An economic evaluation of lung transplantation Anyanwu A C, McGuire A, Rogers C A, Murday A J

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1 An economic evaluation of lung transplantation Anyanwu A C, McGuire A, Rogers C A, Murday A J 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 Three main forms of lung transplantation were examined. These were single-lung, double-lung (including bilateral single-lung transplantation) and heart-lung transplantation. Type of intervention Other: transplantation. Economic study type Cost-utility analysis. Study population The study population comprised patients with end-stage lung disease who were waiting for one of the three forms of lung transplantation. Setting The setting was a transplantation centre. The economic study was carried out in the UK. Dates to which data relate The effectiveness and resource use data were derived from studies published in 2000 and Resource data were also derived from unpublished studies. The price year was Source of effectiveness data The effectiveness evidence was derived from published studies. Modelling The cost-utility was modelled across 15 years using Microsoft Excel. Outcomes assessed in the review The health outcomes assessed from the primary studies were: 1-, 2- and 3-year survival; and utility values before and after transplantation in the first 6 months, between 7 and 18 months, between 19 and 36 months, and after 36 months post-transplantation. A survival analysis was performed using the Kaplan-Meier method, with extrapolation beyond 4 years according to the Weibull method. Page: 1 / 7

2 Study designs and other criteria for inclusion in the review The survival data were estimated from the UK Cardiothoracic Transplant Audit, a national database (from April 1995 through March 1999) comprising data of patients in the waiting list that were used as a proxy for control patients without transplantation (medical treatment). The utility data were obtained from a cross-sectional study that used the EuroQol method. The first author of the current economic evaluation carried out both of these studies. 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 evidence was derived from two primary studies. Methods of combining primary studies Survival was weighted by quality of life in order to calculate the quality-adjusted life-years (QALYs). Investigation of differences between primary studies Results of the review One-year survival (using the Kaplan-Meier method) was 66% without transplantation, 72% with single-lung transplantation, 69% with double-lung transplantation and 69% with heart-lung transplantation. Two-year survival (using the Kaplan-Meier method) was 39% without transplantation, 55% with single-lung transplantation, 59% with double-lung transplantation and 57% with heart-lung transplantation. Three-year survival (using the Kaplan-Meier method) was 29% without transplantation, 43% with single-lung transplantation, 51% with double-lung transplantation and 54% with heart-lung transplantation. The utility value before transplantation was The utility values in the single-lung transplantation group were: in the first 6 months, 0.69; between 7 and 18 months, 0.66; between 19 and 36 months, 0.65; and after 36 months post-transplantation, The utility values in the double-lung transplantation group were: Page: 2 / 7

3 in the first 6 months, 0.75; between 7 and 18 months, 0.83; between 19 and 36 months, 0.81; and after 36 months post-transplantation, The utility values in the heart-lung transplantation group were: in the first 6 months, 0.67; between 7 and 18 months, 0.85; between 19 and 36 months, 0.86; and after 36 months post-transplantation, Methods used to derive estimates of effectiveness The authors made two main assumptions for the analysis. Estimates of effectiveness and key assumptions The authors assumed that patients on the waiting list were a single group, regardless of the diagnosis and type of transplant required. In addition, all patients in the medical treatment arm were assumed to be dead by the end of the 10th year. Measure of benefits used in the economic analysis The summary benefit measures used were the number of QALYs saved and the life-years gained. The QALYs were derived by combining survival and quality of life data from the literature. The utility values were elicited from a sample of transplant recipients. Four-year survival data were extrapolated to 15 years. Therefore, the benefits were estimated for a 15-year period and a 6% discount rate was applied. Direct costs An annual discount rate of 6% was used since the costs were incurred during 15 years. The unit costs and the quantities of resources used were not presented separately. The health services in the economic evaluation were classified into four main categories. More specifically, pre-transplantation services (including transplant assessment and medical care while on the waiting list), donor screening and acquisition, transplant procedure, and long-term follow-up and maintenance. The cost/resource boundary adopted in the study is likely to have been that of the national health care payer. Resource use was estimated using actual data gathered from 1995 to 2000 alongside the UK Cardiothoracic Transplant Audit, which was also used to derive survival data. The costs were obtained from peer-reviewed literature, accounts departments in transplantation units, the Department of Health, the regional transplant coordinator's office, and health authorities. Standardised costs for emergency operating theatre time, intensive care bed-days and hospital stay were weighted by a factor of 1.3, because it was assumed that transplantation was more resource-intensive than other types of surgery. The follow-up costs were estimated from a published model for post-transplantation costs. It was assumed that all transplant recipients had received one year of medical treatment before transplantation (this was the median waiting time in the UK). Costs beyond 4 years were extrapolated to 15 years using the Weibull method. All the costs were expressed in 1999 values. Statistical analysis of costs Page: 3 / 7

