[Translated article] Current situation and evolution of the availability of drugs in the pediatric population in Spain.

OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last 3 years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorized or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022. RESULTS: During the study period, 129 drugs included their indication in the pediatric population. 13.9% of them are not marketed, 46.5% are in a situation of non-financing, under study or without a request for financing, and 4.6% are financed for a specific pediatric subpopulation. 52.7% are original drugs, 4.7% are generic, 38.8% are biological, 3.8% are biosimilar, and 17.8% are orphan drugs. 57.36% of these medicines obtain the pediatric indication due to extension of the indication and 42.64% obtain it because they are new medicines that already include their studies in the pediatric population. CONCLUSIONS: Drugs with authorized indications are increasingly available in the pediatric population and the trend is to extend the indication of authorized drugs to the adult population. However, barriers in terms of financing and marketing need to be expedite and overcome to facilitate access to them.

Asociación de las características del ensayo con la publicación simultánea y su impacto en citas y menciones: un estudio transversal / Association of trial characteristics with simultaneous publication and its impact on citations and mentions: a cross-sectional study

Introducción y objetivos: Los ensayos clínicos aleatorizados a menudo se presentan en conferencias médicas y se publican al mismo tiempo o después. Los predictores de publicación simultánea y sus consecuencias no están determinados. Nuestro objetivo es caracterizar la práctica de la publicación simultánea, identificar sus predictores y evaluar su impacto. Métodos: En este estudio transversal se incluyeron ensayos clínicos aleatorizados presentados en sesiones de ciencia de última hora de importantes conferencias cardiovasculares desde 2015 hasta 2021. Se analizó la asociación entre las características del ensayo y el momento de la publicación. Se investigó el impacto de la publicación simultánea frente a la no simultánea en el número de citas a 1 año y menciones a 1 mes, así como en el total de citas y menciones en el seguimiento más largo observado. Resultados: De los 478 ensayos incluidos en el análisis, el 48,7% se publicó simultáneamente. Las publicaciones simultáneas tenían mayor probabilidad de presentarse en la sala principal de la conferencia (OR=6,09; IC95%, 1,34-36,92; p=0,029) y se caracterizaban por un tiempo de revisión más corto (OR=0,95; IC95%, 0,91-0,96; p<0,001). Las publicaciones simultáneas se asociaron con un mayor número de citas a 1 año (R2=43,81; IC95%, 23,89-63,73; p<0,001), menciones a 1 mes (R2=132,32; IC95%, 85,42-179,22; p<0,001) y total de citas (R2=222,89; IC95%, 127,98-317,80; p<0,001) en el seguimiento. Conclusiones: Los ensayos clínicos aleatorizados presentados en la sala principal de la conferencia y con un tiempo de revisión más corto tienen mayor probabilidad de publicarse simultáneamente. Las publicaciones simultáneas se asocian con más citas y menciones que las publicaciones no simultáneas. (AU)

Introduction and objectives: Randomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. Methods: In this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. Results: Of 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). Conclusions: Randomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications. (AU)

COVID-19 en sujetos de riesgo participantes en ensayos clínicos durante la pandemia en Argentina / COVID-19 in subjects at risk participating in clinical trials during the pandemic in Argentina

Resumen Introducción : Existe poca información sobre la pre sencia de COVID-19 en participantes de ensayos clínicos. El objetivo del estudio fue evaluar la tasa de infección acumulada por SARS-CoV-2 en esta población. Además, investigamos el riesgo, letalidad y mortalidad por CO VID-19. Métodos : Diseño observacional retrospectivo que incluyó adultos participantes en ensayos clínicos de intervención aprobados por nuestro comité de ética du rante los dos primeros años de la pandemia (31/3/2020 a 31/3/2022). Se excluyeron protocolos pediátricos, obser vacionales, de corta duración y con sujetos internados. Resultados : Se incluyeron 513 sujetos adultos que participaron en ensayos clínicos durante ese período de la pandemia por COVID-19. Los pacientes con CO VID-19 se caracterizaron por tener una edad de 59.7 ± 13.7 años (50% sexo femenino) y el 92% presentó riesgo incrementado de letalidad por COVID-19. La tasa acu mulada de COVID-19 fue de 9.74% (IC 95%: 7.32-12.64%) que se situó por debajo del 17% de la población de 60 a 69 años de la Argentina (p<0.0001). La tasa de letalidad por COVID-19 fue de 14% (IC 95%: 5.8-26.7), que se situó por encima del 2.45% de la población de 50 a 69 años de la Argentina (p<0.0001). Conclusión : La tasa de COVID-19 en los sujetos adultos participantes de ensayos clínicos estuvo por debajo de las cifras de la población argentina de simi lar edad. La tasa de letalidad estuvo por encima de las cifras poblacionales y se explica por el alto riesgo de esa población.

