Development of the European Healthcare and Social Cost Database (EU HCSCD) for use in economic evaluation of healthcare programs.

INTRODUCTION: Costs are one of the critical factors for the transferability of the results in health technology assessment and economic evaluation. The objective is to develop a cost database at the European level to facilitate cross-border cost comparisons in different settings and explains the factors that lead to differences in healthcare costs in different countries, taking into account the differences between health systems and other factors. METHODOLOGY: The core of the database is compounded of three main categories (primary resources, composite goods and services, and complex processes and interventions) organized into 13 subcategories. A number of elements providing as detailed information of unit cost as possible were identified in order to mitigate the problem of comparability. Consortium partners validated both the database structure and selected costing items. RESULTS: Twenty-seven costing items included in the EU HCSCD resulted in 1450 unit costs when taking into account all item subtypes and countries. Cross-country differences in costs are driven by the type of resources included in the costing items (e.g., overhead costs in case of complex processes and interventions) or by the variety of existing brands and/or models and the type of unit value in most of the primary resources. CONCLUSION: The EU HCSCD is the only public unit healthcare and social cost database at European level that gather data on unit costs and explains differences in costs across countries. Its maintenance and regular data updating will enable establishing specific systems for generating and recording information that will meet many of its current limitations.

Cost-effectiveness and resource allocation (CERA) 18 years of evolution: maturity of adulthood and promise beyond tomorrow.

Since its inception in 2003, Cost Effectiveness and Resource Allocation journal has come a long way over the past 18 years. Possibly much longer than many of its contemporaries in the blossoming science of health economics might have anticipated. Today, entering 2020 it celebrates the Age of Maturity. We believe that in the third decade of XXI century the interdisciplinary science of health economics, will rejuvenate and come back to us younger than ever from its early historical roots almost a century ago. The spreading of economic globalization in several distinctive ways, either led by multinational business corporations or newly emerged Asian leadership, or both, is likely to make challenges for contemporary health systems far more serious. The fourth industrial revolution (cyber physical systems and artificial intelligence technology) and accelerated innovation in the field of E-Health and digital health, will probably change the workflow in medical and health care, and inevitably transform the labour market in the upcoming decades. So, let us be up to the task. Let us provide academic centres, industry-sponsored pharmaceutical and medical device innovation hubs, and governing authorities alike, with a powerful forum for debate on cost-effective resource allocation in the years to come.

A general framework for classifying costing methods for economic evaluation of health care.

According to the most traditional economic evaluation manuals, all "relevant" costs should be included in the economic analysis, taking into account factors such as the patient population, setting, location, year, perspective and time horizon. However, cost information may be designed for other purposes. Health care organisations may lack sophisticated accounting systems and consequently, health economists may be unfamiliar with cost accounting terminology, which may lead to discrepancy in terms used in the economic evaluation literature and management accountancy. This paper identifies new tendencies in costing methodologies in health care and critically comments on each included article. For better clarification of terminology, a pragmatic glossary of terms is proposed. A scoping review of English and Spanish language literature (2005-2018) was conducted to identify new tendencies in costing methodologies in health care. The databases PubMed, Scopus and EconLit were searched. A total of 21 studies were included yielding 43 costing analysis. The most common analysis was top-down micro-costing (49%), followed by top-down gross-costing (37%) and bottom-up micro-costing (14%). Resource data were collected prospectively in 12 top-down studies (32%). Hospital database was the most common way of collection of resource data (44%) in top-down gross-costing studies. In top-down micro-costing studies, the most resource use data collection was the combination of several methods (38%). In general, substantial inconsistencies in the costing methods were found. The convergence of top-down and bottom-up methods may be an important topic in the next decades.

Mechanical Properties of 3D-Printing Polylactic Acid Parts subjected to Bending Stress and Fatigue Testing.

