An Epidemiology Model for Estimating the Numbers of US Patients With Multiple Myeloma by Line of Therapy and Treatment Exposure.

OBJECTIVES: Estimates on the distribution of patients with multiple myeloma (MM) by line of therapy (LOT) are scarce and get outdated quickly as new treatments become available. The objective of this study was to estimate the number of patients with MM by LOT and the number of patients who have received at least 4 previous LOTs including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies (mAbs). METHODS: A compartmental model was developed to calculate the number of patients by LOT. Two pathways were considered based on stem cell transplant eligibility, and at each pathway, treatments were stratified in 2 types: anti-CD38 mAbs or other. The model population was stratified into 4 subgroups based on age and cytogenetic risk. Model inputs were informed from real-world evidence. RESULTS: The model estimated that, in 2020, 126 869 patients were living with MM in the United States. Of these, 105 701 received treatment in any LOT, with 56 959, 27 252, 11 258, and 5217 in lines 1 to 4, respectively, and 5015 in line 5 or beyond. The model estimated that 3497 patients received at least 4 previous LOTs including proteasome inhibitors, immunomodulatory agents, and anti-CD38 mAbs. The model overall prevalence predictions aligned well with publicly available estimates. CONCLUSIONS: This study proposes a novel framework to estimate MM prevalence. It can assist clinicians to understand future trends in MM epidemiology, healthcare systems to plan for future resource use allocation, and payers to quantify the budget impact of new treatments.

Feasibility Study of a Network Meta-Analysis and Unanchored Population-Adjusted Indirect Treatment Comparison of Niraparib, Olaparib, and Bevacizumab as Maintenance Therapies in Patients with Newly Diagnosed Advanced Ovarian Cancer.

Selecting a first-line (1L) maintenance option for ovarian cancer is challenging given the variety of therapies, differing trials, and the lack of head-to-head data for angiogenesis and poly(ADP-ribose) polymerase (PARP) inhibitors. Thus, indirect treatment comparisons (ITCs) can aid treatment decision making. This study assessed the feasibility of two ITCs, a network meta-analysis (NMA) and a population-adjusted ITC (PAIC), comparing the efficacy of the PARP inhibitor niraparib in the PRIMA trial (NCT02655016) with other 1L maintenance treatments. A systematic literature review was conducted to identify trials using the Cochrane Handbook for Systematic Reviews of Interventions to assess differences in trial design, population characteristics, treatment arms, and outcome measures. All 12 trials identified were excluded from the NMA due to the absence of a common comparator and differences in survival measures and/or inclusion criteria. The PAIC comparing PRIMA and PAOLA-1 trials was also not feasible due to differences in inclusion criteria, survival measures, and the previous receipt of chemotherapy/bevacizumab. Neither ITC met recommended guidelines for analysis; the results of such comparisons would not be considered appropriate evidence when selecting 1L maintenance options in ovarian cancer. ITCs in this setting should be performed cautiously, as many factors can preclude objective trial comparisons.

Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States.

PURPOSE: Estimate the budget impact of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. METHODS: A budget impact analysis (BIA) was developed to estimate the cost difference between current (no belamaf) and projected (with belamaf) market scenarios over 3 years. Comparators were identified from a systematic literature review and included selinexor + dexamethasone or best supportive care. The number of treatment-eligible patients were estimated using an epidemiology model. Base-case analyses were conducted from a US commercial payer perspective (cost year: 2019). Model inputs included market share estimates, treatment duration, and costs of drug acquisition/administration, concomitant medications, adverse event (AE) management, treatment monitoring, and subsequent treatments based on published literature/cost databases. Budget impact, calculated as the difference in costs between current and projected scenarios over 3 years, was reported as cost per member per month (PMPM) and per member per year (PMPY). One-way sensitivity analysis assessed which key parameters most affected model outcomes. Alternative scenarios were tested (1- or 5-year time horizon; Medicare perspective; negligible cost of mental status change AE). RESULTS: In a hypothetical commercial payer health plan with 1 million members, 33 patients were identified as treatment-eligible over 3 years. Introducing belamaf for patients with RRMM resulted in an estimated budget-neutral PMPM cost of -$0.0003 and PMPY of -$0.004, based on n=9/33 patients receiving treatment. Sensitivity analyses showed that budget impact in the base case was most sensitive to changes in treatment duration and drug acquisition costs. Base-case results were consistent across all scenarios assessed. CONCLUSION: BIA indicates that adoption of belamaf in this patient population would be budget neutral for a US health plan.

Belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma in heavily pretreated patients: a US cost-effectiveness analysis.

BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) require several lines of therapy, with typically shorter remission duration with each additional line. RESEARCH DESIGN AND METHODS: The cost-effectiveness of belantamab mafodotin (belamaf; DREAMM-2; NCT03525678) was compared with selinexor plus dexamethasone (SEL+DEX; STORM Part 2; NCT02336815) among patients with RRMM who have received at least four prior therapies. The base case used a US commercial payer's perspective over a 10-year time horizon. Efficacy data were based on parametric survival analysis of DREAMM-2 and matching-adjusted indirect treatment comparison between DREAMM-2 and STORM Part 2, which assessed relative treatment effects between belamaf and SEL+DEX. Cost inputs included drug treatment, concomitant medications, adverse event management, subsequent treatments, and disease management. RESULTS: Belamaf decreased total treatment costs per patient by $14,267 and increased patient life years by 0.74 and quality-adjusted life years (QALYs) by 0.49 versus SEL+DEX. Patients receiving belamaf accrued 0.12 fewer progression-free life years versus patients on SEL+DEX. CONCLUSIONS: From a US commercial payer's perspective, belamaf had lower costs, and increased QALYs and life-year gain, compared with SEL+DEX. Belamaf is therefore likely to be a cost-effective treatment option for patients with RRMM who have received four or more prior lines of therapy.

Utilising artificial intelligence to determine patients at risk of a rare disease: idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension is a rare and life-shortening condition often diagnosed at an advanced stage. Despite increased awareness, the delay to diagnosis remains unchanged. This study explores whether a predictive model based on healthcare resource utilisation can be used to screen large populations to identify patients at high risk of idiopathic pulmonary arterial hypertension. Hospital Episode Statistics from the National Health Service in England, providing close to full national coverage, were used as a measure of healthcare resource utilisation. Data for patients with idiopathic pulmonary arterial hypertension from the National Pulmonary Hypertension Service in Sheffield were linked to pre-diagnosis Hospital Episode Statistics records. A non-idiopathic pulmonary arterial hypertension control cohort was selected from the Hospital Episode Statistics population. Patient history was limited to ≤5 years pre-diagnosis. Information on demographics, timing/frequency of diagnoses, medical specialities visited and procedures undertaken was captured. For modelling, a bagged gradient boosting trees algorithm was used to discriminate between cohorts. Between 2008 and 2016, 709 patients with idiopathic pulmonary arterial hypertension were identified and compared with a stratified cohort of 2,812,458 patients classified as non-idiopathic pulmonary arterial hypertension with ≥1 ICD-10 coded diagnosis of relevance to idiopathic pulmonary arterial hypertension. A predictive model was developed and validated using cross-validation. The timing and frequency of the clinical speciality seen, secondary diagnoses and age were key variables driving the algorithm's performance. To identify the 100 patients at highest risk of idiopathic pulmonary arterial hypertension, 969 patients would need to be screened with a specificity of 99.99% and sensitivity of 14.10% based on a prevalence of 5.5/million. The positive predictive and negative predictive values were 10.32% and 99.99%, respectively. This study highlights the potential application of artificial intelligence to readily available real-world data to screen for rare diseases such as idiopathic pulmonary arterial hypertension. This algorithm could provide low-cost screening at a population level, facilitating earlier diagnosis, improved diagnostic rates and patient outcomes. Studies to further validate this approach are warranted.

High levels of healthcare utilization prior to diagnosis in idiopathic pulmonary arterial hypertension support the feasibility of an early diagnosis algorithm: the SPHInX project.

