Search

Objectives: In the IMPACT trial (NCT02164513), triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) showed clinical benefit compared with dual therapy with either FF/VI or UMEC/VI in the treatment of chronic obstructive pulmonary disease (COPD). We used data from IMPACT to determine whether this translated into differences in COPD-related healthcare resource utilization (HRU) costs in a United Kingdom (UK) setting., Methods: In a within-trial analysis, individual patient data from the IMPACT intention-to-treat (ITT) population were analyzed to estimate rates of COPD-related HRU with FF/UMEC/VI, FF/VI, or UMEC/VI. A Bayesian approach was applied to address issues typically encountered with this kind of data, namely data missing due to early study withdrawal, subjects with zero reported HRU, and skewness. Rates of HRU were estimated under alternate assumptions of data being missing at random (MAR) or missing not at random (MNAR). UK-specific unit costs were then applied to estimated HRU rates to calculate treatment-specific costs., Results: Under each MNAR scenario, per patient per year (PPPY) rates of COPD-related HRU were lowest amongst those patients who received treatment with FF/UMEC/VI compared with those receiving either FF/VI or UMEC/VI. Although absolute HRU rates and costs were typically higher for all treatment groups under MNAR scenarios versus MAR, final economic conclusions were robust to patient withdrawals., Conclusions: PPPY rates were typically lower with FF/UMEC/VI versus FF/VI or UMEC/VI., Competing Interests: Dr Gabrio has nothing to disclose. Dr Gunsoy reports personal fees from AbbVie (current employee, and owns stock), and GlaxoSmithKline (former employee). Dr Baio has nothing to disclose. Dr A. Martin is an employee of GlaxoSmithKline. At the time of the study, Dr Paly was an employee of ICON. Dr Risebrough reports grants from GlaxoSmithKline. Dr Halpin reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Sanofi. Dr Singh reports personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, personal fees from Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, Sanofi, personal fees from Synairgen, personal fees from Teva, Theravance, and Verona. Dr Wise reports research grants from AstraZeneca, 4D Pharma, Chiesi, Savara, Vaxart, Polarean, Boehringer Ingelheim, GlaxoSmithKline, MedImmune, Pearl, and Sanofi-Aventis; is a consultant for AstraZeneca, Circassia, Galderma, MedImmune, Mylan/Theravance, Pearl, Pneuma, Propeller Health, and Verona; is on an advisory board for GlaxoSmithKline; data monitoring committee for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ChemRx, GlaxoSmithKline, Kamada, Kinevant, MedImmune, Merck, Pearl, Pulmonx, PureTech, and Roche-Genentech; steering committee for Boehringer Ingelheim, and GlaxoSmithKline; and clinical endpoint committee for Contrafect, GlaxoSmithKline, and Kiniksa. Dr Han reports analytic and publication support for this research from GlaxoSmithKline. She also reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Pulmonx, Teva, Verona, Merck, Sanofi, DevPro, Aerogen, Polarian, Regeneron, United Therapeutics, Cipla and Chiesi. She has received stock options from Meissa Vaccines. She has received either in kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association. She has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution. Dr Martinez reports receiving honoraria and travel support from AstraZeneca, Boehringer Ingelheim, Canadian Respiratory Society, CME Outfitters, CSL Behring, Genentech, GlaxoSmithKline, Inova Fairfax, MDMagazine, Miller Communications, National Association for Continuing Education/Integritas, Novartis, NYP Methodist Hospital Brooklyn, Patara/Respivant, Peer View, Rare Diseases Healthcare Communications, Sanofi/Regeneron, Sunovion, Teva, University of Birmingham Alabama, and WebMD/MedScape; honoraria from Dartmouth University, New York University, Pearl, Physicians Education Resource, Rockpointe Communications, Theravance/Viatris, Medtronic, UpToDate, and Vindico; travel support from Chiesi and Zambon; research support from ProTerrix Bio and Zambon; publication support from Boehringer