Symptoms of Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Although multiple lines of evidence suggest a negative impact of secondary hyperparathyroidism on patients with kidney failure treated by hemodialysis, it is uncertain whether patients can detect associated symptoms. The objective was to determine whether changes in parathyroid hormone (PTH) levels are associated with changes in symptoms within this patient population. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 165 adults with hyperparathyroidism secondary to kidney failure diagnosed, a range of dialysis vintages, and receiving regular hemodialysis from a US single-provider organization. EXPOSURE: Change in PTH levels over 24 weeks. OUTCOMES: 19 putative symptoms of secondary hyperparathyroidism measured up to 4 times using a self-administered questionnaire that assessed severity on a 5-level ordinal scale. ANALYTICAL APPROACH: Longitudinal associations between changes in PTH levels and symptom severity were assessed using generalized additive models. RESULTS: The 165 participants studied represented 81% of enrollees (N=204) who had sufficiently complete data for analysis. Mean age was 56 years and 54% were women. Increases in PTH levels over time were associated (P<0.1) with worsening of bone aches and stiffness, joint aches, muscle soreness, overall pain, itchy skin, and tiredness, and the effects were more pronounced with larger changes in PTH levels. LIMITATIONS: Findings may have been influenced by confounding by unmeasured comorbid conditions, concomitant medications, and multiple testing coupled with a P value threshold of 0.10. CONCLUSIONS: In this exploratory study, we observed that among patients with secondary hyperparathyroidism, increases in PTH levels over time were associated with worsening of 1 or more cluster of symptoms. Replication of these findings in other populations is needed before concluding about the magnitude and shape of these associations. If replicated, these findings could inform clinically useful approaches for measuring patient-reported outcomes related to secondary hyperparathyroidism.

Real World Use and Effects of Calcimimetics in Treating Mineral and Bone Disorder in Hemodialysis Patients.

BACKGROUND: Calcimimetics are used to treat mineral and bone disorder by reducing parathyroid hormone (PTH), calcium (Ca), and phosphorus (Phos). The study objectives were to assess the control of PTH, Ca, and Phos over time in patients receiving cinacalcet or etelcalcetide as well as dosing and time to discontinuation for etelcalcetide. METHODS: This was a retrospective cohort study using electronic medical records from small and independent dialysis centers. Adults ≥18 years of age were identified as cinacalcet or etelcalcetide users based on the first calcimimetic received in 2018 (index date). Patients were followed from the index date until parathyroidectomy, kidney transplant, death, or end of data (December 31, 2018). Analyses of mean PTH, Ca, and Phos, as well as target achievement of PTH, Ca, and Phos were conducted over a 9-month period. Discontinuation with etelcalcetide was measured with the Kaplan-Meier estimator. RESULTS: There were 1,346 cinacalcet patients (mean age 60.5 years, 43.5% female, and 47.1% Black) and 1,255 etelcalcetide patients (mean age 63.4 years, 46.6% female, and 38.5% Black). At baseline, the proportions in target were similar for etelcalcetide versus cinacalcet: 36 versus 38% for PTH, 79 versus 80% for Ca, and 43 versus 44% for Phos. Overall, 40-47% of cinacalcet users and 48-62% of etelcalcetide users were observed to be in target for PTH over 9 months. The proportion in target for Phos ranged from 41 to 46% for cinacalcet and 46-51% for etelcalcetide. The proportion in target for Ca ranged from 74 to 78% for cinacalcet and 60-73% for etelcalcetide. Etelcalcetide 12-month discontinuation was 37.4%. CONCLUSION: Both calcimimetics were effective in keeping PTH, Ca, and Phos levels within target. Patients receiving etelcalcetide tended to have lower laboratory values for PTH, Ca, and Phos over time, while patients receiving cinacalcet tended to be more likely to be in target for Ca over time.

Hemodialysis patients' preferences for the management of secondary hyperparathyroidism.

