Cost-consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada.

Aim: The costs and consequences of initial and delayed ofatumumab treatment were evaluated in relapsing-remitting multiple sclerosis with active disease in Canada. Materials & methods: A Markov cohort model was used (10-year horizon, annual cycle length, 1.5% discounting). Scenario analyses examined ofatumumab as first-line treatment versus 3 and 5 years following switch from commonly used first-line therapies. Results: Ofatumumab resulted in improvements in clinical outcomes (relapses and disease progression) and productivity (employment and full-time work), and reduction of economic burden (administration, monitoring and non-drug costs) that were comparable to other high-efficacy therapies (ocrelizumab, cladribine and natalizumab). Switching to ofatumumab earlier in the disease course may improve these outcomes. Conclusion: Results highlight the value of a high-efficacy therapy such as ofatumumab as initial treatment (i.e., first-line) in newly diagnosed relapsing-remitting multiple sclerosis patients with active disease.

Cost-Effectiveness Analysis of Ofatumumab for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada.

BACKGROUND: Ofatumumab is a high-efficacy disease-modifying therapy (DMT) approved for first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Canada. OBJECTIVE: The aim of this study was to evaluate the cost effectiveness of ofatumumab from a Canadian healthcare system perspective. METHODS: A Markov cohort model was run over 65 years using annual cycles, 1.5% annual discount rate, and 100% treatment discontinuation at 10 years. The British Columbia database informed natural history transition probabilities. Treatment efficacy for DMTs were sourced from a network meta-analysis. Clinical trial data were used to estimate probabilities for treatment-related adverse events. Health utilities and costs were obtained from Canadian sources (if available) and the literature. RESULTS: Among first-line indicated therapies for RRMS, ofatumumab was dominant (more effective, lower costs) over teriflunomide, interferons, dimethyl fumarate, and ocrelizumab. Compared with glatiramer acetate and best supportive care, ofatumumab resulted in incremental cost-effectiveness ratios (ICERs) of $24,189 Canadian dollars per quality-adjusted life-year (QALY) and $28,014/QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, ofatumumab had a 64.3% probability of being cost effective. Among second-line therapies (scenario analysis), ofatumumab dominated natalizumab and fingolimod and resulted in an ICER of $50,969 versus cladribine. CONCLUSIONS: Ofatumumab is cost effective against all comparators and dominant against all currently approved and reimbursed first-line DMTs for RRMS, except glatiramer acetate.

Health impact of tafamidis in transthyretin amyloid cardiomyopathy patients: an analysis from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and the open-label long-term extension studies.

AIM: The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed that tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to estimate the impact of tafamidis on survival and quality-adjusted life-years (QALYs). METHODS AND RESULTS: A multi-state, cohort, Markov model was developed to simulate the disease course of ATTR-CM throughout a lifetime. For survival extrapolation, survival curves were fitted by treatment arm and New York Heart Association (NYHA) Class I/II (68% of patients) and NYHA Class III (32% of patients) cohorts using the individual patient-level data from both the ATTR-ACT and the corresponding long-term extension study. Univariate and multivariate sensitivity analyses were conducted. The predicted mean survival for the total population (NYHA Class I/II + III) was 6.73 years for tafamidis and 2.85 years for the standard of care (SoC), resulting in an incremental mean survival of 3.88 years [95% confidence interval (CI) 1.32-5.66]. Of the 6.73 life-years, patients on tafamidis spend, on average, 4.82 years in NYHA Class I/II, while patients on SoC spend an average of 1.60 life-years in these classes. The combination of longer survival in lower NYHA classes produced a QALY gain of 5.39 for tafamidis and 2.11 for SoC, resulting in 3.29 incremental QALYs (95% CI 1.21-4.74) in favour of tafamidis. CONCLUSION: Based on the disease simulation model results, tafamidis is expected to more than double the life expectancy and QALYs of ATTR-CM patients compared to SoC. Longer-term follow-up data from the ATTR-ACT extension study will further inform these findings. CLINICAL TRIALS.GOV IDENTIFIER: NCT01994889 (date of registration: 26 November 2013).