Ingelheim; is on an advisory board for AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Gala, Genentech, GlaxoSmithKline, Pearl, Sanofi/Regeneron, Sunovion, Teva, Zambon, and Verona; steering committee for AstraZeneca, AbbVie, Afferent/Merck, Bayer, Biogen, Boehringer Ingelheim, GlaxoSmithKline, Nitto, Patara/Respivant, ProMedior, Shionogi, United Therapeutics, and Veracyte; data monitoring committee for Biogen, Boehringer Ingelheim, Genentech Asthma, and GlaxoSmithKline; is a consultant for AbbVie, IQVIA, ProTerrix Bio, and Raziel; continuing medical education/study presentations for Boehringer Ingelheim, Canadian Respiratory Society, Dartmouth University, France Foundation, Inova Fairfax, National Association for Continuing Education/Integritas, New York University, Novartis, NYP Methodist Hospital Brooklyn, Peer View, Physicians Education Resource, Rare Diseases Healthcare Communications, Rockpointe Communications, University of Birmingham Alabama, Vindico, and WebMD/MedScape; and teleconference without compensation for Bristol Myers Squibb and twoXAR. Dr Criner reports consulting fees from Amgen, AstraZeneca, Auris Health, Boehringer Ingelheim, Broncus, BTG, Chiesi, CSA Medical, EOLO, Fisher Paykel, Gilead, GlaxoSmithKline, Intuitive Surgical Inc, Lungpacer, Medtronic Vascular, Mereo, NGM, Novartis Pharma AG, Nuvaira, Olympus, Pneumrx, Pulmonx, Regeneron Healthcare Solutions Inc, ResMed, Respironics, Sanofi, and Verona; and ownership interest in HGE Health Care Solutions LLC. At the time of the study, Dr N. Martin was an employee of GlaxoSmithKline. Dr Lipson is an employee of and owns stocks/shares in GlaxoSmithKline. Dr Ismaila is an employee of and owns stocks/shares in GlaxoSmithKline; and is an unpaid part-time Professor at McMaster University, Canada. The authors report no other conflicts of interest in this work., (© 2022 Gabrio et al.)

Background: The IMPACT trial demonstrated superior outcomes following 52 weeks of once-daily single-inhaler treatment with fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) (100/62.5/25 μg) compared with once-daily FF/VI (100/25 μg) or UMEC/VI (62.5/25 μg). This study evaluated the cost-effectiveness of FF/UMEC/VI compared with FF/VI or UMEC/VI for the treatment of chronic obstructive pulmonary disease (COPD) from a UK National Health Service perspective., Methods: Patient characteristics and treatment effects from IMPACT were populated into a hybrid decision tree/Markov economic model. Costs (GB£ inflated to 2018 equivalents) and health outcomes were modelled over a lifetime horizon, with a discount rate of 3.5% per annum applied to both. Sensitivity analyses were performed to test the robustness of key assumptions and input parameters., Results: Compared with FF/VI and UMEC/VI, FF/UMEC/VI provided an additional 0.296 and 0.145 life years (LYs) (discounted) and 0.275 and 0.118 quality-adjusted life years (QALYs), at an additional cost of £1129 and £760, respectively. Incremental cost-effectiveness ratios (ICERs) for FF/UMEC/VI were £4104/QALY and £3809/LY gained versus FF/VI and £6418/QALY and £5225/LY gained versus UMEC/VI. At a willingness-to-pay threshold of £20 000/QALY, the probability that FF/UMEC/VI was cost-effective was 96% versus FF/VI and 74% versus UMEC/VI. Results were similar in a subgroup of patients recommended triple therapy in the 2019 National Institute for Health and Care Excellence COPD guideline., Conclusions: FF/UMEC/VI single-inhaler triple therapy improved health outcomes and was a cost-effective option compared with FF/VI or UMEC/VI for patients with symptomatic COPD and a history of exacerbations in the UK at recognised cost-effectiveness threshold levels., Competing Interests: Conflict of interest: A. Martin, G. Anley, G. Okorogheye, M. Schroeder and A.S. Ismaila are/were employees of, and shareholders in, GlaxoSmithKline. A.S. Ismaila is also an unpaid part-time professor at McMaster University, Canada. D. Shah, K. Ndirangu and N. Risebrough are employees of ICON Plc. ICON Plc. received funding from GlaxoSmithKline to conduct this study but were not paid for development of this manuscript., (Copyright ©The authors 2022.)

