Guía metodológica para la evaluación de la eficacia y la seguridad de nuevos fármacos: implementación de las recomendaciones de EUnetHTA / Methodological guideline for the efficacy and safety assessment of new pharmaceuticals: implementation of EUnetHTA's recommendations

La colaboración European Network for Health Technology Assessment (EUnetHTA) es la red colaborativa de agencias y organismos públicos de evaluación de tecnologías sanitarias de la Unión Europea. En este marco se han elaborado guías metodológicas y procedimientos comunes que han dado lugar al denominado HTA Core Model®. La Agencia de Evaluación de Tecnologías Sanitarias de Andalucía (AETSA), miembro de la Red Española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del Sistema Nacional de Salud, y de la colaboración EUnetHTA, participa en la recién iniciada Tercera Acción Conjunta (Joint Action 3) de EUnetHTA (2016-2019). Adicionalmente, la AETSA cuenta con una línea de evaluación de medicamentos. Parte del trabajo se integra en la elaboración de informes de posicionamiento terapéutico (IPT) sobre fármacos que han recibido recientemente la autorización de comercialización, que coordina la Agencia Española de Medicamentos y Productos Sanitarios. Como apoyo a este trabajo, la AETSA elabora «Informes de síntesis de evidencia: medicamentos», en los que se realiza una evaluación comparada de la eficacia y la seguridad de los fármacos de los que va a elaborarse un IPT. La AETSA ha diseñado un proceso para la elaboración de dichos informes, basado en el HTA Core Model® y en las guías metodológicas de EUnetHTA. En este trabajo se describe la metodología empleada en la elaboración de la guía realizada por la AETSA para la elaboración de estos informes y se presentan los distintos apartados en los que esta se estructura (AU)

The European network for Health Technology Assessment (EUnetHTA) is the network of public health technology assessment (HTA) agencies and entities from across the EU. In this context, the HTA Core Model®, has been developed. The Andalusian Agency for Health Technology Assessment (AETSA) is a member of the Spanish HTA Network and EUnetHTA collaboration In addition, AETSA participates in the new EUnetHTA Joint Action 3 (JA, 2016–2019). Furthermore, AETSA works on pharmaceutical assessments. Part of this work involves drafting therapeutic positioning reports (TPRs) on drugs that have recently been granted marketing authorisation, which is overseen by the Spanish Agency of Medicines and Medical Devices (AEMPS). AETSA contributes by drafting ‘Evidence synthesis reports: pharmaceuticals’ in which a rapid comparative efficacy and safety assessment is performed for drugs for which a TPR will be created. To create this type of report, AETSA follows its own methodological guideline based on EUnetHTA guidelines and the HTA Core Model®. In this paper, the methodology that AETSA has developed to create the guideline for ‘Evidence synthesis reports: pharmaceuticals’ is described. The structure of the report itself is also presented (AU)

[Methodological guideline for the efficacy and safety assessment of new pharmaceuticals: implementation of EUnetHTA's recommendations]. / Guía metodológica para la evaluación de la eficacia y la seguridad de nuevos fármacos: implementación de las recomendaciones de EUnetHTA.

The European network for Health Technology Assessment (EUnetHTA) is the network of public health technology assessment (HTA) agencies and entities from across the EU. In this context, the HTA Core Model®, has been developed. The Andalusian Agency for Health Technology Assessment (AETSA) is a member of the Spanish HTA Network and EUnetHTA collaboration In addition, AETSA participates in the new EUnetHTA Joint Action 3 (JA, 2016-2019). Furthermore, AETSA works on pharmaceutical assessments. Part of this work involves drafting therapeutic positioning reports (TPRs) on drugs that have recently been granted marketing authorisation, which is overseen by the Spanish Agency of Medicines and Medical Devices (AEMPS). AETSA contributes by drafting "Evidence synthesis reports: pharmaceuticals" in which a rapid comparative efficacy and safety assessment is performed for drugs for which a TPR will be created. To create this type of report, AETSA follows its own methodological guideline based on EUnetHTA guidelines and the HTA Core Model®. In this paper, the methodology that AETSA has developed to create the guideline for "Evidence synthesis reports: pharmaceuticals" is described. The structure of the report itself is also presented.

