Cost Effectiveness of Paricalcitol Versus Cinacalcet with Low-Dose Vitamin D for Management of Secondary Hyperparathyroidism in Haemodialysis Patients in the USA

In this secondary analysis of US patients enrolled in the IMPACT SHPT study, we found that intravenous paricalcitol-based therapy with or without supplemental cinacalcet was more cost effective than the combination of cinacalcet and low-dose vitamin D in the management of iPTH and calcium levels in patients with SHPT requiring haemodialysis. Whether effectiveness was measured in terms of the proportions of patients meeting the iPTH target of 150–300 pg/mL (the primary outcome), or in any of several other ways (the proportions of patients with ≥30 or ≥50 % reductions in iPTH levels, the proportions of patients who were normocalcaemic, or the proportions of patients who were normocalcaemic and also met the iPTH target), the paricalcitol-based regimen was more effective than the cinacalcet-based regimen. Similarly, when considering both the cost of the study drug and the phosphate binders, the paricalcitol-based regimen was less expensive. As a result, the paricalcitol-based regimen was dominant, compared with cinacalcet.

We used bootstrap analysis to provide a measure of the degree of error around our ICER point estimates. In over 99 % of bootstrap replicates, regardless of the effectiveness endpoint incorporated into the denominator of the ICER, our result remained dominant for paricalcitol over cinacalcet. These results provide a high degree of confidence about the precision of our results.

Our findings are consistent with those of other studies. Using data from all patients in the multinational IMPACT SHPT study, and including those who received either intravenous or oral regimens of paricalcitol or cinacalcet, we previously found that the annualized mean total drug costs (based on 2011 data) were €5387 in the paricalcitol group and €6870 in the cinacalcet group (a difference of €1492, p = 0.0395) [21]. Similarly, a post hoc analysis of the ACHIEVE study found that the average medication costs were 48 % higher (data from 2006) in patients treated with cinacalcet plus low-dose vitamin D than in those receiving either paricalcitol or doxercalciferol (US$5,501 versus US$3,709 in each group, respectively) [23]. Though not a cost-effectiveness analysis, the only other study that examined costs in paricalcitol- and cinacalcet-treated patients focused on costs related to parathyroidectomy—which occurred less frequently in those treated with paricalcitol [25].

The implications of our results are important for patients, health care providers and payers. Under recent Medicare rules, the reimbursement of care for dialysis patients is capitated. By 2016, both oral and injectable medications will be included in a single ‘all-inclusive bundle’ payment to providers. Under this scenario, providers are incentivized to prescribe the most cost-effective therapies. Our results suggest that a paricalcitol-based regimen is more cost effective than cinacalcet, and this may mean both improved outcomes for patients and reduced costs for providers and payers.

Our findings should be interpreted with an understanding of the limitations of our analysis. This was a post hoc analysis of data from the randomized, open-label, phase 4, multinational IMPACT SHPT study. The limitations of the IMPACT SHPT study have been described elsewhere [20, 24]. Here, we focus primarily on limitations that may have influenced the cost-effectiveness analysis. First, both the cost and effectiveness estimates we incorporated into our analysis were influenced by the IMPACT study protocol. For example, although they were based on approved labelling, the dosing of study drugs and phosphate binders in the IMPACT study may not have reflected actual practice for all patients in the USA. Further, like most clinical trials, the IMPACT SHPT study was short-term (28 weeks). Actual treatment of SHPT in patients on haemodialysis is longer term. We attempted to account for this by using a 1-year time horizon for our cost-effectiveness analysis. We annualized costs on the basis of the evaluation period, where dosing had stabilized. We also made the assumption that effectiveness did not change once dosing was stabilized. It is important to note that in the IMPACT study, patients who dropped out before reaching the evaluation period were not included in the analysis. However, the dropout rates were low for a clinical trial (approximately 20 % in the intravenous paricalcitol group and 30 % in the intravenous cinacalcet group).

The actual drug costs included in our analysis were not part of the IMPACT SHPT study data, but instead were estimated post hoc on the basis of the dosages used by each patient. We estimated the costs of the study drugs and phosphate binders by applying unit costs derived from an external database. This approach may have resulted in slightly different estimates than would have been obtained with actual costs. However, it is not likely that such differences would have changed either the direction or the magnitude of our results.

It is important to note that our cost analysis was restricted to study drugs and phosphate binders reported in the IMPACT SHPT study. An advantage of our analysis was that all of the cost and effectiveness results were from the same set of patients. Many cost-effectiveness studies, particularly those that involve modelling, use heterogeneous sources of data for costs and effectiveness and, because of that, they may be subject to bias. However, a limitation of our approach was that certain costs were not included, because they were not collected or recorded in the IMPACT SHPT study. For example, the utilization of laboratory tests, frequency of hospitalizations or physician office visits, and other health care utilization costs were not included. Inclusion of such costs could provide a more complete understanding of the cost effectiveness of paricalcitol and cinacalcet, particularly since we assumed a payer perspective. These additional costs are generally associated with differences in treatment effectiveness, adverse effects or monitoring. However, in the IMPACT SHPT study, the paricalcitol-based regimen was more effective than the cinacalcet-based regimen, and while the reported serious and severe adverse events were no different, adverse events leading to treatment discontinuation in patients receiving intravenous therapy were significantly less common in the paricalcitol group than in the cinacalcet group [20]. Moreover, there is no evidence that monitoring requirements are different between cinacalcet and paricalcitol. Therefore, it is unlikely that the direction of our results would have changed if those costs had been included.

One last potential limitation of our analysis relates to the generalizability of the population studied. A slightly higher percentage of US patients who enrolled in the IMPACT SHPT were Black or Hispanic, compared with the general population of ESRD patients. Data from the United States Renal Data System (USRDS) suggests that 36.1 % of ESRD patients in the USA are black and 15.1 % are Hispanic [26]. Across both groups in the IMPACT SHPT study, 44.9 % of US patients were black and 24.5 % were Hispanic. While this difference is small, because the response to therapy may differ by race and ethnicity, it should be considered.