to be that of the Japanese health care system and it would appear that all the major cost categories and costs, relevant to this perspective, were included. The sources from which the costs were derived were reported. Only limited details of the sensitivity analysis from a societal perspective were reported, and it is not clear if productivity costs were included. The time horizon, the discount rate, and the currency were reported, but the price year was not, which will hamper any future inflationary exercises.
Analysis and results:The costs and benefits were synthesised in a decision analytic Markov model and appropriate details of this model were provided, including a diagram. The impact of uncertainty on the model’s results was tested in a series of one-way sensitivity analyses. This type of analysis goes some way towards assessing the impact of the uncertainty in the model parameters on the results, but it does not evaluate the overall model uncertainty, as probabilistic sensitivity analyses do. The authors adequately reported the limitations of their study, including the fact that the main effectiveness parameters were derived from two studies undertaken in the USA rather than in Japan.
Concluding remarks:The methods were adequate, but few details were reported on how the effectiveness and clinical data were identified. The results were provided in detail and, given the scope of the analysis, the authors’ conclusions appear to be valid. Funding Funded by Japan's Ministry of Health, Labour, and Welfare. Bibliographic details Kondo M, Hoshi SL, Toi M. Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan. British Journal of Cancer 2009; 100(2): 281-290 Other publications of related interest Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, Fehrenbacher L, Pajon ER, Wade JL, Robidoux A, Margolese RG, James J, Lippman SM, Runowicz CD, Ganz PA, Reis SE, McCaskill-Stevens W, Ford LG, Jordan VC, Wolmark N. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006; 295: 2727-2741.
Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. Journal of the National Cancer Institute 2005; 97: 1652-1662. Indexing Status Subject indexing assigned by NLM MeSH Adult; Antineoplastic Combined Chemotherapy Protocols /economics; Breast Neoplasms /prevention & Carcinoma in Situ /prevention & Carcinoma, Lobular /prevention & Cost-Benefit Analysis; Female; Humans; Japan; Markov Chains; Middle Aged; Neoplasm Invasiveness; Postmenopause; Raloxifene Hydrochloride /administration & Risk Factors; Tamoxifen /administration & control; control; control; dosage; dosage AccessionNumber 22009100615 Date bibliographic record published 09/09/2009 Date abstract record published 28/04/2010 |
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