Incorporating the Environmental Impact into a Budget Impact Analysis: The Example of Adopting RESPIMAT® Re-usable Inhaler.

BACKGROUND: RESPIMAT® re-usable enables patients to re-use the inhaler and its availability therefore reduces the number of inhalers and associated wastage. OBJECTIVE: The objective of this study was to perform an economic evaluation that incorporates the ecological impact of adopting RESPIMAT re-usable into the healthcare system in Germany. METHODS: Inhaler costs and environmental impact over 5 years in Germany in a scenario with RESPIMAT re-usable compared to a scenario without RESPIMAT re-usable were estimated using a budget impact model. The carbon emissions were derived for each treatment pattern considering the whole life cycle (cradle-to-grave) of the inhaler product. The cost of carbon emissions was estimated using a societal cost per ton of carbon emission. RESULTS: By introducing RESPIMAT re-usable in Germany, it was estimated that by 2023, the number of inhalers used would have decreased by 5,748,750 compared to a scenario without RESPIMAT re-usable. In addition, this measure would reduce the environmental burden of inhaler use while at the same time reducing medical cost of inhalers. CONCLUSIONS: Adopting RESPIMAT® re-usable to the national healthcare services may be a cost-saving option, which has the additional benefit of reducing the societal cost of carbon emissions.

A Budget Impact Model to Estimate the Environmental Impact of Adopting RESPIMAT® Re-usable in the Nordics and Benelux.

INTRODUCTION: The healthcare sector contributes 5-8% of the global greenhouse gas emissions. Global and regional organizations and governments have started to design and implement measures to reduce global greenhouse gas emissions in the healthcare sector, e.g. by green public procurement policies and inclusion of ecological considerations in the decision-making process for purchasing and funding of healthcare technologies. The objective of this study was to perform budget impact analysis of adopting RESPIMAT re-usable in the Nordics and Benelux that considered both the traditional healthcare costs as well as the environmental impact. METHODS: Inhaler costs and environmental impact over 5 years in the Nordics and Benelux in a scenario with RESPIMAT re-usable compared to a scenario without RESPIMAT re-usable were estimated using an budget impact model. RESPIMAT re-usable enables patients to re-use the inhaler device and its availability therefore reduces the number of inhalers and associated wastage. The carbon emissions were derived for each treatment pattern considering the whole life cycle (cradle-to-grave) of the inhaler product. The cost of carbon emissions was estimated using a societal cost per ton of carbon emission. RESULTS: Progressively introducing RESPIMAT re-usable in the Nordics and Benelux was estimated to decrease the number of inhalers used by 2023 by 7,466,621 compared to a scenario without RESPIMAT re-usable, which would result in a reduction of the environmental burden of inhaler use of 4717 tCO2e and a decrease in societal cost of €205,888. CONCLUSIONS: Adopting RESPIMAT re-usable would lead to a substantial reduction in CO2 emissions, leading to savings from a societal perspective. FUNDING: Boehringer Ingelheim.

Treatment experience, burden, and unmet needs (TRIBUNE) in Multiple Sclerosis study: the costs and utilities of MS patients in The Netherlands.

BACKGROUND: Multiple sclerosis (MS) is an important, highly disabling neurological disease, common among young adults in The Netherlands. Nevertheless, only a few studies to date have measured the burden imposed by MS on society in The Netherlands. OBJECTIVES: To estimate the cost and quality-of-life associated with MS in The Netherlands, while focusing on the burden of relapses and increasing disease severity. METHODS: MS patients in The Netherlands (n = 263) completed a web-based questionnaire which captured information on demographics, disease characteristics and severity (Expanded Disability Status Scale [EDSS]), co-morbidities, relapses, resource consumption, utilities, fatigue and activities of daily living (ADL). RESULTS: Most patients included in the study were receiving treatment for MS (76% of the sample). The mean cost per patient per year increased with worsening disability and was estimated at €30,938, €51,056, and €100,469 for patients with mild (EDSS 0-3), moderate (EDSS 4-6.5), and severe (EDSS 7-9) disability, respectively. The excess cost of relapses was estimated at €8195 among relapsing-remitting patients with EDSS score ≤5. The quality-of-life of patients decreased with disease progression and existence of relapses. CONCLUSIONS: The cost of MS in The Netherlands was higher compared to the results of previous studies. The TRIBUNE study provides an important update on the economic burden of MS in The Netherlands in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue. STUDY LIMITATIONS: Patients were selected from specialized treatment centers, therefore this sample may not be representative of the entire MS population in The Netherlands, i.e., few patients not receiving MS therapies were included. In addition, only a few patients with severe disability were included in the study sample; therefore, results for this disease severity sub-group should be interpreted with caution.

