Kirsi Norrbacka

Differences in the use of guideline-recommended therapies among 14 European countries in patients with acute coronary syndromes undergoing PCI

Aims: Despite common European Society of Cardiology recommendations, adherence to guideline therapy varies, both temporally and geographically. We sought to examine current differences in the use of guideline-recommended therapies among 14 European countries in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods and Results: Data were obtained from the Antiplatelet Therapy Observational Registry (APTOR), a non-interventional, prospective observational cohort study enrolling patients with ACS undergoing PCI. Medication data were captured through 1 year. The large majority of patients in the APTOR registry received statins at hospital discharge (89%) and remained on statins at 1 year (87%), a finding that was consistent across countries. Likewise, beta-blocker use was similar at discharge and 1 year (83 and 81%, respectively). There was large disparity in aspirin loading dose between countries, but the discharge maintenance dose was more consistent, with most receiving ≤100 mg (87%). While 95% of patients were discharged on dual antiplatelet therapy, 71% remained on both treatments by 1 year, with wide variation by country in 1-year use. Conclusions: These data from the APTOR study provide key information on current European ACS patient care management from hospitalization through 1 year. Even with European Society of Cardiology (ESC) guidelines, variations in practice patterns exist among ACS patients treated with PCI between the 14 European countries studied, including the use of proven therapies, as well as appropriate duration and dosing of antiplatelet regimens. Efforts are needed to further explain why such variation exists and to continue to improve adherence to ESC guidelines to improve patient care.

The cost-effectiveness of exenatide once weekly compared with exenatide twice daily and insulin glargine for the treatment of patients with type two diabetes and body mass index ≥30 kg/m2 in Spain

Abstract Objective: The objective of this analysis was to estimate the cost-effectiveness of exenatide once weekly (EQW) for the treatment of type two diabetes mellitus (T2DM) in Spain. EQW was compared against exenatide twice daily (EBID) and insulin glargine (IG). Methods: The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with T2DM treated with EQW, EBID, and IG. Treatment effects and patient baseline characteristics were taken from the DURATION 3 and pooled DURATION 1 and 5 studies, in the comparison against IG and EBID, respectively. Unit costs and health state utility values were derived from published sources. To reflect diabetes progression, patients started on EQW or EBID, switching to insulin glargine after 3 years. The analysis was conducted from the perspective of the Spanish National Health Service over a time horizon of 35 years with costs and outcomes discounted at 3%. The base case included patients with a BMI > 30 kg/m2, which is in line with current prescription restrictions in Spain. Uncertainty was addressed through extensive one-way sensitivity analyses around key model parameters and a comprehensive probabilistic sensitivity analysis. Results: When compared with EBID, EQW was the dominant strategy, i.e., less costly and more effective. When compared to IG, the incremental cost-effectiveness ratio was estimated at €12,084 per QALY gained. Sensitivity analysis indicated that the model projections were robust to the various scenarios tested. Limitations: Primary limitations of the analysis are common to other T2DM analyses and include the extrapolation of short-term clinical data to the 35 year time horizon and uncertainty around optimum treatment durations. Conclusion: The analyses indicate that EQW is a cost-effective option for the treatment of T2DM patients in Spain for patients with a BMI > 30 kg/m2 considering a willingness-to-pay threshold of €30,000 per QALY gained.

Predictors, cost, and outcomes of patients with acute coronary syndrome who receive optimal secondary prevention therapy: results from the antiplatelet treatment observational registries (APTOR).

BACKGROUND We sought to evaluate outcomes, costs of care, quality of life and predictors at 12 months in patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) and evaluated use of optimal secondary prevention therapy, defined as use of aspirin and clopidogrel along with ≥ 3 of the following 4 therapies at both hospital discharge and at one-year post-PCI: statins, beta-blockers, ARB/ACE-inhibitors, and exercise or diet. METHODS Data were from the prospective, observational APTOR study of 14 European countries from 2007 to 2009 (n=4184 patients). RESULTS Optimal therapy was received in 43% of patients. Use of optimal therapy varied significantly by country. Diet or exercise at 1 year was more likely prescribed to the optimal cohort (34% vs 16%) as was dual antiplatelet therapy (99% vs 49%). Rates of CV event (3.1% vs 3.5%), bleeding (2.9% vs 2.8%) and mortality (0.9% vs 1.3%) at 1 year were similar between the optimal and non-optimal cohorts, respectively. Total costs were similar for both cohorts, but differences in post-discharge costs were observed (optimal: £1760 [£1682-£1844]; non-optimal: £1492 [£1434-£1554]), primarily due to post-discharge medication and resource use. CONCLUSIONS In conclusion, in this contemporary, European ACS-PCI registry, optimal therapy was low (<50%) overall, particularly for diet or exercise and dual antiplatelet therapy, highlighting a considerable gap between evidence-based guidelines and implementation of such treatments. Whether this gap reflects a missed opportunity to improve patient outcomes or whether it reflects appropriate deviation from guidelines by front-line clinicians requires further investigation.