UK management costs for COPD, estimated at £1.9 billion/year, are rising. In the FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) study, single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (100/62.5/25 µg) improved clinical outcomes versus budesonide/formoterol (400/12 µg) in patients with symptomatic COPD at risk of exacerbations. We assessed the cost-effectiveness of fluticasone furoate/umeclidinium/vilanterol versus budesonide/formoterol for treating COPD from a UK National Health Service perspective. A model was developed combining a trial-based and Markov component and populated with baseline and treatment effect data from FULFIL, together with UK healthcare resource costs and disease-related utilities. Costs per life year and per quality-adjusted life year gained (costing year 2017) for fluticasone furoate/umeclidinium/vilanterol versus budesonide/formoterol were calculated for a lifetime horizon. Results were explored using deterministic sensitivity, scenario and probabilistic analyses. Fluticasone furoate/umeclidinium/vilanterol was associated with gains in life years (0.533) and quality-adjusted life years (0.506) versus budesonide/formoterol, but at slightly increased total costs (£26 416 versus £25 860). This translated to incremental cost-effectiveness ratios of £1042/life year and £1098/quality-adjusted life year for fluticasone furoate/umeclidinium/vilanterol versus budesonide/formoterol. In scenario analyses, incremental cost-effectiveness ratios ranged from dominant to £1547/quality-adjusted life year gained. Fluticasone furoate/umeclidinium/vilanterol provides a cost-effective treatment option versus budesonide/formoterol for patients with symptomatic COPD in the UK., Competing Interests: Conflict of interest: E. Fenwick reports GSK provided funds to ICON plc to build the model and conduct the analysis in the present study. Conflict of interest: A. Martin is an employee of GlaxoSmithKline. Conflict of interest: M. Schroeder was an employee and shareholder of GlaxoSmithKline plc at the time of the study. Conflict of interest: S.J. Mealing reports grants from GlaxoSmithKline plc during the conduct of the study and outside the submitted work, all of which were paid to ICON Health Economics. Conflict of interest: O. Solanke reports personal fees from GlaxoSmithKline plc during the conduct of the study. Conflict of interest: N. Risebrough has nothing to disclose. Conflict of interest: A.S. Ismaila reports the study was funded GlaxoSmithKline, of which A.S. Ismaila is an employee and shareholder. A.S. Ismaila is also an unpaid, part-time professor at McMaster University., (Copyright ©ERS 2021.)

We conducted an analysis of indirect costs alongside the LY.12 randomized trial in patients with relapsed or refractory (R/R) aggressive non-Hodgkin lymphoma (NHL). Lost productivity data for Canadian patients and caregivers in the trial were collected at baseline and with each chemotherapy cycle pre-transplant, using an adapted Lost Productivity questionnaire. Mean per patient indirect costs were CAD 2999 for patients in the GDP arm and CAD 3400 in the DHAP arm. A substantial majority was not working or had to reduce their workload during this treatment time. Salvage chemotherapy for R/R aggressive NHL is associated with significant indirect costs to patients and their caregivers.

Background: We assessed the cost-effectiveness of single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI from a Canadian public healthcare perspective, incorporating data from the IMPACT trial in chronic obstructive pulmonary disease (COPD) (NCT02164513)., Methods: Baseline inputs and treatment effects from IMPACT were populated into the validated GALAXY-COPD disease progression model. Canadian unit costs and drug costs (Canadian dollars [C$], 2017) were applied to healthcare resource utilization and treatments. Future costs and health outcomes were discounted at 1.5% annually. Analyses were probabilistic, and outputs included exacerbation rates, costs, and life years (LYs) and quality-adjusted life years (QALYs) gained., Results: Compared with FF/VI and UMEC/VI over a lifetime horizon, the analyses predicted that treatment with FF/UMEC/VI resulted in fewer moderate and severe exacerbations, more LYs and more QALYs gained, with a small incremental cost. The base-case incremental cost-effectiveness ratio (ICER) per QALY gained was C$18,989 (95% confidence interval [CI]: C$14,665, C$25,753) versus FF/VI and C$13,776 (95% CI: C$9787, C$19,448) versus UMEC/VI. FF/UMEC/VI remained cost-effective versus both FF/VI and UMEC/VI in all sensitivity analyses, including in scenario analyses that considered different intervention and comparator discontinuation rates, and treatment effects for subsequent therapy., Conclusion: Treatment with FF/UMEC/VI was predicted to improve outcomes and be a cost-effective treatment option for patients with symptomatic