Clinical research and drug regulation in the challenging times of individualized therapies: A pivotal role of clinical pharmacology.

Since the 1980s, medical specialists in Clinical Pharmacology have been playing a crucial role in the development of drug regulation in Spain. In this article we report on the activities carried out and the prospects for development in three very relevant areas from the regulatory perspective: 1) the development of stable public infrastructures to facilitate non-commercial clinical research with medicines, 2) the regulatory aspects of individual access to medicines in special situations, beyond their regular access after marketing approval and funding by the National Health System, and 3) the challenges of development and access to advanced therapies, with special reference to the figure of the hospital exemption.

Mesenchymal stromal cell therapy for COVID-19 acute respiratory distress syndrome: a double-blind randomised controlled trial.

Mesenchymal stromal cells (MSC) have immunomodulatory and tissue-regenerative properties and have shown promising results in acute respiratory distress syndrome (ARDS) of multiple causes, including COVID-19. We conducted a randomised (1:1), placebo-controlled, double-blind clinical trial to assess the efficacy and safety of one bone marrow-derived MSC infusion in twenty patients with moderate to severe ARDS caused by COVID-19. The primary endpoint (increase in PaO2/FiO2 ratio from baseline to day 7, MSC 83.3 versus placebo 57.6) was not statistically significant, although a clinical improvement at day 7 in the WHO scale was observed in MSC patients (5, 50% vs 0, 0%, p = 0.033). Median time to discontinuation of supplemental oxygen was also shorter in the experimental arm (14 versus 23 days, p = 0.007), resulting in a shorter hospital stay (17.5 versus 28 days, p = 0.042). No significant differences were observed for other efficacy or safety secondary endpoints. No infusion or treatment-related serious adverse events occurred during the one-year follow-up. This study did not meet the primary endpoint of PaO2/FiO2 increase by day 7, although it suggests that MSC are safe in COVID-19 ARDS and may accelerate patients' clinical recovery and hospital discharge. Larger studies are warranted to elucidate their role in ARDS and other inflammatory lung disorders.Trial Registration: EudraCT Number: 2020-002193-27, registered on July 14th, 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002193-27/ES . NCT number: NCT04615429, registered on November 4th, 2020, https://clinicaltrials.gov/ct2/show/NCT04615429 .

Análisis descriptivo del electroencefalograma en el síndrome de Angelman / Descriptive analysis of the electroencephalogram in Angelman syndrome

INTRODUCCIÓN: El síndrome de Angelman es un trastorno del neurodesarrollo de origen genético, con importantes manifestaciones clínicas motoras, conductuales, comunicativas y electroencefalográficas, con especial relevancia en lo que concierne a la presencia de crisis epilépticas. OBJETIVOS: Describir las características electroencefalográficas (cualitativa y cuantitativamente) de los pacientes con diagnóstico de síndrome de Angelman y determinar el perfil electroencefalográfico según la edad y la alteración genética. PACIENTES Y MÉTODOS: Estudio observacional retrospectivo donde se analizaron las características demográficas, clínicas y electroencefalográficas de 51 pacientes con síndrome de Angelman. RESULTADOS: Se evidenció una mayor potencia delta en todas las regiones cerebrales, con un pico máximo en las regiones frontopolar y temporal, y una menor potencia en el rango de frecuencias alfa y beta en todas las regiones, con mayor preponderancia en los pacientes más jóvenes, con tendencia decreciente con la edad. La coherencia mostró un predominio delta y theta en la región frontopolar, que fue mayor para todas las frecuencias en el grupo de deleción, con predominio delta, especialmente en la región frontopolar. CONCLUSIÓN: El electroencefalograma podría ser un biomarcador útil como herramienta cualitativa y cuantitativa en la investigación del síndrome de Angelman y en la medición de la respuesta a eventuales terapias en investigación

