1. For a copy of the poster:
ISPOR Annual European Congress 2013, Dublin, PCN135
Cost utility analysis of everolimus in the treatment of metastatic renal cell cancer in the Netherlands J. Mihajlović, I.Minović, A.M.Bruinsma, M.J.Postma University of Groningen, Groningen, The Netherlands
Background
Probability of PFS A B
Probability of OS
Metastatic renal cell cancer (mRCC) is a practically incurable disease.
New targeted therapeutics and monoclonal antibodies enable an increment in progression-free survival (PFS) ranging from 2 to 6 months.
European guidelines recommend sunitinib, pazopanib, sorafenib, bevacizumzab, temsirolimus and everolimus for the therapy of mRCC.
Compared to the best supportive care (BSC), everolimus (EV) demonstrated an additional PFS of 3 months given to the patients with mRCC who had progressed on sunitinib and/or sorafenib.
Due to relatively high cost of novel pharmaceuticals for mRCC, this disease is becoming a reasonable part of Dutch healthcare expenditure.
Sunitinib, sorafenib and EV, have been reimburssed in the Nehterlands according to the Dutch Policy Rule for Expensive Hospital and Orphan Drugs (PREHO).
The primary goal of this study is to conduct a cost utlitity analysis of the application of EV in the Netherlands in comparison to BSC, for mRCC patients who failed to respond to sunitinib/sorafenib.
Time in cycles (1 cycle = 8 weeks)
Time in cycles (1 cycle = 8 weeks)
Figure 2. Estimating survival functions over PFS and OS Kaplan-Meier curves. Red solid lines – observed PFS (A) and OS (B) of EV from RECORD-1, black solid lines – observed PFS of BSC from RECORD-1. Dotted lines represent the estimated lognormal (A) and Weibull (B) survival functions.
Utilities for health states were drawn from published economic assessments of mRCC treatments.
Rates of adverse effects observed in RECORD-1 trial were used to weight the estimates of costs and utilities in the SD state.
Cost and effect estimates were used to create an incremental cost effectiveness ratio (ICER) estimate between EV and BSC
One-way univariate sensitivity analyses were used to asses the impact of uncertainty of a number of key model parameters on the base-case ICER estimate.
Parameter uncertainty was jointly assessed through a probabilistic sensitivity analysis (PSA) which enabled construction of a cost-effectiveness acceptability curve (CEAC).
Methods
A Markov model was designed with respect to the Dutch treatment protocols and a Dutch healthcare payer perspective was taken.
The model followed cohorts of hypothetical mRCC patients treated with EV and BSC, through three discrete health states: stable disease (SD), progressed disease (PD) and death (D).
All patients entered the model in the SD state; once patients progressed they remained in the PD state until death.
Each cohort consisted of 1,000 patients and was followed for 18 cycles, each lasting 8 weeks, which covered the lifetime horizon of all patients.
An annual discount rate of 1.5% for health gains and 4% for costs (0.23 and 0.61% per cycle, respectively) was applied from the second cycle.
Results
The base-case ICER for EV was estimated at €92,258/QALY (Table 1).
Univariate sensitivity analysis indicated the hazard multiplier as the most influential parameter; probabilities of OS and of PFS in the EV arm and the cost of EV were found to be important, but to a smaller extent.
Through PSA a wide 95% confidence interval around the base-case ICER estimate was revealed (€49,677 - €453,941/QALY)
At the informal threshold of €95,700/QALY (3 times Dutch GDP), EV had a 54% probability of being cost-effective
Disease Progression
Stable Disease
Death
Table 1. Base-case cost effectiveness results EV vs BSC
Therapeutic method EV
BSC
Difference
Costs (€)
17,178
663
16,515
Utilities (QALY)
0.49
0.31
0.18
ICER (€/QALY):
92,258
Figure 1: Markov model structure.
Transitions through the health states of the model were based on time-dependent probabilities, extracted from the PFS and overall survival (OS) estimates published in the RECORD-1 clinical trial.
The probability of remaining in the SD state was estimated using a lognormal distribution fitted over the PFS estimates for both EV and BSC arm.
Probabilities of OS for EV were extracted from the OS estimates using a Weibull distribution.
Since the design of the trial allowed cross-over of BSC patients, OS for BSC was estimated indirectly, applying a hazard multiplier estimated through the Inverse Probability of Censoring Weight method.
Transition from SD to PD state was calculated as the difference between PFS and OS for each of the arms in the trial.
From the available OS curves it was impossible to differ OS in SD and PD patients, thus the same probabilities were assumed for transition from SD and PD to D state.
The cost components of mRCC treatment were defined according to the existing guidelines and clinical experts’ opinion; subsequently, cost estimates for each component were sourced from official pricelists of the Health Care Insurance Board (CvZ).
A B
Figure 3. Tornado diagram (A) and CEAC (B) presenting the results of the univariate and probabilisic sensitivity analysis, respectively.
Conclusion
The base-case ICER was just below the upper cost-effectiveness limit recommended by WHO, indicating that everolimus might be a cost-effective option in the Dutch setting
A major drawback on the estimation of cost effectiveness of EV is the uncertainty around the effect of EV on extending OS.
Efforts should be undertaken to perform an integral assessment of the economic attractiveness of all current and new therapeutics in mRCC.
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For a copy of the poster:
PharmacoEpidemiology
&
PharmacoEconomics