Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden.

AIMS: To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden. METHODS: A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability. RESULTS: PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5-83.8%) were for institutional care; indirect costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations. CONCLUSION: PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

Definitions and drivers of relapse in patients with schizophrenia: a systematic literature review.

Relapse in patients with schizophrenia has devastating repercussions, including worsening symptoms, impaired functioning, cognitive deterioration and reduced quality of life. This progressive decline exacerbates the burden of illness on patients and their families. Relapse prevention is identified as a key therapeutic aim; however, the absence of widely accepted relapse definition criteria considerably hampers achieving this goal. We conducted a literature review in order to investigate the reporting of relapses and the validity of hospitalization as a proxy for relapse in patients with schizophrenia. The primary aim was to assess the range and validity of methods used to define relapse in observational or naturalistic settings. The secondary aim was to capture information on factors that predicted or influenced the risk of relapse. A structured search of the PubMed database identified articles that discussed relapse, and hospitalization as a proxy of relapse, in patients with schizophrenia. National and international guidelines were also reviewed. Of the 150 publications and guidelines identified, 87 defined relapse and 62% of these discussed hospitalization. Where hospitalization was discussed, this was as a proxy for, or a component of, relapse in the majority of cases. However, hospitalization duration and type varied and were not always well defined. Scales were used to define relapse in 53 instances; 10 different scales were used and multiple scales often appeared within the same definition. There were 95 references to factors that may drive relapse, including non-adherence to antipsychotic medication (21/95), stress/depression (11/95) and substance abuse (9/95). Twenty-five publications discussed the potential of antipsychotic therapy to reduce relapse rates-continuous antipsychotic therapy was associated with reduced frequency and duration of hospitalization. Non-pharmacological interventions, such as psychoeducation and cognitive behavioural therapy, were also commonly reported as factors that may reduce relapse. In conclusion, this review identified numerous factors used to define relapse. Hospitalization was the factor most frequently used and represents a useful proxy for relapse when reporting in a naturalistic setting. Several factors were reported to increase the risk of relapse, and observation of these may aid the identification of at-risk patients.

Pharmacoeconomic analysis of paliperidone palmitate versus olanzapine pamoate for chronic schizophrenia in Norway.

OBJECTIVE: Paliperidone palmitate long-acting injection (PP-LAI) has recently been approved for treatment of chronic schizophrenia. Its cost-effectiveness has not been established. The objective was to compare direct costs and outcomes between PP-LAI and olanzapine pamoate (OLZ-LAI) in treating chronic schizophrenia in Norway from the perspective of the government payer. METHODS: We used a decision analytic model over a 1-year time horizon. Clinical inputs were derived from the literature and an expert panel; costs were taken from standard lists, adjusted to 2010 Norwegian kroner (NOK). Discounting was not done. Main outcomes included average cost per patient treated, hospitalisations, emergency room (ER) visits and quality-adjusted life years (QALYs). The pharmacoeconomic outcome was the incremental cost per QALY. Robustness was examined using one-way sensitivity analyses on critical variables and a 5000-iteration probabilistic Monte Carlo sensitivity analysis with all variables included. RESULTS: PP-LAI generated 0.845 QALY at a cost of 151 336 NOK of which 23% was due to drugs; 25% of patients were hospitalised and another 12% required ER visits. OLZ-LAI cost 174 351 NOK (21% due to drugs); patient outcomes included 0.844 QALY, 27% hospitalisations and 14% ER visits. PP-LAI dominated OLZ-LAI in the base case. The analysis was reasonably robust against variations in drug cost but sensitive to small changes in adherence and hospitalisation rates. Overall, PP-LAI was dominant over OLZ-LAI in 54.5% of simulations. Replacing OLZ-LAI with PP-LAI would be cost saving for the Norwegian healthcare system. CONCLUSION: PP-LAI was cost-effective compared with OLZ-LAI in treating patients with chronic schizophrenia in Norway but sensitive to changes in adherence and hospitalisation rates.

An analysis of potentially prolactin-related adverse events and abnormal prolactin values in randomized clinical trials with paliperidone palmitate.

