[Study protocol on Socioeconomic and Geographic Inequalities in Cancer Incidence, Mortality and Survival in Spain: Multilevel Population-Base Study: DESOCANES study]. / Protocolo del Estudio Poblacional Multinivel de las Desigualdades Socioeconómicas en la Distribución Geográfica de la Incidencia, la Mortalidad y la Supervivencia Neta del Cáncer en España: Estudio DESOCANES.

Incidence and mortality provide information on the burden of cancer morbidity and the potential years of life lost due to cancer. The Spanish Deprivation Index (SDI) has been developed as a standardized measure to study socioeconomic deprivation in Spain at the census tract level. In addition, SDI information can be combined with ecological variables at the population level and data from the High-Resolution European Studies in Cancer. The aim of this study is to characterize socioeconomic inequalities in incidence, excess mortality, premature mortality and net survival for three of the most incident cancers (lung, colon-rectum and breast) in Spain using the SDI. This national population-based study will assess the impact of socioeconomic inequalities using a multilevel modelling approach. Spatial analysis, multilevel modeling, net survival and economic impact assessment will be used. The results will be useful for supporting decision-making, planning, and management of public health interventions aimed at reducing the impact of socioeconomic inequalities in the diagnosis and prognosis of cancer patients in Spain.

Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero(R)) en España / Economic evaluation of the introduction of 4CMenB (Bexsero(R)) in the national vaccine schedule in Spain

INTRODUCCIÓN: Bexsero® (4CMenB), vacuna contra el meningococo B, fue autorizada en Europa en 2013. En España, a pesar de que el meningococo B es la principal causa de enfermedad meningocócica invasiva (EMI), Bexsero® está recomendada y financiada para pacientes con alto riesgo de EMI pero no de forma sistemática en el calendario vacunal del SNS. OBJETIVO: Evaluar el coste-utilidad, el impacto epidemiológico y los costes totales de la introducción de 4CMenB para una política vacunal informada en España. MÉTODO: Se adaptó para España un análisis de coste-utilidad, árbol de decisión probabilístico. Una cohorte de recién nacidos en 2015 fue modelizada con dos posologías mediante dos estrategias: vacunación sistemática con 4CMenB o no vacunación. Los costes se midieron desde la perspectiva del pagador y los beneficios se calcularon en años de vida ajustados por calidad (AVAC). Se realizó un análisis de Monte Carlo y se consideraron 32 escenarios para valorar la robustez y la incertidumbre de los resultados. RESULTADOS: Con la pauta 3+1, la vacunación sistemática previno el 54% de los casos y de las muertes, y se estimó una razón de coste-utilidad incremental (RCUI) de 351.389 €/AVAC (intervalo de confianza del 95% [IC95%]: 265.193-538.428). La pauta 2+1 previno el 50% de los casos y de las muertes, con una RCUI de 278.556 €/AVAC (IC95%: 210.285-430.122). CONCLUSIONES: Dada la incidencia actual de enfermedad meningocócica invasiva en España y la información disponible sobre 4CMenB, nuestro modelo indica que la vacunación sistemática no es coste-efectiva con el actual precio. Solo con un precio de 1,45 € para la pauta 3+1 o de 3,37 € para la pauta 2+1 podría ser recomendada basándose en su eficiencia

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria

[Economic evaluation of the introduction of 4CMenB (Bexsero®) in the national vaccine schedule in Spain]. / Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero®) en España.

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria.

HTA and decision-making processes in Central, Eastern and South Eastern Europe: Results from a survey.

OBJECTIVE: To gain knowledge and insights on health technology assessment (HTA) and decision-making processes in Central, Eastern and South Eastern Europe (CESEE) countries. METHODS: A cross-sectional study was performed. Based on the literature, a questionnaire was developed in a multi-stage process. The questionnaire was arranged according to 5 broad domains: (i) introduction/country settings; (ii) use of HTA in the country; (iii) decision-making process; (iv) implementation of decisions; and (v) HTA and decision-making: future challenges. Potential survey respondents were identified through literature review-with a total of 118 contacts from the 24 CESEE countries. From March to July 2014, the survey was administered via e-mail. RESULTS: A total of 22 questionnaires were received generating an 18.6% response rate, including 4 responses indicating that their institutions had no involvement in HTA. Most of the CESEE countries have entities under government mandates with advisory functions and different responsibilities for decision-making, but mainly in charge of the reimbursement and pricing of medicines. Other areas where discrepancies across countries were found include criteria for selecting technologies to be assessed, stakeholder involvement, evidence requirements, use of economic evaluation, and timeliness of HTA. CONCLUSIONS: A number of CESEE countries have created formal decision-making processes for which HTA is used. However, there is a high level of heterogeneity related to the degree of development of HTA structures, and the methods and processes followed. Further studies focusing on the countries from which information is scarcer and on the HTA of health technologies other than medicines are warranted. CLASSIFICATION: Reviews/comparative analyses.

