All-cause community acquired pneumonia cost by age and risk in real-world conditions of care in Spain.

BACKGROUND: Economic burden of community-acquired pneumonia (CAP) is recognized. Few studies have documented such burden in adults stratified by age, risk status, and by care setting. Spanish data available is scarce. METHOD: A retrospective, multicenter study in seven regions of Spain (2017-2019) was conducted. Patients ≥18 years with a primary all-cause CAP episode diagnosis were identified. Episode-level variables included risk-stratum based on presence of an immunocompromising/chronic condition, age, number and length of hospitalized and outpatient episodes, and CAP-related healthcare costs/sick leaves were included. RESULTS: 7,108 episodes [mean age (SD): 59.2 (19.6), 50.42% male, 31.0% hospitalized] were analyzed. Low-risk group accounted for 47.7% of all CAP episodes, 31.5% moderate-risk and 20.8% high-risk. Pneumococcus was identified in 42.2% of cases. Mean CAP episode length was 22.9 days for hospitalized and 13.7 days for outpatient episode. Total healthcare cost for episode was higher in inpatient vs. outpatient: €3,955 vs. €511, p < 0.001, with higher sick leave cost (€3,281 vs. €2,632, p < 0.001), respectively. CONCLUSION: CAP required hospitalization cost is high regardless of age or comorbidities for the Spanish NHS. Given that almost half of the patients in this study did not have traditional risk factors for CAP, better preventative strategies should seriously be considered.

Cost-effectiveness analysis of fesoterodine flexible dose in newly diagnosed patients with overactive bladder in routine clinical practice in Spain.

OBJECTIVE: To carry out cost-effectiveness analysis from the Spanish National Health System perspective, of treating overactive bladder (OAB), in newly diagnosed patients with two flexible doses of fesoterodine in routine clinical practice. PATIENTS AND METHODS: Economic evaluation of flexible-dose fesoterodine in newly diagnosed patients, including two treatment groups: standard escalating from 4 to 8 mg or fast escalating to 8 mg. Costs were estimated from health care resources utilization related to OAB, and were expressed in 2015 Euros. Quality-adjusted life-years (QALYs) were obtained from overactive bladder questionnaire-short form. Univariate and probabilistic sensitivity analyses were carried out. RESULTS: Three hundred and ninety symptomatic OAB patients treated with fesoterodine and newly diagnosed (141 in fast escalating group and 249 in standard escalating) were analyzed. Adjusted health care total costs were not statistically different; difference -€4.1 (confidence interval: -153.3; 25.1) P=0.842. QALYs were higher in fast escalating to high dose vs standard escalating group, resulting in a cost of -€16,020/QALY gained for fast escalating vs standard escalating group. CONCLUSION: When the cost-effectiveness threshold is set at a maximum value of €30,000/QALY gained, fesoterodine fast escalating group was cost-effective vs standard escalating group 67.6% of the time. The treatment with fesoterodine, in female patients newly diagnosed, fast escalating to 8 mg was a cost-effective option relative to escalating traditionally from 4 to 8 mg, in the management of OAB in routine clinical practice, from the Spanish National Health System perspective.

Cost Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccination Program in Chronic Obstructive Pulmonary Disease Patients Aged 50+ Years in Spain.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at elevated risk of pneumococcal infection. A 13-valent pneumococcal conjugate vaccine (PCV13) was approved for protection against invasive disease and pneumonia caused by Streptococcus pneumoniae in adults. This study estimated the incremental cost-effectiveness ratio (ICER) of vaccinating COPD patients ≥50 years old with PCV13 compared with current vaccination policy (CVP) with 23-valent pneumococcal polysaccharide vaccine. METHODS: A Markov model accounting for the risks and costs for all-cause non-bacteremic pneumonia (NBP) and invasive pneumococcal disease (IPD) was developed. All parameters, such as disease incidence and costs (€; 2015 values), were based on published data. The perspective of the analysis was that of the Spanish National Healthcare System, and the horizon of evaluation was lifetime in the base case. Vaccine effectiveness considered waning effect over time. Outcomes and costs were both discounted by 3% annually. RESULTS: Over a lifetime horizon and for a 629,747 COPD total population, PCV13 would prevent 2224 cases of inpatient NBP, 3134 cases of outpatient NBP, and 210 IPD extra cases in comparison with CVP. Additionally, 398 related deaths would be averted. The ICER was €1518 per quality-adjusted life-year (QALY) gained for PCV13 versus CVP. PCV13 was found to be cost effective versus CVP from a 5-year modelling horizon (1302 inpatient NBP and 1835 outpatient NBP cases together with 182 deaths would be prevented [ICER €25,573/QALY]). Univariate and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: At the commonly accepted willingness-to-pay threshold of €30,000/QALY gained, PCV13 vaccination in COPD patients aged ≥50 years was a cost-effective strategy compared with CVP from 5 years to lifetime horizon in Spain.