Cost effectiveness of quetiapine in patients with acute bipolar depression and in maintenance treatment after an acute depressive episode.

BACKGROUND: Bipolar disorder has a significant impact upon a patient's quality of life, imposing a considerable economic burden on the individual, family members and society as a whole. Several medications are indicated for the acute treatment of mania and depression associated with bipolar disorder as well as for maintenance therapy; however, these have varying efficacy, tolerability and costs. OBJECTIVE: The objective of this study was to develop a new discrete-event simulation model to analyse the long-term consequences of pharmacological therapy for the management of bipolar I and II disorders (acute treatment of episodes of mania and depression as well as maintenance therapy). METHODS: Probabilities of remission and relapse were obtained from clinical trial data and meta-analyses. Costs (year 2011 values) were assessed from a UK healthcare payer's perspective, and included pharmacological therapy and resource use associated with the treatment of mood events and selected adverse events. The health effects were measured in terms of QALYs. RESULTS: For a patient starting with acute depression or in remission at 40 years of age (which was the average age in the clinical trials), quetiapine 300 mg/day was a cost-effective strategy compared with olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a starting episode, the 5-year medical costs were £323 higher and QALYs were 0.038 higher for quetiapine compared with olanzapine, corresponding to a cost-effectiveness ratio of £8600 per QALY gained. CONCLUSION: Compared with olanzapine, the results suggest that quetiapine is cost effective as a maintenance treatment for bipolar depression.

Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from five European countries.

BACKGROUND: Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The TRIBUNE study provides a detailed exploration of costs in relation to relapses and disease severity, and assesses the quality of life impact on MS patients in terms of utilities, fatigue and activities of daily living (ADL). METHODS: Patients in five European countries (France, Germany, Italy, Spain and the United Kingdom) completed a self-administered web-based questionnaire capturing information on demographics, disease characteristics and severity (EDSS), co-morbidities, relapses, resource consumption, utilities, fatigue, and activities of daily living. RESULTS: In total, 1261 MS patients completed the questionnaire. More than half of the patients (68%) had the relapsing-remitting form of the disease; 87% of the sample reported receiving MS treatments. Costs were higher with advancing disease severity; for mild patients (EDSS score ≤ 3) the costs ranged between €13,534 and €22,461 across countries; for moderate (EDSS score 4 - 6.5) between €28,524 and €43,948; for severe (EDSS ≥ 7) between €39,592 and €65,395. Relapses were also associated with increasing costs; the difference in the cost per patient per year for relapsing-remitting patients with EDSS score ≤ 5 that did experience at least one relapse during the past 12 months and those who did not ranged between €3321 and €9430. The quality of life of patients decreased with disease progression and existence of relapses. CONCLUSION: The TRIBUNE study provides an important update on the economic burden of MS in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity, and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.

Treatment experience, burden, and unmet needs (TRIBUNE) in multiple sclerosis: the costs and utilities of MS patients in Canada.

BACKGROUND: Multiple sclerosis (MS) is the most common neurological disease among young adults in Canada, but few studies to date have measured the burden imposed by MS on Canadian society. OBJECTIVES: To estimate the costs and quality of life of MS patients in Canada, while focusing on the burden of relapses and increasing disease severity. METHODS: MS patients in Canada (N=241) completed a web-based questionnaire which captured information on demographics, disease characteristics, severity (Expanded Disability Status Scale [EDSS]), comorbidities, relapses, as well as resource consumption and quality of life associated with MS. RESULTS: Most patients (74%) reported treatment with disease modifying therapies (DMTs). 54% of patients with the relapsing-remitting form of the disease with an EDSS score ≤ 5 had experienced at least one relapse in the past year. The mean cost per patient per year increased with worsening disability, and was estimated at Can $30,836 for patients with mild disability (EDSS score 0-3), Can $46,622 for patients with moderate disability (EDSS 4-6.5), and Can $77,981 for patients with severe disability due to MS (EDSS score 7-9). The excess costs of relapsing-remitting MS patients with EDSS score ≤ 5 that could be attributable to relapse(s) were estimated at Can $10,512. More severe disease and experiencing a relapse were also associated with poorer quality of life of MS patients. CONCLUSIONS: Costs of MS patients are higher today than shown in previous studies. Disease progression and relapses are associated with increased economic and quality of life burden. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and may help to reduce the societal burden of MS.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials.

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ≥6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5,364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

Treatment options for bipolar depression: a systematic review of randomized, controlled trials.

This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The outcome measures included mean change in Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates of response and remission. Overall, 19 publications were included. Medications included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole, phenelzine, and divalproex. The most trials were identified for quetiapine (5) and lamotrigine (6). Not all medications were associated with symptomatic improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with lamotrigine, paroxetine, aripiprazole, and lithium not being different from placebo. Highest reductions in MADRS scores versus placebo were reported for the olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], -9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, -4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to -3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All medications except paroxetine, lithium, aripiprazole, and phenelzine significantly improved the ratio of probabilities of response (overall rate, 1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo. Variability in efficacy exists between treatments of bipolar depression. Quetiapine and the olanzapine-fluoxetine combination showed the greatest symptomatic improvement. Efficacy considerations will need to be balanced against safety and tolerability of the individual agents.

Cost-utility analysis of interferon beta-1B in secondary progressive multiple sclerosis using natural history disease data.

OBJECTIVES: Different cost-effectiveness analyses have been presented for interferon beta-1b (IFNB) in the treatment of secondary progressive multiple sclerosis (SPMS). All studies have used modeling techniques since any effect on progression of disability achieved during a clinical trial will last beyond the trial. Different approaches to extrapolation have been taken, but generally they have been based on disease progression and relapse rates in clinical trials. The problem with this approach is that the population in clinical trials is a selected group of patients, which has the potential to bias results. A better method for extrapolation is to use epidemiologic data. The objective of this study is to incorporate natural history data for MS into a previously presented cost-utility model and to compare the two methods of extrapolation. METHODS: Clinical trial data were used to model disease progression during the first 3 years in the model. To extrapolate beyond the trial (10 years), data on progression of disability were available from a geographically based epidemiologic study of the natural history of MS in Canada. There were 568 patients who had converted to SPMS during the follow-up that were included in the data set. Mean costs and utilities for each Markov state were calculated from a population-based cross-sectional study in Sweden. RESULTS: The extrapolation using clinical trial data appears to have underestimated the progression of disability in the long term and thus also the potential benefit of treatment. Using the epidemiologic data, the incremental cost per QALY is SEK 257,000 (US $25,700; US $1 = SEK 10; November 2000) when all costs (direct, informal care, and indirect) are included (discounted 3%). This compares to SEK 342,000 in the previous model. The lower cost-effectiveness ratio is mostly due to a larger QALY gain with treatment than in the previous model (0.217 compared with 0.162). CONCLUSIONS: Cost-effectiveness analysis in SPMS requires that the effect of treatment beyond clinical trials be included. The method of extrapolation clearly affects the results, and when available, epidemiologic data should be used. Using the longitudinal data from Canada, the cost-utility ratios for IFNB-1b in the treatment of SPMS appear well within the acceptable range.