What is an "ongoing" clinical trial? An analysis of different sources revealed heterogeneous definitions of when a clinical trial starts and ends: a meta-research study

ABSTRACT BACKGROUND: Although the concept of an "ongoing study" seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of "ongoing clinical trial" across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still "ongoing" during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of "ongoing clinical trials" lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

Longitudinal analyses of composite resin restoration on erosive lesions: effect of dentin treatment with a chitosan nanoformulation containing green tea

Aim To evaluate the influence of the biomodification of erosive lesions with a chitosan nanoformulation containing green tea (NanoCsQ) on the clinical performance of a composite resin. Methods The study was performed in a split-mouth, randomized and double-blinded model with 20 patients with 40 erosive lesions. The patient's teeth were randomized into two groups (n=20) according to the surface treatment: 1) Without biomodification (control), and 2) Biomodification with NanoCsQ solution (experimental). The lesions were restored with adhesive (Tetric N-bond, Ivoclar) and composite resin (IPS Empress Direct, Ivoclar). The restorations were polished and 7 days (baseline), 6 months, and 12 months later were evaluated according to the United States Public Health Service (USPHS) modified criteria, using clinical exam and photographics. Data were analyzed by Friedman's and Wilcoxon signed-rank tests. Results No significant differences were found between the control and experimental groups (p=0.423), and also among the follow-up periods (baseline, six months, and 12 months) (p=0.50). Regarding the retention criteria, 90% of the restoration had an alpha score in the control group. Only 10% of the restorations without biomodification (control) had a score charlie at the 12-month follow-up. None of the patients reported post-operatory sensitivity. Conclusion The NanoCsQ solution did not negatively affect the performance of the composite resin restorations after 12 months.

Can remote assistance for robotic surgery improve surgical performance in simulation training? A prospective clinical trial of urology residents using a simulator in south america

ABSTRACT Introduction: We aimed to evaluate the role of remote proctoring during the initial training phases of a robotics curriculum using surgical robot skills simulator exercises. Materials and Methods: Prospective randomized study comprising 36 urology residents and junior staff urologists without previous robotic training. Group 1 (G1) performed exercises without any assistance or support, group 2 (G2) received support from in-person proctor, and group 3 (G3) from a remote proctor through a telementoring system. Qualitative and quantitative analyses were conducted for each exercise and group. Results: The overall score approval rates (OSA) for the different skill exercises were Ring Walk 2 (RW2) 83%, Energy Dissection 2 (ED2) 81%, and Ring Walk 3 (RW3) 14%. RW2 OSA was higher on attempt 3 than on attempt 1 (83.3% vs. 63.9%, p=0.032). ED2 OSA rate was higher in attempt 3 than in attempt 1 (80.6% vs. 52.8%, p=0.002). RW2 OSA was similar among the groups. In ED2, both remote and live assistance were significantly related to upper OSA (G1=47.2%, G2=75.0%, G3=83.3%, p=0.002). RW3 had similar OSA among the groups, which can be explained by the high level of difficulty and low OSA in all the groups. However, in a sensitive quantitative analysis, the mean overall score of the participants in RW3 was higher in both proctored groups (G1=24, G2=57.5, G3=51.5, p=0.042). Conclusion: Robotic performance increased significantly over three attempts for simulation exercises of low, medium, but not high-complexity. Proctoring, either in-person or remotely, has a positive impact on approval performance, particularly in intermediate tasks.

Efectividad de Cucurbita pepo en el tratamiento de la hiperplasia prostática. Revisión sistemática y meta-análisis / Effectiveness of Cucurbita pepo in the prostatic hyperplasia treatment. Systematic review and meta-analysis