Intervenciones para la mejora de la adherencia al tratamiento en pacientes pluripatológicos: resumen de revisiones sistemáticas / Interventions for improving adherence to treatment in patients with multiple pathologies: overview of systematic reviews

Objetivo: Evaluar la evidencia disponible respecto a la eficacia de intervenciones destinadas a mejorar la adherencia al tratamiento que sean aplicables a pacientes pluripatológicos (PP). Diseño: Revisión de revisiones sistemáticas. Fuentes de datos: Se consultaron (septiembre de 2013): Pubmed, EMBASE, the Cochrane Library, CRD y WoS para detectar intervenciones para la mejora de la adherencia en PP, o en su defecto, pacientes con patologías definitorias de pluripatología o polimedicados. Selección de estudios: Se incluyeron revisiones sistemáticas de ensayos clínicos con PP o de características similares. Estas debían comparar la eficacia de cualquier intervención destinada a mejorar el cumplimiento del tratamiento autoadministrado prescrito con la práctica habitual u otra intervención. Extracción de datos: Se extrajo información sobre la población en estudio, la intervención ensayada y la eficacia de la misma en términos de mejora de la adherencia. Resultados: Se recuperaron 566 artículos de los que se seleccionaron 9 revisiones sistemáticas. Ninguna se centraba específicamente en PP. Sí consideraban pacientes con múltiples patologías crónicas, patologías definitorias de pluripatología o polimedicados. La eficacia global de las intervenciones fue modesta, no observándose diferencias relevantes entre las intervenciones de carácter conductual, educativo o combinado. Algunos componentes de estas intervenciones como son el asesoramiento al paciente o las estrategias de simplificación posológica parecen ser herramientas eficaces en la mejora de la adherencia en este grupo poblacional. Conclusiones: Existe una gran heterogeneidad de intervenciones orientadas a la mejora de la adherencia de eficacia modesta, no habiendo sido diseñadas para una población de PP (AU)

Objective: To assess the available scientific evidence regarding the efficacy of interventions aimed to enhance medication adherence in patients with multiple chronic conditions (PMCC). Design: Overview of systematic reviews. Data sources: The following databases were consulted (September 2013): Pubmed, EMBASE, the Cochrane Library, CRD and WoS to identify interventions aimed to enhance medication adherence in PMCC, or otherwise, patients with chronic diseases common in the PMCC, or polypharmacy. Study selection: Systematic reviews of clinical trials focused on PMCC or similar were included. They should compare the efficacy of any intervention aimed to improve compliance to prescribed and self-administered medications with clinical practice or other interventions. Data extraction: Information about the study population, nature of intervention and efficacy in terms of improved adherence was extracted. Results: 566 articles were retrieved of which 9 systematic reviews were included. None was specifically focused on PMCC but considered patients with chronic diseases common in the PMCC, patients with more than one chronic disease and polypharmacy. The overall effectiveness of interventions was modest without relevant differences between behavioural, educational and combined interventions. Some components of these interventions including patient counselling and regimen simplification appear to be effective tools in improving adherence in this population group. Conclusion: There is a large heterogeneity of interventions aimed to improve adherence with modest efficacy, none in PMCC (AU)

[Interventions for improving adherence to treatment in patients with multiple pathologies: overview of systematic reviews]. / Intervenciones para la mejora de la adherencia al tratamiento en pacientes pluripatológicos: resumen de revisiones sistemáticas.

OBJECTIVE: To assess the available scientific evidence regarding the efficacy of interventions aimed to enhance medication adherence in patients with multiple chronic conditions (PMCC). DESIGN: Overview of systematic reviews. DATA SOURCES: The following databases were consulted (September 2013): Pubmed, EMBASE, the Cochrane Library, CRD and WoS to identify interventions aimed to enhance medication adherence in PMCC, or otherwise, patients with chronic diseases common in the PMCC, or polypharmacy. STUDY SELECTION: Systematic reviews of clinical trials focused on PMCC or similar were included. They should compare the efficacy of any intervention aimed to improve compliance to prescribed and self-administered medications with clinical practice or other interventions. DATA EXTRACTION: Information about the study population, nature of intervention and efficacy in terms of improved adherence was extracted. RESULTS: 566 articles were retrieved of which 9 systematic reviews were included. None was specifically focused on PMCC but considered patients with chronic diseases common in the PMCC, patients with more than one chronic disease and polypharmacy. The overall effectiveness of interventions was modest without relevant differences between behavioural, educational and combined interventions. Some components of these interventions including patient counselling and regimen simplification appear to be effective tools in improving adherence in this population group. CONCLUSION: There is a large heterogeneity of interventions aimed to improve adherence with modest efficacy, none in PMCC.

