Orientador: Iscia Lopes-Cendes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T18:07:18Z (GMT). No. of bitstreams: 1 Bittar_MariaFernandaRibeiro_D.pdf: 985156 bytes, checksum: a785ab239977f1eabf0b737095854940 (MD5) Previous issue date: 2009 / Resumo: É aceita em todos os domínios a relevância da pesquisa com seres humanos. Para guiar eticamente a realização dessas pesquisas, de consideração internacional, temos a última revisão da Declaração de Helsinque (2008). No Brasil temos a Resolução 196/96 do Conselho Nacional de Saúde (CNS) e outras resoluções complementares do mesmo conselho, todas possuem a intenção e a responsabilidade de proteger os sujeitos de pesquisa. Nesse intuito, no Brasil, é exigida a revisão e aprovação da pesquisa por um Comite de Ética em Pesquisa (CEP) que deve analisar diversos aspectos científicos, éticos, legal e social da pesquisa. Dentre todos, este trabalho aborda os aspectos éticos, principalmente o Termo de Consentimento Livre e Esclarecido (TCLE), definido como a autorização voluntária de um indivíduo, para sua inclusão em uma pesquisa. No "Encontro de Comitês de Ética de São Paulo", realizado anualmente desde 2003 em São Paulo, os problemas referentes ao TCLE foram considerados como sendo o maior motivo de pendências dos projetos de pesquisas avaliados. O objetivo do presente estudo foi estabelecer um protocolo de avaliação, acompanhamento e suporte ao pesquisador com o intuito de melhorar a qualidade do termo de consentimento livre e esclarecido utilizado nos projetos de pesquisa acompanhados pelo CEP-UNICAMP. O estudo foi desenvolvido em 3 tópicos relacionados ao mesmo tema: 1- Caracterização dos Projetos encaminhados ao CEP da FCM-UNICAMP. 2- Projetos com pendências no TCLE: oferecimento de suporte ao pesquisador para responder às pendências do CEP em relação ao TCLE. 3- Auditoria: testar um trabalho de auditoria em aspectos éticos dos projetos de pesquisa aprovados pelo mesmo CEP. Cada item teve sujeitos, materiais e instrumentos distintos, adequados aos propósitos e as características da cada um. O modelo de pesquisa seguido foi a integração metodológica. Na observação de 1639 projetos, 675 receberam pendência ou recomendações relativas ao método do trabalho (25%), ao TCLE (39%) ou a ambos, método e TCLE (36%). No TCLE em geral as pendências dividem-se em duas categorias: linguagem e falta de informações, como objetivo, procedimentos, justificativas para a realização e formas de assistência. Aos aspectos éticos ocorre a ausência de esclarecimento da voluntariedade de participação, sobre a utilização e o armazenamento de material biológico, telefones de contato do pesquisador e do CEP, identificação do pesquisador, garantia de sigilo e mesmo a falta do TCLE. Os TCLEs encaminhados para auxílio apresentam elevada dificuldade de entendimento, necessitando em média 16,52 anos de escolaridade e índice de legibilidade médio de 19,47 considerado de alta dificuldade de leitura. Quanto a linguagem, além da dificuldade com palavras complexas, sujeitos de baixa escolaridade têm pouco interesse ou atenção aos termos técnicos mesmo quando fazem parte dos procedimentos a serem realizados. Quando questionados, três sujeitos relataram que se o pesquisador está solicitando deve ser relevante e eles não entendem nada do assunto. Na auditoria, do total de 27 projetos observou-se que três não continham TCLE para todos os participantes da pesquisa, três não utilizavam o termo aprovado pelo CEP- UNICAMP , e 18 estavam inadequadamente preenchidos. Os achados demonstram a continuidade do elevado índice de pendência, a necessidade de orientação ao pesquisador quanto ao seu processo e documentação e também a relevância do acompanhamento pelo CEP dos projetos aprovados. A formação ética e a educação continuada dos profissionais envolvidos em pesquisas com seres humanos são passos importantes no caminho para a formação de pesquisadores com atitudes éticas frente aos avanços científicos, a provisoriedade dos padrões morais e o constante surgimento de novas questões éticas / Abstract: The importance of research with human subjects is universally accepted. To ethically guide this kind of research there is the last revision of the Declaration of Helsinki, an international document, and the Resolution 196/96 in Brazil, from the National Health Council. Their main objective is to protect subjects undergoing research. In Brazil, it is mandatory to submit all research protocols for approval of legal, ethical, scientific and social aspect of the project by a Ethics Committee/ Institutional Review Board (REC/IRB). This thesis deals with the ethical aspects, specially the informed consent, defined as the voluntary authorization by a subject to participate in a research. In the "REC/IRB Meeting in São Paulo state", the informed consent was considered the major reason for non-approval of projects. The main goal of our project was to establish a protocol providing evaluation, guidance and support to the investigator aiming to improve the quality of the informed consents submitted to evaluation at the IRB/EC-UNICAMP. The project was divided in three main areas all related to the informed consent: 1 - Characterization of research protocols sent to the IRB/EC-UNICAMP; 2 - Action at non-approved informed consents: guidance and support to investigator to meet the requirements as per IRB/EC. 3 - Audit: ethical aspects of research protocols approved by the IRB/EC. Each one of those areas had a different set of subjects, materials and instruments in accordance with its goals and characteristics. We followed methodological integration. In the observation of 1,639 projects, 675 received recommendations regarding the methodology (25%), the informed consent (39%) or both (36%). In the informed consent the problems fell into two categories: language and lack of information, such as objective, procedures, justifications for the protocol and forms of assistance. Regarding the ethical aspects there were lack of clarification that participation was voluntary, on the use and storage of biological material, contact information for the investigator and the IRB, investigator identification, confidentiality and even the lack of informed consent. All consent forms referred for aid exhibited a high level of difficulty for understanding, requiring an average of 16.52 years of schooling and average rate of readability of 19.47, which is considered a high level of difficulty in reading. In addition to difficulty with complex words, we observed that subjects with low education have little interest or focus on technical terms even when they are part of the procedures to be performed. In the audit part of the project we observed that three projects did not include informed consent for all research subjects, three did not use the informed consent approved by the IRB-UNICAMP and eighteen were inadequately completed. Our findings demonstrated a high level of non-compliance with IRB/EC requirements regarding the informed consent, the investigator's need for guidance in the documentation process and the importance of IRB/EC follow-up on approved projects is evident. Providing continuous ethical education for the professionals involved in research with human subjects is an important step towards investigators with ethical attitudes when confronted with scientific developments, shifting moral patterns and new ethical questions / Doutorado / Ciencias Biomedicas / Doutor em Ciências Médicas

