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Losartan reduces the burden and cost of ESRD: public health implications from the RENAAL study for the European Union |
Gerth W C, Remuzzi G, Viberti G, Hannedouche T, Martinez-Castelao A, Shahinfar S, Carides G W, Brenner B |
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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 angiotensin-II-receptor antagonist losartan and standard antihypertensive therapy were compared to treatment with placebo and standard antihypertensive therapy. The dose of losartan was altered to achieve a target blood pressure. Standard therapy was non-angiotensin-converting enzyme-1 (ACE-I) and non-angiotensin II antagonist (AIIA).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with Type-2 diabetes and nephropathy. Patients were excluded if they had received a diagnosis of Type-1 diabetes or non-diabetic renal disease. The authors provided a list of other exclusion criteria. These included patients who had had a myocardial infarction or had undergone coronary artery bypass grafting within the previous month.
Setting The setting was secondary care. The economic study was carried out in the USA.
Dates to which data relate The study ended on the 10th February 2001, but the start date was not explicitly stated. However, the authors reported that the maximum follow-up time was 4.6 years, which allowed a start date to be ascertained. The effectiveness data were collected during this time. The authors reported that the prevalence of Type 2 diabetes in Europe was based on calculations for 1999 and that the ESRD costs were also estimated for 1999.
Source of effectiveness data The effectiveness data were derived from a single study. The effectiveness data from this study were combined with population estimates for Type 2 diabetes.
Link between effectiveness and cost data The costs were estimated retrospectively using the percentage absolute risk reduction of ESRD observed in RENAAL. The costing was therefore performed using the same patient sample as that used in the effectiveness study.
Study sample The authors did not report carrying out any power calculations to ensure that their results could not have been obtained by chance alone. In addition, the method of selecting the 1,513 patients in the sample was not described. The aim was to assess the protective effects of losartan. The sample was appropriate since it included men and women aged between 31 and 70 years with a diagnosis of Type 2 diabetes. The losartan group contained 751 individuals and the placebo group contained 762 individuals.
Study design The study was a double-blind, randomised placebo-controlled trial. The patients were reported to have been stratified according to their baseline level of proteinuria before being randomised. The method of randomisation was not described. The study was set in 250 centres in 28 countries in Asia, Europe, Central America, South America and North America. The authors planned to achieve a mean follow-up of 4.5 years. However, after finishing the study earlier than planned the mean follow-up achieved was 3.4 years. The authors reported that three patients were lost to follow-up, and that 7.5% of patients in the losartan group and 7.8% in the placebo group withdrew their consent. The members of an end-points committee determined which patients had reached the given end points, and were blinded to the patients' treatment assignments.
Analysis of effectiveness The basis of the analysis was reported to have been intention to treat principle. The primary health outcomes were the time to doubling of the serum creatinine concentration, the time to ESRD and the time to death. The authors reported that the baseline characteristics of the two groups were similar since there were no statistically significant differences. The authors also carried out a per-protocol analysis in which the results were presented according to the actual treatment received.
Effectiveness results One of the three primary outcome measures was reached in 327 patients (43.5%) in the losartan group and 359 (47.1%) in the placebo group. Treatment with losartan resulted in a 16% (95% confidence interval, CI: 2 - 28; p=0.02) reduction in the risk of reaching one of the end points.
The serum creatinine concentration was doubled in 162 patients (21.6%) in the losartan group and 198 (26.0%) in the placebo group. The risk reduction associated with losartan was 25% (95% CI: 8 - 39; p=0.06).
The number of patients that reached ESRD was 147 (19.6%) in the losartan group and 194 (25.5%) in the placebo group. The risk reduction associated with losartan was 28% (95% CI: 11 - 42; p=0.002).
There were 158 deaths (21.0%) in the losartan group and 155 (20.3%) in the placebo group died. The risk reduction associated with losartan was -2% (95% CI: -27 - 19; p=0.88).
The authors extrapolated from these results to estimate that the reduction in the risk of ESRD corresponded to an average delay of two years in the need for dialysis or transplantation.
Clinical conclusions The authors concluded that "losartan led to a significant improvement in renal outcomes that was beyond that attributable to blood-pressure control in patients with type-2 diabetes".
Measure of benefits used in the economic analysis The authors did not estimate a summary measure of benefit. The study was therefore categorised as a cost-consequences analysis.
