Ética en investigación: desafíos durante la pandemia / Research ethics: challenges during the pandemic

Durante la pandemia de Covid-19 los hospitales pediatricos se vieron menos afectados, debido a la menor infección en niños, y sus recursos fueron reasignados en distintas tareas.. El Comité de Ética en Investigación del Hospital General de Niños Pedro de Elizalde presenta los distintos procedimientos implementados en esta emergencia, para sostener diferentes investigaciones, y que les permitió una rápida respuesta a esta situación.

Ethical and research governance approval across Europe: Experiences from three European palliative care studies.

BACKGROUND: Research requires high-quality ethical and governance scrutiny and approval. However, when research is conducted across different countries, this can cause challenges due to the differing ethico-legal framework requirements of ethical boards. There is no specific guidance for research which does not involve non-medicinal products. AIM: To describe and address differences in ethical and research governance procedures applied by research ethics committees for non-pharmaceutical palliative care studies including adult participants in collaborative European studies. DESIGN: An online survey analysed using descriptive statistics. SETTING/PARTICIPANTS: Eighteen principal investigators in 11 countries conducting one of three European-funded studies. RESULTS: There was variation in practice including whether ethical approval was required. The time to gain full approvals differed with the United Kingdom having governance procedures that took the longest time. Written consent was not required in all countries nor were data safety monitoring committees for trials. There were additional differences in relation to other data management issues. CONCLUSION: Researchers need to take the differences in research approval procedures into account when planning studies. Future research is needed to establish European-wide recommendations for policy and practice that dovetail ethical procedures and enhance transnational research collaborations.

A Rare Opportunity: Examining the Experience of a New Institutional Review Board.

The process of creating a new Institutional Review Board (IRB) or Research Ethics Committee (REC) presents many challenges; however, little has been published to describe this experience. Thus, many questions about creating a new IRB/REC and the challenges they face remain. The establishment of a new federal-wide single IRB provided a rare opportunity to describe these experience and outcomes. A census of the activity and outcomes of this new board is reported for its first 3 years of operation: The convened board approved 50 protocols, required an average of 93.24 days and 2.76 reviews for protocol approval, and issued an average of 31.82 stipulations per protocol. The census data helped to identify several issues that impacted the board's outcomes and it serves as a baseline for future comparisons. The overall dynamics, challenges, and outcomes of this new single IRB are discussed.

Saúde e pesquisa científica com seres humanos: a conformação dos danos decorrentes e o modelo brasileiro de fiscalização / Health and scientific research with human beings: the conformation of the resulting damages and the brazilian method of inspection / Salud e investigación científica con seres humanos: la conformación de los daños resultantes y el modelo brasileño de fiscalización

Objetivo: Este artigo objetiva analisar o ordenamento jurídico brasileiro às pesquisas envolvendo seres humanos no tocante aos danos à saúde decorrentes dos experimentos, com fundamento na Resolução nº 466/2012 do Conselho Nacional de Saúde. Metodologia: Realizou-se pesquisa de natureza bibliográfica, em livros e artigos da área jurídica, em legislações ordinárias e resoluções relacionadas, bem como em artigos publicados em periódicos da área de Saúde. Resultados: Os danos decorrentes dos experimentos devem ser cuidadosamente evitados e, se ocorrerem, deve o participante da pesquisa ser indenizado. Conclusão: Eventuais danos decorrentes dos experimentos devem ser evitados e observados durante todo o curso da pesquisa, iniciando-se com a assinatura do Termo de Consentimento Livre e Esclarecido pelo participante e perpassando pela fiscalização pelo Comitê Nacional de Ética e Pesquisa e pelas Comissões de Ética em Pesquisa. É essencial que o acompanhamento e a fiscalização sejam feito de forma mais próxima, obstando e ressarcindo a ocorrência de eventuais danos, além de garantir a regularidade do processo de consentimento realizado no projeto

Objective: This article objectives to analyze the legal treatment and the procedure adopted by Brazil on clinical research with basis on the Resolution nº 466/2012 from National Health Council towards the occurrence of damages due to the project. Methodology: The research was carried out in nature bibliographical references, in books and articles of the legal area, in ordinary legislations and related resolutions, as well as in articles published in periodicals of the Health area. Results: Damages must be avoided and, when occurring, must provide also an compensation to those who were harmed. Conclusion: Any damages resulting from the experiments should be avoid and noted during the curse of the project, since the moment of the informed consent's signature to the stage of inspection from the National Ethics and Research Committee and Research Ethics Committees. The completion of a closest monitoring is essential to prevent this damages and to indemnify the participant. Furthermore, it guarantees that the process of consent is being held on a satisfactory form

