Contributions of cost-effectiveness analyses (CEA) to influenza vaccination policy for older adults in Europe.

This review describes the importance of economic evaluations and real-world evidence (RWE) for the assessment of enhanced influenza vaccines for older adults in Europe. Individuals ≥65 years of age are at increased risk of severe influenza outcomes and many countries in Europe recommend enhanced vaccines for this population to mitigate immunosenescence. Some National Immunization Technical Advisory Groups (NITAGs) may preferentially recommend a specific enhanced vaccine, necessitating comparative economic evaluation and estimation of relative vaccine effectiveness between enhanced vaccine options in the absence of direct head-to-head efficacy data. Distinct approaches to economic modeling and cost-effectiveness analysis (CEA) guide national vaccination policies in Europe, including how underlying data, such as RWE, are used in these models. RWE is an important evidence source for input into CEA models based on disease factors (e.g., antigenic shift and seasonal variation) and practical factors (e.g., limitations of performing multiple randomized clinical trials to capture seasonal variation; the need to obtain relevant patient-oriented, real-world endpoints, such as hospitalizations). CEA is considered crucial to vaccine assessment among certain countries in Europe, but further harmonization of economic evaluations, including the use of RWE, across NITAGs in Europe may be of benefit, alongside standardized approaches for vaccine appraisal. In the future, more countries may use RWE as an input in CEA models to support NITAG recommendations for enhanced influenza vaccines in older populations, especially considering the value of RWE for the assessment of influenza epidemiology and vaccine effectiveness as stated by the World Health Organization, and the availability of a broad RWE base for certain enhanced vaccines.

Real-World Evidence in Cost-Effectiveness Analysis of Enhanced Influenza Vaccines in Adults ≥ 65 Years of Age: Literature Review and Expert Opinion.

Influenza vaccination can benefit most populations, including adults ≥ 65 years of age, who are at greater risk of influenza-related complications. In many countries, enhanced vaccines, such as adjuvanted, high-dose, and recombinant trivalent/quadrivalent influenza vaccines (aTIV/aQIV, HD-TIV/HD-QIV, and QIVr, respectively), are recommended in older populations to provide higher immunogenicity and increased relative vaccine efficacy/effectiveness (rVE) than standard-dose vaccines. This review explores how efficacy and effectiveness data from randomized controlled trials and real-world evidence (RWE) are used in economic evaluations. Findings from published cost-effectiveness analyses (CEA) on enhanced influenza vaccines for older adults are summarized, and the assumptions and approaches used in these CEA are assessed alongside discussion of the importance of RWE in CEA. Results from many CEA showed that adjuvanted and high-dose enhanced vaccines were cost-effective compared with standard vaccines, and that differences in rVE estimates and acquisition price may drive differences in cost-effectiveness estimates between enhanced vaccines. Overall, RWE and CEA provide clinical and economic rationale for enhanced vaccine use in people ≥ 65 years of age, an at-risk population with substantial burden of disease. Countries that consider RWE when making vaccine recommendations have preferentially recommended aTIV/aQIV, as well as HD-TIV/HD-QIV and QIVr, to protect older individuals.

An Economic Comparison in the Elderly of Adjuvanted Quadrivalent Influenza Vaccine with Recombinant Quadrivalent Influenza Vaccine in Spain.

Influenza infections impose a high burden of morbidity and mortality among older adults, at great cost to individuals and society. Enhanced influenza vaccines, which contain either an immune adjuvant or higher than normal doses of influenza virus antigens, are recommended for older adults. We used a health economics model to evaluate the cost effectiveness in Spain of a recently licensed recombinant quadrivalent influenza vaccine (QIVr), which contains three times the standard dose of influenza virus hemagglutinin but no neuraminidase, compared with an MF59-adjuvanted quadrivalent influenza vaccine (aQIV). Based on current tender prices in Spain and a conservative assumption that QIVr is 10.7% relatively more effective than aQIV, the incremental cost-effectiveness ratio (ICER) for QIVr was EUR 101,612.41 per quality-adjusted life year (QALY) gained. To meet the Spanish willingness-to-pay threshold of EUR 25,000 per QALY gained, QIVr would need to be 34.1% relatively more effective than aQIV. In a probabilistic sensitivity analysis conducted to confirm the robustness of the analysis, 99.7% of simulations for QIVr were higher than the willingness-to-pay curve. These findings suggest that QIVr is not currently a cost-effective influenza vaccine option relative to aQIV for older persons living in Spain.

