Comparison of the predictive value of the Helsinki, Rotterdam, and Stockholm CT scores in predicting 6-month outcomes in patients with blunt traumatic brain injuries / 中华创伤杂志(英文版)

PURPOSE@#Despite advances in modern medicine, traumatic brain injuries (TBIs) are still a major medical problem. Early diagnosis of TBI is crucial for clinical decision-making and prognosis. This study aims to compare the predictive value of Helsinki, Rotterdam, and Stockholm CT scores in predicting the 6-month outcomes in blunt TBI patients.@*METHODS@#This cohort study was conducted on blunt TBI patients of 15 years or older. All of them were admitted to the surgical emergency department of Shahid Beheshti Hospital in Kashan, Iran from 2020 to 2021 and had abnormal trauma-related findings on brain CT images. The patients' demographic data such as age, gender, history of comorbid conditions, mechanism of trauma, Glasgow coma scale, CT images, length of hospital stay, and surgical procedures were recorded. The Helsinki, Rotterdam, and Stockholm CT scores were simultaneously determined according to the existing guidelines. The included patients' 6-month outcome was determined using the Glasgow outcome scale extended. M Data were analyzed by SPSS software version 16.0. Sensitivity, specificity, negative/positive predictive value and the area under the receiver operating characteristic curve were calculated for each test. The Kappa agreement coefficient and Kuder Richardson-20 were used to compare the scoring systems.@*RESULTS@#Altogether 171 TBI patients met the inclusion and exclusion criteria, with the mean age of (44.9 ± 20.2) years. Most patients were male (80.7%), had traffic related injuries (83.1%) and mild TBIs (64.3%). Patients with lower Glasgow coma scale had higher Helsinki, Rotterdam, and Stockholm CT scores and lower Glasgow outcome scale extended scores. Among all the scoring systems, the Helsinki and Stockholm scores showed the highest agreement in predicting patients' outcomes (kappa = 0.657, p < 0.001). The Rotterdam scoring system had the highest sensitivity (90.1%) in predicting death of TBI patients, whereas the Helsinki scoring system had the highest sensitivity (89.8%) in predicting the 6-month outcome in TBI patients.@*CONCLUSION@#The Rotterdam scoring system was superior in predicting death in TBI patients, whereas the Helsinki scoring system was more sensitive in predicting the 6-month outcome.

Academic Exchange at WFAS Turkey 2019 and Review of RCTs Conducted in China / 全日本鍼灸学会雑誌

The WFAS Annual Conference 2019 was held between November 14th and 17th at Kaya Palazzo Hotel, Antalya, Turkey. The WFAS executive committee was convened on the 14th. In the EC (Executive Committee) meeting, the JSAM proposed inclusion of the Declaration of Helsinki (DoH) in the WFAS Code of Ethics. Other issues discussed in the EC meeting included approval of the special consultative status by the the United Nations ECOSOC (Economic and Social Council) and preparation of the next WFAS symposium in the Netherlands in 2020. Individual presentations and other exhibitions in the symposium are also introduced in the present report. In addition, recent large-scale RCTs of acupuncture conducted in China were reviewed.

Value of Helsinki computerized tomography scoring system in prognostic evaluation of patients with traumatic brain injury / 中华创伤杂志

Objective@#To investigate the clinical practicability and prognostic value of Helsinki CT score in patients with traumatic brain injury (TBI).@*Methods@#A retrospective case series study was conducted to analyze the clinical data of 124 TBI patients admitted to First Affiliated Hospital of Xinjiang Medical University from September 2016 to October 2018. There were 91 males and 33 females, aged 14-84 years, with an average age of 49 years. Glasgow coma score (GCS) at admission ranged from 3-8 points in 45 patients, 9-12 points in 42 patients, and 13-15 points in 37 patients. According to Glasgow outcome scale (GOS) at 6 months after injury, 26 patients were classified into the poor prognosis group with GOS of 1-3 points and 98 patients were in the good prognosis group with GOS of 4-5 points. The prognosis-related risk factors were analyzed, and the role of Helsinki CT score to predict the adverse prognosis and mortality of TBI patients in the two groups was investigated. The sensitivity and specificity of Helsinki CT Score for 6-month poor prognosis were evaluated by receiver operation characteristic (ROC) curve and area under the curve (AUC).@*Results@#Univariate analysis suggested that there were significant differences in terms of subdural hematoma, intracranial hematoma, extradural hematoma, hematoma volume >25 cm3, intraventricular hemorrhage and suprasellar cistern pressure between the poor prognosis group and good prognosis group (P<0.05). Multivariate logistic regression analysis showed that the mortality and bad prognosis were related to the hemorrhage of ventricles, the pressure of suprasellar cistern and the disappearance of suprasellar cistern in the poor prognosis group and the good prognosis group (P<0.05), while intracranial hematoma and hematoma volume showed no association with mortality and poor prognosis (P>0.05). The Helsinki CT score could independently predict the adverse prognosis and mortality of TBI patients at 6 months (multivariate logistic regression: ORdeath=1.21, ORadverse prognosis=1.14). Helsinki CT score had a better predictive ability of 6-month mortality (AUC=0.85) than that of 6-month adverse prognosis (AUC=0.76), and had a predictive value for 6-month mortality and adverse prognosis.@*Conclusions@#Subdural hematoma, extradural hematoma, intraventricular hemorrhage and suprasellar cistern state (compression or disappearance) are the risk factors for the poor prognosis of TBI patients. Intraventricular hemorrhage and suprasellar cistern state are the main risk factors for predicting the mortality of 6 months. Helsinki CT score can independently predict the adverse prognosis and mortality of TBI patients at 6 months, and has relatively better value in predicting the mortality.