RESUMEN Fundamento: La hiperplasia prostática benigna es el tumor benigno más frecuente en hombres. El aceite extraído de la semilla de calabaza (Curcubita pepo) se emplea en el tratamiento de los síntomas asociados a dicha enfermedad. Sin embargo, los estudios en humanos son escasos, y la evidencia disponible, insuficiente. Objetivos: determinar la efectividad de la semilla de calabaza en el tratamiento de la hiperplasia prostática benigna realizar revisión sistemática y meta-análisis. Métodos: se realizó revisión sistemática y meta-análisis, de la literatura existente en las bases de datos Pubmed/Medline, Ebsco, Scopus y Scielo. Fueron seleccionados los ensayos clínicos aleatorizados, en cualquier idioma, que evaluaron la efectividad de fitomedicamentos compuestos por la Cucurbita pepo, comparándolo con un placebo; en pacientes con diagnóstico de hiperplasia prostática comprobado; y con un tiempo de evaluación mayor a seis meses. Resultados: la población total estudiada en los estudios seleccionados fue de 1403 hombres, todos mayores de 50 años. Todos los estudios evaluaron la efectividad del aceite de la semilla de calabaza. La diferencia de medias global fue significativa (DM: -0,76 IC 95%: -1,40; -0,13; I 2 =26,75 %). No se encontró una mejoría significativa en cuanto a la calidad de vida, parámetros uroflujométricos, volumen residual, valores del antígeno prostático de superficie y el tamaño de la próstata. Conclusión: Los resultados mostraron, con un nivel de evidencia moderado, que los fitomedicamentos basados en la semilla de calabaza o su extracto no se asoció con una mejoría clínica ni funcional de la hiperplasia prostática benigna.

ABSTRACT Background: Benign prostatic hyperplasia is the most common benign tumor in men. The oil extracted from the pumpkin seed (Curcubita pepo) is used to treat the symptoms associated with this disease. However, human studies are few, and insufficient available evidence. Objectives: to determine the effectiveness of pumpkin seed in the treatment of benign prostatic hyperplasia. To carry out a systematic review and meta-analysis on it. Methods: a systematic review and meta-analysis of the existing literature in the Pubmed / Medline, Ebsco, Scopus and Scielo databases were carried out. Randomized clinical trials were selected, in any language that evaluated the effectiveness of phytomedicines composed of Cucurbita pepo, comparing it with a placebo; in patients with a proven diagnosis of prostatic hyperplasia; and with an evaluation time greater than six months. Results: the total population in the selected studies was 1403 men, all over 50 years of age. All studies evaluated the effectiveness of pumpkin seed oil. The global mean difference was significant (MD: -0.76 95% CI: -1.40, -0.13, I2 = 26.75%). No significant improvement was found in terms of quality of life, uroflowmetric parameters, residual volume, prostate surface antigen values, and prostate size. Conclusion: The results showed, with a moderate level of evidence, that phytomedicines based on pumpkin seed or its extract were not associated with a clinical or functional improvement of benign prostatic hyperplasia.

La regulación de los ensayos clínicos para la COVID-19 en el Perú / The regulation of COVID-19 clinical trials in Peru

RESUMEN La COVID-19 ha afectado la conducción de los ensayos clínicos a nivel mundial. Iniciada la emergencia sanitaria en Perú, el gobierno nacional tomó medidas para promover y garantizar la realización de los ensayos clínicos en COVID-19. Se conformó un comité de ética nacional exclusivo para ensayos clínicos COVID-19 y se implementó una regulación para asegurar la realización ética y oportuna de ensayos clínicos. Hasta el 31 de diciembre del 2020, el Instituto Nacional de Salud autorizó 29 ensayos clínicos, de los cuales cinco evalúan vacunas. El tiempo promedio y desviación estándar de la autorización fue 19,3 y 10,5 días, respectivamente. El 58,6% (n= 17) fueron ensayos clínicos fase II y el 34,5% (n= 10) fueron fase III; el 31,0% (n= 9) tuvo como patrocinador a una institución peruana. La finalidad de las acciones implementadas fue promover la investigación para la COVID-19, respondiendo a las necesidades y tiempos de la emergencia sanitaria, sin afectar la protección de los participantes ni la rigurosidad de los estudios.

ABSTRACT COVID-19 has affected the conduct of clinical trials worldwide. Once the health emergency began in Peru, the national government took measures to guarantee the conduct of COVID-19 clinical trials. A national research ethics committee was exclusively established for COVID-19 clinical trials; and a regulatory framework was implemented to ensure the ethical and timely conduct of these studies. To december 31, 2020, the Peruvian National Health Institute authorized 29 clinical trials, of which 4 test vaccines. The mean and standard deviation of time authorization were 19.3 and 10.5 days, respectively. 58.6% (n= 17) were phase II clinical trials and 34.5% (n= 10) were phase III; 31.0% (n= 9) were sponsored by a Peruvian institution. The aim of the actions implemented was to promote COVID-19 research while responding to the health emergency needs without affecting the protection of participants or the rigor of the studies.

