Mp Rutten-van Mölken

Outcomes for COPD pharmacological trials: from lung function to biomarkers

The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

One-year cost-effectiveness of tiotropium versus ipratropium to treat chronic obstructive pulmonary disease

The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new, once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). This prospective cost-effectiveness analysis was performed alongside two 1‐yr randomised, double-blind clinical trials in the Netherlands and Belgium. Patients had a diagnosis of COPD and a forced expiratory volume in one second (FEV1) ≤65% predicted normal. Patients were randomised to tiotropium (18 µg once daily) or ipratropium (2 puffs of 20 µg administered four times daily) in a ratio of 2:1. The mean number of exacerbations was reduced from 1.01 in the ipratropium group (n=175) to 0.74 in the tiotropium group (n=344). The percentages of patients with a relevant improvement on the St. Georges Respiratory Questionnaire (SGRQ) were 34.6% and 51.2% respectively. Compared to ipratropium, the number of hospital admissions, hospital days and unscheduled visits to healthcare providers was reduced by 46%, 42% and 36% respectively. Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 (sem 160) in the tiotropium group and 1,541 (SEM 163) in the ipratropium group (difference 180). Incremental cost-effectiveness ratios were 667 per exacerbation avoided and 1084 per patient with a relevant improvement on the SGRQ. Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 per patient per year.

Short- and long-term efficacy of a community-based COPD management programme in less advanced COPD: a randomised controlled trial

Background: The effectiveness of pulmonary rehabilitation in advanced COPD is well established, but few data are available in less advanced disease. Methods: In a 2 year randomised controlled trial, 199 patients with an average moderate airflow obstruction but impaired exercise capacity (mean (SD) forced expiratory volume in 1 s (FEV1) 60 (16)%, peak work load (Wmax) <70%) were randomised to the INTERdisciplinary COMmunity-based COPD management programme (INTERCOM) or usual care. Intervention consisted of 4 months multidisciplinary rehabilitation followed by a 20-month maintenance phase. Outcomes (4, 12, 24 months): health-related quality of life (St George’s Respiratory Questionnaire (SGRQ)), exacerbation frequency, MRC dyspnoea score, cycle endurance time (CET), 6-minute walking distance (6MWD), skeletal muscle strength and patients’ and caregivers’ perceived effectiveness. Results: Between-group comparison after 4 months revealed the following mean (SE) significant differences in favour of INTERCOM: SGRQ total score 4.06 (1.39), p = 0.004; activity and impact subscores, p<0.01; MRC score 0.33 (0.13), p = 0.01; Wmax 6.0 (2.3) Watt, p = 0.02; CET 221 (104) s, p = 0.04; 6MWD 13 (6) m, p = 0.02; hand grip force 4.3 (1.5) lb, p<0.01; and fat-free mass index 0.34 (0.13) kg/m2, p = 0.01. Between-group differences over 2 years were as follows: SGRQ 2.60 (1.3), p = 0.04; MRC score 0.21 (0.10), p = 0.048; CET 253 (104) s, p = 0.0156; 6MWD 18 (8) m, p = 0.0155. Exacerbation frequency was not different (RR 1.29 (95% CI 0.89 to 1.87)). Patients’ and caregivers’ perceived effectiveness significantly favoured the INTERCOM programme (p<0.01). Conclusions: This study shows that a multidisciplinary community-based disease management programme is also effective in patients with COPD with exercise impairment but less advanced airflow obstruction. Trial registration number: NCT00840892

Association between health-related quality of life and consultation for respiratory symptoms: results from the DIMCA programme