COPD and a history of exacerbations compared with FF/VI or UMEC/VI, in Canada., Competing Interests: The authors declare the following conflicts of interest during the last three years in relation to this article: A.S. Ismaila, M. Schroeder and A. Martin are employees of, and hold shares in, GlaxoSmithKline plc.; A.S. Ismaila is also an unpaid, part-time professor at McMaster University, Canada. E.C. Goodall is an employee of GlaxoSmithKline plc. N. Risebrough, D. Shah and K. Ndirangu are employees of ICON plc., which received funding from GlaxoSmithKline plc. to conduct this study, but were not themselves paid for development of this article. G. Criner reports grants and personal fees from GlaxoSmithKline plc., Boehringer Ingelheim, Chiesi, Mereo, AstraZeneca, Pulmonx, PneumRx, Olympus, Broncus, Lungpacer, Mereo, Nuvaira, ResMed, Respironics and Patara, Pearl, and Sanofi, personal fees from Verona, BTG, EOLO and NGM, and grants from ALung, Fisher Paykel and Galapagos, outside the submitted work. M. Dransfield reports personal and other fees from GlaxoSmithKline plc. during the conduct of this study, and grants from Department of Defense, personal and other fees from Boehringer Ingelheim, GlaxoSmithKline plc., AstraZeneca and PneumRx/BTG, personal fees from Genentech, Quark Pharmaceuticals and Mereo, grants from NIH and American Lung Association and other fees from Novartis, Yungjin, Pulmonx and Boston Scientific, outside the submitted work. D.M.G. Halpin reports personal fees from AstraZeneca, Chiesi, GlaxoSmithKline plc. and Pfizer, and personal fees and non-financial support from Boehringer Ingelheim and Novartis, outside the submitted work. M.L. Han reports personal fees from GlaxoSmithKline plc. during the conduct of this study, and personal fees from GlaxoSmithKline plc., Boehringer Ingelheim, AstraZeneca, Mylan, and other fees from Novartis and Sunovion, outside of the submitted work. D.A. Lomas reports grants, personal fees and non-financial support from GlaxoSmithKline plc. during the conduct of the study, and personal fees and grants from GlaxoSmithKline plc., and personal fees from Griffols, outside of the submitted work. D.A. Lomas also chaired the Respiratory Therapy Area Board at GlaxoSmithKline plc. between 2012 and 2015. The authors report no other conflicts of interest in this work., (© 2019 Ismaila et al.)

Purpose: Clinically important deterioration (CID) in chronic obstructive pulmonary disease (COPD) is a novel composite endpoint that assesses disease stability. The association between short-term CID and future economic and quality of life (QoL) outcomes has not been previously assessed. This analysis considers 3-year data from the TOwards a Revolution in COPD Health (TORCH) study, to examine this question. Patients and methods: This post hoc analysis of TORCH (NCT00268216) compared costs and utilities at 3 years among patients without CID (CID-) and with CID (CID+) at 24 weeks. A positive CID status was defined as either: a deterioration in forced expiratory volume in 1 second (FEV 1 ) of ≥100 mL from baseline; or a ≥4-unit increase from baseline in St George's Respiratory Questionnaire (SGRQ) total score; or the incidence of a moderate/severe exacerbation. Patients from all treatment arms were included. Utility change was based on the EQ-5D utility index. Costs were based on healthcare resource utilization from 24 weeks to end of follow-up combined with unit costs for the UK (2016 GBP), and reported as per patient per year (PPPY). Adjusted estimates were generated controlling for baseline characteristics, treatment assignment, and number of CID criteria met. Results: Overall, 3,769 patients completed the study and were included in the analysis (stable CID- patients, n=1,832; unstable CID+ patients, n=1,937). At the end of follow-up, CID- patients had higher mean (95% confidence interval [CI]) utility scores than CID+ patients (0.752 [0.738, 0.765] vs 0.697 [0.685, 0.71]; difference +0.054; P <0.001), and lower costs PPPY (£538 vs £916; difference: £378 [95% CI: £244, £521]; P <0.001). The cost differential was primarily driven by the difference in general hospital ward days ( P =0.003). Conclusion: This study demonstrated that achieving early stability in COPD by preventing short-term CID is associated with better preservation of future QoL alongside reduced healthcare service costs., Competing Interests: IN, NBG, and ASI are employees of GSK, and hold stock/shares in GSK. ASI is also an unpaid professor at McMaster University in Canada. MTD was employed by GSK at the time of this study. VFP and NR are employees of ICON Health Economics, who were contracted by GSK to conduct the study analysis. AB received consultancy fees from GSK and ICON Health Economics in relation to this study. AB and ICON employees were not paid for manuscript development. The authors report no other conflicts of interest in this work.

