Prioritization of initiatives 2024-2027 of the strategic map of pharmaceutical outpatient care of the Spanish Society of Hospital Pharmacy. / Priorización de iniciativas 2024­2027 del mapa estratégico de atención farmacéutica al paciente externo de la Sociedad Española de Farmacia Hospitalaria.

OBJECTIVE: To prioritize the initiatives to be developed for the development of the Strategic Map of Outpatient Care (MAPEX) project to improve the quality of care and Pharmaceutical Care for patients seen in Hospital Pharmacy outpatient clinics in the period 2024-2027 in Spain. METHOD: The study was carried out in 4 phases between January and December 2023. For phase 1, a literature review of the evolution of the project was carried out by the coordinating committee with the aim of establishing a basis on which to define a new proposal for initiatives. In addition, an analysis was made of the health trends that will have an impact in the coming years. In phase 2, a working group of 19 specialists from all the autonomous communities was created, who were called regional ambassadors. They all made a preliminary proposal of initiatives and established revisions for their adjustment and final version both online and in telematic meetings. In phase 3, a consensus was established based on the Delphi-Rand/UCLA methodology with two rounds of online voting to select the initiatives classified as: priority and key or breakthrough. Between the first and second round of voting, a face-to-face "Consensus Conference" was held, where the results of the first round were presented. In phase 4, a public presentation was made in scientific forums and through the web. RESULTS: Ten trends in the health sector were identified. A list of 34 initiatives grouped into five lines of work was established. A total of 103 panelists participated in the first round and 76 in the second. Finally, five initiatives were established as priority and 29 as key. Among those prioritized were external visibility, adaptations to the CMO methodology, strengthening certification and improving training. CONCLUSIONS: The initiatives agreed upon as priorities were aimed at improving professional visibility, broadening the methodology of care work, expanding the quality of care, enhancing the training of professionals and the voice of patients.

Autophagy, a relevant process for metabolic health and type-2 diabetes.

Introduction: Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM.

Introducción: La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas de autofagia funcional (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus de tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2.

Achieving the UNAIDS goals by 2030 in people living with HIV: A simulation model to support the prioritization of health care interventions.

OBJECTIVE: We simulated the impact of implementing different health interventions to improve the HIV continuum of care for people diagnosed, on treatment, and virologically suppressed in Spain for the 2020-2030 period. METHODS: The model was carried out in four phases involving a multidisciplinary expert panel: (1) literature review; (2) selection/definition of the interventions and their effectiveness; (3) consensus meeting; and (4) development of an analytical decision model to project the impact of implementing/strengthening these interventions to improve the HIV continuum of care, corresponding to 2017-2019 (87% diagnosed, 97% on treatment, 90% with viral suppression), through the creation of different scenarios for 2020-2030. A total of 19 interventions were selected based on expanding the offer of HIV rapid tests and implementing training/peer programmes, electronic alerts, multidisciplinary care, and mHealth, among others. The effectiveness of the interventions was defined by the percentage increases in diagnosis, treatment, and viral suppression after their implementation, targeting the entire population and specific groups at high-risk (men who have sex with men, migrants, female sex workers, transgender people, and people who inject drugs). RESULTS: Implementing eight interventions for diagnosis, three for treatment, and eight for viral suppression for the target populations during 2020-2030 would increase the continuum of care to approximately 100% diagnosed (remaining residual undetectable cases), 98% treated, and 96% virologically suppressed. CONCLUSIONS: Planification, prioritization, and implementation of selected interventions based on the current HIV continuum of care could allow achievement of the 95-95-95 UNAIDS goals in Spain by 2030.

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Business intelligence for the visualization and data analysis of Telepharmacy activity indicators in a hospital pharmacy service scorecard.

OBJECTIVE: The consolidation of Telepharmacy during the COVID-19 pandemic  has raised the need for managing large volumes of real-time activity data  through data analysis. The aim of this project was to design a dynamic, user- friendly, customizable scorecard in a hospital pharmacy service for the  visualization and analysis of Telepharmacy activity indicators through the use  of advanced business intelligence technology. METHOD: The software tool was developed by a multidisciplinary team between  April and May 2021, driven from the hospital pharmacy service. Once the Telepharmacy indicators of interest were established,  datasets were extracted from raw databases (administrative databases,  Telepharmacy database, outpatient dispensing software, drug catalogues)  through data analysis. The different data sources were integrated in a  scorecard using PowerBI®. The criteria for processing missing and duplicated  data were defined, and data pre-processing, normalization and transformation were performed. Once the pilot scorecard was validated by  different profiles of users, the structure was designed for the panels to  automatically update as databases were updated. RESULTS: Design and implementation of a scorecard of Telepharmacy activity:  general descriptive panel (demographic profile of patients, count and delivery  conditions, program and medical service); geolocation of destination;  pharmacological profile; relative analysis of patients involved in the  Telepharmacy program with respect to the total of outpatients. In the last  updating as of January 2022, data from 16,000 dispensations to more than  4,000 patients had been collected. This means that 21.93% of outpatients had  benefited at some time point from the Telepharmacy service. Filters enable the  visualization of timeline progress and patient characterization, and  measure Telepharmacy activity by program. CONCLUSIONS: The processing of large Telemedicine datasets from various  sources through Business Intelligence in a hospital pharmacy service makes it  possible to synthesize information, generate customized reports, and visualize  information in a dynamic and attractive format. The application of this new  technology will help us improve strategic clinical and management decision  making.