Cost-effectiveness of combinatorial pharmacogenomic testing for depression from the Canadian public payer perspective.

Aim: Evaluate the cost-effectiveness of combinatorial pharmacogenomic (PGx) testing, versus treatment as usual (TAU), to guide treatment for patients with depression, from the Canadian public healthcare system perspective. Materials & methods: Clinical and economic data associated with depression were extracted from published literature. Clinical (quality-adjusted life years; QALYs) and economic (incremental cost-effectiveness ratio) outcomes were modeled using combinatorial PGx and TAU treatment strategies across a 5-year time horizon. Results: With the combinatorial PGx strategy to guide treatment, patients were projected to gain 0.14-0.19 QALYs versus TAU. Accounting for test price, combinatorial PGx saved CAD $1,687-$3,056 versus TAU. Incremental cost-effectiveness ratios ranged from -$11,861 to -$16,124/QALY gained. Conclusion: Combinatorial PGx testing was more efficacious and less costly compared with the TAU for depression.

Comparative effectiveness of catheter ablation devices in the treatment of atrial fibrillation: a network meta-analysis.

Atrial fibrillation (AF) ablation is most commonly performed using radiofrequency (RF) and cryoballoon (CB) catheters. Ablation Index is a novel lesion-quality marker associated with improved outcomes in RF ablation. Due to lack of direct comparative evidence between the latest generations of technologies, there is uncertainty regarding the best treatment option. Aim: To conduct a network meta-analysis to evaluate the comparative effectiveness of RF with Ablation Index to other catheter ablation devices in the treatment of AF. Methods: Searches for randomized and nonrandomized prospective comparative studies of ablation catheters were conducted in multiple databases. The outcome of interest was 12-month freedom from atrial arrhythmias after a single ablation procedure. Studies were grouped as high-, low- and unclear-quality based on study design and balanced baseline patient characteristics. Bayesian hierarchical network meta-analysis was conducted and results presented as relative risk ratios with 95% credible intervals (CrIs). Results: 12 studies evaluating five different catheter ablation devices were included. Radiofrequency ablation with Ablation Index was associated with statistically significantly greater probability of 12-month freedom from atrial arrhythmias than Arctic Front (relative risk: 1.77; 95% CrI: 1.21-2.87), Arctic Front Advance™ (1.41; 1.06-2.47), THERMOCOOL™ (1.34; 1.17-1.48) and THERMOCOOL SMARTTOUCH™ (1.09; 1-1.3). Results were robust in multiple sensitivity analyses. Conclusion: Radiofrequency catheter with Ablation Index is superior to currently available options for 12-month freedom from atrial arrhythmias after AF ablation. This study provides decision-makers with robust, pooled, comparative evidence of the latest ablation technologies.

The Use of Computer Simulation Modeling to Estimate Complications in Patients with Type 2 Diabetes Mellitus: Comparative Validation of the Cornerstone Diabetes Simulation Model.

OBJECTIVE: The objective of this study was to assess the validity of the Cornerstone Diabetes Simulation (CDS), a Microsoft Excel®-based patient-level simulation for type 2 diabetes mellitus based on risk equations from the revised United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2, also known as UKPDS 82). METHODS: Three levels of validation were conducted. Internal validation was assessed through independent review and model stress-testing. External validation was addressed by populating the CDS with baseline characteristics and treatment effects from three major diabetes clinical trials used in the Fifth Mount Hood Diabetes Challenge (MH5) for computer simulation models. Cross-validation of predicted outcomes was tested versus eight models that participated in the MH5. Simulated results were compared with observed clinical outcomes via the coefficient of determination (R2) for both the absolute risk of each clinical outcome and the difference in absolute risk between control and intervention arm in each trial. We ensured transparency of all model inputs and assumptions in reporting. RESULTS: The CDS could be used to predict 18 of 39 single and composite endpoints across the three trials. The model obtained an R2 of 0.637 for predicted versus observed absolute risks, and an R2 of 0.442 for predicted versus observed risk differences between control and intervention. Among the other eight models, only one obtained a higher R2 value under both definitions, albeit based on only four predicted endpoints. CONCLUSIONS: The CDS provides good predictions of diabetes-related complications when compared to observed trial outcomes and previously validated models. The model has value as a validated tool in cost-effectiveness evaluations.