Introduction: The cost-effectiveness of long-acting muscarinic antagonist (LAMA) umeclidinium bromide (UMEC) 62.5 μg as add-on therapy to other maintenance COPD treatments is unknown., Methods: This analysis assessed the cost-effectiveness of the following in COPD: UMEC + fluticasone furoate/vilanterol 100/25 μg (FF/VI); UMEC + fluticasone propionate/salmeterol 250/50 μg (FP/SAL); and UMEC + several alternative choices of inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA). The model was informed with direct and indirect data from previously published studies, with a UK perspective and a lifetime horizon. Sensitivity analyses were also performed., Results: For the lifetime horizon, compared with FF/VI, FP/SAL and ICS/LABAs, addition of UMEC was associated with incremental costs per quality-adjusted life-years (QALY) of £4050, £7210 and £5780, respectively, and incremental costs per life year gain of £3380, £6020 and £4940. All UMEC-containing regimens resulted in numerically lower exacerbation rates versus comparator regimens over a lifetime horizon., Conclusions: Addition of UMEC to various ICS/LABA treatments was associated with higher cost than ICS/LABA alone, but was cost-effective in most scenarios., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Cost-effectiveness of once-daily umeclidinium bromide (UMEC) was compared with once-daily tiotropium (TIO) and once-daily glycopyrronium (GLY) in patients with chronic obstructive pulmonary disease (COPD) from a UK National Health Service (NHS) perspective., Methods: A linked-equation model was implemented to estimate COPD progression, associated healthcare costs, exacerbations rates, life years (LY) and quality-adjusted LY (QALYs). Statistical risk equations for endpoints and resource use were derived from the ECLIPSE and TORCH studies, respectively. Treatment effects [mean (standard error)] at 12 weeks on forced expiratory volume in 1 s and St George's Respiratory Questionnaire score were obtained from the intention-to-treat populations of two head-to-head studies [GSK study identifiers 201316 (NCT02207829) and 201315 (NCT02236611)] which compared UMEC 62.5 mcg with TIO 18 mcg and UMEC 62.5 mcg with GLY 50 mcg, respectively. Treatment costs reflect UK list prices (2016) and NHS unit costs; UMEC and GLY prices being equal and less than TIO. A lifetime horizon, discounted costs and effects at 3.5% were used. Sensitivity analyses were performed to evaluate the robustness of variations in input parameters and assumptions in the model., Results: Over a lifetime horizon, UMEC was predicted to increase LYs (+ 0.195; 95% confidence interval [CI]: 0.069, 0.356) and QALYs (+ 0.118; 95% CI: 0.055, 0.191) and reduce the number of annual exacerbations (- 0.053; 95% CI: - 0.171, 0.028) compared with TIO, with incremental cost savings of £460/patient (95% CI: - £645, - £240). Compared with GLY, UMEC increased LYs (+ 0.124; 95% CI: 0.015, 0.281) and QALYs (+ 0.101; 95% CI: 0.043, 0.179) and reduced annual exacerbation (- 0.033; 95% CI: - 0.135, 0.017) at an additional cost of £132/patient (95% CI: £12, £330), resulting in an incremental cost-effectiveness ratio of £1310/QALY (95% CI: £284, £2060). Similar results were observed in alternative time horizons and additional sensitivity analyses., Conclusions: For treatment of patients with COPD in the UK over a lifetime horizon, treatment with UMEC dominates treatment with TIO, providing both improved health outcomes and cost savings. In comparison with GLY, treatment with UMEC achieved improved health outcomes but was associated with a higher cost. Trial registration 201316, NCT02207829; 201315, NCT02236611.