Value of Helsinki computerized tomography scoring system in prognostic evaluation of patients with traumatic brain injury / 中华创伤杂志

Objective To investigate the clinical practicability and prognostic value of Helsinki CT score in patients with traumatic brain injury(TBI).Methods A retrospective case series study was conducted to analyze the clinical data of 124 TBI patients admitted to First Affiliated Hospital of Xinjiang Medical University from September 2016 to October 2018.There were 91 males and 33 females,aged 14-84 years,with an average age of 49 years.Glasgow coma score(GCS)at admission ranged from 3-8 points in 45 patients,9-12 points in 42 patients,and 13-15 points in 37 patients.According to Glasgow outcome scale(GOS)at 6 months after injury,26 patients were classified into the poor prognosis group with GOS of 1-3 points and 98 patients were in the good prognosis group with GOS of 4-5 points.The prognosis-related risk factors were analyzed,and the role of Helsinki CT score to predict the adverse prognosis and mortality of TBI patients in the two groups was investigated.The sensitivity and specificity of Helsinki CT Score for 6-month poor prognosis were evaluated by receiver operation characteristic(ROC)curve and area under the curve(AUC).Results Univariate analysis suggested that there were significant differences in terms of subdural hematoma,intracranial hematoma,extradural hematoma,hematoma volume＞25 cm3,intraventricular hemorrhage and Suprasellar cistern pressure between the poor prognosis group and good prognosis group(P＜0.05).Multivariate logistic regression analysis showed that the mortality and bad prognosis were related to the hemorrhage of ventricles,the pressure of suprasellar cistern and the disappearance of suprasellar cistern in the poor prognosis group and the good prognosis group(P＜0.05),while intracranial hematoma and hematoma volume showed no association with mortality and poor prognosis(P＞0.05).The Helsinki CT score could independentiy predict the advetse prognosis and mortality of TBI patients at 6 months(multivariate logistic regression: ORdealth=1.21,ORadvene prognosis = 1.14).Helsinki CT score had a better predictive ability of 6-month mortality(AUC = 0.85)than that of 6-month advetse prognosis(AUC = 0.76),and had a predictive value for 6-month mortality and advetse prognosis.Conclusions Subdural hematoma,extradural hematoma,intraventricular hemorrhage and suprasellar cistern state(compression or disappearance)are the risk factots for the poor prognosis of TBI patients.Intraventricular hemorrhage and suprasellar cistern state are the main risk factots for predicting the mortality of 6 months.Helsinki CT score can independently predict the advetse prognosis and mortality of TBI patients at 6 months,and has relatively better value in predicting the mortality.

Value of optic nerve sheath diameter in early assessment of patients with traumatic brain injury / 中华急诊医学杂志

Objective To analyze the relationship between the optic nerve sheath diameter (ONSD) and the scoring of Glasgow Coma Scale(GCS)or CT score(Rotterdam CT score or Helsinki CT score).Methods Sixty-three adult patients with traumatic brain injury in our emergency room were enrolled.All the patients were presented with the data of GCS and the classification of cranial CT,as well as ONSD measured by ultrasound.The correlation between ONSD and classification of cranial CT scores or GCS was analyzed by Spearman correlation analysis.Patients were divided into mild group,moderate group and severe group based on GCS or CT scores.One-way Analysis of Variance (ANOVA) was used to discover the difference in mean ONSD among different groups on account of scoring of GCS or cranial CT scores.The intergroup comparisons were analyzed by the least-significant-difference (LSD) tests.Results ONSD measurements were strongly correlated with GCS(r=-0.540,P＜0.01)or classification of Rotterdam CT scores (r=0.654,P＜0.01) and Helsinki CT scores (r=0.663,P＜0.01).The mean ONSD of the mild,moderate and severe group were (3.89±0.70)mm,(4.50±0.65)mm and (4.81±0.72) mm,respectively.The mean ONSD of the mild group was significantly shorter than that of severe group (P＜0.01) and moderate group(P＜0.05).The same results were found when comparing mean ONSDs among different groups classified by Rotterdam CT scores (low group (3.74±0.64)mm vs.middle group (4.3 l±0.73)mm vs.high group (5.09±0.57)mm,P＜0.01 or P＜0.05) or classified by Helsinki CT scores (low group (3.54±0.61)mm vs.middle group (4.46±0.73)mm vs.high group (5.16±0.37)mm,P＜0.01.Conclusions Ultrasonography used to measure ONSD is significantly correlated with both GCS and classification of head CT including Rotterdam CT score and Helsinki CT score.The results indicate that ultrasonography measurement of ONSD is helpful for early bedside assessment in patients with traumatic brain injury.

