|Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria
|Palmer A J, Annemans L, Roze S, Lapuerta P, Chen R, Gabriel S, Carita P, Rodby R A, de Zeeuw D, Parving H H, De Alvaro F
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.
The study examined the addition of irbesartan (300 mg daily) to standard care for the prevention of end-stage renal disease (ESRD) in Type 2 diabetes patients with hypertension and microalbuminuria. The comparator was standard care alone. Standard antihypertensive medications refer to those required to achieve a target blood pressure of less than 135/85 mmHg, excluding angiotensin-converting enzyme (ACE) inhibitors, other angiotensin II receptor antagonists, and dihydropyridine calcium-channel blockers.
Economic study type
The study population comprised a hypothetical cohort of Type 2 diabetes patients with hypertension and microalbuminuria.
The setting was secondary care. The economic study was designed for Spain.
Dates to which data relate
Most of the effectiveness and resource use data were derived from the decision model published in 2004, as well as from studies published in 2001. The price year was not reported.
Source of effectiveness data
The clinical data used in the model were not reported. Readers are therefore referred to the original study (Palmer et al. 2004).
A peer-reviewed, published Markov model (Palmer et al. 2004) was used to simulate disease progression from microalbuminuria (24-hour urinary albumin excretion (UAE) 20 to 199 microg/minute) to 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, ESRD treated with either dialysis or renal transplant, and death. The time horizon of the model was 25 years. No details of the cycle length, transition probabilities or model structure were given. Readers are therefore referred to the original publication.
Sources searched to identify primary studies
The treatment effect for irbesartan was derived from two clinical trials, the Irbesartan Reduction of Microalbuminuria-2 (IRMA-2) study and the Irbesartan in Diabetic Nephropathy Trial (IDNT). Other data came from other published sources that were not described.
Methods used to judge relevance and validity, and for extracting data
The methods used to derive the clinical data were not reported. It was unclear whether a review of the literature had been undertaken. More information should be available in the publication describing the decision model.
Measure of benefits used in the economic analysis
The measures of benefits used were the years free of ESRD, the cumulative incidence of ESRD, and life-years (LYs). All measures were calculated using the modelling approach. The LYs were discounted at an annual rate of 3%.
The cost categories and resources costed were not reported in this paper, the authors referring the reader to the Palmer study. Information on the unit costs and resource quantities was derived from the published decision model. Discounting was relevant, as the long-term costs were considered, and an annual rate of 3% was applied. The price year was not reported.
Statistical analysis of costs
The costs were treated deterministically in the base-case.
Productivity costs were not considered.
A sensitivity analysis was performed on key model inputs. A Monte Carlo simulation was also carried out by assigning probabilistic distributions to clinical and economic data in order to generate mean, median, standard deviations and 95% confidence intervals (CI) around the total costs and benefits.
Estimated benefits used in the economic analysis
Discounted LYs (undiscounted in brackets) were 11.53 (14.78) with standard care and 12.37 (16.13) with irbesartan. The difference was 0.84 +/- 0.15 (1.40 +/- 0.27).
The years free of ESRD were 13.44 with conventional care and 15.66 with irbesartan.
The cumulative incidence of ESRD was 24% (+/- 1) with standard care and 9% (+/- 2) with irbesartan.
The authors noted that the benefits associated with irbesartan were insensitive to parameter variations.
The discounted 25-year costs per patient were EUR 25,119 (+/- 1,742) with conventional care and EUR 14,038 (+/- 2,292) with irbesartan. The cost-difference was EUR 11,082 (+/- 2,996).
The extra cost of irbesartan was more than offset by a reduction in ESRD treatment costs.
The authors stated that the cost-differences were robust to variations considered in the sensitivity analysis.
Synthesis of costs and benefits
Incremental cost-effectiveness ratios were not calculated since irbesartan was the dominant strategy, being both more effective and less expensive than usual care. The authors stated that the sensitivity analysis revealed that all conclusions were robust under a wide range of plausible assumptions. The results of the probabilistic sensitivity analysis were not reported.
The addition of irbesartan to standard care for diabetic hypertensive individuals with microalbuminuria was projected to reduce the incidence of end-stage renal disease (ESRD), extend life, and reduce costs from the perspective of the Spanish third-party payer.
CRD COMMENTARY - Selection of comparators
The rationale for the selection of the comparators was clear in that it reflected the conventional treatment pattern in the Spanish context. The authors justified the exclusion of ACE inhibitors, beta-blockers, or other angiotensin-II receptor blockers as alternative treatments. You should decide whether this is a valid comparator in your own setting.
Validity of estimate of measure of effectiveness
The approach used to derive the clinical estimates was not reported. It was unclear whether a systematic review had been undertaken, or whether the primary studies had been identified selectively. Some of the evidence came from two clinical trials, which have the potential to provide high internal validity. The authors did not report any additional information about the sources of the data (e.g. sample size, follow-up, methods of randomisation) or the methods used to combine the primary studies.
Validity of estimate of measure of benefit
The summary benefit measures were appropriate given the nature of disease. In effect, both disease-specific and more generalisable measures were considered. In particular, LYs can be compared with the benefits of other health care interventions. You should consider whether irbesartan is likely to have a significant impact on quality of life. Discounting was performed but undiscounted results were also presented.
Validity of estimate of costs
There was little information on the cost analysis since much of the economic study had already been reported in the publication describing the decision model. Probabilistic distributions were given to cost estimates in the sensitivity analysis, although details about the stochastic analysis were not reported. The analysis of the costs included only direct medical costs, which was consistent with the perspective stated. However, the authors pointed out that the inclusion of productivity costs would have further favoured the irbesartan strategy.
The authors stated that irbesartan was also the dominant option in a published study of patients with advanced disease. Therefore, the current findings appear to be comparable with those from previous research. However, it has to be noted that the study to which the authors referred was based on data from the IDNT study, which was also used in the current economic analysis. Overall, little information on the methods of the analysis were reported since much of the data had already been published. The issue of the generalisability of the study results was not extensively addressed. The authors stated that the main limitation of the study was the fact that the model did not consider ACE inhibitors, beta-blockers, or other angiotensin-II receptor blockers as alternative treatments. However, it was pointed out that, at the time the paper was published, there were no head-to-head clinical trials of irbesartan versus any of these possible comparators.
Implications of the study
The study results support the use of irbesartan in diabetic hypertensive individuals with microalbuminuria. The authors stated that future research should compare irbesartan with other relevant comparators such as ACE inhibitors, beta-blockers, or other angiotensin-II receptor blockers.
Source of funding
Funded by grants from Bristol-Myers Squibb and Sanofi-Synthelabo.
Palmer A J, Annemans L, Roze S, Lapuerta P, Chen R, Gabriel S, Carita P, Rodby R A, de Zeeuw D, Parving H H, De Alvaro F. Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria. Kidney International 2005; 67(Supplement 93): S52-S54
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. The cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding angiotensin-converting enzyme 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.
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, Hunsiker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbertasan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60.
Subject indexing assigned by NLM
Albuminuria /economics /epidemiology /etiology; Antihypertensive Agents /economics /therapeutic use; Biphenyl Compounds /economics /therapeutic use; Blood Pressure /physiology; Cost Savings; Diabetes Mellitus, Type 2 /drug therapy /economics /epidemiology; Humans; Hypertension /drug therapy /economics /epidemiology; Life Expectancy; Markov Chains; Spain /epidemiology; Tetrazoles /economics /therapeutic use
Date bibliographic record published
Date abstract record published