Budgetary impact analysis on funding smoking-cessation drugs in patients with COPD in Spain.

The aim of the study was to assess the budgetary impact of funding smoking-cessation drugs in COPD patients in Spain. A hybrid model (cohort and Markov) was developed for a 5-year time horizon. Only approved cessation drugs (varenicline, bupropion, and nicotine replacement therapy) were considered. Irrespective of the drug, the model allowed for an initial cessation attempt, and up to three additional attempts in case of failure or smoking relapse during a 5-year period. Drug effectiveness was based on controlled clinical trials. National Health System perspective was applied; therefore, only medical resources were included. The pharmaceutical costs for smoking-cessation drugs, extra medical follow-up as a consequence of public reimbursement, and annual savings for health costs avoided due to stopping smoking were considered. The model estimated that 17,756 COPD patients would stop smoking if public funding was available, compared with 1,303 without reimbursement. In the reimbursement scenario, the savings accounted for a total of €48.0 million, compensating for expenditures on drugs and medical visits (€40.4 million). Accumulated total additional savings in 5 years (€4.3 million) compared with the scenario without reimbursement was shown. Sensitivity analyses supported the results robustness. Funding smoking-cessation drugs in COPD patients seems to be an efficient option and a National Health System drug reimbursement scheme would represent a cost-saving policy in Spain.

Disability-adjusted-life-years losses in postmenopausal women with osteoporosis: a burden of illness study.

BACKGROUND: To estimate the disability-adjusted life years (DALY) in a nationwide representative sample of postmenopausal women with osteoporosis. The effects of drug-based therapy and risk factors for osteoporotic bone fractures on DALY losses were also explored. METHODS: DALY were estimated based on participant's clinical characteristics and Health-Related Quality-of-Life (HRQoL) data obtained from a cross-sectional, epidemiological one-visit study (the GINERISK study). The study enrolled postmenopausal women (at least 12-months after their last menstrual period) with osteoporosis, above 18-years old, who attended Spanish outpatient Gynaecology clinics. HRQoL was assessed using the generic SF-12v2 questionnaire, which was used to derive disutility values. Mortality rates were extracted from the Spanish national statistics database. Factors explored to be associated with DALY losses were examined using ANOVA, ANCOVA and MANCOVA models. RESULTS: DALY could be computed in 2,782 (67%) out of 4,157 postmenopausal women, with a mean (95% CI) age of 61.0 (60.7-61.2) years. Overall individual undiscounted DALY per woman were 6.1 (5.9-6.2), resulting to be significantly higher in women with severe osteoporosis with prior bone fracture; 7.8 (7.2-8.4) compared to osteoporotic women [5.8 (5.6-6.0)] or postmenopausal women with a BMD > -2.5 T-score that received a drug-based therapy [6.2 (5.8-6.5)]; F = 27.0 (P < 0.01). Models explaining the variation in the levels of health based on the use of a selective estrogen receptor modulator (SERM) or possession of risk factors for osteoporotic BF were found (P < 0.05). CONCLUSIONS: DALY losses were considerable amongst postmenopausal women with osteoporosis. Not having a prior bone fracture, being older, using a SERM and having less osteoporotic risk factors were all linked to less DALY losses.

Clinical and economic outcomes of adjunctive therapy with pregabalin or usual care in generalized anxiety disorder patients with partial response to selective serotonin reuptake inhibitors.