Competition in the off-patent medicine market in Spain: The national reference pricing system versus the regional system of tendering for outpatient prescription medicines in Andalusia.

Spain has a reference price system (RPS) for off-patent medicines since 1997. In addition, from 2012, Andalusia is running a series of tenders for procuring off-patent medicines dispensed by community pharmacies, for those medicines included in the system of homogenous clusters within the national reference price system. Such tenders offer additional savings to the regional payer - in the form of rebates ("economic improvements") from companies winning the tender. This paper estimates that the regional savings were between €43 M to €54 M over the period of study (April - September 2015). The paper also estimates that Spain could have made between 14 and 17 times higher savings than the national reference pricing system savings, had the Andalusian-type tender been implemented at national level over the same period of study. Based on our analysis, we have four remarks. First, the national RPS in Spain is not generating enough price competition for off-patent products dispensed in primary care pharmacies. Second, tenders can be a useful way to generate competition and financial savings in the off-patent market. Third, tenders can lead to discounts offered by medicine providers being redistributed from pharmacies to payers. And fourth, before implementing a national tender in Spain, several key issues need to be addressed to ensure it provides the right incentives both in the short and long run.

Health technology assessment process of a cardiovascular medical device in four different settings.

AIM: Health technology assessment (HTA) is a tool to help the decision-making process. The aim is to describe methods and processes used in the reimbursement decision making for drug-eluting stents (DES) in four different settings. METHODS: DES as a technology under study was selected according to different criteria, all of them agreed by a working group. A survey of key informants was designed. RESULTS: DES was evaluated following well-structured HTA processes. Nonetheless, scope for improvement was observed in relation to the data considered for the final decision, the transparency and inclusiveness of the process as well as in the methods employed. CONCLUSION: An attempt to describe the HTA processes of a well-known medical device.

Adoption of the HPV vaccine: a case study of three emerging countries.

BACKGROUND: The human papillomavirus (HPV) vaccine has recently attracted considerable attention in emerging countries, due to its potential to reduce the impact of HPV-related diseases. This case study sheds new light about the variety of HTA arrangements, methods and processes involved in the adoption and use of HPV vaccines in a selected sample of central, eastern and southern Europe and Latin America and the Caribbean, all of them emerging in the use of HTA. MATERIALS & METHODS: A multi-country case study was designed. Mixed methods, document review, semi-structured surveys and personal communication with experts, were used for data collection and triangulation. RESULTS: This study shows that common elements of good practice exist in the processes and methods used, with all countries arriving at the same appraisal recommendations. However, the influence of socio-politico-economic factors appears to be determinant on the final decisions and restrictions to access made. CONCLUSION: This case study intends to draw useful lessons for policymakers in emerging settings interested in the adoption of the HPV vaccine supported by evidence-informed processes, such as those offered by institutionalized HTA. Future studies are also recommended to elucidate the specific roles that social values and uncertainties play in vaccine decision-making across different societies.

Adoption of trastuzumab for breast cancer in four emerging countries in the use of health technology assessment: a case study.

AIM: To describe processes for the adoption of trastuzumab in four countries in the use of health technology assessment (HTA): Poland, Albania, Brazil and Colombia. MATERIALS & METHODS: Mixed methods were used for collection and triangulation of data. Data were examined following a conceptual framework connecting HTA process steps and key principles. RESULTS: Trastuzumab was generally assessed following well-structured HTA processes. Nonetheless, areas of improvement were detected in terms of transparency and inclusiveness, as well as in methods used. The extent to which different criteria influenced decisions was unclear. CONCLUSION: This study covers an area in which information may not always be available, and sets the example for emerging countries interested in HTA. Further studies to gain a better understanding on decision-making across settings are warranted.