BACKGROUND: Paliperidone palmitate has been associated with serum prolactin elevations in some patients. However, few individuals with elevated prolactin levels (hyperprolactinemia) have symptomatic potentially prolactin-related adverse events (PPR-AEs). OBJECTIVE: To quantify rates of hyperprolactinemia in subjects treated with the newly marketed paliperidone palmitate long-acting injection (PP-LAI) in randomized clinical trials, summarize rates of PPR-AEs in those trials by sex and dose, and determine how many PPR-AEs required treatment. METHODS: Numbers and rates of investigator-reported hyperprolactinemia and PPR-AEs were obtained from the sponsor's clinical trial database and have been included in regulatory filings. Results were tabulated for males, females, and overall, and by dose administered, using descriptive statistics. Those requiring treatment were described as well. RESULTS: There were 3173 subjects (61.4% males) exposed to PP-LAI in 10 clinical trials; 2831 (89.2%) patients had recorded prolactin levels, including 1759 males (90.3% of exposed males) and 1072 females (87.5% of exposed females). Overall, at any time, prolactin levels were elevated for 38.8% of the subjects (39.5% for males and 37.7% for females; p = 0.354 between sexes). However, there was no significant correlation between monthly dose and proportion of subjects with elevated prolactin levels (p = 0.109). There were 115 PPR-AEs in 107 patients (3.4%); 51 (44.3% of PPR-AEs) cases represented asymptomatic hyperprolactinemia. The remaining 64 symptomatic PPR-AEs affected 2.0% of the total number of subjects. Fifteen events in 13 participants (0.41% of patients or 4.7 events/1000 patients) required treatment. CONCLUSIONS: Clinicians should periodically assess patients on paliperidone palmitate for any PPR-AEs and carefully assess the benefits and risks when managing these effects.

Pharmacoeconomic analysis of paliperidone palmitate for treating schizophrenia in Greece.

BACKGROUND: Patients having chronic schizophrenia with frequent relapses and hospitalizations represent a great challenge, both clinically and financially. Risperidone long-acting injection (RIS-LAI) has been the main LAI atypical antipsychotic treatment in Greece. Paliperidone palmitate (PP-LAI) has recently been approved. It is dosed monthly, as opposed to biweekly for RIS-LAI, but such advantages have not yet been analysed in terms of economic evaluation. PURPOSE: To compare costs and outcomes of PP-LAI versus RIS-LAI in Greece. METHODS: A cost-utility analysis was performed using a previously validated decision tree to model clinical pathways and costs over 1 year for stable patients started on either medication. Rates were taken from the literature. A local expert panel provided feedback on treatment patterns. All direct costs incurred by the national healthcare system were obtained from the literature and standard price lists; all were inflated to 2011 costs. Patient outcomes analyzed included average days with stable disease, numbers of hospitalizations, emergency room visits, and quality-adjusted life-years (QALYs). RESULTS: The total annual healthcare cost with PP-LAI was €3529; patients experienced 325 days in remission and 0.840 QALY; 28% were hospitalized and 15% received emergency room treatment. With RIS-LAI, the cost was €3695, patients experienced 318.6 days in remission and 0.815 QALY; 33% were hospitalized and 17% received emergency room treatment. Thus, PP-LAI dominated RIS-LAI. Results were generally robust in sensitivity analyses with PP-LAI dominating in 74.6% of simulations. Results were sensitive to the price of PP-LAI. CONCLUSIONS: PP-LAI appears to be a cost-effective option for treating chronic schizophrenia in Greece compared with RIS-LAI since it results in savings to the health care system along with better patient outcomes.

Relationship between blood glucose and carotid intima media thickness: A meta-analysis.

BACKGROUND: Increased coronary intima media thickness (CIMT) has been associated with adverse cardiovascular outcomes, as have increased glucose levels. The link has not been established between glucose and CIMT; therefore, we sought to assess the relationship between glucose and CIMT. METHODS: Medline, EMBASE, Scopus, and Cochrane databases were searched from inception through 2009 for original research reporting both postprandial glucose levels and CIMT measurements. Glucose was classified as normal, impaired, or diabetic. Outputs included inverse variance weighted effect size and also average correlation (using the Wang and Bushman approach). Data were combined using a random effects meta-analytic model. Heterogeneity as assessed using chi(2) and I(2); bias was examined using Egger plots and Begg-Mazumdar tau. Polynomial functions (i.e., linear, quadratic, cubic, quartic) were fit to the data and the Akaike Information Criteria were used to select the optimal model. RESULTS: We identified 172 papers; 161 were rejected (19 inappropriate design, 8 had selected patients, 101 inappropriate outcomes) leaving 11 accepted. We used data from 15,592 patients (8250 normals, 3013 impaired glucose, 4329 diabetics). There was no evidence of heterogeneity or publication bias. The overall correlation was 0.082 (CI95%:0.066-0.098); the overall effect size was 0.294 (0.245-0.343) between diabetics and normals and 0.137 (0.072-0.202) between normals and those with impaired glucose. The equation of best fit was linear (CIMT = 0.828 + 0.009*glucose). CONCLUSIONS: There is a small but significant relationship between postprandial glucose levels and CIMT, which have both been associated with adverse cardiovascular outcomes.