Idiopathic pulmonary arterial hypertension (iPAH) is a rare progressive, life-shortening disease, usually diagnosed at an advanced stage. We hypothesize that patients with iPAH exhibit patterns of health-seeking behavior before diagnosis that will allow the development of earlier identification tools. The Sheffield Pulmonary Hypertension IndeX (SPHInX) project aims to develop a predictive algorithm based on routinely collected healthcare resource utilization (HCRU) data. This report focuses on the initial feasibility of the project, examining whether Hospital Episode Statistics (HES) data from the National Health Service in England have sufficient richness to support the development of an early diagnosis algorithm. This is a two-stage study. First, hospital interactions during 2009-2014 captured in HES data identified 127,815 adult patients with pulmonary hypertension (PH) ICD-10 codes, containing a probable iPAH cohort with incidence and demographics similar to the reported literature. HCRU was high in the three years before diagnosis. Second, to examine HCRU in patients with a confirmed iPAH diagnosis, we built the SPHInX dataset incorporating all patients investigated for suspected PH in the Sheffield Pulmonary Vascular Disease Unit during 2008-2016 (n = 6674). For the SPHInX dataset, data could be linked to HES in 98.6% of cases and patients with confirmed iPAH had similar levels of pre-diagnosis HCRU. In conclusion, patients with probable iPAH identified using HES and patients with confirmed iPAH have high levels of HCRU for several years before diagnosis. Artificial intelligence models will now be used to develop the SPHInX algorithm to screen for undiagnosed iPAH in the general population.

External Validation of Health Economic Decision Models for Chronic Obstructive Pulmonary Disease (COPD): Report of the Third COPD Modeling Meeting.

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.

Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine?

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 [FEV1] % 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 FEV1% 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 FEV1% 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.

Cost-effectiveness models for chronic obstructive pulmonary disease: cross-model comparison of hypothetical treatment scenarios.

OBJECTIVES: To compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios. METHODS: COPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared. RESULTS: Seven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively. CONCLUSIONS: Mortality was the most important factor determining the differences in cost-effectiveness outcomes between models.

Cost-effectiveness of roflumilast as an add-on treatment to long-acting bronchodilators in the treatment of COPD associated with chronic bronchitis in the United Kingdom.

OBJECTIVE: To estimate the cost-effectiveness of adding a selective phosphodiesterase-4 inhibitor, roflumilast, to a long-acting bronchodilator therapy (LABA) for the treatment of patients with severe-to-very severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis with a history of frequent exacerbations from the UK payer perspective. METHODS: A Markov model was developed to predict the lifetime cost and outcomes [exacerbations rates, life expectancy, and quality-adjusted life years (QALY)] in patients treated with roflumilast, which showed a reduction in the exacerbation rates and lung function improvement in a pooled analysis from two clinical trials, M2-124 and M2-125. Sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness. RESULTS: The addition of roflumilast to concomitant LABA reduced the number of exacerbations from 15.6 to 12.7 [2.9 (95 % CI 0.88-4.92) exacerbations avoided] and increased QALYs from 5.45 to 5.61 [0.16 (95 % CI 0.02-0.31) QALYs gained], at an incremental cost of £3,197 (95 % CI £2,135-£4,253). Cost in LABA alone and LABA + roflumilast were £16,161 and £19,358 respectively. The incremental cost-effectiveness ratios in the base case were £19,505 (95 % CI £364-£38,646) per quality-adjusted life-year gained and 18,219 (95 % CI £12,697-£49,135) per life-year gained. Sensitivity analyses suggest that among the main determinants of cost-effectiveness are the reduction of exacerbations and the case fatality rate due to hospital-treated exacerbations. Probabilistic sensitivity analysis suggests that the probability of roflumilast being cost-effective is 82 % at willingness-to-pay £30,000 per QALY. CONCLUSIONS: The addition of roflumilast to LABA in the treatment of patients with severe-to-very severe COPD reduces the rate of exacerbations and can be cost-effective in the UK setting.

