Mapping the Scientific Research on Suicide and Physical Activity: A Bibliometric Analysis.

This research provides an overview of the current state of scientific literature related to suicide and physical activity (PA). A bibliometric analysis of studies published between 1996 and 2022 in The Web of Science (WoS) was carried out, applying the traditional bibliometric laws, using Microsoft Excel and the VOSviewer software for data and metadata processing. A total of 368 documents (349 primary research and 19 reviews) were extracted from 70 WoS categories. The results revealed an exponential increase in scientific production from 2017 to 2022 (R2 = 88%), revealing the United States hegemony being the most productive country, with 156 of the publications (42.4%), the most cited (4181 citations) being the centre of a collaborative network with links to 35 countries and having April Smith, from the Miami University, as the most prolific author (eight publications) and Thomas Joiner, from the Florida State University, as the most cited author (513 citations). The Psychiatry WoS category, with 155 papers, had the highest number of publications, and The Journal of Affective Disorders, from Elsevier, had the highest number of published papers within this category.

Análisis modal de fallos y efectos aplicado a la elaboración de citostáticos intravenosos / Failure mode effect analysis applied to preparation of intravenous cytostatics

Objetivo. Identificar los riesgos en la elaboración de citostáticos intravenosos de forma proactiva, priorizarlos y establecer medidas de mejora en la seguridad de los procedimientos utilizados. Material y métodos. Se utilizó la metodología «análisis modal de fallos y efectos». Un equipo multidisciplinar identificó los modos de fallo del proceso a través de tormenta de ideas. Se evaluó el impacto asociado a cada modo de fallo con el número de prioridad de riesgo (NPR), en el que intervienen 3 variables: ocurrencia, gravedad y detectabilidad. Se establecieron medidas de mejora para todos los modos de fallo identificados; se consideraron críticos aquellos con un NPR > 100. Se calculó también el NPR final (teórico) que se obtendría con las medidas propuestas y se rediseñó el proceso. Resultados. Se identificaron un total de 34 modos de fallo. El NPR inicial acumulado fue de 3022 (rango: 3-252), y tras las acciones recomendadas el NPR final fue de 1292 (rango: 3-189). Se obtuvieron puntuaciones de NPR > 100 en 13 modos de fallo; solo el subproceso de dispensación estuvo exento de puntos críticos (NPR > 100). Se consiguió una reducción del NPR final >50% en 9 modos de fallo. Conclusiones. Esta metodología de análisis de riesgo prospectiva nos permite priorizar los puntos débiles del sistema para optimizar el empleo de recursos y conseguir una mejora sustancial en la seguridad de la elaboración de citostáticos mediante la introducción del doble chequeo y el etiquetado de productos intermedios (AU)

Objective. To proactively identify risks in the preparation of intravenous cytostatic drugs, and to prioritise and establish measures to improve safety procedures. Material and methods. Failure Mode Effect Analysis methodology was used. A multidisciplinary team identified potential failure modes of the procedure through a brainstorming session. The impact associated with each failure mode was assessed with the Risk Priority Number (RPN), which involves three variables: occurrence, severity, and detectability. Improvement measures were established for all identified failure modes, with those with RPN > 100 considered critical. The final RPN (theoretical) that would result from the proposed measures was also calculated and the process was redesigned. Results. A total of 34 failure modes were identified. The initial accumulated RPN was 3022 (range: 3-252), and after recommended actions the final RPN was 1292 (range: 3-189). RPN scores > 100 were obtained in 13 failure modes; only the dispensing sub-process was free of critical points (RPN > 100). A final reduction of RPN > 50% was achieved in 9 failure modes. Conclusions. This prospective risk analysis methodology allows the weaknesses of the procedure to be prioritised, optimize use of resources, and a substantial improvement in the safety of the preparation of cytostatic drugs through the introduction of double checking and intermediate product labelling (AU)

[Failure mode effect analysis applied to preparation of intravenous cytostatics]. / Análisis modal de fallos y efectos aplicado a la elaboración de citostáticos intravenosos.

OBJECTIVE: To proactively identify risks in the preparation of intravenous cytostatic drugs, and to prioritise and establish measures to improve safety procedures. MATERIAL AND METHODS: Failure Mode Effect Analysis methodology was used. A multidisciplinary team identified potential failure modes of the procedure through a brainstorming session. The impact associated with each failure mode was assessed with the Risk Priority Number (RPN), which involves three variables: occurrence, severity, and detectability. Improvement measures were established for all identified failure modes, with those with RPN>100 considered critical. The final RPN (theoretical) that would result from the proposed measures was also calculated and the process was redesigned. RESULTS: A total of 34 failure modes were identified. The initial accumulated RPN was 3022 (range: 3-252), and after recommended actions the final RPN was 1292 (range: 3-189). RPN scores >100 were obtained in 13 failure modes; only the dispensing sub-process was free of critical points (RPN>100). A final reduction of RPN>50% was achieved in 9 failure modes. CONCLUSIONS: This prospective risk analysis methodology allows the weaknesses of the procedure to be prioritised, optimize use of resources, and a substantial improvement in the safety of the preparation of cytostatic drugs through the introduction of double checking and intermediate product labelling.