Advanced cutaneous malignant melanoma: a systematic review of economic and quality-of-life studies.

OBJECTIVE: Metastatic melanoma (MM), a major concern for health-care providers, is increasing. We systematically reviewed published articles describing the impact of interventions (drugs and screening) on quality of life (QoL) in patients with MM, and articles that measured QoL in MM. METHODS: We searched secondary databases including MEDLINE, Embase, CINAHL, Cochrane, and DARE from inception to 2006 using MESH terms "melanoma" and "metastases." Economic articles were subject to established quality assessment procedures. RESULTS: We found 13 QoL and five economic studies (three cost-effectiveness, two cost-utility; average quality = 83% +/- 7%). No strong evidence was found in this review for cost-effectiveness of interferons in Canada (incremental cost-effectiveness ratio [ICER] = $55,090/quality-adjusted life-year) or temozolomide in the United States (ICER = $36,990/Life-year gained based on nonsignificant efficacy differences). Melanoma screening was not cost-effective in the United States ($150,000-931,000/life-saved) or Germany (no survival benefit). From the 13 QoL studies,eight measured baseline QoL; six studied the same population, generating similar results using different approaches/outcomes. Tools used included GLQ-8, QLQ-C30, QLQ-36, QWB-SA, and SF-36. Baseline scores QoL scores ranged from 0.60 to 0.69. Another five studies (N = 959 patients) were randomized trials analyzing QoL in patients treated with dacarbazine alone, dacarbazine +/- interferon, dacarbazine + fotemustine, interleukin +/- histamine, and temozolomide. Little difference was found in QoL scores between drugs or between baseline and end point. CONCLUSIONS: Cost-effectiveness has not been widely demonstrated for treatment of MM. Only two studies with unimpressive results exist for treatments. Screening was not cost-effective in the United States or Germany. Generally, no significant improvements in QoL were found for any alternative for treating MM. A need exists for effective treatments that improve duration and QoL.

Treatments for metastatic melanoma: synthesis of evidence from randomized trials.

BACKGROUND: Advanced melanomas (non-resectable Stage-III/IV) are fatal, with few effective treatments. It remains unclear if other drugs offer improvements over the standard, dacarbazine. PURPOSE: We quantified objective response rates (Complete+Partial response) of dacarbazine versus comparators for advanced cutaneous melanoma. METHODS: We retrieved all head-to-head randomized controlled trials involving dacarbazine and other drugs/combinations. Two reviewers searched MEDLINE (1966-Jan 2006), EMBASE (1980-2006), CINAHL (1982-2006) and Cochrane library, then compared results. Differences were resolved through consensus. Rates were combined using random effects meta-analysis. chi2 tested heterogeneity; points from Jadad's method were assessed to examine study quality. RESULTS: We found 48 studies having 111 active treatment arms [24 with dacarbazine monotherapy (n=1390), 75 with dacarbazine combinations (n=4962), and 12 with non-dacarbazine treatments (n=783)] treating 7135 patients. Overall, study quality was poor. Response to dacarbazine monotherapy ranged between 5.3% and 28.0% (average 15.3%), OR=1.31, CI(95%): 1.06-1.61; N=3356. Partial responses comprised 73% of successes. Only adding interferons improved response rates (OR=1.69, CI(95%): 1.07-2.68, N=778) but survival duration was not significantly longer (P=0.32), and trials with larger sample sizes found lower success rates. All other treatments alone or in combination were ineffective P>0.05. CONCLUSIONS: Dacarbazine generally produces poor outcomes. Adding other therapies offers minimal clinical advantages (possibly with interferons). In general, study quality was poor and sample sizes were small. This meta-analysis highlights the unmet need for effective treatment options for advanced melanoma.

Short- and long-term health consequences of sleep disruption.

Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption.

A comparative study of orphan drug prices in Europe.