Development, validation and results from the impact of treatment evolution in non-small cell lung cancer (iTEN) model.

OBJECTIVES: Treatment of advanced NSCLC (aNSCLC) is rapidly evolving, as new targeted and immuno-oncology (I-O) treatments become available. The iTEN model was developed to predict the cost and survival benefits of changing aNSCLC treatment patterns from a Canadian healthcare system perspective. This report describes iTEN model development and validation. MATERIALS & METHODS: A discrete event patient simulation of aNSCLC was developed. A modified Delphi process using Canadian clinical experts informed the development of treatment sequences that included commonly used, Health Canada approved treatments of aNSCLC. Treatment efficacy and the timing of progression and death were estimated from published Kaplan-Meier progression free and overall survival data. Costs (2018 CDN$) included were: drug acquisition and administration, imaging, monitoring, adverse events, physician visits, best supportive care, and end-of-life. RESULTS AND CONCLUSION: Clinical validity of the iTEN model was assessed by comparing model survival predictions to published real-world evidence (RWE). Four RWE studies that reported the overall survival of patients treated with a broad sampling of common aNSCLC treatment patterns were used for validation. The validation coefficient of determination was R2 = 0.95, with the model generally producing estimates that were neither optimistic nor conservative. The model estimated that current Canadian practice patterns yield a median survival of almost 13 months, a five-year survival rate of 3% and a life-time per-treated-patient cost of $110,806. Cost and survival estimates are presented and were found to vary by aNSCLC subtype. In conclusion, the iTEN model is a reliable tool for forecasting the impact on cost and survival of new treatments for aNSCLC.

Treatment of Atrial Fibrillation Using Ablation Index-Guided Contact Force Ablation: A Matching-Adjusted Indirect Comparison to Cryoballoon Ablation.

INTRODUCTION: Ablation Index, also known as VISITAG SURPOINT™, is a novel lesion-quality marker that improves outcomes in radiofrequency (RF) catheter ablation of atrial fibrillation (AF). There is no direct evidence on the comparative effectiveness of RF ablation with Ablation Index and cryoballoon (CB). The objective of the present study was to conduct a matching-adjusted indirect comparison (MAIC) using individual patient-level data (IPD) to compare the effectiveness of RF ablation with Ablation Index to that of CB on recurrence of atrial arrhythmias 12 months after catheter ablation in patients with paroxysmal AF (PAF). METHODS: Individual patient-level data for RF ablation with Ablation Index were obtained from two studies: Solimene et al. [J Interv Card Electrophysiol 54(1):9-15, 2019] and Hussein et al. [J Cardiovasc Electrophysiol 28(9):1037-1047, 2017]. Comparable CB studies identified from a systematic literature review were pooled. Prognostic variables for adjustment were ranked a priori by several practicing electrophysiologists. In the absence of a common treatment arm between the Ablation Index and CB studies, an unanchored MAIC was conducted. Primary analysis compared the Solimene et al. study to pooled CB studies. A secondary analysis compared pooled RF ablation with Ablation Index studies to pooled CB studies. Several scenario and sensitivity analyses were conducted. RESULTS: Primary analyses showed statistically significant reductions in the rate of arrhythmia recurrence with RF ablation with Ablation Index compared to CB in unmatched, unadjusted (HR 0.50, 95% CI 0.27-0.95) and matched (0.42, 0.21-0.86) analyses. Greater reductions in the rate of arrhythmia recurrence that favored RF ablation with Ablation Index were observed after matching and adjusting for age (0.41, 0.20-0.85), age and left ventricular ejection fraction (0.37, 0.16-0.88), and age, sex, and left ventricular ejection fraction (0.30, 0.13-0.71). Secondary and sensitivity analyses showed similar reductions. CONCLUSIONS: Radiofrequency ablation with Ablation Index was associated with reductions in recurrence of atrial arrhythmias at 12 months compared to CB in unmatched and unadjusted, matched, and matched and adjusted comparisons.

