Do We Need to Assess Quality-of-Life with Both the St George's Respiratory Questionnaire and the EuroQol 5-Dimension Questionnaire in a Clinical Study with an Economic Component: Insights from the REVOLENS Study in Severe Emphysema.

Introduction: The use of two quality-of-life questionnaires in a single clinical trial with an economic component can be challenging due to the associated workload in terms of data collection and an increased risk of missing data. The aim of our study was to determine whether the questionnaire chosen to measure health status, the St. George's Respiratory Questionnaire (SGRQ), could be administered on its own without adding the EuroQol five dimensions questionnaire (EQ-5D) for economic evaluation in emphysema studies. Materials and Methods: Data were prospectively collected during the REVOLENS trial assessing endobronchial coil treatment in severe emphysema. To quantify the association between the two questionnaires, correlations between the EQ-5D and the SGRQ were first tested and the concordance was then studied in order to know whether the two questionnaires were interchangeable. Finally, the Starkie et al algorithm predicting EQ-5D utility values from the SGRQ was used on REVOLENS's individual patient data. The Student's t-test, correlation and concordance between EQ-5D individual value (from the REVOLENS study) and predicted value (from the Starkie et al algorithm) were studied to test this algorithm. Results: Results showed a strong correlation but no concordance between the EQ-5D and the SGRQ, demonstrating that the two questionnaires are not interchangeable. Moreover, the algorithm predicting EQ-5D utilities from the SGRQ did not provide utility values comparable to those observed in the REVOLENS study. Indeed, our study demonstrated a strong correlation between predicted and individual EQ-5D values but no concordance. Conclusion: The use of both the EQ-5D and the SGRQ in a clinical study with an economic component is justified. Based on our results, the SGRQ should not be used to obtain a utility score to calculate the incremental cost-effectiveness ratio and conclude on the efficiency of an intervention in emphysema patients.

Cost-effectiveness of lung volume reduction coil treatment in patients with severe emphysema: results from the 2-year follow-up crossover REVOLENS study (REVOLENS-2 study).

BACKGROUND: The REVOLENS study compared lung volume reduction coil treatment to usual care in patients with severe emphysema at 1 year, resulting in improved quality-adjusted life-year (QALY) and higher costs. Durability of the coil treatment benefit and its cost-effectiveness at 2 years are now assessed. METHODS: After one year, the REVOLENS trial's usual care group patients received coil treatment (second-line coil treatment group). Costs and QALYs were assessed in both arms at 2 years and an incremental cost-effectiveness ratio in cost per QALY gained was calculated. The uncertainty of the results was estimated by probabilistic bootstrapping. RESULTS: The average cost of coil treatment in both groups was estimated at €24,356. The average total cost at 2 years was €9655 higher in the first-line coil treatment group (p = 0.07) and the difference in QALY between the two groups was 0.127 (p = 0.12) in favor of first-line coil treatment group. The 2-year incremental cost-effectiveness ratio (ICER) was €75,978 / QALY. The scatter plot of the probabilistic bootstrapping had 92% of the replications in the top right-hand quadrant. CONCLUSION: First-line coil treatment was more expensive but also more effective than second-line coil treatment at 2 years, with a 2-year ICER of €75,978 / QALY. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01822795 .

Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy.

Subjects with alpha-1 antitrypsin deficiency who develop pulmonary disease are managed following general treatment guidelines, including disease management interventions. In addition, administration of intravenous infusions of alpha-1 proteinase inhibitor (augmentation therapy) at regular schedules is a specific therapy for individuals with AATD with pulmonary involvement.This chapter summarizes the manufacturing differences of commercially available formulations and the available evidence of the effects of augmentation therapy. Biologically, there is clear evidence of in vivo local antiprotease effects in the lung and systemic immunomodulatory effects. Clinically, there is cumulative evidence of slowing lung function decline and emphysema progression. The optimal dose of augmentation therapy is being revised as well as more individualized assessment of who needs this therapy.

Out-of-pocket healthcare expenditure and chronic disease - do Australians forgo care because of the cost?

