Cost–Effectiveness of Angiotensin-converting Enzyme Inhibitors in Nondiabetic Advanced Renal Disease

Charles Christian Adarkwah; Afschin Gandjour

Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(2):215-223.

Sensitivity Analysis

To address uncertainty around mean incremental costs and effectiveness, we conducted univariate sensitivity analyses, where we varied one variable at a time while keeping all other variables constant at their mean or base-case value. We ran analyses using the upper and lower limit of the 95% confidence intervals (CIs) of the mean. For transplantation costs, we did not have information on the 95% CI and thus varied costs by 20% (see Table 2 for uncertainty ranges).

In order to assess how a simultaneous change of several variables affects the incremental cost–effectiveness ratio, we performed a Monte Carlo simulation, a type of multivariate sensitivity analysis. This technique runs a large number of simulations (in this case 1000) by repeatedly drawing samples from probability distributions of input variables. Thus, it provides a probability distribution for the output variables (incremental costs, incremental effectiveness and incremental cost–effectiveness ratios). Probabilities were assumed to follow a β distribution β(α, β) because they are normally distributed but restricted to take on values between 0 and 1. The standard error of a probability or proportion was calculated according to the following formula:^[32]

where p = probability and n = sample size. Cost data were assumed to follow a γ distribution γ(a, b), which reflects the long right tail and restriction to positive values. Relative risks and odds ratios were assumed to follow a lognormal distribution.

Based on the Monte Carlo simulation, we generated a cost–effectiveness acceptability curve. A cost–effectiveness acceptability curve allows a decision-maker to consider whether a prevention strategy is cost effective in relation to the maximum amount a decision-maker is willing to pay for a QALY. At each willingness-to-pay threshold, the cost–effectiveness acceptability curve shows the probability that treatment is cost effective.

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Cite this: Cost–Effectiveness of Angiotensin-converting Enzyme Inhibitors in Nondiabetic Advanced Renal Disease - Medscape - Apr 01, 2011.

Table 1. Baseline characteristics of patients with chronic kidney disease.
Characteristics	Hou et al. ^†		Ihle et al. ^‡
Characteristics	ACE inhibitor (n = 112)	Placebo (n = 112)	ACE inhibitor (n = 36)	Placebo (n = 34)
Age (years)	44	45	41	48
Male subjects, n (%)	56 (50)	55 (49)	23 (64)	13 (38)
Blood pressure (mmHg): – Systolic – Diastolic	153 87	152 85	147 87	154 88
Renal function: – Serum creatinine (mg/dl) – GFR (ml/min/1.73 m²) – Urine protein excretion (g/day)	4.0 26.3 1.6	3.9 25.8 1.7	5.2 14.6 2.3	4.4 15.8 1.9

ACE: Angiotensin-converting enzyme; GFR: Glomerular filtration rate.
^† Data from [1].
^‡ Data from [14].

Table 2. Data used to determine the cost–effectiveness of angiotensin-converting enzyme inhibitor treatment.
Variable	Base-case estimate	Range tested in sensitivity analysis^†	Ref.
*Annual transition probabilities*
Advanced renal insufficiency to ESRD without ACE inhibitor	0.14	0.08–0.19	[1,14]
Advanced renal insufficiency to death	Age and gender dependent	0.003–0.54	[105]
ESRD to death	0.13	No range tested	[2]
*Effectiveness of ACE inhibitor*
Relative risk of advanced renal insufficiency to ESRD	0.61	0.39–0.95	[1,14]
*Utilities (health states)*
General population (age dependent)	0.83–0.94	No range tested	[22]
Disutility of CKD	0.056	-0.045–0.156	[21]
Disutility of ACE inhibitor treatment	1.00	0.95–1.00	[23]
ESRD	0.62	0.39–0.84	[24]
*Annual costs (€)*
Per-patient cost of CKD compared with non-CKD population	Age dependent	No range tested	[28–30,103,104]
ACE inhibitor (20 mg benazepril daily; 5 mg enalapril daily in the SA)	130.58	53.47–130.58	[102]
Creatinine and potassium screening	1	No range tested	[26,105]
ESRD – Transplantation – Dialysis	45,366 19,958 54,077	32,872–57,879 17,962–21,953 38,387–71,167	[2,3,27,31,101,106]
SMR of CKD	3.41	2.84–4.11	[20]
Discount rate	0.03	0.00–0.10	[15]

^†Based on 95% confidence intervals of the mean except for ESRD (estimate).
ACE: Angiotensin-converting enzyme; CKD: Chronic kidney disease; ESRD: End-stage renal disease; SA: Sensitivity analysis; SMR: Standardized mortality ratio.

Table 3. Results of the base-case analysis based on mean estimates of input variables.
Strategy	Costs (€)	Undiscounted LYs	Discounted QALYs	ICER (€/QALY)
No ACE inhibitor treatment	205,200	11.63	6.77	Dominated
ACE inhibitor treatment	172,676	13.20	8.26	Dominant

ACE: Angiotensin-converting enzyme; ICER: Incremental cost–effectiveness ratio; LY: Life year; QALY: Quality-adjusted life year.

Table 4. Univariate sensitivity analyses from a statutory health insurance perspective^†.
	Incremental costs (€)	Incremental QALYs	Incremental cost– effectiveness ratio
*Base case*
	-32,524	1.49	Dominance
*Annual transition probabilities from advanced renal insufficiency to ESRD*
Without ACE inhibitor
Lower bound	-33,589	1.44	Dominance
Higher bound	-27,154	1.37	Dominance
*Effectiveness of ACE inhibitor*
Relative risk of advanced renal insufficiency to ESRD
Lower bound	-63,736	2.80	Dominance
Higher bound	-2511	0.15	Dominance
*Utilities (health states)*
Chronic kidney disease
Lower bound	-32,524	1.43	Dominance
Higher bound	-32,524	1.54	Dominance
ESRD
Lower bound	-32,524	1.65	Dominance
Higher bound	-32,524	1.33	Dominance
Disutility of ACE inhibitor treatment
Lower bound	-32,524	1.18	Dominance
Higher bound	-32,524	1.49	Dominance
*Costs*
ACE inhibitor
Lower bound	-33,001	1.49	Dominance
Higher bound	-32,524	1.49	Dominance
ESRD
Lower bound	-21,596	1.49	Dominance
Higher bound	-43,469	1.49	Dominance
SMR
Lower bound	-32,364	1.56	Dominance
Higher bound	-32,704	1.41	Dominance
*Discount rate of costs and effects*
0%	-37,860	2.33	Dominance
5%	-29,444	1.14	Dominance
7%	-26,716	0.90	Dominance
10%	-23,207	0.66	Dominance

^†Effects of varying base-case estimates on the incremental cost–effectiveness ratio of treating all patients with advanced renal insufficiency with an ACE inhibitor versus no ACE inhibitor treatment (reference strategy). 'Lower bound' and 'higher bound' refer to the limits of the 95% confidence interval or estimate thereof.
ACE: Angiotensin-converting enzyme; ESRD: End-stage renal disease; QALY: Quality-adjusted life year; SMR: Standardized mortality ratio.

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