Abstract Introduction : There is little information on the pres ence of COVID-19 in clinical trial participants. The objec tive of the study was to evaluate the cumulative infec tion rate for SARS-CoV-2 in this population. Additionally, we investigated the risk, lethality, and mortality from COVID-19. Methods : The design was observational retrospective that included adult subjects participating in clinical intervention trials approved by our ethics committee during the first two years of the pandemic (March 31, 2020 to March 31, 2022). Pediatric, observational, short-term, and inpatient protocols were excluded. Results : We included 513 adult subjects who par ticipated in clinical trials during the first two years of the COVID-19 pandemic. Patients with COVID-19 were characterized as being 59.7 ± 13.7 years old (50% fe male), and 92% had an increased risk of fatality from COVID-19. The cumulative rate of COVID-19 was 9.74% (95% CI: 7.32-12.64%) and its confidence intervals were below 17% of the population aged 60 to 69 in Argentina (p<0.0001). The case fatality rate for COVID-19 was 14% (95% CI: 5.8%-26.7%) and its confidence intervals were above 2.45% of the population aged 50 to 69 in Argentina (p< 0.0001). Conclusion : The rate of COVID-19 in adult subjects participating in clinical trials was below the figures for the Argentine population of similar age. The fatality rate was above the population figures, and it is explained by the high risk of the population.

Historia de la hipertensión arterial: revisión narrativa

Introducción: La medición de la presión arterial es uno de los procedimientos más realizados en la práctica clínica. La presente revisión narrativa pretende sintetizar los aspectos relevantes que rodearon la definición de la hipertensión arterial, el recorrido histórico del tratamiento de esta y el aporte de los estudios a la disminución de la mortalidad por enfermedad cardiovascular en el tiempo. Metodología: Revisión narrativa de la historia de la hipertensión arterial, desde el reconocimiento de la presión arterial alta como un factor asociado al riesgo cardiovascular y la evolución histórica del tratamiento hasta los hallazgos significativos del estudio SPRINT, publicado en 2015. Resultados: Hasta hace aproximadamente 50 años la hipertensión arterial era conocida como una patología esencial, es decir, esta condición no siempre fue considerada como una enfermedad. El descubrimiento de la presión sanguínea ha sido atribuido a Stephen Hales, poeta, orador y sacerdote nacido en Inglaterra. La primera medición de la presión sanguínea e incidentalmente de la presión del pulso la realizó en 1733 en animales. Se describe el origen de la presión arterial, la hipertensión arterial, el camino recorrido para el reconocimiento de esta condición como enfermedad y posteriormente su tratamiento, hasta llegar al estudio SPRINT en 2015, el cual fue contundente en demostrar el beneficio de reducir la cifra de presión arterial sistólica objetivo en una población no diabética. Conclusión: Los resultados de esta revisión narrativa exponen cómo el reconocimiento de la presión arterial alta como un factor de riesgo cardiovascular permitió el avance en la investigación científica para determinar el tratamiento y las cifras de presión arterial que favorecen la reducción de la mortalidad y morbilidad por esta causa.

Background: Blood pressure measurement is one of the most performed procedures in clinical practice. This narrative review aims to expose the relevant aspects surrounding the definition of arterial hypertension, the historical path of its treatment, and the contribution of studies to the decrease in mortality due to cardiovascular disease over time. Methodology: Narrative review of the history of arterial hypertension from recognizing high blood pressure as a factor associated with cardiovascular risk to the historical evolution of treatment up to the SPRINT study published in 2015. Results: Until about 50 years ago, arterial hypertension was known as an essential pathology; this condition was not always considered a disease. The discovery of blood pressure has been attributed to Stephen Hales, a poet, orator and priest born in England. The first measurement of blood pressure and incidentally pulse pressure was made in 1733 in animals. The origin of blood pressure, arterial hypertension, and the path travelled for recognizing this condition as a disease and later its treatment until reaching the SPRINT study in 2015, which demonstrated the benefit of reducing the target systolic blood pressure figure in a non-diabetic population. Conclusion: This narrative review demonstrates that the recognition of high blood pressure as a cardiovascular risk factor allowed progress in scientific research to determine the treatment and blood pressure figures that favor the reduction of mortality and morbidity from this cause.

[Comparison of cervical fusion with autografting of fibula vs titanium cage]. / Comparación de artrodesis cervical mediante autoinjerto de peroné frente a caja de titanio.

Background: The anterior cervical discectomy and fusion (ACDF) is the gold standard in the treatment of cervical compression pathology and the titanium cage for fusion represents the most used procedure at an institutional level. A technique using fibular autograft has been described, with good results, lower morbidity and lower cost. Objective: To compare the rate of fusion, subsidence and functional clinical results after discectomy with titanium cage and fibular autograft. Material and methods: A clinical trial with follow-up at 3 and 6 months was carried out in patients diagnosed with cervical spondylosis, candidates for ACDF. 2 groups were formed: fibular autograft and titanium cage. Pre and post functional evaluation using the cervical disability score was made, as well as radiographic fusion and subsidence evaluation. Descriptive statistics, Fisher's exact test, t-test and ANOVA were obtained, establishing p < 0.05. Results: A sample of 20 patients with an average age of 56 years was obtained, finding a fusion rate of 90% for fibular autograft and 30% for titanium (p = 0.02) at 3 months. 10% of patients with fibular autograft presented subsidence and 70% with titanium cage at 3 and 6 months (p = 0.02). In the functional results was not found difference between both procedures (p = 0.874). Conclusions: The use of autologous fibular graft offers a better rate of fusion and subsidence compared to the titanium cage, as well as similar functional results at 3 months of follow-up. It represents an excellent treatment option for cervical spondylosis.