Declaración de Helsinki: cambios y exégesis / Helsinki Declaration: changes and interpretation

La Declaración de Helsinki es muy citada de en el ámbito de las ciencias médicas y de la salud. En Cuba se utiliza para valorar los aspectos éticos de las investigaciones, sin embargo es escasa la literatura dedicada a la valoración crítica de la misma. Referir sus versiones presupone conocer su devenir histórico para interpretar sus aciertos y limitaciones. La intención del estudio es contribuir a actualizar los conocimientos de los profesionales de la salud sobre la Declaración de Helsinki. Se realizó revisión de la literatura publicada entre 2008 y 2014 (agosto) en las bases de datos bibliográficos Cumed, Lilacs, SciELO PubMed, MedLine, Clinical Key, Cochrane y el motor de búsqueda Google utilizando vocabulario controlado con los siguientes descriptores: Declaración de Helsinki, placebo, ensayo clínico, ética y bioética. Los temas más polémicos fueron: uso del placebo, doble estándar en las investigaciones clínicas y garantía de continuidad de tratamiento a los pacientes participantes. Se destacaron méritos en la versión de 2013 tales como la insistencia para aumentar la transparencia en la investigación, su nuevo diseño estructural y la consideración de la competencia ética como un requisito para los investigadores. Los comentarios sobre la Declaración de Helsinki oscilan desde el elogio hasta la sugerencia de su desaparición o sustitución. La polémica sobre la misma es considerada necesaria por algunos autores pero también estéril por otros. Los problemas más álgidos tratados en las últimas versiones emanan del enfrentamiento entre los intereses de la industria farmacéutica y los derechos de los participantes en las investigaciones(AU)

In the fields of medical and health sciences, the Helsinki Declaration is quoted very often. The Helsinki Declaration is used to evaluate the ethical aspects of research studies; however, literature devoted to critical assessment of those studies is scanty. Making reference to the declaration versions presupposes the knowledge about its historical development in order to construe its good things and limitations. The intention of this study is to help to update the health professionals' knowledge about the Helsinki Declaration. A literature review published between 2008 and August 2014 was made and collected on the following databases: Cumed, Lilacs, SciELO PubMed, MedLine, Clinical Key, Cochrane and Google, using controlled vocabulary with the f subject headings Helsinki Declaration, placebo, clinical trial, ethics and bioethics. The most controversial topics were the use of placebo, application of the double standard possition in clinical research, and guaranteed continuous treatment for the participating patients. The following 2013 version's merits were highlighted: insistence on the research transparency its new structural design, and the concern for ethical competence as a requirement for researchers. Comments about the Helsinki Declaration range from praise to disappearance or replacement suggestions. Some authors deem the controversy necessary but others think it is a wasteful argument. The hottest problems in the most recent versions come from the confrontation between the pharmaceutical industry interests and the rights of participants in research studies(AU)

El uso de placebo en ensayos clínicos de fase III en Brasil / The use of placebos in phase III clinical trials in Brazil

El Consejo Federal de Medicina de Brasil (CFM) -órgano normativo y fiscalizador del ejercicio ético de la medicina- prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase III en Brasil, se analizaron varias características de sus registros en el ClinicalTrials.gov, en los períodos de 2003 a 2007 y de 2009 a 2013. Se concluye que: a) la normativa promulgada por el CFM en 2008 fue ineficaz y prevaleció la posición adoptada por la Declaración de Helsinki; b) el patrocinio de ensayos con placebo por parte de la industria farmacéutica multinacional fue significativo; c) predominaron las investigaciones de fármacos para enfermedades crónicas, y fueron poco significativas para las enfermedades postergadas, de importancia para Brasil.

In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina] (CFM) - regulatory and supervisory agency on the ethical practice of medicine - banned the participation of Brazilian doctors in studies using placebos for diseases with efficient and effective treatment. This position differs with the Helsinki Declaration, which allows the use of placebos in methodologically justified conditions. To ascertain whether the CMF's ethical regulation modified the use of placebos in phase III clinical trials in Brazil, characteristics of the records in ClinicalTrials.gov were researched in the periods from 2003 to 2007 and from 2009 to 2013. The conclusions reached were: a) the regulations issued by the CFM in 2008 were ineffective and the position adopted by the Helsinki Declaration prevails; b) there was significant sponsorship by the multinational pharmaceutical industry of trials with placebos; c) the research was predominantly on new drugs for chronic diseases, with little study done of the neglected diseases which are of great importance to Brazil.

The Revision and Significance of 2013 Declaration of Helsinki / 中国医学伦理学

The new revision of Declaration of Helsinki in 2013 has adjusted the structure, added or deleted some provisions on the content and modification, and modificated on the details of some words.Revision of the new version has improved the architecture, perfected the content of the declaration, strengthened the protection of the subjects, increased demand for researchers, and cleared the duty of country, research institutions and bidders.The enlighten-ment to our country are:constantly revised involving human clinical trials of the relevant laws and regulations , to pro-tect rights and interests of the subjects;National obligations for protection of the subjects, clinical trials explore the establishment of national compensation system;Ethics committee responsibilities and clearly positioning, exploring to establish an independent ethical review body.