La regulación de los ensayos clínicos para la COVID-19 en el Perú / The regulation of COVID-19 clinical trials in Peru

RESUMEN La COVID-19 ha afectado la conducción de los ensayos clínicos a nivel mundial. Iniciada la emergencia sanitaria en Perú, el gobierno nacional tomó medidas para promover y garantizar la realización de los ensayos clínicos en COVID-19. Se conformó un comité de ética nacional exclusivo para ensayos clínicos COVID-19 y se implementó una regulación para asegurar la realización ética y oportuna de ensayos clínicos. Hasta el 31 de diciembre del 2020, el Instituto Nacional de Salud autorizó 29 ensayos clínicos, de los cuales cinco evalúan vacunas. El tiempo promedio y desviación estándar de la autorización fue 19,3 y 10,5 días, respectivamente. El 58,6% (n= 17) fueron ensayos clínicos fase II y el 34,5% (n= 10) fueron fase III; el 31,0% (n= 9) tuvo como patrocinador a una institución peruana. La finalidad de las acciones implementadas fue promover la investigación para la COVID-19, respondiendo a las necesidades y tiempos de la emergencia sanitaria, sin afectar la protección de los participantes ni la rigurosidad de los estudios.

ABSTRACT COVID-19 has affected the conduct of clinical trials worldwide. Once the health emergency began in Peru, the national government took measures to guarantee the conduct of COVID-19 clinical trials. A national research ethics committee was exclusively established for COVID-19 clinical trials; and a regulatory framework was implemented to ensure the ethical and timely conduct of these studies. To december 31, 2020, the Peruvian National Health Institute authorized 29 clinical trials, of which 4 test vaccines. The mean and standard deviation of time authorization were 19.3 and 10.5 days, respectively. 58.6% (n= 17) were phase II clinical trials and 34.5% (n= 10) were phase III; 31.0% (n= 9) were sponsored by a Peruvian institution. The aim of the actions implemented was to promote COVID-19 research while responding to the health emergency needs without affecting the protection of participants or the rigor of the studies.

Perfil e vozes dos participantes de pesquisas clínicas no Brasil / Profiles and voices of participants in clinical research in Brazil / Perfil y voces de los participantes de investigaciones clínicas en Brasil

Resumo Este estudo de caso buscou traçar o perfil socioeconômico de participantes de ensaios clínicos em centro de pesquisa brasileiro, analisando suas decisões, motivações e experiências, seu conhecimento sobre riscos, benefícios e cuidados dispensados e o processo de consentimento. Dados de 327 participantes foram coletados, realizando-se entrevistas semiestruturadas com 19 deles. Nas pesquisas executadas no centro estudado houve maior participação de homens, de pessoas com poucos anos de estudo formal e de baixa renda. A maioria é aposentada, não tem assistência privada à saúde e tende a não perceber os efeitos da investigação ou superestimar os benefícios médicos diretos. A busca pelo tratamento médico foi o principal fator que influenciou suas decisões/participação, e a assinatura do termo de consentimento livre e esclarecido não garantiu a expressão da autonomia. Conclui-se que o perfil e o conteúdo dos discursos dos participantes são sensíveis indicadores de vulnerabilidade e desigualdade social.

Abstract This case study aimed to trace the socioeconomic profile of participants in clinical research at a Brazilian research center, analyzing their decisions, motivations, experiences, knowledge of risks, benefits and health care provided, and the consent process. The data of 327 participants were collected, and semi-structured interviews conducted with 19 of them. In the research carried out at the center studied there was a greater participation of men and of people with few years of formal education and low income. Most are retired and have no private health plan, tend not to notice the effects of the investigation, or to overestimate its direct medical benefits. The search for medical treatment was the main factor influencing their decisions/participation, and signing the informed consent form did not guarantee the expression of autonomy. We concluded that the participants' profile and speeches content are sensitive indicators of vulnerability and social inequality.

Resumen Este estudio de caso trató de esbozar el perfil socioeconómico de participantes de ensayos clínicos en un centro de investigación brasileño, analizando sus decisiones, motivaciones y experiencias, su conocimiento sobre los riesgos, beneficios y cuidados prestados y el proceso de consentimiento. Se recopilaron datos de 327 participantes y se realizaron entrevistas semiestructuradas con 19 de ellos. En las investigaciones realizadas en el centro estudiado hubo una mayor participación de hombres, de personas con pocos años de educación formal y con bajos ingresos. La mayoría es jubilada y no tiene asistencia sanitaria privada, tiende a no percibir los efectos de la investigación o a sobrestimar los beneficios médicos directos. La búsqueda de tratamiento médico fue el factor principal que influyó en sus decisiones/participación, y la firma del término de consentimiento libre e informado no garantizó la expresión de la autonomía. Se concluye que el perfil y el contenido de los discursos de los participantes son sensibles indicadores de vulnerabilidad y desigualdad social.

