A study protocol of a comparative mixed study of the T-Control catheter.

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterization by a multifactorial approach. The general purpose of this study is to determine the effectiveness, comfort, and experience of the patient catheterized with T-Control® compared with patients with a conventional Foley catheter. Study Design: This trial is a mixed-method study comprising a two-arm, pilot comparative study with random allocation to T-Control catheter or traditional Foley catheter in patients with long-term catheterization and a study with qualitative methodology, through discussion groups. Endpoints: The comfort and acceptability of the T-Control® device (qualitative) and the quality of life related to self-perceived health (quantitative) will be analysed as primary endpoints. As secondary endpoints, the following will be analysed: magnitude and rate of infections (symptomatic and asymptomatic); days free of infection; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterization's healthcare resources; and level of satisfaction and workload of health professionals. Patients and Methods: Eligible patients are male and female adults aged ≥18 years, who require a change of long-term bladder catheter. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 4 weeks later, plus the time until the discussion groups take place.

Effectiveness of the T-Control catheter: A study protocol.

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterisation by a multifactorial approach. The general purpose of this study is to evaluate the effectiveness and cost-effectiveness of the T-Control catheter versus the Foley-type catheter in patients with Acute Urine Retention (AUR). Study design: This is a pragmatic, open, multicentre, controlled clinical trial with random allocation to the T-Control catheter or a conventional Foley-type catheter in patients with AUR. Endpoints: The magnitude of infections will be analysed as a primary endpoint. While as secondary endpoint, the following will be analysed: rate of symptomatic and asymptomatic infections; days free of infection; quality of life-related to self-perceived health; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterisation's healthcare resources; level of satisfaction and workload of health professionals and acceptability of the T-Control device as well as the patient experience. Patients and methods: Eligible patients are male adults aged ≥50 years, with AUR and with an indication of bladder catheterisation for at least 2 weeks. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 2 weeks later, plus 2 weeks after this time when the patient will be called for an in-depth interview.

Effectiveness, safety and costs of the FreeStyle Libre glucose monitoring system for children and adolescents with type 1 diabetes in Spain: a prospective, uncontrolled, pre-post study.

OBJECTIVES: This study aimed to evaluate the effectiveness, safety and costs of FreeStyle Libre (FSL) glucose monitoring system for children and adolescents with type 1 diabetes mellitus (T1DM) in Spain. DESIGN: Prospective, multicentre pre-post study. SETTING: Thirteen Spanish public hospitals recruited patients from January 2019 to March 2020, with a 12-month follow-up. PARTICIPANTS: 156 patients were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: glycated haemoglobin (HbA1c) change. Secondary: severe hypoglycaemic events (self-reported and clinical records), quality of life, diabetes treatment knowledge, treatment satisfaction, adverse events, adherence, sensor usage time and scans. Healthcare resource utilisation was assessed for cost analysis from the National Health System perspective, incorporating direct healthcare costs. Data analysis used mixed regression models with repeated measures. The intervention's total cost was estimated by multiplying health resource usage with unit costs. RESULTS: In the whole sample, HbA1c increased significantly (0.32%; 95% CI 0.10% to 0.55%). In the subgroup with baseline HbA1c≥7.5% (n=88), there was a significant reduction at 3 months (-0.46%; 95% CI -0.69% to -0.23%), 6 months (-0.49%; 95% CI -0.73% to -0.25%) and 12 months (-0.43%; 95% CI -0.68% to -0.19%). Well-controlled patients had a significant 12-month worsening (0.32%; 95% CI 0.18% to 0.47%). Self-reported severe hypoglycaemia significantly decreased compared with the previous year for the whole sample (-0.37; 95% CI -0.62 to -0.11). Quality of life and diabetes treatment knowledge showed no significant differences, but satisfaction increased. Adolescents had lower sensor usage time and scans than children. Reduction in HbA1c was significantly associated with device adherence. No serious adverse effects were observed. Data suggest that use of FSL could reduce healthcare resource use (strips and lancets) and costs related to productivity loss. CONCLUSIONS: The use of FSL in young patients with T1DM was associated with a significant reduction in severe hypoglycaemia, and improved HbA1c levels were seen in patients with poor baseline control. Findings suggest cost savings and productivity gains for caregivers. Causal evidence is limited due to the study design. Further research is needed to confirm results and assess risks, especially for patients with lower baseline HbA1c.

