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Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy |
Weaver C H, Buckner C D, Curtis L H, Bajwa K, Weinfurt K P, Wilson-Relyea B J, Schulman K A |
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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 Three drug regimens to mobilise CD34+ cells after myelosuppressive chemotherapy (MC) were studied. The three regimens were filgrastim alone, sargramostim alone, and sequential sargramostim and filgrastim.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with multiple myeloma, malignant lymphoma or breast cancer. Further details were not reported in the paper.
Setting The setting was secondary care. The economic study was carried out in the USA.
Dates to which data relate The effectiveness and resource use data were collected between September 1997 and July 1998. The costs used in the study referred to 1998 prices.
Source of effectiveness data The evidence for the final outcomes was derived from a single study.
Link between effectiveness and cost data The costing was undertaken on the same patient sample as that used in the effectiveness study. Resource use was estimated rather than observed.
Study sample It was not reported whether the sample size was determined in the planning phase of the study to assure a certain power. There were also no details of whether power calculations were performed retrospectively, based on the existing sample size. The method used to select the sample was not reported. Only limited details were reported in this paper because a parent clinical trial provided the effectiveness evidence for this economic analysis (see Other Publications of Related Interest). The trial recruited 158 patients. Of these, 51 were in the filgrastim arm, 54 in the sargramostim arm, and 53 in the sargramostim-filgrastim arm. The authors reported that 2 patients from the sargramostim arm were excluded from the analysis because they received the wrong growth factor regimen. They also reported that another 6 patients did not have peripheral blood stem cells (PBSCs) harvested because of either early treatment-related death or poor clinical condition, but data collected for these 6 patients prior to dropout were included in the economic analysis. There was no report of any patients refusing to participate in the trial.
Study design A randomised controlled trial was used. Further details of the study design were reported elsewhere (see Other Publications of Related Interest).
Analysis of effectiveness From the details given in this paper it was unclear whether the analysis of the clinical study was conducted on an intention to treat basis or for treatment completers only. The primary health outcomes were the rate of recovery of neutrophil count, number of CD34+ cells/kg per apheresis procedure, and the number of days of growth factor treatment. The authors reported that there were no statistically significant differences in the baseline characteristics of the patients included in the economic analysis. Further details of the analysis of effectiveness were provided elsewhere (see Other Publications of Related Interest).
Effectiveness results Patients who received filgrastim had a faster recovery of absolute neutrophil count to >/= 0.5 x 10^9/L (median 11 days) than those who received sargramostim (median 14 days), (p=0.0001).
Patients who received filgrastim yielded more CD34+ cells (median 7.1 x 10^6/kg per apheresis) than those who received sargramostim (median 2.0 x 10^6/kg per apheresis), (p=0.0001). They also achieved >/= 2.5 x 10^6 (94% versus 78%; p=0.021) and >/= 5 x 10^6 (88% versus 53%; p=0.001) CD34+ cells/kg with fewer apheresis procedures (median 2 versus 3; p=0.002) and fewer days of growth factor treatment (median 12 versus 14; p=0.0001).
Clinical conclusions The authors reported that both filgrastim alone and sequential administration of sargramostim and filgrastim were superior to sargramostim alone for optimal mobilisation of CD34+ cells, requiring fewer apheresis procedures and fewer days of growth factor administration.
Measure of benefits used in the economic analysis No summary measure of benefits was used in this study. In effect, a cost-consequences analysis was performed.
Direct costs The direct hospital costs were included in the analysis. These were derived from different sources. Estimated resource quantities were reported separately from the costs. The authors reported that the cost of a hospital inpatient day was derived using the mean costs calculated from one university hospital's cost accounting system for 52 patients undergoing PBSC transplantation. The costs of blood products were derived from the average acquisition costs per unit plus the administration costs of transfusion. The antibiotic costs were calculated according to the average daily dose requirements for a 70 kg person with normal renal function, using the average wholesale price for the generic product plus administration costs. The growth factor administration costs were based on the average wholesale price of 6 microg/kg per day filgrastim and 250 microg/kg per day sargramostim. The cost of sequential sargramostim-filgrastim was an average of the administration costs of filgrastim alone and sargramostim alone. The costs of myelosuppressive therapy were based on the average wholesale price of the specified regimen plus the costs of administration, which were obtained from the Medicare Fee Schedule. The authors also reported that the recommended doses and standard frequencies were based on each patient's body surface. Discounting was not relevant because the time horizon of the study was less than 2 years. The average costs were reported in the study, and all price data referred to 1998.