BACKGROUND: Patient engagement and patient-centered care are critical in optimally managing patients with end-stage renal disease (ESRD). Understanding patient preferences is a key element of patient-centered care and shared decision making. The objective of this study was to elicit patients' preferences for the treatment of secondary hyperparathyroidism (SHPT) associated with ESRD using a discrete-choice experiment survey. METHODS: Clinical literature, nephrologist input, patient-education resources, and a patient focus group informed development of the survey instrument, which was qualitatively pretested before its administration to a broader sample of patients. The National Kidney Foundation invited individuals in the United States with ESRD who were undergoing hemodialysis to participate in the survey. Respondents chose among three hypothetical SHPT treatment alternatives (two medical alternatives and surgery) in each of a series of questions, which were defined by attributes of efficacy (effect on laboratory values and symptoms), safety, tolerability, mode of administration, and cost. The survey instrument included a best-worst scaling exercise to quantify the relative bother of the individual attributes of surgery. Random-parameters logit models were used to evaluate the conditional relative importance of the attributes. RESULTS: A total of 200 patients with ESRD completed the survey. The treatment attributes that were most important to the respondents were whether a treatment was a medication or surgery and out-of-pocket cost. Patients had statistically significant preferences for efficacy attributes related to symptom management and laboratory values, but placed less importance on the attributes related to mode of administration and side effects. The most bothersome attribute of surgery was the risk of surgical mortality. CONCLUSIONS: Patients with ESRD and SHPT who are undergoing hemodialysis understand SHPT and have clear and measurable treatment preferences. These results may help inform clinicians about patients' preferences regarding treatment options for a common complication of ESRD.

Estimating Health-State Utility for Economic Models in Clinical Studies: An ISPOR Good Research Practices Task Force Report.

Cost-utility models are increasingly used in many countries to establish whether the cost of a new intervention can be justified in terms of health benefits. Health-state utility (HSU) estimates (the preference for a given state of health on a cardinal scale where 0 represents dead and 1 represents full health) are typically among the most important and uncertain data inputs in cost-utility models. Clinical trials represent an important opportunity for the collection of health-utility data. However, trials designed primarily to evaluate efficacy and safety often present challenges to the optimal collection of HSU estimates for economic models. Careful planning is needed to determine which of the HSU estimates may be measured in planned trials; to establish the optimal methodology; and to plan any additional studies needed. This report aimed to provide a framework for researchers to plan the collection of health-utility data in clinical studies to provide high-quality HSU estimates for economic modeling. Recommendations are made for early planning of health-utility data collection within a research and development program; design of health-utility data collection during protocol development for a planned clinical trial; design of prospective and cross-sectional observational studies and alternative study types; and statistical analyses and reporting.

Economic Evaluation of Cinacalcet in the United States: The EVOLVE Trial.

BACKGROUND: Previous economic evaluations of cinacalcet in patients with secondary hyperparathyroidism (sHPT) relied on the combination of surrogate end points in clinical trials and epidemiologic studies. OBJECTIVES: The objective was to conduct an economic evaluation of cinacalcet on the basis of the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial from a US payer perspective. METHODS: We developed a semi-Markov model to assess the cost-effectiveness of cinacalcet in addition to conventional therapy, compared with conventional therapy alone, in patients with moderate-to-severe sHPT receiving hemodialysis. We used treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and prespecified covariate-adjusted ITT analysis as our main analyses. We assessed model sensitivity to variations in individual inputs and overall decision uncertainty through probabilistic sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) for cinacalcet was $61,705 per life-year and $79,562 per quality-adjusted life-year (QALY) gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 73.2% chance of the ICER being below a willingness-to-pay threshold of $100,000. Treatment effects from unadjusted ITT analysis yielded an ICER of $115,876 per QALY. The model was most sensitive to the treatment effect on mortality. CONCLUSIONS: In the unadjusted ITT analysis, cinacalcet does not represent a cost- effective use of health care resources when applying a willingness-to-pay threshold of $100,000 per QALY. When using the covariate-adjusted ITT treatment effect, which represents the least biased estimate, however, cinacalcet is a cost-effective therapy for patients with moderate-to-severe sHPT on hemodialysis.

