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Cost-minimization analysis of CHOP, fludarabine and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin's lymphoma in the UK |
Sweetenham J, Hieke K, Kerrigan M, Howard P, Smartt P F, McIntyre A M, Townshend S |
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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 use of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP), fludarabine, and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin's lymphoma.
Economic study type Cost-effectiveness analysis.
Study population Patients with non-Hodgkin's lymphomas.
Setting Hospital. The study was carried out in the UK.
Dates to which data relate Effectiveness data on the use of CHOP were derived from the lymphoma database of the CRC Wessex Medical Oncology Unit, University of Southampton (371 patients with low-grade follicular lymphoma, presented between 1977 and 1997) and effectiveness data on the use of rituximab were derived from a UK phase II study which enrolled patients with recurrent follicular lymphomas from January 1997. Additional effectiveness data were collected from studies published between 1991 and 1998. Resource use data on CHOP and fludarabine were collected using a questionnaire completed by 20 physicians and resource use data on rituximab were derived from the phase II study mentioned above. Cost data were based on data from Southampton University Hospitals NHS Trust and the British National Formulary (March 1998). The price year was 1998.
Source of effectiveness data Effectiveness data were derived from a literature review.
Outcomes assessed in the review The review assessed the following outcomes: time to progression, progression free survival, response rate and duration, number and type of adverse events, number of outpatient attendance and inpatient stays for the administration of chemotherapy.
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 At least 11 studies were included in the review.
Methods of combining primary studies Investigation of differences between primary studies Results of the review Of the 116 patients receiving CHOP, responses were seen in 45% with a median time to progression of 6 months. There was no significant difference between CHOP, fludarabine, and rituximab in terms of response rates and response duration. Patients receiving fludarabine had received more prior courses of therapy than those treated with CHOP or rituximab. No significant differences were found between the number and type of adverse events in the cycles for both CHOP and fludarabine. Significant differences were found between all groups and the incidence of adverse events (p<0.001). The major differences seen in the adverse event profile were the absence of neutropenia and anaemia for patients receiving rituximab, compared with 42% and 44% of CHOP and 62% and 52% of fludarabine patients. There was an incidence of thrombocytopenia of less than 2% for patients receiving rituximab compared to 33% for CHOP and 58% for fludarabine patients. Other notable differences included the higher incidences of nausea and vomiting and other adverse events in the CHOP arm, and the higher incidence of other adverse events for patients receiving rituximab. Fludarabine patients required a total of 30 outpatient visits per patient in order to administer the drug. For CHOP, patients were required to attend for outpatient administration six times and for rituximab four outpatient attendances were required, therapy being completed in 22 days.
Measure of benefits used in the economic analysis The following measures of benefit were considered: time to progression, progression free survival, response rate and duration, number and type of adverse events, number of outpatient attendance and inpatient stays for the administration of chemotherapy. As such, this study was a cost-consequences analysis.
Direct costs Direct costs were evaluated up to 6 months and, hence, were not discounted. Quantities and costs were reported separately. Direct treatment costs included acquisition and administration costs associated with the regimens and treatment costs associated with drug-related adverse events. The quantity/cost boundary adopted was that of the health service. The estimation of quantities and costs was based on actual data. Unit cost data were based on data from Southampton University Hospitals NHS Trust and the British National Formulary (March 1998). The price year was 1998.
Statistical analysis of costs Sensitivity analysis A multi-sensitivity analysis was conducted by varying the cost of adverse events, including the cost of hospitalisation, drugs and blood transfusions, and varying the costs associated with the administration of the regimen (inpatient, outpatient, test) by +/- 20%.
Estimated benefits used in the economic analysis See the Effectiveness Results section above.
Cost results Costs for adverse events per patient were 109 for rituximab, 2,953 for fludarabine, and 5,049 for CHOP. Fludarabine was the most expensive therapy at 10,022 per course, followed by CHOP at 7,210 per course and rituximab at $6,080 per course. The sensitivity analysis generated ranges of 5,892-6,267 for rituximab, 5,975-8,445 for CHOP, and 8,917-11,126 for fludarabine.
Synthesis of costs and benefits Cost and benefit measures were not combined into a cost-effectiveness ratio.
Authors' conclusions Rituximab appeared to have a similar efficacy rate to CHOP and fludarabine, but had significantly fewer adverse events and a lower total cost per patient.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparator was clear. You, as a user of this database, should verify whether these health technologies are relevant to your setting.
Validity of estimate of measure of benefit Relevant measures of benefit were used. The authors did not, however, consider quality of life measures which would have been relevant. The effectiveness data have been derived from, what may have been, a non-systematic review of the literature. The internal validity of effectiveness estimates cannot, therefore, be fully assessed given the limited information provided about the literature review and the quality assessment of the primary studies. The authors noted the lack of effectiveness data on the use of CHOP in this situation. Some effectiveness data were derived from databases comprising a small number of patients. As noted by the authors, the data must also be interpreted with caution in view of the retrospective nature of the study, and the possible selection and reporting bias inherent in questionnaire-based studies.
Validity of estimate of costs Only direct costs incurred by the health service were included. Indirect costs, relating to lost productivity were not considered. Given that data for patients treated with chemotherapy were drawn from a different source to that for rituximab, there is a certain amount of uncertainty regarding the comparability of the data. Cost estimates were derived from local sources and have limited generalisability to other settings.
Other issues Adequate comparisons with other relevant studies were made. The generalisability of the results to other settings or countries was not discussed. The authors do not appear to have presented their results selectively. The study examined patients with non-Hodgkin's lymphomas and this was reflected in the authors' conclusions.
Implications of the study These data require confirmation in a prospective randomised study with formal assessment of cost-effectiveness.
Bibliographic details Sweetenham J, Hieke K, Kerrigan M, Howard P, Smartt P F, McIntyre A M, Townshend S. Cost-minimization analysis of CHOP, fludarabine and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin's lymphoma in the UK. British Journal of Haematology 1999; 106(1): 47-54 Other publications of related interest Armitage J O. Treatment of non Hodgkin's lymphoma. New England Journal of Medicine 1993;328(14):1023-30.
Indexing Status Subject indexing assigned by NLM MeSH Ambulatory Care; Antibodies, Monoclonal /administration & Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols /economics /therapeutic use; Costs and Cost Analysis; Cyclophosphamide /administration & Doxorubicin /administration & Humans; Length of Stay; Lymphoma, B-Cell /drug therapy /economics; Middle Aged; Prednisone /administration & Recurrence; Retrospective Studies; Rituximab; Vidarabine /administration & Vincristine /administration & derivatives /economics; dosage /adverse effects /analogs & dosage /adverse effects /economics; dosage /adverse effects /economics; dosage /adverse effects /economics; dosage /adverse effects /economics; dosage /adverse effects /economics AccessionNumber 21999001487 Date bibliographic record published 31/08/2000 Date abstract record published 31/08/2000 |
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