Main Challenges of Incorporating Environmental Impacts in the Economic Evaluation of Health Technology Assessment: A Scoping Review.

Health technology assessment (HTA) provides evidence-based information on healthcare technology to support decision making in many countries. Environmental impact is a relevant dimension of a health technology's value, but it has been poorly addressed in HTA processes in spite of the commitment that the health sector must have to contribute to mitigating the effects of climate change. This study aims to identify the state of the art and challenges for quantifying environmental impacts that could be incorporated into the economic evaluation (EE) of HTA. We performed a scoping review that included 22 articles grouped into four types of contribution: (1) concepts to draw up a theoretical framework, (2) HTA reports, (3) parameter designs or suitable indicators, and (4) economic or budgetary impact assessments. This review shows that evaluation of the environmental impact of HTAs is still very incipient. Small steps are being taken in EE, such as carbon footprint estimations from a life-cycle approach of technologies and the entire care pathway.

[Cost-effectiveness of universal childhood vaccination against hepatitis A in Spain: a dynamic approach]. / Coste-efectividad de la vacunación universal infantil frente a la hepatitis A en España: un enfoque dinámico.

OBJECTIVE: To evaluate the cost-effectiveness of infant universal vaccination against hepatitis A in Spain. METHOD: Using a dynamic model and decision tree model, a cost-effectiveness analysis was performed to compare three vaccination strategies against hepatitis A: non-vaccination strategy versus universal childhood vaccination of hepatitis A with one or two doses. The perspective of the study was that of the National Health System (NHS) and a lifetime horizon was considered. Both costs and effects were discounted at 3% per year. Health outcomes were measured in terms of quality adjusted life years (QALY) and the cost-effectiveness measure used was the incremental cost-effectiveness ratio (ICER). In addition, deterministic sensitivity analysis by scenarios was performed. RESULTS: In the particular case of Spain, with low endemicity for hepatitis A, the difference in health outcomes between vaccination strategies (with 1 or 2 doses) and non-vaccination are practically non-existent, terms of QALY. In addition, the ICER obtained is high, exceeding the limits of willingness to pay from Spain (€22,000-25,000/QALY). The deterministic sensitivity analysis showed that the results are sensitive to the variations of the key parameters, although in no case the vaccination strategies are cost-effective. CONCLUSIONS: Universal infant vaccination strategy against hepatitis A would not be a cost-effective option from the NHS perspective in Spain.

Coste-efectividad de la vacunación universal infantil frente a la hepatitis A en España: un enfoque dinámico / Cost-effectiveness of universal childhood vaccination against hepatitis A in Spain: a dynamic approach

Objetivo: Evaluar el coste-efectividad de diferentes estrategias de vacunación universal infantil frente a la hepatitis A en España. Método: A partir de un modelo dinámico y un árbol de decisión, se realizó un análisis de coste-efectividad para comparar tres estrategias de vacunación frente a la hepatitis A: no vacunación y vacunación universal infantil con una y dos dosis. La perspectiva del estudio escogida fue la del Sistema Nacional de Salud (SNS) y se consideró como horizonte temporal toda la vida del paciente. Tanto los costes como los efectos se descontaron al 3% anual. Los resultados en salud se midieron en años de vida ajustados por calidad (AVAC) y la medida de coste-efectividad utilizada es la razón de coste-efectividad incremental (RCEI). Además, se llevaron a cabo análisis de sensibilidad determinísticos por escenarios. Resultados: En el caso particular de España, con baja endemicidad de hepatitis A, las diferencias en resultados en salud entre las distintas estrategias de vacunación (con una o dos dosis) y la no vacunación son prácticamente inexistentes, en términos de AVAC. Además, las RCEI obtenidas son elevadas, superando los límites establecidos de disposición a pagar obtenidos en España (22.000-25.000 €/AVAC). El análisis de sensibilidad determinístico muestra que los resultados son sensibles a las variaciones de los parámetros clave, aunque en ningún caso resultan coste-efectivos. Conclusiones: La vacunación universal infantil frente a la hepatitis A no sería una opción coste-efectiva desde la perspectiva del SNS en España en la actualidad. (AU)