Background and Objective: This study assessed price differences by comparing annual treatment costs of similarly available orphan drugs in France, Germany, Italy, Norway, Spain, Sweden, and UK. Methods: Annual treatment costs per drug were calculated using ex-factory prices from IHS POLI and country price databases. The treatment cost in the comparator country was compared to the UK and ratios were analysed. Subanalyses were done on disease areas and UK cost quartiles. Results: 120 orphan drugs were included. Compared to the UK, the average costs were more expensive in France (1.13), Germany (1.11), Italy (1.08), Spain (1.07), and were cheaper in Sweden (0.99) and Norway (0.88). The average ratios offered a restrictive view as ratios were greatly heterogeneous (0.26 to 1.92) which was also seen in the different disease areas. The averaged ratios varied minimally among the cost quartiles which shows that cost differences were similar for the most expensive and least expensive orphan drugs in the UK. Conclusions: Individual orphan drug prices can vary widely across European countries, although on average these differences are relatively minor. This study suggests that in Europe, we may not be able predict which country may have higher or lower prices for orphan drugs.

A systematic literature review of cysteamine bitartrate in the treatment of nephropathic cystinosis.

OBJECTIVES: To summarize available clinical evidence for cysteamine bitartrate preparations in the treatment of nephropathic cystinosis as identified through a systematic literature review (SLR). METHODS: We searched MEDLINE, MEDLINE In-Process and Embase using Ovid with a predefined search strategy through 19 January 2016. All publicly available clinical reports on the use of delayed-release (DR) cysteamine bitartrate (Procysbi 1 ) or immediate-release (IR) cysteamine bitartrate (Cystagon 2 ) in patients with cystinosis were included. RESULTS: We identified a total of 103 publications and 10 trial records. Of these, 9 studies describe DR cysteamine bitartrate (n = 267 patients), 42 describe IR cysteamine bitartrate (n = 1,427 patients) and in 53 studies the exact preparation was not specified (n = 906 patients). The vast majority of the studies used a non-randomized study design, with randomized clinical trials (RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n = 49) being the most common study design representing 47% of the total. CONCLUSION: A substantial evidence base for cysteamine bitartrate in the treatment of nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality, with evidence levels of 3 or 4.

Do payers value rarity? An analysis of the relationship between disease rarity and orphan drug prices in Europe.

Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relationship between the prevalence of rare diseases and the annual treatment cost of orphan drugs in France, Germany, Italy, Norway, Spain, Sweden, and UK. Methods: Approved orphan drugs and prevalence data were extracted from the European Medicines Agency website. Annual treatment costs were calculated using ex-factory price. Simple regression was used to analyse the relationship between costs and prevalence. A specific bivariate analysis was performed for the rarest diseases (≤1 per 10,000). Results: 120 drugs were analysed. Prevalence ranged from 0.001 to 5 per 10,000 (mean 1.24, median 1). Annual treatment costs per patient ranged from €755 to €1,051,956 (mean €100,000, median €39,303). Results show a statistically significant inverse correlation between annual treatment cost and disease prevalence in all countries (France: r = -0.370, p = 0.002; Germany: r = -0.365, p = 0.002; Italy: r = -0.340, p = 0.002; Spain: r = -0.316, p = 0.041; UK: r = -0.358, p = 0.0004; Sweden: r = -0.414, p = 0.014; Norway: r = -0.367, p = 0.002). When analysis was focused on the rarest diseases, a stronger correlation exists in all countries (France: r = -0.525, Germany: r = -0.482, Italy: r = -0.497, Spain: r = -0.531, UK: r = -0.436, Sweden: r = -0.455, Norway: r = -0.466; all p < 0.05 except Sweden p = 0.077). Conclusions: This study shows an inverse correlation between annual treatment cost and prevalence with high statistical significance in the studied countries. Although pricing is a complex process where different attributes are assessed, this study supports the idea that payers value rarity in pricing decisions.

Cost-effectiveness analysis of escitalopram compared with paroxetine in treatment of generalized anxiety disorder in the United Kingdom.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with substantial economic burden. OBJECTIVE: To assess, from a societal perspective, the cost-effectiveness of escitalopram and paroxetine in the treatment of GAD in the UK. METHOD: A decision analytic model with a 9 month time horizon was adapted to the UK setting. Model inputs included drug- and nondrug-specific probabilities from head-to-head trial data, published literature, and expert opinion. Main outcome measures were success (response after 12 wk of treatment and no relapse during the following 24 wk) and costs. Resource use was based on National Institute for Health and Clinical Excellence guidance for GAD patient management, and estimated unit costs came from standard national sources. Human capital approach was used to estimate costs of absence from work. The analysis was performed from the societal perspective. RESULTS: Escitalopram-treated patients were associated with 14.4% higher first-line treatment success and significantly lower discontinuation rates due to adverse events than were those treated with paroxetine. Treatment with escitalopram yielded lower expected costs with greater effectiveness compared with paroxetine. These clinical advantages led to less sick leave and resource use as a result of lower switch rates and use of secondary care. Total expected 9 month costs were 1408 pounds sterling (2560 US dollars) lower for escitalopram-treated patients than for paroxetine-treated patients. Sensitivity analyses on key parameters demonstrated robustness of the model. CONCLUSIONS: Escitalopram appears to be cost-effective compared with paroxetine in the treatment of GAD in the UK.