Metodología de conciliación del tratamiento farmacológico en pacientes pluripatológicos / Pharmacological treatment conciliation methodology in patients with multiple conditions

OBJETIVO: Realizar una revisión bibliográfica para identificar las diferentes metodologías empleadas en el proceso de conciliación de los tratamientos farmacológicos que sean aplicables a pacientes pluripatológicos. DISEÑO: Revisión sistemática. Fuentes de datos: Se realizó una revisión bibliográfica (febrero de 2012) en las bases de datos Pubmed, EMBASE, CINAHL, PsycINFO e Índice Médico Español de métodos de conciliación del tratamiento en pacientes pluripatológicos, o en su defecto, ancianos o polimedicados. Selección de estudios: Se recuperaron 273 artículos, de los que se seleccionaron 25. Extracción de datos: Se extrajo información relativa a la metodología empleada: nivel asistencial en el que se realiza, fuentes de información, uso de formulario, tiempo establecido, profesional responsable, información recogida y variables registradas como errores de conciliación. RESULTADOS: La mayoría de estudios fueron al ingreso y al alta hospitalarios Como principales fuentes de información destacan la entrevista y la historia clínica. En la mayoría de trabajos no se especifica un tiempo preestablecido, ni se usa formulario, y el principal responsable es el farmacéutico clínico. Además de la medicación domiciliaria, los hábitos de automedicación y la fitoterapia también son registrados. Se recogen como errores de conciliación desde omisiones de fármacos hasta interacciones medicamentosas. CONCLUSIONES: Existe gran heterogeneidad en la metodología empleada para la actividad de la conciliación. No existe ningún trabajo realizado específicamente en el paciente pluripatológico, que por su complejidad y susceptibilidad a errores de conciliación requiere una metodología estandarizada

OBJECTIVE: To carry out a ibliographic review in order to identify the different methodologies used along the reconciliation process of drug therapy applicable to polypathological patients. DESIGN: We performed a literature review. Data sources: The bibliographic review (February 2012) included the following databases: Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME). The different methodologies, identified on those databases, to measure the conciliation process in polypathological patients, or otherwise elderly patients or polypharmacy, were studied. Study selection Two hundred and seventy three articles were retrieved, of which 25 were selected. Data extraction Specifically: the level of care, the sources of information, the use of registration forms, the established time, the medical professional in charge and the registered variables such as errors of reconciliation. RESULTS: Most of studies selected when the patient was admitted into the hospital and after the hospital discharge of the patient. The main sources of information to be highlighted are: the interview and the medical history of the patient. An established time is not explicitly stated on most of them, nor the registration form is used. The main professional in charge is the clinical pharmacologist. Apart from the home medication, the habits of self-medication and phytotherapy are also identified. The common errors of reconciliation vary from the omission of drugs to different forms of interaction with other medicinal products (drugs interactions). CONCLUSIONS: There is a large heterogeneity of methodologies used for reconciliation. There is not any work done on the specific figure of the polypathological patient, which precisely requires a standardized methodology due to its complexity and its susceptibility to errors of reconciliation

[Pharmacological treatment conciliation methodology in patients with multiple conditions]. / Metodología de conciliación del tratamiento farmacológico en pacientes pluripatológicos.

OBJECTIVE: To carry out a bibliographic review in order to identify the different methodologies used along the reconciliation process of drug therapy applicable to polypathological patients. DESIGN: We performed a literature review. Data sources The bibliographic review (February 2012) included the following databases: Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME). The different methodologies, identified on those databases, to measure the conciliation process in polypathological patients, or otherwise elderly patients or polypharmacy, were studied. Study selection Two hundred and seventy three articles were retrieved, of which 25 were selected. Data extraction Specifically: the level of care, the sources of information, the use of registration forms, the established time, the medical professional in charge and the registered variables such as errors of reconciliation. RESULTS: Most of studies selected when the patient was admitted into the hospital and after the hospital discharge of the patient. The main sources of information to be highlighted are: the interview and the medical history of the patient. An established time is not explicitly stated on most of them, nor the registration form is used. The main professional in charge is the clinical pharmacologist. Apart from the home medication, the habits of self-medication and phytotherapy are also identified. The common errors of reconciliation vary from the omission of drugs to different forms of interaction with other medicinal products (drugs interactions). CONCLUSIONS: There is a large heterogeneity of methodologies used for reconciliation. There is not any work done on the specific figure of the polypathological patient, which precisely requires a standardized methodology due to its complexity and its susceptibility to errors of reconciliation.