Cost-effectiveness of roflumilast in combination with bronchodilator therapies in patients with severe and very severe COPD in Switzerland.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) represents a burden on patients and health systems. Roflumilast, an oral, selective phosphodiesterase-4-inhibitor reduces exacerbations and improves lung function in severe/very severe COPD patients with a history of exacerbations. This study aimed to estimate the lifetime cost and outcomes of roflumilast added-on to commonly used COPD regimens in Switzerland. METHODS: A Markov cohort model was developed to simulate COPD progression in patients with disease states of severe, very severe COPD, and death. The exacerbation rate was assumed to be two per year in severe COPD. COPD progression rates were drawn from the published literature. Efficacy was expressed as relative ratios of exacerbation rates associated with roflumilast, derived from a mixed-treatment comparison. A cost-effectiveness analysis was conducted for roflumilast added to long-acting muscarinic antagonists (LAMA), long-acting ß2-agonist/ inhaled corticosteroids (LABA/ICS), and LAMA + LABA/ICS. The analysis was conducted from the Swiss payer perspective, with costs and outcomes discounted at 2.5% annually. Parameter uncertainties were explored in one-way and probabilistic sensitivity analyses. RESULTS: In each of the comparator regimens mean life expectancy was 9.28 years and quality-adjusted life years (QALYs) gained were 6.19. Mean estimated lifetime costs per patient in the comparator arms were CHF 83,364 (LAMA), CHF 88,161 (LABA/ICS), and CHF 95,564 (LAMA + LABA/ICS) respectively. Adding roflumilast resulted in a mean cost per patient per lifetime of CHF 86,754 (LAMA + roflumilast), CHF 91,470 (LABA/ICS + roflumilast), and CHF 99,364 (LAMA + LABA/ICS + roflumilast), respectively. Life-expectancy and quality-adjusted life-expectancy were 9.63 years and 6.47 QALYs (LAMA + roflumilast), 9.64 years and 6.48 QALYs (LABA/ICS + roflumilast), and 9.63 years and 6.47 QALYs (LAMA + LABA/ ICS + roflumilast). Incremental cost-effectiveness ratios were CHF 12,313, CHF 11,456, and CHF 13,671 per QALY when roflumilast was added to the three regimens. CONCLUSION: Treatment with roflumilast is estimated to reduce the health and economic burden of COPD exacerbations and represent a cost-effective treatment option for patients with frequent exacerbations in Switzerland.

Long-term cost-utility analysis of exenatide once weekly versus insulin glargine for the treatment of type 2 diabetes patients in the US.

OBJECTIVE: The purpose of this study was to estimate the long-term cost-utility of treating type 2 diabetes mellitus (T2DM) patients with exenatide once weekly (EQW) compared with insulin glargine (IG) from a US payer perspective. METHODS: A validated computer simulation model, the CORE Diabetes Model, was used to project lifetime clinical outcomes and direct medical costs. Direct medical costs included pharmacy costs and costs associated with the management of diabetes and its complications. The model was populated using patient characteristics (mean age: 57.9 years; mean diabetes duration: 7.9 years; mean HbA1(c): 8.3%; mean body mass index [BMI]: 32.3 kg/m(2)) and clinical data from a phase 3 clinical trial that compared EQW with IG in T2DM patients on a background of metformin alone or a combination of metformin and a sulphonylurea (DURATION-3). All EQW patients were assumed to have stayed on treatment for 3 years before switching to IG. Health outcomes and costs were discounted at 3% per year. Complication costs were derived from published sources. A range of sensitivity analyses was performed. RESULTS: Over a lifetime horizon, and compared with IG, EQW was associated with an incremental cost of $3914 (SD = 2923). EQW was projected to increase life expectancy by 0.135 (SD = 0.216) years and to improve quality-adjusted life expectancy by 0.246 (SD = 0.147) quality-adjusted life years (QALYs), generating an incremental cost-effectiveness ratio (ICER) of $15,936/QALY. Assuming a payer's willingness to pay threshold of $50,000/QALY, EQW is therefore cost-effective compared to IG. One-way and probabilistic sensitivity analyses confirmed EQW's cost-effective profile. LIMITATIONS: Short-term changes (26 weeks) in surrogate end-points (e.g., HbA1(c,) weight, complications) from one clinical trial were used to project long-term future effects on clinical outcomes. CONCLUSIONS: Treatment with EQW is projected to be cost-effective compared to treatment with IG.

