Stratification of COPD patients towards personalized medicine: reproduction and formation of clusters.

BACKGROUND: The global initiative for chronic obstructive lung disease (GOLD) 2020 emphasizes that there is only a weak correlation between FEV1, symptoms and impairment of the health status of patients with chronic obstructive pulmonary disease (COPD). Various studies aimed to identify COPD phenotypes by cluster analyses, but behavioral aspects besides smoking were rarely included. METHODS: The aims of the study were to investigate whether (i) clustering analyses are in line with the classification into GOLD ABCD groups; (ii) clustering according to Burgel et al. (Eur Respir J. 36(3):531-9, 2010) can be reproduced in a real-world COPD cohort; and (iii) addition of new behavioral variables alters the clustering outcome. Principal component and hierarchical cluster analyses were applied to real-world clinical data of COPD patients newly referred to secondary care (n = 155). We investigated if the obtained clusters paralleled GOLD ABCD subgroups and determined the impact of adding several variables, including quality of life (QOL), fatigue, satisfaction relationship, air trapping, steps per day and activities of daily living, on clustering. RESULTS: Using the appropriate corresponding variables, we identified clusters that largely reflected the GOLD ABCD groups, but we could not reproduce Burgel's clinical phenotypes. Adding six new variables resulted in the formation of four new clusters that mainly differed from each other in the following parameters: number of steps per day, activities of daily living and QOL. CONCLUSIONS: We could not reproduce previously identified clinical COPD phenotypes in an independent population of COPD patients. Our findings therefore indicate that COPD phenotypes based on cluster analysis may not be a suitable basis for treatment strategies for individual patients.

The impact of the involvement of a healthcare professional on the usage of an eHealth platform: a retrospective observational COPD study.

BACKGROUND: Ehealth platforms, since the outbreak of COVID-19 more important than ever, can support self-management in patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this observational study is to explore the impact of healthcare professional involvement on the adherence of patients to an eHealth platform. We evaluated the usage of an eHealth platform by patients who used the platform individually compared with patients in a blended setting, where healthcare professionals were involved. METHODS: In this observational cohort study, log data from September 2011 until January 2018 were extracted from the eHealth platform Curavista. Patients with COPD who completed at least one Clinical COPD Questionnaire (CCQ) were included for analyses (n = 299). In 57% (n = 171) of the patients, the eHealth platform was used in a blended setting, either in hospital (n = 128) or primary care (n = 29). To compare usage of the platform between patients who used the platform independently or with a healthcare professional, we applied propensity score matching and performed adjusted Poisson regression analysis on CCQ-submission rate. RESULTS: Using the eHealth platform in a blended setting was associated with a 3.25 higher CCQ-submission rate compared to patients using the eHealth platform independently. Within the blended setting, the CCQ-submission rate was 1.83 higher in the hospital care group than in the primary care group. CONCLUSION: It is shown that COPD patients used the platform more frequently in a blended care setting compared to patients who used the eHealth platform independently, adjusted for age, sex and disease burden. Blended care seems essential for adherence to eHealth programs in COPD, which in turn may improve self-management.

Exploring characteristics of COPD patients with clinical improvement after integrated disease management or usual care: post-hoc analysis of the RECODE study.

BACKGROUND: The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated disease management (IDM) in primary care had no effect on quality of life (QOL) in COPD patients compared with usual care (guideline-supported non-programmatic care). It is possible that only a subset of COPD patients in primary care benefit from IDM. We therefore examined which patients benefit from IDM, and whether patient characteristics predict clinical improvement over time. METHOD: Post-hoc analyses of the RECODE trial among 1086 COPD patients. Logistic regression analyses were performed with baseline characteristics as predictors to examine determinants of improvement in QOL, defined as a minimal decline in Clinical COPD Questionnaire (CCQ) of 0.4 points after 12 and 24 months of IDM. We also performed moderation analyses to examine whether predictors of clinical improvement differed between IDM and usual care. RESULTS: Regardless of treatment type, more severe dyspnea (MRC) was the most important predictor of clinically improved QOL at 12 and 24 months, suggesting that these patients have most room for improvement. Clinical improvement with IDM was associated with female gender (12-months) and being younger (24-months), and improvement with usual care was associated with having a depression (24-months). CONCLUSIONS: More severe dyspnea is a key predictor of improved QOL in COPD patients over time. More research is needed to replicate patient characteristics associated with clinical improvement with IDM, such that IDM programs can be offered to patients that benefit the most, and can potentially be adjusted to meet the needs of other patient groups as well. TRIAL REGISTRATION: Netherlands Trial Register, NTR2268. Registered 31 March 2010.