This paper aims to analyse the mechanical properties response of polylactic acid (PLA) parts manufactured through fused filament fabrication. The influence of six manufacturing factors (layer height, filament width, fill density, layer orientation, printing velocity, and infill pattern) on the flexural resistance of PLA specimens is studied through an L27 Taguchi experimental array. Different geometries were tested on a four-point bending machine and on a rotating bending machine. From the first experimental phase, an optimal set of parameters deriving in the highest flexural resistance was determined. The results show that layer orientation is the most influential parameter, followed by layer height, filament width, and printing velocity, whereas the fill density and infill pattern show no significant influence. Finally, the fatigue fracture behaviour is evaluated and compared with that of previous studies' results, in order to present a comprehensive study of the mechanical properties of the material under different kind of solicitations.

Medicine Shortages: Gaps Between Countries and Global Perspectives.

Introduction: Over the last decade, global health policies and different research areas have focused on the relevance and impact of medicine shortages. Published studies suggest there have been difficulties with access to medicines since the beginning of the 20th century, and there have been advances in our understanding and management of the problem since then. However, in view of global and regional health care concerns with shortages, we believe this phenomenon needs to be characterized and described more fully regarding the types of medicines affected, possible causes, and potential strategies to address these. The aim of this scoping review was to identify, compare if possible, and characterize the recent literature regarding the situation of medicines shortages between countries, and provide different perspectives, including a global context and national approaches. Methodology: A scoping study presented as a narrative review of the situation and findings principally based on published articles. Results: Based on the reported cases in the literature, a typology of medicines shortage and supply interruption episodes and their causes were proposed; national approaches to notify and manage the medicines shortages cases were described and classified by update frequency; principal differences between market and supply chain management perspectives of the situation were identified and global and countries' perspectives were described. Conclusion: Policy makers require solutions that prevent those cases in which the population's health is affected by episodes of medicine shortages and/or interruption in the supply chain. There is also a need to generate a glossary related to logistics management and the availability of medicines which will be useful to understand and overcome shortages. In addition, recognize that potential solutions are not only related with actions linked to research, development and innovation, but much wider. Overall, we believe this article can act as a basis for future discussions in this important area.

Effect of different CO2 concentrations on biomass, pigment content, and lipid production of the marine diatom Thalassiosira pseudonana.

The marine diatom Thalassiosira pseudonana grown under air (0.04% CO2) and 1 and 5% CO2 concentrations was evaluated to determine its potential for CO2 mitigation coupled with biodiesel production. Results indicated that the diatom cultures grown at 1 and 5% CO2 showed higher growth rates (1.14 and 1.29 div day-1, respectively) and biomass productivities (44 and 48 mgAFDWL-1 day-1) than air grown cultures (with 1.13 div day-1 and 26 mgAFDWL-1 day-1). The increase of CO2 resulted in higher cell volume and pigment content per cell of T. pseudonana. Interestingly, lipid content doubled when air was enriched with 1-5% CO2. Moreover, the analysis of the fatty acid composition of T. pseudonana revealed the predominance of monounsaturated acids (palmitoleic-16:1 and oleic-18:1) and a decrease of the saturated myristic acid-14:0 and polyunsaturated fatty acids under high CO2 levels. These results suggested that T. pseudonana seems to be an ideal candidate for biodiesel production using flue gases.

How can voluntary cross-border collaboration in public procurement improve access to health technologies in Europe?

This policy brief examines the legal framework put in place by the European Union to foster voluntary cross-border collaboration in the field of public procurement of health technologies; it looks at recent experiences and developments in cross-border collaboration across Europe; and explores the challenges and opportunities that such cross-border collaboration presents. It was written to inform discussions under the Maltese EU Presidency in 2017.

Analysis of economic evaluations of pharmacological cancer treatments in Spain between 1990 and 2010.

Economic evaluation of pharmacological cancer treatment is a critical clinical problem currently under consideration worldwide. We have analysed their main characteristics in Spain between 1990 and 2010 following a systematic review of the 29 complete economic analyses published. The pathology most frequently evaluated was non-small cell lung cancer (31 %). Cost-effectiveness analyses (69 %) were the most frequent analyses. A wide range of incremental cost-effectiveness values (295-160,667 € /QALY) has been reported, and mostly are developed from the perspective of the National Health System (65.5 %). However, none of the studies estimated the indirect costs. The major conclusion is that the absence of regulations concerning the application of the efficiency criterion in decision-making on the subject of price and financing and, most importantly, the fact that these are not included in Spanish hospitals forms make it difficult to analyse the real impact of economic evaluations of cancer treatments on such decisions.