Long-term clinical and economic outcomes associated with liraglutide versus sitagliptin therapy when added to metformin in the treatment of type 2 diabetes: a CORE Diabetes Model analysis.

BACKGROUND: A recent open-label, parallel group trial showed that liraglutide is superior to sitagliptin for reduction of HbA1c, and is well tolerated with minimum risk of hypoglycemia. Although these findings support the use of liraglutide as an effective GLP-1 agent to add to metformin, the value of liraglutide needs to be quantified in the framework of a cost-effectiveness (CE) analysis in a US setting. OBJECTIVE: This current study sets out to assess the long-term cost-effectiveness outcomes of liraglutide vs sitagliptin based on treatment effects data from the 1860-LIRA-DPP-4 52-week trial. METHODS: The IMS CORE Diabetes Model (CDM), a non-product-specific, validated computer simulation model that projects the long-term outcomes related to interventions for type 2 diabetes, is used for simulation of these interventions. In the model, patients were treated initially on one of the three treatment options: liraglutide 1.2 mg daily, 1.8 mg daily, or sitagliptin 100 mg daily, each used as add-on therapy to metformin for 5 years. After 5 years all patients switched to basal insulin treatment for the remainder of the simulation (35-year time horizon overall). Incremental cost-effectiveness ratios (ICERs) were generated for liraglutide 1.2 mg compared with sitagliptin and liraglutide 1.8 mg compared with sitagliptin. Transition probabilities, health state utility values, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the US. Sensitivity analyses were performed to test robustness of the base case scenario. RESULTS: For liraglutide 1.8 mg vs sitagliptin, the ICER was $37,234 per QALY gained, while for liraglutide 1.2 mg vs sitagliptin, the ICER was $25,742 per QALY gained. In all sensitivity analyses, including setting the change in HbA1c to the lower limits of the 95% confidence intervals, the ICERs remained below US$ 50,000/QALY, a commonly accepted threshold in the US, except for the shortest time horizon of 10 years. CONCLUSIONS: The availability of liraglutide 1.2 mg and 1.8 mg with improved efficacy profiles over sitagliptin could improve patient care, with the incremental cost effectiveness ratio below $50,000 per QALY gained as add-on to metformin.

Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis.

PURPOSE: Frequent exacerbations which are both costly and potentially life-threatening are a major concern to patients with chronic obstructive pulmonary disease (COPD), despite the availability of several treatment options. This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting. PATIENTS AND METHODS: A Markov cohort model was developed to predict lifetime costs, outcomes, and cost-effectiveness of various combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta agonist (LABA), an inhaled corticosteroid (ICS), and roflumilast in a fully incremental analysis. Patients willing and able to take ICS, and those refusing or intolerant to ICS were analyzed separately. Efficacy was expressed as relative rate ratios of COPD exacerbation associated with alternative treatment regimens, taken from a mixed treatment comparison. The analysis was conducted from the UK National Health Service (NHS) perspective. Parameter uncertainty was explored using one-way and probabilistic sensitivity analysis. RESULTS: Based on the results of the fully incremental analysis a cost-effectiveness frontier was determined, indicating those treatment regimens which represent the most cost-effective use of NHS resources. For ICS-tolerant patients the cost-effectiveness frontier suggested LAMA as initial treatment. Where patients continue to exacerbate and additional therapy is required, LAMA + LABA/ICS can be a cost-effective option, followed by LAMA + LABA/ICS + roflumilast (incremental cost-effectiveness ratio [ICER] versus LAMA + LABA/ICS: £16,566 per quality-adjusted life-year [QALY] gained). The ICER in ICS-intolerant patients, comparing LAMA + LABA + roflumilast versus LAMA + LABA, was £13,764/QALY gained. The relative rate ratio of exacerbations was identified as the primary driver of cost-effectiveness. CONCLUSION: The treatment algorithm recommended in UK clinical practice represents a cost-effective approach for the management of COPD. The addition of roflumilast to the standard of care regimens is a clinical and cost-effective treatment option for patients with severe COPD, who continue to exacerbate despite existing bronchodilator therapy.