BACKGROUND: This study is done to compare the effect of adjunctive therapy with pregabalin versus usual care (UC) on health-care costs and clinical and patients consequences in generalized anxiety disorder (GAD) subjects with partial response (PR) to a previous selective serotonin reuptake inhibitor (SSRI) course in medical practice in Spain. METHODS: Post hoc analysis of patients with PR to SSRI monotherapy enrolled in a prospective 6-month naturalistic study was done. PR was defined as a Clinical Global Impression (CGI) scale score ≥3 and insufficient response with persistence of anxiety symptoms ≥16 in the Hamilton Anxiety Rating Scale (HAM-A). Two groups were analyzed: 1) adjunctive therapy (AT) with pregabalin (150-600 mg/day) to existing therapy and 2) UC (switching to a different SSRI or adding another anxiolytic different than pregabalin). Costs included GAD-related health-care resources utilization. Consequences were a combination of psychiatrist-based measurements [HAM-A, CGI, and Montgomery-Asberg Depression Rating Scale (MADRS)] and patient-reported outcomes [Medical Outcomes Study Sleep (MOS-sleep) scale, disability (World Health Organization Disability Assessment Schedule II (WHO-DAS II) and quality-of-life (Euro Qol-5D (EQ-5D)]. Changes in both health-care costs and scale scores were compared separately at end-of-trial visit by a general linear model with covariates. RESULTS: Four hundred eighty-six newly prescribed pregabalin and 239 UC GAD patients [mean (SD) HAM-A 26.7 (6.9) and CGI 4.1 (0.5)] were analyzed. Adding pregabalin was associated with significantly higher mean (95% CI) score reductions vs. UC in HAM-A [-14.9 (-15.6; -14.2) vs. -11.2 (-12.2; -10.2), p < 0.001] and MADRS [-11.6 (-12.2; -10.9) vs. -7.8 (-8.7; -6.8), p < 0.001]. Changes in all patient-reported outcomes favored significantly patients receiving pregabalin, including quality-of-life gain; 26.4 (24.7; 28.1) vs. 19.4 (17.1; 21.6) in the EQ-VAS, p < 0.001. Health-care costs were significantly reduced in both cohorts yielding similar 6-month costs; €1,565 (1,426; 1,703) pregabalin and €1,406 (1,200; 1,611) UC, p = 0.777. The effect of sex on costs and consequences were negligible. CONCLUSION: In medical practice, GAD patients with PR to SSRI experienced greater consequence improvements with adjunctive therapy with pregabalin versus UC, without increasing health-care cost. The effect of pregabalin was independent of patient gender.

Disability in bipolar I disorder: the 36-item World Health Organization Disability Assessment Schedule 2.0.

BACKGROUND: The WHODAS 2.0 is an ICF-based multidimensional instrument developed for measuring disability. The present study analyzes the utility of the 36-item interviewer-administered version in a sample of patients with bipolar disorder. There is no study to date that analyses how the scale works in a sample that only comprises such patients. METHODS: A total of 291 patients with bipolar disorder (42.6% males) according to DSM-IV-TR criteria from a cross-sectional study conducted in outpatient psychiatric clinics were enrolled. In addition to the WHODAS 2.0, patients completed a comprehensive assessment battery including measures on psychopathology, functionality and quality of life. Analyses were centered on providing evidence on the validity and utility of the Spanish version of the WHODAS 2.0 in bipolar patients. RESULTS: Participation domain had the highest percentage of missing data (2.7%). Confirmatory factorial analysis was used to test three models formulated in the literature: six primary correlated factors, six primary factors with a single second-order factor, and six primary factors with two second-order factors. The three models were plausible, although the one formed by six correlated factors produced the best fit. Cronbach's alpha values ranged between .73 for the Self-care domain and .92 for Life activities, and the internal consistency of the total score was .96. Relationships between the WHODAS 2.0 and measures of psychopathology, functionality and quality of life were in the expected direction, and the scale was found to be able to differentiate among patients with different intensity of clinical symptoms and work situation. LIMITATIONS: The percentage of euthymic patients was considerable. However, the assessment of euthymic patients is less influenced by mood. Some psychometric properties have not been studied, such as score stability and sensitivity to change. CONCLUSIONS: The Spanish version of the 36-item WHODAS 2.0 has suitable psychometric properties in terms of reliability and validity when applied to patients with bipolar disorder. Disability in bipolar patients is especially prominent in Cognition, Getting along, Life activities, and Participation domains, so functional remediation interventions should emphasize these areas in order to improve the daily living activities of these patients.

Modeling the predictive value of pain intensity on costs and resources utilization in patients with peripheral neuropathic pain.

OBJECTIVE: The aim of the present analysis was to model the association and predictive value of pain intensity on cost and resource utilization in patients with chronic peripheral neuropathic pain (PNP) treated in routine clinical practice settings in Spain. METHODS: We performed a secondary economic analysis based on data from a multicenter, observational, and prospective cost-of-illness study in patients with chronic PNP that is refractory to prior treatment. Pain intensity was measured using the Short-Form McGill Pain Questionnaire. Univariate and multivariate linear regression models were fitted to identify independent predictors of cost and health care/non-health care resource utilization. RESULTS: A total of 1703 patients were included in the current analysis. Pain intensity was an independent predictor of total costs ([total costs]=35.6 [pain intensity]+214.5; coefficient of determination [R(2)]=0.19, P<0.001), direct costs ([direct costs]=10.8 [pain intensity]+257.7; R=0.06, P<0.001), and indirect costs ([indirect costs]=24.8 [pain intensity]-43.4; R(2)=0.20, P<0.001) related to chronic PNP in the univariate analysis. Pain intensity remains significantly associated with total costs, direct costs, and indirect costs after adjustment by other covariates in the multivariate analysis (P<0.001). None of the other variables considered in the multivariate analysis were predictors of resource utilization. DISCUSSION: Pain intensity predicts the health care and non-health care resource utilization, and costs related to chronic PNP. Management of patients with drugs associated with a higher reduction of pain intensity may have a greater impact on the economic burden of that condition.

