Economic evaluation of benazepril in chronic renal insufficiency
van Hout B A, Simeon G P, McDonnell J, Mann J F
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
Benazepril in the treatment of patients with chronic renal insufficiency.
Type of intervention
Treatment; Secondary prevention.
Economic study type
Cost-effectiveness analysis.
Study population
Patients aged between 18 and 70 years who experienced chronic renal insufficiency.
Setting
Hospital. The economic study was carried out in the Netherlands, Switzerland, and Germany.
Dates to which data relate
The effectiveness data were collected between January 1989 and December 1990. The date of data on resource utilization was not specified. The fiscal year was 1996.
Source of effectiveness data
The effectiveness data were extracted from a randomised controlled trial (the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency (AIPRI) Study). The final outcomes were estimated using a time dependent semi-Markov chain model. The survival probabilities and some other transition probabilities were estimated using the data from a Dutch foundation (RENINE) responsible for the registration of all ESRD patients in the Netherlands.
Link between effectiveness and cost data
The costing was performed on a different patient sample from that used in the effectiveness analysis.
Study sample
Power calculations were not used to determine the sample size. From a total of 583 patients, 300 were randomised to receive the benazepril therapy (10 mg once daily) and 283 to receive placebo therapy. Some 12.7% (85/668) were excluded from the study.
Study design
A prospective, double-blind randomised placebo-controlled trial, carried out in 49 European hospitals. The median duration of the treatment was about 3 years. Patients were stratified into two groups according to the level of severity of the renal insufficiency (mild and moderate). The physicians in charge of the examination of the patients were unaware of their group assignment. Several independent committeesreviewed and confirmed the results of the study. The withdrawal rate was 22.6% (68/300) in the intervention group versus 21.5% (61/283) in the control group.
Analysis of effectiveness
The principle used in the analysis of effectiveness results (intention to treat or treatment completers only) was not specified. The primary health outcome was a doubling of the base-line serum creatinine concentration or the need for dialysis. Reduction in the overall risk of progressive renal insufficiency at three years and mortality rates were also reported. The groups were shown to be comparable in their characteristics.
Effectiveness results
31 patients in the benazepril group and 57 in the placebo group reached the main end-point of the study (P<0.001). In patients with mild renal insufficiency the corresponding figures were 5 out of 120 in the benazepril group and 15 out of 107 in the placebo group (P=0.01). The corresponding figures for patients with moderate insufficiency were 26 out of 180 and 42 out of 176, respectively (P=0.01). Reduction in the unadjusted overall risk of progressive renal insufficiency at three years in the benazepril group was 53% (95%CI: 27 - 70). The benazepril group had an overall mortality rate of 1 death per 93 patient-years, whereas the corresponding rate for the placebo group was 1 per 656 patient-years (p=0.04).
Clinical conclusions
"Benazepril provides protection against the loss of renal function in patients with chronic renal insufficiency caused by various disorders. This protective effect is associated with a substantial decrease in blood pressure and urinary protein excretion"."...in the AIPRI trial there was a mortality imbalance, with a very low rate in the placebo group. Mortality was not a predefined endpoint for the study and the imbalance was believed to be due to chance".
Modelling
A semi-Markov chain model was used to combine the estimates of costs and benefits and to extrapolate the results of the AIPRI study to a longer period (10 years).
Measure of benefits used in the economic analysis
The main benefit measure estimated by the model was discounted life years at 3 and 10 years(corresponding to two scenarios, one in which all patients (100 hypothetical patients) were treated with benazepril and the other in which they were treated with the placebo). Other effectiveness outcomes produced by the model were the percentage of patients reaching the level of creatinine required for dialysis (10 mg/dl) after 10 years, and the survival rate without ESRD after 3 and 10 years.
Direct costs
Costs were discounted. Resource quantities were not reported separately from the prices. Cost items per stage per quarter were reported separately and included costs of regular treatment, costs of transplantation,costs of irreversible graft rejection, and cost of dying. Resource utilisation was estimated based on some assumptions made, except for the antihypertensive drugs utilisation which was based on the data from the trial. The estimate of costs of ESRD was derived from the literature and adjusted to the current situation by consulting a panel of experts. The possible lower usage of other hypertensives by the benazepril group was not accounted for. The perspective adopted in the cost calculations was not explicitly specified. The date of the price data was 1996.
Indirect Costs
Not included.
Currency
US dollars ($).
Sensitivity analysis
A one-way sensitivity analysis was conducted on the most critical parameters of the model, i.e.the costs of end-stage renal disease and the costs of the preventive therapy.
Estimated benefits used in the economic analysis
Discounted life years at 3 and 10 years for the benazepril group were 2.80 and 7.59 versus 2.78 and 7.28 in the placebo group. The percentage of patients reaching the level of creatinine required for dialysis (10 mg/dl) after 10 years was 24.7% in the benazepril group versus 39.2% in the placebo group. The survival rates without ESRD after 3 and 10 years were 91.9% and 74.32% in the benazepril group versus 82.59% and 56.18% in the placebo group. The discount rate applied was 5%.
Cost results
The discounted average total costs after 3 and 10 years were estimated to be $8,099 and $39,445 in the benazepril group versus $12,344 and $67,459 in the placebo group, respectively. The discount rate was 5%.
Synthesis of costs and benefits
A synthesis was not performed since the benazepril therapy was the dominant strategy. The sensitivity analysis established the robustness of the results to alterations in the cost parameters examined.
Authors' conclusions
Benazepril treatment is not only an effective treatment in patients with chronic renal failure. By increasing the years spent without dialysis, it is also a cost-effective treatment.
CRD COMMENTARY - Selection of comparators
The reason for the choice of the comparator is clear. You as a database user. should consider whether this is a widely used approach in your own setting.
Validity of estimate of measure of benefit
The estimate of the benefit measure is likely to be internally valid due to use of a randomised controlled trial as the main source of the effectiveness data. However, benefits could have been assessed in terms of QALYs.
Validity of estimate of costs
The main drawback of the cost analysis is that it was not based on the data from a prospective RCT. Resource utilisation was not reported separately from the costs and indirect costs were not included in the economic study.
Other issues
The issue of generalisability to other settings or countries was not addressed and the sensitivity analysis was not fully comprehensive (for example, the effects of changes in discount rate or effectiveness parameters were not assessed).
Source of funding
None stated.
Bibliographic details
van Hout B A, Simeon G P, McDonnell J, Mann J F. Economic evaluation of benazepril in chronic renal insufficiency. Kidney International 1997; 52(Supplement 63): S159-S162