[Controversial Issues in Economic Evaluation (III): health Care Interventions in Special Situations]. / Cuestiones controvertidas en evaluación económica (III). Intervenciones sanitarias en tres situaciones especiales: enfermedades raras, tratamientos al final de la vida y externalidades en las evaluaciones.

The development of the economic evaluation of health care interventions has become a support tool in making decisions on pricing and reimbursement of new health interventions. The increasingly extensive application of these techniques has led to the identification of particular situations in which, for various reasons, it may be reasonable to take into account special considerations when applying the general principles of economic evaluation. In this article, which closes a series of three, we will discuss, using the Metaplan technique, about the economic evaluation of health interventions in special situations such as rare diseases and end of life treatments, as well as consideration of externalities in assessments, finally pointing out some research areas to solve the main problems identified in these fields.

[Controversial Issues in Economic Evaluation (II): health Outcomes of Health Care Interventions]. / Cuestiones controvertidas en evaluación económica (II): medidas de resultado en salud de las intervenciones sanitarias.

In this second article of a series of three, we will discuss using the Metaplan technique on controversial issues of health outcomes in economic evaluation of health care interventions. The four-discussion areas focus on: choice of health outcomes measures, where any outcome measure is superior to another; extrapolation and transferability of health outcomes measures, which should not be assumed the results of an EEIS of one country to another without making certain adjustments; appropriate instruments to measure quality of life in Spain, where the EQ-5D was indicated as convenient due to its widespread international use; and, indirect comparisons, where the combination of both comparisons, direct and indirect, it would be advisable if the test for indirect estimates is consistent and has been validated. Finally, research lines to try to overcome the identified discrepancies were identified in each of these areas, some of those are: doing studies of correlation between scores of specific and generic instruments measuring quality of life; update or create a database of economic evaluations in Spain; estimating utilities for the Spanish population by existing generic and specific instruments; or, establish a common way to show the results of a meta-analysis network.

Cuestiones controvertidas en evaluación económica (III): Intervenciones sanitarias en tres situaciones especiales: Enfermedades raras, tratamientos al final de la vida y externalidades en las evaluaciones / Controversial Issues in Economic Evaluation (III): Health Care Interventions in Special Situations

El desarrollo de la evaluación económica de intervenciones sanitarias se ha convertido en una herramienta de apoyo en la toma decisiones sobre financiación pública y fijación de precios de nuevas intervenciones sanitarias. La aplicación cada vez más extensiva de estas técnicas ha llevado a la identificación de situaciones particulares en las que, por diversas razones, podría ser razonable tener en cuenta consideraciones especiales a la hora de aplicar los principios generales de evaluación. En este artículo, que cierra una serie de tres, debatiremos, empleando la técnica Metaplan, sobre la evaluación económica en tres situaciones especiales: las enfermedades raras y los tratamientos al final de la vida, así como la consideración de las externalidades en las evaluaciones, apuntando finalmente algunas líneas de investigación futuras para resolver los principales problemas identificados en estos ámbitos (AU)

The development of the economic evaluation of health care interventions has become a support tool in making decisions on pricing and reimbursement of new health interventions. The increasingly extensive application of these techniques has led to the identification of particular situations in which, for various reasons, it may be reasonable to take into account special considerations when applying the general principles of economic evaluation. In this article, which closes a series of three, we will discuss, using the Metaplan technique, about the economic evaluation of health interventions in special situations such as rare diseases and end of life treatments, as well as consideration of externalities in assessments, finally pointing out some research areas to solve the main problems identified in these fields (AU)

Cuestiones controvertidas en evaluación económica (II): Medidas de resultado en salud de las intervenciones sanitarias / Controversial issues in economic evaluation (II): Health outcomes of health care interventions