OBJETIVO: La consolidación de la Telefarmacia en el contexto de la pandemia por la COVID-19 exige manejar a tiempo real un gran volumen de datos de actividad mediante análisis de datos. El objetivo de este trabajo fue diseñar un cuadro de mando ágil, personalizable y dinámico para la visualización y análisis de indicadores de actividad en Telefarmacia en un servicio de farmacia de hospital, mediante el empleo de herramientas  avanzadas de inteligencia empresarial (business intelligence).Método: Un equipo de trabajo multidisciplinar desarrolló una herramienta de  software entre abril y mayo de 2021 impulsado desde el servicio de farmacia  de hospital. Una vez consensuados los indicadores de interés en Telefarmacia,  se extrajeron los datos a partir de bases de datos brutas (base de datos de  Telefarmacia, programa de dispensación de pacientes externos, bases de datos  administrativas, catálogos de fármacos) mediante análisis de datos. La  integración de las diferentes fuentes de datos en el cuadro de mando se realizó mediante PowerBI®. Se definió el manejo de los datos perdidos y duplicados y  se aplicó preprocesamiento, normalización y transformación de los datos. Una  vez  validado el piloto por diferentes tipos de usuarios, se diseñó la estructura para actualización automática de los paneles con las sucesivas actualizaciones de las fuentes de datos. RESULTADOS: Diseño e implementación de un cuadro de mando de la actividad  en Telefarmacia: panel descriptivo general (perfil demográfico de pacientes,  recuento y condiciones de envíos, programa y servicio médico); geolocalización  de destino; perfil farmacológico; análisis relativo de los  pacientes beneficiarios de Telefarmacia respecto del total de pacientes  externos. En el último corte, a enero de 2022, se habían incluido datos de  16.000 dispensaciones con entrega informada a más de 4.000 pacientes, lo  que supone que el 21,93% de los pacientes externos han estado en algún momento en el programa de Telefarmacia. La aplicación de filtros permite  visualizar la evolución temporal, caracterizar grupos de pacientes y  dimensionar la actividad por programas. CONCLUSIONES: El procesamiento de paquetes de datos de Telemedicina, de  gran volumen, difícil manejo y procedentes de diversas fuentes relativas a Telefarmacia mediante inteligencia empresarial, en un servicio de farmacia  de hospital, permite sintetizar la información y proporcionar informes  personalizados y visualizaciones dinámicas y atractivas. La aplicación de estas  nuevas tecnologías puede ayudarnos a mejorar la toma de decisiones  estratégicas, tanto clínicas como de gestión.

Contribution of cabotegravir + rilpivirine long-acting for the treatment of HIV-1 infection.

OBJECTIVE: To determine the value contribution of cabotegravir + rilpivirine, the first injectable every two months long-acting antiretroviral  regimen, using multi-criteria decision analysis. METHOD: The study was developed in two phases. After a small pilot, a field  ork study with a larger number of multidisciplinary experts was carried out.  Seven single-tablet regimens, currently recommended by the GeSIDA  guidelines, were selected as comparators. EVIDEM methodology was followed,  with a framework composed by 12 quantitative and 5 contextual criteria. Mean  and standard deviations were calculated for quantitative criteria (1 to 5 scale;  comparative criteria -5 to +5), whereas qualitative criteria were analyzed as  percentages of experts that considered a positive, neutral or negative impact  for the National Health System. RESULTS: 35 experts participated in the study. Human immunodeficiency virus- 1 infection was considered severe (mean ± standard deviation: 3.0 ± 1.0),  with moderate size of affected population (2.7 ± 1.2) and unmet needs (2.8 ±  1.0). Minimal differences were found in comparative efficacy/effectiveness (0.1  ± 0.5), safety/tolerability (-0.5 ± 0.7), and cost criteria: cost of the  intervention (0.5 ± 2.0), other medical costs (0.2 ± 1.8) and non- medical/indirect costs (0.5 ± 1.6). Experts perceived an improvement with  cabotegravir + rilpivirine long-acting, compared  to current daily oral single-tablet regimens, in patient-reported outcomes (2.7 ± 1.4). Therapeutic benefit  of the long-acting regimen was considered moderate-to-high (3.5 ± 1.2).  Experts considered the evidence provided by cabotegravir + rilpivirine long- actingrobust (4.3 ± 0.8), with elevated consensus on its future  recommendation in guidelines (3.2 ± 1.0). In contextual criteria, most experts  considered positive the impact on population priorities and access (91%),  common goal and specific interests (63%) and political, historical, and cultural  context criteria (60%). Impact was neutral in system capacity and appropriate  use (40%), and opportunity costs and affordability criteria (51%). Result of the  weighted global value contribution of cabotegravir + rilpivirine long-acting  was 0.34 (-1 to +1 scale), with Patient Reported Outcomes comparative  criterion bringing the highest added value. CONCLUSIONS: Cabotegravir + rilpivirine long-acting provides added value  contribution to human immunodeficiency virus-1 management in Spain  compared to daily oral single-tablet regimens. Patient Reported Outcomes and  therapeutic benefit of cabotegravir + rilpivirine long-acting were highly valued  by experts, as the expected benefit in adherence and stigma-related issues  would improve overall quality of life for people living with human  immunodeficiency virus-1.