Letter--The Authors Respond.

DISCLOSURES: No additional funding was received for the writing of this letter. The published study referred to in this letter was funded by Janssen Scientific Affairs, which employs Maiese and funded Cornerstone Research Group, a health economic consulting group, to conduct the study. Grima is a founding partner of Cornerstone Research Group, which employs Hollmann, Goyert, and Moldaver.

A U.S. Cost Analysis of Triplet Regimens for Patients with Previously Treated Multiple Myeloma.

BACKGROUND: In recent years, the FDA has approved several 3-agent (i.e., triplet) combinations for previously treated multiple myeloma (MM), and the National Comprehensive Cancer Network (NCCN) now recommends triplet regimens over doublets. Little is known about the real-world cost of triplet combinations because of the limited time that they have been on the market since FDA approval. Furthermore, traditional cost analyses developed to support market entrance rely on utilization assumptions that are difficult to validate when numerous comparators simultaneously enter the market. OBJECTIVE: To perform a 1-year cost analysis of novel triplets used for the treatment of patients with previously treated MM controlling for differences in utilization. METHODS: FDA-approved, NCCN-recommended (preferred and category 1 for previously treated MM) treatments included in the analysis were daratumumab plus lenalidomide plus dexamethasone (DARA/LEN/DEX), daratumumab plus bortezomib plus dexamethasone (DARA/BOR/DEX), elotuzumab plus lenalidomide plus dexamethasone (ELO/LEN/DEX), carfilzomib plus lenalidomide plus dexamethasone (CAR/LEN/DEX), and ixazomib plus lenalidomide plus dexamethasone (IXA/LEN/DEX). To control for market uptake, the model was designed to estimate the cost of treating an average patient over a 1-year time horizon. Drug administration and dosing, required comedications, postprogression therapy, monitoring requirements, and adverse event (AE) rates were based on FDA prescribing information or clinical trials. AEs ≥ grade 3 that occurred in ≥ 5% of patients were included. RED BOOK wholesale acquisition costs were used for drug acquisition costs. Costs of drug administration, AE management, and patient monitoring were based on the 2018 Center for Medicare & Medicaid Services payment rates or from published literature (inflated to 2018 U.S. dollars). The treatment duration for each regimen was estimated from modeled progression-free survival data; the 12-month progression-free survival rate was assumed to be equivalent to the probability that an average patient remained on therapy for at least 1 year after treatment initiation, which was used to estimate time-depended treatment-related costs. The probability of progression within 1 year of treatment initiation was used to inform the average postprogression therapy costs for each regimen. RESULTS: The estimated cost per patient for each triplet regimen was $13,890 (DARA/BOR/DEX), $22,231 (IXA/LEN/DEX), $24,322 (ELO/LEN/DEX), $26,410 (DARA/LEN/DEX), and $27,432 (CAR/LEN/DEX). Drug acquisition costs and treatment duration were the largest drivers of cost. Scenario analyses with plausible alternative input parameters found the maximum per month cost of therapy to be $30,657 (CAR/LEN/DEX) and the minimum per month cost of therapy to be $13,784 (DARA/BOR/DEX). CONCLUSIONS: This analysis controlled for differential utilization rates for 5 FDA-approved, NCCN-recommended triplet therapies for the treatment of previously treated MM. Of the examined regimens, treatment with DARA/BOR/DEX was estimated to have the lowest average monthly cost per patient, while CAR/LEN/DEX was the most expensive. As is common with modeling, some assumptions were necessary, and results may not be generalizable. DISCLOSURES: This study was funded by Janssen Scientific Affairs, which employs Maiese and funded Cornerstone Research Group, a health economic consulting group, to complete the cost analysis, interpret data, and develop the manuscript. Janssen was involved in the design of the analysis, interpretation of results, and manuscript development and approval. Grima is a founding partner of Cornerstone Research Group, which employs Hollmann, Goyert, and Moldaver. Hollmann, Goyert, and Moldaver were responsible for creation of the economic model. This work was peer-reviewed and presented as an abstract at the Lymphoma and Myeloma 2017 International Congress; October 26-28, 2017; New York, NY.