Direct costs The perspective of the cost analysis was not explicitly stated. Since there were few details of which resources were costed, it was not possible to infer which perspective was adopted. The costs of ESRD for Germany in 1999 were used to estimate the cost-savings associated with delayed onset of ESRD and fewer cases of ESRD across Europe. Volumes were estimated by combining the absolute risk reduction from the trial with Type 2 diabetes population estimates for the European Union. The authors reported that the costs of ESRD were a "weighted average of costs for haemodialysis at a centre, hospital or at home, and peritoneal dialysis based on utilization patterns for dialysis services in Germany". The ESRD costs were reported to include specialist dialysis services, medical services, inpatient or outpatient treatment of dialysis complications, transport and erythropoietin medication. The cost estimates appear to have been derived from actual data, although the specific sources were not provided. The authors did not report that discounting was carried out, although it would have been relevant since the ESRD costs were estimated over a 3.5-year period.
Statistical analysis of costs No statistical analysis was reported.
Indirect Costs The authors did not report estimating any indirect costs. Since the patients were required to undergo dialysis, the cost of their time may have been relevant. This may have been estimated on the basis of lost productivity. The authors mentioned this limitation in their discussion. They also acknowledged that the ESRD-related cost-savings would be larger if the indirect costs were included.
Currency The costs were estimated in Euros (Euro). No currency conversions were reported.
Sensitivity analysis No sensitivity analysis was reported.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The authors multiplied the costs of ESRD and the number of ESRD days avoided to estimated a per patient saving of Euro 3,730 over 3.5 years, and Euro 5,206 over 4 years.
The authors extrapolated the per patient savings to the target population in the European Union. This led to savings of Euro 2,6 billion over 3.5 years and Euro 3.6 billion after 4 years.
Synthesis of costs and benefits The costs and benefits were not combined.
Authors' conclusions Treatment with losartan reduced the incidence of end-stage renal disease (ESRD) in diabetic patients with nephropathy. It may also result in substantial cost-savings in the European Union.
CRD COMMENTARY - Selection of comparators The authors compared losartan with a placebo. This allowed the active value of the treatment to be evaluated. You should decide if this represents a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The analysis used a double-blind, randomised placebo-controlled study. This design was appropriate for the stated objective of the study, which was to assess the burden and costs of ESRD. The internal validity of the study is likely to be high given the design. The study sample was representative of the study population since it included patients suffering from Type 2 diabetes. The patients groups were shown to be comparable at analysis. However, no power calculations were reported, thus it is difficult to determine whether the results were obtained by chance.
Validity of estimate of measure of benefit The authors did not derive a summary measure of health benefit. Therefore, the analysis was categorised as a cost-consequences study.
Validity of estimate of costs It is not possible to comment on whether all the relevant costs were included in the study since a cost perspective was not explicitly stated. The costs were not reported separately from the quantities. The authors stated that the costs were based on "utilization patterns for dialysis services in Germany". They did not discuss the generalisability of usage patterns to the rest of Europe. For instance, other countries may have differing guidelines as to the use of dialysis. In this case it would not be appropriate to base the cost estimates for Europe on the patterns observed in Germany. The authors reported the annual direct costs of ESRD in various countries in their discussion. Given the availability of such information, it may have been beneficial for the authors to have used this to estimate the resource use and unit costs, instead of extrapolating from Germany. Discounting was relevant given the time frame of the study, but it was not conducted. The price year was reported, thus aiding reflation exercises.
Other issues The authors compared some of their results by reporting the cost of ESRD in different countries. No cost-savings for other countries were reported, possibly because they have not been estimated. The issue of generalisability of the results to other settings was addressed in the authors' discussion of the limitations of extrapolating per patient trials to at-risk populations. The ability to generalise cost estimates for extrapolation to the European Union was not well discussed. The problems with this have been noted already. The authors' conclusions were an accurate reflection of the results presented.
Implications of the study The authors make no recommendations for changes in policy or practice resulting from their study, nor do they indicate any need for further research.
Bibliographic details Gerth W C, Remuzzi G, Viberti G, Hannedouche T, Martinez-Castelao A, Shahinfar S, Carides G W, Brenner B. Losartan reduces the burden and cost of ESRD: public health implications from the RENAAL study for the European Union. Kidney International 2002; 62(Supplement 82): S68-S72 Other publications of related interest Brenner BM, Cooper ME, DeZeeuw, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type-2 diabetes and nephropathy. New England Journal of Medicine 2001;345:861-9.
Indexing Status Subject indexing assigned by CRD MeSH Antihypertensive Agents /therapeutic use; Blood Pressure /drug effects; Cost-Benefit Analysis; Diabetes Mellitus, Type 2 /complications /economics; Diabetic Nephropathies; Humans; Hypertension, Renal /drug therapy; Kidney Failure, Chronic /drug therapy; Losartan /therapeutic use AccessionNumber 22002001977 Date bibliographic record published 31/12/2003 Date abstract record published 31/12/2003 |
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