Martine Hoogendoorn

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

Long-term effectiveness and cost-effectiveness of smoking cessation interventions in patients with COPD

Background The aim of this study was to estimate the long-term (cost-) effectiveness of smoking cessation interventions for patients with chronic obstructive pulmonary disease (COPD). Methods A systematic review was performed of randomised controlled trials on smoking cessation interventions in patients with COPD reporting 12-month biochemical validated abstinence rates. The different interventions were grouped into four categories: usual care, minimal counselling, intensive counselling and intensive counselling + pharmacotherapy (‘pharmacotherapy’). For each category the average 12-month continuous abstinence rate and intervention costs were estimated. A dynamic population model for COPD was used to project the long-term (cost-) effectiveness (25 years) of 1-year implementation of the interventions for 50% of the patients with COPD who smoked compared with usual care. Uncertainty and one-way sensitivity analyses were performed for variations in the calculation of the abstinence rates, the type of projection, intervention costs and discount rates. Results Nine studies were selected. The average 12-month continuous abstinence rates were estimated to be 1.4% for usual care, 2.6% for minimal counselling, 6.0% for intensive counselling and 12.3% for pharmacotherapy. Compared with usual care, the costs per quality-adjusted life year (QALY) gained for minimal counselling, intensive counselling and pharmacotherapy were €16 900, €8200 and €2400, respectively. The results were most sensitive to variations in the estimation of the abstinence rates and discount rates. Conclusion Compared with usual care, intensive counselling and pharmacotherapy resulted in low costs per QALY gained with ratios comparable to results for smoking cessation in the general population. Compared with intensive counselling, pharmacotherapy was cost saving and dominated the other interventions.

Efficacy and Costs of Nutritional Rehabilitation in Muscle-Wasted Patients With Chronic Obstructive Pulmonary Disease in a Community-Based Setting: A Prespecified Subgroup Analysis of the INTERCOM Trial

RATIONALE Limited data are available on effectiveness and costs of nutritional rehabilitation for patients with COPD in community care. METHODS In a 2-year RCT, 199 COPD patients (FEV(1)%pred. 60% [SD 16%]) and impaired exercise capacity were randomized to the interdisciplinary community-based COPD management program (INTERCOM) or usual care (UC). A prescheduled subgroup analysis was performed on 39 of 199 patients who were muscle wasted and received UC or nutritional therapy in combination with exercise training. Body composition, muscle strength, and exercise capacity were assessed at baseline and 4, 12, and 24 months. RESULTS Between group differences after 4 months in favor of the intervention group: fat free mass index (FFMI 0.9 kg/m(2) [SE = 0.2, P < .001]), body mass index (BMI 1.0 kg/m(2) [SE = 0.4, P = .009]), maximum inspiratory mouth pressure (Pimax 1.4 kPa [SE = 0.5, P = .011]), quadriceps average power (QAP 13.1 Watt [SE=5.8, P = .036]), 6-minute walking distance (6MWD 27 m, [SE = 11.5, P = .028]), cycle endurance time (CET 525 seconds [SE=195, P = .013]), and peak exercise capacity (Wmax 12 Watt [SE = 5, P = .036]). Between group difference over 24 months in favor of the intervention group: Pimax 1.7 kPa (SE = 0.53, P = .004), QAP 19 Watt (SE = 6, P = .005), 6MWD 57 (SE = 19, P = .006), and CET 485 seconds (SE = 159, P = .006). After 4 months total costs were Euro 1501 higher in the intervention group than in the UC group (P < .05), but not significantly different after 24 months. Hospital admission costs were significantly lower in the intervention group -euro 4724 (95% CI -7704, -1734). CONCLUSION This study in muscle-wasted COPD patients with moderate airflow obstruction shows a prolonged positive response to nutritional support integrated in a community-based rehabilitation program.

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

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.

Cost-effectiveness of varenicline compared with bupropion, NRT, and nortriptyline for smoking cessation in the Netherlands

ABSTRACT Objective: To examine the cost-effectiveness of varenicline, a new pharmacotherapy to support smoking cessation, compared with the currently available pharmacologic alternatives in the Netherlands. Methods: The BENESCO-model was used to estimate the long-term health and economic benefits of smoking cessation for a cohort of smokers making a one-time quit attempt. The cohort represented the population of Dutch smokers with respect to gender, age, and prevalence of the smoking-related diseases included in the model: COPD, lung cancer, CHD, stroke, and asthma exacerbations. The model compared the cumulative incidence of smoking-related diseases, (quality-adjusted) life years, intervention costs, and direct medical costs between the cohort treated with varenicline and the same cohort either untreated (unaided cessation) or treated with bupropion, nortriptyline or NRT. The time horizon was lifetime. Future costs were discounted at 4%, health outcomes at 1.5%. Results: The cost of varenicline per additional quitter ranged from 1030 Euro compared with NRT to 4270 Euro compared with nortriptyline. When including the savings due to the reduction in incidence of smoking-related diseases, varenicline generated net savings compared with bupropion and NRT. Compared with nortriptyline and unaided cessation, varenicline was estimated to cost 1650 Euro/QALY and 320 Euro/QALY gained, respectively. At a willingness-to-pay as low as 5000/QALY gained, the probability that varenicline was cost-effective was more than 80% compared to bupropion, NRT, and unaided cessation and about 60% compared to nortriptyline. Conclusion: Treatment with varenicline for smoking cessation is cost-effective compared with nortriptyline and unaided cessation and even cost-saving compared with bupropion and NRT.