OBJETIVO: Determinar la contribución de valor de cabotegravir + rilpivirina, el  primer tratamiento antirretroviral inyectable de acción prolongada, utilizando  metodología de análisis de decisión multicriterio.Método: El estudio se desarrolló en dos fases: una prueba piloto y una fase de  extensión, con un grupo multidisciplinar más grande. Se seleccionaron siete regímenes de comprimido único orales diarios  recomendados en las guías GeSIDA como comparadores. Se utilizó el marco  EVIDEM, compuesto por 12 criterios cuantitativos y 5 contextuales. Los  criterios cuantitativos se analizaron calculando la media y desviación estándar,  y los cualitativos se analizaron mediante el porcentaje de expertos que  consideraron el impacto positivo, neutro o negativo para el Sistema Nacional de Salud. RESULTADOS: Un total de 35 expertos participaron en el estudio. La infección  por virus de la inmunodeficiencia humana 1 se consideró grave (media ±  desviación estándar: 3,0 ± 1,0), con un tamaño de población afectada (2,7 ±  1,2) y unas necesidades no cubiertas (2,8 ± 1,0) moderadas. Las diferencias  fueron mínimas en los criterios comparativos de eficacia/efectividad (0,1 ±  0,5), seguridad/tolerabilidad (­0,5 ± 0,7) y coste: coste del tratamiento (0,5 ±  2,0), otros costes médicos (0,2 ± 1,8) y costes no-médicos/indirectos (0,5  ± 1,6). Los expertos observaron una emtrimejora con cabotegravir + rilpivirina  de acción prolongada en los resultados reportados por los pacientes  (2,7 ± 1,4). El beneficio terapéutico (3,5 ± 1,2) se consideró moderado-alto.  La evidencia de cabotegravir + rilpivirina de acción prolongada fue considerada  robusta (4,3 ± 0,8), con elevado consenso sobre su futura  recomendación en las guías (3,2 ± 1,0). En los criterios contextuales, el  impacto fue positivo en los criterios de prioridades de acceso (91%), objetivo  común (63%) y contexto político (60%). El impacto fue neutro en la capacidad  del sistema (40%) y los costes de oportunidad (51%). El resultado  promedio de la contribución del valor global de cabotegravir + rilpivirina de  acción prolongada fue de 0,34 (escala de ­1 a +1), siendo el criterio de  resultados reportados por el paciente el que proporcionó la mayor contribución de valor (0,04). CONCLUSIONES: Cabotegravir + rilpivirina de acción prolongada aporta un valor  añadido en el manejo del virus de la inmunodeficiencia humana 1 en  España en comparación con los regímenes de comprimido único utilizados  actualmente. Los expertos valoraron positivamente los resultados reportados  por los pacientes y el beneficio terapéutico de cabotegravir + rilpivirina de  acción prolongada, considerando que el beneficio esperado en la adherencia y  los problemas relacionados con el estigma produciría una mejora en la calidad  de vida de las personas con virus de la inmunodeficiencia humana 1.

Patient Experience Evaluation of the CMO-Based Pharmaceutical Care Model vs Usual Care in People Living with HIV.

Objective: To compare patient experience in a real-life population of people living with HIV (PLWH) who received pharmaceutical care (PC) based on the Capacity-Motivation-Opportunity (CMO) model versus the traditional model. Methods: Prospective cohort study in PLWH receiving either CMO-based PC or traditional PC in Spain between October 2019 and June 2021 (24 weeks), performed by the pharmacy department of 14 Spanish hospitals. Participants were adult patients with a clinical diagnosis of HIV treated with antiretrovirals who had been monitored in the participating hospital pharmacies for >1 year. Patient experience (IEXPAC questionnaire), clinical outcomes (cholesterol, triglycerides, HDL, glycated haemoglobin, and blood pressure), adherence to treatment, virologic control and patient satisfaction were determined. Results: Patient experience in the CMO group at week 24 was significantly better (7.6 vs 6.9) than in the traditional group, with a higher mean improvement. Adherence was better in the CMO group, particularly with regard to concomitant medications (53.2% to 91.7%, p<0.001); no changes were observed in the traditional group. Patient satisfaction improved in the CMO group vs the traditional group (48 vs 44, p<0.001). Conclusion: To our knowledge, this is the first study to compare CMO vs traditional methodology. The CMO model showed an overall improvement in real-life patient experience, satisfaction, and adherence to treatment compared to the traditional methodology.