A cross-sectional evaluation of the idiopathic pulmonary fibrosis patient satisfaction and quality of life with a care coordinator.

BACKGROUND: Canadian and international guidelines recommend specialized, multidisciplinary teams for the treatment of patients with idiopathic pulmonary fibrosis (IPF). The objective of this cross-sectional clinical study was to investigate the effect of a care coordinator on IPF patient satisfaction and quality of life. METHODS: Forty IPF patients were enrolled from the practices of two physicians (n=20/physician), with either low (LCU) or high-coordinator use (HCU). Patient satisfaction was measured with modified FAMCARE and IPF Care UK Patient Support Program (UK-CARE) surveys. Health related quality of life (HRQoL) was assessed with the living with IPF impacts (L-IPFi) survey. An economic model assessed the impact of the coordinator; staff surveys informed patient management requirements, and costs were derived from published literature. RESULTS: Patient satisfaction was similar between the clinics; a trend (P=0.1) towards increased satisfaction among HCU patients was observed. Patients in the HCU clinic reported increased satisfaction (P<0.05) with their current care compared with care prior to joining the tertiary-care clinic, while LCU patients did not. IPF patient HRQoL did not differ between clinics. The coordinator was estimated to alleviate approximately 30% of a physician's IPF-related work load, and to facilitate the care of more patients per physician. Modelled estimates suggest the coordinator lead to annual cost-savings of $137,212. CONCLUSIONS: Reliance upon a coordinator during routine management of IPF patients may improve patient satisfaction, spare physician time and lead to annual cost-savings. Future studies should examine the impact of a coordinator on healthcare resource utilization.

Clinical and Economic Benefits of Antimicrobial Stewardship Programs in Hemodialysis Facilities: A Decision Analytic Model.

BACKGROUND AND OBJECTIVES: Infections caused by multidrug-resistant organisms and Clostridium difficile are associated with substantial morbidity and mortality as well as excess costs. Antimicrobial exposure is the leading cause for these infections. Approximately 30% of antimicrobial doses administered in outpatient hemodialysis facilities are considered unnecessary. Implementing an antimicrobial stewardship program in outpatient hemodialysis facilities aimed at improving prescribing practices would have important clinical and economic benefits. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We developed a decision analytic model of antimicrobial use on the clinical and economic consequences of implementing a nationwide antimicrobial stewardship program in outpatient dialysis facilities. The main outcomes were total antimicrobial use, infections caused by multidrug-resistant organisms and C. difficile, infection-related mortality, and total costs. The analysis considered all patients on outpatient hemodialysis in the United States. The value of implementing antimicrobial stewardship programs, assuming a 20% decrease in unnecessary antimicrobial doses, was calculated as the incremental differences in clinical end points and cost outcomes. Event probabilities, antimicrobial regimens, and health care costs were informed by publicly available sources. RESULTS: On a national level, implementation of antimicrobial stewardship programs was predicted to result in 2182 fewer infections caused by multidrug-resistant organisms and C. difficile (4.8% reduction), 629 fewer infection-related deaths (4.6% reduction), and a cost savings of $106,893,517 (5.0% reduction) per year. The model was most sensitive to clinical parameters as opposed to antimicrobial costs. CONCLUSIONS: The model suggests that implementation of antimicrobial stewardship programs in outpatient dialysis facilities would result in substantial reductions in infections caused by multidrug-resistant organisms and C. difficile, infection-related deaths, and costs.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.