Health state utilities associated with major clinical events in the context of secondary hyperparathyroidism and chronic kidney disease requiring dialysis.

BACKGROUND: Patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require dialysis are at increased risk for cardiovascular events and bone fractures. To assist in economic evaluations, this study aimed to estimate the disutility of these events beyond the impact of CKD and SHPT. METHODS: A basic one-year health state was developed describing CKD and SHPT requiring dialysis. Further health states added acute events (cardiovascular events, fractures, and surgical procedures) or chronic post-event effects. Acute health states described a year including an event, and chronic health states described a year subsequent to an event. General population participants in Canada completed time trade-off interviews from which utilities were derived. Pairwise comparisons were made between the basic state and event, and between comparable health states. RESULTS: A total of 199 participants (54.8% female; mean age = 46.3 years) completed interviews. Each health state had ≥130 valuations. The mean (SD) utility of the basic health state was 0.60 (0.34). For acute events, mean utility differences versus the basic state were: myocardial infarction, -0.06; unstable angina, -0.05; peripheral vascular disease (PVD) with amputation, -0.33; PVD without amputation, -0.11; heart failure, -0.14; stroke, -0.30; hip fracture, -0.14; arm fracture, -0.04; parathyroidectomy, +0.02; kidney transplant, +0.06. Disutilities for chronic health states were: stable angina, -0.09; stroke, -0.27; PVD with amputation, -0.30; PVD without amputation, -0.12; heart failure, -0.14. CONCLUSIONS: Cardiovascular events and fractures were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of CKD and SHPT.

Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

BACKGROUND: Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies. METHODS: We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels. RESULTS: A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89). CONCLUSIONS: Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates.

Healthcare use and costs before and after parathyroidectomy in patients on dialysis.

BACKGROUND: Parathyroidectomy (PTX) is often performed in dialysis patients when medical treatment fails to control secondary hyperparathyroidism (SHPT). PTX is viewed by many as a cost-containing measure for patients who have been treated with vitamin D analogs and calcimimetics. Yet, information about health resource utilization and costs before and after PTX is limited. METHODS: This retrospective cohort study used professional service and pharmacy claims to identify subjects on dialysis undergoing PTX from 1/1/2008-12/31/2010. Only subjects with at least six months of information before and after PTX were considered. Subjects with primary hyperparathyroidism or kidney transplant were excluded. Prescription use, physician encounters, and surgical complications were compared during the six months immediately before and after PTX. RESULTS: The mean (SD) age of the 181 study subjects was 51 (15) years; 59% female; and 80% insured by Medicare. Overall, the percentage of patients receiving medications to manage altered mineral metabolism increased from 67% before to 79% after PTX. Specifically, oral vitamin D use increased, while the utilization of cinacalcet decreased resulting in mean (SD) monthly medication charges decreasing from $486 (507) to $226 (288) (p < 0.01). The mean (SD) number of physician encounters rose from 15 (14) before to 21 (22) per 6 months after PTX (p < 0.01) resulting in the corresponding increase in mean (SD) monthly charges from $1531 (2150) to $1965 (3317) (p = 0.08). Hypocalcemia was the predominant diagnosis recorded for post-surgical physician encounters occurring in 31% of all subjects; 84% of hypocalcemic episodes were managed in acute care facilities. CONCLUSIONS: The cost of medications to manage SHPT decreased after PTX largely due to reduction in cinacalcet use, whereas vitamin D use increased likely to manage hypocalcemia. The frequency and cost of physician encounters, especially in acute care settings, were higher in the 6 months after PTX attributable largely to episodes of severe hypocalcemia. Overall, the reduction in prescription costs during the 6 months after PTX is outweighed by the higher costs associated with physician care.