Introducción: la disectomía cervical anterior y fusión (ACDF) es el estándar de oro en el tratamiento de la patología compresiva cervical. La caja de titanio para artrodesis es el procedimiento más usado a nivel institucional. Se ha descrito una técnica con autoinjerto de peroné, con buenos resultados, menor morbilidad y menor costo. Objetivo: comparar la tasa de fusión, subsidencia y resultados clínicos funcionales posteriores a disectomía con caja de titanio y autoinjerto de peroné. Material y métodos: ensayo clínico con seguimiento a tres y seis meses en pacientes con diagnóstico de espondilosis cervical, candidatos a ACDF. Se formaron dos grupos: autoinjerto de peroné y caja de titanio. Se hizo evaluación funcional antes y después mediante la escala de discapacidad cervical, y evaluación de fusión y subsidencia radiográficas. Se usó estadística descriptiva, prueba exacta de Fisher, prueba t y ANOVA, estableciendo una p < 0.05. Resultados: se obtuvo una muestra de 20 pacientes con promedio de 56 años; hubo una tasa de fusión del 90% para autoinjerto de peroné y 30% para titanio (p = 0.02) a los tres meses. De los pacientes con autoinjerto de peroné, 10% presentaron subsidencia y un 70% con caja de titanio a los tres y seis meses (p = 0.02). No se encontró diferencia en los resultados funcionales a tres y seis meses de ambos procedimientos. Conclusiones: el uso de injerto autólogo de peroné ofrece mejor tasa de fusión y subsidencia en comparación con la caja de titanio, así como resultados funcionales similares a los tres meses. Es una excelente opción para tratar la espondilosis cervical.

Association of trial characteristics with simultaneous publication and its impact on citations and mentions: a cross-sectional study.

INTRODUCTION AND OBJECTIVES: Randomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. METHODS: In this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. RESULTS: Of 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). CONCLUSIONS: Randomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications.

Current situation and evolution of the availability of drugs in the paediatric population in Spain. / Situación actual y evolución de la disponibilidad de medicamentos en la población pediátrica en España.

OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last three years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorised or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022. RESULTS: During the study period, 129 drugs included their indication in the pediatric population. 13,9% of them are not marketed, 46,5% are in a situation of non-financing, under study, or without a request for financing, and 4,6% are financed for a specific pediatric subpopulation. 52,7% are original drugs, 4,7% are generic, 38,8% are biological, 3,8% are biosimilar and 17,8% are orphan drugs. 57,36% of these medicines obtain the pediatric indication due to extension of the indication and 42,64% obtain it because they are new medicines that already include their studies in the pediatric population. CONCLUSIONS: Drugs with authorised indications are increasingly available in the paediatric population and the trend is to extend the indication of authorised drugs to the adult population. However, barriers in terms of financing and marketing need to be expedited and overcome to facilitate access to them.

Consideraciones bioéticas sobre los incentivos a participantes voluntarios sanos en investigaciones Fase I

Los ensayos clínicos en Fase I se realzan con la participación de voluntarios sanos de prueban la seguridad y tolerabilidad de los productos farmacéuticos en investigación. En ellos, los participantes están expuestos a riesgos de medicamentos del estudio sin la posibilidad de un beneficio médico directo y, por lo general, deben pasar días o semanas en un centro de investigación. Los incentivos, como pagos monetarios se utilizan para incentivar la inscripción y compensar a los participantes por su tiempo. Estas características de los ensayos voluntarios sanos de fase I crean un contexto de investigación que difiere notablemente de la mayoría de las otras investigaciones clínicas, pues la mayoría de ellos son personas vulnerables económicamente. Este artículo presenta el objetivo de analizar factores bioéticos que inciden en el otorgamiento de incentivos a participantes voluntarios sanos en investigaciones Fase I.

Phase I Clinical Trials are conducted with the participation of healthy volunteers to test the safety and tolerability of pharmaceutical products. In them, participants are exposed to study drug risks without the possibility of direct medical benefit and usually must spend days or weeks at a research site. Incentives such as monetary payments are used to encourage enrollment and compensate participants for their time. These characteristics of Phase I healthy volunteer trials create a research context that differs markedly from most other clinical research, as most of them are financially vulnerable individuals. This paper aims to analyze bioethical factors that influence the granting of incentives to healthy volunteer participants in Phase I research.