An Economic Evaluation of the Adjuvanted Quadrivalent Influenza Vaccine Compared with Standard-Dose Quadrivalent Influenza Vaccine in the Spanish Older Adult Population.

Standard-dose quadrivalent influenza vaccines (QIV) are designed to provide protection against all four influenza strains. Adjuvanted QIV (aQIV), indicated for individuals aged 65+ years, combines MF59® adjuvant (an oil-in-water emulsion of squalene oil) with a standard dose of antigen, and is designed to produce stronger and longer immune response, especially in the elderly where immunosenescence reduces vaccine effectiveness. This study evaluated the cost-effectiveness of aQIV vs. egg-based standard-dose QIV (QIVe) in the elderly population, from the payer and societal perspective in Spain. A dynamic transmission model, which accounts for herd protection, was used to predict the number of medically attended infections in Spain. A decision tree structure was used to forecast influenza-related costs and benefits. Influenza-related probabilities of outpatient visit, hospitalization, work absenteeism, mortality, and associated utilities and costs were extracted from Spanish and European published literature. Relative vaccine effectiveness (rVE) was sourced from two different meta-analyses: the first meta-analysis was informed by laboratory-confirmed influenza studies only, resulting in a rVE = 34.6% (CI95% 2-66%) in favor of aQIV; the second meta-analysis included real world evidence influenza-related medical encounters outcomes, resulting in a rVE = 13.9% (CI95% 4.2-23.5%) in benefit of aQIV. All costs were expressed in 2021 euros. Results indicate that replacing QIVe with aQIV in the Spanish elderly population would prevent on average 43,664 influenza complicated cases, 1111 hospitalizations, and 569 deaths (with a rVE = 34.6%) or 19,104 influenza complicated cases, 486 hospitalizations, and 252 deaths (with a rVE = 13.9%). When the rVE of aQIV vs. QIVe is 34.6%, the incremental cost per quality adjusted life years (QALY) gained was €2240 from the payer; from the societal perspective, aQIV was cost saving compared with QIVe. If the rVE was 13.9%, the incremental cost per QALY was €6694 and €3936 from the payer and societal perspective, respectively. Sensitivity analyses validated the robustness of these findings. Results indicate that replacing QIVe with aQIV in the Spanish elderly population is a cost-effective strategy for the Spanish healthcare system.

Cost-Effectiveness and Burden of Disease for Adjuvanted Quadrivalent Influenza Vaccines Compared to High-Dose Quadrivalent Influenza Vaccines in Elderly Patients in Spain.

Influenza is a contagious respiratory disease that causes severe illness and death, particularly in elderly populations. Two enhanced formulations of quadrivalent influenza vaccine (QIV) are available in Spain. Adjuvanted QIV (aQIV) is available for those aged 65+ and high-dose QIV (HD-QIV) for those aged 60+. In this study, we used a health economic model to assess the costs and outcomes associated with using aQIV or HD-QIV in subjects aged 65+. Using aQIV instead of HD-QIV to vaccinate an estimated 5,126,343 elderly people results in reductions of 5405 symptomatic cases, 760 primary care visits, 171 emergency room visits, 442 hospitalizations, and 26 deaths in Spain each year. Life-years (LYs) and quality-adjusted LYs (QALYs) increases by 260 and 206, respectively, each year. Savings from a direct medical payer perspective are EUR 63.6 million, driven by the lower aQIV vaccine price and a minor advantage in effectiveness. From a societal perspective, savings increase to EUR 64.2 million. Results are supported by scenario and sensitivity analyses. When vaccine prices are assumed equal, aQIV remains dominant compared to HD-QIV. Potential savings are estimated at over EUR 61 million in vaccine costs alone. Therefore, aQIV provides a highly cost-effective alternative to HD-QIV for people aged 65+ in Spain.