INTRODUCTION: Angelman syndrome is a neurodevelopmental disorder of genetic origin, with important clinical motor, behavioural, communicative and electroencephalographic manifestations, with particular relevance as regards the presence of epileptic seizures. AIMS. To describe the electroencephalographic characteristics (qualitatively and quantitatively) of patients diagnosed with Angelman syndrome and to determine the electroencephalographic profile according to age and genetic alteration. PATIENTS AND METHODS: A retrospective observational study in which the demographic, clinical and electroencephalographic characteristics of 51 patients with Angelman syndrome were analysed. RESULTS: A higher delta power was evident in all brain regions, with a maximum peak in the frontopolar and temporal regions, and a lower power in the alpha and beta frequency range in all regions, with a greater preponderance in younger patients, and a trend that decreases with age. The coherence showed a predominance of delta and theta in the frontopolar region, which was higher for all frequencies in the deletion group, where delta was predominant, especially in the frontopolar region. CONCLUSION. The electroencephalogram could be a useful biomarker as a qualitative and quantitative tool in the investigation of Angelman syndrome and in measuring the response to possible therapies under investigation

Biosimilares en el tratamiento de la enfermedad infl amatoria intestinal / Biosimilar therapy for inflammatory bowel disease

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Modificaciones y exenciones del consentimiento informado y las guías Council for International Organizations of Medical Sciences / Modifications and waivers of informed consent and the Council for International Organizations of Medical Sciences guidelines

No disponible

¿Son equivalentes los genéricos y las marcas en el tratamiento de la enfermedad de Alzheimer? / Are generics and brand name medicines equivalent in Alzheimer’s disease treatment?

Los genéricos son a veces objeto de dudas y malentendidos por parte del médico o del paciente. En el caso del paciente con enfermedad de Alzheimer, el «baile» de genéricos puede ser un motivo de preocupación y causar problemas en la identificación del tratamiento habitual. Sin embargo, la eficacia y la seguridad del medicamento genérico están perfectamente avaladas al haberse demostrado su bioequivalencia con el medicamento innovador o de referencia. La bioequivalencia tiene como base una metodología cuyo fundamento es garantizar no solo que el medicamento genérico tiene la misma cantidad de principio activo que el medicamento de referencia, sino también que se absorbe exactamente del mismo modo, lo que permite asumir que producirá los mismos efectos sistémicos. El menor precio del genérico está sujeto a diversos factores, pero no se debe a diferencias en calidad, ya que su fabricación cumple con idénticos estándares a los del medicamento de referencia. Algunos conceptos relevantes en este campo son los de «prescribilidad », intercambiabilidad y políticas de sustitución. Así, un medicamento genérico autorizado puede ser prescrito con las mismas garantías de calidad, eficacia y seguridad que el medicamento de referencia y se debe considerar intercambiable, si bien es preferible evitar sustituciones innecesarias en los pacientes (AU)

The use of generic drugs is often surrounded by misunderstandings and questions, from patients and physicians. The switch between generic drugs is frequently a concern because it can difficult the ability of Alzheimer’s patients to recognize their daily medication. The efficacy and safety of a generic drug is fully endorsed by demonstrating its bioequivalence with the reference drug. The demonstration of bioequivalence guarantees not only that the generic drug contains the same active substance quantity, but it is also absorbed in the same manner than the reference drug. This methodology allows us to conclude that both drugs produce the same systemic effects. The lower price of a generic drug is due to several different factors, but none of them incur in differences in quality, since the manufacture of a generic drug follows identical requirements to those followed by the reference drug. "Prescribility", "interchangeability" and "drug substitution" policies are relevant concepts to discuss in the context of generic drugs use. In that sense, an approved generic drug can be prescribed with the same quality, efficacy and safety guaranties that those of the reference drug and both of them can be considered exchangeable. However, it is preferred to avoid any unnecessary drug substitutions in a patient chronic treatment (AU)

Cambios en la normativa europea de ensayos clínicos ( ii ): por una regulación proporcionada y adaptada al riesgo / Changes in the European normative of clinical trials ( ii ): towards a proportional and risk-adapted regulation

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Cambios en la normativa europea de ensayos clínicos ( i ): una oportunidad para mejorar los trámites de autorización / Changes in the European normative of clinical trials ( i ): a chance to improve the paperwork authorization

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