[The European Medicines Agency rejects the authorization of aducanumab for Alzheimer's disease]. / La Agencia Europea de Medicamentos rechaza la autorización del aducanumab para la enfermedad de Alzheimer.

TITLE: La Agencia Europea de Medicamentos rechaza la autorización del aducanumab para la enfermedad de Alzheimer.

[Aducanumab approval for Alzheimer's disease in the USA: the surrender of science]. / Aprobación del aducanumab para la enfermedad de Alzheimer en Estados Unidos: la claudicación de la ciencia.

TITLE: Aprobación del aducanumab para la enfermedad de Alzheimer en Estados Unidos: la claudicación de la ciencia.

Potential predatory journals are colonizing the ICMJE recommendations list of followers.

BACKGROUND: The International Committee of Medical Journal Editors (ICMJE) has expressed its concerns about predatory journals using the list of ICMJE Recommendations (ICMJE-R) followers to "gain the appearance of legitimacy." We assessed the presence of potential predatory journals on the ICMJE-R list and their adherence to ICMJE recommendations. METHODS: A random sample of 350 journals from the estimated 3,100-3,200 biomedical journals listed as ICMJE-R followers was chosen. Data collected from the ICMJE and journal webpages in English were: adherence to six ICMJE-R policies/requirements, year of journal's listing as ICMJE-R follower, discipline covered, publisher and its country of origin and existence of article processing charge. Potential predatory journal was considered as one open access journal not being a member of a recognized listing in COPE, DOAJ, OASPA, AJOL and/or INASP. RESULTS: Thirty-one percent of journals were considered to be potentially predatory; 94% of them were included in the ICMJE-R list in 2014-2018. Half were published in the United States and 62% were devoted to medicine. Adherence to five of the six policies/requirements was infrequent, ranging from 51% (plagiarism) to 7% (trial registration). Seventy-two percent of journals mentioned a policy on authors' conflicts of interest. Information on article processing charge was available for 76% journals and could not be found for 22%. Authorship policy/ instructions were significantly more present in journals with publishers from India than from the USA (53% vs 30%; p = 0.047), with no differences in the other five policies. CONCLUSION: Predatory journals should be deleted from the ICMJE-R list of followers to prevent misleading authors. ICMJE-R following journals need to be reevaluated with pre-defined published criteria.

[Easing access to all information should be mandatory to medical journals]. / Facilitar el acceso a toda la informacion debe ser una obligacion para las revistas medicas.

TITLE: Facilitar el acceso a toda la informacion debe ser una obligacion para las revistas medicas.

Existe asociación entre la mención en los medios sociales de los artículos científicos y su número de citas? Análisis de las revistas médicas más influyentes / Are article's social media mentions associated to citation counts? An analysis in highly influential medical journals

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

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 that current 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.

TITLE: Asociaciones de pacientes y autorizacion de nuevos farmacos en Estados Unidos. El caso del eteplirseno para la distrofia muscular de Duchenne.Introduccion. En 2016, la Agencia de Medicamentos y Alimentos (FDA) estadounidense autorizo la comercializacion del eteplirseno para el tratamiento de la distrofia muscular de Duchenne. Este hecho ha sido muy controvertido, por cuanto la autorizacion se produjo tras una evaluacion negativa por parte del comite asesor de la FDA y de sus propios tecnicos. Fue la directora del Centro de Investigacion y Evaluacion de Farmacos quien autorizo el medicamento, decision que no revoco el director de la FDA. Objetivo. Informar sobre los acontecimientos mas relevantes que han conducido a la autorizacion del eteplirseno por la FDA. Desarrollo. En el articulo se exponen pormenorizadamente los hechos relevantes que acontecieron durante el desarrollo clinico y la evaluacion reguladora del eteplirseno siguiendo la via de la 'autorizacion acelerada'. Se comentan las razones por las que los tecnicos de la FDA entienden que este medicamento no ha mostrado producir beneficio clinico, la actitud de las asociaciones de pacientes y las exigencias postautorizacion que la FDA ha impuesto a la compañia propietaria del medicamento. Por ultimo, se reflexiona sobre la situacion en que quedan los pacientes espanoles una vez que el eteplirseno esta comercializado en Estados Unidos. Conclusiones. Este caso, unico en la historia de autorizacion de medicamentos en el mundo occidental, pone de manifiesto las dificultades que las regulaciones actuales de autorizacion acelerada de nuevos medicamentos pueden tener en la interpretacion de datos del desarrollo clinico, cuando estos son escasos y de poca calidad, y cuando se trata de enfermedades raras sin terapias disponibles.