Broadening the Perspective of Cost-Effectiveness Modeling in Chronic Obstructive Pulmonary Disease: A New Patient-Level Simulation Model Suitable to Evaluate Stratified Medicine.

OBJECTIVES: To develop a health economic model that included a great diversity of patient characteristics and outcomes for chronic obstructive pulmonary disease (COPD), which can be used to inform decisions about stratified medicine in COPD. METHODS: The choice of patient characteristics and outcomes to include in the model was based on 3 literature reviews on multidimensional prognostic COPD indices, COPD phenotypes, and treatment effects in subgroups. A conceptual model was constructed including 14 patient characteristics, 7 intermediate outcomes (lung function, physical activity, exercise capacity, symptoms, disease-specific quality of life, exacerbations, and pneumonias), and 3 final outcomes (mortality, quality-adjusted life-years [QALYs], and costs). Regression equations describing the statistical associations between the patient characteristics and intermediate and final outcomes were estimated using the longitudinal data of 5 large COPD trials (19,378 patients). A patient-level simulation model was developed in which individual patients from the baseline population of the 5 trials are sampled and their outcomes over lifetime are predicted based on the regression equations. RESULTS: The base-case analysis (single-arm simulation representing treatment with tiotropium) showed that patients had a mean lung function decline of 43 mL/year, 0.62 exacerbations/year, a worsening of their physical activity and quality of life with 1.48 and 1.10 points/year, a life expectancy of 11.2 years, 7.25 QALYs, and total lifetime costs of £24,891. Results for a selection of treatment scenarios and subgroups were shown to demonstrate the potential of the model. CONCLUSIONS: We developed a unique patient-level simulation model that can be used to evaluate COPD treatment options for a variety of subgroups.

Planning, implementation and operation of a personalized patient management system for subjects with first suspect of cancer (OnkoNetwork): system description based on a qualitative study.

BACKGROUND: OnkoNetwork is a recently established integrated care model with a personalized pathway system to manage patients with first suspect of a solid tumour in secondary care, that evolved as a regional initiative in Hungary. The primary aim of OnkoNetwork is the improvement of clinical outcomes via timely access to quality assured and defragmented healthcare services. The Horizon 2020 funded SELFIE project has selected OnkoNetwork for in-depth qualitative and quantitative evaluation. The aim of this study was to provide a qualitative evaluation of OnkoNetwork along the six components of the SELFIE conceptual framework: 1) service delivery, 2) leadership and governance, 3) workforce, 4) financing, 5) technologies and medical products, and 6) information and research. METHODS: Analysis of published and grey programme documentation, followed by 20 semi-structured interviews with representatives of programme initiators, general and financial managers, involved physicians and non-physician professionals, patients and their informal caregivers. Transcripts of all interviews were analysed by Mayring's content analysis method by two independent researchers. RESULTS: This study yielded the first comprehensive description of the programme. OnkoNetwork is a blue dahila in Central and Eastern Europe, providing timely and quality-assured healthcare services for the target patients by personalized patient path monitoring and management in a financially sustainable manner without macro-level financing of its operation. Innovative professional roles were implemented for non-physicians and physicians, and a supporting information technology application was developed. CONCLUSIONS: This paper provides a systematic description of OnkoNetwork on the six components of the SELFIE conceptual framework for integrated care in multimorbidity to understand how and why OnkoNetwork was implemented and cares (better) for its patients. Because integrated care models are designed and adjusted to their specific local needs and context, those few successful and sustainable models that were established in Central and Eastern European countries represent important benchmarks for other initiatives in this region. Experience with OnkoNetwork during its planning, implementation and operation including the description of key success factors and barriers as perceived by various stakeholder groups, may support the development of further integrated care models especially in countries with similar economic status and healthcare settings.

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.

Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

OBJECTIVES: To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. METHODS: We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. RESULTS: The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647. CONCLUSIONS: LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios.

Comprehensive Diagnostic Assessment of Health Status of Patients with Asthma or COPD: A Delphi Panel Study among Dutch Experts.