How can we associate an economic evaluation with a clinical trial?

Abstract Economic evaluations in Dentistry have been increasing in recent years. They are a relevant contribution if an economic issue exists. Knowing if a new intervention is an efficient way of allocating available (and scarce) resources (the concept of opportunity costs), a well-designed economic evaluation may be helpful. One option is to conduct a trial-based economic analysis, which extracts a considerable board of information from a trial. This approach produces a more controlled result since many sources of variations might be reduced. On the other hand, some aspects could not be predicted directly from the trial or even extrapolated. Thus, combining model-based analysis may be an idea. In this paper, we intended to discuss important aspects to be considered by researchers in further economic evaluations. This paper will be systematically divided into sessions related to the study design as time horizon and perspective, health effects, costs, and data analysis. In the end, we expect the reader could be able to plan a trial-based economic evaluation, which should be a careful, meticulous, quite laborious and especially transparent process.

Avaliação da resposta inicial de desenvolvimento de ensaios clínicos para COVID-19 no Brasil / Evaluation of the initial response in clinical trial efforts for COVID-19 in Brazil

RESUMO: Objetivo: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. Métodos: Revisamos o boletim da Comissão Nacional de Ética em Pesquisa - edição especial Coronavírus (CONEP-COVID) (28 de maio de 2020) e as bases International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov e Registro Brasileiro de Ensaios Clínicos (ReBEC) para identificar estudos registrados no Brasil que avaliassem intervenções de tipo de medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. Resultados: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluíam pacientes diagnosticados com teste de laboratório específico (por exemplo, transcrição reversa seguida de reação em cadeia da polimerase - RT-PCR). A maioria desses trabalhos teria poder > 80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos disponíveis na CONEP até maio de 2020 não estavam em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21 de julho de 2020. Conclusão: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com distribuição diferente, tendo número elevado de estudos que avaliam hidroxicloroquina/cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que podem afetar o alcance dos trabalhos.

ABSTRACT: Objective: To describe the methodological characteristics and good research practices of COVID-19 interventional studies developed in Brazil in the first months of the pandemic. Methods: We reviewed the bulletin of the National Research Ethics Committee - Coronavirus Special Edition (Comissão Nacional de Ética em Pesquisa - CONEP-COVID) (May 28, 2020) and the databases of the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC) to identify interventional studies registered in Brazil that assessed drug type, biological therapy, or vaccines. We described their methodological characteristics and calculated their power for different effect magnitudes. Results: A total of 62 studies were included, 55 retrieved from the CONEP website, and 7 from registry databases. The most tested pharmacological interventions in these studies were: chloroquine/hydroxychloroquine, azithromycin, convalescent plasma, tocilizumab, sarilumab, eculizumab, vaccine, corticosteroids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, and lopinavir/ritonavir. Out of 22 protocols published on registry databases until May 2020, 18 (82%) were randomized clinical trials, and 13 (59%) had an appropriate control group. However, 9 (41%) of them were masked, and only 5 (24%) included patients diagnosed with a specific laboratory test (for example, reverse transcription polymerase chain reaction - RT-PCR). Most of these studies had power > 80% only to identify large effect sizes. In the prospective follow-up, 60% of the studies available at CONEP until May 2020 had not been published on any registry platform (ICTRP/ReBEC/ClinicalTrials) by July 21, 2020. Conclusion: The interventions evaluated during the Brazilian research response reflect those of international initiatives, but with a different distribution and a large number of studies assessing hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.