Reflexiones ético-legales entorno a la recogida y análisis de muestras biológicas humanas en los ensayos clínicos promovidos por las compañías farmacéuticas / Reflexions ètico-legals al voltantde la recollida i anàlisi de mostres biològiques humanesenels assaigs clínics promoguts per les companyies farmacèutiques / Ethical and legal considerations on collection and analysis of human biological samples within clinical trials sponsored by the pharmaceutical companies

La recogida de muestras biológicas humanas dentro del contexto de un ensayo clínico promovido por un laboratorio farmacéutico y no relacionada directamente con el ensayo es cada vez más habitual. Este artículo plantea los conflictos bioéticos que dicha recogida, almacenamiento y análisis conllevan, y como afrontarlos.(AU)

La recollida de mostres biològiques humanes dintre del context d ́un assaig clínic promogut per un laboratorio farmacèutic i no relacionada directament amb l ́assaig és cada cop més habitual. Aquest article planteja els conflictes bioètics que aquesta recollida, enmagatzematge i anàlisi comporten i com enfrontar-los.(AU)

The collection of human biological samples within a clinical trial sponsored by a pharmaceutical company and not directly related with the trial it is more and more common. This paper shows the bioethical conflicts regarding the collection, storage, and analysis and how to face them.(AU)

La muestra en ensayos clínicos aleatorizados con análisis interino / Samples in randomized clinical trials with interim analysis

RESUMEN En este artículo se introducen los ensayos clínicos aleatorizados y conceptos básicos de la inferencia estadística. Se presenta como calcular el tamaño de muestra por tipo de desenlace e hipótesis a probar, junto con el código en el lenguaje de programación R para realizar su aplicación. Se presentan cuatro métodos para realizar el ajuste del tamaño de muestra original, cuando se planean análisis interinos. De una manera sencilla y concreta se busca realizar una introducción a estos temas, considerando las expresiones matemáticas que soportan los resultados y su implementación en programas estadísticos disponibles. Con el fin de acercar a los estudiantes de áreas de la salud a la estadística y al uso de programas estadísticos, aspectos poco considerados en su formación.

ABSTRACT This article introduces randomized clinical trials and basic concepts of statistical inference. We present methods for calculating the sample size by outcome type and the hypothesis to be tested, together with the code in the R programming language. We describe four methods for adjusting the original sample size for interim analyses. We sought to introduce these topics in a simple and concrete way, considering the mathematical expressions that support the results and their implementation in available statistical programs; therefore, bringing health students closer to statistics and the use of statistical programs, which are aspects that are rarely considered during their training.

[Health impact of the community intervention programme "Health education in adolescence"]. / Impacto en la salud del programa de intervención comunitaria «Educación para la salud en la adolescencia¼.

OBJECTIVE: To measure the impact of the community health programme "Education for health in adolescence" carried out in the Parquesol neighborhood, Valladolid (Spain), during the years 2015-2019. METHOD: Community-based quasi-experimental pre- and post-test analytical intervention trial with control group. A total of 407 adolescent surveys were collected. The CHIP-AE test validated for Spain was used. Pre- and post-test results were analyzed and compared with the control group. RESULTS: Improvements were found in the female intervention group compared to the control group in the variables resilience (3.68 vs. 3.41; p <0.01), health and safety at home (4.30 vs. 4.00; p <0.01), physical activities (3.16 vs. 2.60; p <0.01) and self-esteem (3.17 vs. 2.79; p <0.05). CONCLUSIONS: The community intervention carried out improves the health profile of adolescents. The baseline perception of health presents differences by gender, with higher scores in males. Post-intervention improvement is substantial in females in resilience, physical activities and health and safety at home. In addition, the worsening due to the passage of time described in previous studies is corrected in the variables self-esteem, satisfaction and well-being.

Analysis of the practice guideline in the conduct of clinical trials in hospital pharmacy. / Análisis de la Guía de excelencia para la realización de ensayos clínicos en farmacia hospitalaria.

The document «Guide to Excellence in the Conduct of Clinical Trials in Hospital Pharmacy¼ was drawn up by hospital pharmacists and representatives of the pharmaceutical industry. Its objective is to unite criteria, introduce improvements in communication, harmonize and digitalize processes in all phases of development of a clinical trial in hospital pharmacy services. This special article includes the reflections of the Working Group of the Spanish Society of Hospital Pharmacy about this document. The analysis is based on its participation in the drawing of the guide of excellence, and includes its most relevant aspects, including those which, despite being discussed during the process of preparing the document, were finally not included, for reasons of synthesis or for further analysis and agreement. While recognizing the undoubted value of a so far unprecedented first document of consensus, the Clinical Trials Working Group also highlights the future challenges that both hospital pharmacists and pharmaceutical companies have ahead in order to improve the quality of the management of clinical trials. The Clinical Trials Working Group believes that the existence of communication routes both with the pharmaceutical industry and other agents involved in the conducting of clinical trials, as well as the improved visibility of the hospital pharmacist as an expert in the management of investigational medicines, will help achieve a better management of clinical trials in our environment and the assignment of the necessary human and material resources to reach excellence.