4 The costs were not treated stochastically and were presented as point estimates. Indirect Costs The indirect costs were not considered. Currency UK pounds sterling (). The costs were also expressed in US dollars ($). The exchange rate in 1999 was 1 = $1.64. Sensitivity analysis Sensitivity analyses were carried out to assess the impact of changes in some parameters on the estimated cost-utility ratio. The changes explored were: an increase in the cost of transplantation; a maximum survival of 5 years after transplantation; survival of 80, 50, 35 and 25% at 1, 5, 10 and 15 years, respectively; an increase in the annual cost of medical treatment; an increase in the mean duration of intensive care admission; an increase in the cost of treating an infection episode; assuming a new one-off therapy for obliterative bronchiolotis costing; an increase in the cost of monthly maintenance; a variation in the long-term utility of between 0.4 and 0.9. It appears that one-way sensitivity analyses have been conducted. No justification was given for the choice of ranges used. Estimated benefits used in the economic analysis Extrapolated survival data showed that 10-year survival was 5% without transplantation, 31% with single-lung transplantation, 37% with double-lung transplantation, and 41% with heart-lung transplantation. The corresponding 15-year survival values were 0% (no transplant), 24% (single-lung), 30% (double-lung) and 34% (heart-lung), respectively. The adjusted (and unadjusted) life-years gained in comparison with medical treatment were 2 (3.2) with single-lung transplantation, 2.4 (3.8) with double-lung transplantation, and 2.5 (4.1) with heart-lung transplantation. The adjusted (and unadjusted) QALYs gained in comparison with medical treatment were 2.1 (3) with single-lung transplantation, 3.3 (4.6) with double-lung transplantation, and 3.6 (5.1) with heart-lung transplantation. Cost results The mean cost per patient over 15 years was 44,856 ($73,564) for medical treatment, 107,707 ($176,640) with singlelung transplantation, 110,078 ($180,528) with double-lung transplantation, and 108,772 ($178,387) with heart-lung transplantation. Synthesis of costs and benefits Page: 4 / 7

5 An incremental analysis was performed to combine the costs and benefits of the transplantation strategies in comparison with medical treatment. The incremental discounted cost per life-year gained was 30,991 ($50,825) with single-lung transplantation, 27,678 ($45,393) with double-lung transplantation, and 25,439 ($41,720) with heart-lung transplantation. The undiscounted values were 19,565 ($32,086) with single-lung transplantation, 17,228 ($28,253) with double-lung transplantation, and 15,721 ($25,782) with heart-lung transplantation. The incremental discounted cost per QALY gained was 29,415 ($48,241) with single-lung transplantation, 20,002 ($32,803) with double-lung transplantation, and 17,856 ($29,285) with heart-lung transplantation. The undiscounted values were 21,077 ($34,567) with single-lung transplantation, 14,076 ($23,084) with double-lung transplantation, and 12,410 ($20,352) with heart-lung transplantation. The sensitivity analyses showed that the results of the analysis were sensitive to variations in the utility weights. These shifted the incremental cost per QALY by about 10,000 ($16,400) when varied from 0.5 to 0.9 in all transplantation groups. Maintenance costs represented a further critical factor. Authors' conclusions Lung transplantation led to gains in survival and quality-adjusted life-years (QALYs), but represented a very expensive strategy in comparison with medical treatment. Therefore, the cost-effectiveness of transplantation was limited by substantial mortality, morbidity and high costs. CRD COMMENTARY - Selection of comparators The choice of the comparators appears to have been appropriate since medical treatment (patients on the waiting list) represents the actual strategy for patients who did not receive a lung transplant. Further, the analysis considered all possible approaches for lung transplantation. You should decide whether medical treatment represents a valid comparator in your own setting. Validity of estimate of measure of effectiveness The data used to derive the effectiveness evidence came from two published studies, both of which were carried out by the first author of this current economic evaluation. Consequently, this represents an extension of prior research, with the incorporation of economic data. The first study consisted of a national database, which covered a large group of patients and was likely to represent the overall study population of lung transplant recipients. The authors stressed that, in the primary study, the patients were selected in several centres. This not only overcame the limitations of the other published studies (which had a small sample size), but also encompassed variations in patient characteristics, patient selection and clinical practice. Further, the three forms of lung transplantation were studied separately and an appropriate control group was selected. The second study evaluated the utility values needed to estimate the QALYs. Few details on this source of data were provided. The primary estimates were combined only in the final calculation of QALYs. However, a review of the literature was not performed to identify all relevant studies concerning lung transplant recipients. Validity of estimate of measure of benefit QALYs and unadjusted survival were appropriately used to assess the benefit of the transplantation strategies on the patients' health. Few details of the utility data were provided as the estimates were derived from a published study. The benefits were discounted and were extrapolated to the long term using standard parametric techniques. The utility values were varied in the sensitivity analysis, which proved that they represented a critical factor. This represents a critical issue as the utility of transplanted patients deteriorates over time. Page: 5 / 7

