[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)

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 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)

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.

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.