Comparison of EQ-5D and SF-6D utilities in Pompe disease.

PURPOSE: Comparative studies between Euroqol-5D (EQ-5D) and ShortForm 6D (SF-6D) utilities have been performed for a number of diseases, but not yet for orphan diseases. Pompe disease is an orphan disease with a prevalence of <5/10,000, characterized by impaired ambulatory and pulmonary functioning. We compared the psychometric properties of EQ-5D and SF-6D in patients with this disease and assessed their convergent validity, discriminative ability and sensitivity to change. METHODS: EQ-5D utilities and SF-6D utilities were computed using the UK value set. Dimensions and utilities of the two instruments were compared by correlation coefficients and descriptive statistics. We assessed whether EQ-5D and SF-6D were able to discriminate between different levels of severity and examined sensitivity to change for patients with multiple observations. RESULTS: Correlations between theoretically related dimensions of the EQ-5D and SF-6D were highly significant and were moderate to strong (range rho = 0.409-0.564). Utility values derived from the two instruments were similar (mean EQ-5D = 0.670; mean SF-6D = 0.699) and correlated strongly (rho = 0.591). Discriminative properties were somewhat better for EQ-5D; mean changes and effect sizes were better for SF-6D. CONCLUSIONS: Overall, we conclude that both instruments appear to be equally appropriate with respect to assessing utilities in Pompe disease, but neither of them performed excellently. The descriptive system of the SF-6D describes health states for Pompe disease more accurately. EQ-5D showed better discriminative properties. The SF-6D performed better with respect to sensitivity to change.

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.

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 (FEV(1)) 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/m(2), 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.

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

The study aimed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease (COPD) management in patients with COPD. We conducted a cost-effectiveness analysis alongside a 2-yr randomised controlled trial, in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care. The INTERCOM programme consisted of exercise training, education, nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses. All-cause resource use during 2 yrs was obtained by self-report and from hospital and pharmacy records. Health outcomes were the St George's Respiratory Questionnaire (SGRQ), exacerbations and quality-adjusted life years (QALYs). The INTERCOM group had 30% (95% CI 3-56%) more patients with a clinically relevant improvement in SGRQ total score, 0.08 (95% CI -0.01-0.18) more QALYs per patient, but a higher mean number of exacerbations, 0.84 (95% CI -0.07-1.78). Mean total 2-yr costs were euro2,751 (95% CI -euro632-euro6,372) higher for INTERCOM than for usual care, which resulted in an incremental cost-effectiveness ratio of euro9,078 per additional patient with a relevant improvement in SGRQ or euro32,425 per QALY. INTERCOM significantly improved disease-specific quality of life, but did not affect exacerbation rate. The cost per QALY ratio was moderate, but within the range of that generally considered to be acceptable.

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.

[Projections of future resource use and the costs of asthma and COPD in the Netherlands]. / Toekomstprojecties van het zorggebruik en de kosten van astma en COPD in Nederland.

OBJECTIVE: To determine the health-care utilisation and associated costs for asthma and chronic obstructive pulmonary disease (COPD) in the Netherlands for the year 2000 and to estimate future costs by means of projections. DESIGN: Descriptive and explorative. METHOD: The costs were based on data regarding resource use in 2000 obtained from representative national registries and surveys. The costs were specified by gender and age category and for COPD also by severity. Three projections for the costs of asthma and COPD were made by means of prevalence projections: first assuming constant resource use and constant prices, second assuming asthma- and COPD-specific trends in the costs for hospital care (asthma, -4.7% and COPD, -4.1% per year) and medication (+4.9% per year), and third by adding general trends for the remaining types of care. RESULTS: Total costs for the year 2000 for asthma (452,000 patients) and COPD (306,000 patients) were estimated to be 141 and 280 million Euros, amounting to 313 en 915 Euros per patient or 9 and 18 Euros per inhabitant, respectively. Projections of total prevalence for the year 2025 varied between 478,000 and 568,000 patients for asthma and between 479,000 and 494,000 patients for COPD. Assuming constant resource use and prices, the costs in 2025 were projected to increase to amounts between 167 and 181 million Euros for asthma and 443 and 495 million Euros for COPD. Projections including the estimated trends in costs for hospital care, medication and the costs for other types of care predicted a sharper increase. CONCLUSION: Costs for asthma and COPD together (421 million Euros) amounted to 1.3% of the total Dutch health-care budget in 2000. Almost 70% of these costs were for COPD. Projections for 2025 showed that the costs for COPD will increase more than the costs for asthma.