Although we do know that out-of-pocket healthcare expenditure is relatively high in Australia, little is known about what health conditions are associated with the highest out-of-pocket expenditure, and whether the cost of healthcare acts as a barrier to care for people with different chronic conditions. Cross-sectional analysis using linear and logistic regression models applied to the Commonwealth Fund international health policy survey of adults aged 18 years and over was conducted in 2013. Adults with asthma, emphysema and chronic obstructive pulmonary disease (COPD) had 109% higher household out-of-pocket healthcare expenditure than did those with no health condition (95% CI: 50-193%); and adults with depression, anxiety and other mental health conditions had 95% higher household out-of-pocket expenditure (95% CI: 33-187%). People with a chronic condition were also more likely to forego care because of cost. People with depression, anxiety and other mental health conditions had 7.65 times higher odds of skipping healthcare (95% CI: 4.13-14.20), and people with asthma, emphysema and chronic obstructive pulmonary disease had 6.16 times higher odds of skipping healthcare (95% CI: 3.30-11.50) than did people with no health condition. People with chronic health conditions in Canada, the United Kingdom, Germany, France, Norway, Sweden and Switzerland were all significantly less likely to skip healthcare because of cost than were people with a condition in Australia. The out-of-pocket cost of healthcare in Australia acts as a barrier to accessing treatment for people with chronic health conditions, with people with mental health conditions being likely to skip care. Attention should be given to the accessibility and affordability of mental health services in Australia.

Cost-effectiveness of endobronchial valve therapy for severe emphysema: a model-based projection based on the VENT study.

BACKGROUND: Endobronchial valve (EBV) therapy is an innovative treatment that has been shown to be safe and effective in selected subgroups of patients with severe emphysema. OBJECTIVES: The objective of our study was to assess the cost-effectiveness of EBV therapy compared to the medical management of patients with high heterogeneity, complete fissures and lobar exclusion in the context of the German health-care system. METHODS: Clinical data from a subset of VENT (Endobronchial Valve for Emphysema Palliation Trial) provided information about clinical events, health-related quality of life, and disease staging for 12 months. This information was subsequently used to project long-term disease progression, mortality, and health resource utilization. We computed the 5- and 10-year incremental cost-effectiveness ratio (ICER) in euros per quality-adjusted life year (QALY). Costs and effects were discounted at 3% per year. RESULTS: EBV therapy led to clinically meaningful disease restaging at 12 months (37.8% of the cohort improved staging, compared to 0% in the controls). Over 5 years, EBV therapy was projected to increase survival from 66.4 to 70.7%, and to add 0.22 QALYs. Costs were estimated to increase by EUR 10,299, resulting in an ICER of EUR 46,322 per QALY. Over 10 years, 0.41 QALYs were gained at an additional cost of EUR 10,425, yielding an ICER of EUR 25,142 per QALY. CONCLUSIONS: Our model-based analysis suggests that EBV therapy leads to clinically meaningful changes in disease staging and progression when compared to medical management, with resulting gains in unadjusted and quality-adjusted life expectancy. Our results indicate that EBV therapy is cost-effective in the German health-care system.

[Cost-effectiveness of lung volume reduction coil treatment in emphysema. STIC REVOLENS]. / Évaluation médico-économique de la réduction volumique endobronchique par spirales. STIC REVOLENS.

BACKGROUND: Medical therapeutic options for the treatment of emphysema remain limited. Lung volume reduction surgery is infrequently used because of its high morbi-mortality. Endobronchial lung volume reduction coil (LVRC(®), PneumRx, Mountain View, CA) treatment has been recently developed and has been shown to be feasible and associated with an acceptable safety profile, while resulting in improvements in dyspnea, exercise capacity and lung function. The objective of this study is to analyze the cost effectiveness of LVRC treatment in severe emphysema. METHODS: This prospective, multicenter study, randomized with a 1:1 ratio (LVRC vs conventional treatment) will include 100 patients who will be followed up for 1year. The primary outcome measure is the 6-month improvement of the 6-minute walk test: the percentage of patients showing an improvement of at least 54m will be compared between groups. A cost-effectiveness study will estimate the cost of LVRC treatment, the global cost of this therapeutic option and will compare the cost between patients treated by LVRC and by medical treatment alone. EXPECTED RESULTS: This study should allow validating the clinical efficacy of LVRC in severe emphysema. The cost-effectiveness study will assess the medical-economic impact of the LVRC therapeutic option.