[Translated article] Analysis of the guide to excellence in the conduct of clinical trials in hospital pharmacy.

The document "Guide to Excellence in the Conduct of Clinical Trials in Hospital Pharmacy" was drawn up by hospital pharmacists and representatives of the pharmaceutical industry. Its objective is "to unite criteria, introduce improvements in communication, harmonize and digitalize processes" in all phases of development of a clinical trial in Hospital Pharmacy Services. This special article includes the reflections of the Working Group of the Spanish Society of Hospital Pharmacy about this document. The analysis is based on its participation in the drawing of the Guide of Excellence, and includes its most relevant aspects, including those which, despite being discussed during the process of preparing the document, were finally not included, for reasons of synthesis or for further analysis and agreement. While recognizing the undoubted value of a so far unprecedented first document of consensus, the Clinical Trials Working Group also highlights the future challenges that both hospital pharmacists and pharmaceutical companies have ahead in order to improve the quality of the management of clinical trials. The Clinical Trials Working Group believes that the existence of communication routes both with the pharmaceutical industry and other agents involved in the conducting of clinical trials, as well as the improved visibility of the hospital pharmacist as an expert in the management of investigational medicines, will help achieve a better management of clinical trials in our environment and the assignment of the necessary human and material resources to reach excellence.

Análisis de la Guía de excelencia para la realización de ensayos clínicos en farmacia hospitalaria / Analysis of the practice guideline in the conduct of clinical trials in hospital pharmacy

El documento «Guía de excelencia para la realización de ensayos clínicos en farmacia hospitalaria» ha sido elaborado por farmacéuticos de hospital y representantes de la industria farmacéutica. Su objetivo es aunar criterios, introducir mejoras en la comunicación, armonizar y digitalizar procesos en todas las fases de desarrollo de un ensayo clínico en los servicios de farmacia hospitalaria.El presente artículo especial recoge las reflexiones del Grupo de Trabajo de Ensayos Clínicos de la Sociedad Española de Farmacia Hospitalaria acerca del documento. El análisis se basa en su participación en la elaboración de la guía de excelencia, y recoge los aspectos más relevantes de la misma, haciendo referencia también a algunos puntos que, pese a ser motivo de discusión durante el proceso de elaboración del documento, finalmente no se incluyeron, por motivos de síntesis o para un posterior desarrollo y acuerdo.Reconociendo el indudable valor de un primer documento de consenso, inédito hasta el momento, desde el Grupo de Trabajo de Ensayos Clínicos se ponen de manifiesto también algunos retos a futuro en la gestión de los ensayos clínicos que se presentan para ambos colectivos, farmacia hospitalaria e industria farmacéutica.En opinión del grupo de trabajo, la apertura de vías de comunicación, tanto con la industria farmacéutica como con otros agentes implicados en la realización de ensayos clínicos, y el consecuente aumento de la visibilidad del farmacéutico de hospital como experto en el manejo del medicamento en investigación, ayudará a mejorar la calidad de la gestión de la medicación de ensayos clínicos en nuestro entorno, así como la asignación de los recursos humanos y los materiales necesarios para alcanzar la excelencia. (AU)

The document «Guide to Excellence in the Conduct of Clinical Trials in Hospital Pharmacy» was drawn up by hospital pharmacists and representatives of the pharmaceutical industry. Its objective is to unite criteria, introduce improvements in communication, harmonize and digitalize processes in all phases of development of a clinical trial in hospital pharmacy services.This special article includes the reflections of the Working Group of the Spanish Society of Hospital Pharmacy about this document. The analysis is based on its participation in the drawing of the guide of excellence, and includes its most relevant aspects, including those which, despite being discussed during the process of preparing the document, were finally not included, for reasons of synthesis or for further analysis and agreement.While recognizing the undoubted value of a so far unprecedented first document of consensus, the Clinical Trials Working Group also highlights the future challenges that both hospital pharmacists and pharmaceutical companies have ahead in order to improve the quality of the management of clinical trials.The Clinical Trials Working Group believes that the existence of communication routes both with the pharmaceutical industry and other agents involved in the conducting of clinical trials, as well as the improved visibility of the hospital pharmacist as an expert in the management of investigational medicines, will help achieve a better management of clinical trials in our environment and the assignment of the necessary human and material resources to reach excellence. (AU)

Evaluación de los comparadores empleados en los estudios pivotales de nuevos medicamentos e indicaciones / Assessment of comparators used in pivotal studies of new medicines and indications