Objective: To evaluate the cost-effectiveness of infant universal vaccination against hepatitis A in Spain. Method: Using a dynamic model and decision tree model, a cost-effectiveness analysis was performed to compare three vaccination strategies against hepatitis A: non-vaccination strategy versus universal childhood vaccination of hepatitis A with one or two doses. The perspective of the study was that of the National Health System (NHS) and a lifetime horizon was considered. Both costs and effects were discounted at 3% per year. Health outcomes were measured in terms of quality adjusted life years (QALY) and the cost-effectiveness measure used was the incremental cost-effectiveness ratio (ICER). In addition, deterministic sensitivity analysis by scenarios was performed. Results: In the particular case of Spain, with low endemicity for hepatitis A, the difference in health outcomes between vaccination strategies (with 1 or 2 doses) and non-vaccination are practically non-existent, terms of QALY. In addition, the ICER obtained is high, exceeding the limits of willingness to pay from Spain (€22,000–25,000/QALY). The deterministic sensitivity analysis showed that the results are sensitive to the variations of the key parameters, although in no case the vaccination strategies are cost-effective. Conclusions: Universal infant vaccination strategy against hepatitis A would not be a cost-effective option from the NHS perspective in Spain. (AU)

Health-Related Quality of Life and Perceived Burden of Informal Caregivers of Patients with Rare Diseases in Selected European Countries.

Most of rare disease (RD) patients are assisted in their homes by their family as informal caregivers, causing a substantial burden among family members devoted to care. The role of informal caregivers has been associated with increased levels of stress, poor physical/mental health and impaired HRQOL. The present study assessed the impact on HRQOL and perceived burden of long-term informal caregiving, as well as the inter-relationships of individuals affected by different RD in six European countries, taking advantage of the data provided by the BURQOL-RD project (France, Germany, Italy, Spain, Sweden and UK). Correlation analysis was used to explore the relation between caregiver HRQOL and caregiver burden (Zarit Burden Interview). Multinomial logistic regression models were used to explore the role of explanatory variables on each domain of caregivers HRQOL measured by EQ-5D. Caregivers' HRQOL is inversely correlated with burden of caring. Mobility dimension of EQ-5D was significantly associated with patients age, time devoted to care by secondary caregivers, patient gender and patient utility index. Patients' age, burden scores and patient utility index significantly predict the capacity of caregivers to perform activities of daily living. Employed caregivers are less likely of reporting 'slight problems' in pain/discomfort dimensions than unemployed caregivers. The EQ-5D instrument is sensitive to measure differences in HRQOL between caregivers with different levels of burden of care.

Cost-effectiveness Analysis of Peripherally Inserted Central Catheters Versus Central Venous Catheters for in-Hospital Parenteral Nutrition.

OBJECTIVE: Our objective was to evaluate the cost-effectiveness of the use of peripherally inserted central venous catheters (PICCs) by a vascular access team (VAT) versus central venous catheters (CVCs) for in-hospital total parenteral nutrition (TPN). METHODS: The study used a cost-effectiveness analysis based on observational data retrospectively obtained from electronic medical records from 2018 to 2019 in a teaching hospital. We included all interventional procedures requiring PICCs or CVCs with the indication of TPN. We recorded the costs of insertion, maintenance, removal, and complications. The main outcome measure was the incidence rate of catheter-associated bacteremia per 1000 catheter days. Cost-effectiveness analysis was performed from the hospital perspective within the context of the publicly funded Spanish health system. Confidence intervals for costs and effectiveness differences were calculated using bootstrap methods. RESULTS: We analyzed 233 CVCs and 292 PICCs from patients receiving TPN. Average duration was longer for PICC (13 versus 9.4 days, P < 0.001). The main reason for complications in both groups was suspected infection (9.77% CVC versus 5.18% PICC). Complication rates due to bacteremia were 2.44% for CVC and 1.15% for PICC. The difference in the incidence of bacteremia per 1000 catheter days was 1.29 (95% confidence interval, -0.89 to 3.90). Overall, costs were lower for PICCs than for CVCs: the difference in mean overall costs was -€559.9 (95% confidence interval, -€919.9 to -€225.4). Uncertainty analysis showed 86.37% of results with lower costs and higher effectiveness for PICC versus CVC. CONCLUSIONS: Placement of PICC by VAT compared with CVC for TPN reduces costs and may decrease the rate of bacteremia.

