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Cost-utility analysis of androgen ablation therapy in metastatic prostate cancer |
Fujikawa K, Awakura Y, Okabe T, Watanabe R, Nishimura S |
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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 androgen ablation therapy for metastatic prostate cancer. Five androgen ablation therapies were evaluated as first-line therapy:
diethylstilbestrol diphosphate (DES),
orchiectomy,
orchiectomy plus nonsteroidal anti-androgen (NSAA),
luteinising hormone-releasing hormone (LHRH) analogue, and
LHRH analogue plus NSAA.
Study population The study population comprised hypothetical male patients aged 65 years, who were diagnosed as suffering from symptomatic metastatic prostate cancer for the first time.
Setting The setting was secondary care. The economic study was carried out at the Shiga Medical Center for Adults and Kyoto University, Japan.
Dates to which data relate The effectiveness data were derived from studies published between 1973 and 2000. The cost data related to 2001.
Source of effectiveness data The effectiveness data were derived from a review of published studies.
Modelling A Markov model was used to carry out cost-utility analyses with the aim of comparing the five androgen ablation therapies. The four health states used were hormone responsive (first-line hormone therapy), second-line therapy (or anti-androgen withdrawal), hormone resistant, and death from prostate cancer. The model used a time horizon of 10 years.
Outcomes assessed in the review The outcomes assessed were:
the progression rate of prostate cancer;
the relative hazard for cancer progression;
the rate of side effects for the five methods compared;
the response rate and response duration to second-line therapy; and
quality of life (QoL) weights for hormone responsive and resistant stages.
Study designs and other criteria for inclusion in the review Not stated. However, the included studies were a combination of observational studies, randomised controlled trials and meta systematic reviews employing meta-analyses.
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 Twenty-two primary studies were included in the review.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The cancer progression rate from hormone responsive stage to hormone resistant stage was 0.033 per month.
Among these patients, 35% responded to second-line therapy (response duration 3.5 months) with anti-androgen withdrawal and then progressed to hormone resistant stage. In the case of second-line therapy with additional NSAA, the response rate was 20% and the response duration was 3 months.
The progression rate from hormone resistant stage to death was 0.043 per month.
Therapy hazard for cancer progression (relative to orchiectomy) was 0.97 for DES, 0.98 for orchiectomy plus NSAA, 1.11 for LHRH, and 0.94 for LHRH plus NSAA.
The probability of minor side effects was 55% (mean of all the methods compared).
The probability of major side effects that require discontinuation of therapy was 14.3% for DES, 9.4% for orchiectomy plus NSAA, 1.3% for LHRH, and 11.0% for LHRH plus NSAA.
In terms of severe side effects, the excess mortality rate was 100 per 10,000 patients-year for DES and 3 per 10,000 patient-years for NSAA.
The QoL weight was 0.8 for the hormone responsive stage and 0.4 for the hormone resistant stage.
The adjustment for living with minor side effects was 0.85 and that for orchiectomy was 0.945.
These data formed the principal input parameters for the model.
Measure of benefits used in the economic analysis The measure of benefits used in the economic analysis was the quality-adjusted life-years (QALYs). These were calculated through model. QoL weights were derived from the literature (as reported in the 'Effectiveness Results' section).
Direct costs The direct costs were for hormone therapy, other treatments (such as for side effects), hospitalisation and orchiectomy. The costs incurred for the treatment of conditions unrelated to prostate cancer, and for blood testing and computed tomography were not included. The costs and the quantities were reported separately only for medication costs (DES, LHRH and NSAA). The cost data were based on the health insurance points for the Japanese Health Care system, set for 2001. A discount rate of 3% was used in the cost calculation.
Statistical analysis of costs No statistical analysis of the costs was carried out.
Indirect Costs The indirect costs were not included.
Sensitivity analysis First, a one-way sensitivity analysis was carried out, in which the QoL weight of orchiectomy relative to that of LHRH was changed in the range of 0.93 to 1.0. The point under which the incremental cost-effectiveness ratio of LHRH analogue was lower than that of orchiectomy was examined. Other parameters used were side effect rates to minor and major injuries, response rates to second-line therapy, QoL for hormone responsive and resistant stages, QoL adjustment for living with minor side effects, medical costs and discount rate.
Second, a one-way sensitivity analysis was carried out to examine whether the incremental cost-effectiveness ratio of orchiectomy plus NSAA and LHRH plus NSAA could come within the acceptable level (below Y6,000,000). The parameters used were side effect rate, medical costs and alternative efficacy ratio. The ranges used appear to have been derived from the literature, but this was not clear from the paper.
Estimated benefits used in the economic analysis The QALYs were 2.51 for DES, 2.54 for orchiectomy, 2.56 for orchiectomy plus NSAA, 2.68 for LHRH, and 2.64 for LHRH plus NSAA.