Long-term cost-consequence analysis of exenatide once weekly vs sitagliptin or pioglitazone for the treatment of type 2 diabetes patients in the United States.

OBJECTIVE: Exenatide once-weekly (ExQW) is a GLP-1 receptor agonist shown to lower glucose and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the clinical benefits and associated economic benefits of treatment with ExQW compared with sitagliptin or pioglitazone in the US. METHODS: The IMS CORE Diabetes Model, a validated computer simulation model, was used to project lifetime clinical outcomes and complication costs. The costs of glucose-lowering drugs were excluded as not all prices were available. Baseline patient characteristics (mean values: age, 52.5 years; diabetes duration, 6 years; HbA1(c), 8.51%; body mass index, 32.12 kg/m(2)) and clinical data were derived from a phase 3 clinical trial that compared ExQW with sitagliptin or pioglitazone in T2DM patients. At 6 months, patients treated with ExQW had greater improvements in HbA1(c) and body weight than those treated with sitagliptin or pioglitazone. Complication costs were extracted from published sources. Health outcomes and costs were discounted at 3% per year. Sensitivity analyses were performed. RESULTS: Over 35 years, and compared with sitagliptin or pioglitazone, ExQW increased life expectancy by, respectively, 0.28 (13.76 ± 0.17 vs 13.48 ± 0.18) and 0.17 years (13.76 ± 0.17 vs 13.59 ± 0.17), and quality-adjusted life years by, respectively, 0.28 (9.56 ± 0.12 vs 9.28 ± 0.12) and 0.24 years (9.56 ± 0.12 vs 9.32 ± 0.12). ExQW was associated with lower lifetime complication costs: compared with sitagliptin or pioglitazone, ExQW saved, respectively US$2215 (US$55,647 ± 2039 vs US$57,862 ± 2159) and US$933 (US$55,647 ± 2039 vs US$56,580 ± 2007) direct cost per patient. Cost-savings resulted mainly from a lower projected cumulative incidence of cardiovascular diseases and neuropathic complications. LIMITATIONS: Short-term changes in surrogate end-points were used to project lifetime effects on clinical outcomes. Pharmacy costs were excluded from the analyses. CONCLUSIONS: Over a patient's lifetime, ExQW was projected to improve health and decrease diabetes-related complication costs compared with sitagliptin or pioglitazone.

Modeling the lifetime costs of insulin glargine and insulin detemir in type 1 and type 2 diabetes patients in Canada: a meta-analysis and a cost-minimization analysis.

BACKGROUND: Two basal insulin analogues, insulin glargine once daily and insulin detemir once or twice daily, are marketed in Canada. OBJECTIVE: To estimate the long-term costs of insulin glargine once daily (QD) versus insulin detemir once or twice daily (QD or BID) for type 1 (T1DM) and type 2 (T2DM) diabetes mellitus from a Canadian provincial government's perspective. METHODS: A cost-minimization analysis comparing insulin glargine (IGlarg) to insulin detemir (IDet) was conducted using a validated computer simulation model, the CORE Diabetes Model. Lifetime direct medical costs including costs of insulin treatment and diabetes complications were projected. T1DM and T2DM patients' daily insulin dose (T1DM: IGlarg QD 26.2 IU; IDet BID 33.6 IU; T2DM: IGlarg QD 47.2 IU; IDet QD 65.7 IU or IDet BID 80.4 IU) was derived from a meta-analysis of randomized trials. All patients were assumed to stay on the same treatment for life. Costs were discounted at 5% per annum and reported in 2010 Canadian Dollars. RESULTS: The meta-analysis showed T1DM and T2DM patients had similar HbA(1c) change from baseline when receiving IGlarg compared to IDet (T1DM: 0.002%-points; p = 0.97; T2DM: -0.05%-points; p = 0.28). Treatment of T1DM patients with IGlarg versus IDet BID resulted in lifetime cost savings of $4231 per patient. Treatment of T2DM patients with IGlarg resulted in lifetime cost savings of $4659 per patient versus IDet QD and cost savings of $8709 per patient versus IDet BID. CONCLUSIONS: Similar HbA(1c) change from baseline can be achieved with a lower IGlarg than IDet dose. From the perspective of a Canadian provincial government, treatment of T1DM and T2DM patients with IGlarg instead of IDet can generate long-term cost savings. Main limitations include trial data were derived from multi-country studies rather than the Canadian population and self-monitoring blood glucose costs were not included.

