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Technology Evaluation Center Special Report: Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure * Assessment Program Volume 19, No. 2 April 2004 Executive Summary Left-ventricular assist devices (LVADs) augment the impaired cardiac pumping ability in patients experiencing end-stage heart failure. The scarcity of donor hearts makes heart transplantation possible for only 2,200 patients per year. Patients with end-stage heart failure who are ineligible for cardiac transplantation are currently managed with angiotensin-converting enzyme (ACE) inhibitors, diuretics, digoxin, beta blockers, and inotropic agents. These patients may be excluded from heart transplantation because of advanced age (e.g., over 65 years), or other major comorbidities such as insulin-dependent diabetes mellitus or chronic renal failure. LVADs are intended to prolong survival and improve functional status in comparison with medical management. A randomized trial on the use LVADs as permanent implants, or as destination therapy, showed they can increase median survival by 7.4 months, while potentially raising the cost of end-of-life care considerably. The present cost-effectiveness analysis addresses use of LVAD destination therapy, compared with optimal medical management, among patients who are not heart transplant candidates. This analysis takes a societal perspective; however, some elements of this perspective, such as use of indirect costs, were not strictly followed. The baseline cost-effectiveness analysis, using parameter estimates from published sources, showed that use of LVADs leads to an increase in cost of $802,700 to gain one QALY, compared with optimal medical management. Within the range of values used in this analysis, the incremental cost-effectiveness ratio (ICER) was fairly stable amid changes in these variables: utility for New York Heart Association (NYHA) category III/IV; utility discount rate; cost of outpatient care; and cost discount rate, cost of rehospitalization, and probability of rehospitalization for LVAD; and probability of rehospitalization for optimal medical management. Results were more sensitive to variations in utility for NYHA category I/II and the cost of LVAD implantation. ICERs of $500,000/QALY or less depended on improbable assumptions of very low costs for LVAD implantation, usually in combination with extreme values on other variables. Although utilities from a general population would be preferred, the estimates used here from LVAD recipients suffice, given the wide range of values surrounding them in the sensitivity analysis. Indirect costs, such as lost wages and costs borne by caretakers, are not included, but as return to work is unlikely for either LVAD or optimal medical management patients, excluding indirect costs would not affect the strategies’ relative standings in the analysis. The short time horizon should limit the impact of excluding indirect costs. ® ® BlueCross BlueShield Association An Association of Independent Blue Cross and Blue Shield Plans * Please note: This Special Report is a cost-effectiveness analysis of left-ventricular assist devices as destination therapy, and complements the 2002 clinical TEC Assessment (Volume 17, Number 19) on the same topic. Special Reports do not attempt to address the question as to whether the TEC criteria are met. NOTICE OF PURPOSE: TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated. ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 1 Technology Evaluation Center Contents Objective 3 Discussion 24 Background 3 Conclusions 26 Methods 4 References 28 Appendix 29 Estimates of Outcomes and Costs 12 Cost-effectiveness Analysis Results 18 Published in cooperation with Kaiser Foundation Health Plan and Southern California Permanente Medical Group. TEC Staff Contributors Author—David Samson; TEC Executive Director—Naomi Aronson, Ph.D.; Managing Scientific Editor—Kathleen M. Ziegler, Pharm.D.; Research/Editorial Staff—Claudia J. Bonnell, B.S.N., M.L.S.; Maxine A. Gere, M.S.; Acknowledgements—Staff would like to thank Alan Garber, M.D., Ph.D., and Gillian Sanders, Ph.D., for their contributions to the research and development of this Special Report. Blue Cross and Blue Shield Association Medical Advisory Panel Allan M. Korn, M.D., F.A.C.P.—Chairman, Senior Vice President, Clinical Affairs/Medical Director, Blue Cross and Blue Shield Association; David M. Eddy, M.D., Ph.D.—Scientific Advisor, Senior Advisor for Health Policy and Management, Kaiser Permanente, Southern California. ■ Panel Members Peter C. Albertsen, M.D., Professor, Chief of Urology, and Residency Program Director, University of Connecticut Health Center; Edgar Black, M.D., Vice President, Chief Medical Officer, BlueCross BlueShield of the Rochester Area; Helen Darling, M.A., President, Washington Business Group on Health; Josef E. Fischer, M.D., F.A.C.S., Mallinckrodt Professor of Surgery, Harvard Medical School and Chair, Department of Surgery, Beth Israel Deaconess Medical Center—American College of Surgeons Appointee; Alan M. Garber, M.D., Ph.D., Professor of Medicine, Economics, and Health Research and Policy, Stanford University; Steven N. Goodman, M.D., M.H.S., Ph.D., Associate Professor, Johns Hopkins School of Medicine, Department of Oncology, Division of Biostatistics (joint appointments in Epidemiology, Biostatistics, and Pediatrics)—American Academy of Pediatrics Appointee; Michael A.W. Hattwick, M.D., Woodburn Internal Medicine Associates, Ltd. American College of Physicians Appointee; I. Craig Henderson, M.D., Adjunct Professor of Medicine, University of California, San Francisco; Bernard Lo, M.D., Professor of Medicine and Director, Program in Medical Ethics, University of California, San Francisco; Barbara J. McNeil, M.D., Ph.D., Ridley Watts Professor and Head of Health Care Policy, Harvard Medical School, Professor of Radiology, Brigham and Women’s Hospital; Brent O’Connell, M.D., M.H.S.A., Vice President and Medical Director, Pennsylvania Blue Shield/Highmark, Inc.; Stephen G. Pauker, M.D., M.A.C.P., F.A.C.C., Sara Murray Jordan Professor of Medicine, Tufts University School of Medicine; and Vice-Chairman for Clinical Affairs and Associate Physician-in-Chief, Department of Medicine, New England Medical Center; William R. Phillips, M.D., M.P.H., Clinical Professor of Family Medicine, University of Washington—American Academy of Family Physicians’ Appointee; Earl P. Steinberg, M.D., M.P.P., President, Resolution Health, Inc.; Paul J. Wallace, M.D., Executive Director, Care Management Institute, Kaiser Permanente; A. Eugene Washington, M.D., M.Sc., Executive Vice Chancellor, University of California, San Francisco; Jed Weissberg, M.D., Associate Executive Director for Quality and Performance Improvement, The Permanente Federation. CONFIDENTIAL: This document contains proprietary information that is intended solely for Blue Cross and Blue Shield Plans and other subscribers to the TEC Program. The contents of this document are not to be provided in any manner to any other parties without the express written consent of the Blue Cross and Blue Shield Association. 2 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Objective Left-ventricular assist devices (LVADs) augment the impaired cardiac pumping ability in patients experiencing end-stage heart failure. The scarcity of donor hearts makes heart transplantation possible for only 2,200 patients per year. Patients with end-stage heart failure who are ineligible for cardiac transplantation are currently managed with angiotensin-converting enzyme (ACE) inhibitors, diuretics, digoxin, beta blockers, and inotropic agents. These patients may be excluded from heart transplantation because of advanced age (e.g., over 65 years), or other major comorbidities such as insulin-dependent diabetes mellitus or chronic renal failure. LVADs are intended to prolong survival and improve functional status in comparison with medical management. A randomized trial on the use LVADs as permanent implants, or as destination therapy, showed they can increase median survival by 7.4 months, while potentially raising the cost of end-of-life care considerably. The present costeffectiveness analysis addresses use of LVAD destination therapy, compared with optimal medical management, among patients who are not heart transplant candidates. This analysis takes a societal perspective; however, some elements of this perspective, such as use of indirect costs, were not strictly followed. Background Heart Failure Chronic heart failure is a common disease responsible for high mortality and morbidity. Heart failure represents a complex clinical syndrome caused by many different etiologies whose clinical manifestations reflect a fundamental abnormality—a decrease in the myocardial contractile state such that cardiac output is insufficient for the metabolic requirements of the tissues and organs. The prevalence of heart failure is estimated at 4 to 5 million cases, with an incidence rate of 400,000 cases per year (Eichorn 2001). The mortality rate is estimated to be as much as 700,000 cases per year. (Zeltsman and Acker 2002). Medical management is the mainstay of supportive care for patients with chronic heart failure. While medical therapies (e.g., angiotensin-converting enzyme (ACE) inhibitors and beta blockers) have improved survival and quality of life outcomes for patients with mild-to-moderate heart failure (Greenberg 2000; Cohn 2000a), irreversible end-stage cardiac disease unresponsive to medical therapy continues to occur at an approximate rate of 60,000 patients per year (Oz et al. 1995). Inotropic agents and the intra-aortic balloon pump are the last options for