What to do when a smoker's CT scan is "normal"?: Implications for lung cancer screening.

Lung cancer is the leading cause of cancer-related mortality in the United States and around the world. There are > 90 million current and ex-smokers in the United States who are at increased risk of lung cancer. The published data from the National Lung Screening Trial (NLST) suggest that yearly screening with low-dose thoracic CT scan in heavy smokers can reduce lung cancer mortality by 20% and all-cause mortality by 7%. However, to implement this program nationwide using the NLST inclusion and exclusion criteria would be extremely expensive, with CT scan costs alone > $2 billion per annum. In this article, we offer a possible low-cost strategy to risk-stratify smokers on the basis of spirometry measurements and emphysema scoring by radiologists on CT scans.

α1-Proteinase inhibitor (human) in the treatment of hereditary emphysema secondary to α1-antitrypsin deficiency: number and costs of years of life gained.

BACKGROUND: α(1)-Antitrypsin deficiency (α-ATD) is a disorder inherited in an autosomal recessive pattern, with co-dominant alleles known as the protease inhibitor system (Pi). The main function of α(1)-antitrypsin (α-AT) is to protect the lungs against a powerful elastase released from neutrophil leucocytes. α-ATD typically presents with a serum α-AT level of <50 mg/dL. In severe α-ATD, phenotype PiZZ, protection of the lungs is compromised, leading to an accelerated decline in forced expiratory volume in 1 second (FEV(1)). As a result, a patient may develop pulmonary emphysema of the panacinar type at a young age (third to fourth decades of life), with cigarette smoking being the most significant additional risk factor. It has been shown that weekly or monthly infusion of human α-AT is effective in raising serum α-AT levels to desired levels (>80 mg/dL), with few, if any, adverse effects. OBJECTIVE: The present study was designed to discern the number of years of life gained, and the expense per year of life gained, associated with use of α-AT augmentation therapy (α(1)-proteinase inhibitor [human]), relative to 'no therapeutic intervention' in persons with α-ATD. METHODS: Monte Carlo simulation (MCS) was used to: (i) estimate the number of years of life gained; and (ii) estimate the health service expenditures per year of life gained for persons receiving, or not receiving, α-AT augmentation therapy. MCS afforded a decision-analytical framework parameterized with both stochastic (random) and deterministic (fixed) components, and yielded a fiscal risk-profile for each simulated cohort of interest (eight total: by sex, smoking status [non-smoker; or past use (smoker)]; and use of α-AT augmentation therapy). The stochastic components employed in the present inquiry were: (i) age-specific body weight, and height; (ii) age-specific mortality; and (iii) the probability distribution for receipt of a lung transplant, as a function of FEV(1). The deterministic components employed in the present inquiry were: (i) age in years for the simulated cohort; (ii) outlays for α-AT augmentation therapy; (iii) health service expenditures associated with receipt of a lung transplant; (iv) annual decline in FEV(1); (v) percent predicted FEV(1); (vi) initiation of α-AT augmentation therapy as a function of percent predicted FEV(1); (vii) need for a lung transplant as a function of percent predicted FEV(1); (viii) annual rate of lung infection; and (ix) mortality as a function of percent predicted FEV(1). Results are reported from a payer perspective ($US, year of costing 2010). RESULTS: Receipt of α-AT augmentation therapy was associated with a significant increase (p < 0.05) in years of life gained, with female smokers gaining an estimated mean 7.14 years (cost per year: $US248 361 [95% CI 104 531, 392 190]); female non-smokers gained an estimated mean 9.19 years (cost per year: $US160 502 [95% CI 37 056, 283 947)]); male smokers gained an estimated mean 5.93 years (cost per year: $US142 250 [95% CI 48 467, 236 032]); and male non-smokers gained an estimated mean 10.60 years (cost per year: $US59 234 [95% CI 20 719, 97 548]). CONCLUSION: Use of α-AT augmentation therapy was associated with an increase in years of life gained by sex and history of tobacco use, and at a cost per year of life gained comparable to that of other evidenced-based interventions.