En este segundo artículo, de una serie de tres, debatiremos, empleando la técnica Metaplan, sobre cuestiones controvertidas de las medidas de resultado en salud en la evaluación económica de intervenciones sanitarias (EEIS). Las cuatro áreas de debate se centraron en: elección de las medidas de resultado en salud: en abstracto ninguna medida es superior a otra. Extrapolación y transferibilidad de las medidas de resultado en salud: los resultados de una EEIS de un país no deberían ser asumidos en otro sin realizar ciertos ajustes de distinto tipo. Instrumentos adecuados para medir la calidad de vida en España: se apuntó el EQ-5D como conveniente debido a su extendido uso internacional. Y comparaciones indirectas: la combinación de ambas comparaciones, directas e indirectas, sería recomendable si la prueba para las estimaciones indirectas fue consistente y estaba validada. Finalmente, se proponen líneas de investigación para tratar de superar las discrepancias identificadas en cada una de estas áreas, entre las cuáles se encuentran: la realización de estudios de correlación entre puntuaciones de instrumentos específicos y genéricos de medición de calidad de vida, actualizar o crear una base de datos de evaluaciones económicas realizadas en España, la estimación de los conjuntos de utilidades de la población española para instrumentos genéricos y específicos preexistentes o bien, establecer una manera común de mostrar los resultados de un meta-análisis en red (AU)

In this second article of a series of three, we will discuss using the Metaplan technique on controversial issues of health outcomes in economic evaluation of health care interventions. The four-discussion areas focus on: choice of health outcomes measures, where any outcome measure is superior to another; extrapolation and transferability of health outcomes measures, which should not be assumed the results of an EEIS of one country to another without making certain adjustments; appropriate instruments to measure quality of life in Spain, where the EQ-5D was indicated as convenient due to its widespread international use; and, indirect comparisons, where the combination of both comparisons, direct and indirect, it would be advisable if the test for indirect estimates is consistent and has been validated. Finally, research lines to try to overcome the identified discrepancies were identified in each of these areas, some of those are: doing studies of correlation between scores of specific and generic instruments measuring quality of life; update or create a database of economic evaluations in Spain; estimating utilities for the Spanish population by existing generic and specific instruments; or, establish a common way to show the results of a meta-analysis network (AU)

Costes y efectividad de un detector de tendencias glucémicas en pacientes con diabetes mellitus / Costs and outcome of a glucometer that detects severe hypoglycemia patterns in patients with diabetes mellitus

OBJETIVO: Evaluar en términos de coste, resultado e impacto económico el uso de un glucómetro para la monitorización ambulatoria de la glucosa capilar (MAGC), con detector de tendencias glucémicas, comparado con otro que carezca de esta herramienta, para la prevención de hipoglucemias graves (HG) en población con diabetes tipo 1 (DM1) y tipo 2 (DM2) en tratamiento con insulina. MATERIAL Y MÉTODOS: Se ha realizado un modelo de análisis a corto plazo a partir de datos recogidos de la literatura. En el análisis de costes e impacto económico se ha asumido que el coste de los medidores y sus correspondientes tiras son idénticos entre las alternativas, incluyendo solo el coste directo derivado del evento de hipoglucemia grave causado por un mal control metabólico. RESULTADOS: El sistema de MAGC muestra bajos valores de sensibilidad y valores predictivos positivos, y altos valores de especificidad y valores predictivos negativos. Con un riesgo basal de HG en torno al 9% para población DM1 y DM2 en tratamiento con insulina y 17% para población con DM1 < 17 años, el algoritmo con detector de tendencias podría evitar entre el 20 y 35% de las hipoglucemias graves, suponiendo un potencial ahorro de costes por paciente de entre 12 y 39 euros, respectivamente. Asimismo, supondría un ahorro potencial en torno a 7,7 millones de euros para el Sistema Nacional de Salud (SNS) en el análisis basal, asumiendo una tasa de incidencia de un evento de HG por paciente/año. CONCLUSIONES: El modelo estima que el sistema de MAGC con detector de tendencias es efectivo y puede ahorrar costes para el SNS respecto a un sistema de MAGC tradicional. Sin embargo, en el caso de las hipoglucemias graves se hace necesario contar con datos empíricos para poder afirmar dicha conclusión