Cost results The total medical costs with discounting were Y103,572 for DES, Y289,049 for orchiectomy, Y727,516 for orchiectomy plus NSAA, Y858,312 for LHRH, and Y1,187,227 for LHRH plus NSAA.
Synthesis of costs and benefits When the QOL weight of orchiectomy was assumed to be 0.94 relative to LHRH, the incremental cost-effectiveness ratio relative to DES was Y5,522,888/QALY for orchiectomy, Y12,499.713/QALY for orchiectomy plus NSAA, Y4,288,295/QALY for LHRH, and Y8,168,254/QALY for LHRH plus NSAA.
LHRH plus NSAA was excluded due to strict dominance, while orchiectomy plus NSAA was excluded due to extended dominance. In terms of the results of the sensitivity analysis, for these two methods to have acceptable levels of cost-effectiveness, the effect of maximum androgen blockade treatment has to be more than 12% higher than that of single treatment methods (orchiectomy and LHRH).
Authors' conclusions Although the luteinising hormone-releasing hormone (LHRH) analogue strategy costs are higher than those of orchiectomy, LHRH analogue can offer more QALYs than orchiectomy. However, the choice of therapy depends to a large extent on the patient's preference.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear. LHRH analogue was reported to be the most commonly used intervention, but the authors noted other findings suggesting this was associated with higher costs and lower effects in comparison with bilateral orchiectomy. DES was the least used among the comparators chosen, but the authors retained it to facilitate historical comparisons with the other alternatives. You should determine if the intervention and comparators used are relevant to your own setting.
Validity of estimate of measure of effectiveness The authors used a good range of studies to determine the input parameters used in the construction of the model, and their reporting and referencing was very clear. However, it is unclear whether the studies were located systematically since the search strategies were not provided in the paper. A number of sensitivity analyses were performed to assess variability in the effectiveness estimates. This enhanced the validity of the results. The authors noted that the disease progression rates, state transitional probabilities and QoL weights relating to side effects were all derived from non-Japanese populations. While the sensitivity analyses did not show that the results were sensitive to these parameters, the authors stated that the validity of the results for a Japanese population would be enhanced by the use of studies conducted in Japan.
Validity of estimate of measure of benefit The measure of benefit used in the analysis, QALYs, was derived through modelling and the utility weights were derived from the literature. The use of QALYs facilitates comparisons across health care programmes, but the authors had doubts about the applicability of the data to their own setting. The data used to derive the QALYs were varied in the sensitivity analyses.
Validity of estimate of costs Details of the resource use and costs were clearly presented, although only medication costs for hormone therapy were given in terms of both the quantities and costs. The price year was based on Social Insurance points for 2001, although it was unclear how the cost data related to true opportunity costs, which would be required to enhance the generalisability of the data to other settings. Discounting was appropriately carried out. Another good feature of the cost analysis was that the costs were used in the sensitivity analysis to assess the impact of changes on the cost-effectiveness ratios.
Other issues The authors made good comparisons with other relevant studies and used the findings of one study as the basis for their present work. The issue of generalisability was discussed in that doubt was expressed about the validity of clinical findings from other studies conducted outside Japan. Even though the results of the sensitivity analyses did not support this concern, there was a desire to use the results of future domestic studies.
Implications of the study The findings of the study showed that the LHRH analogue strategy was associated with higher costs but more QALYs than orchiectomy. However, the choice of therapy may be influenced more by the patient's preference. The authors highlighted that their results were based on modelling and meta-analyses, and that future clinical studies might offer more reliable results.
Bibliographic details Fujikawa K, Awakura Y, Okabe T, Watanabe R, Nishimura S. Cost-utility analysis of androgen ablation therapy in metastatic prostate cancer. Japanese Journal of Urology 2003; 94(4): 503-512 Other publications of related interest Bayoumi AM, Brown AD, Garber AM. Cost-effectiveness of androgen suppression therapies in advanced prostate cancer. J Natl Cancer Inst 2000;92:1731-9.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Androgen Antagonists /economics /therapeutic use; Antineoplastic Agents, Hormonal /economics /therapeutic use; Antineoplastic Combined Chemotherapy Protocols /economics /therapeutic use; Cost-Benefit Analysis; Costs and Cost Analysis; Diethylstilbestrol /economics /therapeutic use; Gonadotropin-Releasing Hormone /analogs & Humans; Male; Orchiectomy /economics; Prostatic Neoplasms /drug therapy /economics /surgery; Quality of Life; Quality-Adjusted Life Years; derivatives /economics AccessionNumber 22003009536 Date bibliographic record published 31/07/2004 Date abstract record published 31/07/2004 |
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