Implementing reflective multicriteria decision analysis (MCDA) to assess orphan drugs value in the Catalan Health Service (CatSalut)

Catalan healthcare; Decision-making; Multi-criteria decision analysis; Orphan drugsSanitat catalana; Presa de decisions; Anàlisi de decisions multicriteri; Medicaments orfesSanidad catalana; Toma de decisiones; Análisis de decisiones multicriteria; Medicamentos huérfanosBACKGROUND: Orphan medicines show some characteristics that hinder the evaluation of their clinical added value. The often low level of evidence available for orphan drugs, together with a high budget impact and an incremental cost-effectiveness ratio many times higher than drugs used for non-orphan diseases, represent challenges in their appraisal and effective access to clinical use. In order to explore how to handle these hurdles, the Catalan Health Service (CatSalut) began an initiative on a multidimensional assessment of drugs value during the appraisal process. Reflective multicriteria decision analysis (MCDA) using analytical methods was chosen, since it may help to standardise and contextualize all the relevant data related with the drug that could contribute to a decision. The aim of the study was to determine whether the implementation of reflective MCDA methodology could support the decision-making process about orphan medicines in the context of CatSalut. METHODS: The assessment and decision-making process for orphan drugs in the Programa d'Harmonització Farmacoterapeutica (PHF) of CatSalut was prioritized to test the implementation of the reflective MCDA both a qualitative and quantitatively. A staged approach was used with the following main steps: selection and structuration of quantitative criteria (Core Model) and qualitative criteria (Contextual Tool), framework scoring and assessment of three orphan drug case studies. This proof-of-concept would grant a continued refinement of the methodology and, if and when validated, its potential integration to other therapeutic areas of the PHF. RESULTS: The final framework was composed by 10 quantitative criteria (Core Model) and 4 qualitative criteria (Contextual Tool) according to the PHF goals being the most important criteria "disease severity", "unmet need", "comparative effectiveness" and "comparative safety /tolerability". The matrix developed for the case studies served as a guide for the selection of the essential information that the decision-makers were expected to include in a framework. The reflective discussion was considered the most relevant phase of the approach to support inputs for health decision-making processes reflecting both drug value and place in therapy. CONCLUSIONS: The study showed that reflective MCDA methodology could be implemented to complement the decision-making process in CatSalut, as an aid to determine the clinical added value for orphan medicines. MCDA provided transparency and a structured discussion during the committee meetings, thus increasing transparency and predictability of the relevant items supporting the agreements adopted on orphan drugs access

Outcomes of off-label drug uses in hospitals: a multicentric prospective study

Purpose: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. Methods: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. Results: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (3362) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.95,872.54). Conclusions: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed

Docencia sobre las fuentes comerciales de información de medicamentos y opinión de los estudiantes de medicina

Objetivo: Conocer la opinión de los estudiantes sobre un seminario que enseña la interacción de los médicos con las fuentes comerciales de información de los medicamentos. Sujetos y métodos: Se realizó una encuesta a los estudiantes de tercero de medicina sobre un seminario que trataba de las fuentes comerciales de información de medicamentos. El seminario incluyó una videograbación de un representante comercial de una empresa farmacéutica que presentaba un nuevo medicamento a un médico, y ejemplos de información sobre medicamentos incluida en el catálogo comercial Vademécum Internacional y en los anuncios publicitarios. Se preguntó a los estudiantes el grado de interés y de satisfacción con el seminario y qué nivel de utilidad creían que podían tener las actividades desarrolladas en el seminario en su futuro profesional. En la valoración de la opinión se utilizó una escala de Likert (de 0 a 10 puntos). Resultados: De 107 estudiantes que asistieron a los seminarios, 101 (94%) participaron en la encuesta. La edad media de los estudiantes fue de 21 años (desviación estándar-DE-: 2,2 años) y 75 fueron mujeres (74%). La puntuación media del grado de interés fue de 7,4 (DE: 1,5), del grado de satisfacción de 7,5 (DE: 1,6) y del grado de potencial utilidad de 7,6 (1,6). Conclusión: Los estudiantes de medicina están interesados en las actividades docentes sobre las fuentes de información comercial, y consideran que pueden ser potencialmente útiles para su futuro profesional. Es necesario formar y preparar a los estudiantes de medicina para la interacción con las fuentes comerciales de medicamentos

Docencia sobre las fuentes comerciales de información de medicamentos y opinión de los estudiantes de medicina