Errores de conciliación al ingreso hospitalario en pacientes pluripatológicos mediante metodología estandarizada / Medication reconciliation on hospital admission in patients with multiple chronic diseases using a standardised methodology

Objetivos: Conocer la incidencia de los errores de conciliación en el ingreso hospitalario en pacientes pluripatológicos a través de una metodología estandarizada. Material y método: Estudio observacional prospectivo en pacientes pluripatológicos ingresados en un hospital de tercer nivel. Se realizó conciliación al ingreso hospitalario siguiendo la metodología considerada como más adecuada para estos pacientes por un panel de expertos, según el método Delphi. La fuente de información principal utilizada fue la historia clínica digital, tanto la hospitalaria como la de atención primaria, recurriendo a la entrevista clínica en caso necesario. Se registraron tanto las discrepancias justificadas por el clínico como los errores de conciliación. Se analizó el tipo de error, los grupos farmacológicos implicados y se valoró la gravedad de cada uno de ellos. Resultados: Se incluyeron 114 pacientes, encontrándose errores de conciliación en el 75,4% de ellos. Los pacientes tenían 1.397 fármacos prescritos, de los cuales 234 presentaron discrepancias que requirieron aclaración con el clínico responsable. De estas 234 discrepancias, el clínico modificó la prescripción en 184 de ellas, consideradas errores de conciliación. Los tipos de error fueron: omisión de medicamentos (139), comisión (9), dosis, pauta o vía diferentes (24) y por prescripción incompleta (12). Entre los subgrupos farmacoterapéuticos más afectados por los errores se encontraron los antianémicos, vitaminas, y psicoanalépticos. Conclusiones: El porcentaje de pacientes pluripatológicos con errores de conciliación es elevado. El desarrollo de una metodología dirigida especialmente a los pacientes pluripatológicos consigue detectar y disminuir en un alto porcentaje los errores de medicación relacionados con los cambios de niveles asistenciales (AU)

Objectives: To determine the incidence of medication errors when admitting patients with multiple chronic conditions to hospital, using a standard method. Material and method: A prospective, observational study was conducted on patients with multiple chronic conditions admitted to a tertiary hospital. The medication reconciliation was performed using the standard method considered the most suitable for these patients by an expert panel, following the Delphi methodology. The main information source used for this was the computerised clinical notes, both in primary care and in the hospital, recurring to a clinical interview if necessary. Discrepancies justified by the clinician, as well as reconciliation errors were recorded. The type of error and the pharmacological group involved were analysed and the seriousness of each one of them was assessed. Results: A total of 114 patients were included, with reconciliation errors being found in 75.4% of cases. The patients had 1397 prescribed drugs, of which 234 had discrepancies that required clarification by the clinician responsible. The clinician modified the prescription in 184 of these discrepancies, which were considered reconciliation errors. The types of error were: medication omission (139), commission (9), dose, prescription or different routes (24) and by incomplete prescription (12). Anti-anaemic drugs, vitamins, and psychoanaleptics were among the pharmacotherapeutic groups most affected by the errors. Conclusions: The percentage of patients with multiple chronic conditions with errors is elevated. The development of methods particularly directed at patients with multiple chronic conditions manages to detect and decrease a high percentage of medication errors associated with changes of care levels (AU)

[Medication reconciliation on hospital admission in patients with multiple chronic diseases using a standardised methodology]. / Errores de conciliación al ingreso hospitalario en pacientes pluripatológicos mediante metodología estandarizada.

OBJECTIVES: To determine the incidence of medication errors when admitting patients with multiple chronic conditions to hospital, using a standard method. MATERIAL AND METHOD: A prospective, observational study was conducted on patients with multiple chronic conditions admitted to a tertiary hospital. The medication reconciliation was performed using the standard method considered the most suitable for these patients by an expert panel, following the Delphi methodology. The main information source used for this was the computerised clinical notes, both in primary care and in the hospital, recurring to a clinical interview if necessary. Discrepancies justified by the clinician, as well as reconciliation errors were recorded. The type of error and the pharmacological group involved were analysed and the seriousness of each one of them was assessed. RESULTS: A total of 114 patients were included, with reconciliation errors being found in 75.4% of cases. The patients had 1397 prescribed drugs, of which 234 had discrepancies that required clarification by the clinician responsible. The clinician modified the prescription in 184 of these discrepancies, which were considered reconciliation errors. The types of error were: medication omission (139), commission (9), dose, prescription or different routes (24) and by incomplete prescription (12). Anti-anaemic drugs, vitamins, and psychoanaleptics were among the pharmacotherapeutic groups most affected by the errors. CONCLUSIONS: The percentage of patients with multiple chronic conditions with errors is elevated. The development of methods particularly directed at patients with multiple chronic conditions manages to detect and decrease a high percentage of medication errors associated with changes of care levels.

Adecuación del tratamiento farmacológico en pacientes pluripatológicos / Suitability of pharmacological treatment in patients with multiple chronic conditions

Objetivo: Identificar herramientas de medida de la adecuación del tratamiento farmacológico de utilidad en el paciente pluripatológico (PP). Diseño: Revisión sistemática. Fuentes de datos: Se consultaron las siguientes bases de datos (diciembre de 2009): Pubmed, EMBASE, CINAHL, Psyc INFO e Índice Médico Español para detectar herramientas de medida de la adecuación del tratamiento en pacientes pluripatológicos o, en su defecto, ancianos o polimedicados. Selección de estudios: Se incluyeron estudios tanto con metodología cualitativa como cuantitativa, tanto trabajos teóricos como de campo, ya fuesen originales o revisiones, y se incluyeron trabajos de todos los ámbitos del sistema sanitario. Se recuperaron 108 artículos, de los que se seleccionaron 39. La consulta de sus referencias bibliográficas permitió incorporar 20 trabajos más, en total 59 artículos. Extracción de datos: De entre todas las herramientas detectadas, fueron seleccionadas aquellas con posible utilidad para el paciente pluripatológico. Se clasificaron los métodos en implícitos y explícitos y se tabularon las características de los trabajos de campo. Resultados: Se identificaron 2 métodos implícitos (MAI y Hamdy) y 6 métodos explícitos (criterios Beers, IPET, STOPP/START, ACOVE, CRIME y NORGEP). Ninguno era específico para pluripatológicos. El cuestionario MAI, los criterios Beers y sus modificaciones son los más usados en la literatura médica. Las ventajas de los criterios explícitos hacen que muchos de ellos se hayan desarrollado recientemente. Conclusiones: Existen diversas herramientas para la medida de la adecuación y, sin embargo, ninguna de ellas ha sido diseñada para una población de PP, que por sus características diferenciales requiere un abordaje específico(AU)

Objective: To identify tools for measuring the appropriateness of drug therapy useful in patients with multiple chronic conditions. Design: We performed a literature review. Data sources: The following database were consulted (December 2009): Pubmed, EMBASE, CINAHL, Psyc INFO and Spanish Medical Index (IME) to detect tools for measuring the appropriateness of treatment in patients with multiple chronic conditions, or otherwise elderly or polypharmacy. Study selection: Studies were identified both qualitative and quantitative methodology, both theoretical and field work, both original and revised work and included work from all areas of the health system. 108 articles were retrieved, of which we selected 59. The consultation of their references include 20 jobs allowed, resulting in a total of 59 articles. Data extraction: Of all the tools identified, the researchers performed a selection of those with possible utility for classified PP. The articles were classified into implicit and explicit methods and the characteristics of the field works were tabulated. Results: We identified two implicit methods (MAI and Hamdy) and 6 explicit methods (Beers criteria, IPET, STOPP/START, ACOVE, CRIME and NORGEP). None was specific to patients with multiple chronic conditions. The questionnaire MAI, the Beers criteria and its modifications are most often used in literature. The advantages of explicit criteria means that many of them have been developed recently. Conclusion: There are several tools to measure the appropriateness and none of them has been designed for a population of patients with multiple chronic conditions yet, which by its nature requires a specific approach spreads(AU)

[Suitability of pharmacological treatment in patients with multiple chronic conditions]. / Adecuación del tratamiento farmacológico en pacientes pluripatológicos.

OBJECTIVE: To identify tools for measuring the appropriateness of drug therapy useful in patients with multiple chronic conditions. DESIGN: We performed a literature review. DATA SOURCES: The following database were consulted (December 2009): Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME) to detect tools for measuring the appropriateness of treatment in patients with multiple chronic conditions, or otherwise elderly or polypharmacy. STUDY SELECTION: Studies were identified both qualitative and quantitative methodology, both theoretical and field work, both original and revised work and included work from all areas of the health system. 108 articles were retrieved, of which we selected 59. The consultation of their references include 20 jobs allowed, resulting in a total of 59 articles. DATA EXTRACTION: Of all the tools identified, the researchers performed a selection of those with possible utility for classified PP. The articles were classified into implicit and explicit methods and the characteristics of the field works were tabulated. RESULTS: We identified two implicit methods (MAI and Hamdy) and 6 explicit methods (Beers criteria, IPET, STOPP/START, ACOVE, CRIME and NORGEP). None was specific to patients with multiple chronic conditions. The questionnaire MAI, the Beers criteria and its modifications are most often used in literature. The advantages of explicit criteria means that many of them have been developed recently. CONCLUSION: There are several tools to measure the appropriateness and none of them has been designed for a population of patients with multiple chronic conditions yet, which by its nature requires a specific approach spreads.

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.