Eticidade do uso de placebo em pesquisa clínica: proposta de algoritmos decisórios / Ethics of the use of placebos in clinical research: a proposal for decision-making algorithms

O uso de placebo em pesquisa clínica tem sido motivo de debate nos últimos anos, sobretudo após a Associação Médica Mundial publicar, em 2002, nota de esclarecimento do parágrafo 29 da Declaração de Helsinki. O Brasil tem se destacado por sua posição firme e contrária ao uso flexível de placebo. Tanto o Conselho Federal de Medicina quanto o Conselho Nacional de Saúde editaram resoluções que normatizam seu uso no Brasil, de forma a não admiti-lo em caso da existência de um método terapêutico melhor. O presente artigo reforça essa posição e tem por objetivo descrever as diversas aplicações de placebo em pesquisa clínica, bem como trazer à luz a complexa decisão sobre a eticidade de seu uso. Além disso, os autores propõem uma reflexão acerca da utilização de placebo no âmbito da pesquisa, por meio de algoritmos decisórios baseados nas normativas éticas brasileiras...

The use of placebos in clinical research has been a matter of considerable debate in recent years, notably when the World Medical Association published, in 2002, a note of clarification for paragraph 29 of the Helsinki Declaration. Brazil is known for its strong opposition to the flexible use of placebos. Both the Federal Council of Medicine and the National Health Council have published resolutions regulating the use of placebos in Brazil, preventing their use if there is a more effective therapeutic method already in place. The present study reinforces that position and aims to describe the various uses of placebos in clinical research, as well as examining the complex decisions relating to the ethics of their use. Additionally, the authors propose a reflection on the use of placebos through decision-making algorithms based on Brazilian ethical standards...

El uso del placebo en la investigación clínica ha sido un tema de debate en los últimos años, sobre todo después de que la Asociación Médica Mundial publicara, en 2002, una nota aclaratoria del párrafo 29 de la Declaración de Helsinki. Brasil se ha destacado por su firme posición en contra de la utilización flexible del placebo. Tanto el Consejo Federal de Medicina como el Consejo Nacional de Salud editaron resoluciones que regulan el uso del placebo en Brasil, no admitiéndose su uso cuando existe un mejor método terapéutico. El presente artículo refuerza esa posición y tiene como objetivo describir diferentes usos del placebo en la investigación clínica, así como contribuir en la discusión sobre la ética de su uso. Además, los autores proponen una reflexión sobre el uso del placebo en la investigación a través de algoritmos para la toma de decisiones, los cuales se basan en las normativas éticas de Brasil...

O placebo e a Declaração de Pachuca: letras mortas? / The placebo and the Declaration of Pachuca: dead letters?

A Confederação Médica Latino-Americana e do Caribe, organização que congrega as entidades congêneres dos países da região, atua em defesa da profissão médica e da saúde da população, guiando-se por documentos internacionais. Em sua Assembleia Geral (Pachuca, México; 2013) foi aprovada a Declaração de Pachuca, com severas críticas à revisão da Declaração de Helsinki ocorrida no Brasil e aos ensaios clínicos que usam placebo em doenças com tratamento definido. O tom duro e enérgico dessa Declaração propõe que entidades-membro denunciem os abusos éticos em todos os foros e aos governantes, e que atuem impedindo o uso do placebo nessas condições. Tais recomendações encontram respaldo no movimento mundial sobre integridade e ética na pesquisa. Conclui-se pela importância do papel educativo dos órgãos de fiscalização ética da medicina, alertando-se os médicos que infringirem essa orientação, a qual também integra o Código de Ética Médica, de que estarão sujeitos a processo ético-profissional...

The Latin American and Caribbean Medical Confederation (CONFEMEL), an organization that brings together related organizations from countries of the region, works on behalf of the medical profession and the population's health guided by international documents. During its General Assembly (Pachuca, Mexico; 2013) the Declaration of Pachuca was approved with strong critics regarding the review of the Declaration of Helsinki that occurred in Brazil and the issue of clinical trials that use placebo in diseases with known treatment. The strong and energetic tone of this Declaration proposes that member entities condemn ethical abuses in all forums and also to administrations so that they engage against the use of placebo in these conditions. These recommendations are supported in the global movement on Integrity and Ethics in Research. The conclusion addresses the importance of the educative role of ethical supervision of Medicine warning physicians who violate these guidelines, which are also incorporated in the Code of Medical Ethics, that they will be subjected to ethical-professional process...

La Confederación Médica Latinoamericana y del Caribe (CONFEMEL), una organización que reúne a instituciones similares de los países de la región, actúa en defensa de la profesión médica y salud de la población, guiándose por los documentos internacionales. En su Asamblea General (Pachuca, México; 2013) se aprobó la Declaración de Pachuca con duras críticas a la revisión de la Declaración de Helsinki que tuvo lugar en Brasil y a los ensayos clínicos que utilizan placebo en enfermedades con tratamiento conocido. El tono duro y enérgico de tal Declaración propone que las entidades-miembros a denunciar los abusos éticos en todos los foros y a los gobernantes, y que actúen impidiendo el uso del placebo en estas circunstancias. Estas recomendaciones se apoyan en el movimiento mundial sobre Integridad y ética en la investigación. Se concluye sobre la importancia del papel educativo de los órganos de supervisión ética da medicina, alertando a los médicos que violen esta norma, que también está contemplada en el Código de Ética Médica, que estarán sujetos a proceso ético-profesional...

