Cost-effectiveness of umeclidinium compared with tiotropium and glycopyrronium as monotherapy for chronic obstructive pulmonary disease: a UK perspective.

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

Cost-effectiveness analysis of a single-inhaler triple therapy for patients with advanced chronic obstructive pulmonary disease (COPD) using the FULFIL trial: A UK perspective

Objectives: The clinical benefit of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily budesonide/formoterol (BUD/FOR) for patients with symptomatic chronic obstructive pulmonary disease (COPD) was demonstrated in a clinical trial setting (FULFIL [NCT02345161]). The lifetime cost-effectiveness analysis of FF/UMEC/VI versus BUD/FOR, based on FULFIL data, is reported here. Methods: A previously developed and validated GALAXY-COPD linked-risk equation model was used to assess the cost-effectiveness of FF/UMEC/VI from the UK National Health Service (NHS) perspective. Baseline characteristics and efficacy results from FULFIL and UK NHS reference cost data (2017) were included as inputs. Exacerbation rates (undiscounted), costs, life years (LYs; undiscounted) and quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were calculated over a lifetime horizon. Costs and QALYs were discounted at 3.5% per year, beyond one year, in accordance with National Institute for Health and Care Excellence (NICE) guidelines. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results. Results: Predicted cumulative exacerbations per patient over a lifetime were 8.393 with FF/UMEC/VI and 10.456 with BUD/FOR. Patients receiving FF/UMEC/VI gained an additional 0.764 LYs and 0.492 QALYs, at an additional mean cost of £1,652, resulting in an ICER of £3,357 per QALY gained (95% confidence interval: £1,816, £5,194) compared with BUD/FOR. The ICER remained below £6,000 in all but one of the scenario and sensitivity analyses. Conclusions: Compared with BUD/FOR, treatment with FF/UMEC/VI was predicted to improve health outcomes at an additional cost that suggests it would be cost-effective for patients with COPD in the UK

Long-term cost and utility consequences of short-term clinically important deterioration in patients with chronic obstructive pulmonary disease: results from the TORCH study.

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 (FEV1) 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

Health Utility Attributes for Chronic Conditions

Objective: To determine the importance of specific health utility attributes that comprise overall utility scores for a number of chronic health state conditions. Study design: Cross-sectional study using data from a prospective national survey of the health of community-dwelling Canadians. Study population: 47 534 individuals who answered both health questions and utility questions (51.8% male). Methods: The attributes making up the Health Utilities Index (HUI-Mark III) scores (i.e. vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain) for 21 chronic conditions were examined from the National Population Health Survey (NPHS) 1996 to 1997. Conditions included Alzheimer's disease, arthritis/rheumatism, asthma, back problems excluding arthritis, bowel disorder, chronic bronchitis or emphysema, cancer, cataracts, diabetes, epilepsy, food allergies, glaucoma, heart disease, hypertension, migraine headaches, other allergies, sinusitis, stroke, stomach/intestinal ulcers, thyroid conditions and urinary incontinence. HUI-Mark III scores for patients without an NPHS-defined chronic condition were also collected. All conditions were mutually exclusive. Results: The mean HUI-Mark III score for patients without a chronic health state was 0.953 +- 0.060. Individuals with Alzheimer's disease (0.846 +- 0.168), stroke (0.869 +- 0.163) and arthritis/rheumatism (0.883 +- 0.132) had the lowest overall HUI-Mark III scores. Individuals with Alzheimer's disease (28.6%), epilepsy (23.1%) and urinary incontinence (19.8%) reported higher scores on the emotional impairment attribute. Individuals with arthritis/rheumatism (24.7%) and back problems (20.6%) had high levels of pain/discomfort. Patients with stroke (16.4%) had low mobility scores. Conclusion: By determining which attributes are important to chronic health conditions, this study provides health economists, researchers and policy makers with a reference of health state attributes for various chronic conditions.Healthcare expenditure, Pharmacoeconomics, Quality of life

Utility Scores for Chronic Conditions in a Community-Dwelling Population

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.Pharmacoeconomics, Quality-of-life

Clinical and Economic Implications of Non-Adherence to HAART in HIV Infection

Highly active antiretroviral therapy (HAART) has dramatically altered the natural history of HIV disease. Studies demonstrate that >=95% adherence is necessary to garner the full benefits of HAART. However, appropriate adherence to treatment is difficult and challenging. This paper provides an overview of potential clinical and economic outcomes associated with poor adherence to HAART. Since there are no studies exploring the costs associated with poor adherence to HAART, we discuss potential direct and indirect costs accrued with more frequent treatment failures, selection of resistant strains, increased hospitalizations and a faster progression to AIDS associated with poor adherence to HAART. Additionally, we review studies of interventions and strategies to improve adherence to HAART. Although, single-focus interventions have enhanced the chances of achieving viral suppression by 10 to 23%, the literature has demonstrated that for long-term treatments, programs employing diverse interventions that continue over time are more effective. Under constrained healthcare budgets, government, healthcare managers and policy makers require accurate and timely information concerning the cost effectiveness of adherence intervention programs. We discuss considerations in determining the cost effectiveness of an adherence intervention program.Antiretrovirals, Cost analysis, HIV infections, Patient compliance, Pharmacoeconomics

COST-effectiveness of salmeterol/fluticasone propionate combination (Advair®) in uncontrolled asthma in Canada

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

Prediction models for exacerbations in different COPD patient populations:Results of five large databases

Background: Exacerbations are important outcomes in COPD both from a clinical and economic perspective. This study aimed to estimate prediction models for exacerbations to compare predictors between populations that differ in COPD severity. Methods: Members of an existing COPD health economic modelling network who had access to a large database (> 500 patients) with longitudinal data on exacerbations were asked to use two-third of the dataset to estimate several prediction models for total and severe exacerbations. The models differed in terms of predictors (depending on availability) and type of model. One-third of the dataset was used for validation. Results: Five COPD databases participated: two population-based studies (COPDGene and OLIN studies), one study in primary care patients (RECODE) and two clinical trials (ECLIPSE and UPLIFT). FEV1% predicted and previous exacerbations were significant predictors for total exacerbations in all five databases. Disease-specific quality of life and gender were predictors in 4 out of 4 and 3 out of 5 databases, respectively. Age was significant only in the two trials including severe COPD patients. Other significant predictors available in one database were cough, wheeze, pack-years and 6 MWD. Predictors for severe exacerbations were about the same, but in addition presence of cardiovascular disease and emphysema were found to be predictors in severe patients. Conclusion: FEV1% predicted, previous exacerbations and disease-specific quality of life were identified as predictors of exacerbations in COPD patients regardless of COPD severity, while age, cardiovascular disease and emphysema seemed to be predictors in severe patients only