Impact of mineral and bone disorder on healthcare resource use and associated costs in the European Fresenius medical care dialysis population: a retrospective cohort study.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is associated with mortality in patients with chronic kidney disease (CKD), but the economic consequences of SHPT have not been adequately studied in the European population. We assessed the relationship between SHPT parameters (intact parathyroid hormone [iPTH], calcium, and phosphate) and hospitalisations, medication use, and associated costs among CKD patients in Europe. METHODS: The analysis of this retrospective cohort study used records of randomly selected patients who underwent haemodialysis between January 1, 2005 and December 31, 2006 at participating European Fresenius Medical Care facilities in 10 countries. Patients had ≥ 1 iPTH value recorded, and ≥ 1 month of follow-up after a 3-month baseline period during which SHPT parameters were assessed. Time at risk was post-baseline until death, successful renal transplantation, loss to follow-up, or the end of follow-up. Outcomes included cost per patient-month, rates of hospitalisations (cardiovascular disease [CVD], fractures, and parathyroidectomy [PTX]), and use of SHPT-, diabetes-, and CVD-related medications. National costs were applied to hospitalisations and medication use. Generalised linear models compared costs across strata of iPTH, total calcium, and phosphate, adjusting for baseline covariates. RESULTS: There were 6369 patients included in the analysis. Mean ± SD person-time at risk was 13.1 ± 6.4 months. Patients with iPTH > 600 pg/mL had a higher hospitalisation rate than those with lower iPTH. Hospitalisation rates varied little across calcium and phosphate levels. SHPT-related medication use varied with iPTH, calcium, and phosphate. After adjusting for demographic and clinical variables, patients with baseline iPTH > 600 pg/mL had 41% (95% CI: 25%, 59%) higher monthly total healthcare costs compared with those with iPTH in the K/DOQI target range (150-300 pg/mL). Patients with baseline phosphate and total calcium levels above target ranges (1.13-1.78 mmol/L and 2.10-2.37 mmol/L, respectively) had 38% (95% CI: 27%, 50%) and 8% (95% CI: 0%, 17%) higher adjusted monthly costs, respectively. Adjusted costs were 25% (95% CI: 18%, 32%) lower among patients with baseline phosphate levels below the target range. Results were consistent in sensitivity analyses. CONCLUSIONS: These data suggest that elevated SHPT parameters increase the economic burden of CKD in Europe.

The burden of adult asthma in the United States: evidence from the Medical Expenditure Panel Survey.

BACKGROUND: It is important to have an accurate picture of the sources and extent of medical expenditures and productivity loss to understand the nature and scope of the burden of asthma in the United States (US). OBJECTIVE: The current study aims to provide recent nationally representative estimates of direct and productivity-related costs attributable to asthma in adults in the US. METHODS: The 2003 and 2005 Medical Expenditure Panel Surveys were used to estimate the effect of asthma on medical expenditures, use, productivity, and chronic comorbidity among adults (≥ 18 years). Productivity-related outcome variables included employment, annual wages, missed work days, days spent sick in bed, and activity limitations. Multivariate regression was conducted, controlling for sociodemographics and comorbidity. RESULTS: Of 44,795 adults, 1,935 reported an encounter for asthma [corrected]. Compared with those without, subjects with asthma were significantly less likely to be employed (odds ratio, 0.78), spent 1.4 more days sick in bed annually, and were significantly more likely to have activity limitations or to be unable to work. Adults with asthma incurred an additional $1,907 (2008 US dollars) annually and experienced higher health care use and comorbidity. The total national medical expenditure attributable to adult asthma was $18 billion. Adults with asthma were more likely to be covered by Medicaid (30%) than the general adult population (10%). The largest contributors to medical expenditures for adults with asthma were prescription drugs, followed by inpatient hospitalizations and home health care. CONCLUSIONS: In recent national data adult asthma is associated with a significant deleterious effect on direct and indirect costs in the US.

Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.

