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Cost-effectiveness of adding granulocyte colony-stimulating factor to primary prophylaxis with antibiotics in small-cell lung cancer |
Timmer-Bonte J N, Adang E M, Smit H J, Biesma B, Wilschut F A, Bootsma G P, de Boo T M, Tjan-Heijnen V C |
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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 study compared the use of antibiotic prophylaxis in combination with granulocyte colony-stimulating factor (GCSF) against the use of antibiotic prophylaxis on in its own in small-cell lung cancer patients at risk of chemotherapy-induced febrile neutropenia (FN). Economic study type Cost-effectiveness analysis Study population The study population comprised small-cell lung cancer patients at 25% risk of suffering FN. Setting The study setting was secondary care. The economic study was undertaken in the Netherlands. Dates to which data relate The authors did not report the dates to which the effectiveness and resource use data related to. The price year was 2002. Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample that provided the effectiveness data. Study sample The authors provided very few details of the clinical trial used to derive the effectiveness and resource use data, as the methods of the trial had already been published (Timmer-Bonte et al. 2005, see 'Other Publications of Related Interest' for bibliographic details). Consequently, only the methods reported in the current article are reported here. The study sample comprised 85 patients in the antibiotics group and 90 patients in the antibiotics plus GCSF group. Study design The study was a multi-centre, phase III randomised controlled trial (RCT). The authors reported no more details of the study design (e.g. they did not report either the duration of the study or the loss to follow-up). Analysis of effectiveness The primary outcome measures were survival and the cases of FN prevented after the first cycle of chemotherapy. The secondary outcome measures were the cases of FN prevented after the entire chemotherapy treatment period. The analysis appears to have been conducted on an intention-to-treat basis. The patient groups were found to be similar in terms of characteristics such as age, prior treatment and extent of disease. Effectiveness results The authors reported that the clinical trial had shown that prophylaxis in combination with GCSF had no impact on survival.
During the first cycle of chemotherapy, 20 patients (24%) in the antibiotics group suffered FN, compared with 9 patients (10%) in the antibiotics plus GCSF group.
After the entire chemotherapy treatment, 27 patients (32%) in the antibiotics group suffered FN, compared with 16 patients (18%) in the antibiotics plus GCSF group.
The authors did not report the results of any statistical analyses that would show if differences between the groups were statistically significant. Clinical conclusions The authors reported that prophylaxis in combination with GCSF had no impact on survival in comparison with antibiotic prophylaxis alone. Measure of benefits used in the economic analysis The measures of benefits used were the cases of FN prevented after the first cycle of chemotherapy and after the entire chemotherapy treatment period. Direct costs The direct costs included in the analysis were those to the health care system. They included the costs of the chemotherapy, antibiotic prophylaxis, prophylactic GCSF, delivered transfusions, hospitalisations due to FN (which included hospitalisation, general practitioner visits, emergency room and outpatient visits, therapeutic antibiotics, laboratory investigations and diagnostic tests) and all other hospitalisations. The resource use data were collected alongside the clinical trial. The unit costs were derived from different sources, including the Dutch Health Care Insurance Board, and the National Health Tariffs Authority. All prices were adjusted to 2002 prices using the health care component of the price index. The costs appear to have been incurred during less than one year, consequently discounting was not relevant and was appropriately not performed. The average costs were reported. Statistical analysis of costs Uncertainty around the mean incremental cost-effectiveness ratio (ICER) was presented using 95% confidence intervals (CIs), which were derived using Fieller's method and presented graphically using a cost-effectiveness acceptability curve. Indirect Costs The productivity costs were not included. Sensitivity analysis A series of threshold analyses were performed per variable to determine at what point both strategies would be as costly as each other. Threshold lines were generated by varying the risk of FN from 10 to 80% and the FN-related costs from EUR 1,000 to 35,000 at given prices of GCSF administration of EUR 250, 500, 1,000, 1,500 and 2,500 per cycle. Estimated benefits used in the economic analysis See the 'Effectiveness Results' section. Cost results During the first cycle of treatment, the mean total costs were EUR 2,130 (95% CI: 1,512 to 2,694) per patient in the antibiotic group and EUR 2,783 (95% CI: 2,359 to 3,208) in the antibiotics plus GCSF group. The mean difference in total costs amounted to EUR 681 (95% CI: -68 to 1,397).
During the entire treatment period, the mean total costs were EUR 4,564 (95% CI: 3,647 to 5,480) per patient in the antibiotic group and EUR 9,687 (95% CI: 8,872 to 10,502) in the antibiotics plus GCSF group. The mean difference in total costs amounted to EUR 5,123 (95% CI: 3,908 to 6,337). Synthesis of costs and benefits The costs and benefits were combined using an ICER (i.e. the additional cost per case of FN prevented). During the first cycle of treatment, the ICER when prophylaxis plus GCSF was compared with prophylaxis alone was EUR 50 (95% CI: -2 to 433) per percentage decrease in the probability of FN. During the entire chemotherapy treatment period, the ICER when prophylaxis plus GCSF was compared with prophylaxis alone was EUR 366 (95% CI: 165 to 4,815) per percentage decrease in the probability of FN.
The results of the threshold analysis demonstrated that, for the first cycle of treatment, the addition of GCSF was cost-saving if the probability of FN was more than 84%, the price of prophylactic GCSF was less than EUR 469 per patient, or the cost of an FN episode was greater than EUR 11,552. Authors' conclusions The authors concluded that the addition of granulocyte colony-stimulating factor (GCSF) to primary antibiotic prophylaxis did not result in cost-savings. In addition, they concluded that if policy makers were willing to pay EUR 240 for each percentage gain in effect, the addition of GCSF could be considered cost-effective. CRD COMMENTARY - Selection of comparators A justification was given for using treatment with prophylactic antibiotics as the comparator. It had been shown to reduce hospitalisation for FN by approximately 50%. You should decide if the comparator used represents current practice in your own settings. Validity of estimate of measure of effectiveness The analysis was based on a multi-centre, phase III RCT. This was appropriate for the study question as well-conducted RCTs are considered to be the 'gold' standard study design when comparing health care interventions. However, as this clinical trial, which was used to derive effectiveness, had already been published (Timmer-Bonte et al. 2005), the authors provided very few details on the methods used and how the data were analysed. Consequently, it is not possible to assess the degree of internal validity of the clinical study. Validity of estimate of measure of benefit Although the authors reported that a cost-minimisation analysis was undertaken, they combined the costs and benefits in the form of an ICER. For this, the measure of health benefit used was the number of cases of FN prevented after the first cycle of chemotherapy and after the entire chemotherapy treatment period. This measure of health benefit was derived directly from the results of the clinical trial. You should consider if this adequately captures the health outcomes of the intervention. Validity of estimate of costs The analysis of the costs was performed from the perspective of the health care system. It appears that all the relevant cost categories and all major relevant costs have been included in the analysis. Resource use was collected alongside the clinical trial. The unit costs were derived from different sources, including the Dutch Health Care Insurance Board and the National Health Tariffs Authority. The time period over which the costs were incurred was not reported, but it would appear that these costs were incurred during less than a year. If this is true, discounting was not relevant and the authors' decision not to discount the costs was appropriate. The price year was reported, which will assist any possible inflation exercises. The authors reported the total costs for each cost category together with their unit cost, which will make their results more generalisable. Other issues The authors compared their results with those from other studies that had found GCSF prophylaxis to be cost-saving, especially after FN thresholds of 20 to 25%. The authors addressed the issue of generalisability to other settings in their scenario and sensitivity analyses. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis. No limitations of the study were reported. Implications of the study The authors reported that the continued use of GCSF beyond the first chemotherapy cycle does not appear to be cost-effective. Source of funding Supported by a research grant from the Dutch Healthcare Insurance Board. Bibliographic details Timmer-Bonte J N, Adang E M, Smit H J, Biesma B, Wilschut F A, Bootsma G P, de Boo T M, Tjan-Heijnen V C. Cost-effectiveness of adding granulocyte colony-stimulating factor to primary prophylaxis with antibiotics in small-cell lung cancer. Journal of Clinical Oncology 2006; 24(19): 2991-2997 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.
Timmer-Bonte JN, de Boo TM, Smit HJ, et al. Prevention of chemotherapy-induced febrile neutropenia by prophylactic antibiotics plus or minus granulocyte colony-stimulating factor in small-cell lung cancer: a Dutch randomized phase III study. J Clin Oncol 2005;23:7974-84.
Lyman GH, Lyman CG, Sanderson RA, et al. Decision analysis of hematopoietic growth factor use in patients receiving cancer chemotherapy. J National Cancer Inst 1993;85:488-93.
Calhoun EA, Schumock GT, McKoy JM, et al. Granulocyte colony-stimulating factor for chemotherapy-induced neutropenia in patients with small cell lung cancer: the 40% rule revisited. Pharmacoeconomics 2005;23:767-75.
Lyman GH, Kuderer N, Greene J, et al. The economics of febrile neutropenia: implications for the use of colony-stimulating factors. Eur J Cancer 1998;34:1857-64. Indexing Status Subject indexing assigned by NLM MeSH Anti-Bacterial Agents /economics /therapeutic use; Antineoplastic Combined Chemotherapy Protocols /adverse effects /therapeutic use; Carcinoma, Non-Small-Cell Lung /drug therapy; Cost-Benefit Analysis; Female; Fever /chemically induced /economics /prevention & Granulocyte Colony-Stimulating Factor /economics /therapeutic use; Humans; Lung Neoplasms /drug therapy; Male; Middle Aged; Neutropenia /chemically induced /economics /prevention & Patient Selection; Prospective Studies; Risk Factors; control; control AccessionNumber 22006006545 Date bibliographic record published 02/10/2006 Date abstract record published 09/08/2008 |
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