[Effectiveness of the Assessment of Burden of COPD tool: a cluster-randomised controlled trial]. / Effectiviteit van de 'Ziektelastmeter COPD'.

OBJECTIVE: Assessment of the effectiveness of the Assessment of Burden of COPD (ABC) tool on disease-specific quality of life in patients with Chronic Obstructive Pulmonary Disease (COPD). DESIGN: Cluster-randomised controlled trial. METHOD: This concerned a trial in 39 Dutch primary care practices and 17 hospitals, involving 357 patients with COPD (postbronchodilator FEV1/FVC ratio < 0.7) aged ≥ 40 years. Healthcare providers were randomized to an intervention or control group. Patients in the intervention group were treated with the ABC tool. This innovative tool consists of a short validated questionnaire and a number of objective parameters, which collectively give a visual overview of the combined integral health; the tool subsequently produces an individualized treatment plan by means of a treatment algorithm. Patients in the control group received usual care. The primary outcome measure was the proportion of patients with a clinically relevant improvement in disease-specific quality of life measured, as measured by means of the St. George's Respiratory Questionnaire (SGRQ) score, between baseline and 18 months follow-up. Secondary outcomes included the SGRQ total score and the Patient Assessment of Chronic Illness Care (PACIC) score. RESULTS: At 18-month follow-up, a significant and clinically relevant improvement in the SGRQ score was seen in 34% of the patients (N=49) in the intervention group, and in the control group this figure was 22% (N=33). This difference between the two groups was significant (OR 1.85, 95% CI 1.08 to 3.16). Patients in the intervention group experienced a higher quality of care than patients in the control group (0.32 points difference in PACIC, 95% CI 0.14 to 0.50). CONCLUSION: Use of the ABC tool increases the disease-specific quality of life and the quality of care for COPD patients; it may therefore offer a valuable contribution to improvements in the daily care of COPD. Replication of this study in other (non-Dutch) health-care settings is recommended.

Costs and effects of new professional roles: Evidence from a literature review.

One way in which governments are seeking to improve the efficiency of the health care sector is by redesigning health services to contain labour costs. The aim of this study was to investigate the impact of new professional roles on a wide range of health service outcomes and costs. A systematic literature review was performed by searching in different databases for evaluation papers of new professional roles (published 1985-2013). The PRISMA checklist was used to conduct and report the systematic literature review and the EPHPP-Quality Assessment Tool to assess the quality of the studies. Forty-one studies of specialist nurses (SNs) and advanced nurse practitioners (ANPs) were selected for data extraction and analysis. The 25 SN studies evaluated most often quality of life (10 studies), clinical outcomes (8), and costs (8). Significant advantages were seen most frequently regarding health care utilization (in 3 of 3 studies), patient information (5 of 6), and patient satisfaction (4 of 6). The 16 ANP studies evaluated most often patient satisfaction (8), clinical outcomes (5), and costs (5). Significant advantages were seen most frequently regarding clinical outcomes (5 of 5), patient information (3 of 4), and patient satisfaction (5 of 8). Promoting new professional roles may help improve health care delivery and possibly contain costs. Exploring the optimal skill-mix deserves further attention from health care professionals, researchers and policy makers.

Cost-Effectiveness of Including a Nurse Specialist in the Treatment of Urinary Incontinence in Primary Care in the Netherlands.

OBJECTIVE: Incontinence is an important health problem. Effectively treating incontinence could lead to important health gains in patients and caregivers. Management of incontinence is currently suboptimal, especially in elderly patients. To optimise the provision of incontinence care a global optimum continence service specification (OCSS) was developed. The current study evaluates the costs and effects of implementing this OCSS for community-dwelling patients older than 65 years with four or more chronic diseases in the Netherlands. METHOD: A decision analytic model was developed comparing the current care pathway for urinary incontinence in the Netherlands with the pathway as described in the OCSS. The new care strategy was operationalised as the appointment of a continence nurse specialist (NS) located with the general practitioner (GP). This was assumed to increase case detection and to include initial assessment and treatment by the NS. The analysis used a societal perspective, including medical costs, containment products (out-of-pocket and paid by insurer), home care, informal care, and implementation costs. RESULTS: With the new care strategy a QALY gain of 0.005 per patient is achieved while saving €402 per patient over a 3 year period from a societal perspective. In interpreting these findings it is important to realise that many patients are undetected, even in the new care situation (36%), or receive care for containment only. In both of these groups no health gains were achieved. CONCLUSION: Implementing the OCSS in the Netherlands by locating a NS in the GP practice is likely to reduce incontinence, improve quality of life, and reduce costs. Furthermore, the study also highlighted that various areas of the continence care process lack data, which would be valuable to collect through the introduction of the NS in a study setting.

