In-patient costs of agitation and containment in a mental health catchment area.

BACKGROUND: There is a scarce number of studies on the cost of agitation and containment interventions and their results are still inconclusive. We aimed to calculate the economic consequences of agitation events in an in-patient psychiatric facility providing care for an urban catchment area. METHODS: A mixed approach combining secondary analysis of clinical databases, surveys and expert knowledge was used to model the 2013 direct costs of agitation and containment events for adult inpatients with mental disorders in an area of 640,572 adult inhabitants in South Barcelona (Spain). To calculate costs, a seven-step methodology with novel definition of agitation was used along with a staff survey, a database of containment events, and data on aggressive incidents. A micro-costing analysis of specific containment interventions was used to estimate both prevalence and direct costs from the healthcare provider perspective, by means of a mixed approach with a probabilistic model evaluated on real data. Due to the complex interaction of the multivariate covariances, a sensitivity analysis was conducted to have empirical bounds of variability. RESULTS: During 2013, 918 patients were admitted to the Acute Inpatient Unit. Of these, 52.8% were men, with a mean age of 44.6 years (SD = 15.5), 74.4% were compulsory admissions, 40.1% were diagnosed with schizophrenia or non-affective psychosis, with a mean length of stay of 24.6 days (SD = 16.9). The annual estimate of total agitation events was 508. The cost of containment interventions ranges from 282€ at the lowest level of agitation to 822€ when verbal containment plus seclusion and restraint have to be used. The annual total cost of agitation was 280,535€, representing 6.87% of the total costs of acute hospitalisation in the local area. CONCLUSIONS: Agitation events are frequent and costly. Strategies to reduce their number and severity should be implemented to reduce costs to the Health System and alleviate patient suffering.

Usefulness of a Cardiovascular Polypill in the Treatment of Secondary Prevention Patients in Spain: A Cost-effectiveness Study.

INTRODUCTION AND OBJECTIVES: To estimate the health benefits and cost-effectiveness of a polypill intervention (aspirin 100 mg, atorvastatin 20 mg, ramipril 10 mg) compared with multiple monotherapy for secondary prevention of cardiovascular events in adults with a history of myocardial infarction from the perspective of the Spanish National Health System. METHODS: An adapted version of a recently published Markov model developed and validated in Microsoft Excel was used to compare the cost-effectiveness of the polypill with that of its combined monocomponents over a 10-year time horizon. The population included in the model had a mean age of 64.7 years; most were male and had a history of myocardial infarction. The input parameters were obtained from a systematic literature review examining efficacy, adherence, utilities, and costs. The results of the model are expressed in events avoided, incremental costs, incremental life years, incremental quality-adjusted life years, and the incremental cost-effectiveness ratio. RESULTS: Over a 10-year period, use of the cardiovascular polypill instead of its monocomponents simultaneously would avoid 46 nonfatal and 11 fatal cardiovascular events per 1000 patients treated. The polypill would also be a more effective and cheaper strategy. Probabilistic analysis of the base case found a 90.9% probability that the polypill would be a cost-effective strategy compared with multiple monotherapy at a willingness-to-pay of 30 000 euros per quality-adjusted life year. CONCLUSIONS: The polypill would be a cost-effective strategy for the Spanish National Health System with potential clinical benefits.

Relationship between patient dependence and direct medical-, social-, indirect-, and informal-care costs in Spain.

OBJECTIVE: The objectives of this analysis were to examine how patients' dependence on others relates to costs of care and explore the incremental effects of patient dependence measured by the Dependence Scale on costs for patients with Alzheimer's disease (AD) in Spain. METHODS: The Co-Dependence in Alzheimer's Disease study is an 18 multicenter, cross-sectional, observational study among patients with AD according to the clinical dementia rating score and their caregivers in Spain. This study also gathered data on resource utilization for medical care, social care, caregiver productivity losses, and informal caregiver time reported in the Resource Utilization in Dementia Lite instrument and a complementary questionnaire. The data of 343 patients and their caregivers were collected through the completion of a clinical report form during one visit/assessment at an outpatient center or hospital, where all instruments were administered. The data collected (in addition to clinical measures) also included sociodemographic data concerning the patients and their caregivers. Cost analysis was based on resource use for medical care, social care, caregiver productivity losses, and informal caregiver time reported in the Resource Utilization in Dementia Lite instrument and a complementary questionnaire. Resource unit costs were applied to value direct medical-, social-, and indirect-care costs. A replacement cost method was used to value informal care. Patient dependence on others was measured using the Dependence Scale, and the Cumulative Index Rating Scale was administered to the patient to assess multi-morbidity. Multivariate regression analysis was used to model the effects of dependence and other sociodemographic and clinical variables on cost of care. RESULTS: The mean (standard deviation) costs per patient over 6 months for direct medical-, social-, indirect-, and informal-care costs were estimated at €1,028.10 (€1,655.00), €843.80 (€2,684.80), €464.20 (€1,639.00), and €33,232.20 (€30,898.90), respectively. Dependence was independently and significantly associated with direct medical-, social-, informal-, and total-care costs. CONCLUSION: The costs of care for patients with AD in Spain are substantial, with informal care accounting for the greatest part. Interventions that reduce patient dependence on caregivers may be associated with important reduction in direct medical-, social-, informal-, and total-care costs.

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.

Disability-adjusted life years lost due to diabetes in France, Italy, Germany, Spain, and the United Kingdom: a burden of illness study.

AIMS: To compare the burden of disease (BoD) attributable to diabetes expressed in disability-adjusted life years (DALYs) for five European countries in 2010. METHODS: DALYs lost to diabetes as the sum of years of life lost and years lived with disability were estimated by sex and age using country-specific epidemiological data and global disability weights. Data from various secondary sources were combined to estimate health loss due to diabetes for France, Germany, Italy, Spain, and the UK. National statistical databases were used and if necessary, community studies were used to derive the prevalence of diabetes by sex and age group, which were weighted proportionately for a national population burden of disease estimate. All identified data were adapted to the Global Burden of Disease methodology (2010) to calculate the burden attributable to diabetes. No age weighting and discounting was applied. Sensitivity to different sources of variation was examined. Germany and Italy lost the largest number of DALYs due to diabetes, with 5.9 and 5.8 per 1,000 inhabitants, respectively, followed by Spain (4.4), France (3.7), and the UK (2.9). The highest burden was caused by mortality due to diabetes, with the exception of the UK, for which the burden due to disability of diabetes was higher. Mean DALYs lost were higher for women in Germany, Italy, and Spain and shown to increase with age for all countries. Sensitivity analysis in variation in disability weights and uncertainty in epidemiological data were shown to have effects on DALYs lost. CONCLUSION: In spite of data limitations, the estimates reported here show that DALY loss due to diabetes imposes a substantial burden on countries. Cross-national variation in disease epidemiology was the largest source of variation in the burden of diabetes between countries.

Cost-utility of denosumab for the treatment of postmenopausal osteoporosis in Spain.

BACKGROUND: The objective of this study was to estimate the cost-effectiveness of denosumab for fracture prevention compared with no treatment, generic bisphosphonates, and strontium ranelate in a cohort of osteoporotic postmenopausal women in Spain. METHODS: A Markov model represented the possible health state transitions of Spanish postmenopausal women from initiation of fracture prevention treatment until age 100 years or death. The perspective was that of the Spanish National Health System. Fracture efficacy data for denosumab were taken from a randomized controlled trial. Fracture efficacy data for alendronate, ibandronate, risedronate, and strontium ranelate were taken from an independent meta-analysis. Data on the incidence of fractures in Spain were either taken from the published literature or derived from Swedish data after applying a correction factor based on the reported incidence from each country. Resource use in each health state was obtained from the literature, or where no data had been published, conservative assumptions were made. Utility values for the various fracture health states were taken from published sources. The primary endpoints of the model were life-years gained, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios for denosumab against the comparators. RESULTS: Denosumab reduced the risk of fractures compared with either no treatment or the other active interventions, and produced the greatest gains in life-years and QALYs. With an annual acquisition cost of €417.34 for denosumab, the incremental cost-effectiveness ratios for denosumab versus no treatment, alendronate, risedronate, and ibandronate were estimated at €6,823, €16,294, €4,895, and €2,205 per QALY gained, respectively. Denosumab dominated strontium ranelate. Sensitivity analyses confirmed the robustness of these findings. CONCLUSION: Our analyses show that denosumab is a cost-effective intervention for fracture prevention in osteoporotic postmenopausal women in Spain compared with alendronate and risedronate, and is a dominant treatment option compared with strontium ranelate.

Costs of surviving meningococcal disease in Spain: evaluation for two cases of severe meningitis and septicaemia.

OBJECTIVES: The aim of this study was to count the lifelong rehabilitation costs associated with surviving meningococcal disease with major sequelae from the perspective of the Spanish National Healthcare System (NHS) and the national government. METHODS: Two severe scenarios describing meningococcal disease were developed, one case that represented meningococcal septicaemia and another case for meningococcal meningitis. The scenarios were developed based on a literature review on severe sequelae of meningococcal disease, and discussions with paediatricians who have been responsible for the treatment of children with this disease in Spain. Second, a detailed list of all health, educational and social care resources used by survivors during their acute illness and during the rest of their lives and by family members was obtained by interviewing survivors and their families. Professionals in health and social care were also interviewed to complete the list of resources and ensure the scenario's were accurate. The costs attributed to these resources were obtained from tariff lists, catalogues and published information by the national authorities. All costs were based on a life expectancy of a survivor of 70 years and expressed in EUR 2012. RESULTS: In this study it was estimated that the lifelong discounted rehabilitation costs associated with the treatment of long-term sequelae due to meningococcal disease are approximately €1180,000-€1400,000. Medical care and social care were the main cost drivers for both septicaemia and meningitis. Annual costs showed to be the largest in the first year after diagnosis of the disease for both cases, due to high hospital admission and medical care costs during this period and decreased significantly over the years. CONCLUSION: This study shows that the lifelong rehabilitation costs associated with the survival of meningococcal disease with severe sequelae place an important burden on the NHS budget and governmental resources in Spain.

Cost-effectiveness of glatiramer acetate and interferon beta-1a for relapsing-remitting multiple sclerosis, based on the CombiRx study.

BACKGROUND: To assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses among Spanish patients aged between 18-60 years old with established Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: A Markov model was developed to represent the transition of a cohort of patients over a 10 year period using the perspective of the Spanish National Health Service (NHS). The model considered five different health states with 1-year cycles including without relapse, patients with suspect, non-protocol defined and protocol defined exacerbations, as well as a category information lost. Efficacy data was obtained from the 3-year CombiRx Study. Costs were reported in 2013 Euros and a 3% discount rate was applied for health and benefits. Deterministic results were presented as the annual treatment cost for the number of relapses. A probabilistic sensitivity analysis was performed to test the robustness of the model. RESULTS: Deterministic results showed that the expected annual cost per patient was lower when treated with GA (€13,843) compared with IFN (€15,589) and the combined treatment with IFN+GA (€21,539). The annual number of relapses were lower in the GA cohort with 3.81 vs 4.18 in the IFN cohort and 4.08 in the cohort treated with IFN+GA. Results from probabilistic sensitivity analysis showed that GA has a higher probability of being cost-effective than treatment with IFN or IFN+GA for threshold values from €28,000 onwards, independent of the maximum that the Spanish NHS is willing to pay for avoiding relapses. CONCLUSION: GA was shown to be a cost-effective treatment option for the prevention of relapses in Spanish patients diagnosed with RRMS. When GA in monotherapy is compared with INF in monotherapy and IFN+GA combined, it may be concluded that the first is the dominant strategy.

Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective.

INTRODUCTION: Pregabalin is an anticonvulsant approved in Europe for the treatment of neuropathic pain, as an adjunct therapy for epileptic seizures, and recently for generalized anxiety disorder. The aim of this study was to conduct a systematic review to evaluate the cost-effectiveness of pregabalin associated with the treatment of its labeled indications from a societal perspective in Spain. METHODS: Data from the MEDLINE database were searched using algorithms to identify relevant economic evaluations published in English or Spanish on pregabalin for the management of neuropathic pain, generalized anxiety disorder (GAD), and epilepsy in Spanish patients over the last 10 years. RESULTS: In total, 52 potentially relevant abstracts were identified from the MEDLINE database. Twenty manuscripts met the inclusion criteria. The majority of the selected papers (14/20) evaluated pregabalin for neuropathic pain from a societal perspective in Spain (5 economic models of pregabalin vs. gabapentin, 4 economic analyses of pregabalin in comparison with usual care, 4 economic evaluations comparing pregabalin monotherapy with add-on strategies, and one that evaluated different times of initiating pregabalin therapy). Five studies analyzed the use of pregabalin in Spain for the management of GAD (one cost-effectiveness model that compared pregabalin with venlafaxine, 2 secondary analyses in benzodiazepine-refractory patients, and 2 studies evaluating pregabalin vs. usual care in patients refractory to standard regimens). The last manuscript described a cost-effectiveness model that compared pregabalin versus levetiracetam use for the treatment of refractory partial epilepsy. CONCLUSION: The majority of published evidence supports the possibility that pregabalin could be a cost-effective and/or cost-saving alternative for the treatment of refractory epilepsy, GAD, and neuropathic pain, in both treatment-naïve patients and in those who have demonstrated inadequate response or intolerance to previous therapy.

Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain.

BACKGROUND: The purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP) in Spain. METHODS: A 4-year budget impact model was developed for the period 2012-2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal). Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model. RESULTS: Patients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in the total costs of BTcP over the next 4 years. Results of the sensitivity analysis showed that the model was most sensitive to drug cost per day for the fentanyl buccal tablet. A 50% decrease in the daily cost of the fentanyl buccal tablet resulted in the largest overall decrease in budget impact of €5.4 million. CONCLUSION: The increase in use of the fentanyl buccal tablet leads to overall savings in the budget impact for the Spanish National Health System. Although the economic impact of treatment for BTcP was shown to increase over 4 years due to population growth, the average annual cost per patient was reduced by €29 with increased use of the fentanyl buccal tablet.

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 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.

Direct medical costs of liquid intravenous immunoglobulins in children, adolescents, and adults in Spain.

The aim of this study was to determine health care resource utilization and direct medical costs in Spanish patients treated with intravenous immunoglobulins (IVIGs) in 2009. Cost-of-illness analyses were performed to estimate direct medical costs of patients treated with IVIGs. Prevalence data were obtained from the Spanish Primary Immunodeficiency registry. A semi-structured questionnaire was used to collect data on health care resource utilization and patient distribution. Drug, administration, and premedication costs were considered from the payer's perspective. Separate analyses were conducted for children and adolescents versus adults. The numbers of children and adolescents with replacement therapy were 724, with immunomodulation 243, and with allogeneic bone marrow transplantation 30. The numbers of adult patients were, respectively, 3450, 1134, and 172. Mean annual costs for children and adolescents were 6293 € with Privigen, 6292 € with Kiovig, 6939 € with Flebogamma, and 6559 € with Octagamocta. For adults, estimations were 17 106 € with Privigen, 17 103 € with Kiovig, 18 077 € with Flebogamma, and 17 423 € with Octagamocta. Direct medical costs for IVIGs were approximately 91.8 million €. Drug costs represented 94% of total costs. The choice for a certain IVIG treatment depends on individual patient characteristics and cost considerations.

Epidemiology and societal costs of gastroesophageal reflux disease and Barrett's syndrome in Germany, Italy and Spain.

AIM: To estimate the economic consequences for society arising from populations with poorly treated gastroesophageal reflux disease (GERD) and Barrett's esophagus in Germany, Italy and Spain. METHODS: The following epidemiologic data were used: total population figures, the prevalence and incidence of GERD and its complications, and data on patients with poorly treated GERD, as well as data on treatment costs and active workers' presenteeism and absenteeism. These data were used to calculate the economic consequences arising from the population with poorly treated GERD and Barrett's esophagus for the healthcare system and employers in each country. RESULTS: The size of the population with poorly treated GERD with Barrett's esophagus was estimated to be 29,678 in Spain, 19,327 in Germany and 10,079 in Italy. Costs for the healthcare systems in Spain, Germany and Italy for the population with poorly treated GERD with Barrett's esophagus were estimated to be €18, 12 and 7 million, respectively, for each country. Total costs for absenteeism and presenteeism for employers due to poorly treated GERD with Barrett's esophagus were €10 million for Germany, €1 million for Italy and none for Spain. CONCLUSION: Costs due to poorly treated GERD with Barrett's esophagus represent a substantial burden for the healthcare systems of all three studied countries. Costs for employers owing to absenteeism or presenteeism of employees were low or no costs were found.