Cost effectiveness of fesoterodine and tolterodine for the treatment of overactive bladder with urge urinary incontinence in Spain and Finland.

BACKGROUND: Overactive bladder is a prevalent condition worldwide that is associated with a considerable burden, both on the patient and on society. OBJECTIVE: Our objective was to assess the economic value of fesoterodine compared with tolterodine extended release (ER) for the treatment of overactive bladder (OAB) with urge urinary incontinence (UUI) in Spain and Finland. METHODS: A decision-tree economic model estimated the 52-week costs and quality-adjusted life-years (QALYs) of OAB/UUI patients initiating treatment with fesoterodine 4 mg/day or tolterodine ER. Individuals were evaluated for treatment response (UUI fewer than one episode/day) and persistence at weeks 4, 12, and 24. Titration from fesoterodine 4 mg/day to 8 mg/day was permitted at week 4. At week 12, non-responders discontinued treatment permanently. Efficacy, discontinuation, and utility data were derived from four clinical trials of fesoterodine. OAB-related costs, including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections, depression, and nursing home) were also included. RESULTS: A total of 19.5 % and 18.0 % of fesoterodine and tolterodine ER patients remained on treatment until week 52, respectively. QALYs were higher with fesoterodine than tolterodine ER (0.762 vs. 0.760). In Spain, fesoterodine treatment had higher total costs than (generic) tolterodine ER (€6,697 vs. 6,597), resulting in a cost of €15,633/QALY gained. In Finland, fesoterodine was cost saving relative to (non-generic) tolterodine ER (€7,885 vs. 8,024). Sensitivity analysis confirmed that these findings were robust to the expected price decrease for generic tolterodine ER in Finland. CONCLUSION: Fesoterodine is cost effective or cost saving relative to tolterodine ER for the treatment of OAB with UUI in two European countries. Payers and prescribers should consider a broad scope of costs to make informed cost-conscious choices of antimuscarinic treatment.

Clinical and resource utilization patterns in patients with refractory neuropathic pain prescribed pregabalin for the first time in routine medical practice in primary care settings in Spain.

CONTEXT AND OBJECTIVE: To describe clinical and resource utilization patterns in patients with refractory neuropathic pain (NeP) who were prescribed pregabalin for the first time in routine medical practice in primary care settings. METHODS: Post-hoc analysis of a 12-week prospective observational study including pregabalin naïve adult patients with refractory chronic NeP of at least 6-months duration. Self-reported pain intensity, disability, sleep disturbances, symptoms of anxiety and depression, disability, health-related quality of life (HRQoL), health care resource utilization, and corresponding costs were assessed in this post-hoc analysis. RESULTS: One thousand three hundred fifty-four patients were enrolled in the study, and three treatment groups were identified: (1) 598 patients replaced prior pain treatments with pregabalin as monotherapy; (2) 589 added pregabalin to their existing pain treatments; and (3) 167 other pain treatments were prescribed according with physician routine medical practice. Statistically significant differences were reported at baseline for intensity of pain, patient disability, severity of depressive symptoms, and HRQoL (P < 0.01 in all cases). No statistically significant differences were reported among the three treatment groups for anxiety severity or sleep disturbances. Subjects who received add-on pregabalin had greater use of direct and indirect resources vs the other groups, resulting in significantly higher quarterly overall costs per patient: €2,397 (2,308), €2,470 (1,857), and €3,110 (2,496), respectively (P < 0.001). CONCLUSION: These findings suggest that primary care physicians chose pregabalin as an option for treating refractory patients who tended to have much more severe NeP profiles, costing society more than when they chose other therapeutic strategies not including pregabalin.

Adding pregabalin or gabapentin for the management of community-treated patients with painful diabetic peripheral neuropathy: a comparative cost analysis.

BACKGROUND AND OBJECTIVE: Painful diabetic peripheral neuropathy (pDPN) is a highly prevalent complication of diabetes mellitus, which is associated with substantial costs to society and national health systems. This economic impact varies depending on the therapeutic management provided to patients. The objective of this study was to compare healthcare resource utilization and costs among pDPN patients newly treated with pregabalin or gabapentin in routine medical practice. METHODS: We performed a retrospective medical records study of pDPN patients newly treated with pregabalin or gabapentin as an add-on therapy who are covered by the Badalona Serveis Assistencials (BSA) health plan, a healthcare provider in Spain, from 2006 to 2009. Healthcare resource utilization and days off work were assessed. The societal perspective was used to estimate costs. RESULTS: Three hundred and ninety-five records were eligible for analysis: 227 (57.5%) included pregabalin and 168 (42.5%) gabapentin. Mean (standard deviation) concomitant use of analgesics throughout the study was higher in the gabapentin cohort [3.9 (2.2) vs. 3.1 (2.1); p < 0.05], mainly due to greater use of non-narcotics (78.0 vs. 71.8%; p < 0.05) and opioids (32.7 vs. 28.6%; p < 0.05). Healthcare costs accounted for 59.2% of total costs, of which 71.9% occurred in primary care, with a mean cost per patient of €2,476 (year 2010 values). Adjusted mean (95% CI) total costs were significantly lower in pregabalin-treated patients [€2,003 (1,427-2,579)] than in gabapentin-treated patients [€3,127 (2,463-3,790)] (p = 0.013), mainly due to lower healthcare costs [€1,312 (1,192-1,432) vs. €1,675 (1,537-1,814); p < 0.001]. CONCLUSIONS: Adding pregabalin to existing pDPN therapy resulted in lower total healthcare costs and lower resource utilization than resulted from adding gabapentin.

Health economics perspective of fesoterodine, tolterodine or solifenacin as first-time therapy for overactive bladder syndrome in the primary care setting in Spain.

BACKGROUND: Overactive bladder (OAB) is associated with high healthcare costs, which may be partially driven by drug treatment. There is little comparative data on antimuscarinic drugs with respect to resource use and costs. This study was conducted to address this gap and the growing need for naturalistic studies comparing health economics outcomes in adult patients with OAB syndrome initiating treatment with different antimuscarinic drugs in a primary care setting in Spain. METHODS: Medical records from the databases of primary healthcare centres in three locations in Spain were assessed retrospectively. Men and women ≥18 years of age who initiated treatment with fesoterodine, tolterodine or solifenacin for OAB between 2008 and 2010 were followed for 52 weeks. Healthcare resource utilization and related costs in the Spanish National Health System were compared. Comparisons among drugs were made using multivariate general linear models adjusted for location, age, sex, time since diagnosis, Charlson comorbidity index, and medication possession ratio. RESULTS: A total of 1,971 medical records of patients (58.3% women; mean age, 70.1 [SD:10.6] years) initiating treatment with fesoterodine (n = 302), solifenacin (n = 952) or tolterodine (n = 717) were examined. Annual mean cost per patient was €1798 (95% CI: €1745; €1848). Adjusted mean (95% bootstrap CI) healthcare costs were significantly lower in patients receiving fesoterodine (€1639 [1542; 1725]) compared with solifenacin (€1780 [€1699; €1854], P = 0.022) or tolterodine (€1893 [€1815; €1969], P = 0.001). Cost differences occurred because of significantly fewer medical visits, and less use of absorbent products and OAB-related concomitant medication in the fesoterodine group. CONCLUSIONS: Compared with solifenacin and tolterodine, fesoterodine was a cost-saving therapy for treatment of OAB in the primary care setting in Spain.

Cost-effectiveness of bazedoxifene versus raloxifene in the treatment of postmenopausal women in Spain.

BACKGROUND: The purpose of this study was to assess the cost-effectiveness of bazedoxifene and raloxifene for prevention of vertebral and nonvertebral fractures among postmenopausal Spanish women aged 55-82 years with established osteoporosis and a high fracture risk. METHODS: A Markov model was developed to represent the transition of a cohort of postmenopausal osteoporotic women through different health states, ie, patients free of fractures, patients with vertebral or nonvertebral fractures, and patients recovered from a fracture. Efficacy data for bazedoxifene were obtained from the Osteoporosis Study. The perspective of the Spanish National Health Service was chosen with a time horizon of 27 years. Costs were reported in 2010 Euros. Deterministic results were presented as expected cost per quality-adjusted life-year (QALY), and probabilistic results were represented in cost-effectiveness planes. RESULTS: In deterministic analysis, the expected cost per patient was higher in the raloxifene cohort (€13,881) than in the bazedoxifene cohort (€13,436). QALYs gained were slightly higher in the bazedoxifene cohort (14.56 versus 14.54). Results from probabilistic sensitivity analysis showed that bazedoxifene has a slightly higher probability of being cost-effective for all threshold values independent of the maximum that the National Health Service is willing to pay per additional QALY. CONCLUSION: Bazedoxifene was shown to be a cost-effective treatment option for the prevention of fractures in Spanish women with postmenopausal osteoporosis and a high fracture risk. When comparing bazedoxifene with raloxifene, it may be concluded that the former is the dominant strategy.