Association between lung function and exacerbation frequency in patients with COPD.

Purpose: To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD. Methods: We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo. Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization. The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects. The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage. Results: Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations. Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46–1.49) for mild, 1.17 (0.93–1.50) for moderate, 1.61 (1.51–1.74) for severe, and 2.10 (1.51–2.94) for very severe COPD. Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67–2.07), 1.44 (1.14–1.87), 1.76 (1.70–1.88), and 2.09 (1.57–2.82), respectively. For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02–0.56), 0.16 (0.07–0.33), 0.22 (0.20–0.23), and 0.28 (0.14–0.63), respectively. Study duration or type of study (cohort versus trial) did not significantly affect the outcomes. Conclusion: This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes.

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.

Developing and Applying a Stochastic Dynamic Population Model for Chronic Obstructive Pulmonary Disease

OBJECTIVES To develop a stochastic population model of disease progression in chronic obstructive pulmonary disease (COPD) that includes the effects of COPD exacerbations on health-related quality of life, costs, disease progression, and mortality and can be used to assess the effects of a wide range of interventions. METHODS The model is a multistate Markov model with time varying transition rates specified by age, sex, smoking status, COPD disease severity, and/or exacerbation type. The model simulates annual changes in COPD prevalence due to COPD incidence, exacerbations, disease progression (annual decline in the forced expiratory volume in 1 second as percentage of the predicted value), and mortality. The main outcome variables are quality-adjusted life years, total exacerbations, and COPD-related health care costs. Exacerbation-related input parameters were based on quantitative meta-analysis. All important model parameters are entered into the model as probability distributions. To illustrate the potential use of the model, costs and effects were calculated for 3-year implementation of three different COPD interventions, one pharmacologic, one on smoking cessation, and one on pulmonary rehabilitation using a time horizon of 10 years for reporting outcomes. RESULTS Compared with minimal treatment the cost/quality-adjusted life year was €8,300 for the pharmacologic intervention, €10,800 for the smoking cessation therapy, €8,700 for the combination of the pharmacologic intervention and the smoking cessation therapy, and €17,200 for the pulmonary rehabilitation program. The probability of the interventions to be cost-effective at a ceiling ratio of €20,000 varied from 58% to 100%. CONCLUSIONS The COPD model provides policy makers with information about the long-term costs and effects of interventions over the entire chain of care, from primary prevention to care for very severe COPD and includes uncertainty around the outcomes.

Self-report versus care provider registration of healthcare utilization: impact on cost and cost-utility

OBJECTIVES This study aims to compare the impact of two different sources of resource use, self-report versus care provider registrations, on cost and cost utility. METHODS Data were gathered for a cost-effectiveness study performed alongside a 2-year randomized controlled trial evaluating the effect of an INTERdisciplinary COMmunity-based management program (INTERCOM) for patients with chronic obstructive pulmonary disease (COPD). The program was offered by physiotherapists, dieticians and respiratory nurses. During the 2-year period, patients reported all resource use in a cost booklet. In addition, data on hospital admissions and outpatient visits, visits to the physiotherapist, dietician or respiratory nurse, diet nutrition, and outpatient medication were obtained from administrative records. The cost per quality-adjusted life-year (QALY) was calculated in two ways, using data from the cost booklet or registrations. RESULTS In total, 175 patients were included in the study. Agreement between self-report and registrations was almost perfect for hospitalizations (rho = 0.93) and physiotherapist visits (rho = 0.86), but above 0.55, moderate, for all other types of care. The total cost difference between the registrations and the cost booklet was 464 euros with the highest difference for hospitalizations 386 euro. Based on the cost booklet the cost difference between the treatment group and usual care was 2,444 euros (95 percent confidence interval [CI], -819 to 5,950), which resulted in a cost-utility of 29,100 euro/QALY. For the registrations, the results were 2,498 euros (95 percent CI, -88 to 6,084) and 29,390 euro/QALY, respectively. CONCLUSIONS This study showed that the use of self-reported data or data from registrations effected within-group costs, but not between-group costs or the cost utility.

Cost-effectiveness of tiotropium versus salmeterol: the POET-COPD trial

The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropium versus salmeterol followed by a 5-yr model-based CEA. The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs). 1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were €126 (95% uncertainty interval (UI) €55–195) and €170 (95% UI €77–260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010–0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of €87 (95% UI €19–157). The incremental cost-effectiveness ratio was €1,961 per exacerbation avoided from the SHI perspective and €2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were €3,488 from the SHI perspective and €8,141 from the societal perspective. Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds.