[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Evaluación positiva de medicamentos: noviembre y diciembre de 2022 y enero de 2023 / Positive assessment of drugs: from November and December of 2022 and January of 2023

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos de noviembre y diciembre de 2022 y enero de 2023, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento. (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public from November 2022 to January of 2023, and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product. (AU)

Artificial intelligence-enhanced drug design and development: Toward a computational precision medicine.

Artificial Intelligence (AI) relies upon a convergence of technologies with further synergies with life science technologies to capture the value of massive multi-modal data in the form of predictive models supporting decision-making. AI and machine learning (ML) enhance drug design and development by improving our understanding of disease heterogeneity, identifying dysregulated molecular pathways and therapeutic targets, designing and optimizing drug candidates, as well as evaluating in silico clinical efficacy. By providing an unprecedented level of knowledge on both patient specificities and drug candidate properties, AI is fostering the emergence of a computational precision medicine allowing the design of therapies or preventive measures tailored to the singularities of individual patients in terms of their physiology, disease features, and exposure to environmental risks.

Evaluar medicamentos también es una actividad clínica / Drug evaluation is also a clinical activity

La especialidad de Farmacia Hospitalaria incorporó con el cuarto año de su programa formativo una parte importante de rotación por unidades clínicas de hospitalización en las que el farmacéutico en formación, acompañado de farmacéuticos especialistas, tiene la oportunidad de trabajar conjuntamente con otros profesionales en la atención directa al paciente. Además de contribuir a esta atención con sus conocimientos de farmacoterapia y farmacocinética, el farmacéutico de hospital puede y debe aportar al equipo su liderazgo en evaluación, selección y posicionamiento de medicamentos. Ningún profesional conoce como él los aspectos relativos a la eficacia o efectividad, seguridad y eficiencia de los tratamientos, y estos conocimientos constituyen una actividad clínica más de las que debe desempeñar en los equipos multidisciplinares, ayudando a la toma de decisiones sobre medicamentos en cada paciente. Es necesario que tanto desde los organismos públicos como desde nuestra propia profesión se ponga en valor este papel y que se potencie de forma adecuada

The addition of a fourth year to the hospital pharmacy residency program has allowed trainees to rotate through various inpatient clinical units where they can, under the supervision of a specialist pharmacist, work shoulder to shoulder with other healthcare providers to ensure that patients receive the care they need. In addition to sharing their pharmacotherapeutic and pharmacokinetic knowledge (among others) with their colleagues, hospital pharmacists can and should contribute with their expertise in the areas of drug evaluation, selection and positioning. As no other healthcare professional masters like a pharmacist the intricacies of treatment efficacy or effectiveness, or of therapeutic safety, conveying this knowledge is yet another of the many clinical activities a hospital pharmacist must perform as a member of a multidisciplinary team, while assisting fellow-team members in deciding what medications are best suited to each patient. Both the public authorities and the pharmaceutical profession as a whole should make sure the pharmacist's role is rightfully valued and given the recognition it deserves

Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19.

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.

The traditional use of southern African medicinal plants in the treatment of viral respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral respiratory infections are amongst the most common infections globally, with most of the world's population contracting at least one infection annually. Numerous plant species are used in traditional southern African healing systems to treat these diseases and to alleviate the symptoms. Despite this, the therapeutic potential of these plants against viral respiratory diseases remains poorly explored. AIM OF THE STUDY: The aim of this study was to document the southern African plant species used in traditional medicine to treat viral respiratory infections. We also examined the extent of scientific evaluations of southern African plant species against the respiratory-infective viruses, with the aim of stimulating interest in this area and focusing on future studies. MATERIALS AND METHODS: We undertook an extensive review of ethnobotanical books, reviews and primary scientific studies to identify southern African plants which are used in traditional southern African medicine to treat viral respiratory diseases. This information was used to identify gaps in the current research that require further study. RESULTS: Two hundred and fifty-seven southern African plant species were identified as traditional therapies for viral respiratory diseases. Surprisingly, only one of those species (as well as twenty-one other species not recorded for these purposes) has been evaluated for the ability to block respiratory virus production. Furthermore, most of these studies screened against a single viral strain and none of those studies examined the mechanism of action of the plant preparations. CONCLUSIONS: Despite well documented records of the use of southern African plants to treat respiratory viral diseases, the field is poorly explored. Nearly all of the plant species used in traditional healing systems to treat these diseases are yet to be tested. Substantial further work is required to verify the efficacy of these traditional medicines.

The traditional use of southern African medicinal plants for the treatment of bacterial respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Multiple plant species were used traditionally in southern Africa to treat bacterial respiratory diseases. This review summarises this usage and highlights plant species that are yet to be verified for these activities. AIM OF THE STUDY: This manuscript reviews the traditional usage of southern African plant species to treat bacterial respiratory diseases with the aim of highlighting gaps in the literature and focusing future studies. MATERIALS AND METHODS: An extensive review of ethnobotanical books, reviews and primary scientific studies was undertaken to identify southern African plants which are used in traditional southern African medicine to treat bacterial respiratory diseases. We also searched for southern African plants whose inhibitory activity against bacterial respiratory pathogens has been conmfirmed, to highlight gaps in the literature and focus future studies. RESULTS: One hundred and eighty-seven southern African plant species are recorded as traditional therapies for bacterial respiratory infections. Scientific evaluations of 178 plant species were recorded, although only 42 of these were selected for screening on the basis of their ethnobotanical uses. Therefore, the potential of 146 species used teraditionally to treat bacterial respiratory diseases are yet to be verified. CONCLUSIONS: The inhibitory properties of southern African medicinal plants against bacterial respiratory pathogens is relatively poorly explored and the antibacterial activity of most plant species remains to be verified.

A Review: New Trends in Electrode Systems for Sensitive Drug and Biomolecule Analysis.

Drug and biomolecule analysis with high precision, fast response, not expensive, and user-friendly methods have been very important for developing technology and clinical applications. Electrochemical methods are highly capable for assaying the concentration of electroactive drug or biomolecule and supply excellent knowledge concerning its physical and chemical properties such as electron transfer rates, diffusion coefficients, electron transfer number, and oxidation potential. Electrochemical methods have been widely applied because of their accuracy, sensitivity, cheapness, and can applied on-site determinations of various substances. The progress on electronics has allowed developing reliable, more sensitive and less expensive instrumentations, which have significant contribution in the area of drug development, drug and biomolecule analysis. The developing new sensors for electrochemical analysis of these compounds have growing interest in recent years. Screen-printed based electrodes have a great interest in electrochemical analysis of various drugs and biomolecules due to their easy manufacturing procedure of the electrode allow the transfer of electrochemical laboratory experiments for disposable on-site analysis of some compounds. Paper based electrodes are also fabricated by new technology. They can be preferred due to their easy, cheap, portable, disposable, and offering high sensitivity properties for many application field such as environmental monitoring, food quality control, clinical diagnosis, drug, and biomolecules analysis. In this review, the recent electrochemical drug and biomolecule (DNA, RNA, µRNA, Biomarkers, etc.) studies will be presented that involve new trend disposable electrodes.

The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B: Considerations for future novel therapeutics.

Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussed.

El papel del farmacéutico / No disponible

No disponible

Asociaciones de pacientes y autorización de nuevos fármacos en Estados Unidos. El caso del eteplirseno para la distrofia muscular de Duchenne / Patients organizations and new drug approval in the US. Eteplirsen and Duchenne muscular dystrophy case

Introducción. En 2016, la Agencia de Medicamentos y Alimentos (FDA) estadounidense autorizó la comercialización del eteplirseno para el tratamiento de la distrofia muscular de Duchenne. Este hecho ha sido muy controvertido, por cuanto la autorización se produjo tras una evaluación negativa por parte del comité asesor de la FDA y de sus propios técnicos. Fue la directora del Centro de Investigación y Evaluación de Fármacos quien autorizó el medicamento, decisión que no revocó el director de la FDA. Objetivo. Informar sobre los acontecimientos más relevantes que han conducido a la autorización del eteplirseno por la FDA. Desarrollo. En el artículo se exponen pormenorizadamente los hechos relevantes que acontecieron durante el desarrollo clínico y la evaluación reguladora del eteplirseno siguiendo la vía de la ‘autorización acelerada’. Se comentan las razones por las que los técnicos de la FDA entienden que este medicamento no ha mostrado producir beneficio clínico, la actitud de las asociaciones de pacientes y las exigencias postautorización que la FDA ha impuesto a la compañía propietaria del medicamento. Por último, se reflexiona sobre la situación en que quedan los pacientes españoles una vez que el eteplirseno está comercializado en Estados Unidos. Conclusiones. Este caso, único en la historia de autorización de medicamentos en el mundo occidental, pone de manifiesto las dificultades que las regulaciones actuales de autorización acelerada de nuevos medicamentos pueden tener en la interpretación de datos del desarrollo clínico, cuando éstos son escasos y de poca calidad, y cuando se trata de enfermedades raras sin terapias disponibles (AU)