A comparative cost-analysis of initiating pregabalin or SSRI/SNRI therapy in benzodiazepine-resistant patients with generalized anxiety disorder in Spain.

OBJECTIVE: To compare the relative healthcare costs, from the perspective of the Spanish National Healthcare System (NHS), of initiating treatment with either pregabalin, or SSRI/SNRI, as add-on therapies, in patients with generalized anxiety disorder (GAD), who are resistant to benzodiazepine-based therapy (BR). METHODS: BR out-patients with GAD (DSM-IV) who were included in a 6-month, prospective, multicentre, observational cohort study were selected for this post-hoc economic analysis. BR was defined as insufficient response, with persistence of symptoms of anxiety (HAM-Anxiety scale≥16), after a 6-month course of benzodiazepines. Patients had not been previously exposed to pregabalin or SSRI/SNRI. Healthcare resource utilization (drugs, medical visits, hospitalizations, etc.) associated with GAD was collected at baseline and end-of-trial visits. Related costs were estimated at each visit and adjusted changes were compared using ANCOVA. RESULTS: A total of 128 patients with refractory GAD were treated with pregabalin and 126 SSRI/SNRI. Compared with SSRI/SNRI, pregabalin was associated with significantly lower percentage of benzodiazepines users; 57.0% vs 87.3%, p<0.001, and greater reduction in medical visits; -15.1 vs -13.0, p=0.029. Mean total healthcare resource utilization costs decreased significantly in the pregabalin cohort only; -289 (p=0.003), although six months costs were not significantly different in both groups; 977 vs 822, respectively. CONCLUSION: Initiating treatment with pregabalin was associated with significant reduction in medical visits and total health care resource costs of GAD compared to SSRI/ SNRI in BR patients in the Spanish NHS setting. Compared with SSRI/SNRI, pregabalin therapy was accompanied by significantly less percentage of patients on concomitant benzodiazepines therapy.

A simulation model to estimate 10-year risk of coronary heart disease events in patients with schizophrenia spectrum disorders treated with second-generation antipsychotic drugs.

BACKGROUND: The risk for cardiovascular (CV) events has been shown to be considerably higher among schizophrenia patients than the general population. OBJECTIVE: The aim of this study was to describe a general stochastic simulation model for the treatment of schizophrenia related to CV-associated risks of second-generation antipsychotics (SGAs). METHODS: A model to simulate the expected 10-year incidence of all types of coronary heart disease (CHD) events in patients treated with SGAs was developed from the Cardiovascular, Lipid and Metabolic Outcomes Research in Schizophrenia (CLAMORS) study to reproduce baseline conditions. The CHD event risk was estimated through a locally adjusted Framingham risk function using the expected mean change in the CV risk factors from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study. RESULTS: The 10-year CHD event rate after treatment with SGAs was 0.181, 0.179, 0.176, and 0.172 for olanzapine, quetiapine, risperidone, and ziprasidone, respectively. Relative risk was calculated relative to no treatment, and values were as follows: olanzapine, 1.03 ± 1.05 (95% CI, 0.74 to 1.42), quetiapine, 1.02 ± 1.05 (95% CI, 0.74 to 1.41), risperidone, 1.00 ± 0.99 (95% CI, 0.73 to 1.36), and ziprasidone, 0.97 ± 0.95 (95% CI, 0.72 to 1.31). There were approximately 25,269 CHD events over a 10-year period in schizophrenia patients treated with olanzapine, 25,157 events with quetiapine, 24,883 with risperidone, and 24,514 events with ziprasidone. CONCLUSIONS: The estimated outcomes suggest that each SGA shows a different level of CV event risk, with ziprasidone showing the lowest rate without any association for increased risk of CHD.

Cost savings associated with early initiation of pregabalin in the management of peripheral neuropathic pain.

