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.

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.

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.

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.

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.

Validation of an economic model of paliperidone palmitate for chronic schizophrenia.

OBJECTIVE: Model validation is important, but seldom applied in chronic schizophrenia. Validation consists of verifying the model itself for face validity (i.e., structure and inputs), cross-validation with other models assessing the same issue, and comparison with real-life outcomes. The primary purpose was to cross-validate a recent pharmacoeconomic model comparing long-acting injectable (LAI) antipsychotics for treating chronic schizophrenia in Sweden. The secondary purpose was to provide external validation. METHODS: The model of interest was a decision tree analysis with a 1-year time horizon with costs in 2011 Swedish kroner. Drugs analyzed included paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol (HAL-LAI), and oral olanzapine (oral-OLZ). Embase and Medline were searched from 1990-2012 for models examining LAIs. Articles were retrieved, with data extracted for all drugs compared including: expected costs, rates of hospitalization, proportion of time not in relapse, and associated QALYs. Outcomes from the model of interest were compared with those from other articles; costs were projected to 2012 using the consumer price index. RESULTS: Twenty-six studies were used for validation; 14 of them provided evidence for cross-validation, 13 for external validation, and four for cost. In cross-validation, cost estimates varied -1.8% (range: -12.4-20.1%), hospitalizations 5.2% (-12.1-3.1%), stable disease 2.5% (-5.6-1.5%), QALYs 9.0% (4.3% after removing outliers). All estimates of clinical outcomes were within 15%. In external validation, hospitalization rates varied by 6.3% (-0.7-11.3%). The research was limited by data availability and validity of the original results. CONCLUSION: Other models validated the outputs of our model very well.

Cost-effectiveness analysis of atypical long-acting antipsychotics for treating chronic schizophrenia in Finland.

OBJECTIVE: In Finland, regional rates of schizophrenia exceed those in most countries, impacting the healthcare burden. This study determined the cost-effectiveness of long-acting antipsychotic (LAI) drugs paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), and risperidone (RIS-LAI) for chronic schizophrenia. METHOD: This study adapted a decision tree analysis from Norway for the Finnish National Health Service. Country-specific data were sought from the literature and public documents, guided by clinical experts. Costs of health services and products were retrieved from literature sources and current price lists. This simulation study estimated average 1-year costs for treating patients with each LAI, average remission days, rates of hospitalization and emergency room visits and quality-adjusted life-years (QALY). RESULTS: PP-LAI was dominant. Its estimated annual average cost was €10,380/patient and was associated with 0.817 QALY; OLZ-LAI cost €12,145 with 0.810 QALY; RIS-LAI cost €12,074 with 0.809 QALY. PP-LAI had the lowest rates of hospitalization, emergency room visits, and relapse days. This analysis was robust against most variations in input values except adherence rates. PP-LAI was dominant over OLZ-LAI and RIS-LAI in 77.8% and 85.9% of simulations, respectively. Limitations include the 1-year time horizon (as opposed to lifetime costs), omission of the costs of adverse events, and the assumption of universal accessibility. CONCLUSION: In Finland, PP-LAI dominated the other LAIs as it was associated with a lower cost and better clinical outcomes.

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic.

PURPOSE: The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots. METHODS: An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables. RESULTS: Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates. CONCLUSIONS: PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.

Cost-Utility Analysis of Depot Atypical Antipsychotics for Chronic Schizophrenia in Croatia.

OBJECTIVES: As a nation with a developing economy, Croatia is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. We conducted a pharmacoeconomic analysis to determine the cost-effectiveness of atypical depots in Croatia. METHODS: A 1-year decision-analytic framework modeled drug use. We determined the average direct cost to the Croatian Institute for Health Insurance of using depot formulations of paliperidone palmitate long-acting injectable (PP-LAI), risperidone LAI (RIS-LAI), or olanzapine LAI (OLZ-LAI). An expert panel plus literature-derived clinical rates populated the core model, along with costs adjusted to 2012 by using the Croatian consumer price index. Clinical outcomes included quality-adjusted life-years, hospitalization rates, emergency room treatment rates, and relapse days. Robustness of results was examined with one-way sensitivity analyses on important inputs; overall, all inputs were varied over 10,000 simulations in a Monte Carlo analysis. RESULTS: Costs (quality-adjusted life-years) per patient were €5061 (0.817) for PP-LAI, €5168 (0.807) for RIS-LAI, and €6410 (0.812) for OLZ-LAI. PP-LAI had the fewest relapse days, emergency room visits, and hospitalizations. Results were sensitive against RIS-LAI with respect to drug costs and adherence rates, but were generally robust overall, dominating OLZ-LAI in 77.3% and RIS-LAI in 56.8% of the simulations. CONCLUSIONS: PP-LAI dominated the other drugs because it had the lowest cost and best clinical outcomes. Compared with depots of olanzapine and risperidone and oral olanzapine, PP-LAI was the cost-effective atypical LAI for treating chronic schizophrenia in Croatia. Using depot paliperidone in place of either olanzapine or risperidone would reduce the overall costs of caring for these 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.