Clinical trials on drug repositioning for COVID-19 treatment / Ensayos clínicos de reposicionamiento de medicamentos para el tratamiento de la COVID-19 / Ensaios clínicos de reposicionamento de medicamentos para o tratamento do COVID-19

ABSTRACT The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants' clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.(AU)

RESUMEN En diciembre de 2019 fue informado a la Organización Mundial de la Salud (OMS) un brote de neumonía por coronavirus en Wuhan, provincia de Hubei, China. Al 12 de marzo de 2020, se habían notificado 125 048 casos y 4 614 muertes. El coronavirus es un virus ARN envuelto del género Betacoronavirus distribuido en aves, seres humanos y otros mamíferos. La OMS ha denominado a la nueva enfermedad por coronavirus COVID-19. Se han puesto en marcha más de 80 ensayos clínicos para evaluar un tratamiento para el coronavirus, que incluyen algunos ensayos de reposicionamiento de medicamentos para la COVID-19. En marzo de 2020 se llevó a cabo una búsqueda de los ensayos clínicos registrados en la base de datos clinicaltrials.gov. Los criterios de elegibilidad para los estudios recuperados fueron tener un número de identificación de la base de datos clinicaltrials.gov; describir el número de participantes y el período del estudio; describir las condiciones clínicas de los participantes; y emplear intervenciones con medicamentos ya estudiados o aprobados para cualquier otra enfermedad en pacientes infectados con el nuevo coronavirus SARS-CoV-2 (2019-nCoV). Es esencial destacar que este artículo solo recoge los ensayos que figuran en la base de datos clinicaltrials. gov. Se identificaron 24 ensayos clínicos relacionados con más de 20 medicamentos, como inmunoglobulina humana, interferones, cloroquina, hidroxicloroquina, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, metilprednisolona, bevacizumab y medicina tradicional china. Aunque el reposicionamiento de medicamentos tiene algunas limitaciones, el reposicionamiento de los ensayos clínicos puede representar una estrategia atractiva porque facilita el descubrimiento de nuevas clases de medicamentos; estos tienen costos más bajos y tardan menos en llegar al mercado; y existen cadenas de suministro farmacéutico que apoyan la formulación y la distribución.(AU)

RESUMO A Organização Mundial da Saúde (OMS) foi informada, em dezembro de 2019, sobre um surto de pneumonia por coronavírus em Wuhan, província de Hubei (China). Posteriormente, em 12 de março de 2020, 125 048 casos e 4 614 mortes haviam sido registrados. O coronavírus é um vírus RNA envelopado do gênero Betacoronavírus, distribuído em aves e em humanos e outros mamíferos. A OMS designou a nova doença por coronavírus como COVID-19. Mais de 80 ensaios clínicos foram iniciados para testar tratamentos para o coronavírus, incluindo alguns de reposicionamento de medicamentos para o COVID-19. Assim, em março de 2020 realizou-se uma busca na base de dados clinicaltrials.gov. Os critérios de elegibilidade para os estudos recuperados foram: conter o número identificador da base de dados clinicaltrials.gov; descrever o número de participantes e o período do estudo; descrever as condições clínicas dos participantes; e utilizar intervenções para tratamento de doentes infectados com o novo coronavírus SARS-CoV-2 (2019-nCoV) com medicamentos já estudados ou aprovados para qualquer outra doença. É essencial salientar que este artigo apenas capturou ensaios listados na base de dados clinicaltrials.gov. Foram identificados 24 ensaios clínicos envolvendo mais de 20 medicamentos, tais como imunoglobulina humana, interferons, cloroquina, hidroxicloroquina, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, metilprednisolona, bevacizumabe e medicamentos chineses tradicionais. Embora o reposicionamento de medicamentos tenha algumas limitações, os ensaios clínicos de reposicionamento podem representar uma estratégia atraente, porque facilitam a descoberta de novas classes de medicamentos, têm custos mais baixos, levam menos tempo para chegar ao mercado e se beneficiam de cadeias de fornecimento farmacêutico já existentes para formulação e distribuição.(AU)

Consideraciones acerca del reporte y la evaluación del fallo terapéutico en farmacovigilancia / Considerations regarding the reporting and evaluation of therapeutic failure in pharmacovigilance