OBJECTIVE: Peripheral neuropathic pain (PNP) is associated with significant economic burden. Guidelines recommend the early adoption of appropriate pharmacological interventions. The aim of this study was to explore whether early initiation of pregabalin was associated with lower economic burden, than later initiation, in the management of refractory chronic PNP. METHODS: A secondary analysis of a multicenter, observational cost-of-illness study was carried out in adults older than 18 years of age with refractory chronic PNP. Patients were pregabalin naive, with a poor response to previous analgesic therapy, defined as pain >40 in a 0 to 100 mm visual analog scale after, at least, 1 analgesic. The total costs, health care and indirect, assessed 12 weeks before the initiation of pregabalin were analyzed according to the time elapsed since diagnosis. RESULTS: One thousand one hundred thirty-nine outpatients, 59.3 (12.8) years old, 59.3% women, 2.0 (3.5) years with a diagnosis of PNP, fulfilled the criteria for analysis. Adjusted (pain intensity, sex, age, and body mass index) mean total costs 12 weeks before the baseline visit were significantly lower when pregabalin was initiated early (<6 mo; n=389) in comparison with later initiation; 6 to 12 months (n=328), or >12 months (n=422) after diagnosis; €2439 (2197; 2681) versus €3011 (2758; 3264) and €2945 (2717; 3173), respectively (P<0.01 in both cases). Lower health care costs and fewer lost-workday equivalents with early initiation of pregabalin were the main factors contributing to these findings. DISCUSSION: Early initiation of pregabalin treatment after diagnosis in patients with refractory chronic PNP may result in substantial cost savings from a societal perspective in daily practice in Spain.

Modelling the cost-effectiveness of pregabalin versus usual care in daily practice in the treatment of refractory generalised anxiety disorder in Spain.

PURPOSE: To model the cost-effectiveness (CEA) of the use of pregabalin versus usual care (UC) in outpatients with refractory generalised anxiety disorder (GAD) treated in daily practice in mental health settings in Spain. METHODS: This CEA model used data extracted from a 6-month prospective non-interventional trial: the Amplification of Definition of ANxiety (ADAN) study, which was conducted to determine the cost-of-illness in GAD subjects. Refractory subjects were those who reported persistent symptoms of anxiety and showed suboptimal response in the Hamilton-anxiety scale (HAM-A ≥ 16) after a standard dose regimen of anxiolytics other than pregabalin, alone or in combination, over 6 months. The pregabalin arm was documented with data extracted from patients who received pregabalin in the study for the first time, added or replacing the existing therapy. In the UC arm, treatment might include one or more of the following: a serotonin selective reuptake inhibitor, a serotonin-norepinephrine reuptake inhibitor, other anti-depressants, a benzodiazepine or an anti-epileptic drug other than pregabalin. The time horizon of the modelling was 6 months in the base-case scenario, and the National Health System perspective was chosen to calculate costs. Effectiveness was expressed as quality-adjusted life years (QALYs) gained, which were derived using the EQ-5D questionnaire, at baseline and end-of-trial visits. Results of the CEA model was expressed as an incremental cost-effectiveness ratio (ICER) per QALY gained. Probabilistic sensitivity analysis using bootstrapping techniques was also carried out to obtain the cost-effectiveness plane and the corresponding acceptability curve. RESULTS: Data from a total of 429 subjects per arm (mean HAM-A score 25.7) meeting eligible criteria for inclusion in CEA modelling were extracted from the original trial. Compared with UC, pregabalin (average dose 218 mg/day) was associated with significantly higher QALY gain; 0.1209 ± 0.1030 versus 0.0994 ± 0.0979 (P = 0.003), but increased healthcare costs as well; 1,272 ± 1,240 versus 1,070 ± 1,177 (P < 0.069) and drug costs 525 ± 252 versus 219 ± 211 (P < 0.001), resulting in an ICER of 15,804/QALY (95 % CI 6,661; 37,186) for healthcare costs and 15,165/QALY (7,947; 31,754) when drug costs were considered alone. A total of 94 % of re-samples fell below the threshold of 30,000 per QALY. CONCLUSIONS: This evaluation modelling suggests that pregabalin may be cost-effective in comparison with UC in outpatients with refractory GAD treated in mental healthcare settings in daily practice in Spain.

The assessment of generalized anxiety disorder: psychometric validation of the Spanish version of the self-administered GAD-2 scale in daily medical practice.

AIM: To psychometrically validate the Spanish version of the self-administered 2-item GAD-2 scale for screening probable patients with generalised anxiety disorder (GAD). METHODS: The GAD-2 was self-administered by patients diagnosed with GAD according to DSM-IV criteria and by age- and sex-matched controls who were recruited at random in mental health and primary care centres. Criteria validity was explored using ROC curve analysis, and sensitivity, specificity and positive and negative predictive values were determined for different cut-off values. Concurrent validity was also established using the HAM-A, HADS, and WHODAS II scales. RESULTS: The study sample consisted of 212 subjects (106 patients with GAD) with a mean age of 50.38 years (SD = 16.76). No items of the scale were left blank. Floor and ceiling effects were negligible. No patients with GAD had to be assisted to complete the questionnaire. Reliability (internal consistency) was high; Cronbach's α = 0.875. A cut-off point of 3 showed adequate sensitivity (91.5%) and specificity (85.8%), with a statistically significant area under the curve (AUC = 0.937, p < 0.001), to distinguish GAD patients from controls. Concurrent validity was also high and significant with HAM-A (0.806, p < 0.001), HADS (anxiety domain, 0.825, p < 0.001) and WHO-DAS II (0.642, p < 0.001) scales. CONCLUSION: The Spanish version of the GAD-2 scale has been shown to have appropriate psychometric properties to rapidly detect probable cases of GAD in the Spanish cultural context under routine clinical practice conditions.