Systematic review of models used in economic analyses in moderate-to-severe asthma and COPD.

BACKGROUND: Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed. PURPOSE: To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD). METHODS: This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor. RESULTS: This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder. CONCLUSIONS: Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.

Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.

PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS. METHODS: A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates. RESULTS: Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times. IMPLICATIONS: Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.

A cost-effectiveness model of escitalopram, citalopram,and venlafaxine as first-line treatment for major depressive disorder in Belgium.

BACKGROUND: Economic evaluations aim to combine costs and patient outcomes in one analysis. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of escitalopram (vs all available competitors) for first-line treatment of major depressive disorder (MDD) in Belgium. METHODS: A 2-path decision analytic model with a 6-month horizon was used. All patients (baseline scores on the Montgomery-Asberg Depression Rating Scale [MADRS], > or =18 to < or =40) started at the primary path, and were referred to specialist care in the secondary care path. Model inputs included the following: probabilities from a meta-analysis of comparative trials data, an ad-hoc survey to evaluate pharmacologic treatment of depression in Belgium, literature, and a panel of experts. Main outcome measures were success (ie, remission [defined as MADRS < or =12]) and costs of treatment (ie, drug costs and medical care). Analyses were performed from the perspectives of the Belgian insurance system (IS) and society. The friction-cost method was used to estimate costs of lost productivity. Monetary values are reported in year-2003 Euros (1.0 approximately USD 1.1 in 2003). RESULTS: The expected success rate was 62.3% (95% CI, 60.1%-64.5%) for escitalopram compared with 57.2% (95% CI, 55.0%-59.4%) for citalopram. From the IS perspective, the expected cost per patient was Euros 390 (95% CI, Euros 372-Euros 409) for escitalopram compared with Euros 411 (95 % CI, Euros 391-Euros 431) for citalopram. From the societal perspective, these costs were Euros 1162 (95% CI, Euros 1106-Euros 1221) and Euros 1276 (95% CI, Euros 1216-Euros 1336), respectively. The success rates of venlafaxine (66.6% [95% CI, 64.2%-69.0%]) and escitalopram (67.0% [95% CI, 64.7%-69.4%]) were similar, but higher total costs were observed with venlafaxine, due to acquisition and secondary care costs. The use of data from various sources may have introduced bias. However, sensitivity analyses demonstrated that results of the model were robust. CONCLUSIONS: In this analysis, the treatment of MDD with escitalopram appeared to be a cost-effective alternative compared with citalopram and venlafaxine, leading to better clinical outcomes and cost savings compared with citalopram in the model used. The success rates were similar between venlafaxine and escitalopram, but higher total costs were observed with venlafaxine.

A pharmacoeconomic evaluation of escitalopram versus citalopram in the treatment of severe depression in the United Kingdom.