6 Validity of estimate of costs The authors stated that a societal perspective was adopted. However, the indirect costs did not form part of the economic evaluation, although the authors discussed the reasons for their exclusion. Therefore, the perspective may be more appropriately described as that of the national health care payer (i.e. the UK National Health Service). Details of the unit costs and the quantities of resources used were not reported separately, which limits the possibility of replicating the study in other settings. In fact, only gross categories of costs were presented and a breakdown of all cost items was not provided. The price year was given, thus enhancing reflation exercises in other timeframes or other contexts. The source of the cost data was reported. Some assumptions were made in relation to resource use, which were estimated mainly from the national database used in the effectiveness analysis. The costs were discounted and extrapolated in a similar manner to the benefits. The costs were varied in the sensitivity analysis. Other issues The authors made extensive comparisons of their findings with those from other studies and described differences in both the methods and results. In terms of the generalisability of the study results, the authors stated that, because of differences in health care systems, costs and funding, the economic results of their analysis should not be extrapolated to other countries. However, the use of a sensitivity analysis enhanced the external validity of the analysis. The authors noted that the use of extrapolated data might represent a limitation to the validity of the analysis. In addition, all patients with lung failure were considered as a homogeneous group and this may not be the case in real life. Implications of the study The usefulness of studies evaluating the cost-effectiveness of lung transplantation remains limited because of the scarcity of lung donors. This in turn limits the burden of lung transplantation. However, within the lung transplantation approach, double-lung and heart-lung transplants were similar in terms of their cost-effectiveness. Single-lung transplantation was associated with a less convenient cost-effectiveness ratio. However, the last approach would be ethically correct since, with single-lung transplantation, more lungs would remain available for further transplants. The availability of long-term data would be helpful to address some critical issues. Source of funding None stated. Bibliographic details Anyanwu A C, McGuire A, Rogers C A, Murday A J. An economic evaluation of lung transplantation. Journal of Thoracic and Cardiovascular Surgery 2002; 123(3): PubMedID Other publications of related interest Anyanwu AC, Rogers CA, Murday J. Where are we today with pulmonary transplantation? Current results from a national cohort. Transplant International 2000;13 Suppl 1:S Anyanwu AC, McGuire A, Rogers CA, Murday AJ. Assessment of quality of life in lung transplantation using a simple generic tool. Thorax 2001;56: Comment: Journal of Thoracic and Cardiovascular Surgery 2002;123: Indexing Status Subject indexing assigned by NLM MeSH Page: 6 / 7

7 Powered by TCPDF ( Cost-Benefit Analysis; Great Britain; Heart-Lung Transplantation /economics; Humans; Life Expectancy; Lung Transplantation /economics /methods /mortality; Quality-Adjusted Life Years AccessionNumber Date bibliographic record published 31/08/2004 Date abstract record published 31/08/2004 Page: 7 / 7