BACKGROUND: The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. METHODS: We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. RESULTS: We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. CONCLUSIONS: Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.

Cost-effectiveness of insulin glargine versus sitagliptin in insulin-naïve patients with type 2 diabetes mellitus.

PURPOSE: In the EASIE (Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-Naïve Patients) trial, insulin glargine found a significant reduction in glycosylated hemoglobin compared with sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin. The objective of this study was to assess the cost-effectiveness of insulin glargine compared with sitagliptin in type 2 diabetes patients, from the perspective of the publicly funded Canadian health care system. METHODS: The IMS CORE Diabetes Model, a standard Markov structure and Monte Carlo simulation model, was used. The model used a lifetime horizon to capture the long-term complications associated with type 2 diabetes. The efficacy of insulin glargine and sitagliptin in terms of glycosylated hemoglobin reduction and corresponding rates of hypoglycemia were obtained from the EASIE trial. Health utility and cost data were obtained from recently published Canadian publications. Univariate and probabilistic sensitivity analyses were conducted. FINDINGS: In the lifetime base-case analysis, treatment with insulin glargine resulted in cost savings of $1434 CAD in 2012 and a gain of 0.08 quality-adjusted life years per patient. A probabilistic sensitivity analysis found the robustness of the base-case analysis, with 88% probability of insulin glargine being dominant (ie, cost savings and more quality-adjusted life years). IMPLICATIONS: Insulin glargine is a clinically superior and cost-effective alternative to sitagliptin in patients with type 2 diabetes who are inadequately controlled with metformin.

Cost-effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes in Canada.

BACKGROUND: Ticagrelor demonstrated a significant reduction in major cardiac events in patients with acute coronary syndrome (ACS) compared with clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. The objective of this study was to assess the cost-effectiveness of ticagrelor compared with clopidogrel in ACS patients from the perspective of the Canadian publicly funded health care system. METHODS: A two-part model was developed consisting of a 1-year decision tree and a lifetime Markov model. Within the decision tree, patients remained event-free, experienced a nonfatal myocardial infarction, a nonfatal stroke, or death due to vascular or nonvascular related causes based on data from the PLATO trial. The lifetime Markov model followed these patients and allowed for subsequent myocardial infarction, stroke, and death. Patient utility and resource use were derived from the PLATO trial. Transition probabilities and specific Canadian unit costs were derived from published sources. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: In the base case lifetime analysis, treatment with ticagrelor resulted in more years of life per person (0.097), more quality-adjusted life years per person (QALYs, 0.084), and an incremental cost per QALY gained of $9,745 (Canadian$), assuming a generic cost for clopidogrel. A probabilistic sensitivity analysis demonstrated the robustness of the base case analysis, with a 93% probability of being below $20,000 per QALY gained and a 99% probability of being below $30,000 per QALY gained. CONCLUSION: Ticagrelor is a clinically superior and cost-effective option for the prevention of thrombotic events among ACS patients in Canada.

A modeled economic evaluation of sevelamer for treatment of hyperphosphatemia associated with chronic kidney disease among patients on dialysis in the United Kingdom.

