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Health economic implications of irbesartan plus conventional antihypertensive medications versus conventional blood pressure control alone in patients with type 2 diabetes, hypertension, and renal disease in Switzerland |
Palmer A J, Roze S, Valentine W J, Ray J A, Frei A, Burnier M, Hess B, Spinas G A, Brandle M |
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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 irbesartan, 300 mg daily, plus conventional antihypertensive therapy in patients with Type 2 diabetes, hypertension and microalbuminuria.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of patients with Type 2 diabetes, hypertension and microalbuminuria. The latter was defined as a urinary albumin excretion (UAE) of 20 to 199 microg/minute on two out of three consecutive occasions.
Setting The setting was secondary care. The economic study was carried out in Switzerland.
Dates to which data relate The effectiveness data and some resource use data were derived from studies published between 2000 and 2004. No dates for the majority of the resource use data were reported. The price year was 2003.
Source of effectiveness data The effectiveness evidence was derived from a synthesis of published studies and authors' opinions.
Modelling A published Markov model was used to simulate the long-term progression of renal disease in patients with Type 2 diabetes and the impact of the two treatments under investigation. Patients could move across the following health states:
microalbuminuria (UAE 20 to 199 microg/minute),
early overt nephropathy (UAE 200 microg/minute to median UAE 1,900 mg/24 hours),
advanced overt nephropathy (median UAE on entry >/= 1,900 mg/24 hours),
doubling of serum creatinine (DSC),
ESRD treated with dialysis,
ESRD treated with renal transplant, and
death.
A simplified version of the model was presented. The time horizon was 25 years and the cycle length appears to have been 1 year.
Outcomes assessed in the review The outcomes estimated from the literature were the transition probabilities across health states and the mortality rates.
Study designs and other criteria for inclusion in the review It was not stated whether a systematic review of the literature was undertaken to identify the primary studies. The clinical data were mainly derived from two clinical trials, the Irbesartan in Reduction of Microalbuminuria-2 study and the international Irbesartan in Diabetic Nephropathy Trial. The first study included 590 patients with Type 2 diabetes or microalbuminuria, while the second enrolled 1,715 patients with Type 2 diabetes, hypertension or advanced overt nephropathy. Mortality for transplant patients was obtained from a European transplant register and a German dataset. All-cause mortality was based on Danish data. No information on the other studies was provided.
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 Nine primary studies provided the clinical evidence.
Methods of combining primary studies A narrative approach appears to have been used to combine the primary estimates.
Investigation of differences between primary studies Results of the review The clinical estimates derived from the literature were reported selectively. Transition probabilities were reported for very few health states. For example, the rate of transition from transplant to dialysis was 17.1% in the first year and 5% in subsequent years.
It was stated that 0.35% of patients diagnosed with ESRD received renal transplantation.
Approximately 95.2% of patients started haemodialysis and 4.8% received peritoneal dialysis.
The annual rate of dialysis patients receiving a transplant was 4.2%.
The relative risk (RR) of mortality for patients with Type 2 diabetes, hypertension and microalbuminuria was 2.03.
The RR for mortality in patients with Type 2 diabetes, hypertension and overt nephropathy was 4.4 compared with the general population.
Annual mortality in dialysis patients was 16.91%.
Methods used to derive estimates of effectiveness The authors made some assumptions that were used in the decision model when published data were not found.
Estimates of effectiveness and key assumptions The rate of progression from early overt nephropathy to advanced overt nephropathy was assumed to be the same in both treatment arms. The RRs for all-cause mortality in the early overt nephropathy, advanced overt nephropathy and DSC states were conservatively assumed to be the same.
Measure of benefits used in the economic analysis The summary benefit measures used were life expectancy, years free of ESRD and the cumulative incidence of ESRD. All measures were estimated using the modelling approach. An annual discount rate of 5% was used.
Direct costs The analysis was carried out from the perspective of the third-party payer. It included the costs of irbesartan and the treatment of ESRD, which included resources associated with renal transplant and dialysis. The costs of other medications were not considered since they were assumed to have been comparable between treatment arms. The unit costs were not presented separately from the quantities of resources used. The unit costs for renal transplant and follow-up treatment because of ESRD were estimated from Swiss national insurance data, while the unit costs of haemodialysis were obtained from Swiss national tariffs. The cost of peritoneal dialysis was derived from published data and expert opinion. Resource use associated with medications was taken directly from the clinical trial, while the sources of other resource consumption were not explicitly stated. Discounting was relevant, as the long-term costs were evaluated, and an annual rate of 5% was used. The price year was 2003.
Statistical analysis of costs No statistical analyses of the costs were performed.
Indirect Costs The indirect costs were not considered.
Sensitivity analysis A univariate sensitivity analysis was carried out to assess the robustness of the expected costs and benefits to variations in three key model assumptions. First, the UAE threshold for advanced overt nephropathy was set to the minimum required (585 mg/24 hours). Second, recent UK mortality data for no renal disease, microalbuminuria, or overt nephropathy were used. Third, the RR of mortality in the states leading up to ESRD was set to 1.0 in order to simulate only the effects of treatment on delaying the onset of ESRD and its increase in associated mortality.
Estimated benefits used in the economic analysis The discounted life expectancy was 9.80 years in the control group and 10.37 years in the irbesartan group (difference 0.57).
The undiscounted life expectancy was 14.39 years in the control group and 15.61 years in the irbesartan group (difference 1.22).
