|Cost-effectiveness of letrozole versus tamoxifen as first-line hormonal therapy in treating postmenopausal women with advanced breast cancer in Japan
|Okubo I, Kondo M, Toi M, Ochiai T, Miki S
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.
The use of letrozole and tamoxifen as first-line hormonal treatments in advanced breast cancer were compared.
Economic study type
The study population comprised a hypothetical cohort of postmenopausal women with advanced breast cancer.
The setting was secondary care. The economic study was carried out in Japan
Dates to which data relate
The effectiveness data were derived from studies published between 1998 and 2001. The price year was 2003.
Source of effectiveness data
The effectiveness data were derived from the results of a multinational Phase III trial, a review of the literature, and the opinions of expert panels.
A Markov model was used to extrapolate the effectiveness data to a longer time horizon, and to estimate the costs and effects of letrozole and tamoxifen. The Markov model had nine health states corresponding to hormonal therapy (HT; first- to third-line), chemotherapy (first- to third-line), observational care, end-stage palliative care and death.
Outcomes assessed in the review
The outcomes assessed in the review were the probabilities of progression from disease, treatment failure, death and selection of alternative therapy in the first and second states of HT.
Study designs and other criteria for inclusion in the review
The authors did not report the criteria for inclusion in the review. However, they reported that the main key transition probabilities were derived from a multinational Phase III trial.
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
Number of primary studies included
Five primary studies were included in the review.
Methods of combining primary studies
Investigation of differences between primary studies
Results of the review
The proportion of patients ending first-line letrozole varied from 0.07 in months 34 - 36 to 0.22 in months 46 - 48.
The transition probabilities for patients ending first-line letrozole and moving to the following states were as follows:
death ranged from 0.00 in months 25 - 48 to 0.35 in months 0 - 3;
first-line chemotherapy ranged from 0.00 in months 28 - 48 to 0.35 in months 0 - 3;
second-line HT ranged from 0.34 in months 0 - 3 to 1 in months 28 - 30; and
end-stage palliative care ranged from 0 in months 22 - 48 to 0.23 in months 0 - 3.
The proportion of patients ending first-line tamoxifen ranged from 0.09 in months 37 - 39 and 43 - 45 to 0.33 in months 46 - 48.
The transition probabilities for patients ending first-line tamoxifen and moving to the following states were as follows:
death ranged from 0.00 in months 10 - 48 to 0.12 in months 0 - 3;
first-line chemotherapy ranged from 0.00 in months 25 - 48 to 0.36 in months 0 - 3;
second-line HT ranged from 0.31 in months 0 - 3 to 1 in months 28 - 48; and
end-stage palliative care ranged from 0 in months 28 - 30 to 0.33 in months 22 - 24.
The authors also reported the transition probabilities for states beyond first-line HT.
Methods used to derive estimates of effectiveness
The opinions of an expert panel, in conjunction with the published literature, were used to determine transition probabilities for several health states beyond first-line HT. The expert panel comprised Japanese oncologists.
Estimates of effectiveness and key assumptions
The experts were asked to derive, in conjunction with data from the literature, transition probabilities from second- and third-line chemotherapy, second- and third-line chemotherapy maintenance, observational care and end-stage palliative care.
Measure of benefits used in the economic analysis
The measure of health benefit used was the life-years gained (LYG).
The direct costs of the payer were included in the analysis. The costs included were for outpatient visits, hospitalisation, drugs used, laboratory tests and other health care resources. The resources were estimated for each cycle of 3 months, based on the results of a survey on standard breast cancer therapy in Japan and by forming an expert panel composed of Japanese clinical oncologists. The unit costs for each of the health care resources were determined according to the National Health Insurance medical fee table and drug price list as of April 2003. Since the costs were incurred over the lifetime of the patient, discounting was relevant and was appropriately undertaken at an annual rate of 3%. The study reported the average costs.
Statistical analysis of costs
The costs and resource use were treated as point estimates (i.e. the data were deterministic).
No indirect costs were included.
Japanese yen (JPY) and US dollars ($). The exchange rate used was $1 = JPY 110 (30 September 2003).
A probabilistic sensitivity analysis was undertaken. The uncertainties of individual parameters were represented by appropriate probability distributions to determine variance. Beta-distributions were used to describe the uncertainty around the probabilities of first-line treatment failure in sequential cycles. Triangular distributions were used to represent uncertainty in the transition probabilities from second-line HT. The remaining transition probabilities were described by triangular distributions or point estimates.