In general practice, diagnosis of chronic obstructive pulmonary disease (COPD) is hampered by underpresentation. A substantial proportion of subjects experiencing respiratory complaints do not consult their general practitioner (GP). In this study, the relationship between disease-specific quality of life and presentation of respiratory symptoms to a GP is investigated. A random sample from the general population (undiagnosed subjects) was screened for symptoms and objective signs of COPD (n=1,155). The lung function of subjects with symptoms of COPD was monitored for 6 months. During this period, 48 new COPD patients with a persistently reduced lung function (forced expiratory volume in one second (FEV1) less than or equal to the predicted value minus 2 SD) were detected. A disease-specific quality-of-life questionnaire (chronic respiratory questionnaire (CRQ)) was administered and clinical and GP consultation data were collected. Multivariate analysis showed that quality-of-life impairments due to dyspnoea and fatigue and variability in lung function (bronchial hyperresponsiveness, reversibility and peak expiratory flow rate variability) were related to medical consultation. Only 31% of the newly detected patients reported that they had ever visited their GP for respiratory complaints. A similarly low percentage was found in the rest of the sample (26%). It is concluded that the mere presence of respiratory symptoms or a (gradually) reduced lung function is insufficient reason for patients to seek medical help. Subjects are more likely to consult their general practitioner once their quality of everyday life is affected or they experience variability in lung function.

A dynamic population model of disease progression in COPD

To contribute to evidence-based policy making, a dynamic Dutch population model of chronic obstructive pulmonary disease (COPD) progression was developed. The model projects incidence, prevalence, mortality, progression and costs of diagnosed COPD by the Global Initiative for Chronic Obstructive Lung Disease-severity stage for 2000–2025, taking into account population dynamics and changes in smoking prevalence over time. It was estimated that of all diagnosed COPD patients in 2000, 27% had mild, 55% moderate, 15% severe and 3% very severe COPD. The severity distribution of COPD incidence was computed to be 40% mild, 55% moderate, 4% severe and 0.1% very severe COPD. Disease progression was modelled as decline in forced expiratory voume in one second (FEV1) % predicted depending on sex, age, smoking and FEV1 % pred. The relative mortality risk of a 10-unit decrease in FEV1 % pred was estimated at 1.2. Projections of current practice were compared with projections assuming that each year 25% of all COPD patients receive either minimal smoking cessation counselling or intensive counselling plus bupropion. In the projections of current practice, prevalence rates between 2000–2025 changed from 5.1 to 11 per 1,000 inhabitants for mild, 11 to 14 per 1,000 for moderate, 3.0 to 3.9 per 1,000 for severe and from 0.5 to 1.3 per 1,000 for very severe COPD. Costs per inhabitant increased from \#8364;1.40 to 3.10 for mild, \#8364;6.50 to 9.00 for moderate, \#8364;6.20 to 8.50 for severe and from \#8364;3.40 to 9.40 for very severe COPD (price level 2000). Both smoking cessation scenarios were cost-effective with minimal counselling generating net savings. In conclusion, the chronic obstructive pulmonary disease progression model is a useful instrument to give detailed information about the future burden of chronic obstructive pulmonary disease and to assess the long-term impact of interventions on this burden.

Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries

Objective: To assess direct costs associated with ankylosing spondylitis (AS). To determine which variables, including country, predict costs. Methods: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year observational study and filled in bimonthly economic questionnaires. Disease related healthcare resource use was measured and direct costs were calculated from a societal perspective (true cost estimates) and from a financial perspective (country-specific tariffs). Predictors of costs were assessed using Cox’s regression analysis. Results: 209 patients provided sufficient data for cost analysis. Mean annual societal direct costs for each patient were €2640, of which 82% were direct healthcare costs. In univariate analysis costs were higher in the Netherlands than in Belgium, but this difference disappeared after adjusting for baseline differences in patients’ characteristics among countries. Longer disease duration, lower education, worse physical function, and higher disease activity were predictors of costs. Mean annual direct costs from a financial perspective were €2122, €1402, and €941 per patient in the Netherlands, France, and Belgium, respectively. For each country, costs from a financial perspective were significantly lower than costs from a societal perspective. Conclusion: Direct costs for AS are substantial in three European countries but not significantly different after adjusting for baseline characteristics among countries. Worse physical function and higher disease activity are important determinants of costs, suggesting better disease control might reduce the costs of AS. The difference in costs from a societal and financial perspective emphasises the importance of an economic analysis.

