Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom

Abstract

Background: The use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective.

Materials and methods: This cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses.

Results: Patients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (-€ 4,196 in France, - € 3,880 in Germany, and -€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67-77% of simulations, depending on the country. The cost per QALY gained for ZOL versus placebo was below € 30,000 per QALY gained threshold in approximately 93-94% of multivariate sensitivity analyses simulations.

Conclusions: The present analysis suggests that ZOL saves costs and increases QALYs compared to placebo in French, German, and UK RCC patients with bone metastases. Additional prospective research may be needed to confirm these results in a larger sample of patients.

Fig. 1

Costs of SRE by SRE type and country see Appendix for detail description and sources of SRE cost by country

Fig. 2

Univariate Sensitivity Analysis around the NMB of Zometa versus Placebo Legend: This figure presents the results of the univariate sensitivity analysis on the NMB (assuming a λ = € 30,000) of ZOL versus placebo using tornado diagrams in the three countries of interest. The model parameters with the largest influence on the NMB (i.e., for which the change in parameter value is associated with the larges change in NMR) is placed at the top of the tornados. Other variables are placed in decreasing order of influence. The vertical lines at the center of the tornadoes represent the point estimates of the NMB (€ 6,049 in France, € 5,913 in Germany, and € 5,444 in the UK). None of the changes in the value of the parameters resulted in the NMB to be less than € 0, implying that none of these changes resulted in the Cost per QALY to be higher than € 30,000 (=λ)

Fig. 3

Acceptability Curve for the Cost-Effectiveness of ZOL Legend: The acceptability curve shows the probability that ZOL is cost-effective compared to placebo, given the results of the 1,000 PSA simulations, across a range of maximum monetary values that decision makers might be willing to pay for a QALY saved (along the “x” axis). For instance, if decision makers are not willing to pay anything for a QALY saved (i.e., they demand that ZOL is cost saving, regardless of the impact on QALYs), then approximately 67% (for the UK) to 77% (for France) of the 1,000 model runs in PSA met this requirement (the acceptability curve crosses the Y axis at the 67% to 77% mark). As the willing to pay for a QALY saved increases, the proportion of 1,000 simulations that meet the decision makers’ criteria also increases, to reach a maximum of 94% for France and Germany around € 22,000 and 93% for the UK around € 34,000