An alternative model in the provision of CPAP in sleep apnea: a comparative cost analysis.

BACKGROUND: To conduct a pilot study on an alternative model for the provision of respiratory therapies in sleep apnea-hypopnea syndrome (SAHS) by internalizing the service with the purchase, monitoring and control of continuous positive airway pressure (CPAP) equipment by the hospital. METHODS: An observational, prospective pilot study of comparative cost analysis by internalizing the service to include all patients up to a budget limit of 5000 euros. The cost of internalizing the service included the acquisition of CPAP equipment and all the necessary accessories in addition to the nursing days necessary to track the patients. Patient satisfaction was assessed by a survey of the hospital service. RESULTS: Twenty-one patients with 23,046 patient-days of follow-up were included. The cost of the internalized system was 6825.11 €. The cost of the outsourced system over the same period would have been 22,781.18 €; thus, the direct saving was 15,956.07 €. The cost per device per day of the internalized system was 0.30 € versus the 0.99 € that the outsourced system would have cost during the study period. In the satisfaction survey, 12 (70.6%) patients indicated that they preferred the service of the hospital over that of the external company. No patient preferred the outsourced system. CONCLUSIONS: The internalization of CPAP service represents significant cost savings from a hospital perspective and an improvement in patients' perceptions of the quality of service.

Evaluación de la eficacia y seguridad de tigeciclina en el tratamiento de infecciones del tracto respiratorio: Revisión sistemática de la literatura científica / Evaluation of the efficacy and safety of tigecycline for treatment of respiratory tract infections: Systematic review of literature

Background: Tigecycline is indicated for the treatment of complicated skin infections, soft tissue and intraabdominal infections. Its use could be extended to community-acquired pneumonia (CAP) and hospital pneumonia (HN). The objective was to evaluate the efficacy and safety of tigecycline in the treatment of respiratory infections. Methods: systematic review (2012). Databases used were MEDLINE, EMBASE, Cochrane Library, CRD and WOK. We identified clinical trials of adults with respiratory infection, treated with tigecycline. The quality of the studies was assessed using CASPe checklist. Results: We selected four clinical trials of high-moderate quality. Three studies with patients with CAP and a trial with HN patients. In patients with CAP, efficacy of tigecycline (88.6 to 90.6%) was higher than levofloxacin (85.3 to 87.2%). The non inferiority testing was statistically significant (p < 0.001). In the study of patients with HN tigecycline showed an efficiency of 67.9% versus 78.2% for imipenem/cilastatin. Main adverse effects were gastrointestinal. Conclusions: The efficacy of tigecycline is non inferior than levofloxacin in patients with CAP, but less than imipenem in patients with HN. Tigecycline demonstrates noninferiority versus others tested antibiotics, and it shows a good safety profile.

Introducción: Tigeciclina está indicada en el tratamiento de infecciones complicadas de piel, tejidos blandos e intra-abdominales. Su utilización podría extenderse para neumonías adquiridas en la comunidad (NAC) y neumonías hospitalarias (NH). El objetivo ha sido evaluar la eficacia y seguridad de tigeciclina en el tratamiento de infecciones respiratorias. Material y Métodos: Revisión sistemática (2012). Se realizaron búsquedas en MedLine, Embase, Cochrane Library, CRD y WOK. Se localizaron ensayos clínicos de adultos con infección respiratoria, tratados mediante tigeciclina. La calidad de los estudios se valoró mediante los criterios CASPe. Resultados: Se seleccionaron cuatro ensayos clínicos de calidad alta-moderada. Tres estudios incluyeron pacientes con NAC y un estudio a pacientes con NH. En pacientes con NAC la eficacia de tigeciclina (88,6-90,6%) fue no inferior a la de levofloxacina (85,3-87,2%). El "test de no inferioridad" fue estadísticamente significativo (p < 0,001). En el estudio de pacientes con NH, tigeciclina presentó una eficacia de 67,9% frente a 78,2% de imipenem/cilastatina. Los principales efectos adversos fueron gastrointestinales. Conclusiones: la eficacia de tigeciclina es no inferior a la de levofloxacina en pacientes con NAC, pero inferior a imipenem en pacientes con NH. Tigeciclina ha demostrado no inferioridad frente a los otros antimicrobianos testados. Tigeciclina demuestra tener un buen perfil de seguridad.