Cost Effectiveness of Inhaled Corticosteroid plus Bronchodilator Therapy versus Bronchodilator Monotherapy in Children with Asthma

SummaryIn an incremental cost-effectiveness analysis. combined inhaled β2-receptor agonist plus inhaled coricosteroid therapy (BA + CS) was compared with inhaled β2-agonist plus placebo (BA + PL) in 116 asthmatic children aged 7 to 16 years. Clinical data have been reported previously. To account for the selective withdrawal rate due to pulmonary problems that occurred in the group receiving BA + PL costs were calculated using 2 approaches: (1) the cumulative cost approach and (2) the patient-year approach.Besides improvements in forced expiratory volume in 1 second (FEV1) and airway responsiveness expressed as the provocative dose of histamine required to give a 20% fall in FEV1 (PD20). the frequency of asthma symptoms and school absenteeism were significantly reduced in the BA + CS group. Annual drug acquisition costs for the group receiving BA + CS were NLG480 higher than for the BA + PL group (

Costs of ankylosing spondylitis in three European countries: the patient’s perspective

US1 = NLG2.12, 1989 prices). Based on conservative calculations using the cumulative cost approach, annual savings due to reduced healthcare utilisation. excluding the cost of study drugs, by the group receiving BA + CS compared with BA + PL were estimated to be about NLG273 per patient. The incremental cost effectiveness of BA + CS was estimated to be about NLG17S per 10% increase in FEV1, or somewhat less than NLG10 per symptom-free day gained. The patient-year approach estimated savings due to conicosteroids of about 43% of the costs of BA + PL (95% confidence intervals, 21 to 58%). Savings were larger when the indirect costs that a family incurred during school absenteeism were considered.Addition of an inhaled corticosteroid 10 an inhaled β2-receptor agonist is a cost-effective treatment option that could even result in net healthcare savings.

Case fatality of COPD exacerbations: A meta-analysis and statistical modelling approach

Objective: To assess a patient’s out of pocket costs, income loss, time consumption, and quality of life (QoL) due to ankylosing spondylitis (AS) in three European countries and to assess variables predicting these outcomes. Methods: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year study. Health resource use, days absent from work, time lost, and quality of life (EuroQol) were assessed by bimonthly questionnaires. AS related healthcare and non-healthcare expenditure and income loss were calculated taking into account country-specific regulations. Predictors of costs, time consumption, and QoL were analysed by Cox’s regression. Results: 209 patients provided data for cost analysis. Average annual healthcare and non-healthcare expenditure was €431 per patient and average annual income loss was €1371 per patient. Healthcare costs were highest for Belgian and lowest for French patients, while non-healthcare costs were highest for Dutch patients. A patient’s total costs were associated with higher age and worse physical function. On average, patients with AS needed 75 minutes additional time a day because of AS. Worse physical function and higher disease activity predicted time consumption. After adjusting for baseline confounders, QoL was worse in Belgian and French than in Dutch patients. Peripheral arthritis, worse physical function, higher disease activity, and loss of income contributed to worse QoL. Conclusion: AS is time consuming and associated with substantial out of pocket costs. Belgian patients incur the highest healthcare payments. Poor physical function increases patient’s costs and time consumption. Loss of income is associated with lower QoL.

Is INTERdisciplinary COMmunity-based COPD management (INTERCOM) cost-effective?

The aim of our study was to estimate the case fatality of a severe exacerbation from long-term survival data presented in the literature. A literature search identified studies reporting ≥1.5 yr survival after a severe chronic obstructive pulmonary disease (COPD) exacerbation resulting in hospitalisation. The survival curve of each study was divided into a critical and a stable period. Mortality during the stable period was then estimated by extrapolating the survival curve during the stable period back to the time of exacerbation onset. Case fatality was defined as the excess mortality that results from an exacerbation and was calculated as 1 minus the (backwardly) extrapolated survival during the stable period at the time of exacerbation onset. The 95% confidence intervals (CI) of the estimated case fatalities were obtained by bootstrapping. A random effect model was used to combine all estimates into a weighted average with 95% CI. The meta-analysis based on six studies that fulfilled the inclusion criteria resulted in a weighted average case-fatality rate of 15.6% (95% CI 10.9–20.3), ranging from 11.4% to 19.0% for the individual studies. A severe COPD exacerbation requiring hospitalisation not only results in higher mortality risks during hospitalisation, but also in the time-period after discharge and contributes substantially to total COPD mortality.