medical management of patients with severe heart failure. Cardiac transplantation is widely accepted as the most effective therapy for the treatment of end-stage cardiac failure, for which survival rates for patients transplanted within the past five years are 85.6% and 79.5% after 1 and 5 years, respectively (Miniati and Robbins 2002). In contrast, patients with New York Heart Association (NYHA) class IV heart failure not receiving transplantation have achieved 20–30% survival rates (Oz et al. 1995). Despite documented success with long-term survival and improved quality of life, use of transplantation is limited to about 2,200 patients per year (United Network for Organ Sharing 2001). The limited supply of donor hearts prevents heart transplantation from being a treatment option for many patients with end-stage heart failure. Patients who have very poor baseline function, advanced age and comorbidities, such as insulin-dependent diabetes mellitus, are less likely to survive the transplantation procedure and would be expected to have poorer long-term survival. Such patients are excluded from transplant eligibility. Ventricular Assist Devices Left-ventricular assist devices (LVADs) are intended to augment native left-ventricular function in several settings. One setting is to allow short-term recovery in patients with postcardiotomy shock. A second is to serve as a bridge to heart transplantation, helping patients survive long enough on the waiting list to reach a transplant date. The third setting is the focus of this report, comprising a permanent alternative to transplantation, or destination therapy, among patients who are not transplant candidates. Different LVAD designs may be distinguished by whether they are powered electrically or pneumatically and whether a pulsatile pump is used or a rotor mechanism, allowing for continuous blood flow. The model for which its manufacturer submitted a supplemental premarket approval application (PMA) to the U.S. Food and Drug Administration (FDA) for destination therapy is the Thoratec ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 3 Technology Evaluation Center Heartmate ® VE (vented electric) Left Ventricular Assist System (LVAS). The device consists of a fully implantable pump served by a percutaneous driveline, which provides for power and venting. The patient can achieve a high degree of mobility with a wearable battery pack and system controller. An apical anastomosis links the left ventricle with the pump via an inflow cannula. An outflow cannula is anastomosed to the aorta. FDA Status. A pneumatically powered predecessor to the Heartmate® VE LVAS was originally approved by the FDA in September 1994 as a bridge to transplantation for cardiac transplant candidates. The electrically powered VE version was approved in September 1998 for the same indication. Thoratec submitted a supplemental premarket approval application for use as destination therapy in patients with end-stage left ventricular failure who are ineligible for cardiac transplantation. The FDA approved this application on November 6, 2002. Methods Time Horizon and Perspective This cost-effectiveness analysis encompasses the entire remainder of a patient’s lifetime, to a maximum of 3 years. The 3-year limit is based on randomized trial survival data suggesting that all trial patients were likely to be dead by that time. This analysis takes a societal perspective; however, some elements of this perspective, such as use of indirect costs, were not strictly followed. For example, utilities were estimated from a study of LVAD recipients, whereas a societal perspective would prefer utilities obtained from a general population. A wide range of utility values will be used in sensitivity analysis to assess whether utilities have an important impact on the results of the analysis. As stated, indirect costs, such as lost wages and costs borne by caretakers, are not included. Given the complicated overall condition of these patients, it is unlikely that patients receiving either LVADs or optimal medical management would return to work, so excluding indirect costs would not greatly affect the strategies’ relative standings in the analysis. The short time horizon should limit the impact of excluding indirect costs, as well. Patient Population and Setting The REMATCH trial determines the specific patient population, strategies, and outcomes 4 of interest to this analysis (Rose et al. 2001; 1999). Patients were selected for the REMATCH trial primarily for belonging to NYHA Class IV for at least 90 days, despite use of ACE inhibitors, diuretics and digoxin. Patients also had a left-ventricular ejection fraction of 25% or less and a peak oxygen concentration of 12 mL/kg or less, or continued need for intravenous (IV) inotropic therapy for symptomatic hypotension, decreasing renal function, or worsening pulmonary congestion. Patients were allowed to continue on beta-blockers if given for at least 60 of the 90 days before randomization. Cardiac transplantation contraindications included: age older than 65 years; insulin-dependent diabetes mellitus with end-organ damage; chronic renal failure, and other major physical or mental comorbidities. This analysis focuses on patients similar to those selected for the REMATCH trial. Results will apply to institutions similar to those that participated in the REMATCH trial, which included 20 experienced cardiac transplantation centers. Strategies The REMATCH trial used the Heartmate® VE LVAS. The device was implanted in either a preperitoneal pocket or intraperitoneally. Rose et al. (1999) described optimal medical management as follows: “Patients randomized to the optimal medical management only treatment group will be treated with digoxin, diuretics and an angiotensin-converting enzyme inhibitor. If angiotensin-converting enzyme inhibitors cannot be tolerated because of allergy or hypotension, then angiotensin II antagonists should be considered. Patients can receive treatment with a β-blocker at the investigator’s discretion. The goals of therapy are twofold: to ensure that systemic perfusion maintains organ function sufficiently to meet the resting metabolic needs necessary for survival and to reduce ventricular filling pressures sufficiently to achieve and maintain relief from symptomatic resting congestion. Stabilization in some patients may require short-term intravenous pharmacologic support or mechanical fluid removal, which can subsequently be discontinued in favor of other therapies.” Surgeons were required to follow a committee’s management guidelines. Optimal medical management guidelines were also developed by a committee and gave specific recommendations on use of ACE inhibitors. Discontinuation ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure of IV inotropic agents was encouraged for medically managed patients. Decision Model/Markov Model Quality-adjusted life years (QALYs) will be the effectiveness metric used in this analysis. Figures 1 and 2 show the decision model and Markov model that were used. The same Markov model will be used for both treatment modalities, but transition probabilities will be estimated separately. Each includes “alive” and “dead” as health states. Table 1 shows the transition probability matrix. Time-dependent transition probabilities were used for Markov cohort simulations. Both Data 4.0 and Excel software were used to construct the models. Two quality-of-life categories were taken into account in the model, based on whether the patient belonged in New York Heart Association Functional Classes I/II or Classes III/IV*. It was assumed that the utilities for NYHA categories did not differ between LVAD and optimal medical management patients. *New York Heart Association Functional Classification System for Heart Failure Class I No limitation on physical activity (symptoms with greater than ordinary activity) Class II Slight limitation on physical activity (symptoms with ordinary activity) Class III Marked limitation on physical activity (symptoms with less than ordinary activity) Class IV Inability to carry on physical activity (symptoms at rest) Calculation of QALYs in the Model Cycle-specific contributions to QALYs in these Markov models are shown in Table 2 (row #4). Utilities will be estimated for the 2 quality of life categories: NYHA I/II and NYHA III/IV. QALYs in each cycle were the product of the cycle-specific survival probability and a weighted average derived from a sum of the products of the probability of being in a quality-of-life category and each category’s utility (Table 2, row #6). The probability of belonging to the 2 quality-of-life categories varies over time. Monthly estimates of these probabilities could be used to let NYHA class status contribute to quality-of-life measurement in a dynamic way without creating separate Markov states for the 2 NYHA categories. Utility values for each NYHA category will be discounted at a rate of 3%. Cost Categories Three main categories of costs were included: implantation costs, rehospitalization costs, and outpatient costs. Implantation costs apply only to LVAD recipients, while rehospitalization costs and outpatients costs apply to both strategies. Costs were estimated from a REMATCH costing study (Oz et al. 2003) and on a study of long-term LVAD use in bridge-to-transplant patients at Columbia University (Moskowitz et al. 2001; Gelijns et al. 1997). These studies used the ratio of cost to charges method of estimating hospital costs, market prices for drugs and devices, and payments for physician services. Subcategories for hospitalization (implantation) included: LVAD, professional payment, length of stay, special care days, regular floor, operating room, diagnostics, laboratory, blood products, drugs, miscellaneous costs, and rehabilitation. Outpatient costs included professional payments, laboratory tests, and drugs. It was assumed that monthly rehospitalization and outpatient costs were the same for patients receiving LVADs and optimal medical management. The following costs were not considered in this analysis: any amounts that may have increased the monthly rehospitalization due to device malfunction, removal or reimplantation; any added costs associated with specific types of adverse events that were more common among LVAD recipients in the REMATCH trial; and indirect costs. Evidence on adverse events was presented in the 2002 TEC Assessment of LVADs as destination therapy (Volume 17, Number 19). Calculation of Costs in the Model Costs in each cycle of the Markov model were the product of the cycle-specific survival probability and a weighted average derived from a sum of the products of the probability of being rehospitalized or not and the cost of rehospitalization or outpatient care (Table 2, row #11). The probability of being in the hospital was derived from data on the mean percentage of life spent in the hospital. It was assumed that this percentage was constant over time and could be applied as a fixed weight within each cycle. Costs were valued in 2002 $US and were discounted at a 3% rate. When costs had to be revalued, the Gross Domestic Product Deflator was used (2004). ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 5 Technology Evaluation Center Figure 1. Decision Model ����� ����� ���� ���� � ����� ���� ���� ����������������� ����� ����� ��� ���� � ���� OMM: optimal medical management Figure 2. State-cycle Diagram of the Markov Model ��� � ��� ����� ���� Table 1. Transition Probability Matrix (P) for Markov Model �� ����� ���� ���� ��� ��� ����� � � ������������ ���� 6 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. ����� ���� No. Characteristic Baseline Value 1 Survival, cyclespecific probabilities, extrapolation past last follow-up REMATCH Kaplan-Meier curves, see Table 3, Figure 3; maximum follow-up of 27 months for LVAD, 26 months for OMM. Sensitivity Analysis Range of Values not applicable Comment Source Cycle-specific survival probabilities were estimated from graph of Kaplan-Meier curves. Method for obtaining cycle-specific survival transition probabilities for Markov cohort simulations is described in Figure 4. Data update from February 2002 CDRH FDA (2002) All patients in both groups were assumed to be dead by 36 months. Extrapolation past last follow-up performed by interpolating between last observed survival probability and 0% at 36 months. When cycle-specific survival probability dropped below 0.005, a value of 0 was substituted. 2 Survival, relation between LVAD and OMM Hazard ratio cited in 2001: 0.52. Hazard ratio 95% CI: 0.34, 0.78. An exponential survival curve was fit to OMM data, with a hazard rate of 0.128. Survival was assumed to be 0 when the cycle-specific survival probability fell below 0.005. At the lower limit of the 95% CI, the hazard ratio is 0.78; the survival probability fell to 0 after 42 months for OMM and after 53 months for LVAD. At the upper limit of the 95% CI, the hazard ratio is 0.34, and the survival probability fell to 0 after 121 months. Rose et al. (2001) Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Table 2. Underlying Assumptions for Cost-effectiveness Analysis 7 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Sensitivity Analysis Range of Values No. Characteristic Baseline Value Comment Source 3 Extrapolation of survival past point of last followup. Linear interpolation from survival probability at 26 months to assumed 0% survival at 36 months. Three other methods of extrapolation were explored: stop and drop; exponential; and Gompertz/exponential. The first method, stop and drop, assumes that all patients surviving to 26 months die immediately thereafter. The second method used exponential survival models for both LVAD and OMM. The OMM model used the same hazard rate as mentioned above for the analysis on the hazard ratio confidence interval. The LVAD model was fit on the Kaplan-Meier curve before 23 months, where the hazard appears fairly constant (0.062). The third method used a Gompertz model to extrapolate for LVAD and an exponential model for OMM. The LVAD Kaplan-Meier curve shows an increasing hazard between 23 and 26 months, so a Gompertz model was fit for this interval and further. 4 Probability of being in NYHA classes I/II or III/IV REMATCH data on NYHA class membership at 0, 1, 3, 6, 9, 12, 18 and 24 months. not applicable Cycle-specific probabilities are based on available data or interpolations between successive reported probabilities. For extrapolations beyond 24 months, it is assumed that 24 month probabilities stayed constant. Thoratec, Inc. (2002) 5 Utility of NYHA classes NYHA I/II: 0.81 NYHA III/IV: 0.55 NYHA I/II: 0.50–1.00 NYHA III/IV: 0.30–0.80 Standard gamble utilities were elicited from 29 bridge-to-transplant patients before LVAD implantation and during LVAD support. The mean utility for pre-implantation was assigned to NYHA III/IV and the mean for LVAD support was assigned to NYHA I/II. It was assumed that the utilities for NYHA categories did not differ between LVAD and OMM patients. Moskowitz et al. (1997) Technology Evaluation Center 8 Table 2. Underlying Assumptions for Cost-effectiveness Analysis (cont’d) Sensitivity Analysis Range of Values No. Characteristic Baseline Value 6 Cycle-specific contribution to QALYs Utility within each cycle was calculated as a weighted average (see right). not applicable $277,000 (2002 $US) $125,000–425,000 7 LVAD implantation cost Comment Source QALYt = St [(PI/II * UI/II) + (PIII/IV * UIII/IV)]t / 12 Where t is the monthly cycle, St is the survival probability, PI/II and PIII/IV are the probabilities of being in the two NYHA categories and UI/II and UIII/IV are the utilities associated with NYHA categories. This method allows NYHA class to contribute to quality of life measurement in a dynamic way without creating separate Markov states for the two NYHA categories. The average cost of the implantation, excluding professional fees, in 52 destination LVAD patients was reported by Oz et al. as $210,187 (±193,295). Oz did not specify the year by which costs were valued, but because data collection ended in June, 2002, this analysis assumes valuation in 2002 $US. Professional fees were estimated from Moskowitz study of 12 bridge-to-transplant patients. Fees for mean 17.5-day hospital stay were prorated to a 43.5-day stay, then adjusted for inflation factor from 1995 $US to 2002 $US: (43.5 / 17.5) * $23,935 * 1.123 = $66,814 Oz et al. (2003); Moskowitz et al. (2001); Gelijns et al. (1997) Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Table 2. Underlying Assumptions for Cost-effectiveness Analysis (cont’d) 9 Table 2. Underlying Assumptions for Cost-effectiveness Analysis (cont’d) ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Characteristic Baseline Value Sensitivity Analysis Range of Values 8 Monthly rehospitalization cost $39,896 $10,000–70,000 Comment Source The average annual readmission cost, reported by Oz et al. was $105,326. The probability of being rehospitalized was 0.22. (see below). The annual readmission cost was prorated to a full year of hospitalization, then divided by 12 to yield a monthly rehospitalization cost: Oz et al. (2003); Moskowitz et al. (2001); Gelijns et al. (1997) [(1 / 0.22) * $105,326] / 12 = $39,896 This amount excludes professional fees. It includes the cost of LVAD replacements. It was assumed that inpatient costs were the same for both groups of patients. 9 Monthly outpatient cost $1,719 $250–3,250 In a study of bridge-to-transplant patients, the average weekly outpatient cost was $352, yielding a full month cost of $1,531 (1995 $US). This amount was revalued in 2002 $US. It was assumed that outpatient costs were the same for both groups of patients. Moskowitz et al. (2001); Gelijns et al. (1997) 10 Probability of rehospitalization LVAD: 0.22 OMM: 0.15 LVAD: 0.10–0.35 OMM: 0.05–0.30 There were a total of 18,406 LVAD support days, of which 3,896 days (22%) were spent in the hospital. Data were lacking on whether the probability of rehospitalization changed over time, so it was assumed that the proportion of days spent in the hospital could be applied to each cycle as a constant weight. The probability of being an outpatient was calculated as one minus the probability of rehospitalization. Oz et al. 2003; CDRH FDA (2002) CDRH FDA data for OMM patients state that there were a total of 10,085 days alive, of which 1,756 (15%) were spent in the hospital Technology Evaluation Center 10 No. No. Characteristic Baseline Value 11 Cycle-specific contribution to costs Cost within each cycle was calculated as a weighted average (see right). 12 Cost correction for cycle 1 and cycle 2, LVAD $11,673 13 Discount rate for costs, utilities 3% Sensitivity Analysis Range of Values Comment not applicable Ct = St [(Prehosp * Crehosp) + (Poutpt * Coutpt)] Where Ct is the total cycle-specific cost, Prehosp is the probability of rehospitalization, Crehosp is the cost of rehospitalization, Poutpt is the probability of being an outpatient, and Coutpt is the cost of outpatient care. Implantation cost is entered as an initial cost for LVAD, at cycle 0. Since the average hospital stay for implantation is 43.5 days (1.429 months), cycle specific costs for rehospitalization and outpatient care for all of cycle 1 and 0.429 of cycle 2 should be excluded This total is subtracted from the initial cost of LVAD implantation, then added back in cycles 1 and 2. 