[Off-label use of oncology drugs: national survey results]. / Uso de medicamentos fuera de ficha la técnica en oncohematología: resultado de una encuesta nacional.

PURPOSE: identify by means of a survey the off-label treatments more often used in the oncohaematology area, as well as to know the established procedures and criteria used to authorise those treatments. METHODS: a four-section survey was designed: 1) demographic data and hospital activity, 2) Off-label treatments protocol, 3) Approval criteria and 4) Off-label oncology treatments conducted during the last year. RESULTS: in 42.1% of the hospitals it's needed an authorisation before dispensing in more tan 80% of the treatments. The most influential factor in the approval-dispensation system is the available evidence. The consent of the hospital management with previous Pharmacy department's report was the most common authorisation procedure. 55.3% of the hospitals settled specific patient criteria to help the decision-making altogether with the available safety and efficacy data of the drug for the requested indication. In most centers a lower level of evidence is accepted if there are no therapeutic alternatives as well as in tumors of low prevalence. Most of the centers have not clearly established a criterion of effectiveness to consider a benefit as clinically relevant, nor the cost-effectiveness threshold for approving a FFT. CONCLUSIONS: there is a great variability in the off-label treatments use and also in the criteria used for its approval.

Objetivo: identificar mediante una encuesta los tratamientos fuera de la ficha tecnica (FFT) que mas frecuentemente se utilizan en el area de oncohematologia. Conocer los procedimientos y criterios que se han establecido para autorizar estos tratamientos. Método: se diseno una encuesta con cuatro secciones: 1) datos demograficos y de actividad del hospital, 2) procedimiento de utilizacion de medicamentos FFT, 3) criterios de aprobacion y 4) tratamientos oncologicos FFT tramitados durante el ano anterior. Resultados: en el 42,1% de los centros la proporcion en la que es necesaria autorizacion previa a la dispensacion es mayor del 80%. El factor mas importante que influye en el circuito de autorizacion-dispensacion de estos farmacos es la evidencia disponible. El procedimiento de autorizacion mas habitual es la autorizacion de la direccion del hospital previo informe del servicio de farmacia. En un 55,3% de los hospitales se han establecido criterios especificos del paciente que ayudan a la toma de decisiones, junto con los aspectos de eficacia y seguridad de los farmacos en la indicacion solicitada. En la mayoria de los centros se acepta un menor nivel de evidencia en el caso de que no existan alternativas terapeuticas, asi como en los tumores de baja prevalencia. La mayor parte de los centros no tienen claramente establecido un criterio de eficacia para considerar un beneficio como clinicamente relevante, y tampoco el umbral coste-eficacia para aprobar un FFT. Conclusiones: existe una gran variabilidad en el procedimiento de utilizacion de los FFT y en los criterios que se utilizan para su aprobacion.

Economic evaluation in collaborative hospital drug evaluation reports.

OBJECTIVE: economic evaluation is a fundamental criterion when deciding a drug's place in therapy. The MADRE method (Method for Assistance in making Decisions and Writing Drug Evaluation Reports) is widely used for drug evaluation. This method was developed by the GENESIS group of the Spanish Society of Hospital Pharmacy (SEFH), including economic evaluation. We intend to improve the economic aspects of this method. As for the direction to take, we have to first analyze our previous experiences with the current methodology and propose necessary improvements. METHOD: economic evaluation sections in collaboratively conducted drug evaluation reports (as the scientific society, SEFH) with the MADRE method were reviewed retrospectively. RESULTS: thirty-two reports were reviewed, 87.5% of them included an economic evaluation conducted by authors and 65.6% contained published economic evaluations. In 90.6% of the reports, a Budget impact analysis was conducted. The cost per life year gained or per Quality Adjusted Life Year gained was present in 14 reports. Twenty-three reports received public comments regarding the need to improve the economic aspect. Main difficulties: low quality evidence in the target population, no comparative studies with a relevant comparator, non-final outcomes evaluated, no quality of life data, no fixed drug price available, dosing uncertainty, and different prices for the same drug. CONCLUSIONS: proposed improvements: incorporating different forms of aid for non-drug costs, survival estimation and adapting published economic evaluations; establishing criteria for drug price selection, decision-making in conditions of uncertainty and poor quality evidence, dose calculation and cost-effectiveness thresholds depending on different situations.