A comprehensive diagnostic assessment is needed to improve understanding of the health status of patients with chronic obstructive pulmonary disease (COPD) or asthma. Therefore, this study investigated which components and subsequent instruments should be part of a holistic assessment in secondary care. We also explored which data need to be exchanged for an adequate transfer of patients between primary and secondary care, and vice versa. A cross-sectional Web-based survey was conducted among Dutch healthcare professionals using a Delphi-like procedure; these included professionals working in primary or secondary care, medical advisors of health insurance companies and patients' representatives. The national guidelines were used as a starting point, resulting in a questionnaire addressing 55 components related to a comprehensive diagnostic assessment, covering the domains physiological impairments, symptoms, functional limitations and quality of life. Of the 151 experts and stakeholders invited, 92 (60.9%) completed the first round and 79 (52.3%) the second round; most respondents were pulmonologists. There was a high level of agreement between respondents from primary versus secondary care regarding which components should be measured during a comprehensive assessment of patients with asthma or COPD in secondary care and the instruments to measure these components. Regarding the exchange of information, upon referral, pulmonologists required little information from the general practitioners, whereas general practitioners required more extensive information after referral. An overview is provided of what should be part of a holistic assessment of health status in asthma and COPD. This information can be used as input for integrated care pathways.

e-Monitoring of Asthma Therapy to Improve Compliance in children (e-MATIC): a randomised controlled trial.

Real-time medication monitoring (RTMM) is a promising tool for improving adherence to inhaled corticosteroids (ICS), but has not been sufficiently tested in children with asthma. We aimed to study the effects of RTMM with short message service (SMS) reminders on adherence to ICS, asthma control, asthma-specific quality of life and asthma exacerbation rate; and to study the associated cost-effectiveness.In a multicentre, randomised controlled trial, children (aged 4-11 years) using ICS were recruited from five outpatient clinics and were given an RTMM device for 12 months. The intervention group also received tailored SMS reminders, sent only when a dose was at risk of omission. Outcome measures were adherence to ICS (RTMM data), asthma control (childhood asthma control test questionnaire), quality of life (paediatric asthma quality of life questionnaire) and asthma exacerbations. Costs were calculated from a healthcare and societal perspective.We included 209 children. Mean adherence was higher in the intervention group: 69.3% versus 57.3% (difference 12.0%, 95% CI 6.7%-17.7%). No differences were found for asthma control, quality of life or asthma exacerbations. Costs were higher in the intervention group, but this difference was not statistically significant.RTMM with tailored SMS reminders improved adherence to ICS, but not asthma control, quality of life or exacerbations in children using ICS for asthma.

Cardiovascular risk factor management in patients with RA compared to matched non-RA patients.

OBJECTIVE: RA is associated with a 50-60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. METHODS: A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. RESULTS: Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. CONCLUSION: There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management.

Current and Future Incidence and Costs of Osteoporosis-Related Fractures in The Netherlands: Combining Claims Data with BMD Measurements.

This study aims to estimate the incidence and costs of osteoporosis-related fractures in The Netherlands in 2010 and project them to 2030. The incidence and costs of five different types of fractures (spine, hip, upper extremity, lower extremity, wrist/distal forearm, other) were derived from claims data of all Dutch healthcare insurers. Given that fracture-codes in claims data do not indicate whether fractures are related to osteoporosis, we used a large dataset with DXA measurements to attribute fractures to osteoporosis. Future projections used four scenarios: (1) demographic, (2) demographic + annual trend in incidence rates, (3) demographic + annual trend in incidence rates + annual trend in costs, and (4) treatment. Of all registered fractures, 32 % was attributed to osteoporosis (36 % in women and 21 % in men). Over time (2010-2030) the increase in incidence of osteoporosis-related fractures was estimated to be 40 % (scenario 1); for the hip 60-79 % (scenario 1-2). In 2010, approximately €200 million was spent on treatment of osteoporosis-related fractures, most on fractures of the hip followed by wrist/distal forearm. In both men and women, the excess costs due to osteoporosis-related fractures were highest for hip fractures (€11,000-€13,000 per person), followed by spine fractures (€6000-€7000).The costs for osteoporosis-related fractures were projected to increase with 50 % from 2010 to 2030 (scenario 1); for the hip 60-148 % (scenario 1-3). Pharmacotherapeutic prevention can lead to cost-savings of €377 million in 2030 (scenario 1 and 4 combined). The projected increase in incidence and costs of osteoporosis-related fractures calls for a wider use of prevention and treatment.

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 comparison of two implantable cardiac monitors in two different settings: Reveal XT in a catheterization laboratory vs. Reveal LINQ in a procedure room.