. Objetivos: Trabajo destinado al análisis jurídico de la protección conferida por el ordenamiento brasileño a las investigaciones involucrando a seres humanos en lo que se refiere a los daños a la salud derivados de los experimentos, con base en la Resolución 466/2012 del Consejo Nacional de Salud. Metodología: Se realizó investigación de naturaleza bibliográfica, en libros y artículos del área jurídica, en legislaciones ordinarias y resoluciones relacionadas, así como en artículos publicados en periódicos del área de Salud. Resultados: Los daños resultantes de los experimentos deben ser cuidadosamente evitados y, si ocurren, el participante de la investigación debe ser indemnizado. Conclusión: Eventuales daños resultantes de los experimentos deben ser evitados y observados durante todo el curso de la investigación, iniciándose con la firma del Término de Consentimiento Libre y Esclarecido por el participante y pasando por la fiscalización por el Comité Nacional de Ética e Investigación y por las Comisiones de Ética en Investigación. Es esencial que el seguimiento y la fiscalización se haga de forma más cercana, obstaculizando y resarciendo la ocurrencia de eventuales daños, además de garantizar la regularidad del proceso de consentimiento realizado en el proyecto

Time to institutional review board approval with local versus central review in a multicenter pragmatic trial.

BACKGROUND/AIMS: Central institutional review board (IRB) review will be required for National Institutes of Health-funded multisite human subjects research as of January 2018, with similar requirements extending to most US multisite human research in 2020. Nonetheless, little is known regarding the relative efficiency of central versus local IRB review for multicenter studies. We compared the amount of time required for central versus local IRB review and approval for sites in one ongoing multicenter randomized trial. METHODS: The REGAIN Trial (Regional versus General Anesthesia for Promoting Independence after Hip Fracture; clinicaltrials.gov number: NCT02507505) is an ongoing randomized trial comparing standard-care spinal anesthesia to standard-care general anesthesia for patients undergoing hip fracture surgery. After approval of the protocol by the sponsor IRB, each participating US site opted either to submit the protocol for local IRB review or to designate the sponsor IRB as the IRB of record (i.e. central IRB) via an authorization agreement after a limited local review. For each US REGAIN site approved through 18 April 2017, we assessed (1) the time in calendar days from protocol receipt to IRB submission, (2) the time in calendar days from IRB submission to IRB approval, and (3) the total time in calendar days from protocol receipt to IRB approval (i.e. time from protocol receipt to IRB submission plus time from IRB submission to IRB approval). RESULTS: The main study protocol was submitted to the sponsor IRB on 25 May 2015 and approved on 8 July 2015 (44 days). Out of 34 sites, 9 received initial approval from the central (sponsor) IRB; 25 sought initial approval via local review. The median time from protocol receipt to IRB submission was 39 days for sites approved by the central IRB (interquartile range: 35-134) versus 58 days for sites approved via local review (interquartile range: 41-105; p = 0.711). The median time from IRB submission to IRB approval for sites approved by the central IRB was 27 days (interquartile range: 14-32) versus 66 days (interquartile range: 29-138) for sites approved via local review (p = 0.026). The median total time from protocol receipt to IRB approval was 100 days (interquartile range: 71-148) for centrally approved sites versus 132 days (interquartile range: 87-209) for locally approved sites (p = 0.191). CONCLUSION: While central IRB review was associated with a shorter time from IRB submission to IRB approval compared to local IRB review, the total time from protocol receipt to IRB approval varied markedly across sites.

Institutional Scientific Review of Cancer Clinical Research Protocols: A Unique Requirement That Affects Activation Timelines.

PURPOSE: The National Cancer Institute (NCI) requirement that clinical trials at NCI-designated cancer centers undergo institutional scientific review in addition to institutional review board evaluation is unique among medical specialties. We sought to evaluate the effect of this process on protocol activation timelines. METHODS: We analyzed oncology clinical trials that underwent full board review by the Harold C. Simmons Comprehensive Cancer Center Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through June 30, 2013. We analyzed associations between trial characteristics, PRMC decisions, protocol modifications, and process timelines using the χ2 test, Fisher's exact test, Wilcoxon rank sum test, Kruskal-Wallis test, and logistic regression. RESULTS: A total of 226 trials were analyzed. Of these, 77% were industry sponsored and 23% were investigator initiated. The median time from submission to PRMC approval was 55 days. The length of review was associated with trial phase, timing of approval, and number of committee changes/clarifications requested. The median process time was 35 days for those approved at first decision, 68 days for second decision, and 116 days for third decision ( P < .001). The median process time was 39 days if no changes/clarifications were requested, 64 days for one to three changes/clarifications, and 73 days for four or more changes/clarifications ( P < .001). Requested changes/clarifications had a greater effect on industry-sponsored trials than on investigator-initiated trials. CONCLUSION: NCI-mandated institutional scientific review of oncology clinical trials contributes substantially to protocol activation timelines. Further evaluation of this process and the value added to research quality is warranted.