How Do Hospital Pharmacists Approach Substitution of Nanomedicines? Insights from a Qualitative Pilot Study and a Quantitative Market Research Analysis in Five European Countries.

We conducted research to assess hospital pharmacists' familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid-follow-ons approved via the generic pathway), two biologic drugs (insulin glargine and etanercept-follow-ons approved via the biosimilar pathway), a non-biologic complex drug (NBCD; glatiramer acetate-follow-ons approved via the hybrid pathway) and a nanomedicine, ferric carboxymaltose (no follow-ons approved as yet). The study was conducted in two phases: an initial qualitative pilot study with 30 participants, followed by a quantitative stage involving 201 pharmacists from five European countries. Most expected negligible safety/efficacy differences between reference and follow-on products. Head-to-head clinical data showing therapeutic equivalence as a prerequisite for reference product/follow-on substitution was perceived to be needed most for biologics (47%), followed by NBCDs (44%)/nanomedicines (39%) and small molecules (23%). Overall, 28% did not know the data requirements for follow-on approval via the hybrid pathway; 16% were familiar with this pathway, compared with 50% and 55% for the generic and biosimilar pathways, respectively. Overall, 19% of respondents thought the European Medicines Agency (EMA) was responsible for defining the substitutability of follow-ons. Education is required to increase hospital pharmacist's knowledge of regulatory approval frameworks and their relevance to substitution practices.

Matching-Adjusted Indirect Comparisons in the assessment of hemato-oncological drugs.

OBJECTIVE: Matching-Adjusted Indirect Comparison is a methodology that has been developed to assess new treatments vs alternatives when a direct comparison is not available through a randomized controlled trial. These comparisons are of particular interest in the areas of oncology and hematology where uncertainty in decision-making on the inclusion of new drugs is frequently accentuated by both the severity of the disease and the high cost of treatment. The objective of this study was to describe how Matching-Adjusted Indirect Comparison methodology has been used to date in the assessment of hematological cancer drugs by international agencies. METHOD: Between January 2015 and October 2019, an exhaustive search was conducted of the websites of European National Agencies that provided public information on the assessment process. The assessments provided by these agencies were reviewed to obtain a list of hematological cancer drugs for which the presentation of a Matched-Adjusted Indirect Comparison was recorded. For this list of drugs, the role of the comparison in the assessment process was analyzed for each selected agency. RESULTS: Thirteen hematological and oncological treatments were found in which the pharmaceutical marketing authorization holder had presented Matching-Adjusted Indirect Comparisons: most of this information referred to the first half of 2018. Acceptance of this methodology diverges among agencies, ranging from 50% in the case of the British National Institute for Health and Clinical Excellence, to 40% in the case of French National Authority for Health, to not having been taken into account in any of the 3 cases assessed by the German Institute for Quality and Efficiency in Health Care. The main cause of non-acceptance was matching-related problems. CONCLUSIONS: Matching- Adjusted Indirect Comparison methodology is a tool that is being utilized in the decision-making process for assessing new hematological cancer treatments.

Objetivo: La comparación indirecta ajustada con emparejamiento es una metodología desarrollada para la evaluación de nuevos tratamientos frente a sus alternativas cuando no se dispone de comparación directa mediante un ensayo clínico aleatorizado y controlado. Estas comparaciones son de especial interés en el área de la hematooncología, en la que la incertidumbre en la toma de decisiones sobre la inclusión de nuevos fármacos se ve frecuentemente acentuada tanto por la gravedad de la enfermedad como por el elevado coste del tratamiento. El objetivo de este artículo es describir cómo la metodología de comparación indirecta ajustada con emparejamiento ha sido empleada hasta la fecha en la evaluación de fármacos hematooncológicos por parte de agencias internacionales.Método: Para la obtención de los datos del análisis se ha realizado una búsqueda exhaustiva en las páginas web de las agencias nacionales europeas entre enero de 2015 y octubre de 2019 que mostraran información pública del proceso evaluativo. Se revisaron las evaluaciones de estas agencias para obtener un listado de fármacos oncohematológicos para los que constara la presentación de documentación de una comparación indirecta ajustada con  emparejamiento. Para este listado de fármacos se analizó para cada agencia seleccionada el papel que dicha comparación tuvo en la evaluación.Resultados: Se han encontrado 13 tratamientos para patologías hematooncológicas en las que el laboratorio había presentado comparaciones con metodología de comparación indirecta ajustada con emparejamiento en su documentación, principalmente a partir del primer semestre de 2018. La aceptación de la metodología diverge entre agencias, pasando de un 50% en el caso del Instituto Nacional para la Salud y la Excelencia Clínica británico, a un 40% en el Alto Comisionado de Salud francés, a no haberse tenido en cuenta en ninguno de los tres casos evaluados por el Instituto para la Calidad y Eficiencia en los cuidados de salud alemán. La principal causa de no aceptación fue la existencia de problemas relacionados con el emparejamiento.Conclusiones: La metodología de comparación indirecta ajustada con emparejamiento es una herramienta de comparación indirecta que está siendo considerada por las agencias analizadas en el proceso de toma de decisiones de evaluación de nuevos medicamentos.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Biosimilars of monoclonal antibodies in inflammatory diseases and cancer: current situation, challenges, and opportunities.