Comparative results of non-resectional lung volume reduction performed by awake or non-awake anesthesia.

OBJECTIVE: In a prospective non-randomized study, we compared results and costs of non-resectional lung volume reduction surgery (LVRS) performed through awake or non-awake anesthesia that was freely chosen by recruited patients. METHOD: Non-resectional LVRS was performed by epidural anesthesia in 41 patients (awake group) and by general anesthesia in 19 patients (non-awake group). Perioperative outcome included analysis of oxygenation (PaO(2)/FiO(2)) at fixed time points and global time spent in the operating room (anesthesia plus surgery plus weaning plus recovery times). Costs were evaluated at discharge. Forced expiratory volume in 1s (FEV(1)), plethysmographic residual volume (RV(plet)) and maximal incremental treadmill test (MITT) score were assessed preoperatively and every 6 months, postoperatively. RESULTS: Perioperative outcome was better in the awake group with better oxygenation 1h after the operation (P=0.004) and shorter global in-operating room stay (P<0.0001). There was no operative mortality. In the awake group, median hospital stay was shorter (6 days vs 7 days, P=0.006), whereas median hospital charges were lower than in the non-awake group (7800 euros vs 8600 euros, P=0.006). At 6 months, there was no difference (awake vs non-awake) in median ΔFEV (0.33l vs 0.28l, P=0.09), ΔRV (-0.99l vs -0.98l, P=0.95), and ΔMITT score (1.0 vs 0.75, P=0.31). CONCLUSION: In our study, awake non-resectional LVRS was preferred by the majority of patients. It resulted in better perioperative outcome, shorter hospital stay, and lower costs than equivalent procedures performed by non-awake anesthesia. Six months' clinical results were comparable, showing that the awake approach had no impact on late clinical benefit.

A forensic evaluation of the National Emphysema Treatment Trial using the expected value of information approach.

BACKGROUND/RATIONALE: Expected value of information (EVI) analyses allow researchers to estimate the returns to conducting research. We used EVI techniques to estimate the value of the National Emphysema Treatment Trial (NETT), a multicenter randomized trial of lung-volume-reduction surgery (LVRS) versus medical therapy (MT) for patients with severe emphysema, then compared that result to the trial cost. METHODS: We gathered information on costs and benefits of LVRS and MT before the trial and the costs of conducting the NETT, and compared these data with the results of the cost-effectiveness analysis conducted alongside the trial. We used 2 thresholds to represent the societal value of a quality-adjusted life year (QALY): USD 50,000 and USD100,000. RESULTS: The cost effectiveness of LVRS versus MT using historical (nontrial) information was USD 305,000/QALY. Based on these data and the threshold incremental cost-effectiveness ratio values, the expected value of perfect information was USD 46 million and USD 670 million for thresholds USD 50,000 and USD 100,000 per QALY, respectively. The NETT was powered for 1,250 patients in each arm; ultimately approximately 600 patients in each arm were recruited. With 1,250 patients per arm, the expected value of sample information was USD 660 million for the threshold of USD100,000. The actual cost of the NETT was approximately USD 60 million. The expected net benefit of sampling was USD 600 million. CONCLUSIONS: Given the difference between the cost of the trial and the economic benefits of the information, the EVI analyses suggest that federal investment in the NETT trial represented good value for money.

Costs of pulmonary rehabilitation and predictors of adherence in the National Emphysema Treatment Trial.

This study reports the costs associated with rehabilitation among participants in the National Emphysema Treatment Trial (NETT), and evaluates factors associated with adherence to rehabilitation. Pulmonary rehabilitation is recommended for moderate-to-severe COPD and required by the Centers for Medicare and Medicaid Services (CMS) prior to lung volume reduction surgery (LVRS). Between January 1998 and July 2002, 1,218 subjects with emphysema and severe airflow limitation (FEV(1) < or = 45% predicted) were randomized. Primary outcome measures were designated as mortality and maximal exercise capacity 2 years after randomization. Pre-randomization, estimated mean total cost per patient of rehabilitation was $2,218 (SD $314; 2006 dollars) for the medical group and $2,187 (SD $304) for the surgical group. Post-randomization, mean cost per patient in the medical and surgical groups was $766 and $962 respectively. Among patients who attended > or = 1 post-randomization rehabilitation session, LVRS patients, patients with an FEV(1) > or = 20% predicted, and higher education were significantly more likely to complete rehabilitation. Patients with depressive and anxiety symptoms, and those who live > 36 miles compared to < 6 miles away were less likely to be adherent. Patients who underwent LVRS completed more exercise sessions than those in the medical group and were more likely to be adherent with post-randomization rehabilitation. A better understanding of patient factors such as socioeconomic status, depression, anxiety and transportation issues may improve adherence to pulmonary rehabilitation.