Estructura y funcionamiento de los comités de ética en investigación de la Ciudad Autónoma de Buenos Aires y el Gran Buenos Aires / Structure and functioning of research ethics committees in the Autonomous City of Buenos Aires and Greater Buenos Aires

En función de los escasos estudios publicados sobre los comités de ética en investigación (CEI) de Argentina, este trabajo tiene como objetivo describir la estructura y funcionamiento de los CEI de instituciones de la Ciudad Autónoma de Buenos Aires y el Gran Buenos Aires. Con ese fin, se realizó un estudio descriptivo, cuali-cuantitativo, a partir de la aplicación de una encuesta entre marzo y julio de 2012. La muestra quedó conformada por 46 CEI. El 40% de sus miembros eran médicos y la distribución por sexo y edad se adecuaba a la normativa. Se encontraron falencias en la cantidad de metodólogos, representantes de la comunidad, abogados y miembros externos a las instituciones, falta de personal administrativo y de lugar fijo para las reuniones, presupuestos escasos para gastos y poco entrenamiento en ética de la investigación. Algunos de los encuestados reportaron problemas de relación con la institución y los investigadores, y con el tiempo disponible para realizar la tarea.

Given the few existing studies on research ethics committees (RECs) in Argentina, this paper aims to describe the structure and functioning of institutional RECs in the Autonomous City of Buenos Aires and Greater Buenos Aires. A descriptive, qualitative and quantitative research study was carried out using a survey conducted between March and July 2012. The sample was made up of 46 RECs. Forty percent of committee members were doctors and the age and sex distribution met standards. Inadequate numbers of methodologists, community representatives, lawyers and members external to the institution were identified, as well as shortcomings regarding administrative staff, fixed locations for meetings, budgets adequate to expenditures and training in research ethics. Some of those surveyed reported problems in their relationship with the institution and with researchers, in addition to difficulties regarding the time available to perform tasks.

O Núcleo de Apoio ao Pesquisador e o Comitê de Ética em Pesquisa: uma estratégia de fomento à pesquisa na Fundação Hospitalar do Estado de Minas Gerais / Researcher Support Centre and the Research Ethics Committee: a strategy of research promotion in Hospital Foundation of Minas Gerais

Introdução: Como integrante do Sistema Único de Saúde, a Fundação Hospitalar do Estado de Minas Gerais (Fhemig) considera estratégico o desenvolvimento da pesquisa para qualificação profissional e melhoria da assistência à saúde. O Núcleo de Apoio ao Pesquisador, já completamente implantado, e os Comitês de Ética em Pesquisa trabalham nessa perspectiva. Objetivos: Descrever os projetos de pesquisa cadastrados na Fhemig. Métodos: Realizou-se análise descritiva dos projetos submetidos ao Núcleo de Apoio ao Pesquisador e aos Comitês de Ética em Pesquisa da Fhemig, em 2010-2011. Resultados: Dos 330 projetos de pesquisa avaliados, 243 foram considerados adequados para se desenvolver nas Unidades da Rede Fhemig. Desses, 164 (50%) foram aprovados após um único parecer favorável por parte dos profissionais do Núcleo de Apoio ao Pesquisador e 79 (24%) foram aprovados após atender as recomendações quanto às questões metodológicas, principalmente. O Comitê de Ética em Pesquisa da Fhemig avaliou 196 projetos de pesquisa e o do Hospital Eduardo de Menezes avaliou 41 sendo que nenhum projeto de pesquisa foi reprovado. No entanto, a maior deles apresentou inadequações quanto ao Termo de Consentimento Livre e Esclarecido (54,3%). Conclusões: O grande número de projetos aprovados na primeira submissão ao Núcleo de Apoio ao Pesquisador indica uma maior qualidade desses projetos no biênio. O Núcleo de Apoio ao Pesquisador tem cumprido sua função de apoio aos pesquisadores em seus projetos de pesquisa.