Introduction. In 2016 the US Food and Drug Administration (FDA) granted the marketing authorization for eteplirsen for Duchenne muscular dystrophy. This has been a very controversial decision since it happened after a negative assessment from both the Advisory Committee and the technical FDA evaluation team. The FDA’s Center for Drug Evaluation and Research (CDER) director was who ultimately approved the product, while the FDA Commissioner did not overrule that decision. Aim. To report about the most relevant events regarding the approval of eteplirsen by the US FDA. Development. All relevant facts that occurred during the clinical development and evaluation phase following "accelerated approval" procedure of eteplirsen are discussed in detail. The technical FDA evaluation team reasons supporting that the drug has not proven clinical benefit, the attitude of patient advocacy groups and the post-approval FDA requirements to the marketing authorization holder are discussed. Finally, we reflect on what is the situation Spanish patients face once eteplirsen is on the US market. Conclusions. This is a unique case in the history of drug authorizations in western countries, that shows the difficulties thatcurrent regulations on accelerated approval of new medicines could have when interpreting scarce and low quality clinical development data, when dealing with rare diseases with no available therapies (AU)

Evaluación positiva de medicamentos: marzo, abril y mayo 2017 / Possitive assessment of drugs: March, April and May 2017

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en marzo, abril y mayo 2017, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in March, April and May of 2017, and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product (AU)

Ensayos clínicos precoces en oncología pediátrica en España: una perspectiva nacional / Early clinical trials in paediatric oncology in Spain: a nationwide perspective

Introducción: El cáncer es la primera causa de muerte por enfermedad entre el primer año de vida y la adolescencia. Algunos tipos de enfermedad siguen constituyendo un reto en términos de curación. Existe por tanto una necesidad imperiosa de nuevos fármacos. Algunos descubrimientos recientes en la biología del cáncer abren la puerta al desarrollo de terapias dirigidas contra alteraciones moleculares concretas e inmunoterapia. Esto se ha traducido en resultados prometedores sobre todo en oncología de adultos, y en menor medida todavía en niños. Presentamos la actividad en ensayos clínicos precoces (fase I-II) en oncología pediátrica en España. Material y métodos: A través de la Sociedad Española de Oncología y Hematología Pediátrica (SEHOP) contactamos a sus miembros para identificar los ensayos fase I-II en cáncer pediátrico abiertos entre 2005 y 2015. Resultados: En este periodo se abrieron 30 ensayos: 21 (70%) en tumores sólidos y 9 (30%) en hemopatías malignas y se incluyó a 212 pacientes. La mayoría están promovidos por la industria farmacéutica (53%). Desde 2010, 4 centros se han integrado en el consorcio internacional ITCC cuyo objetivo es desarrollar nuevas terapias en cáncer infantil. Esto ha permitido ampliar el abanico de posibilidades terapéuticas. Los resultados de ensayos clínicos terminados muestran la contribución de los investigadores españoles, la introducción de terapias dirigidas y sus beneficios. Conclusiones: La actividad en ensayos clínicos precoces ha aumentado en estos años. La SEHOP está comprometida a desarrollar y participar en ensayos clínicos académicos colaborativos, que favorezcan el avance en las terapias frente al cáncer infantil (AU)

Introduction: Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. Material and methods: All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. Results: A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. Conclusions: The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer (AU)

Assessment of off-label prescribing: profile, evidence and evolution / Evaluación de las prescripciones fuera de ficha técnica: perfil, evidencia y evolución

Objective: 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, methotrexate, 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 (AU)

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 offlabel 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 (AU)

Evaluación positiva de medicamentos: diciembre 2016-enero/febrero 2017 / Possitive assessment of drugs: December 2016, January and February 2017

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en diciembre de 2016, enero y febrero de 2017, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in December of 2016, January and February of 2017, and considered of interest to the health care professional, are reviewed. These are positive technical reports prior to the authorization and placing of the product on the market (AU)

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance.