Cost effectiveness, quality-adjusted life-years and supportive care: recombinant human erythropoietin as a treatment of cancer-associated anaemia Cremieux P, Finkelstein S N, Berndt E R, Crawford J, Slavin M B 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 Recombinant human erythropoietin (epoetin) as supportive care treatment for anaemic patients with cancer undergoing chemotherapy. Type of intervention Supportive care; Treatment. Economic study type Cost-effectiveness analysis and cost-utility analysis. Study population Anaemic patients with cancer undergoing chemotherapy. Setting Secondary care. The economic study was carried out in the United States. Dates to which data relate Effectiveness and resource use data were derived from studies published between 1993 and 1998. 1997 prices were used. Source of effectiveness data The estimate for final outcomes was based on a synthesis of completed studies. Modelling A model was developed to examine the cost-effectiveness of epoetin compared with standard care. Outcomes assessed in the review Change in haemoglobin levels and quality of life (QoL) were the outcomes assessed in the review. Study designs and other criteria for inclusion in the review A placebo-controlled randomised clinical trial (RCT) and two large community-based trials were used as the main sources of effectiveness data. The eligibility criteria from these trials were similar and included: diagnoses of a nonmyeloid malignancy, presence of chronic anaemia, the administration of concomitant chemotherapy and life expectancy greater than 24 weeks. In each trial, a heterogeneous population of clinically anaemic patients with cancer Page: 1 / 5
and mixed tumour types was treated concomitantly with epoetin (or placebo, in the RCT) and given blood transfusions as required within parameters of standard care. 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 Three primary studies were included: one randomised controlled trial and two community-based clinical trials (CS-1 and CS-2 data sets). There were 290 patients in the phase III, randomised, double-blind, placebo-controlled trial as well as approximately 4,500 patients who were part of two separate non-blind, non-randomised, community-based clinical trials. Methods of combining primary studies Effectiveness measures and clinical assumptions were drawn from the RCT, CS-1 and CS-2 data sets. The frequency of the procedure or prevalence of the condition was derived from the RCT. Detailed salient characteristics of the data set from the above studies were reported. The Linear Analogue Scale Assessment (LASA) of overall quality of life, a generic health status measure, was self-administered by patients in the RCT at the beginning and end of the trial, using the protocol recommended in the literature. Investigation of differences between primary studies Differences between the primary studies in terms of the epoetin dose administration were reported and investigated in the sensitivity analyses. Results of the review At the end of the RCT the average change in haemoglobin level was 0.4g/dl for patients who received placebo and 2.1g/dl for patients who received epoetin, an average incremented gain over placebo of 1.7g/dl for patients who received epoetin. Expressed as cumulative haemoglobin gains this resulted in a cumulative effectiveness measure of 21 for epoetin and 3.2 for standard care. Quality of life effectiveness based on the quality of life change at the end of the study was -1.0mm for patients who received placebo and +8.3mm for patients who received epoetin. This results in an average incremental gain of 9.3mm for patients treated with epoetin. Measure of benefits used in the economic analysis Haemoglobin levels and quality adjusted life years (QALYs) were used as the outcome measures in the economic analysis. A model was developed to examine the cost-effectiveness of epoetin compared with standard care. The Linear Analogue Scale Assessment (LASA) of overall quality of life, a generic health status measure, was self-administered by patients in the RCT at the beginning and end of the trial, using the protocol recommended in the literature. Benefits were assumed to end with treatment. Direct costs Costs were not discounted due to the short (16 weeks) time frame of the study (costs were assumed to end with Page: 2 / 5
treatment and, therefore, discounting was not applied). Resource quantities and costs were reported separately. The cost of each medical procedure was estimated using published literature. The principal cost components were treatment duration, number of transfusions, epoetin, physicians' visits and treatment of epoetin non-respondents. The perspective adopted in the cost analysis was that of society. When cost assumptions gathered from the literature were not contemporaneous, the authors adjusted for inflation using the appropriate consumer price index. 1997 price data were used. The costs of adverse events for both treatment modalities were not included because of their infrequent occurrence. The cost analysis did not cover the costs of dynamic change in blood supply, immunosuppressive effects of transfusion and patient aversion to transfusion because of consensus on low relative magnitudes or lack of data. Indirect Costs Costs were not discounted due to the short (16 weeks) time frame of the study. Patients' own opportunity costs were included in the analysis. The perspective adopted in the cost analysis was that of society. 1997 price data were used. Because of lack of data, costs resulting from caregiver time were omitted. Currency US dollars ($). Sensitivity analysis A series of one-way sensitivity analyses was performed on plausible changes in underlying assumptions of the economic analysis. Estimated benefits used in the economic analysis The effectiveness of the epoetin arm of the RCT study, measured by cumulative haemoglobin points in excess of a starting average value of 9.6 g/dl is 21.0, compared with 3.2 for the standard-care group. Quality of life effectiveness based on the quality of life change at the end of the study was -1.0mm for patients who received placebo and +8.3mm for patients who received epoetin. This results in an average incremental gain of 9.3mm for patients treated with epoetin. The authors reported that due in part to the health-state dependence of the significance patients attached to incremental changes in their responses on the LASA (which was investigated by performing multivariate regressions), QALY results were ambiguous in the context of supportive care. Cost results The costs for a 16-week treatment with epoetin were: epoetin ($4,560), physician visits ($960), opportunity cost of time lost during treatment ($600) and a baseline erythropoietin concentration and a monthly complete blood count ($443). For transfusions among patients receiving epoetin, treatment costs were: opportunity cost of time lost during transfusions ($123) and transfusions ($866). The total cost was $7,551 for patients who received epoetin and $1,416 for patients receiving standard care, a cost ratio of approximately 5.3 to 1 in favour of transfusions. Synthesis of costs and benefits Epoetin is cost effective relative to standard care when the haemoglobin level is the preferred measure of effectiveness. The effectiveness resulting from $1 spent on standard care can be achieved with only $0.81 of epoetin care. Using quality of life as an effectiveness measure, the results are even more favourable for epoetin: with an effectiveness ratio of 8.3 to -1.0. Sensitivity analysis indicated that these results were quite robust to plausible changes in the underlying assumptions. Treatment with epoetin which induces a 9.3 point increase in quality of life over 16 weeks could yield costs per QALY ranging from $110,769 to $214,391, depending on the value attached to the change in quality of life. Because of the disease state dependence of the value of a change in the Linear Analogue Scale Assessment (LASA), resulting costs per QALY vary widely, even in the absence of sensitivity analyses. Page: 3 / 5
Authors' conclusions Under a broad range of plausible assumptions, epoetin can be used cost-effectively in the treatment of anaemic patients with cancer. Further, QALYs have limited applicability here because, as a short term supportive treatment, epoetin enhances the quality but not the length of life. CRD COMMENTARY - Selection of comparators A justification was given for the choice of the comparator (the use of transfusions). It was regarded as the standard care in the context in question. You, as a database user, should consider whether this is a widely used health technology in your own setting. Validity of estimate of measure of benefit The effectiveness results, when measured in terms of haemoglobin levels, are likely to be internally valid given their reliance on a randomised study and two community-based trials. When assessed in terms of QALYs, as the authors clearly indicate, the estimate of the benefit is problematic in the context of this supportive care intervention. Validity of estimate of costs Resource quantities were reported separately from the costs and adequate details of methods of cost estimation were given. Other issues The authors' conclusion is justified given the quality of the primary studies used in the analysis as sources of effectiveness data, and the sensitivity analyses performed to address uncertainties in the data. The issue of generalisability to other settings or countries was addressed by the sensitivity analyses. Adequate comparisons with other studies were not possible in view of the scarcity of published papers dealing with the cost effectiveness of epoetin for oncology patients. Implications of the study Further research examining the value of changes in quality of life in the context of supportive care is warranted. Source of funding Supported by Ortho Biotech, Inc. Bibliographic details Cremieux P, Finkelstein S N, Berndt E R, Crawford J, Slavin M B. Cost effectiveness, quality-adjusted life-years and supportive care: recombinant human erythropoietin as a treatment of cancer-associated anaemia. PharmacoEconomics 1999; 16(5 Part 1): 459-472 PubMedID 10662393 Indexing Status Subject indexing assigned by NLM MeSH Anemia /drug therapy /economics /etiology; Combined Modality Therapy; Cost-Benefit Analysis; Erythropoietin /economics /therapeutic use; Humans; Neoplasms /complications /economics /therapy; Pain Measurement; Quality- Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins Page: 4 / 5
Powered by TCPDF (www.tcpdf.org) AccessionNumber 21999008337 Date bibliographic record published 31/07/2000 Date abstract record published 31/07/2000 Page: 5 / 5