La cohabitación de la academia y la industria: ¿qué postura toman las revistas médicas en relación con los artículos de opinión? / The cohabitation of academia and industry: what position do the medical journals take regarding opinion articles?

¿Deben las revistas médicas publicar editoriales y artículos de carácter educativo escritos por autores que presentan conflictos de intereses financieros con las industrias farmacéutica y biotecnológica de cuyos productos (o sus competidores) opinan? En los últimos 18 meses se ha desatado una polémica entre The New England Journal of Medicine y BMJ, que plantean 2 posturas opuestas: la primera entiende que el prejuicio negativo contra autores con conflicto de intereses con la industria es excesivo y, por tanto, acepta artículos de cualquier experto procurando que presenten el mínimo sesgo posible. BMJ, por el contrario, prohíbe publicar ese tipo de artículos por autores que tienen conflicto de intereses financieros con la industria. En este artículo se desarrollan las actitudes de ambas (y otras) revistas y se reflexiona sobre este tipo de conflicto en la profesión médica (AU)

Should medical journals publish editorials and educational articles written by authors who have financial conflicts of interest with pharmaceutical and biotechnology industries on whose products (or their competitors) they discuss? In the last 18 months, a controversy was sparked between The New England Journal of Medicine and BMJ, who took 2 opposite positions: the former stated that the negative bias against authors with conflicts of interest with industry is excessive and therefore accept articles from any expert, ensuring that they have the minimum possible bias. BMJ, in contrast, prohibits the publication of these types of article by authors who have financial conflicts of interest with industry. This article discusses the approaches of the 2 journals (and those of others) and reflects on this type of conflict in the medical profession (AU)

The cohabitation of academia and industry: What position do the medical journals take regarding opinion articles? / La cohabitación de la academia y la industria: ¿qué postura toman las revistas médicas en relación con los artículos de opinión?

Should medical journals publish editorials and educational articles written by authors who have financial conflicts of interest with pharmaceutical and biotechnology industries on whose products (or their competitors) they discuss? In the last 18 months, a controversy was sparked between The New England Journal of Medicine and BMJ, who took 2 opposite positions: the former stated that the negative bias against authors with conflicts of interest with industry is excessive and therefore accept articles from any expert, ensuring that they have the minimum possible bias. BMJ, in contrast, prohibits the publication of these types of article by authors who have financial conflicts of interest with industry. This article discusses the approaches of the 2 journals (and those of others) and reflects on this type of conflict in the medical profession.

Si le llaman la atención los resultados de un artículo, léalo completo, no se fíe solo del resumen / If the results of an article are noteworthy, read the entire article; do not rely on the abstract alone

Es habitual que los clínicos actualicen sus conocimientos con la lectura de artículos a través de Internet. El fácil acceso al resumen de los artículos y la falta de tiempo para acceder a otros tipos de fuentes de información hace que exista el riesgo de que, en ocasiones, se puedan tomar decisiones terapéuticas o diagnósticas tras la sola lectura de los resúmenes. Ocasionalmente, sin embargo, en los resúmenes de artículos de ensayos clínicos que no han obtenido diferencias estadísticamente significativas en la variable principal de evaluación, se informa de otros resultados positivos, por ejemplo, de una variable secundaria o en un subgrupo de participantes. En el artículo, no obstante, se informa correctamente de todos los resultados obtenidos, incluso de los de la variable principal de evaluación. En el resumen, la información de seguridad del tratamiento experimental suele ser deficiente. Se debe leer el artículo completo si se va a tomar una decisión clínica (AU)

Clinicians typically update their knowledge by reading articles on the Internet. Easy access to the articles’ abstracts and a lack of time to access other information sources creates a risk that therapeutic or diagnostic decisions will be made after reading just the abstracts. Occasionally, however, the abstracts of articles from clinical trials that have not obtained statistically significant differences in the primary study endpoint have reported other positive results, for example, of a secondary endpoint or a subgroup analysis. The article, however, correctly reports all results, including those of the primary endpoint. In the abstract, the safety information of the experimental treatment is usually deficient. The whole article should be read if a clinical decision is to be made (AU)

If the results of an article are noteworthy, read the entire article; do not rely on the abstract alone. / Si le llaman la atención los resultados de un artículo, léalo completo, no se fíe solo del resumen.