OBJECTIVE: There is limited information regarding the cost-effectiveness of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease (CKD) patients on dialysis in the UK. Using a UK National Health Service (NHS) perspective and final results of the Dialysis Clinical Outcomes Revisited (DCOR) study, an evaluation was performed to determine the cost-effectiveness of sevelamer compared to calcium-based phosphate binders for the first-line treatment of hyperphosphatemia in CKD patients on dialysis. METHODS: A Markov model was developed to estimate life years, quality-adjusted life years (QALYs), costs, incremental cost per life year (LY) gained, and QALY gained. Treatment-specific overall survival up to 44 months, hospitalizations, and resource utilization were derived from the DCOR study. Survival was extrapolated to a lifetime horizon using Weibull regression analysis. Unit costs and utility estimates specific to the UK were obtained from the published literature. Sub-group analyses were conducted based on data reported from the DCOR study for increasing age cut-points. Outcomes and costs were modeled for a lifetime horizon. RESULTS: In the base case analysis, the use of sevelamer resulted in a gain of ∼0.73 LYs and 0.44 QALYs per patient (discounted at 3.5% per year). Total per-patient costs were higher for sevelamer, resulting in an incremental cost of £22,157 per QALY gained and £13,427 per LY gained (in £2009). Increasingly favorable cost per QALY ratios were observed with increasing age cut-points, ranging from £15,864 for patients ≥45 to £13,296 for patients ≥65 years of age. Results were most sensitive to assumptions regarding overall survival and the inclusion of dialysis costs. Key limitations of the analysis included the use of non-UK trial data for survival and hospitalizations, and the exclusion of quality-of-life impacts associated with hospitalization. CONCLUSIONS: In CKD patients receiving dialysis, treatment of hyperphosphatemia with sevelamer offers good value for money compared with calcium-based binders.

Impact of sevelamer versus calcium-based binders on hospitalizations and missed in-center dialysis treatments among CKD patients on dialysis: a modeled analysis.

PURPOSE: The avoidance of hospitalizations and the maintenance of in-center dialysis sessions in patients receiving dialysis for end-stage renal disease (ESRD) have obvious benefits to patients, dialysis providers and payers. Benefits include better continuity of care, better patient outcomes, improved quality of life, and reduced healthcare expenditures. The objective of this study was to quantify, from the perspective of a dialysis provider in the US, the potential impact of sevelamer versus calcium-based binders (CBBs) on hospitalization days and maintenance of in-center dialysis sessions among hyperphosphatemic dialysis patients. METHODS: A Microsoft Excel-based model was developed to simulate the number of missed dialysis sessions among three hypothetical cohorts of hyperphosphatemic patients treated with either sevelamer or CBBs. The cohorts were characterized by their size to represent a small, mid-size, or large dialysis organization (75, 30,000, and 120,000 patients, respectively). In any given month, a patient in the model could receive dialysis treatments within the center, experience a hospitalization, or die. Treatment-specific monthly survival rates, hospitalization rates, length of stay, and binder dosages were derived from the Dialysis Clinical Outcomes Revisited (DCOR) study. A dialysis schedule of three treatments per week was assumed. Analyses were conducted for a 1-year time horizon. RESULTS: For a small dialysis center, CBBs were associated with an increased number of missed in-center dialysis treatments (447) compared to sevelamer (395). Thus, sevelamer use avoided 52 missed in-center dialysis sessions during 1 year of treatment compared to CBBs. The magnitude of sevelamer's impact on maintaining in-center dialysis treatments increased with the size of the dialysis organization; for a mid-size dialysis organization sevelamer use avoided 20,571 missed in-center dialysis sessions and for a large dialysis organization sevelamer use avoided 82,286 missed in-center dialysis sessions. CONCLUSIONS: Treatment of hyperphosphatemic dialysis patients with sevelamer relative to CBBs was associated with a reduction in the number of missed in-center dialysis treatments across small, mid-size, and large dialysis organizations. This reduction could contribute to improved patient outcomes via undisrupted delivery of care within the dialysis clinic. The use of sevelamer versus CBBs could also result in an increased number of reimbursement payments to dialysis clinics and providers by avoiding missed in-center dialysis sessions due to hospitalization.

How rebates, copayments, and administration costs affect the cost-effectiveness of osteoporosis therapies.

