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Markov-modeling for the administration of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-line chemotherapy with epithelial ovarian carcinoma |
Hartmann M, Fedders M, Schneider A, Kath R, Camara O, Oelschlager H |
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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 investigated four treatment options for women with epithelial ovarian carcinoma:
first-line chemotherapy with carboplatin plus paclitaxel followed by second-line chemotherapy with liposomal doxorubicin;
first-line chemotherapy with carboplatin plus paclitaxel followed by second-line chemotherapy with topotecan;
first-line chemotherapy with carboplatin monotherapy followed by second-line chemotherapy with topotecan; and
first-line chemotherapy with carboplatin monotherapy followed by second-line chemotherapy with liposomal doxorubicin. Economic study type Cost-effectiveness analysis Study population The study population comprised a hypothetical cohort of women with epithelial ovarian carcinoma, FIGO Stage I-IV. Setting The study setting was secondary care. The economic study was carried out in Germany. Dates to which data relate The effectiveness data were derived from studies published between January 1995 and June 2003. The resource use data were derived in the year 2002. The price year was 2002. Modelling A decision analytic Markov model was developed in order to assess the costs and outcomes of different treatment options for epithelial ovarian carcinoma. The patients were followed-up for a maximum of 5 years. Study designs and other criteria for inclusion in the review The clinical and epidemiological data used in the economic evaluation were the probabilities of: therapy discontinuation; reduced response with therapy discontinuation; complete response with treatment; death; erythropoietin administration; neutropenia; neuropathy; progression-free survival; hand and foot syndrome; cancer progression; and response. Sources searched to identify primary studies The majority of the clinical and epidemiological data were derived from a systematic review of phase II and phase III trials. The probabilities of reduced response given therapy discontinuation were derived from expert opinion. Methods used to derive estimates of effectiveness The authors reported that a systematic review of the literature was conducted using MEDLINE, EMBASE, CancerLit and the Cochrane Controlled Trials Register. As further sources of data, the summaries of scientific conference contributions were evaluated. The main aim of the review was to identify papers on first-line treatment of epithelial ovarian carcinoma with paclitaxel and platinum analogues. Excluded from the review were studies involving intraperitoneal or oral administration of chemotherapeutics or high-dosage chemotherapy. Furthermore, studies that did not contain survival data and for which therapeutic success was recorded entirely in the form of rates of responsiveness, without declaration of survival times, were excluded from the review. In the first instance the literature review focused on meta-analyses and randomised phase III studies. If less than two phase III studies were identified, the search was extended to phase II studies. The selection criteria for phase II studies were a study sample of at least 40 patients, the inclusion of demographic data, a prospective design and multicentricity. Measure of benefits used in the economic analysis The measure of benefits used was the years of life saved (YOLS). Since benefits could be generated over a 5-year period, discounting was relevant and was appropriately performed at an annual rate of 3%. Direct costs The direct costs included in the economic analysis were those to the health care provider. These covered medication and chemotherapy costs; the direct and indirect costs of chemotherapy administration; outpatient visits; inpatient costs; and the costs of partial inpatient treatment. Both resource use and cost data were derived from the hospital pharmacy and the finance department of a university hospital in Jena, Germany. The price year was 2002. The study reported the average costs. Since the costs could be incurred over a 5-year period, discounting was relevant and was appropriately performed at an annual rate of 5%. Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic). Indirect Costs Productivity costs were not included. Sensitivity analysis The authors did not perform any sensitivity analyses to test the effects of uncertainty in the model and/or its parameters on the results. Estimated benefits used in the economic analysis The YOLS were:
2.55 for carboplatin followed by topotecan, 2.70 for carboplatin followed by liposomal doxorubicin, 2.60 for carboplatin/paclitaxel followed by topotecan, and 2.64 for carboplatin/paclitaxel followed by liposomal doxorubicin. Cost results The total cost per patient was:
EUR 20,123.91 for carboplatin followed by topotecan, EUR 22,336.57 for carboplatin followed by liposomal doxorubicin, EUR 29,820.64 for carboplatin/paclitaxel followed by topotecan, and EUR 31,550.47 for carboplatin/paclitaxel followed by liposomal doxorubicin. Synthesis of costs and benefits The costs and benefits were combined using an average cost-effectiveness ratio (i.e. the cost per YOLS). The cost per YOLS was:
EUR 7,891.73 for carboplatin followed by topotecan, EUR 8,270.35 for carboplatin followed by liposomal doxorubicin, EUR 11,453.62 for carboplatin/paclitaxel followed by topotecan, and EUR 11,958.35 for carboplatin/paclitaxel followed by liposomal doxorubicin. Authors' conclusions The authors concluded that, based on a cost-effectiveness threshold of EUR 45,000 per year of life saved (YOLS), the four treatment options consisting of first-line carboplatin were cost-effective. CRD COMMENTARY - Selection of comparators A justification was given for the comparator used, namely that first-line therapy with carboplatin and paclitaxel following a radical operation is considered standard. Validity of estimate of measure of effectiveness The majority of the model parameters were derived from published research, although some were derived from expert opinion. It was unclear whether any synthesis of the study results took place. The authors reported in detail the search methods and inclusion criteria used to identify relevant studies for the literature review. In addition, they provided a justification for their selection. The epidemiological and clinical data used in the model were derived, generally, from phase II and III trials and meta-analyses of these, thus the effectiveness data will have high internal validity. Validity of estimate of measure of benefit The estimation of health benefit (YOLS) was derived appropriately using a Markov model. Since benefits could be generated over a 5-year period, they were appropriately discounted. Validity of estimate of costs The analysis of the costs was performed from the perspective of the health care provider paying for the treatment. Given this perspective, it appears that all the relevant categories of costs and all major costs were included in the analysis. The cost data were derived from the authors’ settings. It was unclear whether charges were used to proxy prices. Since the costs could be incurred over a 5-year period, discounting was appropriately performed. No statistical or sensitivity analysis of the costs was performed. The authors reported the price year, which will aid any future inflation exercises. Other issues The authors reported that no published analysis of the cost-effectiveness of the paclitaxel/platinum analogue combination versus carboplatin monotherapy was available at the time of the study. The issue of generalisability to other settings was not addressed. The authors do not appear to have reported their results selectively. However, they did not perform an incremental cost-effectiveness analysis and, as a result, cannot claim that all four treatment strategies were cost-effective, as in head-to-head comparisons some might have incremental cost-effectiveness ratios in excess of EUR 45,000. The authors acknowledged a number of further limitations to their study. First, the Markov model did not take into account prognostic factors such as genetic disposition, age, post-operative tumour remnants and any possible toxicities, nor quality of life. Second, rarely occurring side-effects such as allergic reactions or neutropenic fever were not included in the model. Implications of the study The reader should treat the authors’ conclusions with caution as the authors did not provide a head-to-head comparison of the four treatment options and, as a result, cannot claim that all four were cost-effective. Bibliographic details Hartmann M, Fedders M, Schneider A, Kath R, Camara O, Oelschlager H. Markov-modeling for the administration of platinum analogues and paclitaxel as first-line chemotherapy as well as topotecan and liposomal doxorubicin as second-line chemotherapy with epithelial ovarian carcinoma. Journal of Cancer Research and Clinical Oncology 2007; 133(9): 619-625 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.
Bennett CL, Golub R, Watrs TM, et al. Economic analyses of phase II cooperative cancer group clinical trials: are they feasible? Cancer Invest 1997;115:227-33.
Ortega A, Dranitsaris G, Sturgeon J, et al. Cost-utility analysis of paclitaxel in combination with cisplatin for patients with advanced ovarian cancer. Gynecol Oncol 1997;66:454-63. Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Combined Chemotherapy Protocols /economics /therapeutic use; Cost-Benefit Analysis; Doxorubicin /administration & Female; Humans; Markov Chains; Neoplasms, Glandular and Epithelial /drug therapy /economics; Ovarian Neoplasms /drug therapy /economics; Paclitaxel /administration & Platinum Compounds /administration & Topotecan /administration & dosage /economics; dosage /economics; dosage /economics; dosage /economics AccessionNumber 22007001625 Date bibliographic record published 15/08/2007 Date abstract record published 09/08/2008 |
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