Resumen Introducción. Los fallos terapéuticos representan un problema de salud pública. Aunque existe abundante información al respecto, se requiere una revisión crítica de las definiciones existentes. Objetivo. Realizar una revisión crítica del concepto actual de fallo terapéutico, su clasificación y su importancia en farmacovigilancia. Materiales y métodos. Dos revisores independientes realizaron una búsqueda sistemática de las definiciones de fallo terapéutico existentes en la literatura y de los sistemas de clasificación descritos. Con base en esta información, se realizó un análisis crítico y la proposición de una nueva definición consensuada de fallo terapéutico. Resultados. La concepción actual de fallo terapéutico es imperfecta, pues desconoce la disminución del efecto de un medicamento en el uso real en comparación con el periodo de precomercialización, donde la estimación de la eficacia se basa en ensayos clínicos controlados. Aunque la clasificación actual es adecuada, tanto el algoritmo de Vaca-González et al. como las otras herramientas empleadas para evaluar la causalidad en farmacovigilancia dependen de la calidad del reporte. Conclusiones. Es necesario ]perfeccionar las definiciones actuales de fallo terapéutico y mejorar la calidad del reporte para sacar el máximo provecho de los sistemas de clasificación. Se propone realizar estudios clínicos pragmáticos para los medicamentos comercializados recientemente con el fin de establecer su verdadero perfil de efectividad y seguridad.

Abstract Introduction: Therapeutic failure is a public health problem. Although there is abundant theory, a critical review of existing definitions is required. Objective: To critically review the current concept of therapeutic failure, its classification and importance in pharmacovigilance. Materials and methods: Two independent reviewers conducted a systematic search of the existing definitions of treatment failure, as well as the classification systems described in the relevant literature. Based on this information, a critical analysis was carried out and a new consensual definition of therapeutic failure was proposed. Results: The current understanding of therapeutic failure is defective as it does not consider the decrease in drug effect in real life use compared to the premarketing period, where the estimate of efficacy is based on controlled clinical trials. Although the current classification is adequate, both the algorithm of Vaca-González et al. and other tools used to assess pharmacovigilance causality depend on the quality of the report. Conclusions: It is necessary to improve the current definitions of therapeutic failure, as well as the quality of the reports to take full advantage of the classification systems. Pragmatic clinical studies for newly marketed drugs are proposed in order to establish their true effectiveness and safety profile.

Comparison of effectiveness between a conventional catheter and a manual commercial catheter: randomized trial of simulation of intraosseous access in a biological model / Comparación de la eficacia entre un catéter convencional y un catéter comercial manual: ensayo aleatorizado de simulación de acceso intraóseo en modelo biológico

Abstract Introduction: In the emergency services an action of paramount importance in critically ill patients is to obtain an early vascular access. When vascular access is not established, an intraosseous route should be obtained; otherwise, the mortality of these critically ill patients is almost 100%. In Colombia, the intraosseous access is not used because of the high costs of the devices and the lack of training of the healthcare staff to conduct the procedure. Objective: To determine the efficacy of a low-cost device to establish intraosseous access. Materials and methods: Quantitative approach, experimental design in a simulated environment with chicken tarsus and metatarsus. An analysis was conducted using frequency tables and central tendency measurements. Likewise, further analyses were done using Fisher's exact test, Chi2, and Mann-Whitney test. Results: A total of 99% of the procedures were successful with both catheters. The average time for intraosseous access was 6.6 seconds with Insyte 14 catheter and 4.7 seconds with Din 1515x Illinois Desch device (P = 0.001). There were no significant differences in the number of attempts to secure a successful intra-osseous access using any of the 2 devices (P = 0.56). Conclusion: There was no significant difference between the Ci 14 and the Si 14 catheter to establish a successful intraosseous access in the chicken tarsus and metatarsus in a simulated environment.

Resumen Introducción: En los servicios de urgencias una acción de primordial importancia en pacientes críticamente enfermos es obtener un acceso vascular temprano. En los casos en que no se logre obtener un acceso venoso, se debe obtener una vía intraósea, o de lo contrario la mortalidad de estos pacientes críticamente enfermos asciende casi al 100%. En Colombia no se realiza el uso del acceso intraóseo por los altos costos de los dispositivos requeridos y la falta de entrenamiento del personal de salud para dicho procedimiento. Objetivo: Determinar la eficacia de un dispositivo de bajo costo para el acceso intraóseo. Materiales y métodos: Enfoque cuantitativo, diseño experimental en ambiente simulado con tarso-metatarso de pollo. Se realizó un análisis mediante tablas de frecuencia y medidas de tendencia central. Así mismo, se realizaron análisis mediante el test exacto de Fisher, ji cuadrado y test de Mann Whitney. Resultados: El 99% de los procedimientos fueron exitosos con los dos catéteres. La mediana del tiempo para el acceso intraóseo fue de 6.6 segundos con el catéter Insyte 14® y de 4.7 segundos con el dispositivo Din 1515x Illinois Desch® (p=0.001). No se encontraron diferencias significativas en el número de intentos para lograr un acceso intraóseo exitoso con ambos dispositivos (p = 0.56). Conclusiones: No existe diferencia significativa entre el catéter Ci 14 y el Di 15 para lograr un acceso intraóseo exitoso en el tarso metatarso del pollo en un ambiente simulado.