Statistical analysis of costs No statistical analysis of the costs was undertaken.
Indirect Costs No indirect costs were included in the study.
Sensitivity analysis One-way simple sensitivity analyses were performed. The effect of doubling and halving the cost of hospital stay was examined, as was the effect of increasing the cost of apheresis by the same factors. The area of uncertainty investigated appears to have been that affecting the generalisability of the results. No details of the methods or rationale used to determine the ranges tested were given.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The total cost per patient was $20,193 for the sargramostim group, compared with $14,764 for the filgrastim group, (p=0.002) and $15,309 for the group that received sequential sargramostim and filgrastim, (p=0.007).
After controlling for age and prior chemotherapy, the adjusted total mean cost was $21,347 for the sargramostim group, compared with $15,406 for the filgrastim group, (p=0.001) and $15,975 for the group that received the sequential regimen, (p=0.002).
The costs of adverse effects or knock-on costs were not reported.
Synthesis of costs and benefits The costs and benefits were not combined. Filgrastim alone and sequential sargramostim and filgrastim were less costly than sargramostim alone after myelosuppressive chemotherapy, and were therapeutically more beneficial.
CRD COMMENTARY - Selection of comparators This study followed on from a clinical trial comparing the effectiveness of the three drug regimens (see Other Publications of Related Interest). The study compared three regimens, although no 'do nothing' option was included. You should decide if these are widely used health technologies in your own setting.
Validity of estimate of measure of effectiveness The analysis was based on a randomised controlled trial, which was appropriate for the study question. It is not possible to comment on whether the study sample was representative of the study population, as the paper did not report full details of the study population and sample. Further details were reported elsewhere (see Other Publications of Related Interest). The patient groups were shown to be comparable at analysis. The analysis of effectiveness appears to have been handled credibly.
Validity of estimate of measure of benefit The authors did not derive a summary measure of health benefit. The analysis was, in effect, a cost-consequences study.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted, and all relevant costs, appear to have been included in the analysis. The costs were reported separately from the quantities. However, no indirect costs (such as lost productivity) were included in the analysis. Resource use was derived from a single study, while the costs were taken from the authors' setting. The authors did not report any statistical or other analysis of the quantities or prices. Charges were not used to proxy prices, except in the case of the cost of administrating myelosuppressive chemotherapy, which was obtained from the Medicare Fee Schedule. The date to which the prices referred was reported.
Other issues The authors appear to have made appropriate comparisons of their findings with those from other studies, although comparability is hampered by variations in methods and patient samples. The issue of generalisability to other settings was not addressed. However, the fact that the resources and costs were reported separately enhances the generalisability of the study. The authors do not appear to have presented their results selectively, and their conclusions appear to reflect the scope of the analysis. The authors reported two further limitations of their study. First, the resource costs were estimated and not directly observed. Second, they suggested that, because the cost estimates were based on data gathered as part of a clinical trial, protocol-induced costs might have exerted an upward bias on the cost estimates.
Implications of the study The authors suggested that the favourable findings from the filgrastim and the sequential sargramostim-filgrastim arms of the trial might indicate that the delayed administration of filgrastim may be crucial to the mobilisation of stem cells. The authors implied that this is an area worthy of future research.
Source of funding Supported in part by the Community Cancer Research Foundation, Seattle (WA), USA, and the Joseph Steiner Foundation, Bern, Switzerland.
Bibliographic details Weaver C H, Buckner C D, Curtis L H, Bajwa K, Weinfurt K P, Wilson-Relyea B J, Schulman K A. Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy. Bone Marrow Transplantation 2002; 29(2): 159-164 Other publications of related interest Weaver CH, Schulman KA, Wilson-Reylea B, et al. Randomized trial of filgrastim, sargramostim, or sequential sargramostim and filgrastim after myelosuppressive chemotherapy for the harvesting of peripheral-blood stem cells. Journal of Clinical Oncology 2000;18:43-53.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Antineoplastic Agents /economics /therapeutic use; Breast Neoplasms /therapy; Costs and Cost Analysis; Drug Costs /statistics & Drug Therapy, Combination; Female; Filgrastim; Granulocyte Colony-Stimulating Factor /economics /therapeutic use; Granulocyte-Macrophage Colony-Stimulating Factor /economics /therapeutic use; Health Care Costs /statistics & Humans; Immunosuppressive Agents /economics /therapeutic use; Lymphoma /therapy; Male; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; numerical data; numerical data AccessionNumber 22002000395 Date bibliographic record published 28/02/2005 Date abstract record published 28/02/2005 |
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