Introduction: Hospital Foundation of Minas Gerais (Fhemig), member of Unified Health System, considers strategic the research development for qualifying professionals and improve health assistance. The Researcher Support Centre, now completely implanted, and the Research Ethics Committees work based in this perspective. Objectives: To describe research projects registered in Fhemig. Methods: Descriptive analysis of projects registered in the Researcher Support Centre and the Research Ethics Committees from Fhemig, were done in 2010-2011. Results: 243 out of 330 research projects analyzed were considered appropriate to develop in the Fhemig Network Units. Out of those, 164 (50%) were approved after only one favorable feedback from professionals of the Researcher Support Centre and 79 (24%) after complying with, mostly, of the methodological recommendations. Fhemig's Research Ethics Committee evaluated 196 projects and Eduardo de Menezes' Hospital Ethics Committee evaluated 41. None them was reproved. However, most of them presented inadequacies on their Term of Informed Consent (54,3%). Conclusions: The great number of approved projects in the first submission to the Research Support Centre indicates a higher quality of such projects in the couple of years. The Research Support Centre has reached its role in supporting researchers in their research projects.(AU)

Protocolo de pesquisa: o desafio do aprimoramento ético / Research protocol: the challenge of ethical improvement

O trabalho analisa protocolos de pesquisas no âmbito universitário submetidos nos últimos três anos ao Comitê de Ética em Pesquisa da Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória (CEP/Emescam). Este CEP avalia 200 projetos/ano. Os dados foram restritos ao título dos projetos e número de sujeitos. Os achados foram agrupados conforme a Biblioteca Virtual de Saúde (BVS). As pesquisas concentram-se nas categorias saúde do trabalhador; aleitamento materno, saúde materna e da mulher; adolescência, criança e idoso. Economia, indicadores de saúde, alta complexidade e ciência e tecnologia estão ausentes. Considerando que a preferência pela área temática advém da familiaridade com o tema, os dados levantados foram comparados com a experiência dos pesquisadores, registrada na Plataforma Lattes. Sabe-se que hoje as pesquisas são resultado dos esforços passados dos pesquisadores e conhecer o cenário atual da pesquisa acadêmica é importante para planejar o futuro da pesquisa em saúde no país.

Reasons for resubmission of research projects to the research ethics committee of a University Hospital in São Paulo, Brazil

INTRODUCTION: It is important to know the reasons for resubmitting research projects to the Research Ethics Committee in order to help researchers to prepare their research projects, informed consent forms and needed research documentation. OBJECTIVES: To verify the reasons for resubmitting projects that were previously rejected by the Ethics Committee. METHOD: This is a cross-sectional study that evaluated research projects involving human beings. Research projects were submitted in 2007 to the Research Ethics Committee of the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. RESULTS: One thousand two hundred and fifty six research projects were submitted to the ethics committee and the average time for evaluating the research projects and related documents until a final decision was reached was 49.95 days. From the total, 399 projects were reviewed in 2 or more meetings until a final decision was reached. Of these, 392 research projects were included in the study; 35 projects were subsequently excluded for involving animals. Among the research projects included, 42.5 percent concerned research with new drugs, vaccines and diagnostic tests, 48.5 percent consisted of undergraduate students' research projects, 68.9 percent of the research had no sponsorship, and 97.5 percent were eventually approved. The main reasons for returning the projects to the researchers were the use of inadequate language and/or difficulty of understanding the informed consent form (32.2 percent), lack of information about the protocol at the informed consent form (25.8 percent), as well as doubts regarding methodological and statistical issues of the protocol (77.1 percent). Other reasons for returning the research projects involved lack of, inaccuracy on or incomplete documentation, need of clarification or approval for participation of external entities on the research, lack of information on financial support. CONCLUSION: Among the ...

"Conflict-of-interest" and participation in IRB deliberations: an alternative perspective.

A natural tension exists as an IRB attempts of fulfill its mission of providing an independent and unbiased evaluation of a study while also insuring appropriate consideration of all relevant risks, benefits, and alternative strategies. IRB members with often critically relevant knowledge of unique issues involved in a protocol under review may be the individuals with the greatest potential for a perceived "conflict," due to current or past involvement in sponsor-associated research in the particular area. Management of real or perceived conflict must include full disclosure, but exclusion of such individuals from the deliberative process may result in undesirable consequences.

Surgical pathology--second reviews, institutional reviews, audits, and correlations: what's out there? Error or diagnostic variation?