Cost-effectiveness of multicomponent interventions in type 2 diabetes mellitus in a cluster randomised controlled trial: the INDICA study.

OBJECTIVE: To analyse the cost-effectiveness of multicomponent interventions designed to improve outcomes in type 2 diabetes mellitus (T2DM) in primary care in the Canary Islands, Spain, within the INDICA randomised clinical trial, from the public health system perspective. DESIGN: An economic evaluation was conducted for the within-trial period (2 years) comparing the four arms of the INDICA study. SETTING: Primary care in the Canary Islands, Spain. PARTICIPANTS: 2334 patients with T2DM without complications were included. INTERVENTIONS: Interventions for patients (PTI), for primary care professionals (PFI), for both (combined intervention arm for patients and professionals, CBI) and usual care (UC) as a control group. OUTCOMES: The main outcome was the incremental cost per quality-adjusted life-years (QALY). Only the intervention and the healthcare costs were included. ANALYSIS: Multilevel models were used to estimate results, and to measure the size and significance of incremental changes. Missed values were treated by means of multiple imputations procedure. RESULTS: There were no differences between arms in terms of costs (p=0.093), while some differences were observed in terms of QALYs after 2 years of follow-up (p=0.028). PFI and CBI arms were dominated by the other two arms, PTI and UC. The differences between the PTI and the UC arms were very small in terms of QALYs, but significant in terms of healthcare costs (p=0.045). The total cost of the PTI arm (€2571, 95% CI €2317 to €2826) was lower than the cost in the UC arm (€2750, 95% CI €2506 to €2995), but this difference did not reach statistical significance. Base case estimates of the incremental cost per QALY indicate that the PTI strategy was the cost-effective option. CONCLUSIONS: The INDICA intervention designed for patients with T2DM and families is likely to be cost-effective from the public healthcare perspective. A cost-effectiveness model should explore this in the long term. TRIAL REGISTRATION NUMBER: NCT01657227.

In Search for Comparability: The PECUNIA Reference Unit Costs for Health and Social Care Services in Europe.

Improving the efficiency of mental healthcare service delivery by learning from international best-practice examples requires valid data, including robust unit costs, which currently often lack cross-country comparability. The European ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions (PECUNIA) aimed to harmonize the international unit cost development. This article presents the methodology and set of 36 externally validated, standardized reference unit costs (RUCs) for five health and social care services (general practitioner, dentist, help-line, day-care center, nursing home) in Austria, England, Germany, Hungary, The Netherlands, and Spain based on unambiguous service definitions using the extended DESDE PECUNIA coding framework. The resulting PECUNIA RUCs are largely comparable across countries, with any causes for deviations (e.g., country-specific scope of services) transparently documented. Even under standardized methods, notable limitations due to data-driven divergences in key costing parameters remain. Increased cross-country comparability by adopting a uniform methodology and definitions can advance the quality of evidence-based policy guidance derived from health economic evaluations. The PECUNIA RUCs are available free of charge and aim to significantly improve the quality and feasibility of future economic evaluations and their transferability across mental health systems.

Health Related Quality of Life in Major Depressive Disorder: evolution in time and factors associated.

Major Depressive Disorder (MDD) is the most prevalent mental disorder. We aimed to analyze which factors were associated to their Health-Related Quality of Life (HRQoL) perception in patients diagnosed of MDD and how they evolved over six months.

La calidad de vida relacionada con la salud en el trastorno depresivo mayor: factores asociados con su evolución / Health-related quality of life in major depressive disorder: factors associated with its evolution

