|
Economic consequence of local control with radiotherapy: cost analysis of internal mammary and medial supraclavicular lymph node radiotherapy in breast cancer |
Lievens Y, Kesteloot K, van den Bogaert W |
|
|
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 study evaluated the use of internal mammary and medial supraclavicular lymph node region radiotherapy (IM-MS RT) after surgery for Stage I-III breast cancer patients.
Type of intervention Treatment and secondary prevention.
Economic study type Cost-effectiveness analysis and cost-utility analysis.
Study population The study population comprised a hypothetical cohort of women with Stage I-III breast cancer who underwent surgery (either mastectomy or tumorectomy with axillary clearance).
Setting The setting was secondary care. The study was carried out in Leuven, Belgium.
Dates to which data relate The effectiveness data were collected from two studies published in 1997 and 2000. The cost data were from studies published between 2000 and 2003. The price year was 2000.
Source of effectiveness data The effectiveness data were derived from a synthesis of published studies and from authors' assumptions.
Modelling A Markov model was developed to estimate the cost-effectiveness of IM-MS RT versus no RT. The timeframe was 20 years, with each cycle lasting for 6 months. Four health states were considered. These were no disease progression, locoregional and/or distant disease progression, dead from breast cancer progression, and dead from non breast cancer causes.
Outcomes assessed in the review The outcomes assessed were the transition probabilities used to populate the model:
the probability of relapse with and without IM-MS RT,
the probability of death not related to breast cancer, and
the probability of death related to breast cancer (for both patients with no evidence of the disease and patients alive with disease).
Study designs and other criteria for inclusion in the review The authors did not identify any inclusion criteria for reviewing studies. A meta-analysis (Early Breast Cancer Trialists' Collaborative Group 2000, see 'Other Publications of Related Interest' below for bibliographic details) and a randomised trial (Overgaard et al. 1997, see 'Other Publications of Related Interest' below for bibliographic details) were reviewed.
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 At least two studies were reviewed.
Methods of combining primary studies Not stated, but a narrative method seems to have been used.
Investigation of differences between primary studies The authors mentioned that there were relevant differences in the extent of the radiation fields used and the technical quality of the radiation between studies included in the reviewed meta-analysis. They noted that these differences might have affected the type of outcomes reported and the outcome results, although no statistical tests of homogeneity were presented in this study.
Results of the review The probability of relapse was:
0.0319 at 1 year, 0.1137 at 2 years, 0.1064 at 3 years, 0.0720 between years 4 and 5, and 0.0221 after 5 years without IM-MS RT; and
0.0174 at 1 year, 0.0644 at 2 years, 0.0625 at 3 years, 0.0521 between years 4 and 5, and 0.0173 after 5 years with IM-MS RT.
The probability of death not related to breast cancer was:
0.0016 during the first 5 years, 0.0053 between years 5 and 10, 0.0084 between years 10 and 15, and 0.0105 after 15 years without IM-MS RT; and
0.0017 during the first 5 years, 0.0061 between years 5 and 10, 0.0101 between years 10 and 15, and 0.0131 after 15 years with IM-MS RT.
The probability of death related to breast cancer was:
0.35 during the first 2.5 years, 0.1 between 2.5 and 5 years, 0.05 between years 5 and 10, 0.035 between years 10 and 15, and 0.015 after 15 years when IM-MS RT was not administered; and
0.7 during the first 2.5 years, 0.225 between 2.5 and 5 years, 0.09 between years 5 and 10, 0.065 between years 10 and 15, and 0.025 after 15 years when IM-MS RT was administered.
Methods used to derive estimates of effectiveness The authors made assumptions in order to derive several estimates of effectiveness.
Estimates of effectiveness and key assumptions Due to lack of evidence, the authors assumed that the effectiveness of IM-MS RT in terms of both relapse and survival would be similar to that observed for general postoperative RT in breast cancer (see parameters reported under the 'Results of the Review' section).
Measure of benefits used in the economic analysis The summary measures of benefit used were the life-years gained (LYG) and the quality-adjusted life-years (QALYs). Survival curves were estimated from those for postoperative RT versus no RT, as reported in the meta-analysis (Early Breast Cancer Trialists' Collaborative Group 2000), while utilities to estimate QALYs were obtained from a published study (Tengs and Wallace 2000, see 'Other Publications of Related Interest' below for bibliographic details). The utilities for IM-MS RT were adjusted to reflect the negative impact of RT on quality of life. The health benefits were discounted at a rate of 3% and were reported for a 20-year timeframe.
Direct costs The direct costs included in the cost estimation appear to have been those of the health service. These included RT costs (only for the IM-MS RT group), hospital costs (such as length of stay, outpatient visits, operative time, emergency admission, wages, pharmaceutical agents, materials and travel costs) and follow-up community costs. The resource quantities were not reported separately from the costs since aggregated average costs were imputed for each cycle. The cost data were based on actual data obtained from the Leuven University Hospital and from a previous analysis of travel costs. The authors reported that they excluded adverse event-related costs and costs due to patient's time lost as they were considered to be included through the utility adjustments conducted for the estimation of QALYs (see 'Measure of Benefits used in the Economic Analysis'). Discounting was conducted at a rate of 3%. The price year was 2000. The costs reported appear to have been the average cost per patient for a 20-year time horizon.
Statistical analysis of costs No statistical analyses of the costs were reported.
Indirect Costs No indirect costs were estimated.
Currency Euros (EUR). The exchange rate was EUR 1 = $1 in 2000.