Objetivo: la evaluación económica es un criterio fundamental en el posicionamiento de medicamentos. El método MADRE (Método de Ayuda para la toma de Decisiones y la Realización de Evaluaciones de medicamentos) es ampliamente utilizado en la evaluación de medicamentos. Fue desarrollado por el grupo GENESIS de la Sociedad Española de Farmacia Hospitalaria (SEFH), e incluye una evaluación económica. Con objeto de mejorar los aspectos económicos de este método, analizaremos la experiencia previa con esta metodología y propondremos mejoras. Método: revisión retrospectiva de las evaluaciones económicas en los informes de evaluación de medicamentos realizados de forma colaborativa (como SEFH) con el método MADRE. Resultados: se revisaron 32 informes, el 87,5% incluían una evaluación económica realizada por los autores y un 65,6% una publicada. El 90,6% incluían un análisis de impacto presupuestario. 14 informes incluían el coste por año de vida o por año de vida ganado ajustado por calidad. 23 informes recibieron alegaciones relacionadas con la evaluación económica. Las principales dificultades fueron: baja calidad de la evidencia en la población diana, falta de estudios comparativos con el comparador relevante, resultados finales no evaluados, falta de datos de calidad de vida, precio del medicamento no fijado, incertidumbre en la dosis y diferentes precios del medicamento. Conclusiones: mejoras propuestas: incorporar ayudas para inclusión de costes no farmacológicos, estimación de la supervivencia y adaptación de evaluaciones económicas publicadas; establecer criterios para: selección de precios, toma de decisiones en condiciones de incertidumbre o evidencia pobre, cálculo de dosis y umbrales de coste-efectividad en diferentes situaciones.

Uso de medicamentos fuera de ficha la técnica en oncohematología: resultado de una encuesta nacional / Off-label use of oncology drugs: national survey results

Objetivo: identificar mediante una encuesta los tratamientos fuera de la ficha técnica (FFT) que más frecuentemente se utilizan en el área de oncohematología. Conocer los procedimientos y criterios que se han establecido para autorizar estos tratamientos. Método: se diseñó una encuesta con cuatro secciones: 1) datos demográficos y de actividad del hospital, 2) procedimiento de utilización de medicamentos FFT, 3) criterios de aprobación y 4) tratamientos oncológicos FFT tramitados durante el año anterior. Resultados: en el 42,1% de los centros la proporción en la que es necesaria autorización previa a la dispensación es mayor del 80%. El factor más importante que influye en el circuito de autorización-dispensación de estos fármacos es la evidencia disponible. El procedimiento de autorización más habitual es la autorización de la dirección del hospital previo informe del servicio de farmacia. En un 55,3% de los hospitales se han establecido criterios específicos del paciente que ayudan a la toma de decisiones, junto con los aspectos de eficacia y seguridad de los fármacos en la indicación solicitada. En la mayoría de los centros se acepta un menor nivel de evidencia en el caso de que no existan alternativas terapéuticas, así como en los tumores de baja prevalencia. La mayor parte de los centros no tienen claramente establecido un criterio de eficacia para considerar un beneficio como clínicamente relevante, y tampoco el umbral coste-eficacia para aprobar un FFT. Conclusiones: existe una gran variabilidad en el procedimiento de utilización de los FFT y en los criterios que se utilizan para su aprobación (AU)

Purpose: identify by means of a survey the off-label treatments more often used in the oncohaematology area, as well as to know the established procedures and criteria used to authorise those treatments. Methods: a four-section survey was designed: 1) demographic data and hospital activity, 2) Off-label treatments protocol, 3) Approval criteria and 4) Off-label oncology treatments conducted during the last year. Results: in 42.1% of the hospitals it’s needed an authorisation before dispensing in more tan 80% of the treatments. The most influential factor in the approval-dispensation system is the available evidence. The consent of the hospital management with previous Pharmacy department’s report was the most common authorisation procedure. 55.3% of the hospitals settled specific patient criteria to help the decision-making altogether with the available safety and efficacy data of the drug for the requested indication. In most centers a lower level of evidence is accepted if there are no therapeutic alternatives as well as in tumors of low prevalence. Most of the centers have not clearly established a criterion of effectiveness to consider a benefit as clinically relevant, nor the cost-effectiveness threshold for approving a FFT. Conclusions: there is a great variability in the off-label treatments use and also in the criteria used for its approval (AU)

Economic evaluation in collaborative hospital drug evaluation reports / Evaluación económica en los informes de medicamentos realizados de forma colaborativa