The approval pathway for biosimilars of monoclonal antibodies in the European Union is aimed at ruling out the presence of significant  differences with the original biological in quality attributes, efficacy,  immunogenicity and safety. It also provides the rationale for  extrapolating the evidence obtained with a biosimilar in at least one  indication to the rest of the approved indications of its original  biological, thus simplifying the development programme of biosimilars.  Biosimilars of monoclonal antibodies available in the European Union for  the treatment of inflammatory diseases and cancer have fulfilled all the  requirements for approval, and many of them have additional evidence  available. Moreover, real world data confirms the safety and efficacy of  these drugs in the indications they are being used for. In Spain, many  scientific societies endorse the regulatory pathway of biosimilars and  acknowledge their role in the efficiency of the healthcare system. Even  so, some barriers remain that limit their use. The implementation of  different measures at the patient, prescriber, institutional, and national  levels might increase the penetration of biosimilars, freeing up resources that may be invested in other therapies and, potentially, boost  innovation.

El proceso de aprobación de los biosimilares de anticuerpos  monoclonales en la Unión Europea está dirigido a descartar la presencia  de diferencias significativas con el biológico original en los atributos de  calidad, eficacia, inmunogenicidad y seguridad. Proporciona además la  justificación para extrapolar la evidencia obtenida con un biosimilar en al  menos una indicación al resto de indicaciones aprobadas para su  biológico original, simplificando el programa de desarrollo de los  biosimilares. Los biosimilares de anticuerpos monoclonales disponibles  en la Unión Europea para el tratamiento de enfermedades inflamatorias  y del cáncer han cumplido todos los requerimientos establecidos para la  aprobación, y en muchos casos disponen de evidencia adicional.  Además, los datos de uso en la vida real están confirmando la seguridad  y eficacia de estos fármacos en las distintas patologías en las  que se están utilizando. En España, varias sociedades médicas  avalan el proceso regulatorio de los biosimilares y reconocen su papel  en la eficiencia del sistema sanitario. No obstante, todavía existen  algunas barreras que limitan su uso. La aplicación de diferentes medidas  a nivel de paciente, prescriptor, institucional y  nacional podría aumentar la penetración de los biosimilares, liberando  recursos que podrían invertirse en otras terapias y, potencialmente,  favorecer la innovación.

A Multiple Stakeholder Multicriteria Decision Analysis in Diabetic Macular Edema Management: The MULTIDEX-EMD Study.

BACKGROUND: The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) offers the potential to overcome the challenges associated with traditional decision-making tools. OBJECTIVES: A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. METHODS: Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defined all of the criteria that could influence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was fitted by applying the backward elimination algorithm (relevant criteria: p value < 0.05). Finally, the results were discussed in a deliberative process (phase C). RESULTS: Thirty-one criteria were initially defined (phase A) and grouped into 5 categories: efficacy/effectiveness, safety, organizational and economic impact, patient-reported outcomes, and other therapeutic features. The DCE results (phase B) showed that 10 criteria were relevant to the decision-making process for a 50- to 65-year-old DME patient: mean change in best corrected visual acuity (p value < 0.001), percentage of patients with an improvement of ≥ 15 letters (p value < 0.001), effect duration per administration (p value = 0.008), retinal detachment (p value < 0.001), endophthalmitis (p value = 0.012), myocardial infarction (p value < 0.001), intravitreal hemorrhage (p value = 0.021), annual treatment cost per patient (p value = 0.001), health-related quality of life (HRQoL) (p value = 0.004), and disability level (p value = 0.021). CONCLUSIONS: From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment effect duration. It should also contribute to system sustainability by being affordable, it should have a positive impact on HRQoL, and it should prevent disability.

Burden of diabetes mellitus in patients with acromegaly treated with second-line pharmacotherapy in Spain.

OBJECTIVE: To evaluate the burden of diabetes mellitus (DM) in adult patients with acromegaly treated with second-line pharmacotherapy, from the perspective of the Spanish National Health System (NHS). METHODS: A Markov model was developed including three states: normal glucose metabolism, DM and death. The evolution of a hypothetical cohort of acromegaly patients requiring second-line pharmacological treatment (pegvisomant or pasireotide) after first generation somatostatin analogues therapy was analyzed. Direct healthcare costs regarding acromegaly management, diabetes management and drugs costs were obtained from Spanish sources. Transition probabilities between health states were obtained from published studies. Deterministic and probabilistic sensitivity analyses were undertaken. RESULTS: Compared to pasireotide, pegvisomant increased the likelihood of glucose normalization and reduced the likelihood of DM. Consequently, in a cohort of 1,000 patients with acromegaly, treatment with pegvisomant compared to pasireotide would prevent 243, 413 and 453 cases of DM after 1, 2 and 5 years, respectively, and would reduce mortality by 0.1% after 5 years of treatment. This would result in 1 million euros savings for the NHS in 5 years. These health benefits would be obtained with savings of €1,512, €3,422 and €10,162 per patient treated with pegvisomant, after 1, 2 and 5 years, respectively. After 5 years of treatment, the probability that pegvisomant generated savings versus pasireotide would be 65.3%. CONCLUSION: The favorable effects of pegvisomant on glucose metabolism would allow a considerable number of cases of DM to be avoided compared to pasireotide, resulting in savings for the NHS in Spain.