1–5% Source Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Table 2. Underlying Assumptions for Cost-effectiveness Analysis (cont’d) 11 Technology Evaluation Center Sensitivity Analyses One-way sensitivity analyses were conducted for the following variables: ■ ■ ■ ■ ■ ■ ■ ■ ■ Uncertainty about the relative survival of LVAD and optimal medical management (OMM) groups Methods for extrapolating survival past the point of last follow-up Utilities for NYHA categories I/II and III/IV Utility discount rate Cost of LVAD implantation Cost of rehospitalization Cost of outpatient care Probability of rehospitalization for LVAD and OMM Cost discount rate Two-way sensitivity analyses were performed for pairwise combinations of these variables: ■ ■ ■ ■ ■ Utilities for NYHA categories I/II and III/IV Cost of LVAD implantation Cost of rehospitalization Cost of outpatient care Probability of rehospitalization for LVAD and OMM An additional analysis was performed that set several variables at values that would be highly favorable to LVAD, described as the “best case” scenario. Estimates of Outcomes and Costs Survival Staff from the Center for Devices and Radiological Health at the Food and Drug Administration (CDRH FDA, 2002) made a presentation to the Circulatory System Devices Advisory Committee in March 2002. The presentation included an update of survival data through February 2002. These data were used rather than earlier published data (Rose et al. 2001). Kaplan-Meier curves were overlaid with grids to derive survival probabilities at monthly marks (Table 3). Follow-up ended at 26 months for both groups; the survival probability was 1% for OMM patients and 10% for LVAD patients. The published REMATCH report cited a hazard ratio of 0.52, with a 95% confidence interval between 0.34 and 0.78. To assess the impact on the analysis of uncertainty around relative survival, an exponential survival model with a hazard rate of 0.128 was fit to the OMM Kaplan- 12 Meier curve and the hazard ratios for the confidence interval limits were applied to produce LVAD exponential survival models. Extrapolation of survival past the point of last follow-up was performed according to 4 methods: stop and drop; linear interpolation to 36 months; exponential survival models for both LVAD and OMM; and a Gompertz LVAD survival model along with an exponential OMM survival model. The stop and drop method assumed that all remaining patients in both groups expired immediately after 26 months. Linear interpolation was based on the assumption that all patients in both groups would be deceased at 36 months, with the additional stop rule of substituting 0% survival when the survival probability fell below 0.005. The method using exponential survival models applied a hazard rate of 0.128 for OMM, and a rate of 0.062 for LVAD. The OMM model used the same hazard rate as mentioned above for the analysis on the hazard ratio confidence interval. The LVAD model was fit on the Kaplan-Meier curve before 23 months, where the hazard appears fairly constant. The third method used a Gompertz model to extrapolate for LVAD and an exponential model for OMM. The LVAD Kaplan-Meier curve shows an increasing hazard between 23 and 26 months, so a Gompertz model was fit for this interval and further. A stop rule was applied for all methods in which survival probabilities below 0.005 were considered as 0. Table 4 shows values for median and mean survival that can be derived from the KaplanMeier curves. Extrapolation of survival curves was performed by linear interpolation to 36 months. Mean survival reflects area under the curve, or life expectancy. For the Markov model, transition probabilities were derived by the method described in Figure 3. NYHA Functional Class Categories The proportions of LVAD and OMM patients in NYHA categories were obtained from a presentation made by representatives of LVAD manufacturer, Thoratec, to the FDA Circulatory Systems Devices Advisory Committee meeting in March 2002 (Thoratec, Inc. 2002). Table 5 shows the probabilities for the proportions in NYHA I/II or III/IV. Cycle-specific probabilities between given values were imputed using linear ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Table 3. Cycle-specific Survival Probabilities (Extrapolations in Italics) Month Probability of Survival, LVAD Probability of Survival, OMM 0 1.000 1.000 1 0.810 0.800 2 0.810 0.690 3 0.720 0.640 4 0.710 0.540 5 0.640 0.490 6 0.590 0.460 7 0.590 0.460 8 0.590 0.390 9 0.540 0.340 10 0.540 0.290 11 0.520 0.280 12 0.510 0.280 13 0.510 0.240 14 0.500 0.210 15 0.440 0.180 16 0.410 0.160 17 0.410 0.160 18 0.360 0.110 19 0.360 0.080 20 0.360 0.080 21 0.360 0.080 22 0.330 0.080 23 0.310 0.080 24 0.240 0.080 25 0.160 0.020 26 0.100 0.010 27 0.090 0.009 28 0.080 0.008 29 0.070 0.007 30 0.060 0.006 31 0.050 0.005 32 0.040 0.000 33 0.030 0.000 34 0.020 0.000 35 0.010 0.000 36 0.000 0.000 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 13 Technology Evaluation Center Table 4. Median and Mean Survival Median Survival Mean Survival LVAD OMM days 405 180 months 13.30 5.90 years 1.11 0.49 days 392 221 months 12.87 7.26 years 1.07 0.61 Difference 7.40 5.61 Figure 3. Derivation of Transition Probabilities for Markov Cohort Simulations ���������������������������������������� ��������������������������������������� ������������������������������������ ���������������������������������������� ������������������������������������������� ��������������������������������� ��������������������������������������� ����������� ����� ������������������������ ���������������������� ������������������������ �� ���������������������������������������������������������������������������������������� �������������������������������������� ������������������������������������������������������������������������������ �� ��������������������������� �� ����� �� ��������� ��������� �� ��������������������������� �� ����� �� ���������������������������� � � � � ������ ������������������ �� ����� �� �������� ����� � �� ���������������� Table 5. New York Heart Association Function Class LVAD OMM Month Post-Enrollment % NYHA I/II % NYHA III/IV % NYHA I/II % NYHA III/IV 0 0 100 0 100 1 54 46 0 100 3 68 32 3 97 6 80 20 9 91 9 82 18 0 100 12 71 29 0 100 18 44 56 0 100 24 71 29 33 67 14 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure interpolation. It was assumed that the probabilities for the last given follow-up point, 24 months, stayed constant for all remaining cycles. and a lower mean score on SF-36 physical functioning subscale (17 vs. 26, p=0.0747). Survival did not differ between subgroups. Utilities A study by Moskowitz et al. (1997) assessed quality of life for 29 bridge-to-transplant LVAD recipients at Columbia University. Standard gamble utilities were elicited before implantation and during LVAD support. The mean utility value (standard deviation [SD]) for the preimplantation period was 0.548 (0.276). The utility associated with preimplantation in this group should be analogous to being in NYHA category III/IV, so the cost-effectiveness analysis used a value of 0.55 for this category. During LVAD support, the mean utility was 0.809 (SD=0.136). It was assumed that LVAD support in this group is representative of being in NYHA category I/II. The cost-effectiveness analysis used 0.81 for this category. To determine hospitalization costs, the REMATCH data set was combined with CMS data and line item bills from clinical centers. Institution-specific cost reports were used to calculate ratio-of-cost-to-charges for each major resource category. There were 17 in-hospital deaths and 35 hospital survivors. Hospital survivors had mean hospitalization costs of $159,271 ± 106,423; hospital nonsurvivors had mean costs of $315,015 ± 278,713. The average cost of the implantation, excluding professional fees, was $210,187 (± 193,295). Oz et al. (2003) excluded professional fees and did not mention whether costs valued in a constant $year. Since data collection ended in 2002, it was assumed that costs were expressed as 2002 $US. Professional fees were estimated from the study by Moskowitz et al. (2001) of 12 bridgeto-transplant patients (Table 7). Fees for mean 17.5-day hospital stay were prorated to a 43.5day stay, then adjusted for inflation factor from 1995 $US to 2002 $US: Rehospitalization Data on the probability of rehospitalization were obtained from a paper by Oz et al. (2003) and a Center for Devices and Radiologic Health (CDRH) presentation at the FDA Circulatory Systems Devices Advisory Committee meeting in March 2002. According to Oz et al. (2003), LVAD patients spent a total of 18,406 days on LVAD support, of which 3,896 days (22%) were spent in the hospital. CDRH data for OMM patients showed a total of 10,085 days alive, of which 1,756 (15%) were spent in the hospital. No data are available on whether the probability of rehospitalization changed over time, so it was assumed that the proportion of days spent in the hospital could be applied to each cycle as a constant weight. The probability of being an outpatient was calculated as one minus the probability of rehospitalization. Costs Oz et al. (2003) reported on the costs associated with LVAD in the REMATCH trial (Table 6). Of the 68 LVAD recipients in the REMATCH trial, 52 comprised the costing subgroup. Patients were excluded for not being in CMS database or participating hospitals were unable to provide cost data. There were no significant differences between the costing subgroup and the excluded subgroup on baseline characteristics. However, the LVAD costing subgroup had a nonsignificantly lower percentage of patients using ACE inhibitors (56% vs. 81%, p=0.083) Oz et al. (2003) reported that the average annual readmission cost was $105,326. Based on a probability of being rehospitalized of 0.22, the annual readmission cost was prorated to a full year of hospitalization, then divided by 12 to yield a monthly rehospitalization cost of $39,896. This amount includes the cost of LVAD replacements but excludes professional fees. It was assumed that inpatient costs were the same for both groups of patients. Outpatient costs were estimated from studies by Moskowitz et al. (2001) and Gelijns et al. (1997), which analyzed costs associated with long-term LVAD implantation in bridge-totransplant patients (Table 7). All cost estimates were given in 1995 $US. The average cost of the implantation was reported as $141,287. The 17.5-day average length of stay associated with implantation was derived from a simulation. Clinical discharge criteria were applied to the sample, which had longer actual stays because the FDA required long hospitalization periods for these patients. The average weekly outpatient cost was $352, yielding a full month cost of $1,531. When valued in 2002 $US, the monthly outpatient cost is $1,719. ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 15 Technology Evaluation Center Table 6. Oz et al. (2003) Report on Costs of Destination LVADs Patients LVAD costing subgroup: 52 of 68 LVAD recipients from REMATCH trial. LVAD noncosting subgroup: 16 patients excluded for not being in CMS database, participating hospitals unable to provide cost data. No significant difference between subgroups on baseline characteristics. The LVAD costing subgroup had a nonsignificantly lower percentage of patients using ACE inhibitors (56% vs. 81%, p=0.083) and a lower mean score on SF-36 physical functioning subscale (17 vs. 26, p=0.0747). Survival did not differ between subgroups. Costs Clinical data set closed 6/20/02. Survival and costs truncated at 22 months of follow-up. To determine hospitalization costs, REMATCH data set combined with CMS data and line item bills from clinical centers. Institution-specific cost reports were used to calculate ratio-of-cost-to-charges for each major resource category. Analysis excluded professional fees. Report did not mention whether costs valued in constant $year. Initial hospitalization, average length of stay 43.5 days, with 17 in-hospital deaths, 35 hospital survivors. Hospital survivors had mean hospitalization costs of $159,271 ± 106,423; hospital nonsurvivors had mean costs of $315,015 ± 278,713. Resource Category LVAD ICU days Regular floor Operating room Diagnostics Laboratory Blood products Drugs Medical Supplies Therapy Renal Other Total, initial hospitalization Average Cost $62,308 ± 11,651 $50,262 ± 82,076 $18,807 ± 45,286 $10,983 ± 9,913 $3,833 ± 3,222 $10,426 ± 14,161 $6,773 ± 10,731 $15,685 ± 20,219 $12,376 ± 21,536 $13,784 ± 35,534 $1,674 ± 5,988 $79 ± 161 $210,187 ± 193,295 % of Total Cost 29.64% 23.91% 8.95% 8.95% 1.82% 1.52% 3.22% 7.46% 5.89% 6.56% 0.80% 0.04% 100% Initial hospitalization cost predicted by: perioperative bleeding, pump housing infection, and sepsis. Total LVAD support days In hospital (%) Out of hospital (%) 18,406 3,896 (22%) 15,510 (78%) 16 patients had 17 LVAD replacements. 152 readmissions involved 34 patients and 1,634 hospital days. Mean readmission cost: $30,627 ± 61,569. Mean annual readmission cost per patient: $105,326. Mean annual cost for initial hospitalization and readmission: $309,273. Outpatient costs not mentioned. 16 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Table 7. Moskowitz et al. (2001) Report on Costs of Long-Term LVAD Implantation in Bridge Patients. Patients 12 individuals implanted with LVAD at Columbia University during 1994 and 1995. FDA prohibited discharge in 1994 and dictated minimum stay in 1995. To simulate discharge dates guided by clinical concerns, predefined discharge criteria applied to patient records – – – – – – Recovery from surgery with adequate general health status Absence of fever or evidence of systemic or driveline infections Normal liver function test results (transaminases, bilirubin) White blood cell count (<11,000/mm3) Serum creatinine (<2 mg/dL) Echocardiographic evidence indicating that the patient’s native heart has sufficient contractility to open the aortic valve and maintain an arterial pressure with the LVAD operating at its lowest rate – Ability of patients/caretakers to change batteries, maintain device, and perform ADLs. By end of study period, 2 patients died, 8 had heart transplantation, and 2 remained on LVAD. Mean duration of LVAD support, 177 days (13–481 days) Mean length of stay, implantation, 17.5 days (± 5.32 days) Costs Initial Hospitalization, average length of stay 17.5 days (± 5.32 days), costs generally estimated by ratio of charges to costs method in 1995 $US. Resource Category LVAD Professional payment Length of stay Special care days Regular floor Operating room Diagnostics Laboratory Blood products Drugs Miscellaneous Rehabilitation Total, initial hospitalization Average Cost $67,085 $23,935 ± 10,897 $14,765 ± 10,874 $7,071 ± 7,376 $10,818 ± 1,725 $3,900 ± 3,574 $3,407 ± 1,767 $2,873 ± 2,562 $3,257 ± 3,229 $3,235 ± 1,695 $670 ± 423 $141,287 ± 18,513 Total LVAD support days In hospital (%) Out of hospital (%) 2,012 746 (37%) 1,266 (63%) % of Total Cost 48% 17% 10% 5% 8% 3% 2% 2% 2% 2% 0% 100% Outpatient and Rehospitalization 124 hospital days, total cost $215,093 ($1,735 per day, $52,802 per month) The average outpatient cost was $352 per week ($1,531 per month) ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 17 Technology Evaluation Center Cost-effectiveness Analysis Results Total Costs for One Year Table 8 shows the costs of 1 year on 3 interventions: LVAD as a bridge to transplantation; LVAD as destination therapy; and OMM. Discounting was not used in calculating these costs. Baseline Analysis Using the values for all parameters listed in Table 2, the LVAD Markov model produced a total of 0.755 QALYs at a total cost of $391,900. The OMM Markov model yielded 0.332 QALYs at a cost of $53,025. The incremental costeffectiveness ratio (ICER) was $802,700 per QALY (Figure 4). Sensitivity Analyses Uncertainty Around Relative Survival. Table 9 shows that the lower limit on the hazard ratio for LVAD relative to OMM produces an ICER of $1,350,700/QALY. The survival probability fell to 0 after 41 months in the OMM group and after 53 months for the LVAD group. At the upper limit of the confidence interval, the ICER is $447,600/QALY. In this case, survival in the LVAD group dropped to 0 after 121 months. Extrapolation of Survival. Of the 4 methods used to extrapolate survival past the point of last follow-up, the exponential method produces an ICER most favorable to LVAD ($641,600/QALY). This is also the least plausible of the 4 because both the original survival data (Rose et al. 2001) and the update (CDRH FDA 2002) show an increasing hazard for the LVAD group between 23 and 26 months. The exponential survival model for LVAD allows the hazard to stay constant based on a fit with the earlier segment of the survival curve. The curve remains elevated past the period of accelerated hazard at 23–26 months and falls to a survival probability of 0 after 86 months. At last follow-up (26 months), the survival probability was 10% in the LVAD group and 1% in the OMM group; thus an extrapolation with an extended tail on the survival curve seems quite unlikely. The Gompertz/exponential method used a Gompertz model for the LVAD group to fit the portion of the curve with an accelerating hazard. This method produced an ICER that was least favorable to LVAD ($846,900/QALY). The stop and drop method differs slightly from Gompertz/exponential, probably due to the 18 low survival probabilities in both groups at last follow-up. The 3 methods besides exponential achieve similar findings and the method using linear interpolation to 36 months is the most favorable, yielding an ICER of $802,700/QALY. This method was used for the baseline analysis and all sensitivity analyses. Utilities for NYHA Categories I/II and III/IV. Figure 5 shows how ICER values are affected by varying the utility for NYHA category I/II from 0.50 to 1.00. Across this range, ICERs vary from $1,588,900/QALY to $615,900/QALY. In Figure 6, the utility for NYHA category III/IV ranges from 0.30 to 0.80. The resulting ICERs are between $708,400/QALY and $926,000/QALY. Utility Discount Rate. The discount rate for utilities was allowed to vary from 1% to 5% (Figure 7). ICERs did not vary substantially, taking values between $784,500/QALY and $821,100/QALY. Cost of LVAD Implantation. The cost of the initial hospital stay for LVAD implantation was valued between $125,000 and $425,000 (Figure 8). The ICER varied from $442,600/ QALY to $1,153,200/QALY. Cost of Rehospitalization. The cost for 1 month of being readmitted to the hospital varied between $20,000 and $70,000 (Figure 9). The low estimate for rehospitalization cost led to an ICER of $701,400/QALY, while the higher estimate produced an ICER of $904,700/QALY. Cost of Outpatient Care. This cost category had little impact on the ICER, across values of $250 per month to $3,250 per month (Figure 10). ICERs were between $792,900/QALY and $812,900/QALY. Probability of Rehospitalization for LVAD and OMM. Figure 11 shows how ICERs are affected by varying the probability of rehospitalization for LVAD between 0.10 and 0.35. The lowest probability yields an ICER of $679,400/QALY, while the highest has an ICER of $936,200/QALY. It is important to note that while the probability of rehospitalization for LVAD was allowed to vary, the probability for OMM stayed constant at 0.15. Thus, when the LVAD probability of rehospitalization was 0.10, it was lower than the value for OMM. A lower relative probability of rehospitalization for ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Table 8. Total One Year Costs for Bridge LVAD, Destination LVAD and Optimal Medical Management Intervention 1995 $US 2002 $US Bridge LVAD 222,460 249,823 Destination LVAD 450,035 505,373 OMM 178,693 Figure 4. Baseline Cost-effectiveness Analysis ��� ���� ��� ������������������� ��� Cost ��� OMM LVAD $53,025 $391,906 $338,881 Incr Cost Eff ��� 0.332 QALYs 0.755 QALYs Incr Eff 0.422 QALYs ICER $802,674/QALY ��� � ���� ���� ���� ���� ���� ���� ���������������������� Table 9. Sensitivity Analysis on 95% Confidence Interval Around Hazard Ratio Cost LVAD Cost OMM Cost Difference QALYs LVAD QALYs OMM QALYs Difference ICER Lower limit, 95% CI $357,812 $53,160 $304,652 0.560 0.334 0.226 $1,350,746 Baseline $391,906 $53,025 $338,882 0.755 0.332 0.422 $802,674 Upper limit, 95% CI $477,413 $53,160 $424,253 1.282 0.334 0.948 $447,645 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 19 Technology Evaluation Center Table 10. Sensitivity Analysis on Method of Survival Extrapolation Extrapolation Method Cost LVAD Cost OMM Cost Difference QALYs LVAD QALYs OMM QALYs Difference ICER (per QALY) Gompertz/ exponential $389,361 $54,650 $334,711 0.739 0.344 0.395 $846,888 Stop and drop $387,678 $52,782 $334,896 0.729 0.331 0.398 $840,738 Linear interpolation $391,906 $53,025 $338,882 0.755 0.332 0.422 $802,674 Exponential $417,516 $54,650 $362,866 0.910 0.344 0.566 $641,592 Figure 5. Sensitivity Analysis on Utility NYHA I/II ��������������������������������������� ����� ����� ���� ��� ����� ����� ��� ��� Utility NYHA I/II ICER 0.50 $1,588,874 0.60 $1,207,387 0.70 $973,622 0.80 $815,693 0.90 $701,849 1.00 $615,890 ��� � ���� ���� ���� ���� ���� ���� ����������������� 20 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Figure 6. Sensitivity Analysis on Utility NYHA III/IV ��������������������������������������� ����� ��� ��� ��� � ���� ���� ��� ���� ���� ���� ���� Utility NYHA III/IV ICER 0.30 $708,363 0.40 $743,296 0.50 $781,854 0.60 $824,632 0.70 $872,361 0.80 $925,955 Utility Discount Rate ICER 0.01 $784,499 0.02 $793,554 0.03 $802,674 0.04 $811,856 0.05 $821,103 ���� ������������������� Figure 7. Sensitivity Analysis on Utility Discount Rate ��������������������������������������� ����� ��� ��� ���� ��� ��� � ���� ���� ���� ���� ���� ��������������������� ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 21 Technology Evaluation Center Figure 8. Sensitivity Analysis on Cost of Implantation ��������������������������������������� ����� ����� ��� ���� ��� ��� Cost of Implantation ICER $125,000 $442,644 $200,000 $620,289 $275,000 $797,934 $350,000 $975,579 $425,000 $1,153,224 Cost of Rehospitalization ICER $10,000 $701,399 $20,000 $735,275 $30,000 $769,150 $40,000 $803,026 $50,000 $836,901 $60,000 $870,777 $70,000 $904,652 ��� � ��� ��� ��� ��� ��� ���������������������������������� Figure 9. Sensitivity Analysis on Cost of Rehospitalization per Month ��������������������������������������� ����� ��� ��� ���� ��� ��� � �� �� �� �� �� ������������������������������������������������� 22 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Figure 10. Sensitivity Analysis on Cost of Outpatient Care Post-implant per Month ��������������������������������������� ����� ��� ��� ���� ��� ��� Cost of Outpatient Care ICER $250 $792,915 $1,000 $797,897 $1,750 $802,879 $2,500 $807,862 $3,250 $812,844 Probability of Rehospitalization LVAD ICER 0.10 $679,442 0.15 $730,789 0.20 $782,135 0.25 $833,481 0.30 $884,828 0.35 $936,174 � ��� ����� ����� ����� ����� ������������������������������������� Figure 11. Sensitivity Analysis on Probability of Rehospitalization LVAD ��������������������������������������� ����� ��� ��� ���� ��� ��� � ���� ���� ���� ���� ���� ���� ������������������������������������� ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 23 Technology Evaluation Center LVAD seems very unlikely given evidence from the REMATCH trial of a significantly higher rate of serious adverse events for LVAD. In Figure 12, the probability of rehospitalization for OMM ranged from 0.05 to 0.30, assuming a constant probability of 0.22 for LVAD. At the upper end of the range, the probability of rehospitalization for OMM is higher than that for LVAD, which as noted above, is very unlikely. ICERs varied from $867,000/QALY to $706,100/QALY. the LVAD unit alone is approximately $65,000. It is unlikely that all other initial costs associated with implantation would commonly be covered by an amount as low as $60,000. Best Case Scenario. An analysis was performed in which variables were set at values that would be quite favorable to LVAD (Table 11). An ICER of $214,700 is obtained. Such values would be highly unlikely to occur both alone and in combination. Discussion Cost Discount Rate. When the cost discount rate was varied from 1% to 5%, ICERs were between $806,700/QALY and $798,800/QALY. Two-Way Sensitivity Analyses. Appendix Tables A1–A21 present 2-way sensitivity analyses for selected variables. When paired with other variables, the cost of LVAD implantation appears to have the greatest influence on the results. Tables A2, A7, A12, A13, and A14 comprise all tables in which the cost of LVAD implantation is paired with another variable. These are the only analyses in which ICERs below $500,000/QALY are observed. Such results depend on estimates of LVAD costs at the low extremes (e.g., $125,000). The cost of Limitations of this Analysis Simplicity of the Markov Models. Although 2 health states were included in the Markov models, these are analogous to 3-state models given that QALY calculations allowed surviving patients to make transitions between 2 NYHA categories, in addition to a death state. It would be interesting to construct a model that has separate states for being rehospitalized versus being at home. LVAD patients spend 22% of their days in the hospital compared with 15% for OMM patients. LVAD patients also had a significantly higher rate of serious adverse events (Rose et al. 2001). The device was Figure 12. Sensitivity Analysis on Probability of Rehospitalization OMM ��������������������������������������� ����� ��� ��� ���� ��� ��� � ���� ���� ���� ���� ���� Probability of Rehospitalization OMM ICER 0.05 $867,072 0.10 $834,873 0.15 $802,674 0.20 $770,474 0.25 $738,275 0.30 $706,076 ���� ������������������������������������ 24 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Figure 13. Baseline Cost-effectiveness Analysis ��������������������������������������� ����� ��� ��� ���� ��� ��� � ���� ���� ���� ���� Cost Discount Rate ICER 0.01 $806,703 0.02 $804,672 0.03 $802,674 0.04 $800,706 0.05 $798,770 ���� ������������������ Table 11. Values of Best Case Scenario Variable Value Utility for NYHA I/II 1.00 Utility for NYHA III/IV 0.30 Cost of LVAD Implantation $125,000 Cost of rehospitalization (per mo) $10,000 Cost of outpatient care (per mo) $250 Probability of rehospitalization, LVAD 0.10 Probability of rehospitalization, OMM 0.10 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 25 Technology Evaluation Center replaced 17 times in 16 patients and the probability of device failure was 35% at 2 years (Oz et al. 2003; Rose et al. 2001). A more complex model might be better able to show the impact on quality of life of rehospitalization due to adverse events and device malfunction. The models used here were based on NYHA class data that likely included a mix of inpatients and outpatients, but a more detailed approach might better reflect patients’ experiences. Unfortunately, data were unavailable from the REMATCH trial to permit constructing more complex models. Utilities for NYHA Categories I/II and III/IV. Uncertainty exists about which utility values should be used for being in NYHA categories I/II or III/IV. This analysis used published mean standard gamble utilities derived from 29 bridge-to-transplant patients (Moskowitz et al. 1997). The preimplantation mean utility was assigned to NYHA category III/IV, while the mean utility for LVAD support was assigned to NYHA category I/II. The Moskowitz paper does not provide data on NYHA class for patients in this study before or after implantation. However, previous studies of bridge-to-transplant patients have shown that patients were generally in NYHA class III or IV before implantation and in class I or II after transplantation (Frazier et al. 1995; 1994). Also, utilities for bridge-to-transplant patients may differ from destination patients, even within the same NYHA categories. Furthermore, the mean utilities from Moskowitz may be biased because they were not taken from a healthy population, consistent with a societal perspective. Because the sensitivity analyses used wide ranges for utility values, and ICERs did not vary substantially, these concerns are not critical. Cost Estimates and Assumptions. The REMATCH destination therapy costing study by Oz et al. (2003) provided estimates for LVAD implantation costs and rehospitalization costs. Earlier costing studies on bridge-to-transplant LVAD patients gave information on outpatient costs and professional fees for LVAD implantation (Moskowitz et al. 2001; Gelijns et al. 1997). The REMATCH estimate on LVAD implantation excluded professional fees, but this analysis used bridge-to-transplant professional fee data to augment the overall estimate. The REMATCH estimate on rehospitalization also excluded professional fees and no useful data are available for estimating them. So the rehospitalization estimate of approximately $40,000 26 per month for LVAD may be too low. The sensitivity analysis on the cost of rehospitalization ranged up to $70,000 per month, and at that extreme, the ICER increased by about $100,000 relative to the baseline analysis result. This cost-effectiveness analysis used monthly rehospitalization costs and outpatient costs based only on LVAD patients and assumed that these costs were the same for LVAD and OMM. No estimates of these costs for OMM patients are available from the REMATCH trial. The highly selected nature of REMATCH trial participants makes it prohibitively difficult to estimate OMM costs from some other source. It is likely that both cost categories would be higher for LVAD; in fact, the rehospitalization costs from REMATCH include some individuals who had device replacement, so the present analysis may be conservative. Outpatient costs were estimated from LVAD bridge patients and it was assumed that costs for outpatient care were the same for LVAD and OMM patients. Outpatient costs for LVAD destination are probably not lower than those for LVAD bridge patients, so estimates used here may be conservative. It is unclear whether outpatient costs are similar between LVAD destination patients and OMM patients. However, the sensitivity analysis on outpatient costs showed it to have little impact on ICERs, so this issue does not appear critical. Probability of Rehospitalization for LVAD and OMM. The only data available on rehospitalization described the proportion of days alive spent in the hospital. These proportions were applied as constant weights within each cycle of the Markov models for LVAD and OMM. Evidence was lacking on whether the probability of rehospitalization changed over time, so the simplest assumption was to hold it constant. Conclusions The baseline cost-effectiveness analysis, using parameter estimates from published sources, showed that use of LVADs leads to an increase in cost of $802,700 to gain 1 QALY, compared with optimal medical management. Within the range of values used in this analysis, the ICER was fairly stable amid changes in these variables: utility for NYHA category III/IV; utility discount rate; cost of outpatient care; and cost discount rate, cost of rehospitalization, ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure probability of rehospitalization for LVAD; and probability of rehospitalization for OMM. Results were more sensitive to variations in utility for NYHA category I/II and the cost of LVAD implantation. ICERs of $500,000/QALY or less depended on improbable assumptions of very low costs for LVAD implantation, usually in combination with extreme values on other variables. This analysis takes a societal perspective; however, some elements of this perspective, such as use of indirect costs, were not strictly followed. Although utilities from a general population would be preferred, the estimates used here from LVAD recipients suffice given the wide range of values surrounding them in the sensitivity analysis. As stated, indirect costs, such as lost wages and costs borne by caretakers, are not included, but as return to work is unlikely for either LVAD or OMM patients, excluding indirect costs would not affect the strategies’ relative standings in the analysis. The short time horizon should limit the impact of excluding indirect costs. NOTICE OF PURPOSE: TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated. CONFIDENTIAL: This document contains proprietary information that is intended solely for Blue Cross and Blue Shield Plans and other subscribers to the TEC Program. The contents of this document are not to be provided in any manner to any other parties without the express written consent of the Blue Cross and Blue Shield Association. ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 27 Technology Evaluation Center References Center for Devices and Radiologic Health, Food and Drug Administration. (2002). Presentation to Food and Drug Administration Circulatory System Devices Advisory Panel, March 4, 2002. Cohn JN. (2000a). The management of heart failure. In: JT Willerson and JN Cohn (eds.), Cardiovascular Medicine, Churchill Livingstone, Philadelphia, 1165-83. Cohn JN. (2000b). Pathophysiology and clinical recognition of heart failure. In: JT Willerson and JN Cohn (eds.), Cardiovascular Medicine, Churchill Livingstone, Philadelphia, 1147-64. Eichhorn EJ. (2001). Prognosis determination in heart failure. Am J Med, 110(7A):14S-36S. Frazier OH, Rose EA, McCarthy P et al. (1995). Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system. Ann Surg, 222(3):327-38. Frazier OH, Macris MP, Myers TJ et al. (1994). Improved survival after extended bridge to cardiac transplantation. Ann Thorac Surg, 57:1416-22. Frazier OH, Macris MP. (1994). Current methods for circulatory support. Inst J, 21:288-95. Gross Domestic Product Deflator (2004). Source: Budget of the United States Government, Fiscal Year 2001, Historical Tables. Table 10.1--Gross Domestic Product and Deflators Used in the Historical Tables: 1940-2005. Accessed online at: http://www.jsc.nasa.gov/bu2/ inflateGDP.html, March 17, 2004. Gelijns AC, Richards AF, Williams DL et al. (1997). Evolving costs of long-term left ventricular assist device implantation. Ann Thorac Surg, 64:1312-9. Greenberg BH. (2000). The medical management of chronic congestive heart failure. In JD Hosenpud and BH Greenberg (eds.), Congestive Heart Failure, Second Edition, 2000, Lippincott, Williams and Wilkins, Philadelphia, 673-95. Moskowitz AJ, Rose EA, Gelijns AC. (2001). The cost of long-term LVAD implantation. Ann Thorac Surg, 71:S195-8. Moskowitz AJ, Weinberg AD, Oz MC et al. (1997). Quality of life with an implanted left ventricular assist device. Ann Thorac Surg, 64:1764-9. Oz MC, Gelijns AC, Miller L et al. (2003). Left ventricular assist devices as permanent heart failure therapy. The price of progress. Ann Surg, 238(4):577-85. Oz MC, Rose EA, Levin HR. (1995). Selection criteria for placement of left ventricular assist devices. Am Heart J, 129(1):173-7. Rose E. (2002). REMATCH trial clinical results. Presentation to Food and Drug Administration Circulatory System Devices Advisory Panel, March 4, 2002. Rose EA, Gelijns AC, Moskowitz AJ et al. (2001). Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med, 345(20):1435-43. Rose EA, Moskowitz AJ, Packer M et al. (1999). The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg, 67(3):723-30. Thoratec, Inc. (2002). REMATCH trial clinical results. Presentation to Food and Drug Administration Circulatory System Devices Advisory Panel, March 4, 2002. United Network for Organ Sharing. (2001). 2001 Annual report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry for Transplant Recipients: Transplant Data 1991-2000. Department of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation, Rockville, MD; United Network for Organ Sharing, Richmond, VA; University Renal Research and Education Association, Ann Arbor, MI. Zeltsman D, Acker MA. (2002). Surgical management of heart failure: an overview. Annu Rev Med, 53:383-91. Miniati DN, Robbins RC. (2002). Heart transplantation: a thirty-year perspective. Annu Rev Med, 53:189-205. 28 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Appendix Table A1. Sensitivity Analysis – Utility for NYHA Classes I/II by Utility for NYHA Classes III/IV. ICERs (per QALY) Utility NYHA I/II Utility NYHA III/IV 0.50 0.60 0.70 0.80 0.90 1.00 0.30 $1,257,472 $1,005,931 $838,248 $718,483 $628,663 $558,804 0.40 $1,371,933 $1,077,870 $887,614 $754,447 $656,026 $580,320 0.50 $1,509,318 $1,160,890 $943,157 $794,204 $685,879 $603,557 0.60 $1,677,281 $1,257,766 $1,006,120 $838,381 $718,579 $628,736 0.70 $1,887,308 $1,372,283 $1,078,086 $887,760 $754,553 $656,106 0.80 $2,157,462 $1,509,742 $1,161,141 $943,323 $794,321 $685,967 Table A2. Sensitivity Analysis – Utility for NYHA Classes I/II by Cost of LVAD Implantation ICERs (per QALY) Utility NYHA I/II 0.50 0.60 0.70 0.80 0.90 1.00 $125,000 $876,204 $665,829 $536,916 $449,824 $387,043 $339,640 $200,000 $1,227,847 $933,044 $752,395 $630,350 $542,374 $475,947 $275,000 $1,579,491 $1,200,259 $967,874 $810,876 $697,704 $612,253 $350,000 $1,931,135 $1,467,474 $1,183,353 $991,403 $853,035 $748,560 $425,000 $2,282,779 $1,734,688 $1,398,832 $1,171,929 $1,008,365 $884,867 Cost Implant Table A3. Sensitivity Analysis – Utility for NYHA Classes I/II by Cost of Rehospitalization ICERs (per QALY) Utility NYHA I/II 0.50 0.60 0.70 0.80 0.90 1.00 $10,000 $1,388,403 $1,055,050 $850,780 $712,776 $613,295 $538,183 $20,000 $1,455,459 $1,106,006 $891,870 $747,201 $642,916 $564,175 $30,000 $1,522,515 $1,156,962 $932,960 $781,626 $672,536 $590,168 $40,000 $1,589,570 $1,207,918 $974,050 $816,051 $702,156 $616,160 $50,000 $1,656,626 $1,258,874 $1,015,141 $850,476 $731,777 $642,153 $60,000 $1,723,682 $1,309,829 $1,056,231 $884,901 $761,397 $668,146 $70,000 $1,790,738 $1,360,785 $1,097,321 $919,326 $791,017 $694,138 Cost Rehosp ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 29 Technology Evaluation Center Table A4. Sensitivity Analysis – Utility for NYHA Classes I/II by Cost of Outpatient Care ICERs (per QALY) Utility NYHA I/II 0.50 0.60 0.70 0.80 0.90 1.00 $250 $1,569,556 $1,192,709 $961,786 $805,776 $693,315 $608,402 $750 $1,576,131 $1,197,705 $965,815 $809,151 $696,220 $610,951 $1,250 $1,582,706 $1,202,701 $969,844 $812,527 $699,124 $613,499 $1,750 $1,589,281 $1,207,698 $973,873 $815,902 $702,028 $616,048 $2,250 $1,595,856 $1,212,694 $977,902 $819,278 $704,933 $618,597 $2,750 $1,602,431 $1,217,690 $981,931 $822,653 $707,837 $621,145 $3,250 $1,609,006 $1,222,687 $985,960 $826,028 $710,742 $623,694 Cost Outpt Care Table A5. Sensitivity Analysis – Utility for NYHA Classes I/II by Probability of Rehospitalization for LVAD ICERs (per QALY) Utility NYHA I/II 0.50 0.60 0.70 0.80 0.90 1.00 0.10 $1,344,939 $1,022,022 $824,146 $690,463 $594,096 $521,335 0.15 $1,446,578 $1,099,258 $886,428 $742,642 $638,993 $560,733 0.20 $1,548,217 $1,176,494 $948,710 $794,821 $683,890 $600,131 0.25 $1,649,856 $1,253,729 $1,010,992 $847,000 $728,786 $639,529 0.30 $1,751,495 $1,330,965 $1,073,274 $899,180 $773,683 $678,927 0.35 $1,853,134 $1,408,201 $1,135,556 $951,359 $818,580 $718,325 P Rehosp LVAD Table A6. Sensitivity Analysis – Utility for NYHA Classes I/II by Probability of Rehospitalization for OMM ICERs (per QALY) 0.50 0.60 0.70 0.80 0.90 1.00 0.05 $1,716,348 $1,304,257 $1,051,737 $881,136 $758,158 $665,303 0.10 $1,652,611 $1,255,822 $1,012,680 $848,414 $730,003 $640,596 0.15 $1,588,873 $1,207,388 $973,623 $815,693 $701,848 $615,890 0.20 $1,525,135 $1,158,954 $934,566 $782,971 $673,694 $591,184 0.25 $1,461,398 $1,110,519 $895,509 $750,250 $645,539 $566,477 0.30 $1,397,660 $1,062,085 $856,452 $717,528 $617,385 $541,771 P Rehosp OMM 30 Utility NYHA I/II ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Table A7. Sensitivity Analysis – Utility for NYHA Classes III/IV by Cost of LVAD Implantation ICERs (per QALY) Utility NYHA III/IV 0.30 0.40 0.50 0.60 0.70 0.80 $125,000 $390,636 $409,900 $431,163 $454,753 $481,075 $510,630 $200,000 $547,408 $574,403 $604,200 $637,257 $674,143 $715,559 $275,000 $704,181 $738,907 $777,237 $819,762 $867,211 $920,488 $350,000 $860,954 $903,410 $950,274 $1,002,266 $1,060,279 $1,125,417 $425,000 $1,017,726 $1,067,914 $1,123,311 $1,184,770 $1,253,347 $1,330,346 Cost Implant Table A8. Sensitivity Analysis – Utility for NYHA Classes III/IV by Cost of Rehospitalization ICERs (per QALY) Utility NYHA III/IV 0.30 0.40 0.50 0.60 0.70 0.80 $10,000 $618,989 $649,513 $683,206 $720,586 $762,295 $809,127 $20,000 $648,884 $680,883 $716,203 $755,388 $799,112 $848,205 $30,000 $678,779 $712,252 $749,200 $790,191 $835,928 $887,283 $40,000 $708,675 $743,622 $782,197 $824,993 $872,745 $926,362 $50,000 $738,570 $774,992 $815,194 $859,795 $909,561 $965,440 $60,000 $768,465 $806,361 $848,191 $894,597 $946,378 $1,004,519 $70,000 $798,361 $837,731 $881,187 $929,399 $983,195 $1,043,597 Cost Rehosp Table A9. Sensitivity Analysis – Utility for NYHA Classes III/IV by Cost of Outpatient Care ICERs (per QALY) Utility NYHA III/IV 0.30 0.40 0.50 0.60 0.70 0.80 $250 $699,751 $734,259 $772,348 $814,605 $861,756 $914,698 $1,000 $704,148 $738,873 $777,201 $819,724 $867,171 $920,445 $1,750 $708,545 $743,487 $782,054 $824,842 $872,586 $926,193 $2,500 $712,942 $748,100 $786,907 $829,961 $878,001 $931,941 $3,250 $717,339 $752,714 $791,761 $835,080 $883,416 $937,688 Cost Outpt Care ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 31 Technology Evaluation Center Table A10. Sensitivity Analysis – Utility for NYHA Classes III/IV by Probability of Rehospitalization for LVAD ICERs (per QALY) Utility NYHA III/IV 0.30 0.40 0.50 0.60 0.70 0.80 0.10 $599,611 $629,180 $661,819 $698,028 $738,432 $783,797 0.15 $644,925 $676,729 $711,833 $750,779 $794,236 $843,030 0.20 $690,238 $724,277 $761,848 $803,530 $850,040 $902,262 0.25 $735,552 $771,825 $811,862 $856,281 $905,844 $961,495 0.30 $780,865 $819,373 $861,877 $909,032 $961,649 $1,020,728 0.35 $826,179 $866,921 $911,892 $961,783 $1,017,453 $1,079,960 P Rehosp LVAD Table A11. Sensitivity Analysis – Utility for NYHA Classes III/IV by Probability of Rehospitalization for OMM ICERs (per QALY) Utility NYHA III/IV 0.30 0.40 0.50 0.60 0.70 0.80 0.05 $765,196 $802,930 $844,582 $890,791 $942,351 $1,000,245 0.10 $736,780 $773,113 $813,218 $857,711 $907,357 $963,100 0.15 $708,364 $743,296 $781,854 $824,631 $872,362 $925,955 0.20 $679,948 $713,479 $750,490 $791,551 $837,367 $888,811 0.25 $651,532 $683,661 $719,126 $758,471 $802,372 $851,666 0.30 $623,116 $653,844 $687,762 $725,391 $767,378 $814,521 P Rehosp OMM Table A12. Sensitivity Analysis – Cost of LVAD Implantation by Cost of Rehospitalization ICERs (per QALY) Cost Implant Cost Rehosp $125,000 $200,000 $275,000 $350,000 $425,000 $10,000 $341,370 $519,016 $696,661 $874,306 $1,051,951 $20,000 $375,246 $552,891 $730,536 $908,181 $1,085,827 $30,000 $409,122 $586,767 $764,412 $942,057 $1,119,702 $40,000 $442,997 $620,642 $798,287 $975,932 $1,153,578 $50,000 $476,873 $654,518 $832,163 $1,009,808 $1,187,453 $60,000 $510,748 $688,393 $866,038 $1,043,684 $1,221,329 $70,000 $544,624 $722,269 $899,914 $1,077,559 $1,255,204 32 ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Table A13. Sensitivity Analysis – Cost of LVAD Implantation by Cost of Outpatient Care ICERs (per QALY) Cost Implant $125,000 $200,000 $275,000 $350,000 $425,000 $250 $432,886 $610,531 $788,176 $965,821 $1,143,466 $1,000 $437,868 $615,513 $793,159 $970,804 $1,148,449 $1,750 $442,851 $620,496 $798,141 $975,786 $1,153,431 $2,500 $447,833 $625,478 $803,123 $980,769 $1,158,414 $3,250 $452,815 $630,461 $808,106 $985,751 $1,163,396 Cost Outpt Care Table A14. Sensitivity Analysis – Cost of LVAD Implantation by Probability of Rehospitalization for LVAD ICERs (per QALY) Cost Implant $125,000 $200,000 $275,000 $350,000 $425,000 0.10 $319,413 $497,058 $674,704 $852,349 $1,029,994 0.15 $370,760 $548,405 $726,050 $903,695 $1,081,340 0.20 $422,106 $599,751 $777,396 $955,042 $1,132,687 0.25 $473,453 $651,098 $828,743 $1,006,388 $1,184,033 0.30 $524,799 $702,444 $880,089 $1,057,735 $1,235,380 0.35 $576,146 $753,791 $931,436 $1,109,081 $1,286,726 P Rehosp LVAD Table A15. Sensitivity Analysis – Cost of LVAD Implantation by Probability of Rehospitalization for OMM ICERs (per QALY) Cost Implant $125,000 $200,000 $275,000 $350,000 $425,000 0.05 $507,043 $684,688 $862,334 $1,039,979 $1,217,624 0.10 $474,844 $652,489 $830,134 $1,007,779 $1,185,425 0.15 $442,645 $620,290 $797,935 $975,580 $1,153,225 0.20 $410,445 $588,091 $765,736 $943,381 $1,121,026 0.25 $378,246 $555,891 $733,537 $911,182 $1,088,827 0.30 $346,047 $523,692 $701,337 $878,982 $1,056,628 P Rehosp OMM ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 33 Technology Evaluation Center Table A16. Sensitivity Analysis – Cost of Rehospitalization by Cost of Outpatient Care ICERs (per QALY) Cost Rehosp $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $250 $691,641 $725,517 $759,393 $793,268 $827,144 $861,019 $894,895 $1,000 $696,624 $730,499 $764,375 $798,250 $832,126 $866,002 $899,877 $1,750 $701,606 $735,482 $769,357 $803,233 $837,108 $870,984 $904,859 $2,500 $706,589 $740,464 $774,340 $808,215 $842,091 $875,966 $909,842 $3,250 $711,571 $745,447 $779,322 $813,198 $847,073 $880,949 $914,824 Cost Outpt Care Table A17. Sensitivity Analysis – Cost of Rehospitalization by Probability of Rehospitalization for LVAD ICERs (per QALY) Cost Rehosp $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 0.10 $674,670 $676,267 $677,863 $679,460 $681,056 $682,653 $684,249 0.15 $685,808 $700,854 $715,900 $730,946 $745,992 $761,038 $776,084 0.20 $696,945 $725,441 $753,937 $782,432 $810,928 $839,424 $867,920 0.25 $708,083 $750,028 $791,973 $833,919 $875,864 $917,809 $959,755 0.30 $719,220 $774,615 $830,010 $885,405 $940,800 $996,195 $1,051,590 0.35 $730,358 $799,202 $868,047 $936,891 $1,005,736 $1,074,580 $1,143,425 P Rehosp LVAD Table A18. Sensitivity Analysis – Cost of Rehospitalization by Probability of Rehospitalization for OMM ICERs (per QALY) $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 0.05 $715,369 $766,113 $816,857 $867,601 $918,345 $969,089 $1,019,833 0.10 $708,385 $750,694 $793,004 $835,314 $877,624 $919,933 $962,243 0.15 $701,400 $735,276 $769,151 $803,027 $836,902 $870,778 $904,654 0.20 $694,416 $719,857 $745,299 $770,740 $796,181 $821,623 $847,064 0.25 $687,432 $704,439 $721,446 $738,453 $755,460 $772,467 $789,474 0.30 $680,447 $689,020 $697,593 $706,166 $714,739 $723,312 $731,885 P Rehosp OMM 34 Cost Rehosp ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Cost-Effectiveness of Left-Ventricular Assist Devices as Destination Therapy for End-Stage Heart Failure Table A19. Sensitivity Analysis – Cost of Outpatient Care by Probability of Rehospitalization for LVAD ICERs (per QALY) Cost Outpt Care $250 $1,000 $1,750 $2,500 $3,250 0.10 $664,942 $672,346 $679,749 $687,152 $694,556 0.15 $718,265 $724,659 $731,054 $737,448 $743,843 0.20 $771,587 $776,973 $782,359 $787,745 $793,130 0.25 $824,909 $829,286 $833,663 $838,041 $842,418 0.30 $878,231 $881,600 $884,968 $888,337 $891,705 0.35 $931,553 $933,913 $936,273 $938,633 $940,992 P Rehosp LVAD Table A20. Sensitivity Analysis – Cost of Outpatient Care by Probability of Rehospitalization for OMM ICERs (per QALY) Cost Outpt Care $250 $1,000 $1,750 $2,500 $3,250 0.05 $859,792 $863,510 $867,227 $870,944 $874,661 0.10 $826,354 $830,704 $835,054 $839,403 $843,753 0.15 $792,916 $797,898 $802,881 $807,863 $812,845 0.20 $759,477 $765,092 $770,707 $776,322 $781,937 0.25 $726,039 $732,287 $738,534 $744,782 $751,029 0.30 $692,601 $699,481 $706,361 $713,241 $720,121 P Rehosp OMM Table A21. Sensitivity Analysis – Probability of Rehospitalization for LVAD by Probability of Rehospitalization for OMM ICERs (per QALY) P Rehosp LVAD 0.10 0.15 0.20 0.25 0.30 0.35 0.05 $743,842 $795,188 $846,535 $897,881 $949,227 $1,000,574 0.10 $711,642 $762,989 $814,335 $865,682 $917,028 $968,375 0.15 $679,443 $730,790 $782,136 $833,482 $884,829 $936,175 0.20 $647,244 $698,590 $749,937 $801,283 $852,630 $903,976 0.25 $615,045 $666,391 $717,737 $769,084 $820,430 $871,777 0.30 $582,845 $634,192 $685,538 $736,885 $788,231 $839,578 P Rehosp OMM ©2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 35 Technology Evaluation Center Technology Evaluation Center Blue Cross and Blue Shield Association 225 North Michigan Avenue Chicago, Illinois 60601-7680 888.832.4321 www.bcbs.com ® Registered marks of the Blue Cross and Blue Shield Association, an Association of Independent Blue Cross and Blue Shield Plans ®’ Registered trademark of Kaiser Permanente © 2004 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.