CONTEXT: A variety of methodologies have been used to report error rates in surgical pathology within the peer-reviewed medical literature. The media has selectively and superficially reported these error rates creating a climate of disinformation between physicians and the public. OBJECTIVES: To review the medical literature on diagnostic error in surgical pathology and summarize and compare these data with selected reports in the print and broadcast media. DESIGN: A search of the medical literature from the National Library of Medicine database using the heading "Error and Pathology Diagnosis." RESULTS: Three thousand nine hundred ninety-two citations were found, of which 83 directly measured in some manner errors in surgical and cytopathology. Major error rates ranged from 1.5% to 5.7% globally for institutional consults. Error rates were less, 0.26% to 1.2% for global in-house prospective review and 4.0% for in-house and retrospective blinded review. Error rates also varied by anatomic site: skin, institutional consult, 1.4%; prostate, institutional consult, 0.5%; and thyroid, institutional consult, 7.0%. Error rates reported in citations used by the Wall Street Journal were as follows: prostate, Gleason score changed by 1 point, 44% and resultant change in treatment for prostate cancer, 10%; for breast, altered lumpectomy or mastectomy plan, 8%; and diagnosis changed for thyroid lesions, 18%. Errors in second opinion on breast lesions (single pathologist author for the study) fall within the range of global reviews. Errors for second opinions on prostate cancer were principally 81% upgrades in Gleason score for prostate core needle biopsies. However, this resulted in an upgrade of patient risk category in only 10.8% of patients. Data for the article on change in diagnosis of thyroid lesions were incomplete. There appeared to be 3 significant diagnostic errors (4.5%). CONCLUSIONS: Pathology is not immune to the power of the media to create concern about accuracy of diagnosis in surgical pathology and cytopathology. Detailed analysis of the medical literature cited by the media determines that painting the big picture and hitting the highlights can be profoundly misleading.

Clinical trials in New Zealand--treading water in the knowledge wave?

AIMS: To describe the number and type of clinical trials in New Zealand 1998-2003, and to identify the number of trials for which approval was sought in 2003 that were listed with trial registries. METHODS: Annual reports (1998-2003) from all regional ethics committees were reviewed for clinical trials. Trials must have been referred to as phase I, II, or III clinical trials; employ descriptors such as randomised controlled trials or controlled trials; or been known to the authors as randomised controlled trials. Trials registers at ClinicalTrials.gov, Current Controlled Trials, NHMRC Clinical Trials Centre, National Cancer Research Network, CenterWatch, Trans-Tasman Radiation Oncology Group, as well as industry registers were searched using keyword identifiers for the trials submitted for ethical review in 2003. RESULTS: Ethics approval was sought for 665 clinical trials (1998, 118 trials; 1999, 91 trials; 2000, 103 trials; 2001, 104 trials; 2002, 108 trials; 2003, 141 trials). The majority of applications (481, 72%) were submitted to either the Auckland or Canterbury committees. 581 (87%) applications were for phase III trials. 522 (78%) applications were for trials involving pharmacological agents, and 115 applications (17%) were for trials involving procedures, processes, or medical devices. The remaining 28 applications (4%) involved interventions such as diet, complementary therapies, or dental care. Of all applications, 332 (50%) were in the fields of cancer, cardiovascular disease, and respiratory disease. Only 45 (32%) of the 141 trials submitted for review in 2003 were listed in a public domain register. CONCLUSIONS: The number of randomised controlled trials (RCTs) in New Zealand has not clearly increased in recent years despite the greater than ever need for such evidence. Information currently in the public domain could support registers of clinical trials.

Trust and confidence: towards mutual acceptance of ethics committee approval of multicentre studies.

AIMS: To compare issues raised by Human Research Ethics Committees (HREC) during the ethics review process and to determine the length of time taken to gain HREC approval for multicentre research studies. METHODS: Review and analysis of HREC documentation and correspondence for all multicentre research studies were conducted through three HREC under the auspices of Cancer Trials Australia, Melbourne, Victoria, Australia, between November 1997 and March 2001 to determine the variance of documentation, correspondence and recommendations across the three HREC and the time taken for study approval. RESULTS: Thirty-one projects were submitted to any two of the HREC (16 studies) or all three HREC (15 studies). The median time for study approval at an individual HREC was 75 days, but it was 111 days for approval at all participating sites. There were 554 clarifications or comments made by the reviewing HREC, the majority of which had no significant bearing on the ethical or scientific calibre of the study. There was only one study in which a significant protocol change was requested by a HREC. CONCLUSIONS: Multicentre study approvals are delayed when submitted to multiple HREC. The three HREC raised similar issues without substantive differences in their recommendations. A process for the mutual acceptance of HREC recommendations could facilitate multicentre research.