Evaluating health-related quality of life in type 1 diabetes: a systematic literature review of utilities for adults with type 1 diabetes

Background and aims Type 1 diabetes is a chronic condition associated with micro- and macrovascular complications that have a notable impact on health-related quality of life, the magnitude of which can be quantified via the use of utility values. The aim of this review was to conduct a systematic literature review to identify and compare published health state utility values for adults with type 1 diabetes both, with and without diabetes-related complications. Methods Literature searches of the PubMed, EMBASE, and Cochrane Library databases were performed to identify English language studies on adults with type 1 diabetes, published from 2000 onward, reporting utility values for patients with or without diabetes-related complications or assessing the impact of changes in HbA1c or body mass index on quality of life. For inclusion, studies were required to report utilities elicited using validated methods. Results A total of 20 studies were included in the final review that included utility values elicited using the EuroQuol five dimensions questionnaire (n=9), 15D questionnaire (n=2), Quality of Well-Being scale (n=4), time trade-off (n=3), and standard gamble (n=2) methods. For patients with no complications, reported utility values ranged from 0.90 to 0.98. Complications including stroke (reported disutility range, −0.105 to −0.291), neuropathy (range, −0.055 to −0.358), and blindness (range, −0.132 to −0.208) were associated with the largest decrements in utility values. The magnitude of utility values and utility decrements was influenced by the assessment method used. Conclusion Complications lead to impaired health-related quality of life in patients with type 1 diabetes, the magnitude of which is influenced by the method used to determine utilities. There is currently a lack of utility data for certain complications of type 1 diabetes, meaning that many economic evaluations have relied on a combination of type 1 and type 2 diabetes utilities, despite differences between the conditions and populations, or type 1 diabetes-specific utilities derived from different instruments.

The Prime Diabetes Model: Novel Methods for Estimating Long-Term Clinical and Cost Outcomes in Type 1 Diabetes Mellitus

BACKGROUND Recent publications describing long-term follow-up from landmark trials and diabetes registries represent an opportunity to revisit modeling options in type 1 diabetes mellitus (T1DM). OBJECTIVES To develop a new product-independent model capable of predicting long-term clinical and cost outcomes. METHODS After a systematic literature review to identify clinical trial and registry data, a model was developed (the PRIME Diabetes Model) to simulate T1DM progression and complication onset. The model runs as a patient-level simulation, making use of covariance matrices for cohort generation and risk factor progression, and simulating myocardial infarction, stroke, angina, heart failure, nephropathy, retinopathy, macular edema, neuropathy, amputation, hypoglycemia, ketoacidosis, mortality, and risk factor evolution. Several approaches novel to T1DM modeling were used, including patient characteristics and risk factor covariance, a glycated hemoglobin progression model derived from patient-level data, and model averaging approaches to evaluate complication risk. RESULTS Validation analyses comparing modeled outcomes with published studies demonstrated that the PRIME Diabetes Model projects long-term patient outcomes consistent with those reported for a number of long-term studies. Macrovascular end points were reliably reproduced across five different populations and microvascular complication risk was accurately predicted on the basis of comparisons with landmark studies and published registry data. CONCLUSIONS The PRIME Diabetes Model is product-independent, available online, and has been developed in line with good practice guidelines. Validation has indicated that outcomes from long-term studies can be reliably reproduced. The model offers new approaches to long-standing challenges in diabetes modeling and may become a valuable tool for informing health care policy.

The cost-effectiveness of dulaglutide versus liraglutide for the treatment of type 2 diabetes mellitus in Spain in patients with BMI ≥30 kg/m2

Abstract Objective: Dulaglutide 1.5 mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8 mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30 kg/m2. Methods: The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon. Comparative safety and efficacy data were derived from direct comparison of dulaglutide 1.5 mg vs liraglutide 1.8 mg from the AWARD-6 trial in patients with a body mass index (BMI) ≥30 kg/m2. All patients were assumed to remain on treatment for 2 years before switching treatment to basal insulin at a daily dose of 40 IU. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to explore the sensitivity of the model to plausible variations in key parameters and uncertainty of model inputs. Results: Under base case assumptions, dulaglutide 1.5 mg was less costly and more effective vs liraglutide 1.8 mg (total lifetime costs €108,489 vs €109,653; total QALYS 10.281 vs 10.259). OWSA demonstrated that dulaglutide 1.5 mg remained dominant given plausible variations in key input parameters. Results of the PSA were consistent with base case results. Limitations: Primary limitations of the analysis are common to other cost-effectiveness analyses of chronic diseases like T2DM and include the extrapolation of short-term clinical data to the lifetime time horizon and uncertainty around optimum treatment durations. Conclusion: The model found that dulaglutide 1.5 mg was more effective and less costly than liraglutide 1.8 mg for the treatment of T2DM in Spain. Findings were robust to plausible variations in inputs. Based on these results, dulaglutide may result in cost savings to the Spanish National Health System.

