2. Methods
A decision analysis model focusing on hospitalisation, survival rates and utilities for paricalcitol and calcitriol was used (Figure 1). Costs included yearly cost for medications and the costs associated with hospitalisation.
Figure 1.
Decision analysis model and model assumptions for treatment of secondary hyperparathyroidism. IV = intravenous.
A MEDLINE search was conducted for the period January 1960 through February 2005 (inclusive) to identify publications on the comparative incidence of hospitalisation and survival rates in patients treated with paricalcitol, calcitriol or alfacalcidol.
All costs were based on 2005 euro costs without discounting. A 1-year time period was used based on the available published literature relating to probability of outcomes.
2.1 Medication Cost
For calculation of the medication costs for oral alfacalcidol and calcitriol, we assumed a daily dosage of 0.5 μg/day, and an intravenous alfacalcidol dose of 1.5μg three times a week administered continuously for 1 year. Since haemodialysis is characterised as long-term treatment, pharmacy retail prices of the highest package size (N3) were used to calculate the cost of each vitamin D medication. These assumptions were based on treatment recommendations in the German pharmaceutical guidelines.[25]
The medication cost per dialysis was calculated by determining the yearly cost and then dividing it by 156 dialyses/year (three dialyses per week for 52 weeks). The costs of alfacalcidol and calcitriol for the treatment of secondary hyperparathyroidism in haemodialysis ranged from 2.35 to 3.00 per dialysis based on the administration of capsules. Since German regulations do not allow ampoules to be split for several applications or patients, intravenous alfacalcidol cost was calculated by increments of 2μg, with a cost of alfacalcidol per dialysis of 15.84 (see Table I ).
Intravenous paricalcitol (Zemplar®)1 is administered not more than three times a week during dialysis, with initial dose depending on PTH-level (dose [μg] = iPTH [pg/mL/80]).[26] The annual paricalcitol dose was determined based on data from a double-blind, randomised, multicentre study comparing the efficacy and safety of intravenous paricalcitol and calcitriol in suppressing PTH in haemodialysis patients.[24] Since the study treatment duration was 8 months, the mean dosing at months 5 through 8 was extrapolated to months 9 through 12. The calculated mean weighted dose ratio was 3.14:1μg paricalcitol:calcitriol, over 12 months.[27] Again, since Germany does not allow ampoules to be split for multiple administrations to patients, increments of 5μg per dialysis session were used for this study. According to the German Yellow List, 5 × 5μg Zemplar® cost 127.18, which is 5.09 per μg and 25.44 per dialysis.[28]
For the calculation of medication costs per day and per year we assumed dialysis was conducted three times a week, equivalent to a ratio of 3/7.
2.2 Hospitalisation Costs
The number of hospitalisations was derived from the publication by Dobrez et al.[22] These authors analysed data from adult end-stage renal disease patients (n = 11443), new to haemodialysis, who started treatment with intravenous paricalcitol or intravenous calcitriol. Inpatient costs per patient per year were calculated using the total number of all-cause hospitalisations for patients who started and remained on paricalcitol or calcitriol. This approach was used instead of using days hospitalised in order to be consistent with the new diagnosis-related group (DRG)-system in Germany (G-DRG), which was introduced in 2004. In Germany, the economic value of each DRG is composed of points per indication-specific procedure multiplied by a basic hospital valuation that is expressed in euro. Three G-DRGs L60A, L60B and L60C were used, with a countrywide average base-case value of 2800 as shown in Table II . We used G-DRG L60B as the base case because of the relatively high percentage of International Classification of Diseases, Revision 10 (ICD-10) N.18.0 'end stage renal disease´ entries that served as the key diagnosis.[29]
Calcitriol and alfacalcidol are the two main drugs used to treat secondary hyperparathyroidism during haemodialysis in Germany. Calcitriol is available only in the oral dosage form, whereas alfacalcidol is available in both intravenous and oral dosage forms. Since alfacalcidol is hydroxylated in the liver to form calcitriol following administration, this model assumes that alfacalcidol is associated with the same number of hospitalisations as calcitriol.
2.3 Survival Rates
Survival rates were derived from historical cohort data (n = 67399) comparing patients new to intravenous paricalcitol versus calcitriol therapy who were undergoing haemodialysis.[23] The authors reported annual survival rates at month 12 of 0.84% for paricalcitol and 0.80% for calcitriol.[23,30] These rates were used in the decision analysis model (figure 1). Again, according to the aforementioned rationale relating to the metabolism of alfacalcidol (see section 2.2), this model assumes that alfacalcidol is associated with the same survival rate as calcitriol.
2.4 Utilities
Utilities were based on two comprehensive tables of cost-utility ratios published between 1976 and 2001.[31] These tables include all published ratios, sorted by disease area. Utility data specifically focusing on end-stage renal disease and haemodialysis were selected ( Table III ). On the basis of these published patient utility values, a score range between 0.61 and 0.41 was reported. No utility studies that differentiated haemodialysis patients with second-ary hyperparathyroidism from haemodialysis patients who were hospitalised were found. Typical signs and symptoms of secondary hyperparathyroidism include bone pain, fatigue and itching. Therefore, based on the range of utility scores published (0.610.41), a mean value of 0.51 was selected for non-hospitalised haemodialysis patients with secondary hyperparathyroidism.
De Wit et al.[38] evaluated utility scores for inpatient dialysis compared with outpatient dialysis in both cases for patients with end-stage renal disease with an absolute score difference of 0.15. As congestive heart failure (CHF) is a common diagnosis and reason for hospitalisation in haemodialysis patients,[3] CHF utilities were used to estimate utility in the hospitalised patients. When Capomolla et al.[42] examined utility differences between hospitalised and non-hospitalised patients with CHF, they reported utility scores of 0.63 and 0.72, respectively (p < 0.008), representing a 0.09 decrease in utility for hospitalised patients. In another study, Glick and colleagues[43] compared hospitalisation rates and utility in heart failure patients receiving placebo and those receiving spironolactone. The placebo group had more hospital admissions and a decrease in utility of 0.13 compared with spironolactone-treated patients.
On the basis of this information, the difference between patient utilities per time-point for being hospitalised was estimated to be 0.100 for this analysis. The probability of an inpatient admission was derived from Dobrez et al.[22] These authors reported that 59.6% of patients taking paricalcitol were hospitalised compared with 75.2% of those taking calcitriol. The incremental utilities were calculated on the basis of multiplication of the reported probability of hospitalisation by the probability of death/survival and the utility scores according to hospitalisation/non-hospitalisation status.
Clin Drug Invest. 2006;26(11):629-638. © 2006 Adis Data Information BV
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Cite this: Health-Economic Comparison of Paricalcitol, Calcitriol and Alfacalcidol for the Treatment of Secondary Hyperparathyroidism during Haemodialysis - Medscape - Nov 01, 2006.
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