BACKGROUND: Severe depression can increase the risk of psychiatric hospitalization, as well as inpatient and outpatient care; it may also lead to long-term absenteeism from work. However, the cost-effectiveness of antidepressant therapy for severe depression has been little studied. OBJECTIVE: The aim of this work was to investigate the cost-effectiveness of escitalopram compared with citalopram in patients with severe depression (Montgomery-Asberg Depression Rating Scale [MADRS] total score > or = 30) in the United Kingdom. METHODS: A probabilistic decision tree with a 6-month time horizon was adapted to the UK setting. The model incorporated clinical data, resource use directly related with care of severe depression, and lost productivity costs due to absenteeism. Primary results were remission (MADRS < or = 12) and costs (in year-2003 British pounds [1.00 British pound = 0.62 US dollars in January 2003]) of treatment calculated from the perspectives of UK society and the National Health Service (NHS). Secondary outcome was first-line success of treatment (ie, remission [MADRS < or = 12] without switch of drug). Remission, discontinuation, and response rates were derived from a meta-analysis of 506 patients with severe depression and extrapolated to 6 months. Standard UK price lists and literature were used to identify costs of resources. Societal costs of lost productivity were calculated using the human capital approach. RESULTS: Treatment of patients with escitalopram instead of citalopram rendered a higher overall remission rate (relative difference, 10.3%) and first-line success rate (relative difference, 35.4%). The mean cost per successfully treated patient was 15.7% (146 British pounds) lower for escitalopram (786 British pounds [range, 702-876 British pounds]) compared with citalopram (932 British pounds [range, 843-1028 British pounds]) from the NHS perspective and 15.6% (238 British pounds) lower for escitalopram (1283 British pounds [range, 1157-1419 British pounds]) than for citalopram (1521 British pounds [range, 1383-1675 British pounds]) from the societal perspective. The mean cost per severely depressed patient treated (overall study group) was 32 British pounds lower for escitalopram (422 British pounds [range, 404-441 British pounds]) than citalopram (454 British pounds [range, 436-471 British pounds]) from an NHS perspective and 50 British pounds lower for escitalopram (690 British pounds [range, 665-714 British pounds]) than citalopram (740 British pounds [range, 715-767 British pounds]) from the societal perspective. Using multivariate sensitivity analyses, we found that, in 99.8% of the cases, escitalopram was dominant from both perspectives at all ranges of probabilities tested. A sensitivity analysis on the acquisition cost of citalopram verified that, from the societal perspective, escitalopram remained the dominant strategy, even at a cost of 0.00 British pounds for citalopram. CONCLUSIONS: These results suggest that escitalopram is a cost-saving alternative to citalopram for the treatment of severe depression in the United Kingdom from the perspectives of both the NHS and society. Therefore, a possible advantage may exist at the population level in the treatment of severe depression with escitalopram in the United Kingdom.

A probabilistic cost-effectiveness analysis of escitalopram, generic citalopram and venlafaxine as a first-line treatment of major depressive disorder in the UK.

OBJECTIVES: To determine if escitalopram is cost-effective in the UK when compared with venlafaxine and generic citalopram in primary care treatment of Major Depressive Disorder (MDD). METHODS: A pre-existing cost-effectiveness model was adapted to reflect the practice in the UK. Adult patients (> 18 years) with MDD [baseline scores >/= 18 and

Utilities for asthma and COPD according to category of severity: a comprehensive literature review.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are incurable diseases that impact quality-of-life. OBJECTIVE: To summarize original research articles that measured or utilized preference-based utilities or disutilities according to disease severity. METHODS: Medline and Embase were searched from inception until the end of November 2014. Two reviewers independently searched the literature with differences settled through discussion. Data extracted included utility scores as determined in original research categorized according to disease severity as well as disutilities associated with exacerbations or comorbidities. Data were tabulated and analyzed descriptively. RESULTS: In total, 862 articles were identified, 790 were rejected, and 69 analyzed. There were 44 dealing with COPD and 25 with asthma. Average utilities determined by research were 0.828 ± 0.062, 0.765 ± 0.090, 0.711 ± 0.120, and 0.607 ± 0.120 for mild, moderate, severe, and very severe COPD, respectively. Utilities used in economic analyses were 0.866 ± 0.038, 0.770 ± 0.024, 0.739 ± 0.045, and 0.596 ± 0.075, respectively. Disutilities (annual) ranged from 0.002-0.378; major and minor exacerbations had respective disutilities of 0.287 and 0.108. For asthma patients, utilities were for 0.86 ± 0.32, 0.83 ± 0.065, and 0.74 ± 0.029, for mild, moderate, and severe disease, respectively. CONCLUSIONS: Utilities have been summarized according to severity category of asthma and COPD. These values should be useful for researchers undertaking economic analyses of these diseases.

Patient preferences in severe COPD and asthma: a comprehensive literature review.

BACKGROUND: Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult. Incorporation of patient preferences is widely encouraged. PURPOSE: To summarize original research articles determining patient preference in moderate-to-severe disease. METHODS: Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma. The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease. We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences. Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion. Data were tabulated and analyzed descriptively. RESULTS: About 478 articles identified, 448 were rejected and 30 analyzed. There were 25 on COPD and five on asthma. Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient-physician relationship, quality-of-life impairments, and information availability. Patients strongly preferred sponsors' inhalers. At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention. While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience. Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler. CONCLUSION: Few studies have examined patient preference in these diseases. More research is needed to fill in knowledge gaps.