AIMS: Implantable cardiac monitors (ICMs) are used for long-term heart rhythm monitoring, e.g. to diagnose unexplained syncope or for detection of suspected atrial and ventricular arrhythmias. The newest ICM, Reveal LINQ™ (Medtronic Inc.), is miniaturized and inserted with a specific insertion tool kit. The procedure is therefore minimally invasive and can be moved from catheterization laboratory (cath lab) to a less resource intensive setting. This study aims to assess the change in procedure costs when performed outside the cath lab. METHODS AND RESULTS: A bottom-up costing methodology was used. Data were collected from interviews with physicians, cath lab managers, and financial controllers. Hospitals in the Netherlands, France, and the UK were included in this study. The cost comparison of a Reveal XT implantation in a cath lab setting vs. a Reveal LINQ insertion outside a cath lab resulted in an estimated reduction of €662 for the UK, €682 for the Netherlands, and €781 for France. These cost savings were primarily realized through fewer staff, less equipment, and overhead costs. The net effect on savings depends on the price differential between these two technologies. The patient care pathway can be improved due to the possibility to move the procedure out of the cath lab. CONCLUSION: Inserting the miniaturized version of the ICM is simpler and faster, and the procedure can take place outside the cath lab in a less resource intensive environment. Hospitals save resources when the higher price of the Reveal LINQ does not outweigh these savings.

THE EARLY BIRD CATCHES THE WORM: EARLY COST-EFFECTIVENESS ANALYSIS OF NEW MEDICAL TESTS.

OBJECTIVES: There is little specific guidance on performing an early cost-effectiveness analysis (CEA) of medical tests. We developed a framework with general steps and applied it to two cases. METHODS: Step 1 is to narrow down the scope of analysis by defining the test's application, target population, outcome measures, and investigating current test strategies and test strategies if the new test were available. Step 2 is to collect evidence on the current test strategy. Step 3 is to develop a conceptual model of the current and new test strategies. Step 4 is to conduct the early-CEA by evaluating the potential (cost-)effectiveness of the new test in clinical practice. Step 5 involves a decision about the further development of the test. RESULTS: The first case illustrated the impact of varying the test performance on the headroom (maximum possible price) of an add-on test for patients with an intermediate-risk of having rheumatoid arthritis. Analyses showed that the headroom is particularly dependent on test performance. The second case estimated the minimum performance of a confirmatory imaging test to predict individual stroke risk. Different combinations of sensitivity and specificity were found to be cost-effective; if these combinations are attainable, the medical test developer can feel more confident about the value of further development of the test. CONCLUSIONS: A well-designed early-CEA methodology can improve the ability to develop (cost-)effective medical tests in an efficient manner. Early-CEAs should continuously integrate insights and evidence that arise through feedback, which may convince developers to return to earlier steps.

The Assessment of Burden of COPD (ABC) Scale: A Reliable and Valid Questionnaire.

The newly developed Assessment of Burden of COPD (ABC) scale is a 14-item self-administered questionnaire which measures the physical, psychological, emotional and/or social burden as experienced by patients with chronic obstructive pulmonary disease (COPD). The ABC scale is part of the ABC tool that visualises the outcomes of the questionnaire. The aim of this study was to assess the reliability and construct validity of the ABC scale. This multi-centre survey study was conducted in the practices of 19 general practitioners and 9 pulmonologists throughout the Netherlands. Next to the ABC scale, patients with COPD completed the Saint George Respiratory Questionnaire (SGRQ). Reliability analyses were performed with data from 162 cases. Cronbach's alpha was 0.91 for the total scale. Test-retest reliability, measured at a two week interval (n = 137), had an intra-class correlation coefficient of 0.92. Analyses for convergent validity were performed with data from 133 cases. Discriminant and known-groups validity was analysed with data from 162 cases. The ABC scale total score had a strong correlation with the total score of the SGRQ (r = 0.72, p < 0.001) but a weak correlation with the forced expired volume in 1 second predicted (r = -0.28, p < 0.001). Subgroups with more severe disease, defined by GOLD-stage, frequency of exacerbations, activity level and depression scored statistically significantly (p < 0.05) worse on almost all domains of the ABC scale than the less severe subgroups. The ABC scale seems a valid and reliable tool with good discriminative properties.

Cost-Effectiveness of Disease Management Programs for Cardiovascular Risk and COPD in The Netherlands.