De Helsinki à Fortaleza: uma declaração dessangrada / De Helsinki a Fortaleza: una Declaración desangrada / From Helsinki to Fortaleza: a bled declaration

La Declaración de Helsinki 1964 ha sido sometida a numerosas revisiones y enmiendas, la más reciente siendo Fortaleza (2013), una frecuencia considerada necesaria dado los avances de la medicina contemporánea, pero también criticada por restarle estabilidad y autoridad al documento. La versión de Edimburgo (2000) enfatizó la tolerancia al uso de placebos y restó apoyo de los beneficios post-estudio para los probandos y la comunidad huésped, pese a los esfuerzos de Argentina y Brasil por robustecer la protección de las personas incorporadas a los estudios. Queda aceptado - de hecho - el doble estándar en la ética de investigación que debilita la Declaración como normativa ética de la investigación con seres humanos. La dominancia acentuada de los intereses corporativos de investigadores y patrocinadores sugiere que la bioética latinoamericana debiera desarrollar su propio documento normativo, en respeto a nuestra realidad social, y enfocado a la protección de las comunidades de la región...

A Declaração de Helsinki de 1964 vem sendo submetida a numerosas revisões e emendas, sendo a mais recente a de Fortaleza (2013). A frequência dessas reformulações tem sido considerada necessária, dados os avanços da medicina contemporânea, mas também criticada por conferir pouca estabilidade e autoridade ao documento. A versão de Edimburgo (2000) marcou a política de tolerância ao uso de placebo e de escasso apoio aos benefícios pós-estudo aos sujeitos e à comunidade, desestimulando os esforços da Argentina e Brasil para reforçar a proteção aos participantes dos estudos. Se aceita assim - de fato - o duplo standart em ética em pesquisa, que de forma progressiva debilita a Declaração como normativa ética para a pesquisa envolvendo seres humanos. A dominação cada vez mais acentuada de interesses corporativos de investigadores e patrocinadores sugere que a bioética latino-americana deve desenvolver seu próprio documento normativo, em respeito a nossa realidade social, voltado a proteção às comunidades da região...

The original Declaration of Helsinki (1964) has been subjected to numerous revisions and reformulations, supposedly necessary to keep apace with medical progress, but in fact leading to its loss of stability and authority. The Edinburgh 2000 revision made provisions for increased tolerance in the use of placebos, and loss of commitment to assure post-investigational benefits to individuals and communities involved. In spite of Argentina's and Brazil's manifest opposition, a double standard for research ethics became a de facto reality which has increasingly weakened the Declaration. Corporative interests of major stakeholders -researchers and sponsors- have been strongly supported as the Declaration becomes less protective of individuals and communities involved. It is therefore suggested that Latin American bioethicists would be well advised to develop a regionally pertinent normative in accordance with our social reality and the need of protecting our population...

Análisis de los principales conflictos éticos entre la Declaración de Helsinki 2008 y su propuesta de cambio / Analysis of the main ethical conflicts in the 2008 declaration of Helsinki and the proposed changes in the new version

The Declaration of Helsinki (DoH) of the World Medical Association is the basis of the rules governing research on human beings. The latest version (enacted in Korea, 2008) has been a source of ethical discussions, particularly regarding the use of placebos, the measures to assure the access of study subjects to interventions identified as beneficial once the study has ended, and the need of a better protection of potentially vulnerable groups. These issues led to draft a revised version, that was approved in 2013. In this paper, we present an ethical analysis of the main changes contained in the DoH, including the proposed changes in the new version, referring, when appropriate, to relevant Chilean laws governing research on human subjects. In our opinion, the 2008 DoH contains significant imprecisions on some of these issues, making a new version of the declaration necessary to fully protect subjects participating in biomedical research, as stated by the new version approved in 2013.

Declaración de Helsinki y sus repetidos "ajustes" - un tema fatigoso..

El texto discute de modo crítico los repetidos ajustes hechos a la Declaración de Helsinki (DH) desde su creación hasta el año 2013, algunas necesarias y otras sin necesidad aparente. A partir del 2008, después de la Asamblea Médica Mundial (AMM) anual realizada en Seúl, Corea, algunas modificaciones sustanciales en la DH empezaron a generar fuertes controversias. El presente estudio analiza especialmente los temas relacionados con el "double standard" de investigaciones y el no-compromiso de los patrocinadores de las investigaciones clínicas con los sujetos de las mismas después de terminado el ensayo, además de tratar sobre el uso excesivo del placebo en el contexto clínico internacional. Trata, además, del concepto de vulnerabilidad social relacionado con la mayoría de los pacientes participantes de estos estudios en los países periféricos. Como la más reciente reunión se llevó a cabo en Brasil, en 2013, el texto termina analizando los problemas que ocurrieron en este país con relación a las fuertes divisiones registradas entre sus dos principales entidades médicas nacionales en el sentido de aprobar (o no) los cambios, además de la posición oficial contraria del gobierno.