Objective: economic evaluation is a fundamental criterion when deciding a drug’s place in therapy. The MADRE method (Method for Assistance in making Decisions and Writing Drug Evaluation Reports) is widely used for drug evaluation. This method was developed by the GENESIS group of the Spanish Society of Hospital Pharmacy (SEFH), including economic evaluation. We intend to improve the economic aspects of this method. As for the direction to take, we have to first analyze our previous experiences with the current methodology and propose necessary improvements. Method: economic evaluation sections in collaboratively conducted drug evaluation reports (as the scientific society, SEFH) with the MADRE method were reviewed retrospectively. Results: thirty-two reports were reviewed, 87.5% of them included an economic evaluation conducted by authors and 65.6% contained published economic evaluations. In 90.6% of the reports, a Budget impact analysis was conducted. The cost per life year gained or per Quality Adjusted Life Year gained was present in 14 reports. Twenty-three reports received public comments regarding the need to improve the economic aspect. Main difficulties: low quality evidence in the target population, no comparative studies with a relevant comparator, non-final outcomes evaluated, no quality of life data, no fixed drug price available, dosing uncertainty, and different prices for the same drug. Conclusions: proposed improvements: incorporating different forms of aid for non-drug costs, survival estimation and adapting published economic evaluations; establishing criteria for drug price selection, decision-making in conditions of uncertainty and poor quality evidence, dose calculation and cost-effectiveness thresholds depending on different situations (AU)

Objetivo: la evaluación económica es un criterio fundamental en el posicionamiento de medicamentos. El método MADRE (Método de Ayuda para la toma de Decisiones y la Realización de Evaluaciones de medicamentos) es ampliamente utilizado en la evaluación de medicamentos. Fue desarrollado por el grupo GENESIS de la Sociedad Española de Farmacia Hospitalaria (SEFH), e incluye una evaluación económica. Con objeto de mejorar los aspectos económicos de este método, analizaremos la experiencia previa con esta metodología y propondremos mejoras. Método: revisión retrospectiva de las evaluaciones económicas en los informes de evaluación de medicamentos realizados de forma colaborativa (como SEFH) con el método MADRE. Resultados: se revisaron 32 informes, el 87,5% incluían una evaluación económica realizada por los autores y un 65,6% una publicada. El 90,6% incluían un análisis de impacto presupuestario. 14 informes incluían el coste por año de vida o por año de vida ganado ajustado por calidad. 23 informes recibieron alegaciones relacionadas con la evaluación económica. Las principales dificultades fueron: baja calidad de la evidencia en la población diana, falta de estudios comparativos con el comparador relevante, resultados finales no evaluados, falta de datos de calidad de vida, precio del medicamento no fijado, incertidumbre en la dosis y diferentes precios del medicamento. Conclusiones: mejoras propuestas: incorporar ayudas para inclusión de costes no farmacológicos, estimación de la supervivencia y adaptación de evaluaciones económicas publicadas; establecer criterios para: selección de precios, toma de decisiones en condiciones de incertidumbre o evidencia pobre, cálculo de dosis y umbrales de coste-efectividad en diferentes situaciones (AU)

Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation reporta / / Trastuzumab emtansina en cáncer de mama her2 positivo metastásico o localmente avanzado; informe de evaluación genesis-sefh

Trastuzumab emtansina (T-DM1) is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC), who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS) and the overall survival (OS). It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 Euros. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at 70,490,850 Euros. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients (AU)

T-DM1 es un conjugado anticuerpo-fármaco dirigido contra el HER2 para el tratamiento del cáncer de mama metastásico (CMM) HER2 +, que ha recibido previamente trastuzumab más un taxano. De acuerdo con los resultados del ensayo EMILIA frente a lapatinib más capecitabina T-DM1 muestra una mejora en la supervivencia libre de progresión (SLP) y la supervivencia global (SG). Tiene un perfil favorable reducir la incidencia de reacciones adversas grado 3-4 tales como el síndrome mano-pie y la diarrea. Sin embargo, aumenta significativamente el riesgo de trombocitopenia grave y debe monitorizarse el riesgo de hemorragia y la función hepática. Con el precio de importación actual T-DM1 tiene un coste por AVAC de más de 120.000 Euros. El precio del fármaco para el Sistema Nacional de Salud en España aún no ha sido establecido. El precio del fármaco sería el factor clave en el análisis de sensibilidad y una reducción del 50% en el precio lo situaría cerca del umbral de coste-efectividad generalmente considerada en nuestro medio como aceptable. De acuerdo con el modelo de impacto presupuestario utilizado, se trataría un máximo de 1.218 pacientes / año y el impacto presupuestario de todo el estado español estaría entorno a 70.490.850 Euros para este volumen de pacientes. En el análisis inicial no se encontró ninguna ventaja para T-DM1 en aquellos pacientes sin afectación visceral. Aunque un re-análisis posterior de los resultados de SLP en el que se especifica la definición de la afectación visceral se muestra un beneficio significativo en este subgrupo. Creemos que este enfoque presenta un alto grado de incertidumbre, y no garantiza el beneficio logrado para este subgrupo de pacientes (AU)