Clinicians typically update their knowledge by reading articles on the Internet. Easy access to the articles' abstracts and a lack of time to access other information sources creates a risk that therapeutic or diagnostic decisions will be made after reading just the abstracts. Occasionally, however, the abstracts of articles from clinical trials that have not obtained statistically significant differences in the primary study endpoint have reported other positive results, for example, of a secondary endpoint or a subgroup analysis. The article, however, correctly reports all results, including those of the primary endpoint. In the abstract, the safety information of the experimental treatment is usually deficient. The whole article should be read if a clinical decision is to be made.

Management and return of incidental genomic findings in clinical trials.

Whole-genome/exome sequencing used in clinical trials (CTs) to identify 'druggable' mutations and targets uncovers incidental findings unrelated to the trial objectives but of value for participants, although ethically challenging. To be disclosed to trial participants, the analytical validity, clinical validity, clinical utility, clinical relevance and actionability of incidental genomic findings (IGFs) must be established. Special considerations should be taken with minors to disclose only those findings related to early-onset conditions or diseases and in cases where early implementation of measures is necessary to prevent the occurrence of diseases. A plan for disclosing incidental findings that classifies the types that can be found, and who, when and how these findings will be disclosed to participants, should be included in the trial protocol to be approved by the relevant institutional review board. IGFs in CTs raise new ethical challenges that must be discussed by CT stakeholders, professional associations and patient advocates.

El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él / Therapeutic misconception in clinical trials: fighting against it and living with it

Un ensayo clínico busca obtener datos para el beneficio de futuros pacientes y no necesariamente para los que participan en él. Sin embargo, hay pacientes que creen que obtendrán un beneficio terapéutico directo por participar en un ensayo clínico: es el denominado «equívoco terapéutico». En este artículo se describe la naturaleza y la extensión del equívoco terapéutico, que también pueden presentar los investigadores. Su presencia es especialmente relevante en ensayos con grupo placebo y en los de fase 1 de oncología. Para intentar limitar su aparición hay que asegurar que las hojas de información para los participantes estén bien redactadas, y que los investigadores establezcan una conversación efectiva y transparente en el proceso de obtención del consentimiento informado, de forma que el paciente conozca todos los matices de su participación en la investigación y valore lo que esto significa (AU)

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception». In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails (AU)

Therapeutic misconception in clinical trials: fighting against it and living with it. / El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él.

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception¼. In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails.

Ensayos clínicos con... ¿medicamentos? A propósito de 2 proyectos en enfermedad de Alzheimer y paludismo / Clinical trials with ... drugs? Based on 2 projects in Alzheimer's disease and malaria

La ley de investigación biomédica (LIB) regula la investigación en seres humanos pero no la relativa a los ensayos clínicos con medicamentos. Este artículo describe los fundamentos científicos y normativos por los que 2 proyectos que pueden ser observados como ensayos clínicos pueden seguir los requerimientos de la LIB. Uno es el estudio de tomografía por emisión de positrones con radiofármaco para determinar la presencia de proteína β amiloide en ciertas áreas del cerebro de adultos cognitivamente sanos. El otro es un estudio de infección controlada de paludismo en voluntarios sanos, mediante la inoculación de esporozoitos de Plasmodium falciparum asépticos, purificados y criopreservados. En ambos estudios, al incluir procedimientos invasivos, la LIB exige la autorización del estudio por las autoridades autonómicas competentes. Estos 2 estudios han sido los primeros que han utilizado este procedimiento normativo en Cataluña(AU)

The biomedical research act (BRA) regulates clinical research in humans, but not that related to clinical trials with medicinal products. This article describes the scientific and regulatory foundations supporting 2 projects which could be observed as clinical trials, can follow the BRA requirements. One is a positron emission tomography study with radiopharmaceutical to determine the presence of amyloid-β protein deposition in certain areas of the brain of cognitively healthy adults. The other is a study on controlled malaria infection in healthy volunteers using the inoculation of aseptic, purified and cryopreserved Plasmodium falciparum sporozoites. Since in both studies subjects undergo invasive procedures, the BRA requires the approval of the study by the relevant regional health authorities. These 2 studies have been the first ones that have used this regulatory procedure in Catalonia(AU)