Patient preferences in Italy: health state utilities associated with attributes of weekly injection devices for treatment of type 2 diabetes

Objectives Several glucagon-like peptide-1 receptor agonists are administered as weekly injections for treatment of type 2 diabetes (T2D). These medications vary in their injection processes, and a recent study in the UK found that these differences had an impact on patient preference and health state utilities. The purpose of this study was to replicate the UK study in Italy to examine preferences of an Italian patient sample, while allowing for comparison between utilities in the UK and Italy. Materials and methods Participants with T2D in Italy valued health states in time trade-off interviews. All health states had the same description of T2D, but differed in description of the treatment process. As in the original UK study, the first health state described an oral treatment regimen, while additional health states added a weekly injection. The injection health states differed in three injection-related attributes: requirements for reconstituting the medication, waiting during medication preparation, and needle handling. Results Interviews were completed by 238 patients (58.8% male; mean age = 60.2 years; 118 from Milan, 120 from Rome). The oral treatment health state had a mean (SD) utility of 0.90 (0.10). The injection health states had significantly (p < 0.0001) lower utilities, which ranged from 0.87 (requirements for reconstitution, waiting, and handling) to 0.89 (weekly injection with none of these requirements). Differences in health state utility scores suggest that each administration requirement was associated with a disutility (ie, negative utility difference): −0.006 (reconstitution), −0.006 (needle handling), −0.011 (reconstitution, needle handling), and −0.022 (reconstitution, waiting, needle handling). Conclusion Disutilities associated with the injection device characteristics were similar to those reported with the UK sample. Results suggest that injection device attributes may be important to some patients with T2D, and it may be useful for clinicians to consider these attributes when choosing medication for patients initiating these weekly treatments.

Utilization patterns of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus in Germany: a retrospective cohort study

Abstract Objective: This retrospective database analysis complements previous research to understand treatment patterns for German patients newly-initiating or switching to subsequent GLP-1 RAs. Methods: Adult patients (≥18 years) initiating GLP-1 RA (Cohort 1 [C1]) or switching from a previous GLP-1 RA (Cohort 2 [C2]) to exenatide twice-daily (exBID), exenatide once-weekly (exQW), dulaglutide (DULA), or liraglutide (LIRA) were included in this analysis using IQVIA LRx from January 1, 2014–March 31, 2017. Patients were required to have ≥1 oral anti-hyperglycemic prescription during the 6-month pre-index period and ≥12 months follow-up. Persistence and treatment modifications were assessed within and beyond 12 months follow-up. Average daily/weekly dosage (ADD/AWD) was calculated during persistence. Results: C1 included 13,417 patients, while C2 included 4,264 patients. Mean ± standard deviation (SD) age was similar (57.7 ± 11.1 years [C1], 58.9 ± 10.1 years [C2]). Most patients using DULA in C2 had switched from LIRA (56.6%). For C1, mean ADD for LIRA was 1.41 ± 0.10 mg, slightly higher in C2, and increased over time. ADD for exBID was 16.9 ± 1.0 mcg, slightly greater in C2. AWD was 2.00 ± 0.05 mg for exQW users and 1.42 ± 0.03 mg for DULA users in C1, similar to C2. For C1, 27.0% exBID, 35.3% exQW, 50.9% DULA, and 48.1% LIRA users remained persistent at 12 months. Patients using DULA had a higher probability of remaining persistent over time (Kaplan-Meier) for both cohorts. Conclusions: Patients using DULA had the highest probability of remaining persistent over time, followed by LIRA. ADD/AWD for DULA, exQW, and exBID were aligned with the recommended combination therapy dose; LIRA ADD suggests some patients use the 1.8 mg dose.

Assessing Consistency in a Network Meta-Analysis to Compare Once Weekly Dulaglutide Versus Other Glp-1 Receptor Agonists in Patients with Type 2 Diabetes

 The ‘node-splitting’ model (Dias et al. 2010)  The direct and indirect evidence for each pairwise contrast are split out and compared  Model assesses whether relaxing the consistency constraint improves model fit  The ‘inconsistency’ model (Dias et al. 2010; Dias et al. 2013)  Independent treatment effects, whereby the consistency constraint is relaxed, are estimated for each treatment comparison for which trial evidence is available.  Where trials have more than two treatment arms, independent treatment effects are estimated for the comparisons against a common reference arm rather than for all the possible comparisons within a trial.  This can be compared to the ‘consistency’ model which is the traditional NMA approach assuming consistency between studies in the treatment effects.  The ‘design-by-treatment interaction’ model (Higgins et al. 2012).  ‘design’ refers to the combination of treatments included in a study e.g. estimating the relative treatment effect of A vs B using different designs AB (two arm study comparing A and B) or ABC (3 arm study comparing A, B and C).  The inconsistency between treatment effects using alternative study designs is estimated (Higgins et al. 2012)  These models were applied to the datasets to determine whether inconsistency was present and to examine potential causes. Table 2: Inconsistency results from ‘design-by-treatment’ model (16-36 week add-on to MET ± SU ± TZD) Assessing consistency in a network meta-analysis to compare once weekly dulaglutide versus other GLP-1 receptor agonists in patients with type 2 diabetes

A Review Of Cost Of Illness Studies In Patients With End Stage Renal Disease.

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