The analysis of life-years saved with irbesartan showed that survival benefits were observed after 7 years of treatment
The years free of ESRD were 12.90 in the control group and 15.04 in the irbesartan group.
The cumulative incidence of ESRD was 26.6% in the control group and 10.7% in the irbesartan group.
Cost results The total costs per patient would be CHF 46,956 in the control group and CHF 25,469 in the irbesartan group (cost-difference CHF 21,487).
The extra cost of irbesartan treatment was more than offset by savings associated with a reduction in ESRD treatment.
Synthesis of costs and benefits The incremental costs and benefits were not combined in a cost-effectiveness ratio since irbesartan was the dominant strategy (being both more effective and less expensive than the comparator).
The sensitivity analysis showed that the base-case results were unchanged when variations in key assumptions were made. In other words, irbesartan remained the dominant strategy in all cases.
Authors' conclusions Compared with conventional therapy, the use of irbesartan to treat Type 2 diabetes patients with hypertension and microalbuminuria improved life expectancy and reduced total costs from the perspective of the Swiss health system.
CRD COMMENTARY - Selection of comparators The choice of the comparators was appropriate because a new medication was compared with the conventional therapy for patients with Type 2 diabetes, hypertension and microalbuminuria. Doses and frequency of administration were reported. Angiotensin-converting enzyme inhibitors, other angiotensin-2-receptor antagonists and dihydropyridine calcium-channel blockers were excluded because of contrasting evidence on their efficacy. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness data were derived from published studies. The authors did not report the methods and conduct of a systematic review, so it is possible that the primary studies might have been identified selectively. Different sources of data were used, including clinical trials and international registries. In general, the use of clinical trials ensures a high internal validity of the primary estimates. Similarly, the European registry should have provided good-quality data. Some assumptions were also made, owing to the lack of published evidence. The authors acknowledged the uncertainty surrounding some clinical estimates, which were varied in the sensitivity analysis. The issue of heterogeneity among the primary studies was not addressed.
Validity of estimate of measure of benefit Both disease-specific and generic benefit measures were used in the analysis. Life expectancy represents a valid measure as the disease in question has a strong impact on mortality. It has the further advantage of being comparable with the benefits of other health care interventions. The effect of the treatments under examination on quality of life was not explicitly assessed, but the use of a summary measure such as years free of ESRD captures, in part, this aspect of patient health. Discounting was performed in accordance with international recommendations.
Validity of estimate of costs The costs included were appropriate given the perspective adopted in the analysis. The authors justified the choice of excluding some categories of costs. However, a detailed breakdown of the cost items was not provided and all costs were presented as macro-categories. In addition, details of the unit costs and quantities of resources used were not given. This represents a limitation of the analysis as it will prevent its replication in other settings. The sources of the costs were reported and most costs were derived from national databases. However, less detailed information on the source of resource use was provided. No statistical analyses of the costs were carried out, and the cost estimates were specific to the authors' setting as sensitivity analyses were not carried out. The price year was reported, thus facilitating reflation exercises in other time periods.
Other issues The authors did not compare their findings with those from other studies. They also did not explicitly address the issue of the transferability of the study results to other settings. Limited sensitivity analyses were carried out but these were restricted to the clinical side of the analysis. Therefore, caution will be required if extrapolating the results of the study to other contexts. The authors acknowledged some limitations of their study. First, owing to the lack of direct clinical comparisons, it was not possible to compare the projections for irbesartan treatment with those of angiotensin-converting enzyme inhibitors or other angiotensin-2-receptor antagonists. Second, there was a lack of published data about the distribution of treatment of ESRD with haemodialysis, continuous ambulatory peritoneal dialysis or transplant in Switzerland, so data from other countries were needed to populate the decision model.
Implications of the study The study results support the use of irbesartan for the treatment of Type 2 diabetes patients with hypertension and microalbuminuria. The authors pointed out that head-to-head clinical trials comparing angiotensin-converting enzyme inhibitors and angiotensin-2-receptor antagonists should be carried out.
Source of funding Funded by an unrestricted grant from Birtol-Myers Squibb and Sanofi Synthelabo.
Bibliographic details Palmer A J, Roze S, Valentine W J, Ray J A, Frei A, Burnier M, Hess B, Spinas G A, Brandle M. Health economic implications of irbesartan plus conventional antihypertensive medications versus conventional blood pressure control alone in patients with type 2 diabetes, hypertension, and renal disease in Switzerland. Swiss Medical Weekly 2006; 136(21-22): 346-352 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
Palmer AJ, Annemans L, Roze S, et al. Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease. Diabetes Care 2004;27:1897-903.
Rodby RA, Chiou CF, Borenstein J, et al. The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy. Clin Ther 2003;25:2103-19.
Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:910-2.
Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60.
Indexing Status Subject indexing assigned by NLM MeSH Albuminuria /drug therapy /economics; Angiotensin II Type 1 Receptor Blockers /administration & Antihypertensive Agents /administration & Biphenyl Compounds /administration & Cohort Studies; Cost Savings; Creatinine /blood; Diabetes Mellitus, Type 2 /drug therapy /economics; Diabetic Nephropathies /drug therapy /economics; Follow-Up Studies; Humans; Hypertension /complications /drug therapy /economics; Life Expectancy; Markov Chains; Practice Guidelines as Topic; Switzerland; Tetrazoles /administration & Time Factors; Treatment Outcome; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use; dosage /economics /therapeutic use AccessionNumber 22006001342 Date bibliographic record published 28/02/2007 Date abstract record published 28/02/2007 |
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