Introducción. La Depresión Mayor (DM) es el trastorno de salud mental más prevalente. Se pretende analizar el peso de los factores asociados a la percepción de la Calidad de Vida Relacionada con la Salud (CVRS) en pacientes con diagnóstico de DM y su evolución durante seis meses. Metodología. Se incluyeron 432 sujetos con DM (DSMIV-TR) de consultas hospitalarias, centros de salud mental y centros de atención primaria en País Vasco, Madrid y Canarias. Se siguió a los pacientes durante 6 meses. Se recogieron variables clínicas, sociodemográficas y de abordaje terapéutico. La CVRS se midió mediante el EQ-5D-5L, expresado como “utilidades”. Se construyeron Modelos Lineales Generalizados para responder los objetivos. Resultados. Las mujeres, las personas de mayor edad, los grupos sociales menos favorecidos y aquellos con mayor comorbilidad “orgánica” expresaron una peor CVRS inicial. A los 6 meses permanecían en seguimiento 305 sujetos. El cambio medio en las “utilidades” fue de 0,033 (IC95%: 0,008-0,059), y de 0,132 (IC95%: 0,093-0,171) en los 109 sujetos (35,51%) que expresaron mejoría en su estado de salud. Se asociaron negativamente con la evolución de la CVRS la comorbilidad “orgánica”, la presencia de trastornos de la conducta alimentaria, una mayor edad, el pertenecer a grupos socioeconómicos desfavorecidos o la necesidad de un mayor esfuerzo terapéutico. Conclusiones. La DM se asocia con un gran impacto en la CVRS, que revierte parcialmente en el grupo con buena evolución clínica. La mayor edad, la comorbilidad y el grupo socioeconómico se asocian a una peor evolución de la CVRS.(AU)

Introduction. Major Depressive Disorder (MDD) is the most prevalent mental disorder. We aimed to analyze which factors were associated to their Health-Related Quality of Life (HRQoL) perception in patients diagnosed of MDD and how they evolved over six months. Methods. We included 432 subjects with MDD (DSM-IVTR) from hospital consultations, mental health centres and primary care centres in Basque Country, Madrid and Canary Islands. Patients were followed for 6 months. Clinical, sociodemographic and therapeutic variables were collected. HRQoL was measured by EQ-5D-5L, expressed as “utilities”. Generalized Linear Models were constructed to meet the objectives. Results. Women, older people, disadvantaged social groups and those with higher “physical comorbidity” expressed a worse HRQoL at inclusion. At 6 months, 305 subjects remained in follow-up. The average change in “utilities” was 0.033 (CI95%: 0.008-0.059), and 0.132 (CI95%: 0.093-0.171) in the 109 subjects (35.51%) who expressed improvement in their health status. “Physical comorbidity”, the presence of eating disorders, older age, belonging to disadvantaged socioeconomic groups or the need for greater therapeutic effort were negatively associated with HRQoL evolution. Conclusion. MDD is associated with a great impact on HRQoL, which partially reverts when the patients showed good clinical evolution. Older age, comorbidity and disadvantaged socioeconomic group are associated with a worse evolution of HRQOoL.(AU)

Coste-efectividad del desfibrilador automático implantable para la prevención primaria de la muerte súbita cardiaca / Cost-effectiveness of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death

Introducción y objetivos: El desfibrilador automático implantable (DAI) es una alternativa coste-efectiva para la prevención secundaria de la muerte súbita cardiaca, pero sigue habiendo dudas sobre su eficiencia en prevención primaria, sobre todo en pacientes con cardiopatía no isquémica.Métodos: Análisis de coste-utilidad del DAI más tratamiento médico convencional frente a tratamiento médico convencional para la prevención primaria de arritmias cardiacas desde la perspectiva del Sistema Nacional de Salud. Se simuló el curso de la enfermedad mediante modelos de Markov en pacientes con y sin cardiopatía isquémica. Los parámetros del modelo se basaron en los resultados obtenidos mediante metanálisis de los ensayos clínicos publicados entre 1996 y 2018 en los que se comparaba el DAI con el tratamiento médico convencional, los resultados de seguridad del ensayo DANISH y el análisis de la práctica clínica habitual en un hospital terciario.Resultados: Se estimó un beneficio del DAI sobre la muerte por cualquier causa con HR = 0,70 (IC95%, 0,58-0,85) en cardiopatía isquémica y HR = 0,79 (IC95%, 0,66-0,96) en no isquémica. La razón de coste-efectividad incremental estimada mediante análisis probabilístico fue de 19.171 euros/año de vida ajustado por calidad (AVAC) en pacientes con cardiopatía isquémica, 31.084 euros/AVAC en pacientes con miocardiopatía dilatada no isquémica y 23.230 euros/AVAC en los menores de 68 años.Conclusiones: La eficiencia del DAI monocameral ha mejorado en la última década y este resulta coste-efectivo para los pacientes con disfunción ventricular izquierda de origen isquémico o no isquémico menores de 68 años considerando una disposición a pagar 25.000 euros/AVAC. En pacientes no isquémicos mayores, la razón de coste-efectividad incremental estimada se sitúa alrededor de los 30.000 euros/AVAC (AU)