La Cátedra Multidisciplinaria de Ensayos Clínicos a diez años de su creación en Villa Clara / The Multidisciplinary professorship of Clinical Trials ten years after its creation in Villa Clara

RESUMEN Fundamento: la Cátedra Multidisciplinaria de Ensayos Clínicos fue creada en la Universidad de Ciencias Médicas de Villa Clara en el año 2007 como una necesidad para garantizar mayor calidad en la actividad de los ensayos clínicos en la provincia. Objetivo: describir la labor desarrollada por la cátedra en sus diez años de trabajo ininterrumpido. Métodos: se realizó una investigación descriptiva retrospectiva en el año 2017. Se emplearon métodos teóricos: análisis-síntesis, inducción-deducción y el histórico-lógico; empíricos: la revisión documental, informes de los frentes emitidos cada año, expedientes e informes sobre los cursos impartidos, los balances anuales, la proyección de la cátedra hacia el pregrado y la atención primaria de salud, y se realizaron entrevistas a docentes y directivos de la Universidad de Ciencias Médicas de Villa Clara. Resultados: se impartieron cursos de posgrado y entrenamientos en los diversos perfiles relacionados con la actividad, se presentaron trabajos científicos y se defendieron tesis de maestrías y especialidades médicas. En el pregrado se ofrecieron cursos electivos y conferencias en fórums estudiantiles, se tutoraron investigaciones y trabajos de diploma y se apoyó la docencia de Farmacología. Se capacitaron más de mil profesionales en correspondencia con la extensión de la actividad en Villa Clara. Conclusiones: la cátedra ha desarrollado una labor ininterrumpida en las esferas de capacitación e investigación científica, con mayor presencia en el posgrado para propiciar la calidad en los ensayos clínicos.

ABSTRACT Background: the Multidisciplinary professorship of Clinical Trials was created in Villa Clara University of Medical Sciences in 2007 as a need to guarantee higher quality in the activity of clinical trials in the province. Objective: to describe the work developed by the professorship in its ten years of uninterrupted work. Methods: a retrospective descriptive research was carried out from 2007 to 2017. Theoretical methods were used: analysis-synthesis, induction-deduction and historical-logical; empirical ones: the documentary review, reports of the areas issued each year, dossiers and reports on the courses taught, the annual balances, the projection of the professorship to undergraduate and primary health care, and interviews were held with teachers and executives of Villa Clara University of Medical Sciences. Results: postgraduate courses and training sessions were given in the different profiles related to the activity, scientific papers were presented and masters and medical specialties theses were defended. In the undergraduate program, elective courses and lectures were offered in student forums, research and diploma work were taught and pharmacology teaching was supported. More than one thousand professionals were trained in correspondence with the extension of the activity in Villa Clara. Conclusions: the professorship has developed an uninterrupted work in the areas of training and scientific research, with a greater presence in the postgraduate course to promote quality in clinical trials.

Discussions on real-world acupuncture treatments for chronic low-back pain in older adults / 中西医结合学报

Chronic low-back pain (CLBP) is one of the most common pain conditions. Current clinical guidelines for low-back pain recommend acupuncture for CLBP. However, there are very few high-quality acupuncture studies on CLBP in older adults. Clinical acupuncture experts in the American Traditional Chinese Medicine Association (ATCMA) were interested in the recent grant on CLBP research announced by the National Center for Complementary and Integrative Health. The ATCMA experts held an online discussion on the subject of real-world acupuncture treatments for CLBP in older adults. Seven participants, each with more than 20 years of acupuncture practice, discussed their own unique clinical experience while another participant talked about the potential mechanism of acupuncture in pain management. As a result of the discussion, a picture of a similar treatment strategy emerged across the participants for CLBP in older adults. This discussion shows that acupuncture may have complicated mechanisms in pain management, yet it is effective for the treatment of chronic pain involving maladaptive neuroplasticity; therefore, it should be effective for CLBP in older adults.