PURPOSE: Because of rising drug expenditures, cost considerations have become essential, necessitating the requirement for cost-effectiveness analyses for managed care organizations (MCOs). The study objective is to examine the impact of various drug-cost components, in addition to wholesale acquisition cost (WAC), on the cost-effectiveness of osteoporosis therapies. DESIGN: A Markov model of osteoporosis was used to exemplify different drug cost scenarios. METHODOLOGY: We examined the effect of varying rebates for oral bisphosphonates--risedronate and ibandronate--as well as considering the impact of varying copayments and administration costs for intravenous zoledronate. The population modeled was 1,000 American women, > or = 50 years with osteoporosis. Patients were followed for 1 year to reflect an annual budget review of formularies by MCOs. The cost of therapy was based on an adjusted WAC, and is referred to as net drug cost. The total annual cost incurred by an MCO for each drug regimen was calculated using the net drug cost and fracture cost. We estimated cost on a quality adjusted life year (QALY) basis. PRINCIPAL FINDINGS: When considering different rebates, results for risedronate versus ibandronate vary from cost-savings (i.e., costs less and more effective) to approximately $70,000 per QALY. With no risedronate rebate, an ibandronate rebate of approximately 65% is required before cost per QALY surpasses $50,000. With rebates greater than 25% for risedronate, irrespective of ibandronate rebates, results become cost-saving. Results also showed the magnitude of cost savings to the MCO varied by as much as 65% when considering no administration cost and the highest coinsurance rate for zoledronate. CONCLUSION: Our study showed that cost-effectiveness varies considerably when factors in addition to the WAC are considered. This paper provides recommendations for pharmaceutical manufacturers and MCOs when developing and interpreting such analyses.

Cost-effectiveness analysis of therapies for chronic kidney disease patients on dialysis: a case for excluding dialysis costs.

In many jurisdictions, cost-effectiveness analysis (CEA) plays an important role in determining drug coverage and reimbursement and, therefore, has the potential to impact patient access. Health economic guidelines recommend the inclusion of future costs related to the intervention of interest within CEAs but provide little guidance regarding the definition of 'related'. In the case of CEAs of therapies that extend the lives of patients with chronic kidney disease (CKD) on dialysis but do not impact the need for or the intensity of dialysis, the determination of the relatedness of future dialysis costs to the therapy of interest is particularly ambiguous. The uncertainty as to whether dialysis costs are related or unrelated in these circumstances has led to inconsistencies in the conduct of CEAs for such products, with dialysis costs included in some analyses while excluded in others. Due to the magnitude of the cost of dialysis, whether or not dialysis costs are included in CEAs of such therapies has substantial implications for the results of such analyses, often meaning the difference between a therapy being deemed cost effective (in instances where dialysis costs are excluded) or not cost effective (in instances where dialysis costs are included). This paper explores the issues and implications surrounding the inclusion of dialysis costs in CEAs of therapies that extend the lives of dialysis patients but do not impact the need for dialysis. Relevant case studies clearly demonstrate that, regardless of the clinical benefits of a life-extending intervention for dialysis patients, and due to the high cost of dialysis, the inclusion of dialysis costs in the analysis essentially eliminates the possibility of obtaining a favourable cost-effectiveness ratio. This raises the significant risk that dialysis patients may be denied access to interventions that are cost effective in other populations due solely to the high background cost of dialysis itself. Finally, the paper presents a case for excluding dialysis costs in CEAs of therapies that extend the lives of patients receiving dialysis but do not impact the need for dialysis. The argument is founded on the following: (i) health economic guidelines imply that dialysis costs are unrelated to such therapies and therefore should not be included in CEAs of such therapies; (ii) the high cost and cost-effectiveness ratio associated with dialysis place an unreasonable and insurmountable barrier to demonstrating the cost effectiveness of such therapies, particularly since the decision to fund dialysis has already been made; and (iii) current clinical and reimbursement practices include the use of such therapies for patients with CKD receiving dialysis. We conclude that the exclusion of dialysis costs in such cases is methodologically correct given current health economic guidelines and is consistent with current practices regarding the treatment of dialysis patients.