Estimated benefits used in the economic analysis
The mean expected LYG were 3.68 when using letrozole and 3.09 when using tamoxifen.
The average cost per patient was JPY 3,644,588 ($33,133) when using letrozole and JPY 3,322,111 ($30,201) when using tamoxifen.
Synthesis of costs and benefits
The costs and benefits were combined using an incremental cost-effectiveness ratio (i.e. the additional cost required per LYG). Compared with tamoxifen, the additional cost per LYG of using letrozole was JPY 546,571 ($4,969). The results of the sensitivity analysis showed that at the fifth percentile letrozole dominated tamoxifen (i.e. it was both cheaper and more effective), whereas at the 95th percentile the incremental cost-effectiveness ratio of letrozole was JPY 2,310,593 ($21,003).
Compared with tamoxifen, letrozole was a clinically beneficial and cost-effective treatment option for first-line therapy for advanced breast cancer in Japan.
CRD COMMENTARY - Selection of comparators
Although no explicit justification was given for using tamoxifen as the comparator, it would appear to represent current practice in the authors' setting. You should decide if the comparator represents current practice in your own setting.
Validity of estimate of measure of effectiveness
The authors did not report that a systematic review of the literature had been undertaken to identify research and minimise biases. They also, provided very few details of the methodology used in their review. The authors reported that many of the key transition probabilities were derived from a multinational Phase III clinical trial. Although the authors undertook probabilistic sensitivity analysis, the uncertainties in all parameters were not investigated as the authors reported that point estimates were used in the sensitivity analysis. Further, the use of bounded distributions (i.e. triangular distributions in the study) would not appear to capture all the uncertainty, as values cannot take values below or above the minimum and maximum values set by the authors.
Validity of estimate of measure of benefit
The estimation of benefits was modelled using a Markov model, which was appropriate for the study question.
Validity of estimate of costs
All the categories of cost relevant to the perspective adopted were included in the analysis, as were all major cost categories. The costs and the quantities were reported separately, which will increase the generalisability of the authors' results. Resources were estimated for each cycle of 3 months, based on the results of a survey on standard breast cancer therapy in Japan and by forming an expert panel composed of Japanese clinical oncologists. The unit costs for each of the health care resources were determined according to the National Health Insurance medical fee table and drug price list. It was unclear if cost and resource use parameters were included in the sensitivity analysis. The authors performed appropriate currency conversions, and reported costs in both the national currency (Japanese yen) and US dollars. Since the costs were incurred during the lifetime of the patient, future costs were appropriately discounted. The price year was reported, which will aid any future inflation exercises.
The authors made appropriate comparisons of their findings with those from other studies that had also found letrozole to be cost-effective. However, they reported their results cannot be directly compared with those reported in other countries, as the health care systems and medical practices differ from country to country. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis. The authors reported no further limitations to their study.
Implications of the study
The authors appear to recommend the use of letrozole for advanced breast cancer in Japan.
Okubo I, Kondo M, Toi M, Ochiai T, Miki S. Cost-effectiveness of letrozole versus tamoxifen as first-line hormonal therapy in treating postmenopausal women with advanced breast cancer in Japan. Cancer and Chemotherapy 2005; 32(3): 351-363
Other publications of related interest
Karnon J, Jones T. A stochastic economic evaluation of letrozole vs. tamoxifen as a first-line hormonal therapy for advanced breast cancer in postmenopausal patients. Pharmacoeconomics 2003;21:513-25.
Nuijten M, Meester L, Waibel F, et al. Cost effectiveness of letrozole in the treatment of advanced breast cancer in postmenopausal women in the UK. Pharmacoeconomics 1999:16;379-97.
Nuijten M, McCormic J, Waibel F, et al. Economic evaluation of letrozole in the treatment of advanced breast cancer in menopausal women in Canada. Value Health 2000;3:31-9.
Subject indexing assigned by NLM
Aged; Antineoplastic Agents, Hormonal /administration & Aromatase Inhibitors /administration & Breast Neoplasms /drug therapy /economics; Cost-Benefit Analysis; Drug Administration Schedule; Female; Humans; Middle Aged; National Health Programs /economics; Nitriles /administration & Postmenopause; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Tamoxifen /administration & Triazoles /administration & dosage /economics; dosage /economics; dosage /economics; dosage /economics; dosage /economics
Date bibliographic record published
Date abstract record published