Healthcare and economic impact. / Atención sanitaria e impacto económico.

This chapter reviews the current model of HIV patient care and its economic impact. There are clinical and geographical differences in the care HIV patients receive and a need to develop new models of comprehen-sive HIV care has been identified. HIV infection in Spain is an important and expensive public health problem. The main costs are due to an-tiretroviral therapy, indirect costs and the cost of admission, consultation and diagnostic testing. A strong correlation between severity and cost has been identified. Patients diagnosed late have a poorer clinical course, increased mortality and require more medical and therapeutic resources. Early detection of the disease significantly improves the clinical outcomes of patients. The increased number of patients receiving treatment and their progressive ageing will increase costs of HIV healthcare in the coming years.

Economic impact of optimising antiretroviral treatment in human immunodeficiency virus-infected adults with suppressed viral load in Spain, by implementing the grade A-1 evidence recommendations of the 2015 GESIDA/National AIDS Plan. / Impacto económico asociado a la implementación de las recomendaciones con grado de evidencia A-I del documento de consenso de GeSIDA/PNS (2015) relativas a la optimización del tratamiento antirretroviral en adultos infectados por virus de la inmunodeficiencia humana con carga viral suprimida en España.

INTRODUCTION: The objective of this study is to estimate the economic impact associated with the optimisation of triple antiretroviral treatment (ART) in patients with undetectable viral load according to the recommendations from the GeSIDA/PNS (2015) Consensus and their applicability in the Spanish clinical practice. METHODS: A pharmacoeconomic model was developed based on data from a National Hospital Prescription Survey on ART (2014) and the A-I evidence recommendations for the optimisation of ART from the GeSIDA/PNS (2015) consensus. The optimisation model took into account the willingness to optimise a particular regimen and other assumptions, and the results were validated by an expert panel in HIV infection (Infectious Disease Specialists and Hospital Pharmacists). The analysis was conducted from the NHS perspective, considering the annual wholesale price and accounting for deductions stated in the RD-Law 8/2010 and the VAT. RESULTS: The expert panel selected six optimisation strategies, and estimated that 10,863 (13.4%) of the 80,859 patients in Spain currently on triple ART, would be candidates to optimise their ART, leading to savings of €15.9M/year (2.4% of total triple ART drug cost). The most feasible strategies (>40% of patients candidates for optimisation, n=4,556) would be optimisations to ATV/r+3TC therapy. These would produce savings between €653 and €4,797 per patient per year depending on baseline triple ART. CONCLUSION: Implementation of the main optimisation strategies recommended in the GeSIDA/PNS (2015) Consensus into Spanish clinical practice would lead to considerable savings, especially those based in dual therapy with ATV/r+3TC, thus contributing to the control of pharmaceutical expenditure and NHS sustainability.

Cost-utility analysis of the fixed-dose combination of dolutegravir/abacavir/lamivudine as initial treatment of HIV+ patients in Spain.

OBJECTIVE: Fixed-dose combinations of antiretroviral drugs have meant an important step forward in simplifying treatment and improving compliance and has led to an increased effectiveness of therapy, a viral load decrease and improving the quality of life of patients. The single-table formulation of dolutegravir with abacavir and lamivudine (DTG/ABC/3TC) is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ABC/3TC) versus the combinations emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and darunavir/r (DRV/r) or raltegravir (RAL) with emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) as initial antiretroviral therapy in patients infected with HIV-1 from the perspective of the Spanish National Health System. METHOD: The ARAMIS model, which uses a microsimulation approach to simulate the individual changes in each patient from the start of treatment to death through a Markov chain of descriptive health states of the disease, was adapted to Spain. The alternatives used for comparison were the fixed-dose combination of emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and the fixed- dose combinations of emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) with darunavir/r (DRV/r) or raltegravir (RAL). The probability of achieving virological suppression by the treatments included in the model was obtained from clinical trials SINGLE, SPRING-2 and FLAMINGO and the costs were expressed in € (2015). The model use the perspective of the Spanish National Health System, with a lifetime horizon and a discount rate of 3% was applied to cost and effectiveness. RESULTS: Treatment initiation with DTG/ABC/3TC was dominant when it was compared with treatment initiation with all the comparators: vs. FTC/TDF/EFV (-67 210.71€/QALY), vs. DRV/r + FTC/TDF or ABC/3TC (-1 787 341.44€/QALY), and vs. RAL + FTC/TDF or ABC/3TC (-1 005 117.13€/QALY). All the sensitivity analyses performed showed the consistency of these findings. CONCLUSIONS: With the premises considered, treatment initiation with DTG/ABC/3TC STR appears to be the most cost-effective option in ARTnaïve HIV infected patients from the Spanish Health System perspective.