The cost of generalized anxiety disorder in primary care settings: results of the ANCORA study.

To assess the cost of illness of generalized anxiety disorder (GAD) in a primary healthcare setting in Spain. A cross-sectional, retrospective study was conducted. The sample comprised patients diagnosed with GAD according to ICD-10 criteria and a control group. Healthcare/non-healthcare resource utilization was recorded retrospectively for the 12 months prior to the study visit. Costs were estimated from a societal perspective. Two models have been produced to study the variables that influence the cost of the illness both, without and with controls. The study enrolled 456 patients [76.8 % women, 49.2 (17.0) years] with GAD and 74 controls without GAD [42.5 % women, 47.9 (16.7) years]. 67.8 % of subjects were on combination therapy (antidepressant + anxiolytic); 6 % were using 2 or more drugs to treat anxiety; and 23.4 % were on monotherapy. Total annual average costs were higher in the GAD group (€7,739 vs. €2,609), with mean costs attributable to GAD of €5,139 (healthcare costs: €1,329, indirect costs: 75 % of total cost, approximately). Age and health status measured by Hamilton Anxiety Rating Scale and clinical global impression were related to costs. The improvements in quality of life measured by EQ-5D index are associated to lower cost. GAD treated in Spanish primary healthcare settings generated considerable healthcare costs and, particularly, loss-of-productivity costs.

Impacto del informe de la Comisión sobre Determinantes Sociales de la Salud cuatro años después / Impact of the Report of the WHO Commission on Social Determinants of Health four years after publication

Tras más de tres años de trabajo, la Comisión de Determinantes Sociales de la Salud de la Organización Mundial de la Salud, presentó a finales de agosto de 2008 su informe final traducido en su versión castellana como "Subsanar las desigualdades en una generación: alcanzar la equidad sanitaria actuando sobre los determinantes sociales de la salud". El informe, muy probablemente uno de los textos de mayor interés en el campo de la salud pública de las últimas décadas, no ha dejado indiferente. Ha recibido notables alabanzas, desaforadas críticas y algunas -las menos hasta el momento- críticas con un carácter más equilibrado y razonable. El objetivo de este texto es apreciar críticamente dicho informe y valorar su impacto cuatro años después de su publicación. Para ello, en primer lugar, se revisa el origen y objetivos de la Comisión resumiendo la visión y difusión del informe; segundo, se valoran las características y contenidos del informe desde distintos puntos de vista ideológicos y políticos: neoliberal y conservador, desde la epidemiología social y desde una visión radical de salud pública; y tercero, se evalua el impacto global del informe cuatro años después de su publicación. El texto concluye con algunas reflexiones finales.

After more than three years of work, the WHO Commission on Social Determinants of Health launched its final Report "Closing the gap in a generation: Health equity through action on the social determinants of health" at the end of August 2008. This report, which is probably one of the most interesting texts in the field of public health in recent decades, has attracted a lot of attention. It has been the object of remarkable praises, of ardent criticism, and to lesser extent, of more balanced and reasonable critiques. The aim of this paper was to critically evaluate the report and to assess its impact four years after its publication. Firstly, the origins and objectives of the Commission was reviewed, outlining the vision and dissemination of the report; secondly, the characteristics and contents of the report were assessed from different ideological and political points of view including neoliberal, conservative, social epidemiology and radical view of public health; and finally, the overall impact of the Report four years after publication was evaluated. The paper concluded with some final reflections.

Nutritional assessment of residents in long-term care facilities (LTCFs): recommendations of the task force on nutrition and ageing of the IAGG European region and the IANA.

Unintentional weight loss and Undernutrition are major problems among older people living in Long-Term Care Facilities (LTCF). Undernutrition manifests in LTCF particularly as weight loss and low Body Mass Index (BMI) and is associated with increased morbidity and mortality as well as with functional decline. There are many factors associated with poor nutritional status and affecting protein-energy intake and/or energy expenditure. These include age of 85 years or older, low nutrient intake, loss of ability to eat independently, swallowing and chewing difficulties, becoming bed-ridden, pressure ulcers, history of hip fracture, dementia, depressive symptoms and suffering from two or more chronic illnesses. Nutritional evaluation is an essential part of the Comprehensive Geriatric Assessment (CGA). This evaluation ranges from methods such as BMI to several validated tools such as Mini-Nutritional Assessment (MNA). After diagnosis, the management of undernutrition in LTCF requires a multidisciplinary approach which may involve dietary and environmental improvements and managing multiple co-morbidities, while avoiding polypharmacy as far as possible. Finally, the need for supplementation or artificial (tube) feeding may be considered taking into account the CGA and individual needs. This document presents a succinct review and recommendations of evaluation and treatment of undernutrition.

Optimal design of clinical trials with computer simulation based on results of earlier trials, illustrated with a lipodystrophy trial in HIV patients.

The designer of a clinical trial needs to make many assumptions about real-life practice based on prior knowledge. Simulation allows us to learn from experience by using the information obtained from a trial to improve the original estimators of population parameters. We propose using data from a previous trial to formulate assumptions that can be used to simulate trials and thus improve the design of new trials. To demonstrate our method, we used data from a real clinical trial which had been designed to evaluate cholesterol level changes as a surrogate marker for lipodystrophy in HIV patients. We were able to identify the optimal design that would have minimised the cost of a trial subject to a statistical power constraint which could then be used to design a new trial. In particular, we focused on three factors: the distribution of cholesterol levels in HIV patients, trial recruitment rates and trial dropout rates. We were able to verify our hypothesis that the total cost resulting from carrying out a clinical trial can be minimised by applying simulation models as an alternative to conventional approaches. In our findings the simulation model proved to be very intuitive and a useful method for testing the performance of investigators' assumptions and generating an optimal clinical trial design before being put into practice in the real world. In addition, we concluded that simulation models provide a more accurate determination of power than conventional approaches, thus minimising the total cost of clinical trials.

Area deprivation and trends in inequalities in self-rated health in Spain, 1987--2001.

AIMS: This study examined the impact that individual social position and municipal area deprivation levels had on trends in inequalities in self-rated health in Spain, between 1987 and 2001. METHODS: The study was based on cross-sectional data of the National Health Surveys of Spain for the years 1987, 1993, 1995, 1997, and 2001 (n=84,567). The indicators used were educational level and occupational class, and deprivation level as the indicator of municipal areas. Multilevel logistic regression models were made, with individuals nested into municipal areas. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. To evaluate trends, the relative index of inequality was calculated. RESULTS: At the individual level, the likelihood of less-than-good health between those with no formal education as compared to those with graduate-level education increased from OR=2.66 (95% CI: 2.06-3.38) in 1987 to OR=3.62 (95% CI: 2.95-4.63) in 2001 among women. The values for men were OR=2.27 (95% CI: 1.89-2.72) and OR=2.94 (95% CI: 2.36-3.68) respectively. Living in areas with the highest deprivation levels as compared to the lowest systematically increased the likelihood of less-than-good health. The likelihood of reporting less-than-good health among women with no formal education as compared to women with graduate-level education in municipal areas with the highest deprivation levels increased from OR=3.61 (95% CI: 2.39-5.45) in 1987 to 4.85 (95% CI: 3.06-7.69) in 2001. Among men, the corresponding magnitudes were OR=2.07 (95% CI: 1.39-3.08) and OR=4.16 (95% CI: 2.52-6.89). CONCLUSIONS: Inequalities in self-rated health increased in Spain in this period. These inequalities may be explained by the social conditions existing throughout the period of reference, and the pattern varies according to gender, municipal area deprivation levels, and the individual indicator of social position used.