Mortality and functional performance in severe emphysema after lung volume reduction or transplant.

The purpose of this endeavor is to compare the morbidity, mortality and costs of LVRS versus transplantation in severe emphysema. This was a retrospective review of severe emphysema patients who received LVRS (n = 70) from 1994-1999, or transplant (n = 87) from 1994-2004. Change in functional status was calculated by the change in modified BODE (mBODE) score. Financial data included physician, hospital and medication costs. Preoperatively, there was no significant difference between the transplant and LVRS groups (mean +/- SD) in age (57.7 +/- 5.7 vs. 59.1 +/- 8.3 years), BMI, Borg dyspnea score, 6-minute walk distance or mBODE (10.4 +/- 2.6 vs. 9.6 +/- 2.7, p = 0.4). Preoperatively, FEV1% (23.6 +/- 8.5 vs. 31.9 +/- 17.7, p = 0.008) was significantly lower in the transplant group. One year post-operatively, transplantation patients had a significantly greater improvement in mBODE (-5.7 vs. -2.0, p = 0.0004), FEV1% (43.4 vs. 2.2%, p = 0.0004) and Borg score (-3.0 vs. -1.4, p = 0.04). Transplantation patients had lower long-term survival compared to LVRS patients (p = 0.01). The only variable that affected survival was type of surgery favoring LVRS (hazard ratio 1.7, 95% confidence limits 1.05-2.77). During a mean follow-up of 2.4 +/- 2.5 years after transplant and 5.0 +/- 3.1 years after LVRS, transplantation mean total costs were greater ($381,732 vs. $140,637, p < 0.0001). Transplantation patients spent more time in the hospital (74.3 +/- 81.3 vs. 39.5 +/- 66.7 days, p = 0.009) and had more outpatient visits (29.9 +/- 28.8 vs. 12.3 +/- 12.6 visits, p < 0.0001). In patients who survive over 1 year, transplantation provides a higher level of functional status and a greater improvement in airflow obstruction, dyspnea, exercise tolerance, and mBODE score, but costs more and carries greater mortality.

Updated evaluation of the cost-effectiveness of lung volume reduction surgery.

BACKGROUND: The National Emphysema Treatment Trial, a randomized clinical trial of lung volume reduction surgery (LVRS) vs medical therapy for severe emphysema, included a prospective economic analysis. We present an updated analysis of cost-effectiveness with 1-year additional follow-up data. METHODS: Following pulmonary rehabilitation, 1,218 patients at 17 medical centers were randomized to receive LVRS or continued medical treatment. The cost-effectiveness of LVRS vs medical therapy was calculated over the duration of the trial (January 1998 to December 2003) and estimated at 10 years using modeling based on observed trends in survival, cost, and quality of life. RESULTS: The cost-effectiveness of LVRS vs medical therapy was $140,000 per quality-adjusted life-year (QALY) gained (95% confidence interval, $40,155 to $239,359) at 5 years, and was projected to be $54,000 per QALY gained at 10 years. In subgroup analysis, the cost-effectiveness of LVRS in patients with upper-lobe emphysema and low exercise capacity was $77,000 per QALY gained at 5 years, and was projected to be $48,000 per QALY at 10 years. Compared to the initial results, the updated results are similar for the overall cohort but vary substantially for the subgroups. CONCLUSIONS: LVRS is costly relative to other health-care programs during the time horizon when costs and outcomes are known. The extended follow-up period offers more certainty regarding the long-term value and economic impact of this procedure.

A randomized clinical trial of lung volume reduction surgery versus best medical care for patients with advanced emphysema: a two-year study from Canada.