Pregabalin versus SSRIs and SNRIs in benzodiazepine-refractory outpatients with generalized anxiety disorder: a post hoc cost-effectiveness analysis in usual medical practice in Spain.

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent health condition which seriously affects both patient quality of life and the National Health System. The aim of this research was to carry out a post hoc cost-effectiveness analysis of the effect of pregabalin versus selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) in treated benzodiazepine-refractory outpatients with GAD. METHODS: This post hoc cost-effectiveness analysis used secondary data extracted from the 6-month cohort, prospective, noninterventional ADAN study, which was conducted to ascertain the cost of illness in GAD subjects diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Benzodiazepine-refractory subjects were those who claimed persistent symptoms of anxiety and showed a suboptimal response (Hamilton Anxiety Rating Scale ≥ 16) to benzodiazepines, alone or in combination, over 6 months. Patients could switch to pregabalin (as monotherapy or addon) or to an SSRI or SNRI, alone or in combination. Effectiveness was expressed as quality-adjusted life years gained, and the perspective was that of the National Health System in the year 2008. A sensitivity analysis was performed using bootstrapping techniques (10,000 resamples were obtained) in order to obtain a cost-effectiveness plane and a corresponding acceptability curve. RESULTS: A total of 282 subjects (mean Hamilton Anxiety Rating Scale score 25.8) were identified, comprising 157 in a pregabalin group and 125 in an SSRI/SNRI group. Compared with SSRI/SNRI, pregabalin (average dose 163 mg/day) was associated with higher quality-adjusted life years gained (0.1086 ± 0.0953 versus 0.0967 ± 0.1003, P = 0.334), but increased health care costs (€1014 ± 762 versus €846 ± 620, P = 0.166) and drug costs (€376 ± 252 versus 220 ± 140, P < 0.001), resulting in an incremental cost-effectiveness ratio of €25,304 (95% confidence interval dominant 149,430) per quality-adjusted life years gained for health care costs and €25,454 (dominant 124,562) when drug costs were considered alone. Eighty-six percent of resamples fell below the threshold of €30,000 per quality-adjusted life years. CONCLUSION: This evaluation suggests that pregabalin may be cost-effective in comparison with SSRIs/SNRIs in benzodiazepine-refractory outpatients with GAD treated in mental health care settings under usual medical practice in Spain.

A cost-effectiveness analysis of the effect of pregabalin versus usual care in the treatment of refractory neuropathic pain in routine medical practice in Spain.

OBJECTIVE: The objective of this study was to estimate the cost-effectiveness of pregabalin vs usual care (UC) in outpatients with refractory neuropathic pain (NeP), treated according to routine medical practice in primary care settings in Spain. METHODS: Patients were extracted from a 12-week noninterventional prospective study conducted to ascertain the costs of NeP. Pairs of pregabalin-naïve patients receiving UC or pregabalin, matched by age, gender, pain intensity, and refractory to previous treatment, were selected in a 1:1 ratio. Refractory was considered a patient with actual pain (scoring >40 in a 100 mm in a pain visual analog scale) after receiving a course of a standard analgesic, at its recommended doses. Perspectives of the Spanish National Healthcare System and society were included in the analysis. Effectiveness was expressed as quality-adjusted life-year (QALY) gain. Results of the cost-effectiveness analysis were expressed as an incremental cost per QALY (ICER) gained. Probabilistic sensitivity analysis using bootstrapping techniques was also carried out. RESULTS: A total of 160 pairs were extracted. Compared with UC, pregabalin was associated with significantly higher QALY gain; 0.0374 ± 0.0367 vs 0.0224 ± 0.0313 (P < 0.001). Despite drug acquisition costs being higher for pregabalin (€251 ± 125 vs €104 ± 121; P < 0.001), total and health care costs incurred for pregabalin were similar in both groups; €1,335 ± 1,302 vs €1,387 ± 1,489 (P = 0.587) and €529 ± 438 vs €560 ± 672 (P = 0.628), respectively, yielding a dominant ICER for both total and health care costs in the base case scenario; 95% confidence intervals, respectively, dominant to €17,268, and dominant to €6,508. Sensitivity analysis confirmed results of the basecase scenario. CONCLUSION: This study showed that pregabalin may be cost-effective in the treatment of refractory NeP patients when compared with UC in routine medical practice in Spain.