BACKGROUND: Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial. OBJECTIVE: To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation. METHODS: This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma. At baseline, patients had an ACQ score ≥1.5. Exacerbations were defined as requirement for systemic corticosteroids. A Cox proportional hazards model was used, with ACQ score as the time-dependent covariate. The analysis was repeated for individual components of the ACQ. RESULTS: Each 1-point increase in ACQ was associated with a 50% increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the following 2-week period. Evaluation of individual ACQ components also demonstrated a similar trend, though each to a lesser degree than the full composite ACQ. CONCLUSION: Although based on a retrospective analysis, with small number of exacerbations, these findings support the utility of the composite ACQ score measurement to predict risk of future exacerbation in clinical trials and clinical practice. The composite ACQ score measurement was found to be a better predictor of future risk than individual ACQ components.

An epidemiological study of hemodialysis patients based on the European Fresenius Medical Care hemodialysis network: results of the ARO study.

BACKGROUND/AIMS: ARO, an observational study of hemodialysis (HD) patients in Europe, aims to enhance our understanding of patient characteristics and practice patterns to improve patient outcome. METHODS: HD patients (n = 8,963) from 134 Fresenius Medical Care facilities treated between 2005 and 2006 were randomly selected from 9 European countries (Czech Republic, France, Hungary, Italy, Poland, Portugal, Spain, Slovak Republic and Slovenia) and Turkey. Information was captured on demographics, comorbidities, medications, laboratory and dialysis parameters, and outcome. RESULTS: Patients were followed for 1.4 ± 0.7 years. Wide variation by country was observed for age, sex and diabetes as a cause of chronic kidney disease. Cardiovascular disease was present in 73% of patients. Dialysis parameters were homogeneous across countries. Arteriovenous fistulas were frequently used (73%). More incident patients had hemoglobin <11 g/dl than prevalent patients (50 vs. 33%, respectively). Phosphatemia and intact parathyroid hormone were similar between incident and prevalent patients (4.7 ± 1.2 mg/dl and 190 vs. 213 ng/l, respectively). Medication use varied widely by country. In total, 5% of patients underwent renal transplantation. Overall death rate was 124/1,000 patient-years. CONCLUSION: ARO revealed differences in HD practice patterns and patient characteristics in the 10 participating countries. Future ARO studies will fill gaps in the knowledge about the care of European HD patients.

The association of vitamin D use with hypercalcemia and hyperphosphatemia in hemodialysis patients: a case-crossover study.

PURPOSE: Elevated levels of phosphorus (P) and calcium (Ca) have been shown in observational studies to be associated with an increased risk of adverse clinical outcomes including mortality. Vitamin D sterols have been shown to increase the risk of hypercalcemia and hyperphosphatemia in clinical trials. We sought to explore these risks in real-world clinical practice. METHODS: We employed a case-crossover design, which eliminates confounding by non-time-varying patient characteristics by comparing, within each patient, vitamin D doses before the event with those at an earlier period. Using this method, we estimated the risk of hypercalcemic (Ca ≥ 11 g/dL) and hyperphosphatemic (P ≥ 8 g/dL) events for patients at different dose quartiles of vitamin D relative to patients not on a vitamin D sterol. RESULTS: There was a dose-dependent association between vitamin D dose quartile and risk of hypercalcemia or hyperphosphatemia. In adjusted analyses, each increase in vitamin D quartile was associated with a multiple of hypercalcemia risk between 1.7 and 19 times compared with those not on vitamin D and a multiple of hyperphosphatemia risk between 1.8 and 4. CONCLUSION: Use of vitamin D sterols is associated with an increased risk of hypercalcemic and hyperphosphatemic events in real-world clinical practice. Other potential predictors of these events, such as phosphate binder use and dialysate Ca levels, were not examined in this analysis.

Healthcare resource utilization and associated cost of patients with bone metastases from solid tumors who are naïve to bone-targeting agents: a comparative analysis of patients with and without skeletal-related events.