Patient utilities in chronic musculoskeletal pain: how useful is the standard gamble method?

The main goal of current pain management approaches is to increase the patients' quality of life by improving pain coping skills and by reducing the levels of disability in daily life, often despite persistent pain. Direct measurement of quality of life is of crucial importance in economic evaluation research, in which not only is the estimation of financial costs and benefits included, but so is the evaluation of costs and benefits in terms of changes in health states. The purpose of this study is to compare the psychometric qualities of two instruments for assessing patients' utilities, the rating scale (RS) and the standard gamble (SG). Such instruments are designed for their application in economic evaluation research, but have seldomly been used in chronic pain trials. Both methods provide a single measure between 0 and 1. The relationship between these utility measures and descriptive and domain-specific quality of life measures was examined in 133 fibromyalgia patients and 148 patients with chronic non-specific low back pain. Mean utility score at baseline was 0.43 with the RS and 0.78 for the SG. The correlation between both methods was found to be poor (r = 0.21). Both measures appeared to be fairly stable in a 2-week test-retest period (intra class correlation coefficient (ICC) = 0.74 and 0.77). Scores on the description of patient's own health on six domains, global assessment of change and domain specific measures correlated moderately with the RS scores and low with the SG. Multiple regression analyses demonstrated that 32% of the variance in RS values and only 13% of the variance in SG utilities could be explained by domain-specific measures. These results suggest an acceptable construct validity for the RS but insufficient construct validity for the SG. Valuations of ones own health appear only partially to be related to the assessment of the pain-specific measures and measures of distress. It can be concluded that the RS and domain-specific measures assess partly different, but nevertheless complementary aspects of health-related quality of life. It is therefore recommended to include in economic evaluation studies both domain-specific measures and valuation measures. Finally, in chronic musculoskeletal pain patients, RS scores were found to be more responsive in detecting significant changes in preferences than SG scores. For use in patients with chronic musculoskeletal pain, the RS is preferred to the SG for establishing accurate decisions about the impact of new interventions on their health outcomes.

The cost diary: a method to measure direct and indirect costs in cost-effectiveness research.

From a societal perspective long-term clinical trials or follow-up studies should preferably not only include an evaluation of the health effect for the patient, but also an economic evaluation. In order to yield comprehensive medical and nonmedical resource use data, we at least partly depend on respondents' recall for collecting these costing data. A patient cost diary was developed in order to estimate total resource use, expenses, and lost production due to illness and treatment. We applied the cost diary in two randomized clinical trials evaluating the cost-effectiveness of behavioral rehabilitation in 205 fibromyalgia and chronic low back pain patients. The use of the diary was evaluated, studying the feasibility, the influence of the period of data collection on the results, and some aspects of validity. Eighty-five percent of the patients completed at least one diary and in total 68% of the diaries were returned. Although the results for the three alternative periods of data collection (keeping the diary 1 week every month, 2 weeks every 2 months, or a full year) were not significantly different, they were only moderately correlated. Finally, self-reported specialist care contacts were generally in agreement with data from an insurance company. However, for physiotherapy contacts there were differences between the self-reported and insurance data. This study shows how the cost diary might be used successfully in cost-effectiveness studies.

Two-year bronchodilator treatment in patients with mild airflow obstruction. Contradictory effects on lung function and quality of life.

In a two-year randomized controlled study, we studied the effects of bronchodilator treatment on the lung function and the quality of life in patients with mild airflow obstruction. The patients were randomly divided to receive either continuous or symptomatic bronchodilator treatment. Within these treatment groups, they received salbutamol in the first year and ipratropium bromide in the second or vice versa. In addition, the quality of life of the patients was compared to that of the general population. One hundred and forty-four patients completed the study. When compared to the general population, these patients showed a serious impairment in quality of life. No differences between the two drugs were found, but the results indicated that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group. However, this was not reflected in a significant deterioration of the quality of life in the continuous group as measured by means of the Nottingham Health Profile and the Inventory of Subjective Health. Decline in FEV1 showed no correlation with changes in quality of life scores. This may be due to a relatively rapid adjustment of the patients to a decline in FEV1, as a result of which it has no direct effect on the experienced quality of life. Another reason may be that continuous bronchodilation masks the worsening of the disease. This lack of awareness might in turn be caused by the continuous symptom relief of bronchodilators.