[Evaluation of the efficacy and safety of tigecycline for treatment of respiratory tract infections: systematic review of literature]. / Evaluación de la eficacia y seguridad de tigeciclina en el tratamiento de infecciones del tracto respiratorio: Revisión sistemática de la literatura científica.

BACKGROUND: Tigecycline is indicated for the treatment of complicated skin infections, soft tissue and intraabdominal infections. Its use could be extended to community-acquired pneumonia (CAP) and hospital pneumonia (HN). The objective was to evaluate the efficacy and safety of tigecycline in the treatment of respiratory infections. METHODS: systematic review (2012). Databases used were MEDLINE, EMBASE, Cochrane Library, CRD and WOK. We identified clinical trials of adults with respiratory infection, treated with tigecycline. The quality of the studies was assessed using CASPe checklist. RESULTS: We selected four clinical trials of high-moderate quality. Three studies with patients with CAP and a trial with HN patients. In patients with CAP, efficacy of tigecycline (88.6 to 90.6%) was higher than levofloxacin (85.3 to 87.2%). The non inferiority testing was statistically significant (p < 0.001). In the study of patients with HN tigecycline showed an efficiency of 67.9% versus 78.2% for imipenem/cilastatin. Main adverse effects were gastrointestinal. CONCLUSIONS: The efficacy of tigecycline is non inferior than levofloxacin in patients with CAP, but less than imipenem in patients with HN. Tigecycline demonstrates noninferiority versus others tested antibiotics, and it shows a good safety profile.

Control ambulatorio de los pacientes con trombosis venosa profunda y cáncer: estudio de seguridad, costes e impacto presupuestario / Outpatient management of patients with deep vein thrombosis and cancer: A study of safety, cost and budget impact

Fundamento y objetivo: Realizamos un estudio sobre seguridad, costes comparados y análisis de impacto presupuestario del tratamiento ambulatorio de pacientes con cáncer y trombosis venosa profunda (TVP) frente al tratamiento hospitalario. Material y métodos: Estudio observacional y prospectivo de pacientes con neoplasia conocida y diagnosticados de TVP desde 2003 hasta 2007. Las variables de resultados fueron mortalidad, recidivas y hemorragias a un mes. Realizamos un análisis económico para evaluar el coste comparado de los pacientes tratados ambulatoriamente frente al procedimiento habitual. Resultados: Se incluyeron 317 pacientes, 55 (17%) con cáncer. La edad media (DE) de los pacientes fue de 63 (11) años. Las complicaciones a un mes fueron: 2 sangrados, 2 recidivas y 6 muertes. De todos los pacientes, solo 7 (13,7%) necesitaron ingreso hospitalario. Todas las muertes excepto una fueron debidas a la progresión de su enfermedad de base. Cuando realizamos el análisis económico observamos que el tratamiento ambulatorio es 6 veces menos costoso que el hospitalario, lo que implicaría una reducción de costes de un 85%. Conclusiones: El tratamiento ambulatorio a través de una consulta monográfica de los pacientes con cáncer y TVP es seguro y podría ahorrar importantes recursos económicos (AU)

Background and objective: This is a safety and cost comparison study with an analysis of budgetary impact of ambulatory management of patients with cancer and deep vein thrombosis (DVT) compared with hospital management. Material and methods: Prospective observational study of patients with known malignancy and diagnosed with DVT from 2003 to 2007. The outcome variables were mortality, relapse and bleeding in one month. We conducted an economic analysis to evaluate the comparative cost of ambulatory patients. Results: Three hundred and seventeen patients, 55 (17%) had cancer. The mean age of patients was 63±11 years. There were 2 hemorrhagic events, 2 recurrences and 6 deaths in one month of follow-up. Of all patients, only 7 (13,7%) required hospitalization. All but one deaths were due to progression of the underlying disease. Economic analysis concluded that outpatient management is 6 times less expensive than hospital management, which would imply a cost reduction of 85%. Conclusions: Specialized outpatient treatment of cancer patients with DVT is safe and could save significant financial resources (AU)

[Outpatient management of patients with deep vein thrombosis and cancer: a study of safety, cost and budget impact]. / Control ambulatorio de los pacientes con trombosis venosa profunda y cáncer: estudio de seguridad, costes e impacto presupuestario.

