The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation.

OBJECTIVES To establish the effectiveness and cost-effectiveness of cinacalcet for the treatment of secondary hyperparathyroidism (SHPT) for people on dialysis due to end-stage renal disease (ESRD). DATA SOURCES Electronic databases were searched up to February 2006. REVIEW METHODS Included randomised controlled trials (RCTs) on the clinical effectiveness of cinacalcet for SHPT in ESRD were critically appraised, had relevant data extracted and were summarised narratively. A Markov (state transition) model was developed that compared cinacalcet in addition to current standard treatment with phosphate binders and vitamin D to standard treatment alone. A simulated cohort of 1000 people aged 55 with SHPT was modelled until the whole cohort was dead. Incremental costs and quality-adjusted life-years (QALYs) were calculated. Extensive one-way sensitivity analysis was undertaken as well as probabilistic sensitivity analysis. RESULTS Seven trials comparing cinacalcet plus standard treatment with placebo plus standard treatment were included in the systematic review. A total of 846 people were randomised to receive cinacalcet. Cinacalcet was more effective at meeting parathyroid hormone (PTH) target levels (40% vs 5% in placebo, p < 0.001). In those patients meeting PTH targets, 90% also experienced a reduction in calcium-phosphate product levels, compared with 1% in placebo. Significantly fewer people treated with cinacalcet were hospitalised for cardiovascular events, although no difference was seen in all-cause hospitalisation or mortality. Significantly fewer fractures and parathyroidectomies were also seen with cinacalcet. Findings on all patient-based clinical outcomes were based on small numbers. The authors' economic model estimated that, compared to standard treatment alone, cinacalcet in addition to standard care costs an additional 21,167 pounds and confers 0.34 QALYs (or 18 quality-adjusted weeks) per person. The incremental cost-effectiveness ratio (ICER) was 61,890 pounds/QALY. In most cases, even extreme adjustments to individual parameters did not result in an ICER below a willingness-to-pay threshold of 30,000 pounds/QALY with probabilistic analysis showing only 0.5% of simulations to be cost-effective at this threshold. Altering the assumptions in the model through using different data sources for the inputs produced a range of ICERs from 39,000 pounds to 92,000 pounds/QALY. CONCLUSIONS Cinacalcet in addition to standard care is more effective than placebo plus standard care at reducing PTH levels without compromising calcium levels. However, there is limited information about the impact of this reduction on patient-relevant clinical outcomes. Given the short follow-up in the trials, it is unclear how data should be extrapolated to the long term. Together with the high drug cost, this leads to cinacalcet being unlikely to be considered cost-effective. Recommendations for future research include obtaining accurate estimates of the multivariate relationship between biochemical disruption in SHPT and long-term clinical outcomes.