BACKGROUND: Disease management programs (DMPs) for cardiovascular risk (CVR) and chronic obstructive pulmonary disease (COPD) are increasingly implemented in The Netherlands to improve care and patient's health behavior. OBJECTIVE: The aim of this study was to provide evidence about the (cost-) effectiveness of Dutch DMPs as implemented in daily practice. METHODS: We compared the physical activity, smoking status, quality-adjusted life-years, and yearly costs per patient between the most and the least comprehensive DMPs in four disease categories: primary CVR prevention, secondary CVR prevention, both types of CVR prevention, and COPD (N = 1034). Propensity score matching increased comparability between DMPs. A 2-year cost-utility analysis was performed from the health care and societal perspectives. Sensitivity analysis was performed to estimate the impact of DMP development and implementation costs on cost-effectiveness. RESULTS: Patients in the most comprehensive DMPs increased their physical activity more (except for primary CVR prevention) and had higher smoking cessation rates. The incremental QALYs ranged from -0.032 to 0.038 across all diseases. From a societal perspective, the most comprehensive DMPs decreased costs in primary CVR prevention (certainty 57%), secondary CVR prevention (certainty 88%), and both types of CVR prevention (certainty 98%). Moreover, the implementation of comprehensive DMPs led to QALY gains in secondary CVR prevention (certainty 92%) and COPD (certainty 69%). CONCLUSIONS: The most comprehensive DMPs for CVR and COPD have the potential to be cost saving, effective, or cost-effective compared with the least comprehensive DMPs. The challenge for Dutch stakeholders is to find the optimal mixture of interventions that is most suited for each target group.

Mapping the clinical chronic obstructive pulmonary disease questionnaire onto generic preference-based EQ-5D values.

OBJECTIVES: To develop a model to predict EuroQol five-dimensional questionnaire (EQ-5D) values from clinical chronic obstructive pulmonary disease (COPD) questionnaire (CCQ) scores. METHODS: We used data from three clinical trials (the Randomized Clinical Trial on Effectiveness of Integrated COPD Management in Primary Care [RECODE], the Assessment Of Going Home Under Early Assisted Discharge [GO-AHEAD], and the Health Status Guided COPD Care [MARCH]). Data were randomly split into an estimation sample and a validation sample. The conceptual similarity between patient-reported CCQ and preference-based EQ-5D scores was assessed using correlation and principal-component analysis. Different types of models were estimated with increasing complexity. We selected the final models on the basis of mean absolute error and root mean square error when comparing predicted and observed values from the same population (internal validity) and from different trial populations (external validity). We also developed models for different country-specific EQ-5D value sets. RESULTS: The principal-component analysis showed that the CCQ domains functional state and mental state are associated with four dimensions of the EQ-5D. The EQ-5D dimension pain/discomfort formed a separate construct on which no CCQ item loaded. The mean observed EQ-5D values were not significantly different from the mean predicted EQ-5D values in internal validation samples but did significantly differ in external validation samples. The models underestimated EQ-5D values in milder health states and overestimated them in more severe health states. The predictive ability of the models was similar across different EQ-5D value sets. CONCLUSIONS: The models can predict mean EQ-5D values that are similar to observed mean values in a similar population. The overestimating/underestimating of the low/high EQ-5D values, however, limits its use in Markov models. Therefore, mapping should be used cautiously.

Tiotropium versus salmeterol for the prevention of exacerbations of COPD.

BACKGROUND: Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a ß(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the ß(2)-agonist salmeterol in preventing exacerbations of COPD. METHODS: In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 µg of tiotropium once daily with that of 50 µg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. RESULTS: A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group. CONCLUSIONS: These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).

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.

Should I stay or should I go home? A latent class analysis of a discrete choice experiment on hospital-at-home.

OBJECTIVES: This study aimed 1) to quantify the strength of patient preferences for different aspects of early assisted discharge in The Netherlands for patients who were admitted with a chronic obstructive pulmonary disease exacerbation and 2) to illustrate the benefits of latent class modeling of discrete choice data. This technique is rarely used in health economics. METHODS: Respondents made multiple choices between hospital treatment as usual (7 days) and two combinations of hospital admission (3 days) followed by treatment at home. The latter was described by a set of attributes. Hospital treatment was constant across choice sets. Respondents were patients with chronic obstructive pulmonary disease in a randomized controlled trial investigating the cost-effectiveness of early assisted discharge and their informal caregivers. The data were analyzed using mixed logit, generalized multinomial logit, and latent-class conditional logit regression. These methods allow for heterogeneous preferences across groups, but in different ways. RESULTS: Twenty-five percent of the respondents opted for hospital treatment regardless of the description of the early assisted discharge program, and 46% never opted for the hospital. The best model contained four latent classes of respondents, defined by different preferences for the hospital and caregiver burden. Preferences for other attributes were constant across classes. Attributes with the strongest effect on choices were the burden on informal caregivers and co-payments. Except for the number of visits, all attributes had a significant effect on choices in the expected direction. CONCLUSIONS: Considerable segments of respondents had fixed preferences for either treatment option. Applying latent class analysis was essential in quantifying preferences for attributes of early assisted discharge.