BACKGROUND: We present a summary report evaluating the efficacy of lung volume reduction surgery (LVRS) in patients with advanced emphysema in the Canadian setting. METHODS: Quality of Life measures assessed the efficacy of adding LVRS to best medical care including rehabilitation in this blinded randomized multicentered controlled trial with 2 years of follow-up. Health utility and quality-adjusted life years (QALY) were outcomes central to our economic assessment. RESULTS: None of the 32 patients randomized to the LVRS arm or 30 patients in the best medical care (BMC) arm crossed-over and no patients were lost to follow-up. Overall surgical mortality was 16% at 2 years while the overall medical mortality was 13% (p = 0.914). There were no 30-day postoperative deaths but 2 deaths (6%) occurred within 90 days of randomization. Surgery reduced the residual volume measured at 6 months by 23% (5,385 mL to 4,322 mL, p = 0.007). There was an increase in forced expiratory volume in 1 second (FEV1) of 30% (265 mL, p = 0.013) from baseline, an improvement in the six minute walk test (6MWT) of 78 meters (p = 0.045), and an increase in Health Utility Index 3 (HUI3) which peaked at 6 months with a difference of 0.16 (p = 0.129). There was a gain in QALYs of 0.21 (p = 0.19) in the LVRS-arm over the BMC-arm. The LVRS costs an additional 28,119 Canadian dollars (CAD) compared with BMC or 133,900 CAD/QALY gained. CONCLUSIONS: The addition of LVRS to best medical care including pulmonary rehabilitation improves pulmonary function, exercise activity, and quality of life in selected patients with advanced emphysema. Cost is high but in keeping with other treatment modalities currently available.

Epidemiology and global impact of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that causes a heavy health and increasing economic burden both in the United States and around the world. Most of the risk factors for COPD are well known and include smoking, occupational exposures, air pollution, airway hyperresponsiveness, asthma, and certain genetic variations, although many questions, such as why a minority of smokers develop significant airway obstruction, remain. Major medical organizations have agreed on a common definition of COPD, although newer measures, such as functional status or exercise capability, have emerged as important in determining the prognosis of COPD patients. In most of the world, COPD prevalence and mortality are still increasing and will likely continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention, COPD education and early detection, and better treatment will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.

Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery.

BACKGROUND: The National Emphysema Treatment Trial, a randomized trial comparing lung volume reduction surgery with medical therapy for severe emphysema, included randomized and nonrandomized comparisons of the median sternotomy and video-assisted thoracoscopic approaches for lung volume reduction surgery. METHODS: Lung volume reduction surgery was performed by median sternotomy only at 8 centers and video-assisted thoracoscopy only at 3 centers; 6 centers randomized the approach to lung volume reduction surgery. Mortality, morbidity, functional status, and costs were assessed. RESULTS: In the nonrandomized comparison, 359 patients received lung volume reduction surgery by median sternotomy, and 152 patients received lung volume reduction surgery by video-assisted thoracoscopy. The 90-day mortality was 5.9% for median sternotomy and 4.6% for video-assisted thoracoscopy (P =.67). Overall mortality was 0.08 deaths per person-year for median sternotomy and 0.10 deaths per person-year for video-assisted thoracoscopy (video-assisted thoracoscopy-median sternotomy risk ratio, 1.18; P =.42). Complication rates were low and not statistically different for the 2 approaches. The median hospital length of stay was longer for median sternotomy than for video-assisted thoracoscopy (10 vs 9 days; P =.01). By 30 days after surgery, 70.5% of median sternotomy patients and 80.9% of video-assisted thoracoscopy patients were living independently (P =.02). Functional outcomes were similar for median sternotomy and video-assisted thoracoscopy at 12 and 24 months. Costs for the operation and the associated hospital stay and costs in the 6 months after surgery were both less for video-assisted thoracoscopy than for median sternotomy (P <.01 in both cases). Similar results were noted for the randomized comparison. CONCLUSIONS: Morbidity and mortality were comparable after lung volume reduction surgery by video-assisted thoracoscopy or median sternotomy, as were functional results. The video-assisted thoracoscopic approach to lung volume reduction surgery allowed earlier recovery at a lower cost than median sternotomy.