This text discusses, critically, the many adjustments made to the Helsinki statement (HS) from its creation to 2013, some of which are necessary and others have no evident usefulness. After 2008, after the World Medical Assembly in Seoul, Korea, some substantial modifications to the HAS started to generate strong controversies. This study analyzes, specially, the topics related to the "double standard" in research and the lack of commitment of the sponsors of the clinical research works with the subjects of the studies once the tests are finished, plus the excessive use of placebos in the international clinical context. It also approaches to the concept of social vulnerability related to most of the patients that participate in these studies in peripheral countries. As the most recent meeting took place in Brazil in 2013, the text finishes with an analysis of the problems that occurred in this country due to the strong divisions registered between its two main medical entities concerning the denial or the approval of the changes and the official position, opposite to that of the government.

O texto discute de modo crítico os repetidos ajustes feitos à Declaração de Helsinki (DH) desde sua criação até o ano 2013, algumas necessárias e outras sem necessidade aparente. A partir do 2008, depois da Assembleia Médica Mundial (AMM) anual realizada em Seul, Coréia, algumas modificações substanciais na DH começaram a gerar fortes controvérsias. O presente estudo analisa especialmente os temas relacionados com o "double standard" de investigações e o não-compromisso dos patrocinadores das investigações clínicas com os sujeitos das mesmas depois de findo o ensaio, além de tratar sobre o uso excessivo do placebo no contexto clínico internacional. Trata, ademais, do conceito de vulnerabilidade social relacionado com a maioria dos pacientes participantes destes estudos nos países periféricos. Como a mais recente reunião se levou a cabo no Brasil, em 2013, o texto termina analisando os problemas que ocorreram neste país com relação às fortes divisões registradas entre suas dois principais entidades médicas nacionais no sentido de aprovar (ou não) as mudanças, além da posição oficial contrária do governo.

Off-label use-the problem and challenge in clinical practice in China / 中华实验眼科杂志

Unregistered drug use,also called off-label drug use,has become a universal phenomenon in clinical practice worldwide.At present,there is still no definite laws and regulations in the field of off-label medication in China.The article gives an overview about the current criterion for prescription in China,the definition of off-label use,analysis of this situation and causes,how to regulate this practice to protect the patient's rights and safety,and also doctor's rights of prescription.

Qualidade dos estudos clínicos publicados na RBGO ao longo de uma década (1999-2009): aspectos metodológicos, éticos e procedimentos estatísticos / Quality of clinical studies published in the RBGO over one decade (1999-2009): methodological and ethical aspects and statistical procedures

OBJETIVO: Avaliar a evolução metodológica e do delineamento estatístico nas publicações da Revista Brasileira de Ginecologia e Obstetrícia (RBGO) a partir da resolução 196/96. MÉTODOS: Uma revisão de 133 artigos publicados nos anos de 1999 (65) e 2009 (68) foi realizada por dois revisores independentes com formação em epidemiologia clínica e metodologia da pesquisa científica. Foram incluídos todos os artigos clínicos originais, séries e relatos de casos, sendo excluídos os editoriais, as cartas ao editor, os artigos de revisão sistemática, os trabalhos experimentais, artigos de opinião, além dos resumos de teses e dissertações. Características relacionadas com a qualidade metodológica dos estudos foram analisadas por artigo, por meio de check-list que avaliou dois critérios: aspectos metodológicos e procedimentos estatísticos. Utilizou-se a estatística descritiva e o teste do χ2 para comparação entre os anos. RESULTADOS: Observa-se que houve diferença entre os anos de 1999 e 2009 no tocante ao desenho dos estudos e ao delineamento estatístico, demonstrando maior rigor nos respectivos procedimentos com o uso de testes mais robustos, relativamente, entre os anos de 1999 e 2009. CONCLUSÕES: Na RBGO, observou-se evolução metodológica dos artigos publicados entre os anos de 1999 e 2009 e aprofundamento nas análises estatísticas com o uso de testes mais sofisticados, como o uso mais frequente das análises de regressão e da análise multinível, que são técnicas primordiais na produção do conhecimento e planejamento de intervenções em saúde. Isso pode resultar em menos erros de interpretações.

PURPOSE: To evaluate the methodological and statistical design evolution of the publications in the Brazilian Journal of Gynecology and Obstetrics (RBGO) from resolution 196/96. METHODS: A review of 133 articles published in 1999 (65) and 2009 (68) was performed by two independent reviewers with training in clinical epidemiology and methodology of scientific research. We included all original clinical articles, case and series reports and excluded editorials, letters to the editor, systematic reviews, experimental studies, opinion articles, besides abstracts of theses and dissertations. Characteristics related to the methodological quality of the studies were analyzed in each article using a checklist that evaluated two criteria: methodological aspects and statistical procedures. We used descriptive statistics and the χ2 test for comparison of the two years. RESULTS: There was a difference between 1999 and 2009 regarding the study and statistical design, with more accuracy in the procedures and the use of more robust tests between 1999 and 2009. CONCLUSIONS: In RBGO, we observed an evolution in the methods of published articles and a more in-depth use of the statistical analyses, with more sophisticated tests such as regression and multilevel analyses, which are essential techniques for the knowledge and planning of health interventions, leading to fewer interpretation errors.