Assessing the economic challenges posed by orphan drugs.

Historically, patients with rare diseases have been underserved by commercial drug development. In several jurisdictions, specific legislation has been enacted to encourage the development of drugs for rare diseases (orphan drugs), which would otherwise not be commercially viable. However, because of the small market, these drugs are often very expensive. Under the standard methods of health technology assessment (HTA) incorporating economic evaluation, orphan drugs do not usually prove to be cost-effective and this, coupled with their high cost, means that funding and patient access may be limited. However, these restrictions may not be in line with societal preferences. Therefore, this study discusses whether the standard methods of HTA are adequate for assisting decisions on patient access to and funding of orphan drugs and outlines a research agenda to help understand the societal value of orphan drugs and issues surrounding their development, funding, and use.

Clinical trial optimization: Monte Carlo simulation Markov model for planning clinical trials recruitment.

INTRODUCTION: The patient recruitment process of clinical trials is an essential element which needs to be designed properly. METHODS: In this paper we describe different simulation models under continuous and discrete time assumptions for the design of recruitment in clinical trials. RESULTS: The results of hypothetical examples of clinical trial recruitments are presented. The recruitment time is calculated and the number of recruited patients is quantified for a given time and probability of recruitment. The expected delay and the effective recruitment durations are estimated using both continuous and discrete time modeling. CONCLUSION: The proposed type of Monte Carlo simulation Markov models will enable optimization of the recruitment process and the estimation and the calibration of its parameters to aid the proposed clinical trials. A continuous time simulation may minimize the duration of the recruitment and, consequently, the total duration of the trial.

Analysis of the World Bank's pharmaceutical lending.

This article analyzes the World Bank's lending activity on pharmaceuticals and medical products (PMP) during the fiscal years (FY) 1999-2001 by regions, borrower and supplier country, and procurement method. Data for the study derived from the World Bank Project and the Business Warehouse databases. The information included all Bank projects approved during the study period. Information for the PMP procurement contracts was extracted for the health sector components of all sector projects awarded. Contract dollar amount was aggregated by borrower and supplier countries. A total of 365 contracts of PMP for a value of US$ 364.5 million (2001 prices) were awarded. International competitive bidding was the most common procurement method used representing 46.0% of the total PMP contracts amount. Domestic providers supplied 52.5% of the PMP contracts managed by the borrower countries. Twenty-two countries accounted for 97.0% of the total PMP purchased during the period of analysis. Only a small fraction of the Bank activity was directed to the pharmaceutical sector. There is a need for more involvement of the World Bank to increase accessibility, affordability and rational use of pharmaceuticals and medical products. An evaluation of the different procurement methods and their implications on drug quality and prices should be performed.

Validation by simulation of a clinical trial model using the standardized mean and variance criteria.

OBJECTIVE: To develop and validate a model of a clinical trial that evaluates the changes in cholesterol level as a surrogate marker for lipodystrophy in HIV subjects under alternative antiretroviral regimes, i.e., treatment with Protease Inhibitors vs. a combination of nevirapine and other antiretroviral drugs. METHODS: Five simulation models were developed based on different assumptions, on treatment variability and pattern of cholesterol reduction over time. The last recorded cholesterol level, the difference from the baseline, the average difference from the baseline and level evolution, are the considered endpoints. Specific validation criteria based on a 10% minus or plus standardized distance in means and variances were used to compare the real and the simulated data. RESULTS: The validity criterion was met by all models for considered endpoints. However, only two models met the validity criterion when all endpoints were considered. The model based on the assumption that within-subjects variability of cholesterol levels changes over time is the one that minimizes the validity criterion, standardized distance equal to or less than 1% minus or plus. CONCLUSION: Simulation is a useful technique for calibration, estimation, and evaluation of models, which allows us to relax the often overly restrictive assumptions regarding parameters required by analytical approaches. The validity criterion can also be used to select the preferred model for design optimization, until additional data are obtained allowing an external validation of the model.