BACKGROUND AND OBJECTIVE: This is a safety and cost comparison study with an analysis of budgetary impact of ambulatory management of patients with cancer and deep vein thrombosis (DVT) compared with hospital management. MATERIAL AND METHODS: Prospective observational study of patients with known malignancy and diagnosed with DVT from 2003 to 2007. The outcome variables were mortality, relapse and bleeding in one month. We conducted an economic analysis to evaluate the comparative cost of ambulatory patients. RESULTS: Three hundred and seventeen patients, 55 (17%) had cancer. The mean age of patients was 63 ± 11 years. There were 2 hemorrhagic events, 2 recurrences and 6 deaths in one month of follow-up. Of all patients, only 7 (13,7%) required hospitalization. All but one deaths were due to progression of the underlying disease. Economic analysis concluded that outpatient management is 6 times less expensive than hospital management, which would imply a cost reduction of 85%. CONCLUSIONS: Specialized outpatient treatment of cancer patients with DVT is safe and could save significant financial resources.

Evaluación del sistema de navegación magnética intracardiaca Niobe, revisión sistemática de la literatura científica / Assessment of intracardiac magnetic navigation system Niobe, systematic review

Introducción y objetivos. Los métodos actuales de ablación conllevan sistemas de navegación manual y ablación cardiaca, y presentan ciertas limitaciones. El objetivo de este trabajo ha sido evaluar la eficacia y seguridad de los nuevos sistemas de navegación magnética intracardiaca. Métodos. Se hizo una revisión sistemática en las bases MedLine, Embase, Cochrane Library, CRD, ECRI, Hayes y bases de datos de HTA. Como términos Mesh se usaron: "electrophisiologic techniques", "magnetics", "stereotaxic techniques", "heart catheterization" y "catheter ablation". Los criterios de inclusión fueron estudios con adultos y lesiones cardíacas. La intervención fue el sistema de navegación magnética intracardiaca Niobe®. Los resultados medidos fueron: tiempos totales de procedimiento, tiempo de fluoroscopia, tiempo de colocación del catéter, tiempo de mapeo y tiempo de ablación. La calidad se evaluó con los cuestionarios CASPe y STROBE...

Introduction and objective: Current methods of ablation involving manual navigation systems and cardiac ablation have some limitations. The aim of this study was to evaluate the efficacy and safety of intracardiac magnetic navigation systems. Methods: Systematic review in MedLine, Embase, Cochrane Library, Center for Review and Dissemination, ECRI, Hayes and HTA databases was performed. The used Mesh terms were: electrophisiologic techniques, magnetic, stereotaxic techniques, heart catheterization, and catheter ablation. Inclusion criteria werestudies whose populations were adults with cardiac lesions. The intervention was intracardiac magnetic navigation system Niobe ® versus manual cardiacnavigation techniques and manual ablation. The outcomes were total procedure time, fluoroscopy time, time of catheter positioning, mapping and ablation time. Quality of studies was assessed by CASPe and STROBE...

Evaluación de las técnicas de amplificación genómica (NAT) para el tamizaje de hepatitis B en donantes de sangre: revisión sistemática / Assessment of nucleic acid testing (NAT) for screening hepatitis B in blood donors: systematic review