Objetivo: Conocer la opinión de los estudiantes sobre un seminario que enseña la interacción de los médicos con las fuentes comerciales de información de los medicamentos. Sujetos y métodos: Se realizó una encuesta a los estudiantes de tercero de medicina sobre un seminario que trataba de las fuentes comerciales de información de medicamentos. El seminario incluyó una videograbación de un representante comercial de una empresa farmacéutica que presentaba un nuevo medicamento a un médico, y ejemplos de información sobre medicamentos incluida en el catálogo comercial Vademécum Internacional y en los anuncios publicitarios. Se preguntó a los estudiantes el grado de interés y de satisfacción con el seminario y qué nivel de utilidad creían que podían tener las actividades desarrolladas en el seminario en su futuro profesional. En la valoración de la opinión se utilizó una escala de Likert (de 0 a 10 puntos). Resultados: De 107 estudiantes que asistieron a los seminarios, 101 (94%) participaron en la encuesta. La edad media de los estudiantes fue de 21 años (desviación estándar-DE-: 2,2 años) y 75 fueron mujeres (74%). La puntuación media del grado de interés fue de 7,4 (DE: 1,5), del grado de satisfacción de 7,5 (DE: 1,6) y del grado de potencial utilidad de 7,6 (1,6). Conclusión: Los estudiantes de medicina están interesados en las actividades docentes sobre las fuentes de información comercial, y consideran que pueden ser potencialmente útiles para su futuro profesional. Es necesario formar y preparar a los estudiantes de medicina para la interacción con las fuentes comerciales de medicamentos

Implementing reflective multicriteria decision analysis (MCDA) to assess orphan drugs value in the Catalan Health Service (CatSalut)

Catalan healthcare; Decision-making; Multi-criteria decision analysis; Orphan drugsSanitat catalana; Presa de decisions; Anàlisi de decisions multicriteri; Medicaments orfesSanidad catalana; Toma de decisiones; Análisis de decisiones multicriteria; Medicamentos huérfanosBACKGROUND: Orphan medicines show some characteristics that hinder the evaluation of their clinical added value. The often low level of evidence available for orphan drugs, together with a high budget impact and an incremental cost-effectiveness ratio many times higher than drugs used for non-orphan diseases, represent challenges in their appraisal and effective access to clinical use. In order to explore how to handle these hurdles, the Catalan Health Service (CatSalut) began an initiative on a multidimensional assessment of drugs value during the appraisal process. Reflective multicriteria decision analysis (MCDA) using analytical methods was chosen, since it may help to standardise and contextualize all the relevant data related with the drug that could contribute to a decision. The aim of the study was to determine whether the implementation of reflective MCDA methodology could support the decision-making process about orphan medicines in the context of CatSalut. METHODS: The assessment and decision-making process for orphan drugs in the Programa d'Harmonització Farmacoterapeutica (PHF) of CatSalut was prioritized to test the implementation of the reflective MCDA both a qualitative and quantitatively. A staged approach was used with the following main steps: selection and structuration of quantitative criteria (Core Model) and qualitative criteria (Contextual Tool), framework scoring and assessment of three orphan drug case studies. This proof-of-concept would grant a continued refinement of the methodology and, if and when validated, its potential integration to other therapeutic areas of the PHF. RESULTS: The final framework was composed by 10 quantitative criteria (Core Model) and 4 qualitative criteria (Contextual Tool) according to the PHF goals being the most important criteria "disease severity", "unmet need", "comparative effectiveness" and "comparative safety /tolerability". The matrix developed for the case studies served as a guide for the selection of the essential information that the decision-makers were expected to include in a framework. The reflective discussion was considered the most relevant phase of the approach to support inputs for health decision-making processes reflecting both drug value and place in therapy. CONCLUSIONS: The study showed that reflective MCDA methodology could be implemented to complement the decision-making process in CatSalut, as an aid to determine the clinical added value for orphan medicines. MCDA provided transparency and a structured discussion during the committee meetings, thus increasing transparency and predictability of the relevant items supporting the agreements adopted on orphan drugs access

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.5-7,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.5-7,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice

Hospital doctors' views and concerns about pharmacovigilance

Purpose: The aim of the study was to evaluate the opinions and concerns of hospital doctors about adverse drug reactions (ADRs) and pharmacovigilance. Methods: A qualitative study was undertaken using focus groups in sessions on pharmacovigilance activities conducted in thirteen clinical services of a tertiary university hospital. A total of 296 physicians participated in these sessions by giving their opinions or expressing their doubts about ADR and pharmacovigilance activities which were recorded by different observers and subsequently analysed. Results: Doctors remarked on: a) the importance, concern, frequency and specific types of ADRs that were observed in clinical practice; b) problems of clinical decision making related to the suspected ADRs; c) methods for improving detection and reporting ADRs; d) monitoring of specific ADRs or ADRs caused by specific drugs; e) and measures to prevent and minimize the risk of ADRs. Physicians expressed doubts related to: a) the basic concepts of ADRs; b) the methods of ADR identification and evaluation; c) the objectives and procedures of pharmacovigilance programmes; d) and the impact of pharmacovigilance activities. Conclusions: Hospital doctors believe that ADRs are a matter for concern in their daily clinical practice, and monitoring ADRs as well as measures for preventing the risk of ADRs are needed. Nevertheless, doctors have doubts about what an ADR is, the accuracy of diagnostic methods, the development of pharmacovigilance activities and their impact on clinical practice. Pharmacovigilance should be better explained through a continuous feedback and close relationship with hospital doctors