Objetivo: En algunos casos, los estudios pivotales para aprobar nuevos medicamentos no emplean el comparador más adecuado. El objetivo es cuantificar este problema analizando los Informes de Posicionamiento Terapéutico (IPT) publicados por el Ministerio de Sanidad español.Métodos: El comparador se clasificó en seis categorías según la adecuación del tratamiento, es decir, si coincidía con el estándar de tratamiento al ser autorizado: A-“inicialmente adecuado”, B-“sin comparador por causa ética”, C-“sin comparador excluyendo los clasificados en B”, D-“inadecuado” y E-“parcialmente subóptimo” (cuando era estándar solo para parte de los pacientes).La variable principal fue la proporción de nuevos fármacos/indicaciones con comparación suficiente (categorías A, B y C) o deficiente (el resto). La información sobre comparadores y tratamiento estándar se extrajo del IPT. Resultados: Se analizaron aleatoriamente 186 IPT con nuevos medicamentos/indicaciones, publicados entre 2013 y 2022. La comparación se consideró suficiente en un 73,7% (IC95 66,9-79,5) de los casos. El 26,3% restante (IC95 20,5-33,1) presentaba comparaciones deficientes en el ensayo pivotal, ya fuera por comparador inadecuado (11,3%), parcialmente subóptimo (5,4%) o ausencia de un estudio comparativo (9,7%). No hubo diferencias en relación con el año de aprobación.Conclusiones: Aproximadamente uno de cada cuatro nuevos medicamentos o indicaciones carece de una comparación suficiente en el momento de empezar a ser utilizado en la práctica clínica. La proporción no mejora a lo largo de los últimos 10 años. Las agencias reguladoras deben ser más exigentes en la selección del comparador para los ensayos clínicos pivotales, por cuestiones éticas y sanitarias. (AU)

Objective: Pivotal studies to approve new medicines often do not use the most appropriate comparator. The objective is to quantify this problem by analysing the Therapeutic Positioning Reports (IPT for its acronym in Spanish) published by the Spanish Health Ministry.Methods: The comparator was classified into six categories, based on the appropriateness of the treatment, i.e. whether it matched the standard of treatment when authorised: A-«initially adequate» (at the start of the study), B-«no comparator for ethical reasons», C-«no comparator -excluding B-«, D-«inadequate» and E-«partially suboptimal» (when it was standard for part of the included patients but not for all of them).The primary endpoint was the proportion of new drugs/indications with sufficient (categories A, B and C) or poor comparator (the rest). Information on comparators and standard treatment was extracted from the IPT. Results: We randomly analysed 186 IPTs with new drugs or indications, published between 2013 and March 2022. Comparability was assessed as sufficient in 73.7% (95%CI 66.9-79.5) of cases. The remaining 26.3% (95%CI 20.5-33.1) had poor comparisons in the pivotal trial, either due to inadequate comparator (11.3%), partially suboptimal (5.4%) or absence of a comparative study excluding ethical justification (9.7%). Conclusions: Approximately one in four new medicines or indications lacks sufficient comparability at the time of entry into clinical practice. The proportion has not improved over the last 10 years. Regulatory agencies need to be more stringent in comparator selection for pivotal clinical trials, for ethical and health reasons. (AU)

Impacto en la salud del programa de intervención comunitaria «Educación para la salud en la adolescencia» / Health impact of the community intervention programme “Health education in adolescence”

Objetivo: Medir el impacto del programa de intervención comunitaria «Educación para la salud en la adolescencia» llevado a cabo en el barrio de Parquesol, Valladolid, durante los años 2015-2019. Método: Ensayo comunitario de intervención cuasi experimental analítico pre- y postest con grupo control. Se recogieron 407 encuestas de adolescentes. Se utilizó el test CHIP-AE validado para España. Se analizaron los resultados pre- y postest y se compararon con el grupo control. Resultados: Se encontraron mejoras en el grupo de intervención femenino frente al grupo control en las variables resistencia (3,68 vs. 3,41; p < 0,01), salud y seguridad en el hogar (4,30 vs. 4,00; p < 0,01), actividades físicas (3,16 vs. 2,60; p < 0,01) y autoestima (3,17 vs. 2,79; p < 0,05). Conclusiones: La intervención comunitaria realizada mejora el perfil de salud de los/las adolescentes. La percepción basal de la salud presenta diferencias por sexo, con mayor puntuación en los hombres. La mejoría posintervención es sustancial en las mujeres en resistencia, actividades físicas y salud y seguridad en el hogar. Además, se corrige en la variable autoestima el empeoramiento debido al paso de los años descrito en estudios previos.(AU)

Objective: To measure the impact of the community health programme “Education for health in adolescence” carried out in the Parquesol neighborhood, Valladolid (Spain), during the years 2015-2019. Method: Community-based quasi-experimental pre- and post-test analytical intervention trial with control group. A total of 407 adolescent surveys were collected. The CHIP-AE test validated for Spain was used. Pre- and post-test results were analyzed and compared with the control group. Results: Improvements were found in the female intervention group compared to the control group in the variables resilience (3.68 vs. 3.41; p < 0.01), health and safety at home (4.30 vs. 4.00; p < 0.01), physical activities (3.16 vs. 2.60; p < 0.01) and self-esteem (3.17 vs. 2.79; p < 0.05). Conclusions: The community intervention carried out improves the health profile of adolescents. The baseline perception of health presents differences by gender, with higher scores in males. Post-intervention improvement is substantial in females in resilience, physical activities and health and safety at home. In addition, the worsening due to the passage of time described in previous studies is corrected in the variables self-esteem, satisfaction and well-being.(AU)