Introduction and objective: Implantable cardioverter-defibrillators (ICD) are a cost-effective alternative for secondary prevention of sudden cardiac death, but their efficiency in primary prevention, especially among patients with nonischemic heart disease, is still uncertain.Methods: We performed a cost-effectiveness analysis of ICD plus conventional medical treatment (CMT) vs CMT for primary prevention of cardiac arrhythmias from the perspective of the national health service. We simulated the course of the disease by using Markov models in patients with ischemic and nonischemic heart disease. The parameters of the model were based on the results obtained from a meta-analysis of clinical trials published between 1996 and 2018 comparing ICD plus CMT vs CMT, the safety results of the DANISH trial, and analysis of real-world clinical practice in a tertiary hospital.Results: We estimated that ICD reduced the likelihood of all-cause death in patients with ischemic heart disease (HR, 0.70; 95%CI, 0.58-0.85) and in those with nonischemic heart disease (HR, 0.79; 95%CI, 0.66–0.96). The incremental cost-effectiveness ratio (ICER) estimated with probabilistic analysis was €19 171/quality adjusted life year (QALY) in patients with ischemic heart disease and €31 084/QALY in those with nonischemic dilated myocardiopathy overall and €23 230/QALY in patients younger than 68 years.Conclusions: The efficiency of single-lead ICD systems has improved in the last decade, and these devices are cost-effective in patients with ischemic and nonischemic left ventricular dysfunction younger than 68 years, assuming willingness to pay as €25 000/QALY. For older nonischemic patients, the ICER was around €30 000/QALY (AU)

Are Estimates of the Health Opportunity Cost Being Used to Draw Conclusions in Published Cost-Effectiveness Analyses? A Scoping Review in Four Countries.

BACKGROUND: When healthcare budgets are exogenous, cost-effectiveness thresholds (CETs) used to inform funding decisions should represent the health opportunity cost (HOC) of such funding decisions, but HOC-based CET estimates have not been available until recently. In recent years, empirical HOC-based CETs for multiple countries have been published, but the use of these CETs in the cost-effectiveness analysis (CEA) literature has not been investigated. Analysis of the use of HOC-based CETs by researchers undertaking CEAs in countries with different decision-making contexts will provide valuable insights to further understand barriers and facilitators to the acceptance and use of HOC-based CETs. OBJECTIVES: We aimed to identify the CET values used to interpret the results of CEAs published in the scientific literature before and after the publication of jurisdiction-specific empirical HOC-based CETs in four countries. METHODS: We undertook a scoping review of CEAs published in Spain, Australia, the Netherlands and South Africa between 2016 (2014 in Spain) and 2020. CETs used before and after publication of HOC estimates were recorded. We conducted logit regressions exploring factors explaining the use of HOC values in identified studies and linear models exploring the association of the reported CET value with study characteristics and results. RESULTS: 1171 studies were included in this review (870 CEAs and 301 study protocols). HOC values were cited in 28% of CEAs in Spain and in 11% of studies conducted in Australia, but they were not referred to in CEAs undertaken in the Netherlands and South Africa. Regression analyses on Spanish and Australian studies indicate that more recent studies, studies without a conflict of interest and studies estimating an incremental cost-effectiveness ratio (ICER) below the HOC value were more likely to use the HOC as a threshold reference. In addition, we found a small but significant impact indicating that for every dollar increase in the estimated ICER, the reported CET increased by US$0.015. Based on the findings of our review, we discuss the potential factors that might explain the lack of adoption of HOC-based CETs in the empirical CEA literature. CONCLUSIONS: The adoption of HOC-based CETs by identified published CEAs has been uneven across the four analysed countries, most likely due to underlying differences in their decision-making processes. Our results also reinforce a previous finding indicating that CETs might be endogenously selected to fit authors' conclusions.

Psychometric properties of the EQ-5D-5L in patients with major depression: factor analysis and Rasch analysis.

BACKGROUND: The EQ-5D is one of the most recommended questionnaires for cost-effectiveness studies. AIMS: To study the psychometric properties of the EQ-5D-5L in patients with major depression. METHODS: This prospective observational study included 433 patients with major depression who completed the EQ-5D-5L and Patient Health Questionnaire-9 (PHQ-9) questionnaires at baseline, of whom 310 also did six months later. The structural validity was assessed by confirmatory factor analysis, the item functioning by item response analysis, and reliability by Cronbach's alpha. Convergent validity and known-groups validity was studied using the PHQ-9 and a general health question. To assess responsiveness effect sizes were calculated. RESULTS: The results supported the unidimensionality and showed adequate item functioning, with somewhat age-related item differential functioning for the mobility dimension. Cronbach's alpha was 0.77. The EQ-5D-5L showed a high correlation with the PHQ-9 and general health. The more severe the depression level and the poorer the general health, the lower the EQ-5D-5L scores (p < 0.001). Responsiveness parameters showed moderate changes among "improved" patients. CONCLUSIONS: These findings support the adequate psychometric properties of the EQ-5D-5L in patients with major depression. It could be very useful for clinicians and researchers as an outcome measure and for use in economic evaluation.

Cost-effectiveness of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death.

INTRODUCTION AND OBJECTIVES: Implantable cardioverter-defibrillators (ICD) are a cost-effective alternative for secondary prevention of sudden cardiac death, but their efficiency in primary prevention, especially among patients with nonischemic heart disease, is still uncertain. METHODS: We performed a cost-effectiveness analysis of ICD plus conventional medical treatment (CMT) vs CMT for primary prevention of cardiac arrhythmias from the perspective of the national health service. We simulated the course of the disease by using Markov models in patients with ischemic and nonischemic heart disease. The parameters of the model were based on the results obtained from a meta-analysis of clinical trials published between 1996 and 2018 comparing ICD plus CMT vs CMT, the safety results of the DANISH trial, and analysis of real-world clinical practice in a tertiary hospital. RESULTS: We estimated that ICD reduced the likelihood of all-cause death in patients with ischemic heart disease (HR, 0.70; 95%CI, 0.58-0.85) and in those with nonischemic heart disease (HR, 0.79; 95%CI, 0.66-0.96). The incremental cost-effectiveness ratio (ICER) estimated with probabilistic analysis was €19 171/quality adjusted life year (QALY) in patients with ischemic heart disease and €31 084/QALY in those with nonischemic dilated myocardiopathy overall and €23 230/QALY in patients younger than 68 years. CONCLUSIONS: The efficiency of single-lead ICD systems has improved in the last decade, and these devices are cost-effective in patients with ischemic and nonischemic left ventricular dysfunction younger than 68 years, assuming willingness to pay as €25 000/QALY. For older nonischemic patients, the ICER was around €30 000/QALY.

Patient-reported outcome measures for knowledge transfer and behaviour modification interventions in type 2 diabetes-the INDICA study: a multiarm cluster randomised controlled trial.

OBJECTIVE: This study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients' (T2DM) reported outcomes measures (PROMs) in the long-term. Design: open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions. PARTICIPANTS: A total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres. SETTING: Primary Care Centers in Canary Islands (Spain). INTERVENTION: The intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients' results. A third group received both PTI and PFI (combined intervention, CBI). OUTCOME MEASURE: Cognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables. RESULTS: Compared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p<0.001) and distress (p=0.01). The PFI group improved at 24 months in distress (p=0.03) and at 12 months there were improvements in depression (p=0.003), anxiety (p=0.05), HQoL (p=0.005) and self-empowerment (p<0.001). The CBI group improved at 24 months in self-empowerment (p=0.008) and adherence to dietary recommendations (p=0.004) and at 12 months in knowledge (p=0.008), depression (p=0.006), anxiety (p=0.003), distress (p=0.01), HQoL (p<0.001) and neuropathic symptoms (p=0.02). Statistically significant improvements were also observed at 24 months in the proportion of patients who quit smoking for PTI and CBI (41.5% in PTI and 42.3% in CBI vs 21.2% in the UC group). CONCLUSIONS: Assessed interventions to improve PROMs in T2DM attain effectiveness for knowledge, self-empowerment, distress, diet adherence and tobacco cessation. PTI produced the most lasting benefits. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01657227 (6 August 2012) https://clinicaltrials.gov/ct2/show/NCT01657227.

