Assessment of off-label prescribing: profile, evidence and evolution.

OBJECTIVES: The objectives of the study were to describe the extent and profile of off-label prescriptions, to evaluate the level of evidence supporting these indications, to assess the research activity in these conditions, and to determine to what extent these were authorized as new indications five years after the application. METHODS: A cross-sectional study including all applications conducted in the Hospital Universitario Reina Sofía in Córdoba during 2010. ANALYSIS:  level of evidence according to the criteria by SIGN-NICE (Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence) and CEBM (Centre for Evidence-based Medicine), registered clinical trials (source: ClinicalTrials.gov), and review of product specifications and monthly newsletters from the Spanish Agency of Medicines and Medical Devices. RESULTS: There were 190 applications for off-label prescription for 82 different indications. The most requested medications were: tacrolimus, mycophenolate, colistimethate and everolimus; the immunosuppressant group had the highest number of uses for non-approved indications. Out of the applications, 52.4% were based on some clinical trial, while the rest had a low level of evidence (observational studies and case reports). We have found on-going clinical trials for 67% of the indications, but new indications in their product specifications have only been authorized for nine drugs (bevacizumab, deferasirox, everolimus, lenalidomide, methotreate, sildenafil, sorafenib, raltegravir and tenofovir). CONCLUSIONS: We have detected a major volume of off-label prescription without good supporting evidence, which identifies these indications and medications as interesting research lines, but that require follow-up in terms of effectiveness and costs.

Objetivo: Los objetivos del estudio fueron describir la magnitud y el perfil de las prescripciones fuera de ficha técnica (off-label), evaluar el nivel de evidencia en el que se sustentan estas indicaciones, valorar la actividad investigadora en estas enfermedades y determinar en qué grado se autorizan como nuevas indicaciones transcurridos cinco años desde la solicitud.Métodos: Estudio transversal que incluyó todas las solicitudes realizadas en el Hospital Universitario Reina Sofía de Córdoba durante 2010. Análisis: nivel de evidencia según criterios de SIGN-NICE (Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence) y del CEBM (Centre for Evidence-based Medicine), ensayos clínicos registrados (fuente: ClinicalTrials.gov) y la revisión de fichas técnicas e informes mensuales de la Agencia Española del Medicamento.Resultados: Hubo 190 solicitudes off-label para 82 indicaciones distintas. Los medicamentos más solicitados fueron tacrolimus, micofenolato, colistimetato y everolimus, constituyéndose el grupo de inmunosupresores como el de mayor número de usos en indicaciones no aprobadas. El 52,4% de las solicitudes estaban basadas en algún ensayo clínico, mientras que el resto tuvo un bajo nivel de evidencia (estudios observacionales y casos). Hemos encontrado ensayos clínicos en activo para el 67% de las indicaciones, pero solo nueve fármacos han visto autorizadas nuevas indicaciones en su ficha técnica (bevacizumab, deferasirox, everolimus, lenalidomida, metotrexato, sildenafilo, sorafenib, raltegravir y tenofovir).Conclusiones: Se ha detectado un importante volumen de usos offlabel en ausencia de buena evidencia, lo que identifica a estas indicaciones y medicamentos como líneas de investigación interesantes pero con necesidad de seguimiento de efectividad y costes.

Economic evaluation of botulinum toxin versus thoracic sympathectomy for palmar hyperhidrosis: data from a real-world scenario.

INTRODUCTION: Local botulinum toxin injections and endoscopic thoracic sympathectomy (ETS) have shown clinical effectiveness for the treatment of palmar hyperhidrosis in several studies. Although both strategies cause considerable costs for health-care systems, at the moment there are no studies examining directly their cost-effectiveness performance. The aim of the study was to assess the incremental cost-effectiveness of botulinum toxin when compared with ETS for palmar hyperhidrosis. MATERIALS AND METHODS: Costs, effectiveness, and incremental cost-effectiveness ratio (ICER) were calculated. Costs were assessed from a Spanish National Health System perspective in a historical cohort of patients with palmar hyperhidrosis attending a tertiary referral hospital. Effectiveness was evaluated by using the Hyperhidrosis Disease Severity Scale (HDSS). A responder was defined as a patient who reported at least a two-grade improvement on the HDSS scale with respect to the baseline value. The horizon of time was 1 year. RESULTS: Effectiveness was greater for ETS (n = 128) when compared with botulinum toxin (n = 100) for the treatment of palmar hyperhidrosis (92% vs. 68%; odds ratio (OR) = 6.22 [2.80, 13.80]; absolute risk ratio (ARR) = -0.24 [-0.45, -0.14]; number-needed-to-treat (NNT) = -4 [-2, -11]). Botulinum toxin had an ICER of 125 € when compared with ETS during the first year of treatment. CONCLUSIONS: In this retrospective real-world observational sample of patients with palmar hyperhidrosis, treatment with ETS appears to be more effective and less costly when compared with botulinum toxin during the first year of treatment. Analyses such as this give decision makers the tools to choose a better treatment option which is both highly effective and yet has a low cost.

Análisis y minimización del riesgo de rotura de stock aplicado a la gestión en farmacia hospitalaria / Stockout risk analysis and minimization applied to hospital pharmacy management

Objetivo Determinar el valor que debería tomar el stock de seguridad de los fármacos dispensados en un hospital de tercer nivel en función del nivel de riesgo y del número de días que se desee resistir sin rotura de stock. Método Se ha analizado estadísticamente la demanda registrada durante 120 días consecutivos de infliximab, un fármaco que, por su alto coste y la inmediatez de abastecimiento esperada en la clínica, tiene un adecuado perfil para el estudio. A partir del histórico de datos de adquisición y dispensación existentes en nuestro servicio, se generó una tabla para relacionar el nivel de riesgo asumido con el número de unidades en stock y el número de días que debe durar el stock de seguridad. Adicionalmente, se calcula en el artículo el valor que debería tomar dicho stock conforme a diferentes reglas heurísticas utilizadas por los Servicios de Farmacia. Resultados En el periodo analizado, la demanda diaria fue de 11,4±14,8 unidades de infliximab. Utilizando la metodología propuesta se debería fijar un stock de seguridad de 79 unidades. Este valor es comparado con las 47 y 119 unidades que ofrecen otras reglas utilizadas en el ámbito hospitalario. Conclusiones El método propuesto permite conocer el nivel de riesgo que se asume en la elección del stock de seguridad. Por tanto, permite diseñar una política de stocks de seguridad coherente con el nivel de riesgo adoptado. Bajo ciertas asunciones sería posible reducir la cota del stock de seguridad proporcionada por el método. Finalmente, es destacable la notable diferencia que puede llegar a existir entre los valores de stock de seguridad sugeridos por distintas reglas, tal y como se demuestra en el artículo (AU)

Objective To determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout. Methods We statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments. Results In the period being studied, the daily order was 11.4±14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units. Conclusions The method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article (AU)

Stockout risk analysis and minimization applied to hospital pharmacy management.

OBJECTIVE: To determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout. METHODS: We statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments. RESULTS: In the period being studied, the daily order was 11.4±14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units. CONCLUSIONS: The method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article.