Rehabilitation programs of executive functions in young and middle adulthood based on computational systems: a scoping review

Introduction: The use of computational systems has ventured into different healthcare areas, such as rehabilitation and stimulation of cognitive processes. To this date, it is possible to identify some reviews collecting studies on the efficacy and effects of those programs in groups such as older adults, children, and teenagers; there is a lack of academic literature giving an account of young and middle-aged adults. Objective: To identify empirical studies that measured the feasibility and effect of computer-based stimulation and rehabilitation programs for cognitive functions in young and middle-aged adults. Materials and methods: The PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) extension was used as a base for a scoping review, as suggested by Cochrane Collaboration. Five databases -Science Direct, Scopus, Springer, PubMed, and Taylor & Francis- were used to trace information. The data registry and synthesis of the results was carried out independently by two reviewers. Results: 896 registries were found between 2015 and 2022, of which 91 met the eligibility principles, which evaluated the effects of programs based on computational systems on executive functions on young and middle-aged adults. Conclusion: Most of the interventions based on computational systems showed to be feasible and had moderate to significant effects on executive functions in young and middle-aged adults.

Introducción: El uso de los sistemas computacionales ha incursionado de forma notable en diferentes áreas de la salud, como la rehabilitación y estimulación de los procesos cognitivos. Si bien a la fecha se pueden identificar algunas revisiones que recopilan estudios sobre la eficacia y efectos de estos programas en grupos como adultos mayores, niños y adolescentes, existe poca literatura orientada a la adultez joven y la adultez media. Objetivo: Identificar estudios empíricos que midieron la viabilidad y el efecto de los programas de estimulación y rehabilitación de las funciones ejecutivas basados en computadora en la población adulta joven y media. Materiales y métodos: Se realizó revisión de alcance basado en la extensión PRISMA ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensión for Scoping Reviews) sugerido por Cochrane Collaboration. Para el rastreo de información se seleccionaron cinco bases de datos: Science Direct, Scopus, Springer, PubMed y Taylor & Francis. El proceso de registro de datos y la síntesis de los resultados fue realizada por dos revisores de forma independiente. Resultados: Se encontraron 896 registros desde el 2015 al 2022, de los cuales 91 cumplieron los principios de elegibilidad, en los que se evaluaron los efectos de programas basados en sistemas computacionales sobre las funciones ejecutivas en adultos jóvenes y adultos medios. Conclusión: La mayoría de las intervenciones basadas en sistemas computacionales mostraron ser viables y tener efectos favorables de moderados a significativos sobre las funciones ejecutivas de adultos jóvenes y medios.

Ensayos clínicos con medicamentos estériles. Análisis del Registro Español de ensayos clínicos / Clinical trials with steril preparations. Analysis of Spain clinical trial registry

Objetivo: Analizar el régimen jurídico para la preparación de productos estériles en el contexto de los ensayos clínicos.Método: Se ha completado una revisión bibliográfica de diferentes normas, guías e informes de organismos, así como de realizarse un análisis del Registro Español de Ensayos Clínicos (REec) para conocer la tendencia del tipo de ensayos clínicos que se realizan en España.Resultados: En la Unión Europea no existe una regulación específica en este asunto siendo responsabilidad de cada estado miembro legislar sobre ello. En el caso de España, existe una guía de buenas prácticas de preparación de medicamentos en servicios de farmacia hospitalaria.En cuanto al análisis del Registro Español de ensayos clínicos, se han obtenido datos que indican que aproximadamente el 50% de los estudios podrían requerir que estos fármacos en investigación sean preparados en condiciones de esterilidad, así como dentro de este grupo de estudios, el 79% son estudios de carácter internacional.Conclusiones: España tiene un marco normativo robusto en materia de preparación de medicamentos estériles tanto dentro de la práctica habitual como para fármacos en investigación clínica. Todos los profesionales involucrados en investigación clínica deben conocer esta regulación para seguir garantizando la posición de excelencia que tiene España en investigación clínica a nivel internacional. (AU)

Objective: To review the legal regime for sterile products preparation in the context of clinical trials.Method: A literature review of different rules, guideliness and reports from different organisms has been completed. Furthermore, an analysis of Spanish Clinical Trials Registry (REec) was performed in order to know the trend of what is the type of clinical trials that are being conducted in Spain.Results: at Europe Union there is not a specific regulation about this matter, being a member state responsibiliy to have a local law. In Spain, there is a guideline regarding Good Practices of preparation for drugs on Hospital Pharmacy Services. Spain Clinical Trials Registry analysis indicates that approximately 50% of studies could requiered that those study drugs to be pre-pared on sterile conditions, and on this group, 79% are international studies.Conclusions: Spain has solid regulations on sterile preparation drugs for routine practice and for clinical research drugs. All professionals involved in clinical research should be aware of these regulations in order to maintain Spain’s position of excellence in clinical research at the international level. (AU)

