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Clin Ther. 2013 Dec;35(12):1909-22. doi: 10.1016/j.clinthera.2013.10.004. Epub 2013 Nov 13.

Cost-effectiveness of everolimus for second-line treatment of metastatic renal cell carcinoma in Serbia.

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Unit of PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands. Electronic address:
Unit of PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands; Toronto Health Economics and Health Technology Assessment (THETA) Collaborative, University of Toronto, Toronto, Canada.
Department of Pharmacology & Toxicology, Medical Faculty, University of Novi Sad, Novi Sad, Serbia.
Unit of PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands.



New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and/or sorafenib. The only targeted therapy for mRCC currently reimbursed in Serbia is sunitinib.


The aim of this study was to estimate the cost-effectiveness and the budget impact of the introduction of everolimus in Serbia in comparison to best supportive care, for mRCC patients refractory to sunitinib.


A Markov model was designed corresponding with Serbian treatment protocols. A health care payer perspective was taken, including direct costs only. Treated and untreated cohorts were followed up over 18 cycles, each cycle lasting 8 weeks, which covered the lifetime horizon of mRCC patients refractory to the first-line treatment. Annual discounted rates of 1.5% for effectiveness and 3% for costs were applied. Transitions between health states were modeled by time-dependent probabilities extracted from published Kaplan-Meier curves of PFS and overall survival (OS). Utility values were obtained from the appraisals of other mRCC treatments. One-way and probabilistic sensitivity analyses were done to test the robustness and uncertainty of the base-case estimate. Lastly, the potential impacts of everolimus on the overall health care expenditures on annual and 4-year bases were estimated in the budget-impact analysis.


The incremental cost-effectiveness ratio for everolimus was estimated at €86,978 per quality-adjusted life-year. Sensitivity analysis identified the hazard multiplier, a statistical approximator of OS gain, as the main driver of everolimus cost-effectiveness. Furthermore, probabilistic sensitivity analyses revealed a wide 95% CI around the base-case incremental cost-effectiveness ratio estimate (€32,594-€425,258 per quality-adjusted life-year). Finally, an average annual budgetary impact of everolimus in first 4 years after its potential reimbursement would be around €270,000, contributing to <1% of the total budget in Serbian oncology.


Everolimus as a second-line treatment of mRCC is not likely to be a cost-effective option under the present conditions in Serbia, with a relatively limited impact on its budget in oncology. A major constraint on the estimation of the cost-effectiveness of everolimus relates to the uncertainty around the everolimus effect on extending OS. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to construct an economically rational treatment strategy within the mRCC field.


Serbia; cost-effectiveness; everolimus; renal cell carcinoma

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