Sensitivity analysis One-way and multi-way sensitivity analyses were conducted to test for uncertainty related to variability in the effectiveness and cost data (i.e. costs of locoregional and/or distant progression, IM-MS, relapse and palliative episode, transition probabilities related to recurrence and mortality, and utility values) and methodological assumptions (i.e. discount rates). The authors stated that clinically useful ranges were considered for the variations in the parameters. Threshold analyses were also conducted.
Estimated benefits used in the economic analysis The number of LYG was 9.367 with IM-MS RT and 9.132 without IM-MS RT (the incremental LYG with IM-MS RT were 0.235).
The number of QALYs gained was 7.104 with IM-MS RT and 6.877 without IM-MS RT (the incremental QALYs gained with IM-MS RT were 0.228).
The authors reported that adverse events related to RT were accounted for in the quality of life adjustments conducted.
Cost results The cost was EUR 20,000 with IM-MS RT versus EUR 30,000 without IM-MS RT (a saving of EUR 10,000 in favour of IM-MS RT).
These costs did not include the costs related to adverse events and to time lost by the patient.
Synthesis of costs and benefits Incremental cost-effectiveness and cost-utility ratios were not estimated as IM-MS RT turned out to be the dominant strategy (i.e. more effective at a lower cost) when compared with no IM-MS RT.
Average cost-effectiveness and cost-utility ratios were estimated as the cost per unit of health outcome obtained with each alternative.
The average cost-effectiveness ratios were EUR 2,164 per LYG with IM-MS RT versus EUR 3,276 per LYG with no IM-MS RT.
The average cost-utility ratios were EUR 2,853 per QALY gained with IM-MS RT versus EUR 4,350 per QALY gained with no IM-MS RT.
The results of the sensitivity analyses showed that IM-MS RT was the dominant strategy for the whole range of tested parameter values and for realistic variations in the costs of IM-MS RT, the costs of relapse and the utility values.
Authors' conclusions Internal mammary and medial supraclavicular lymph node region radiotherapy (IM-MS RT) was a cost-effective and dominant strategy as it was more effective and less costly in comparison with no radiotherapy (RT).
CRD COMMENTARY - Selection of comparators No IM-MS RT was used as the comparator since there is no consensus about the use of IM-MS RT across industrialised countries, with some of them, but not all, using IM-MS RT systematically.
Validity of estimate of measure of effectiveness A systematic review of the literature does not appear to have been conducted. Although data were obtained from a meta-analysis of randomised controlled trials and from a clinical trial, the methods used to find, select and combine the studies were not reported. Therefore, it was difficult to assess the validity of the included studies, and there might have been relevant studies that were not identified and included. This could have introduced bias into the effectiveness results. In addition, the authors reported important variations across the studies included in the meta-analysis in terms of RT and study patients.
The lack of data meant that the effectiveness results depended greatly on the assumption that the effectiveness of IM-MS RT would be similar to those for general postoperative RT. Extensive sensitivity analyses were conducted to test the robustness of the results when this assumption and other effectiveness parameters were modified. There are several factors that may influence the effectiveness of IM-MS RT which were not considered in the model, such as whether women were or were not menopausal, the type of treatment received, and the type of surgery undergone. This introduces uncertainty into the reliability of the results.
Validity of estimate of measure of benefit The estimation of health benefits was modelled. Appropriate methods appear to have been used to estimate the LYG and QALYs. Moreover, as the authors reported, the internal validity of the model was tested by comparing estimated survival curves obtained through the model with the actual survival curves observed from clinical trials.
Validity of estimate of costs Although the authors reported that a societal perspective had been adopted, the indirect costs related to productivity losses were not estimated. The actual perspective therefore appears to have been that of the health service. The resource quantities were not reported separately from the costs, which may limit the transferability of the results to other settings. Extensive sensitivity analyses were conducted to test for variations in the cost data. The costs were appropriately discounted (as a time horizon longer than 2 years was considered for the cost estimation) and the price year was reported.
Other issues The results obtained were compared with those from other economic evaluations assessing postoperative RT for early breast cancer patients. Great variation was found, which the authors explained may have been due to relevant methodological and data differences across studies. The issue of the generalisability of the results to other setting was not directly addressed. The authors do not appear to have presented the results selectively and their conclusions reflected the general aims of the study.
Implications of the study Given the limitations presented by this study (see 'CRD Commentary' above) and the differences in the findings across the available economic evaluations, it would be desirable to conduct a further economic evaluation once the results of the clinical trial conducted by the European Organisation for Research and Treatment of Cancer (which assessed specifically the use of IM-MS RT postoperatively for early breast cancer patients) become available. This may help reduce the uncertainty surrounding the cost-effectiveness of postoperative IM-MS RT for breast cancer patients.
Bibliographic details Lievens Y, Kesteloot K, van den Bogaert W. Economic consequence of local control with radiotherapy: cost analysis of internal mammary and medial supraclavicular lymph node radiotherapy in breast cancer. International Journal of Radiation Oncology, Biology, Physics 2005; 63(4): 1122-1131 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.
Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for breast cancer: an overview of the randomised trials. Lancet 2000;533:1757-70.
Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. New Engl J Med 1997;337:949-55.
Tengs TO, Wallace A. One thousand health-related quality-of-life estimates. Med Care 2000;38:583-637.
Indexing Status Subject indexing assigned by NLM MeSH Breast Neoplasms /radiotherapy; Costs and Cost Analysis; Female; Humans; Lymphatic Irradiation /economics /methods; Markov Chains; Models, Economic AccessionNumber 22006006103 Date bibliographic record published 30/04/2007 Date abstract record published 30/04/2007 |
|
|
|