MVA-B como candidato vacunal frente al VIH/SIDA: de la investigación básica a los ensayos clínicos profiláctico y terapéutico / MVA-B as HIV/AIDS vaccine candidate: from basic science to prophylactic and therapeutic clinical trials

El virus vaccinia modificado de Ankara (MVA) ha alcanzado la madurez como sistema de administración de antígenos y como candidato vacunal frente a un amplio espectro de enfermedades infecciosas gracias al conocimiento derivado de las investigaciones sobre la interacción entre el virus y la célula hospedadora, el perfil de expresión génica que estimula, la distribución tras su inoculación y la inmunogenicidad mostrada en ensayos preclínicos y clínicos. En esta revisión, se engloban las principales aportaciones que hemos realizado desde el conocimiento básico de la biología del vector MVA, tanto in vitro como in vivo, en comparación con la cepa atenuada NYVAC, hasta su evaluación como candidato vacunal frente al VIH/SIDA en ensayos clínicos. Detallaremos la generación y caracterización del vector recombinante MVA que expresa los antígenos Env, Gag, Pol y Nef del subtipo B del VIH-1 (denominado MVA-B) y revisaremos los datos preclínicos que respaldaron la evaluación de MVA-B como la primera vacuna profiláctica y terapéutica frente al VIH-1 ensayada en humanos en España. Además, valoraremos los resultados de los ensayos clínicos y discutiremos las líneas de investigación en las que estamos trabajando actualmente considerando los últimos avances científicos en el campo de vacunas frente al VIH. (AU)

The highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA) has reached maturity as antigen delivery system and as a vaccine candidate against a broad spectrum of infectious diseases. This has been largely recognized from research on virus–host cell interactions, gene expression profiling, virus distribution and immunological studies in preclinical and clinical trials. This review includes our main contributions from the basic knowledge of the biology of the MVA vector, both in vitro and in vivo, in comparison with the attenuated NYVAC strain, to its evaluation as a vaccine candidate against HIV/AIDS in clinical trials. We will detail the generation and characterization of the recombinant poxvirus vector MVA expressing the HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B) and review the preclinical data that supported the evaluation of MVA-B as the first in human HIV-1 prophylactic and therapeutic vaccine in Spain. In addition, we will assess the results of clinical trials and discuss the research projects we are currently working on considering the latest scientific advances in the HIV vaccine field. (AU)

Comitês de monitoramento para a proteção de participantes de pesquisa / Monitoring committees for research participant protection / Comités de seguimiento para la protección de los participantes en investigación

Resumo O tema segurança tem sido intensamente discutido, mostrando-se cada vez mais relevante na saúde pública e em projetos de pesquisa envolvendo seres humanos. Participantes de estudos clínicos estão sujeitos a riscos, físicos ou não, que impactam em sua integridade, direitos ou autonomia. Este trabalho apresenta e discute a atuação do Comitê de Monitoramento de Dados e de Segurança para a proteção do participante de pesquisa e minimização de riscos em pesquisa clínica. A metodologia consiste em revisão integrativa da literatura, realizada com o propósito de identificar as funções dos comitês e seu papel na proteção dos participantes. Identificou-se que grande parte das publicações analisadas confirmam que os comitês de monitoramento têm como responsabilidade principal a proteção do participante de pesquisa, além da garantia de integridade e credibilidade da pesquisa.

Abstract Of increasingly relevance in public health and research projects involving human beings, the topic of safety has been intensely discussed. Participants in clinical trials are subject to risks, physical or otherwise, that impact their integrity, rights, or autonomy. This study outlines and discusses the performance of the Data and Safety Monitoring Committee for research participant protection and risk minimization in clinical research. An integrative literature review was conducted to identify the committees' duties and role in protecting participants. Most of the analyzed articles confirm that the monitoring committees are mainly responsible for protecting research participants, as well as ensuring research integrity and credibility.

Resumen La seguridad ha sido un tema muy discutido, por lo que muestra su relevancia para la salud pública y los proyectos de investigación que involucran a seres humanos. Los participantes en estudios clínicos están sujetos a riesgos físicos o de otro tipo, que impactarán su integridad, derechos o autonomía. Este texto realiza un debate sobre el desempeño del Comité de Seguimiento de Datos y Seguridad destinado a la protección de los participantes de investigación y la mitigación de los riesgos en investigación clínica. Se realizó una revisión integradora de la literatura, con el propósito de identificar las funciones de los comités y su rol en la protección de los participantes. La mayoría de las publicaciones analizadas confirman que los comités de seguimiento tienen como principal responsabilidad la protección del participante de la investigación, además de garantizar la integridad y credibilidad de la investigación.