Can implant surfaces affect implant stability during osseointegration? A randomized clinical trial

Abstract This randomized clinical trial evaluated the insertion torque (IT), primary, and secondary stability of dental implants with different surface treatments during the osseointegration period. Nineteen patients with bilateral partial edentulism in the posterior mandibular region were randomly allocated to two implant brand groups and received implants with different surface treatments in the opposite site of the arch: Osseotite and Nanotite or SLA and SLActive. During implant placement, the maximum IT was recorded using a surgical motor equipped with a graphical user interface. The implant stability quotient (ISQ) was assessed immediately after the IT, and was measured weekly via resonance frequency analysis during 3 months. The data were analyzed by a one-way ANOVA, the Bonferroni test, paired t tests and Pearson's correlation coefficient. The IT values were similar (p > 0.05) for all implant types ranging from 43.82 ± 6.50 to 46.84 ± 5.06. All implant types behaved similarly until the 28th day (p > 0.05). Between 35 and 56 days, Osseotite and SLActive showed lower ISQ values (p < 0.001) compared to Nanotite and SLA implants. After 56 days, only Osseotite maintained significantly lower ISQ values than the other implants (p < 0.05). After 91 days the ISQ values were significantly higher than the baseline for all four implant types (p < 0.001). The ISQ and IT values were significantly correlated at the baseline and at the final evaluation for Osseotite, Nanotite, and SLActive implants (p < 0.001). After 91 days, ISQ and IT values were only significantly correlated for the Osseotite implants (p < 0.05). All implants types exhibited acceptable primary and secondary stability.

Moderate to severe psoriasis treatment challenges through the era of biological drugs

Abstract: Biological therapy has revolutionized moderate to severe psoriasis treatment. However, despite being more effective than conventional systemic treatments, some patients do not respond or lose response to biotechnological treatments or develop drug-antibodies, interfering with its safety and efficacy. There are also clinical forms of the disease and patient profiles for which is pending further scientific evidence for more sustained therapeutic interventions. The continuous and more detailed knowledge of psoriasis pathophysiology has allowed identifying new therapeutic targets, which is expected to help overcome the challenges of individualized psoriasis treatment.

Declaración de la Academia Chilena de Medicina sobre el Título V de la Ley 20. 850 (Ley Ricarte Soto) y su proyecto de reglamento "De los ensayos clínicos de productos farmacéuticos y elementos de uso médico" / Declaration of the Chilean Academy of Medicine of Law 20. 850 "On clinical trials of pharmaceutical products and medical devices" and of the bylaw that will regulate its application

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1) The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2) The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3) Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians’ interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients’ ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.

En Chile los tratamientos de alto costo requeridos por seleccionadas condiciones médicas son financiados por el Estado, de acuerdo a la Ley 20.85, que se hizo efectiva en noviembre de 2015. Un reglamento de esta ley -actualmente en discusión por el Senado- incluye la regulación de los ensayos clínicos y plantea importantes aspectos que van a poner en riesgo la realización de investigaciones clínicas avanzadas: 1) El control exclusivo y mandatorio otorgado al Instituto de Salud Pública durante todas las etapas de los ensayos y la vigilancia de las instituciones que los realizan, que sobrepasa las atribuciones de los Comités de Ética Científica Institucionales; 2) El período de hasta 10 años después de la aparición de cualquier efecto adverso, durante el cual se asume causado por el medicamento o dispositivo evaluado en el ensayo, mientras no se demuestre lo contrario en un proceso judicial; 3) Los participantes de los estudios tienen derecho a continuar con el tratamiento recibido durante el estudio una vez terminado este, financiado por las entidades que patrocinan los estudios y mientras el fármaco o dispositivo se consideren útil. Estamos de acuerdo con la necesidad de contar con un Registro Nacional de Ensayos Clínicos. Sin embargo, predecimos que los aspectos críticos del reglamento causarán dificultades y procesos judiciales innecesarios, lo que limitará el interés de los clínicos en realizar investigación. Proponemos que el reglamento debe modificarse a fin de excluir responsabilidades sobre eventos asociados con la evolución natural de la condición clínica, el envejecimiento del paciente, comorbilidades y eventos clínicos no predecibles cuando se aceptó el estudio. Recomendamos que el acceso gratuito posterior al estudio debe constituir una decisión conjunta del paciente y su médico tratante, considerando los riesgos y la carga a que se expuso el paciente, o al riesgo vital secundario a la suspensión del tratamiento del estudio mientras no esté disponible en el mercado nacional.