Las nuevas técnicas de biología molecular, denominadas técnicas de amplificación del ADN genómico “nucleic acid testing” (NAT), permiten la detección de partículas del ADN viral de la hepatitis B, independientemente de la fase de la enfermedad. Estas técnicas aumentan la sensibilidad del tamizaje, así el riesgo de infección mediante transfusiones podría reducirse. Se han evaluado las técnicas NAT para el tamizaje de hepatitis B en donantes de sangre. Se ha realizado una revisión sistemática en las bases Medline y Embase (2000-2008), así como en INAHTA, Cochrane Library y Euroscan con términos MeSH “Hepatitis B”, “Blood Transfusion”, “Blood Donors", y “Nucleic Acid Amplification Techniques”, y la terminología libre “hepatitis b”, “hbv”, “nat”, “nat-hbv” y “nucleic acid amplification testing”. Se incluyeron doce estudios, cuatro de ellos utilizaron PCR de fabricación propia, obteniendo resultados dispares; tres emplearon Procleix® (dos determinaron muestras mediante NAT que fueron HBsAg (-), 0,05 por ciento y 0,013 por ciento y el tercero, con 135 pacientes con terapia anti-VHB y HBsAg (-), obtuvo un 80 por ciento de muestras positivas mediante técnicas NAT). Cuatro trabajos con MPX® registraron porcentajes comprendidos entre 0,083 y 0,0015. En el estudio de pruebas diagnósticas incluido, las dos técnicas resultaron tener la misma sensibilidad. Por ello, se puede afirmar que las dos técnicas NAT poseen buena capacidad de tamizaje de hepatitis B, ofreciendo resultados en sensibilidad similares y podrían constituir un avance significativo en la automatización de los bancos de sangre y aumentar la seguridad de los pacientes que reciben transfusiones.

The new techniques of molecular biology called “nucleic acid testing” (NAT), enable the detection of particles of viral DNA in hepatitis B, regardless of the disease stage. These NAT techniques increase the sensitivity of screening, so the risk of infection through transfusion could be reduced. The aim of the study was to assess NAT techniques for screening hepatitis B in blood donors. We carried out a systematic review in Medline and Embase databases (2000-2008), as well as INAHTA, Cochrane Library and EuroScan. MeSH terms used were “Hepatitis B”, “Blood Transfusion”, “Blood Donors”, and “Nucleic Acid Amplification Techniques”, and free terms as “hepatitis B”, “hbv”, “nat”, “nat-hbv” and “nucleic acid amplification testing”. Twelve studies were included, four of them used self-made PCRs, obtaining mixed results, three used Procleix® (two samples identified by NAT were HBsAg (-), 0.05 percent and 0.013 percent; and the third study with 135 patients who received anti-HBV therapy and had HBsAg (-), showed 80 percent of positive samples by NAT techniques). Four papers about MPX® reported percentages ranging between 0.083 and 0.0015. In the study of diagnostic tests including the two techniques, they showed the same sensitivity. Both NAT techniques, have a good capacity for screening hepatitis B and showed similar results in sensitivity. They may be a significant advance in automation of blood banks and increase the safety of transfused patients.

[Assessment of nucleic acid testing (NAT) for screening hepatitis B in blood donors. Systematic review]. / Evaluación de las técnicas de amplificación genómica (NAT) para el tamizaje de hepatitis B en donantes de sangre. Revisión sistemática.

The new techniques of molecular biology called "nucleic acid testing" (NAT), enable the detection of particles of viral DNA in hepatitis B, regardless of the disease stage. These NAT techniques increase the sensitivity of screening, so the risk of infection through transfusion could be reduced. The aim of the study was to assess NAT techniques for screening hepatitis B in blood donors. We carried out a systematic review in Medline and Embase databases (2000-2008), as well as INAHTA, Cochrane Library and EuroScan. MeSH terms used were "Hepatitis B", "Blood Transfusion", "Blood Donors", and "Nucleic Acid Amplification Techniques", and free terms as "hepatitis B", "hbv", "nat", "nat-hbv" and "nucleic acid amplification testing". Twelve studies were included, four of them used self-made PCRs, obtaining mixed results, three used Procleix (two samples identified by NAT were HBsAg (-), 0.05% and 0.013%; and the third study with 135 patients who received anti-HBV therapy and had HBsAg (-), showed 80% of positive samples by NAT techniques). Four papers about MPX reported percentages ranging between 0.083 and 0.0015. In the study of diagnostic tests including the two techniques, they showed the same sensitivity. Both NAT techniques, have a good capacity for screening hepatitis B and showed similar results in sensitivity. They may be a significant advance in automation of blood banks and increase the safety of transfused patients.