OBJECTIVE: To estimate the cost, outcome and economic impact, of the use of a Blood Glucose Monitoring System (BGMS) with pattern alert technology compared with standard BGMS, for the prevention of severe hypoglycemia (SH) in the insulin-treated type 1 and type 2 diabetes populations. MATERIAL AND METHODS: A short term model has been constructed from literature data. It has been assumed that the cost of both BGMS and their corresponding strips are identical between alternatives, including only the direct cost of the severe hypoglycemia event caused by poor metabolic control. RESULTS: BGMS shows low sensitivity and positive predictive value, and high specificity and negative predictive value. With a baseline risk of hypoglycemia of around 9% for the insulintreated DM1 and DM2 population, and 17% for DM1 population < 17 years, the trend detector algorithm could prevent between 20% and 35% of severe hypoglycemias. Cost saving per patient would be between Euros 12 and Euros 39, respectively. Moreover, this monitoring system could save costs of around Euros 7.7 million Euros for the Health System in a baseline analysis. CONCLUSIONS: BGMS with pattern alert technology is effective in preventing severe hypoglycemia and can be cost saving for Spanish health system. Nevertheless, empirical data on the probability of reducing Severe Hypoglycemia is necessary in order to reach any firm conclusions

Systematic review of economic evaluation studies and budget impact on ambulatory monitoring of capillary glucose in type 2 diabetics.

OBJECTIVE: Realise a review of studies of economic evaluation about the ambulatory monitoring of capillary glucose (AMGC) in diabetic type II persons. METHODOLOGY: A review of the literature was conducted, in MedLine, various websites, referenced paper and provided by expert's persons. RESULTS: Five studies concluded that the AMGC was a cost-effective strategic, of this papers use Kaiser Permanente data base, its make that these studies could be considered a solely one study. The rest of the papers did not find difference in the AMGC use. CONCLUSIONS: The use of AMGC has an uncertainty efficiency. More studies are needed.

Análisis de coste-efectividad de la prueba de citología cervicovaginal / Cost-effectiveness analysis of conventional and liquid cervicovaginal cytology

Introducción. El cáncer de cérvix es un importante problema de salud pública, ya que produce cerca del 10% de las defunciones femeninas por cáncer en el todo el mundo. Objetivo. Determinar el ratio coste-efectividad de la citología de base líquida frente a la citología convencional para la detección de lesiones precancerosas de cérvix. Metodología. Se ha realizado un modelo de análisis de decisión, desde la perspectiva del sistema sanitario público. Las alternativas de comparación han sido la citología convencional frente a la citología líquida. La evaluación económica comparó la efectividad a corto plazo y el coste de realización de la prueba. Las medidas de efectividad utilizadas han sido los casos encontrados y los casos efectivos (casos encontrados menos falsos negativos). Los valores de exactitud diagnóstica (sensibilidad y especificidad) y prevalencia se extrajeron de un metaanálisis y los costes fueron facilitados por el Hospital Virgen de las Nieves de Granada. Con objeto de evaluar la incertidumbre de las variables incluidas en el modelo, se realizaron diversos análisis de sensibilidad univariante y probabilístico. Resultados. El coste de la determinación de lesiones mediante citología líquida en lugar de citología convencional será de 919,49euros por cada lesión superior a CIN1 encontrada. De la misma manera, al utilizar como medida de efectividad los casos efectivos se observa una efectividad incremental de 0,0375, siendo el ratio coste-efectividad incremental de 574,33euros por lesión identificada (AU)

Introduction. Cervical cancer is a major public health concern, causing approximately 10% of deaths from cancer in women worldwide. Objective. To determine the cost-effectiveness ratio of liquid-based cytology compared with the conventional cytological smear test for the detection of precancerous lesions of the cervix. Methods. A decision analysis model was constructed from the perspective of the public healthcare system. The alternatives compared were conventional and liquid-based cytology. The economic evaluation compared the short-term effectiveness and cost of testing. The measures of effectiveness used were the yield of the test (the proportion of correctly identified cases of cervical lesion in the population) and the «adjusted yield» (the proportion of cases identified minus false negatives). Data on diagnostic accuracy (sensitivity and specificity) and prevalence were obtained from a meta-analysis. Cost values were provided by the Virgen de las Nieves Hospital (Granada, Spain). To assess the uncertainty of the variables included in the model, several univariate and probabilistic sensitivity analyses were carried out. Results. The incremental cost of liquid-based cytology compared with conventional cytology was €919.49 for each cervical intraepithelial neoplasia (CIN1) or higher-stage lesion found. When the adjusted yield was used as the measure of effectiveness, the incremental cost-effectiveness ratio increased to €574 per lesion identified (AU)