La evaluación axiológica de los proyectos en los comités de ética de la investigación / The axiological assessment of projects into research ethics committees

El objetivo de este trabajo es demostrar que la existencia de los Comités de Ética de la Investigación (CEIs) es congruente con el tiempo histórico que nos ha tocado vivir. La idea de una ciencia neutra se remonta a la creación de la Royal Society. Putnam y otros investigadores propusieron el término de valores epistémicos para los valores propios de la ciencia. A esta transformación axiológica se le ha denominado de varias formas: modo 2 de conocimiento, ciencia postnormal, ciencia postacadémica y también tecnociencia. No hay innovación sin valoración previa, e incluso sin múltiples valoraciones previas. La existencia actual de los Comités de Ética de la Investigación (CEIs) es un hecho congruente con el desarrollo histórico de la epistemología durante el siglo XX. Una de las funciones más importantes de los CEIs, es la evaluación axiológica (valores epistémicos) de los proyectos de investigación

The aim of this paper is to show that the existence of Ethics Research Committees is consistent with the historical time in which we reside. The idea of a neutral science dates back to the creation of the Royal Society. Putnam and other researchers proposed the term "epistemic values" to the values of science. This axiological transformation has been called in several ways: knowledge mode 2, post-normal science, post-academic science and technoscience. There is no innovation without evaluation, even without multiple previous assessments. The actual existence of the Research Ethics Committees (RECs) is a fact consistent with the historical development of epistemology in the twentieth century. One of the most important functions of RECs, is the axiological evaluation (epistemic values) of research projects

Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report.

Trastuzumab emtansina (T-DM1) is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC), who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS) and the overall survival (OS). It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients.

T-DM1 es un conjugado anticuerpo-farmaco dirigido contra el HER2 para el tratamiento del cancer de mama metastasico (CMM) HER2 +, que ha recibido previamente trastuzumab mas un taxano. De acuerdo con los resultados del ensayo EMILIA frente a lapatinib mas capecitabina T-DM1 muestra una mejora en la supervivencia libre de progresion (SLP) y la supervivencia global (SG). Tiene un perfil favorable reducir la incidencia de reacciones adversas grado 3-4 tales como el sindrome mano- pie y la diarrea. Sin embargo, aumenta significativamente el riesgo de trombocitopenia grave y debe monitorizarse el riesgo de hemorragia y la funcion hepatica. Con el precio de importacion actual T-DM1 tiene un coste por AVAC de mas de 120.000 €. El precio del farmaco para el Sistema Nacional de Salud en Espana aun no ha sido establecido. El precio del farmaco seria el factor clave en el analisis de sensibilidad y una reduccion del 50% en el precio lo situaria cerca del umbral de coste-efectividad generalmente considerada en nuestro medio como aceptable. De acuerdo con el modelo de impacto presupuestario utilizado, se trataria un maximo de 1.218 pacientes / ano y el impacto presupuestario de todo el estado espanol estaria entorno a 70.490.850 € para este volumen de pacientes. En el analisis inicial no se encontro ninguna ventaja para T-DM1 en aquellos pacientes sin afectacion visceral. Aunque un re-analisis posterior de los resultados de SLP en el que se especifica la definicion de la afectacion visceral se muestra un beneficio significativo en este subgrupo. Creemos que este enfoque presenta un alto grado de incertidumbre, y no garantiza el beneficio logrado para este subgrupo de pacientes.

Use of monoclonal antibodies for metastatic colorectal cancer in the Andalusian public health system.

BACKGROUND: The place of monoclonal antibodies in metastatic colorectal cancer has not been clearly defined. OBJECTIVE: To determine the treatment pattern of monoclonal antibodies in colorectal cancer patients in the Andalusian Public Healthcare System. METHOD: Data were collected from all patients treated with these drugs from July 2009 to December 2010 from pharmacy programs and medical records. RESULTS: Three hundred patients were included, of whom 227 received the antibody at the forefront. The proportion of patients who received bevacizumab in the first line is greater than that of cetuximab (62.1 vs. 37.5 % respectively) and similar in the second line and subsequent (47.8 vs. 53.8 % and 48.5 vs. 46.2 % respectively). XELOXbevacizumab was the most frequently prescribed scheme (35.3 %) followed by FOLFOX-monoclonal antibody schemes, regardless that this was bevacizumab or cetuximab (22.5 %). The median progression free survival (PFS) was 11.7 months for patients receiving cetuximab, 9.6 months for patients receiving bevacizumab and 8.2 months for those who received no monoclonal antibody in the first line. CONCLUSION: Bevacizumab was the antibody of choice in first line, showing utilization rates similar to cetuximab in second line and subsequent. The median PFS in our study is related to the PFS of the major clinical trials.

