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Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer |
Berthelot J M, Will B P, Evans W K, Coyle D, Earle C C, Bordeleau L |
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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 Nine chemotherapy regimens to palliate cancer-related symptoms and modestly improve survival were considered:
vindesine plus cisplatin (VDS+P),
etoposide plus cisplatin (VP-16+P),
vinblastine plus cisplatin (VLB+P),
vinorelbine plus cisplatin (NVB+P),
paclitaxel 135 mg/m2 plus cisplatin (T+P 135 mg/m2),
paclitaxel 200 mg/m2 plus cisplatin (T+P 200 mg/m2),
paclitaxel 250 mg/m2 plus cisplatin (T+P 250 mg/m2),
gemcitabine (GEM), and
vinorelbine alone (NVB).
Economic study type Cost-effectiveness and cost-utility analyses.
Study population The study population comprised hypothetical patients suffering from advanced NSCLC.
Setting The setting was a hospital. The economic study was carried out in Canada.
Dates to which data relate The effectiveness evidence and resource used data were gathered between 1993 and 2000. The price year was 1995.
Source of effectiveness data The effectiveness data were derived from a review of published studies.
Modelling The authors used the Population Health Model (POHEM) in combination with the lung cancer submodel. The model integrated data on risk factors for major diseases affecting Canadians (disease onset and outcomes, health care utilisation and direct health care costs). Then, by using a hypothetical population of patients, the model generated the cost and effectiveness data for the diseases.
Outcomes assessed in the review The outcomes assessed in the review were the survival rates of the nine chemotherapy regimens and BSC, and some data regarding the treatment regimens, such as the number of cycles.
Study designs and other criteria for inclusion in the review 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 The effectiveness estimates used in the analysis were derived from approximately ten primary studies.
Methods of combining primary studies The method used to combine the primary studies was not reported. However, some estimates were not combined, given that, for some values, only a single study was used.
Investigation of differences between primary studies Results of the review The average survival was 0.49 years for BSC, 0.76 years for VDS+P, VLB+P and VP-16+P, 0.77 years for NVB, 0.90 years for GEM, 0.93 years for NVB+P, and 1.06 years for T+P 135 mg/m2, T+P 200 mg/m2 and T+P 250 mg/m2.
The average actual number of cycles administered was 3 with VDS+P, VLBN+P, NVB and NVB+P, 4 with VP-16+P, 3.3 with GEM, 5.3 with T+P 200 mg/m2 and T+P 250 mg/m2, and 5.6 with T+P 135 mg/m2.
The other outcomes were not reported.
Methods used to derive estimates of effectiveness The utility values associated with the various chemotherapy regimens were derived from the opinions of 24 oncologists with expertise in the medical, surgical and radiation treatment of lung cancer. The experts were given different clinical scenarios describing the toxic effects, inconveniences and potential benefits of the nine treatments and BSC. The utilities were estimated on the basis of a visual analogue scale ranging from 0 (death) to 1 (perfect health). The mean utility estimates for each regimen was selected. The utility value for VDS+P was not calculated because this regime was rarely used in Canada.
Estimates of effectiveness and key assumptions The utility values were 0.53 for BSC, 0.52 for VLB+P, 0.60 for NVB and NVB+P, 0.65 for GEM, 0.55 for VP-16+P, and 0.63 for T+P 135 mg/m2, T+P 200 mg/m2 and T+P 250 mg/m2.
Measure of benefits used in the economic analysis The benefit measures in the analysis were the number of life-years saved and the quality-adjusted life-years (QALYs). The utility values used to calculate the QALYs were based on oncologists' preferences.
Direct costs The authors stated that discounting was not conducted, and it was not relevant because the costs were occurred within 2 years of diagnosis. The costs and the quantities were not reported separately. The costs measured were for chemotherapy and BSC. The chemotherapy costs were for the drugs, their preparation and administration, inpatient and outpatient facilities, and the treatment of treatment-related toxic effects. The BSC costs were for palliative radiotherapy, the antibiotics used to treat infections, nutritional support, and other supportive care measures as appropriate. The length of hospital stay was considered a crucial variable. The cost/quantity boundary adopted was that of the health care payer. The quantities and the costs were estimated from published studies, the POHEM model, and actual data provided by the Ottawa Regional Cancer Centre. The resource used data were gathered between 1993 and 2000. The price year was 1995.
Statistical analysis of costs No statistical analysis of the costs was reported.
Indirect Costs The indirect costs were not included.
Sensitivity analysis Sensitivity analyses were undertaken to investigate the robustness of the analysis. The type of analyses conducted was not specified. The survival gains were reduced by 25 and 50%, while the number of days of terminal care hospitalisation was set equal to 23 for both the chemotherapy regimens and BSC. The authors did not explicitly state the justification for the chosen ranges.
