ROBUSTNESS OF COST-EFFECTIVENESS ESTIMATES FOR CINACALCET IN SECONDARY HYPERPARATHYROIDISM BASED ON THE ADVANCE TRIAL

Purpose: To estimate the cost-effectiveness of cinacalcet and vitamin D for treatment of secondary hyperparathyroidism (SHPT) compared to vitamin D alone.

Methods: We developed a patient-level simulation Markov model that closely reproduces relevant data of patients in the ADVANCE trial, including serum levels of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) as they changed over time. After the trial, each life history is projected by expected probabilities of events, similar to a population-level Markov model. Projections of effects are based on relationships of PTH, Ca, and P with mortality, cardiovascular events, fractures, and parathyroidectomies as reported from different published data sources. Three model variations concern dose-effect relationships based on: Block, a large observational study; Cunningham, a combined analysis of four randomized trials of cinacalcet; and Danese, a study investigating the effect of duration in recommended targets. Two other model variations for mortality, cardiovascular events, fractures, and parathyroidectomies after the end of the trial concern: USRDS, the national registry of end-stage renal disease (event rates derived from all dialysis patients); and LDO, the large dialysis organizations registry (event rates derived from subjects with elevated levels of PTH, Ca, and P). The probabilistic sensitivity analysis (PSA) of the Block/USRDS variant considered trial result uncertainty by bootstrapping the set of patients as well as uncertainties of the model parameters used to project post-trial health effects.

Results: Results of the main model variants

	Cost difference / QALY gained			Difference of cost / year treated
Event rates	LDO	USRDS		LDO	USRDS
Dose-effect relationship
Block	$54,560	$68,906		$3,155	$2,910
Cunningham	Dominating	Dominating		-$2,698	-$8,904
Danese	$72,456	$78,250		$2,638	$2,217

The PSA showed a 95% likelihood to be cost-effective at a $100,000/QALY threshold. Approximately 70% of uncertainty in estimated net-benefit is from the limited trial size. The remainder is caused by the model parameters; of these, the (literature-derived) utility of dialysis patients and the cost of cardiovascular events cause the largest uncertainty. We also found that the structural assumptions around post-trial extrapolation of serum levels and therapy doses had limited effect on the cost-effectiveness ratio.

Conclusion: The cinacalcet ADVANCE economic model was robust to variations in key parameters used in the cost-effectiveness analysis, demonstrating that cinacalcet treatment could be considered cost-effective for treatment of SHPT in the United States healthcare setting.