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.

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.

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

Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis.

BACKGROUND: Due to the high prevalence of depression in women of childbearing age and coupled with the fact that approximately 50% of the pregnancies are unplanned, there is a high chance that these women have been exposed to antidepressants in early pregnancy. OBJECTIVE: To determine baseline rates of spontaneous abortions (SAs) and whether antidepressants increase those rates. METHODS: Rates of SAs in women taking antidepressants compared with non-depressed women were combined into a relative risk using a random effects model. MEDLINE, EMBASE, Healthstar, Toxline, Psychlit, Cochrane database, and Reprotox were searched for studies published in any language from 1966 to 2003. Key words used to identify articles included pregnancy outcome, abortion, miscarriage, spontaneous, antidepressant, depression, and the generic names of each antidepressant and class. Bibliographies, review articles, and reference lists from studies were also used to identify potential articles expected to provide evidence of safety of antidepressants in pregnancy. RESULTS: Of 15 potential articles, 6 cohort studies of 3567 women (1534 exposed, 2033 nonexposed) provided extractable data. All matched on important confounders. Tests found no heterogeneity (chi2 3.13; p = 0.98), and all quality scores were adequate (>50%). The baseline SA rate (95% CI) was 8.7% (7.5% to 9.9%; n = 2033). For antidepressants, the rate was 12.4% (10.8% to 14.1%; n = 1534), significantly increased by 3.9% (1.9% to 6.0%); RR was 1.45 (1.19 to 1.77; n = 3567). No differences were found among antidepressant classes. CONCLUSIONS: Maternal exposure to antidepressants may be associated with increased risk for SA; however, depression itself cannot be ruled out.

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.

Paternal organic solvent exposure and adverse pregnancy outcomes: a meta-analysis.

BACKGROUND: Organic solvents are widely used, but conflicting reports exist concerning paternal exposure and adverse pregnancy outcomes. We conducted a meta-analysis to assess the risks of spontaneous abortions (SAs) and major malformations (MMs) after paternal exposure to organic solvents. METHODS: Medline, Toxline, Reprotox, and Embase from 1966 to 2003 were searched. Two independent reviewers searched for cohort and case-control studies in any language on adult human males exposed chronically to any organic solvent. Two non-blinded independent extractors used a standardized form for data extraction; disagreements were resolved through consensus discussion. RESULTS: Forty-seven studies were identified; 32 exclusions left 14 useable studies. Overall random effects odds ratios and 95% confidence intervals (CI95%) were 1.30 (CI95%: 0.81-2.11, N=1,248) for SA, 1.47 (CI95%: 1.18-1.83, N=384,762) for MMs, 1.86 (CI95%: 1.40-2.46, N=180,242) for any neural tube defect, 2.18 (CI95%: 1.52-3.11, N=107,761) for anencephaly, and 1.59 (CI95%: 0.99-2.56, N=96,517; power=56.3%) for spina bifida. CONCLUSIONS: Paternal exposure to organic solvents is associated with an increased risk for neural tube defects but not SAs.

Economic evaluation of an extended acellular pertussis vaccine programme for adolescents in Ontario, Canada.

PURPOSE: Pertussis is a frequent cause of cough illness in adolescents. In Canada, until recently immunization against pertussis in public programmes has been restricted to children under the age of 7. The purpose of this analysis was to estimate the health and economic impact of an additional booster dose of the acellular vaccine in adolescents in Ontario. METHODS: We performed a cost effectiveness analysis, based on a predictive spreadsheet dynamic model following a cohort of 144,000 adolescents in Ontario from the age of 12 years over a 10-year-period from the Ontario Ministry of Health (MoH) and societal perspectives. The model was used to compare costs and benefits of a combined vaccination programme (CVP) including tetanus, diphtheria, and acellular pertussis (dTacp) administered at age 12, compared to current practice. RESULTS: From the MoH perspective, booster vaccination of dacpT at 12 years via the CVP would produce a yearly additional expected cost of CAD $0.52 per adolescent in Ontario with an incremental cost-effectiveness ratio of CAD $168 per pertussis case avoided based on a 10-year-period. If outcomes are discounted at 3%, the incremental cost-effectiveness ratio rises to $188/discounted pertussis case avoided. From the societal perspective, the CVP would be cost saving CAD $858,106 at 10 years for the cohort. Over the 10-year-period, more than 4400 cases of pertussis would be prevented with approximately 50 hospital admissions averted. CONCLUSIONS: This study suggests that administering a booster dose of dTacp at 12 years of age to replace diphtheria and tetanus vaccination at 14 years may reduce the economic burden of pertussis treatment in the long term at a reasonable cost.