Estimated benefits used in the economic analysis The survival rate was equal to that calculated in the effectiveness analysis. The number of QALYs associated with each regimen was not reported, but could be easily calculated from the data provided in the study.
Cost results The length of stay was equal to 23 days with BSC and 17 days for all the chemotherapy regimens. The average cost per case was Can$25,643 for BSC, Can$30,387 for VDS+P, Can$24,828 for VLB+P, Can$26,184 for NVB, Can$28,463 for GEM, Can$27,446 for NVB+P, Can$27,654 for VP-16+P, Can$34,488 for T+P 135 mg/m2, Can$30,019 for T+P 200 mg/m2, and Can$41,178 for T+P 250 mg/m2.
Synthesis of costs and benefits Incremental cost-effectiveness and cost-utility analyses were performed to combine the costs and benefits of each different chemotherapy regimen. When each single chemotherapy regimen was compared with BSC (but not with the others), the VBL+P-based treatment was dominant both with respect to the cost per life-year saved and the QALYs gained (lower costs and higher effectiveness). When the interventions were compared with each other (including BSC), a ranking was determined on the basis of alternative threshold values (Can$5,00, Can$10,000, Can$25,000, Can$50,000, Can$75,000, and Can$100,000). The preferred therapy in the ranking represented the strategy with a cost lower than the threshold value and with the maximum survival in comparison with the other regimens. With respect to the cost per life-year saved, the preferred option was NVB+P at the common thresholds of Can$25,000 and Can$50,000. With respect to the QALYs gained, the preferred option was GEM at the threshold of Can$50,000 and NVB+P at the threshold of Can$25,000. VLB+P was the preferred strategy for lower thresholds, while for higher thresholds, T+P 135 mg/m2 was selected in both QALY and life-year settings. The sensitivity analyses indicated that the results were fairly robust to different assumptions.
Authors' conclusions The analysis has provided "additional support for the abandonment of BSC (best supportive care) as a standard care for metastatic NSCLC (non-small-cell lung cancer)". In addition, the choice of the most cost-effective treatment has to be made on the basis of the values (threshold) that policy maker's attribute to life-years saved or quality-adjusted life-years (QALYs) gained.
CRD COMMENTARY - Selection of comparators The selection of the comparators was clear. The most common chemotherapy regimens were included in the study. These were compared with BSC, which is considered to be the standard care for patients with advanced NSCLC. You should consider whether they are widely used in your own setting.
Validity of estimate of measure of effectiveness The estimates of effectiveness were derived from published studies. However, a systematic review of the literature was not undertaken and estimates from the primary studies were not combined. The search methods and the criteria used to ensure the validity of the primary studies were not reported. In addition, the authors did not consider the impact of differences between the primary studies when estimating the effectiveness measures.
Validity of estimate of measure of benefit The estimation of benefits was obtained from the effectiveness analysis (survival) and from the opinions of experts (QALYs). However, the values used to assess the utility were derived from the physicians' preferences rather than the patients'. The preferences of physicians are a proxy for those of the patient, and consequently, may not give a realistic indication of the patients' preferences.
Validity of estimate of costs The estimation of the costs was obtained from different sources (actual data and published studies). It appears that all the categories of costs relevant to the perspective adopted have been included in the analysis. However, the costs and the quantities were not reported separately, and statistical analyses on the resources were not conducted. It would have been interesting to have adopted a societal perspective and included the indirect costs, which appear to be relevant in the treatment of metastatic lung cancer patients.
Other issues The robustness of the results was addressed by performing sensitivity analyses on several parameters. The authors acknowledged some limitations of the study. These were mainly related to the source of the clinical data, which was based on a cohort of hypothetical patients, drawn from the general population. Both the effectiveness and cost analyses were mainly derived from Canadian data, and therefore, the generalisability of the study results to other settings may be limited. The authors did not compare their findings with those of other studies. However, the conclusions that they have drawn from the study appear justified within the caveats outlined.
Implications of the study The study results suggest that current practice in Canada should change to adopt chemotherapy regimens on an ambulatory basis for patients suffering from advanced NSCLC.
Bibliographic details Berthelot J M, Will B P, Evans W K, Coyle D, Earle C C, Bordeleau L. Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer. Journal of the National Cancer Institute 2000; 92(16): 1321-1329 Indexing Status Subject indexing assigned by NLM MeSH Algorithms; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols /economics /therapeutic use; Carcinoma, Non-Small-Cell Lung /drug therapy /economics /secondary; Cost-Benefit Analysis; Decision Trees; Humans; Lung Neoplasms /drug therapy /economics /pathology; Palliative Care /economics /methods; Quality of Life; Quality-Adjusted Life Years; Survival Analysis; Treatment Outcome; United States; Value of Life AccessionNumber 22000001368 Date bibliographic record published 28/02/2003 Date abstract record published 28/02/2003 |
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