Biological treatments for moderate-to-severe psoriasis: indirect comparison.

WHAT IS KNOWN AND OBJECTIVE: Psoriasis is a chronic skin disease for which there is an increasing range of treatment options. Biological agents (ustekinumab, adalimumab, infliximab and etanercept) are indicated for moderate-to-severe plaque-type psoriasis in adults who fail to respond to, have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA Unfortunately, with new drugs, the pivotal trials leading to their licensing are often placebo-controlled trials rather than comparative trials vs. established therapies. Therefore, inference on comparative effectiveness of the newer agents must be derived indirectly, through estimation of effects of the new agents vs. a common comparator. The objective of this study is to compare the relative efficacy of the biological agents through a systematic review of the indirect clinical trial evidence. METHODS: A systematic literature search was performed for clinical trials of biological agents in psoriasis. Pivotal, randomized, double-blind, controlled (placebo) trials using intention-to-treat analysis were selected for detailed analysis. Trials must include PASI 75 as a primary end point. The indirect comparison was performed using the method of Bucher adjusted with the ITC calculator (Indirect Treatment Comparisons of the Canadian Agency for Drugs and Technologies in Health), etanercept being the reference drug. We defined delta value for therapeutic equivalence as a difference in the efficacy of 25% among the different treatment options. RESULTS AND DISCUSSION: Fourteen studies (four for ustekinumab, three for adalimumab, three for infliximab and four for etanercept) were included. The indirect comparison results reveal that ustekinumab, adalimumab and infliximab were statistically superior to etanercept with an absolute risk difference for PASI 75 of 12% (95% CI = 5·9-18%), 11% (95% CI = 5·3-16·7%) and 24% (29·7-18·3%) respectively. However, in all situations, the 95% confidence interval does not achieve clinical relevance as no delta exceeds the previously set value (25%). WHAT IS NEW AND CONCLUSION: Ustekinumab, adalimumab, infliximab and etanercept can be regarded as clinical equivalents for the treatment of psoriasis. Choice between these agents therefore depends on their relative safety profiles, individual contra-indications and cost effectiveness.

Autorización de usos de medicamentos fuera de indicación en un hospital de tercer nivel / Off-label approval of drug use in a tertiary hospital

Fundamento y objetivo. Comisión de Farmacia y Terapéutica (CFT) evalúa peticiones de usos fuera de indicación con un modelo de informe abreviado. El objetivo fue realizar un análisis descriptivo de esta actividad y estudiar la tasa de autorizaciones. Material y métodos. Estudio descriptivo de los informes de la CFT del hospital entre septiembre de 2009 y abril de 2011. Se analizó tipo de fármaco por grupo terapéutico y por tipo de dispensación, indicación y servicio peticionario. Además, se estudió la decisión final adoptada como variable principal y porcentaje de solicitudes aprobadas según características del medicamento evaluado, indicación solicitada, alternativas usadas, evidencia y coste, como resultados secundarios. Resultados. De un total de 51 solicitudes analizadas, un 60,8% fueron medicamentos de uso hospitalario y un 54,9% citostáticos. Destacaron las indicaciones oncohematológicas (43,2%) y autoinmunes (35,3%). Los servicios con más peticiones fueron Hematología (11 peticiones aprobándose el 72,7%), Oncología y Pediatría (10 peticiones aprobándose el 50% para ambas). Se aprobaron el 60,8% de las peticiones. De las no autorizadas, 11 no agotaron las alternativas terapéuticas y 8 no presentaban evidencia suficiente para ser aceptadas. El 47,1% de los medicamentos solicitados tenían un coste/paciente entre 10.000-100.000 euros aprobándose el 58,3% (coste por tratamiento completo si tenía duración definida o coste por año en tratamientos crónicos). Conclusión. Hay una gran actividad de la CFT que crece con los años. La mayoría de las solicitudes son de fármacos de uso hospitalario, sobre todo de citostáticos por Oncohematología. Existe una alta tasa de autorización con una alta variabilidad según servicio y tipo de evidencia. La diferencia, entre aprobados y no aprobados respecto al coste sigue una lógica de coste-efectividad(AU)

Background and objective. The Pharmacy and Therapeutics Committee (PTC) evaluates the requests for off-label uses with an abbreviated report format. The aim of this study is to perform a descriptive analysis of this activity and to study the rate of approvals. Material and Methods. A descriptive study was performed on the PTC reports in a tertiary hospital between September 2009 and April 2011. The type of drug by treatment group and by type of dispensing, indication and requesting department was analysed. The final decision adopted was studied as the primary outcome, and the percentage of requests approved according to the characteristics of the drug evaluated, indication requested, alternatives used, evidence and cost, as secondary outcomes. Results. A total of 51 applications were analysed, of which 60.8% were drugs for hospital use and 54.9% cytostatic. The most requested indications were the onco-haematological (43.2%) and autoimmune (35.3%). Haematology was the department that made most requests (11 requests with 72.7% approved), Oncology and Paediatrics (both with 10 requests, with 50% approved). Almost two-thirds (60.8%) of the requests were approved. Of those that were not approved, 11 had not used up the therapeutic alternatives, and 8 had no evidence. Just under half (47.1%) of the drugs requested had a cost/patient between 10,000-100,000 euros,of which 58.3% were approved (cost per course of treatment if it had a defined period, or cost of treatment per year for chronic treatment). Conclusion. There is an increase in the activity of the PTC that is growing over the years. Most applications focus on drugs for hospital use and cytostatic drugs by Onco-haematology. There is a high rate of approval by the PTC, and high variability in the percentage of approval depending on the department and the evidence of use. The difference between approved and unapproved requests followed a logic of cost-effectiveness(AU)

[Off-label approval of drug use in a tertiary hospital]. / Autorización de usos de medicamentos fuera de indicación en un hospital de tercer nivel.

BACKGROUND AND OBJECTIVE: The Pharmacy and Therapeutics Committee (PTC) evaluates the requests for off-label uses with an abbreviated report format. The aim of this study is to perform a descriptive analysis of this activity and to study the rate of approvals. MATERIAL AND METHODS: A descriptive study was performed on the PTC reports in a tertiary hospital between September 2009 and April 2011. The type of drug by treatment group and by type of dispensing, indication and requesting department was analysed. The final decision adopted was studied as the primary outcome, and the percentage of requests approved according to the characteristics of the drug evaluated, indication requested, alternatives used, evidence and cost, as secondary outcomes. RESULTS: A total of 51 applications were analysed, of which 60.8% were drugs for hospital use and 54.9% cytostatic. The most requested indications were the onco-haematological (43.2%) and autoimmune (35.3%). Haematology was the department that made most requests (11 requests with 72.7% approved), Oncology and Paediatrics (both with 10 requests, with 50% approved). Almost two-thirds (60.8%) of the requests were approved. Of those that were not approved, 11 had not used up the therapeutic alternatives, and 8 had no evidence. Just under half (47.1%) of the drugs requested had a cost/patient between 10,000-100,000 euros,of which 58.3% were approved (cost per course of treatment if it had a defined period, or cost of treatment per year for chronic treatment). CONCLUSION: There is an increase in the activity of the PTC that is growing over the years. Most applications focus on drugs for hospital use and cytostatic drugs by Onco-haematology. There is a high rate of approval by the PTC, and high variability in the percentage of approval depending on the department and the evidence of use. The difference between approved and unapproved requests followed a logic of cost-effectiveness.

Prevalence of drug interactions in hospital healthcare.

AIM OF THE REVIEW: To study the prevalence of drug interactions in hospital healthcare by reviewing literature. METHOD: A review was carried out of studies written in Spanish and English on the prevalence of drug interactions in hospital care published in Pubmed between January 1990 and September 2008. The search strategy combined free text and MeSH terms, using the following keywords: "Drug interaction", "prevalence" and "hospital". For each article, we classified independent variables (pathology, age of population, whether patients were hospitalized or not, geographical location, etc.) and dependent variables (number of interactions per 100 patients studied, prevalence of patients with interactions, most common drug interactions, and others). RESULTS: The search generated 436 articles. Finally, 47 articles were selected for the study, 3 provided results about drug interactions with real clinical consequences, 42 about potential interactions, and 2 described both. The prevalence of patients with interactions was between 15 and 45 % and the number of interactions per 100 patients was between 37 and 106, depending on the group of studies analyzed. There was a considerable increase in these rates in patients with heart diseases and elderly persons. CONCLUSION: There is a large number of studies on the prevalence of drug interactions in hospitals but they report widely varying results. The prevalence is higher in patients with heart diseases and elderly people.

Selection of tools for reconciliation, compliance and appropriateness of treatment in patients with multiple chronic conditions.

BACKGROUND: The healthcare models developed for patients with multiple chronic diseases agree on the need for improving drug therapy in these patients. The issues of patient compliance, appropriateness of prescriptions and the reconciliation process are of vital importance for patients receiving multiple drug treatment. OBJECTIVE: To identify and select the most appropriate tools for measuring treatment compliance and appropriateness in multiple-disease patients, as well as the best reconciliation strategy. METHODS: The study used the Delphi methodology. We identified compliance and appropriateness questionnaires and scales, as well as functional organisation models for reconciliation that had been used in patients with multiple chronic conditions. Based on the strength of the evidence, their usefulness in these patients and ease of use, the panel selected the most appropriate ones. RESULTS: We selected 46 indications for the panel: 5 on compliance, 20 on appropriateness, and 31 on reconciliation. The tool considered most appropriate and with a high degree of agreement was the "Adherence to Refills and Medication Scale" questionnaire. For appropriateness, the Medication Appropriateness Index questionnaire was considered appropriate. The STOPP/START criteria were the most appropriate. The greatest degree of agreement regarding reconciliation was on the information that needed to be collected and the variables considered as discrepancies. CONCLUSIONS: The "Adherence to Refills and Medication Scale" questionnaire for compliance, the STOPP/START criteria, the Medication Appropriateness Index questionnaire for appropriateness and the development of a specific strategy for reconciliation were considered appropriate for the assessment of drug therapy in patients with multiple chronic conditions.

Consensus method to update the GINF formulary request form

Objective: To update the Guideline for the Introduction of New Drugs in the Formulary (GINF form) using the RAND/UCLA appropriateness method, which combines the best available evidence and an expert panel’s judgement. Study Design/Methods: Two procedures were employed to detect where improvements could be made to the former versions of the request form and to transform them into concrete scenarios, found from a telephone survey with GINF form users, and a structured review of the scientific literature. The list of scenarios was later assessed by an expert panel. In a series of successive rounds, the rest of the research team critically assessed the expert panel’s result, applying a score. Results: A total of 52 improvement proposals were registered; 31 of them dealt with the form structure and the remaining 21 referred to the form process. Six formulary request forms were selected from the literature review. The final version included 24 assessed scenarios mainly addressing clinical trials’ validity, qualitative assessment and local implications of the requested drug. Conclusions: A new version of the GINF form has been developed. Much improvement has been made based on the guide users’ opinion, available evidence and similar experiences that have been carried out internationally. The whole process has been subject to the experts’ opinion following a contrasted, consensus methodology: RAND/UCLA appropriateness method (AU)

Objetivo: Diseñar una nueva versión de la Guía para la Introducción de Nuevos Fármacos (GINF), ˜utilizando para ello la metodología RAND/UCLA sobre el uso adecuado, que combina la mejor evidencia disponible con el juicio de un panel de expertos. Diseño del estudio/métodos: ˜ Se emplearon 2 procedimientos para detectar oportunidades de mejora de las versiones anteriores de la guía, que fueron transformadas en escenarios concretos: una encuesta telefónica a usuarios de la GINF, y una revisión estructurada de la literatura científica. Esta lista de escenarios fue evaluada por un panel de expertos mediante rondas sucesivas. El resto del equipo de investigación evaluó críticamente el resultado del panel de expertos. Resultados: Se registraron 52 propuestas de mejora, 31 de ellas se refieren a la estructura de la guía y las 21 restantes se refieren al procedimiento de utilización de la guía. En cuanto a la búsqueda bibliográfica, 6 de las guías de inclusión de nuevos medicamentos fueron seleccionadas. La versión final incluyó 24 de los escenarios propuestos orientados principalmente a la validez del ensayo clínico, la evaluación cualitativa y las consecuencias locales del fármaco solicitado. Conclusiones: La nueva versión de la guía GINF llevada a cabo incluye muchas mejoras extraídas tanto de la opinión de los usuarios de guía como de la mejor evidencia disponible y las experiencias similares que se han llevado a cabo a nivel internacional. Todo el proceso ha sido sometido a la opinión de los expertos tal como indica la metodología de consenso RAND/UCLA (AU)

Consensus method to update the GINF formulary request form.

OBJECTIVE: To update the Guideline for the Introduction of New Drugs in the Formulary (GINF form) using the RAND/UCLA appropriateness method, which combines the best available evidence and an expert panel's judgement. STUDY DESIGN/METHODS: Two procedures were employed to detect where improvements could be made to the former versions of the request form and to transform them into concrete scenarios, found from a telephone survey with GINF form users, and a structured review of the scientific literature. The list of scenarios was later assessed by an expert panel. In a series of successive rounds, the rest of the research team critically assessed the expert panel's result, applying a score. RESULTS: A total of 52 improvement proposals were registered; 31 of them dealt with the form structure and the remaining 21 referred to the form process. Six formulary request forms were selected from the literature review. The final version included 24 assessed scenarios mainly addressing clinical trials' validity, qualitative assessment and local implications of the requested drug. CONCLUSIONS: A new version of the GINF form has been developed. Much improvement has been made based on the guide users' opinion, available evidence and similar experiences that have been carried out internationally. The whole process has been subject to the experts' opinion following a contrasted, consensus methodology: RAND/UCLA appropriateness method.