BACKGROUND: This study analyzes the impact of skeletal-related events (SRE) on healthcare resource utilization (HCRU) and costs incurred by patients with bone metastases (BM) from solid tumors (ST), who are therapy-naïve to bone targeting agents (BTAs). METHODS: German claims data from 01/01/2010 to 30/06/2018 were used to conduct a retrospective comparative cohort analysis of BTA-naive patients with a BM diagnosis and preceding ST diagnosis. HCRU and treatment-related costs were compared in two matched cohorts of patients with and without a history of SREs, defined as pathological fracture, spinal cord compression, surgery to bone and radiation to bone. The first SRE was defined as the patient-individual index date. Conversely, for the non-SRE patients, index dates were assigned randomly. RESULTS: In total, 45.20% of 9,832 patients reported experiencing at least one SRE (n = 4444) while 54.80% experienced none (n = 5388); 2,434 pairs of SRE and non-SRE patients were finally matched (mean age: 70.87/71.07 years; females: 39.07%/38.58%). Between SRE and non-SRE cohorts, significant differences in the average number of hospitalization days per patient-year (35.80/30.80) and associated inpatient-care costs (14,199.27€/10,787.31€) were observed. The total cost ratio was 1.16 (p < 0.001) with an average cost breakdown of 23,689.54€ and 20,403.27€ per patient-year in SRE and non-SRE patients. CONCLUSION: The underutilization of BTAs within a clinical setting poses an ongoing challenge in the real-world treatment of BM patients throughout Germany. Ultimately, the economic burden of treating SREs in patients with BM from ST was found to be considerable, resulting in higher direct healthcare costs and increased utilization of inpatient care facilities.

Comparison of health state utility estimates from instrument-based and vignette-based methods: a case study in kidney disease.

OBJECTIVE: We take advantage of a rare occurrence when two different studies report on the estimation of quality of life utilities for the same health states to assess convergence of the reported measures. Health state utilities are important inputs into health economic models that estimate the impact of new medical technologies using a common metric of health gain-the quality adjusted life-year. RESULTS: We find low concordance between the two measures which is concerning in that this could have important ramifications for health care decision making based on estimated cost-effectiveness. We explore possible reasons for the discrepancy between the two measures and draw implications for the design of future studies.

Variability in Cinacalcet Prescription across US Hemodialysis Facilities.

BACKGROUND AND OBJECTIVES: Calcimimetic drugs used to treat secondary hyperparathyroidism are being considered for inclusion in the Medicare ESRD Prospective Payment System bundle after an evaluation period. Understanding of utilization patterns of calcimimetics across dialysis facilities may help align financial incentives with clinical objectives. Our study's purpose was to describe the distribution of cinacalcet prescription across United States hemodialysis facilities and to explore factors that may influence cinacalcet utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used monthly cross-sectional data from the Dialysis Outcomes and Practice Patterns Study in 2014 to characterize the distribution of cinacalcet prescription across 203 United States hemodialysis facilities (10,521 patients). On the basis of associations with parathyroid hormone levels from patient-level analyses, we used linear mixed-effects regressions to estimate the associations between three facility-level exposures (black race, <65 years old, and having ≥3 years on dialysis [vintage]) and the prevalence of cinacalcet prescription, adjusting for facility- and patient-level potential confounders. RESULTS: The mean percentage of patients in each facility with cinacalcet prescription was 23% in June 2014 (median, 22%; interquartile range, 13%-30%). Adjusted for facility-level and nonexposure patient-level variables, the difference in prevalence of cinacalcet prescription between facilities with the highest and lowest quartiles of percentage of black patients was 7.8% (95% confidence interval [95% CI], 0.8% to 14.8%; P for trend =0.03). The adjusted prevalence difference was 7.3% for the percentage of patients aged <65 years (95% CI, -0.1% to 14.7%; P for trend =0.06) and 11.9% for the percentage of patients with ≥3 years of dialysis (95% CI, 2.4% to 21.4%; P for trend =0.02). These associations changed appreciably, becoming much weaker or even reversing, after further adjusting for the patient-level exposure variables. CONCLUSIONS: Facilities treating more patients who are black, under age 65 years, and having dialysis vintage ≥3 years have higher average levels of cinacalcet prescription. However, these differences were strongly attenuated after accounting for the unbalanced distributions of these patient case-mix variables.

