Medication costs and fracture reduction efficacy were

assumed to be proportional to compliance. The annual cost of strontium Tanespimycin in vitro ranelate was estimated at €477.2 (Protelos®, €109.82 for a package of 84 sachets) [48], and we assigned the cost of one physician visit (€22.67) per year of treatment and the cost of one bone density measurement (€58.05) every second year. Adverse events with strontium ranelate are usually mild and transient. In pooled STI571 data from the SOTI and TROPOS trials [5, 7], treatment with strontium ranelate, however, was associated with an increase in the annual incidence of VTE, including pulmonary embolism (PE). To account for this in the analysis, VTE was included as a health state in the model during treatment with strontium ranelate. The annual absolute risk of VTE with strontium ranelate was estimated at 0.31 % in women [5, 7]. In the model, VTE was assumed to be associated with a 10 % utility loss the first year after the event and any utility loss in the second or following years after the event, in agreement with previous health economic publications [49, 50]. The survival rate after PE was estimated at 81.6 % in the clinical trials [5, 7]. Using Belgian estimates of resource utilization based on panel experts [51], the cost of VTE was estimated at €2,622. Simulation and analyses

Microsimulations were performed to estimate the cost-effectiveness of strontium ranelate. Each model was run ten click here times with 200,000 trials (patients) to guarantee the stability of the results and enable variability analyses [23]. For each analysis, the incremental cost-effectiveness ratio (ICER) was computed as the difference between Morin Hydrate strontium ranelate and no treatment in terms of total costs (expressed in €2,010)

divided by the difference between them in terms of effectiveness, expressed in accumulated QALYs. It represents the cost of strontium ranelate (compared with no treatment) per one QALY gained. In Belgium, as in many other countries, no threshold values for ICERs have been defined [52]. Commonly accepted thresholds for cost-effectiveness are in the range of €50,000 [11]. Uncertainty related to model parameters and assumptions was investigated using deterministic and probabilistic sensitivity analyses. Deterministic sensitivity analyses were performed to evaluate the impact of single parameter variations on the results. The baseline parameters for discount rates, fracture risk, fracture disutility, fracture cost and excess mortality were varied over plausible ranges. Changes in therapy cost, monitoring cost, adverse events, offset time and time horizon were also evaluated. Probabilistic sensitivity analyses were performed with 200 simulations to analyze the effects of uncertainty in all model parameters simultaneously. Distributions used for key model inputs are provided in Table 1. Log-normal distributions were also assumed for fracture risk reduction with strontium ranelate.