Mental health care reforms in Europe: Rehabilitation and social inclusion of people with mental illness in Russia.

Long-established Medico-Social Expert Commissions (MSECs) play a pivotal role in the Russian mental health system. They act as gatekeepers to pensions, rehabilitation, and employment services. This column describes their role in encouraging or impeding the social inclusion of people with mental illness, drawing on findings of a three-year project in Sverdlovsk Oblast. In Russia the emphasis remains on medical aspects of treatment, without adequate consideration of social and occupational rehabilitation. Links with local employment services are weak. To promote social inclusion, steps must be taken to encourage and facilitate cooperation and collaboration between the MSECs, employment services, and medical services.

Cost-effectiveness of stroke unit care followed by early supported discharge.

BACKGROUND AND PURPOSE: Stroke places a significant burden on the economy in England and Wales with the overall societal costs estimated at pound7 billion per annum. There is evidence that both stroke units (SUs) and early supported discharge (ESD) are effective in treating patients with stroke. This study assesses the cost-effectiveness of the combination of these 2 strategies and compares it with the care provided in SU without ESD and in a general medical ward without ESD. The objective of this study was to model the long-term (10 years) cost-effectiveness of SU care followed by ESD. METHODS: The study design was cost-effectiveness modeling. The study took place in SUs in the coverage area of the South London Stroke Register, UK. The modeled population was incident ischemic stroke cases (N=844) observed between 2001 and 2006. SU care followed by ESD was compared with SU care without ESD and general medical ward care without ESD. Main outcome measures were health service and societal costs and cost per quality-adjusted life-year gained. RESULTS: Using the cost-effectiveness threshold of pound30000, as commonly used in the UK, SU care followed by ESD is the cost-effective strategy compared with the other 2 options. The incremental cost-effectiveness ratio of SU care followed by ESD is pound10661 compared with the general medical ward without ESD care and pound17721 compared with the SU without ESD. CONCLUSIONS: SU care followed by ESD is both an effective and a cost-effective strategy with the main gains in years of life saved.

Mental health reform in the Russian Federation: an integrated approach to achieve social inclusion and recovery.

OBJECTIVE: To facilitate mental health reform in one Russian oblast (region) using systematic approaches to policy design and implementation. METHODS: The authors undertook a three-year action-research programme across three pilot sites, comprising a multifaceted set of interventions combining situation appraisal to inform planning, sustained policy dialogue at federal and regional levels to catalyse change, introduction of multidisciplinary and intersectoral-working at all levels, skills-based training for professionals, and support for nongovernmental organizations (NGOs) to develop new care models. FINDINGS: Training programmes developed in this process have been adopted into routine curricula with measurable changes in staff skills. Approaches to care improved through multidisciplinary and multisectoral service delivery, with an increase in NGO activities, user involvement in care planning and delivery in all pilot sites. Hospital admissions at start and end of the study fell in two pilot sites, while the rate of readmissions in all three pilot sites by 2006 was below that for the region as a whole. Lessons learned have informed the development of regional and federal mental health policies. CONCLUSION: A multifaceted and comprehensive programme can be effective in overcoming organizational barriers to the introduction of evidence-based multisectoral interventions in one Russian region. This can help facilitate significant and sustainable changes in policy and reduce institutionalization.