Objectives: To validate outcomes of presently available chronic obstructive pulmonary disease (COPD) cost-effectiveness models against results of two large COPD trials-the 3-year TOwards a Revolution in COPD Health (TORCH) trial and the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial., Methods: Participating COPD modeling groups simulated the outcomes for the placebo-treated groups of the TORCH and UPLIFT trials using baseline characteristics of the trial populations as input. Groups then simulated treatment effectiveness by using relative reductions in annual decline in lung function and exacerbation frequency observed in the most intensively treated group compared with placebo as input for the models. Main outcomes were (change in) total/severe exacerbations and mortality. Furthermore, the absolute differences in total exacerbations and quality-adjusted life-years (QALYs) were used to approximate the cost per exacerbation avoided and the cost per QALY gained., Result: Of the six participating models, three models reported higher total exacerbation rates than observed in the TORCH trial (1.13/patient-year) (models: 1.22-1.48). Four models reported higher rates than observed in the UPLIFT trial (0.85/patient-year) (models: 1.13-1.52). Two models reported higher mortality rates than in the TORCH trial (15.2%) (models: 20.0% and 30.6%) and the UPLIFT trial (16.3%) (models: 24.8% and 36.0%), whereas one model reported lower rates (9.8% and 12.1%, respectively). Simulation of treatment effectiveness showed that the absolute reduction in total exacerbations, the gain in QALYs, and the cost-effectiveness ratios did not differ from the trials, except for one model., Conclusions: Although most of the participating COPD cost-effectiveness models reported higher total exacerbation rates than observed in the trials, estimates of the absolute treatment effect and cost-effectiveness ratios do not seem different from the trials in most models., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: To assess how suitable current chronic obstructive pulmonary disease (COPD) cost-effectiveness models are to evaluate personalized treatment options for COPD by exploring the type of heterogeneity included in current models and by validating outcomes for subgroups of patients., Methods: A consortium of COPD modeling groups completed three tasks. First, they reported all patient characteristics included in the model and provided the level of detail in which the input parameters were specified. Second, groups simulated disease progression, mortality, quality-adjusted life-years (QALYs), and costs for hypothetical subgroups of patients that differed in terms of sex, age, smoking status, and lung function (forced expiratory volume in 1 second [FEV 1 ] % predicted). Finally, model outcomes for exacerbations and mortality for subgroups of patients were validated against published subgroup results of two large COPD trials., Results: Nine COPD modeling groups participated. Most models included sex (seven), age (nine), smoking status (six), and FEV 1 % predicted (nine), mainly to specify disease progression and mortality. Trial results showed higher exacerbation rates for women (found in one model), higher mortality rates for men (two models), lower mortality for younger patients (four models), and higher exacerbation and mortality rates in patients with severe COPD (four models)., Conclusions: Most currently available COPD cost-effectiveness models are able to evaluate the cost-effectiveness of personalized treatment on the basis of sex, age, smoking, and FEV 1 % predicted. Treatment in COPD is, however, more likely to be personalized on the basis of clinical parameters. Two models include several clinical patient characteristics and are therefore most suitable to evaluate personalized treatment, although some important clinical parameters are still missing., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data., Methods: The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided., Results: The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations., Conclusions: GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the cost-utility of the treatment with a long acting beta-agonist (LABA) and inhaled corticosteroid (ICS) combination inhaler [salmeterol xinafoate (SAL)/fluticasone propionate (FP) combination inhaler (SFC) (Advair(®))] to continuing on current ICS dose (no ICS dose change) or increased ICS dose [fluticasone propionate (FP)] in patients with uncontrolled asthma in Canada., Methods: A cost-utility analysis was conducted from a Canadian public healthcare perspective with a one year time horizon. In the no FP dose change scenarios, remaining on daily low (FP 100 ug BID) or medium (FP 200-250 ug BID) or high dose (FP 500 ug BID) was considered. In the increased FP dose scenarios, doubling the FP dose from low to medium dose and from medium to high dose regimens were considered. A decision model was developed with two health states: "symptom free" or "with symptoms". Clinical efficacy was based on a meta-analysis of relevant randomized controlled trials. Over the one year time horizon the percentage with symptom free days (SFD) was used as the measure of differential treatment scenario effectiveness. Drug costs and non-drug costs were incorporated into the analysis. Utilities, derived from EQ5D scores and health services resource use based on patient diaries for 'symptom free' and 'with symptoms' were based on regression analyses of individual patient data from the Gaining Optimal Asthma controL (GOAL) trial. Costs were assessed by assigning unit cost for each health services resource use for each patient. The incremental cost-utility ratios (ICUR) for SFC vs no FP dose change or increased FP dose were estimated using descriptive statistics. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis (PSA)., Results: Over one year, SFC resulted in an incremental cost per patient of $544-$655 compared to no FP dose change and $47-$380 per year compared to increased FP dose. SFC results in incremental QALYs per patient of 0.0100-0.0149 compared to no FP dose change and 0.0136-0.0152 compared to increased FP dose. The one year ICURs were $43,000 to $54,400 per QALY gained for SFC compared to no FP dose change and $25,000 to $3500 per QALY gained compared to increased FP dose scenarios. The probability of SFC being cost-effective at $50,000 per QALY gained was greater than 75% compared to increased FP dose scenarios and compared to no dose change for patients on low or medium dose FP. The results were robust to changes in assumptions within the model., Conclusion: In Canadian patients with inadequately controlled asthma on FP, it is cost-effective to use SFC for patients 12 years and over compared to doubling their FP dose. It is also cost-effective to use SFC for patients on low or medium dose FP compared to remaining on the current FP dose in patients with uncontrolled asthma., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Our goal was to determine the economic value of azacitidine in Canada compared with conventional care regimens (ccrs), including best supportive care (bsc) and low- or standard-dose chemotherapy plus bsc in the treatment of higher-risk myelodysplastic syndromes (mdss) and acute myeloid leukemia (aml) with 20%-30% blasts., Methods: The cost-utility model is a lifetime probabilistic Markov model with a 35-day cycle length consisting of 3 health states: mds; transformation to aml with more than 30% blasts; and death. A third-party public payer perspective was adopted. Overall survival was extrapolated beyond the time horizon of the aza-001 trial comparing azacitidine with ccr. Resource use was determined through a questionnaire completed by Canadian hematologists. Utility values were obtained from two studies in which EQ-5D health questionnaire values were mapped from the European Organization for Research and Treatment of Cancer qlq-C30 survey, and SF-6D scores were mapped from the Short Form 12, elicited from 191 and 43 patients in two different trials., Results: In the base case, azacitidine had an incremental cost-effectiveness ratio (icer) of $86,182 (95% confidence limits: $69,920, $107,157) per quality-adjusted life year (qaly) gained relative to ccr. Comparing azacitidine with bsc, low-dose chemotherapy plus bsc, and standard-dose chemotherapy plus bsc, the icers were, respectively, $86,973, $84,829, and $2,152 per qaly gained. Results were most sensitive to the utility for azacitidine after 6 months of treatment and to overall survival., Conclusions: The prolonged 9-month median overall survival with azacitidine relative to ccr fills a gap w hen treating patients with higher-risk mds and aml with 20%-30% blasts. The economic value of azacitidine is within the threshold of willingness-to-pay for third-party public payers for oncology treatments in Canada.

Objective: To assess the cost-utility of celecoxib in three treatment strategies for arthritis in Quebec, considering both upper gastrointestinal (GI) and cardiovascular (CV) events., Methods: A Markov analytic framework was used to model patients with osteoarthritis and rheumatoid arthritis at low/average and high risk of GI and CV toxicity over 5 years with monthly cycles. Treatment strategies were modelled in line with Canadian clinical practice. In first-line treatment, patients started on celecoxib; second-line, patients started on a non-selective non-steroidal anti-inflammatory drug (NSAID) and switched to celecoxib after a first GI event; third-line, patients started on a non-selective NSAID, added a proton pump inhibitor (PPI) after a first GI event, and switched to celecoxib after a second GI event (while maintaining the PPI). Model inputs were determined through comprehensive literature searches (MEDLINE and EMBASE) from 1995 to 2006. Included studies evaluated GI (dyspepsia, uncomplicated and complicated ulcers, death) and CV (myocardial infarction, stroke, death) events. Drug and procedure costs were derived from Canadian published sources (Can$2005)., Results: Total costs per patient for celecoxib first-, second-, and third-line treatment were Can$4,790, $3,390, and $3,466, and total quality-adjusted life-years (QALY) were 3.251, 3.231, and 3.230, respectively. In all risk categories, celecoxib second-line was less costly and as effective as celecoxib third-line, producing savings to the healthcare system. Although celecoxib first-line generated incremental expenditures versus celecoxib second-line, it was also more effective. The resulting cost-utility ratio for the high-risk population was Can$54,696/QALY. Based on this analytical approach, a treatment strategy where celecoxib is used before the combination of a non-selective NSAID plus a PPI possesses cost advantages for the Quebec provincial drug programme. One-way sensitivity analysis (varying GI and CV event rates, utilities, and cost) generally showed second-line treatment with celecoxib as the dominant strategy compared with third-line treatment with celecoxib., Conclusion: Although effectiveness of second- and third-line celecoxib use is similar, total cost is lower for second-line. These results suggest that the use of celecoxib before the combination of a non-selective NSAID plus a PPI is relatively cost-effective in the treatment of arthritis pain and support the full benefit listing of celecoxib in Quebec's drug programme.