Objetivo: Las combinaciones a dosis fijas de medicamentos antirretrovirales han significado un importante paso adelante en la simplificación del tratamiento y la mejora del cumplimiento, así como hacia una mayor eficacia de la terapia, una disminución de la carga viral y una mejora de la calidad de vida de los pacientes. La formulación de un comprimido único una vez al día con dosis fijas de dolutegravir, abacavir y lamivudina (DTG/ABC/3TC) para pacientes infectados con VIH es un régimen altamente eficaz y bien tolerado. El objetivo del estudio fue evaluar la relación coste- utilidad incremental de la combinación de dosis fija de (DTG/ABC/3TC) versus las combinaciones de emtricitabina/tenofovir/efavirenz (TDF/FTC/EFV) y darunavir/r (DRV/r) o raltegravir (RAL) con emtricitabina/tenofovir (FTC/TDF) o abacavir/lamivudina (ABC/3TC) como tratamiento antirretroviral inicial en pacientes infectados con VIH-1 desde la perspectiva del Sistema Nacional de Salud Español.Método: Se adaptó en España el modelo ARAMIS. Este utiliza un enfoque de microsimulación para emular los cambios individuales en cada paciente desde el inicio del tratamiento hasta su muerte mediante una cadena de Markov de estados de salud descriptivos de la enfermedad. Las alternativas empleadas para la comparación fueron la combinación de dosis fijas de emtricitabina/tenofovir/efavirenz (TDF/FTC/EFV) y las combinaciones de dosis fijas de emtricitabina/tenofovir (FTC/TDF) o abacavir/lamivudina (ABC/3TC) con darunavir/r (DRV/r) o raltegravir (RAL). La probabilidad de lograr la supresión virológica mediante los tratamientos incluidos en el modelo se ha obtenido de ensayos clínicos individuales, SPRING2 y FLAMINGO, y los costes fueron expresados en € (2015). El uso del modelo de la perspectiva del Sistema Nacional de Salud español, con un horizonte de vida útil y una tasa de descuento del 3% se, aplicó a coste y efectividad.Resultados: El inicio de tratamiento con DTG/ABC/3TC fue dominante cuando se comparó con el inicio del tratamiento con el resto de comparadores: frente a TDF/FTC/EFV (-67.210,710 € / AVAC) vs DRV/r FTC/TDF o ABC/3TC (-1,787,341.44 € / AVAC) y vs RAL FTC/TDF o ABC/3TC (-1,005,117.13 € / AVAC). Todos los análisis de sensibilidad realizados demostraron la consistencia de estos hallazgos.Conclusiones: Con las premisas consideradas, el inicio del tratamiento con la combinación a dosis fijas de DTG/ABC/3TC parece ser la opción más rentable para el tratamiento de pacientes infectados con el VIH desde la perspectiva del Sistema Nacional de Salud español.

Development of a risk stratification model for pharmaceutical care in HIV patients.

BACKGROUND: The increasing number of HIV-patients and their complexity makes it necessary to develop risk classification tools to improve the optimization of resources. OBJECTIVE: To design a risk-stratified model for pharmaceutical care (PC) in HIV-patients. METHODS: A cross-sectional, multicenter study. An expert panel was created by Hospital Pharmacist experienced in PC for HIV-patients. The study was designed in 4 phases. The first phase included a review of literature and the development of a summary of the scientific evidence available. According to their score, patients were stratified into three levels of PC. In the second and third phases, a sample of patients was assessed and data information was recorded. The overall analysis also allowed pharmacists to define the actions to be applied at each level of priority.Finally, each stratification model was applied to a new sample of patients to verify their applicability and usefulness. Results: All variables included in the model were weighted in terms of their relative relevance compared to the rest. A sample of 215 patients was evaluated to obtain their score and distribution: Priority-1: score ≥ 32 and 10% of the sample; Priority-2: 18-31.9 and 30%; Priority-3: ≤ 17 and 60%. The PC interventions corresponding to each level of priority were classified into "pharmacotherapeutic monitoring", "training, education and patient tracking" and "coordination of all the healthcare team members". CONCLUSIONS: This study supported the design and adaptation of a selection and stratification model for PC in HIV-patients as a tool to identify those who may benefit from priority intervention.