Emancipação na luta pela equidade em pesquisas com seres humanos / Emancipation in the struggle for equality in research involving human volunteers

Este artigo apresenta como estudo de caso os aspectos mais controversos de pesquisa conduzida na Guatemala (1946-1948), patrocinada pelo Serviço de Saúde Pública dos Estados Unidos e envolvendo participantes infectados intencionalmente pelo Treponema pallidum. Analisando as alterações de 2008 na Declaração de Helsinque e a ainda pequena adesão a outros instrumentos internacionais, como a Declaração Universal sobre Bioética e Direitos Humanos, da Unesco, a discussão enfatiza a importância da implantação de diretrizes éticas internacionalmente aceitas para impedir que voluntários humanos sejam envolvidos em pesquisas não éticas. Conclui considerando que é indispensável o envolvimento de cientistas e ativistas para alcançar padrões éticos universalmente aceitos e aplicáveis, visando evitar duplo standard. Além disso, que a participação igualitária em pesquisas e distribuição justa de seus benefícios será importante passo para atingir o acesso universal a cuidados de saúde de qualidade para todos.

This manuscript presents as a case study the most controversial aspects of a research conducted in Guatemala(1946-1948), sponsored by the United States Public Health Service in which participants were intentionallyinfected with Treponema pallidum. The analysis of changes in the 2008 Declaration of Helsinki and the stillinsufficient adherence to UNESCO ́s Universal Declaration on Bioethics and Human Rights emphasizes theimportance of applying internationally accepted ethical standards for human volunteers to prevent unethicalresearch. It concludes that the involvement of scientists and activists is crucial to achieve internationally accepted ethical standards to be equally applied throughout the world, avoiding the risks of double standards,and also that egalitarian participation in research and fair distribution of its benefits will be an important steptowards universal access to good quality healthcare for all people.

A nova declaração de Helsinque e o uso de placebo em estudos clínicos no Brasil: a polêmica continua / The new declaration of Helsinki and the use of placebo in brazilian clinical trials: controversy remains

Em 2000, dada a urgência de adequação à realidade científica vigente, iniciativas de revisão dos aspectos polêmicos da Declaração de Helsinque (DoH) à publicação de sua quinta versão na qual ficou estabelecido que o uso do placebo seria aceito apenas quando nenhum tratamento existisse. A Federal Drug Administration nos E.U.A., todavia, continuou a exigir controle-placebo, adotando o Guia de Boas Práticas Clínicas. Também a Agência ReguladoraEuropeia considerou tal proibição arbitrária e, junto a outras entidades, lançaram-se numa campanha contra a DoH. Em 2002 e 2004, Notas de Clarificação publicadas na DoH provocaram grande comoção mundial, culminando na versão de 2008. Apesarda divergência dentre vários grupos, sobretudo, quanto ao uso do placebo, o texto atual assumiu uma posição neutra, flexibilizando sua aplicação. Todavia, uma vez norma ética, a atual DoH fomentou o reinício das discussões sobre a necessidade de um documento mais ampla e uniformemente aceito. Hoje, esta polêmica ainda continua em alguns países, principalmente no Brasil, onde o Conselho Federal de Medicina (CFM) e a Comissão Nacional de Ética em Pesquisa (CONEP) proíbem o uso de placebo em estudos clínicos em território nacional, quando existir qualquer tratamento disponível. Este fato eliciou grande polêmica entre agências regulatórias e pesquisadores brasileiros. Assim, dado que, desde Nuremberg, a garantia do não enfraquecimento das normas de proteção dos sujeitos de pesquisa recrutados mundo afora é razão primordial de ser da DoH, a reabertura de diálogo em níveis nacional einternacional se faz premente perante a nova revisão comemorativa de seus 50 anos em 2014...

In 2000, given the urgency for the ethical guidelines adequacy to the present scientific standards, revision initiatives of the most controversial aspects of the Declaration of Helsinki (DoH). These efforts culminated with the publication of its fifth version stating that the use of placebo was acceptable when proven treatmentdoes not exist. The US Federal Drug Administration, however, continued demanding the placebo control and adopted the Good Clinical Practice Guidelines. The European regulatory agency also considered such prohibition arbitrary and, amongst other entities,started a campaign against the DoH. In 2002 and 2004, Clarification Notes published on the DoH promoted extensive controversy worldwide, concluded at its version of 2008. Despite the divergence amongst many groups, especially on placebo use, the current text assumed a more neutral positioning, flexibilising its application. Being an ethical norm, the current DoH re-started the discussions about thenecessity of a document of uniform worldwide acceptance. Today, the controversy still remains in a few countries, especially in Brazil, where governmental regulatory agencies – namely the Federal Council of Medicine and the National Commission for Research Ethics – posed a ban on the placebo use in clinical trials nationally,when there is available treatment, corroborating with the ongoingcontroversy amongst regulatory agencies and researchers in Brazil.Therefore, since Nuremberg, given the warranty of not weakening the protection of research subjects recruited throughout the worldconstitutes the DoH most desired aim, dialogue must be resumed both nationally and internationally, considering the upcoming revisionin 2014, at the DoH 50th anniversary...