Stepped care for the treatment of depression: a systematic review and meta-analysis.

BACKGROUND: The Stepped Care Model (SCM) proposes a sequential approach in the treatment of depression, applying interventions of increasing intensity according to the level of severity of the individual. METHODS: A systematic review was carried out until January 2020 in eight electronic databases. We included randomized (RCT) and non-randomized controlled trials comparing the SCM to usual non-sequential care. RESULTS: Eighteen RCT with patients with confirmed or probable depression diagnosis were included. Meta-analyses yielded high heterogeneity, and subgroup analyses showed significant effects of the SCM only in studies with baseline moderately severe symptoms on average, compared to samples with mild/moderate depression. In the former subgroup, effects at 3-6 and 9-12 months were small for symptoms' reduction (g = -0.33, 95%CI: -0.55, -0.17 and -0.34, 95%CI: -0.53, -0.16) and moderate-to-strong in response and remission (Risk Ratios between 1.70-1.90). Overall, a significant benefit on quality of life was also observed (6 months: g = 0.31, 95%CI: 0.12, 0.49; 12 months: g = 0.18, 95%CI: 0.06, 0.31). More patients in the SCM groups were prescribed antidepressants at 6 months (RR = 1.31, 95%CI: 1.09, 1.57; I² = 87%). LIMITATIONS: The search does not guarantee the identification of all the relevant literature. Most included studies show uncertain or high risk of bias. CONCLUSIONS: The SCM seems to outperform usual care in populations with at least moderately severe symptoms on average. Results show high heterogeneity and future research should explore its sources.

Response Mapping Methods to Estimate the EQ-5D-5L From the Western Ontario McMaster Universities Osteoarthritis in Patients With Hip or Knee Osteoarthritis.

OBJECTIVES: The mapping technique can estimate generic preference-based measure scores through a specific measure that cannot be used in economic evaluations. This study compared 2 response mapping methods to estimate EQ-5D-5L scores using the Western Ontario McMaster Universities Osteoarthritis (WOMAC). METHODS: The sample consisted of 758 patients with the hip or knee osteoarthritis recruited in baseline. Bayesian networks (BN) and multinomial logistic regression (ML) were used as response mapping models. Predictions were obtained using the 6-month follow-up as a validation sample. The mean absolute error, mean squared error, deviation from the root mean squared error and intraclass correlation coefficient were calculated as precision measures. RESULTS: There was 5.5% of missing data, which was removed. The mean age was 69.6 years (standard deviation = 10.5), with 61.6% of women. The BN model presented lower mean absolute error, mean squared error, root mean squared error and higher intraclass correlation coefficient than the ML model. Only the WOMAC items pain and physical function items were related with the EQ-5D-5L dimensions. CONCLUSION: BN response mapping models are more robust methods, with better prediction results, than ML models. The BN model also provided a graphic representation of the dependency relationships between the EQ-5D-5L dimensions and the different WOMAC items that could be useful in the clinical investigation of patients with hip or knee osteoarthritis.

Cost-of-illness studies in rare diseases: a scoping review.

OBJECTIVE: The aim of this scoping review was to overview the cost-of-illness studies conducted in rare diseases. METHODS: We searched papers published in English in PubMed from January 2007 to December 2018. We selected cost-of-illness studies on rare diseases defined as those with prevalence lower than 5 per 10,000 cases. Studies were selected by one researcher and verified by a second researcher. Methodological characteristics were extracted to develop a narrative synthesis. RESULTS: We included 63 cost-of-illness studies on 42 rare diseases conducted in 25 countries, and 9 systematic reviews. Most studies (94%) adopted a prevalence-based estimation, where the predominant design was cross-sectional with a bottom-up approach. Only four studies adopted an incidence-based estimation. Most studies used questionnaires to patients or caregivers to collect resource utilisation data (67%) although an important number of studies used databases or registries as a source of data (48%). Costs of lost productivity, non-medical costs and informal care costs were included in 68%, 60% and 43% of studies, respectively. CONCLUSION: This review found a paucity of cost-of-illness studies in rare diseases. However, the analysis shows that the cost-of-illness studies of rare diseases are feasible, although the main issue is the lack of primary and/or aggregated data that often prevents a reliable estimation of the economic burden.