Abnormal bone and mineral metabolism in kidney transplant patients--a review.

BACKGROUND/AIMS: Abnormal bone and mineral metabolism is common in patients with kidney failure and often persists after successful kidney transplant. METHODS: To better understand the natural history of this disease in transplant patients, we reviewed the literature by searching MEDLINE for English language articles published between January 1990 and October 2006 that contained Medical Subject Headings and key words related to secondary or persistent hyperparathyroidism and kidney transplant. RESULTS: Parathyroid hormone levels decreased significantly during the first 3 months after transplant but typically stabilized at elevated values after 1 year. Calcium tended to increase after transplant and then stabilize at the higher end of the normal range within 2 months. Phosphorus decreased rapidly to within or below normal levels after surgery and hypophosphatemia, if present, resolved within 2 months. Low levels of 1,25(OH)2 vitamin D typically did not reach normal values until almost 18 months after transplant. CONCLUSION: This review provides evidence demonstrating that abnormal bone and mineral metabolism exists in patients after kidney transplant and suggests the need for treatment of this condition. However, better observational and interventional research is needed before advocating such a treatment guideline.

Cost-effectiveness of early versus late cinacalcet treatment in addition to standard care for secondary renal hyperparathyroidism in the USA.

OBJECTIVES: The objective of this research was to estimate lifetime cost-effectiveness of treating patients with cinacalcet early (when parathyroid hormone [PTH] levels are in the range of 300-500 pg/ml) versus delaying treatment with cinacalcet (cinacalcet initiated when PTH levels are > 800 pg/ml) in patients with secondary hyperparathyroidism (SHPT) in the US setting. METHODS: A Markov model was developed to simulate the effects of early versus delayed use of cinacalcet (plus standard of care). Four different PTH ranges (< or = 300 pg/ml; 301-500 pg/ml; 501-800 pg/ml; > 800 pg/ml) were used to represent four different health states within the Markov model. Associated with each Markov state (PTH range) were varying risks of major SHPT complications, including cardiovascular disease (CVD), fracture (Fx), and parathyroidectomy (PTx). Baseline cohort characteristics and risks of CVD, Fx, and PTx by PTH category were derived from a large US renal database and published sources. Costs were estimated from the US Renal Data System database and reported in 2006 US Dollars ($). Clinical and economic outcomes were discounted at 3.0% per annum. RESULTS: Early treatment was projected to improve quality-adjusted life years (QALYs) by 0.337 years compared to delaying treatment. The incremental cost-effectiveness ratio was $17,275 per QALY gained. CONCLUSIONS: Early treatment with cinacalcet was associated with improvements in QALYs and would represent good value for money compared to delaying treatment with cinacalcet.

Prices For Common Cardiovascular Drugs In The US Are Not Consistently Aligned With Value.

Health care reimbursement agencies in countries other than the US often rely on cost-effectiveness evidence for drug coverage decisions, signaling to drug manufacturers their expectations for value-based pricing. To see whether drug prices in the US are influenced by value, we estimated the range of cost-effectiveness for thirty frequently prescribed cardiovascular drugs. We extrapolated evidence from randomized controlled trials to determine average lifetime quality-adjusted life-years (QALYs) and payer-related costs and to calculate incremental cost-effectiveness ratios (ICERs), the principal metric of cost-effectiveness studies. Across the thirty drugs, the ICERs ranged from cost-saving with increased QALYs to more costly with decreased QALYs. This range suggests that drug pricing is not consistently influenced by value, or that such influence is masked by inaccessible factors, such as price discounts. Our findings highlight the need to debate how to define and use value-based evidence to inform US coverage and reimbursement decision making.

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.