An update on research ethics in Asia / Journal of the ASEAN Federation of Endocrine Societies

There are many international guidelines that have been developed to ensure that the conduct of researches by countries, institutions and individuals are ethical. There are, however, unique opportunities as well as challenges in research in the ASEAN region which mandate not only adherence to these guidelines but which necessitate regional as well as individual country efforts to ensure that biomedical researches uphold the dignity, ensure safety and protect the rights of participants. Some of the challenges are: the widespread poverty or uneven distribution of resources in developing countries which cause patients to participate in clinical trials to avail of services that otherwise are inaccessible, lack of a research infrastructure that makes ethics review of protocols inadequate or slow, and lack of post-trial access to medications which have been tested in precisely the populations that need these drugs. The aim of this paper is to review the ethical challenges in health research encountered in Asia and to describe the regional efforts being undertaken to address them.

Ética na publicação de pesquisas sobre leishmaniose visceral humana em periódicos nacionais / Ética en la publicación de investigaciones sobre leishmaniasis visceral humana en periódicos brasileños / Ethics in the publication of studies on human visceral leishmaniasis in Brazilian periodicals

OBJETIVO: Analisar os aspectos éticos dos artigos nacionais sobre leishmaniose visceral humana publicados após a Resolução CNS 196/1996 e analisar a política de periódicos brasileiros sobre ética em pesquisa. MÉTODOS: Estudo exploratório de natureza bibliográfica e documental. A seleção das publicações sobre pesquisas envolvendo seres humanos foi realizada na base SciELO Brasil a partir de 1996. Foram analisadas lacunas relacionadas às políticas editoriais dos periódicos médicos a partir de informações obtidas da seção "Instruções aos autores" de cada periódico. RESULTADOS: Observou-se que, enquanto no primeiro quadriênio (1997 a 2000) nenhum artigo mencionou o cumprimento dos aspectos éticos, no ano de 2009 do quadriênio (2009 a 2012), 75 por cento cumpriram pelo menos uma das orientações éticas avaliadas. Seis em 11 periódicos indicaram que as informações sobre os aspectos éticos deveriam ser citadas no corpo do artigo. Três periódicos fizeram exigências quanto ao envio de carta ou documento assinado pelo(s) autor(es) informando o cumprimento dos aspectos; dois solicitaram cópia do documento de obtenção do termo de consentimento livre e esclarecido; um explicitou a necessidade do envio de cópia da autorização da aprovação pelo comitê de ética em pesquisa; e em quatro periódicos analisados não foi identificada nenhuma exigência sobre aspectos éticos. CONCLUSÕES: Houve melhora em relação à descrição do cumprimento dos aspectos éticos nos artigos. Sugere-se a padronização das orientações éticas relacionadas à pesquisa com seres humanos nos periódicos nacionais. Isso pode estimular o cumprimento dos pressupostos de documentos que regem a experimentação humana.

OBJETIVO: Analizar los aspectos éticos de los artículos nacionales sobre leishmaniasis visceral humana publicados posterior a la Resolución CNS 196/1996 (Brasil) y analizar la política de periódicos brasileños sobre ética en investigación.MÉTODOS: Estudio exploratorio de naturaleza bibliográfica y documental. La selección de las publicaciones sobre investigaciones envolviendo seres humanos fue realizada en la base SciELO Brasil a partir de 1996. Fueron analizadas lagunas relacionadas con las políticas editoriales de los periódicos médicos a partir de informaciones obtenidas de la sección "Instrucciones a los autores" de cada periódico.RESULTADOS: Se observó que mientras en el primer cuatrienio (1997 a 2000) ningún artículo mencionó el cumplimiento de los aspectos éticos, en el año 2009 del cuatrienio (2009 a 2012), 75% cumplieron por lo menos una de las orientaciones éticas evaluadas. Seis en 11 periódicos indicaron que las informaciones sobre los aspectos éticos deberían ser citadas en el cuerpo del artículo. Tres periódicos hicieron exigencias con relación al envío de carta o documento firmado por el(los) autor(es) informando el cumplimiento de los aspectos; dos solicitaron copia del documento de obtención del termo de consentimiento libre e esclarecido; uno dejó explicita la necesidad de envío de copia de la autorización de la aprobación por el comité de ética en pesquisa y en cuatro periódicos analizados no fue identificada ninguna exigencia sobre aspectos éticos.CONCLUSIONES: Hubo mejoría con relación a la descripción del cumplimiento de los aspectos éticos en los artículos. Se sugiere la estandarización de las orientaciones éticas relacionadas con la investigación con seres humanos en los periódicos brasileños. Esto puede estimular el cumplimiento de las suposiciones de documentos que rigen la experimentación humana.