Chronic low-back pain: what does cognitive coping skills training add to operant behavioral treatment? Results of a randomized clinical trial.

This study examined the supplemental value of a cognitive coping skills training when added to an operant-behavioral treatment for chronic low-back pain patients. The complete treatment package (OPCO) was compared with an operant program + group discussion (OPDI) and a waiting-list control (WLC). After the WL period, the WLC patients received a less protocolized operant program usually provided in Dutch rehabilitation centers (OPUS). Regression analyses showed that, compared with WLC, both OPCO and OPDI led to less negative affect, higher activity tolerance, less pain behavior, and higher pain coping and pain control. At posttreatment, OPCO led to better pain coping and pain control than OPDI. Calculation of improvement rates revealed that OPCO and OPDI had significantly more improved patients than OPUS on all the dependent variables. The discussion includes findings regarding treatment credibility, compliance, and contamination bias.

Current and future medical costs of asthma and chronic obstructive pulmonary disease in The Netherlands.

The aim of this study was to estimate the healthcare costs of asthma and chronic obstructive pulmonary disease (COPD), in the Netherlands, in 1993. Also studied was the future development of these costs, as a result of ageing and possible changes in smoking behavior. A prevalence-based cost-of-illness approach was used to estimate direct medical costs. Age- and gender-specific data were obtained from representative national registries and large, representative surveys. To model future costs, cost estimates were linked to an epidemiological model based on a dynamic multi-state lifetable. It describes 1 yr changes, from one state to another, that result from ageing, birth, migration, incidence, recovery from asthma and death due to asthma, COPD or other causes, and starting or quitting smoking. Three different scenarios were modelled: 1) a reference scenario which primarily predicts the impact of ageing. 2) an 'attainable' smoking reduction scenario and 3) an 'extreme' smoking reduction scenario. Direct medical costs were estimated to be $US 346 million in 1993. With increasing age, the relative importance of asthma in total asthma and COPD costs decreased from 91% to less than 4%. Annual costs per patient were estimated to be $US 499 for asthma and $US 876 for COPD. The breakdown of costs differed considerably between asthma and COPD. The reference scenario predicted the costs to increase by 60% to reach $US 555 million by 2010, COPD prevention as modelled in the second and the third scenario reduced the projected cost increase from 60%, to 57% and 48%, respectively. Together, the direct costs of asthma and COPD represent 1.3% of the Dutch health care budget. The breakdown of the costs shows different patterns for asthma and COPD. The costs of these diseases are expected to increase by 60% in the near future. In the short run the impact of smoking reduction on reducing this increase is relatively small, but it will be greater in the long run.

Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma.

OBJECTIVE: The aim of this study was to determine the relative economic consequences of treating asthmatics with twice daily dry powder formoterol 12 micrograms as compared with salmeterol 50 micrograms from a societal perspective. DESIGN AND SETTING: A randomised, 6-month, open-label study including 482 patients with asthma was conducted in Italy, Spain, France, Switzerland, the UK and Sweden. Medical costs included the costs of medications, physician services, emergency room visits, hospital admissions and lung function and other tests. Travel costs and costs of production loss were also calculated. Unit prices were estimated from external sources. To pool the costs of the 6 countries, European currencies were converted to US dollars using 1995 exchange rates. Outcome measures were the number of episode-free days (EFDs) and the number of patients reaching a clinically relevant improvement in quality of life as measured using the St. Georges Respiratory Questionnaire. MAIN OUTCOME MEASURES AND RESULTS: There were no significant differences between the 2 treatment arms in the frequency of emergency room visits, hospital admissions, use of rescue medication or contacts with general practitioners (GPs), specialists or nurses. Median medical costs over 6 months were $US828 per patient with formoterol and $US850 with salmeterol. This difference was not statistically significant. In both groups, about 60% of all days were episode-free. Average costs per EFD were about $US9 for both treatments. The average cost per patient reaching a clinically relevant improvement in quality of life was between $US1300 and $US1400. Incremental cost-effectiveness ratios were not calculated because both costs and outcomes were not significantly different. Asthma-related absenteeism ranged between 3 days and 6 months per patient in both groups. CONCLUSIONS: There was no evidence to suggest that either treatment was more cost effective than the other.