Primary prophylaxis is the emerging standard treatment for boys with severe haemophilia. Tailored (escalating-dose) prophylaxis (EscDose), beginning at a low frequency and escalating with repeated bleeding may prevent arthropathy at a lower cost than standard prophylaxis (SP). From a societal perspective, we compared the incremental cost per joint-haemorrhage that is avoided and quality-adjusted-life-year (QALY) gained of SP and EscDose to on-demand (Demand) therapy in severe haemophilia A boys treated to age 6 using a decision analytic model. Costs included factor VIII (FVIII), professional visits and tests, central venous placement/complications, hospitalization, home programmes and parents' lost work-days. Resource utilization was estimated by surveying 17 Canadian clinics. The natural history of bleeding and other probabilities were determined from a longitudinal chart review (n = 24) and published literature. EscDose costs an additional $3192 per joint-haemorrhage that was avoided compared with Demand whereas SP costs an additional $9046 per joint-haemorrhage that was avoided compared with EscDose. Clinic costs and lost wages were reduced by 60-80% for EscDose and SP compared with Demand. EscDose attained more QALYs than SP and Demand on account of less bleeding than Demand and lower need for ports than SP. The incremental cost per QALY for EscDose vs. Demand was $542 938. EscDose was less expensive with similar QALYs compared to SP. Sensitivity analysis was performed on all probability- and cost-estimates, and showed the model was sensitive to the cost of FVIII and the SP and target joint utilities. In conclusion, prophylaxis will substantially improve clinical outcomes and quality of life compared to Demand treatment, but with substantial cost.

Objective: To determine whether there is a clinically relevant difference in the health state utilities of obese and non-obese individuals as measured by the Health Utility Index Mark III., Methods: Secondary analysis of the population-based, cross-sectional, interviewer-administered National Population Health Survey (NPHS), 1996-1997. A probability sample of house-dwelling Canadians, excluding populations on First Nations Reserves, Canadian Armed Forces Bases, the Yukon and Northwest Territories, and long-term residents of hospitals or residential care facilities. The sub-sample used in this analysis consisted of 38 151 respondents (52.4% male) between the ages of 20 and 64 y, excluding pregnant women. Health Utilities Index-Mark III (HUI3) scores were used to define normal weight (body mass index (BMI) 19-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), obese (BMI 30-34.9 kg/m(2)), and morbidly obese (BMI> or =35 kg/m(2)) individuals. HUI3 scores were age- and gender-standardized., Results: The overall prevalence of obesity (BMI> or =30 kg/m(2)) in this Canadian population was 13.3%. The average difference in HUI3 scores between normal weight and morbidly obese respondents was 0.04 (P<0.001). Statistically significant (P<0.05) differences across BMI categories were found in each of the eight component attributes of the HUI3. The attributes with the most substantial difference between normal and obese patients were cognition, mobility and pain. All demonstrated a > or =2-fold increase in the proportion of individuals in poorer classifications of health when normal weight respondents were compared with the morbidly obese. The magnitude of the decrement in utility ratings associated with obesity was comparable with other chronic non-cardiovascular conditions such as migraine or colitis., Conclusion: The results indicate that changes in self-rated health status appear to be due to significant changes across several relevant domain attributes. Obesity has a significant impact on both quality of life and health.

Objective: The objective of this study was to determine utility scores for various chronic conditions., Design and Setting: This study is a descriptive analysis. Health Utilities Index (HUI) scores for 20 chronic conditions were examined from the National Population Health Survey (NPHS) from 1994 to 1995., Patients and Participants: 17,626 individuals were surveyed (54.3% women). Chronic conditions included: acne (requiring medication), Alzheimer's disease, arthritis/rheumatism, asthma, back problems excluding arthritis, chronic bronchitis or emphysema, cancer, cataracts, diabetes, epilepsy, food allergies, glaucoma, heart disease, high blood pressure, migraine headaches, other allergies, sinusitis, stroke, stomach/intestinal ulcers and urinary incontinence., Interventions: Health Utilities Index-Mark III (HUI-Mark III) scores for patients with and without a NPHS-defined chronic condition were collected. Utility scores were examined according to age, gender and comorbidity., Main Outcome Measures and Results: 42.6% of individuals reported having no NPHS-defined chronic condition. The most commonly reported health conditions were allergies other than food (17.6%) and rheumatism/arthritis (16.5%). The mean HUI-Mark III scores for patients without a health state was 0.933 +/- 0.079. Individuals with Alzheimer's disease (0.580 +/- 0.263), stroke (0.676 +/- 0.230) and urinary incontinence (0.698 +/- 0.230) had the lowest overall HUI-Mark III scores. Utility scores decreased as age and as the number of comorbid conditions increased., Conclusions: This study provides health economists, researchers and policy-makers with a reference for health utilities of various chronic conditions, different age groups, gender and comorbidities.