Antecedentes: El aumento del número de pacientes VIH+ en las consultas de atención farmacéutica (AF) y de su complejidad implica la necesidad de desarrollar herramientas de estratificación para mejorar la optimización de recursos.Objetivo: Diseñar un modelo de estratificación en atención farmacéutica al paciente VIH+.Métodos: Estudio multicéntrico trasversal llevado a cabo por un panel de experto en Farmacia Hospitalaria con experiencia en AF al paciente VIH+. El estudio consta de 4 fases. En primer lugar, se realizó una revisión de la literatura y un resumen de la evidencia científica hasta la fecha estableciendo 3 niveles de estratificación. En las fases 2 y 3 una muestra de pacientes fue analizada para definir las intervenciones específicas de cada nivel de estratificación.Finalmente, se empleó el modelo de estratificación en una nueva muestra de pacientes para comprobar su utilidad y correcta aplicación.Resultados: Las variables incluidas en el modelo fueron ponderadas en función de su relevancia. Se analizaron 215 pacientes con el nuevo modelo obteniéndose una puntuación y distribución como sigue: Prioridad-1: puntuación ≥32 y 10% de la muestra; Prioridad-2: 18-31.9 y 30%; Prioridad-3: ≤17 y 60%. Las diferentes intervenciones de cada nivel se clasificaron en "seguimiento farmacoterapéutico", "entrenamiento y formación de pacientes" y coordinación con el resto del equipo multidisciplinar".Conclusión: Este el primer modelo de estratificación para la atención farmacéutica al paciente VIH+. Su uso permitirá identificar aquellos pacientes que más se podrán beneficiar de cada tipo de intervención.

Perceptions about HIV pre-exposure prophylaxis among healthcare professionals in Spain (PERPPRES Study).

OBJECTIVE: To determine the level of support, knowledge and perceptions of pre-exposure prophylaxis (PrEP) by Infectious Disease Specialists and Hospital Pharmacists in Spain. METHODS: Cross-sectional study through an on-line 31-item survey (sociodemographical data, employment status/experience, knowledge of PrEP, use, identified barriers and economic issues). A univariate analysis was performed to evaluate the variables associated with support for PrEP, and compare the assessments by Specialists and Pharmacists. The questions about support for PrEP and agreement with the indication approval were repeated after showing data from published studies. The significance of the change in the answers was analyzed using the McNemar Test. RESULTS: 211 questionnaires were received (80.1% from Pharmacists). 40.3% had low/no familiarity with PrEP (46.2% Pharmacists vs. 16.7% Physicians; p < 0.01). A 53.6% of them would support the use of PrEP (49.7% Pharmacists vs. 69% Physicians; p = 0.038). The minimum acceptable efficacy in order to support PrEP was 85.0 ± 15.5% (82.6 ± 12.1% by Physicians vs. 85.6 ± 15.0% by Pharmacists; p = 0.02). The variables associated with support were: medical profession (OR = 2.26; 95%CI 1.1-4.6; p = 0.038) and lower demand for efficacy (difference = 10.5%; 95%CI 6.9 to 14.1; p < 0.001). After receiving the information, there was an increase in their support for use and indication approval. Most participants (81.5%) did not support its reimbursement. The main barriers identified were: an increase in risk behaviour (24.1%), increase in sexually transmitted diseases (19.0%), resistance (16.6%) and cost (16.0%). CONCLUSIONS: More than half of participants were familiar with PrEP. The majority of them would support its use and the approval of the indication, but would not reimburse it. The use of PrEP in real practice is currently low.

Objetivo: Determinar el grado de apoyo, conocimientos y percepciones respecto a la profilaxis preexposición (PrEP) de los médicos infectólogos y farmacéuticos hospitalarios en España. Métodos: Estudio transversal mediante encuesta de 31 ítems (datos sociodemográficos, situación laboral/experiencia, conocimiento sobre PrEP, uso, opiniones, barreras detectadas y aspectos financieros). Se realizó un análisis univariante para evaluar las variables relacionadas con el apoyo a PrEP y comparar las valoraciones de médicos y farmacéuticos. Las preguntas sobre apoyo a la PrEP y el acuerdo sobre aprobar la indicación se repitieron tras mostrar datos de estudios publicados. Se analizó la significación del cambio en la respuesta mediante la prueba de McNemar. Resultados: Se recibieron 211 cuestionarios (80,1% farmacéuticos). El 40,3% estuvieron nada/poco familiarizados con la PrEP (46,2% farmacéuticos vs. 16,7% médicos; p < 0,01). El 53,6% apoyaría su uso (49,7% farmacéuticos vs. 69% médicos; p = 0,038). La eficacia mínima considerada aceptable fue 85,0 ± 15,5% (82,6 ± 12,1% médicos vs. 85,6 ± 15,0% farmacéuticos; p = 0,02). Las variables relacionadas con el apoyo fueron: profesión médica (OR = 2,26 IC95% 1,1-4,6; p = 0,038) y menor exigencia de eficacia (diferencia 10,5% IC95% 6,9-14,1; p < 0,001). Tras recibir la información, aumentaron el apoyo al uso y la aprobación. El 81,5% no apoyaron la financiación. Las principales barreras señaladas fueron: aumento de conductas de riesgo (24,1%), aumento de enfermedades de transmisión sexual (19,0%), resistencias (16,6%) y coste (16,0%). Conclusiones: Más de la mitad de los encuestados estaban familiarizados con la PrEP. La mayoría apoyaría su uso y la aprobación de la indicación, pero no la financiaría. El uso en la práctica real de la PrEP es escaso en la actualidad.