Clinical trials of medicinal products is increasingly important area of pharmaceutical law. Number of clinical trials and amount of financial resources is constantly rising and therefore the rules and principles of the clinical trials itself are being clarified overtime. This diploma thesis aims to provide an overview of the basic aspects of clinical trials of medicinal products for human use from a legal point of view. The author focuses in particular on the national legislation of clinical trials, which is complemented by the legislation of the European Union and important sources of the international law. Author is more closely analysing the particular procedures performed within the clinical trials, especially from the point of view of the administrative law. Particular attention is paid to the ethical review of the clinical trials, their particular aspects and the overall concept. The thesis is divided into twelve chapters. In the introduction, the author focuses on the development of the clinical trials and mentions the crucial moments that contributed to the formulation of the basic rules of the clinical trials. The following chapter focuses on the sources of law. Firstly, sources of international law are described, where more general sources and specific sources of law of medicinal products...

The issue of legislative and ethical requirements on research of innovative medicines became more intense in connection to the expansion of the pharmaceutical industry in last few decades. This master thesis aims to complexly describe and analyse theoretical bases of current legislative regulating the process of clinical trials of medicinal products for human use in the Czech Republic, as well as to take a closer look to the issue of ethical review administered by specialized ethical review committees. The author also deals with some specific responsibilities of the committees from the perspective of administrative law, especially focusing on aspects of legal nature of the positive opinions, which are one of the conditions for commencement of a clinical trial. The thesis is divided into nine chapters and the introductory chapter is focused on the general outline of the issue of clinical trials of medicines for human use in the Czech Republic. The aim of the second chapter is to define the basic concepts stated in the Czech medicinal products act, which are specific for this area of pharmaceutical law. The next chapter analyses the relevant competencies of individual state authorities over the clinical studies. The fourth chapter contains the list of sources of law, whereas a particular emphasis is...

Introduction. This thesis analyzes how researchers views the data management plans, how they use them and how they interact with the data support functions at the university. Theory & Method.  The theoretical underpinnings of the study are Janken Myrdals theory of the research method as signifier of natural or humanistic research, and the research method is semi-structured interviews. The study’s empirical material consists of six interviews with researchers from four different scientific fields, which have been transcribed and processed through a qualitative thematic and comparative analysis. Results & Analysis. Five main themes have been identified: (1) bureaucratic demands, (2) a lack of support or a lack of interest?, (3) the data management plans connection to ethical review, (4) the impact of the method on the view of the data management plan, (5) time constraints and the plan as support in the research work. Conclusions. Researchers experience of working with data management plans does not give an unambiguous picture: some see it as an administrative burden or as something of a time sink. Others view it as something that benefits both their own work and when collaborating with colleagues. Moreover divided views exist regarding the support offered by the university when working with data management plans. Some respondents view it as adequate while others suggest that researchers needs to inform themselves on how to write the plan.

<p><em>Syfte</em>: Det övergripande syftet med denna uppsats är att ur ett moraliskt perspektiv ge  en vidare och mer ingående förståelse för marknadsföringen av läkemedel samt  att utforska om det finns anledning att skilja mellan reklam och information i läkemedelsbranschen.</p><p><em>Metod</em>: Problemet i denna studie belyses via en kvalitativ ansats. De metoder som använts  för datainsamlingen har varit semistrukturerade intervjuer med representanter  från Läkemedelsindustriföreningen samt observationer av annonser i Läkartidningen  och reklamfilmer på TV4. I arbetet har det använts en egenframställd  mall för att koda och sammanställa datamaterialet från reklamobservationerna.  Det empiriska materialet från både intervjuer och observationer har sedan  analyserats via kontraproduktivitetsteorin samt en modell för etisk revision.</p><p><em>Resultat</em>: Marknadsföring av läkemedel bedöms av författarna till denna studie vara en  moraliskt rättfärdigad handling. En av anledningarna till detta är att läkemedelsföretagen  genom sin forskning bidrar till ett ökat välbefinnande för samhällets  medborgare. Forskningen finansieras till viss del av försäljningsintäkter, vilka i  sin tur har större chans att öka då marknadsföring bedrivs. En annan anledning är  att företagen genom sin marknadsföring tar sitt ansvar vad gäller informationsspridning  om läkemedlen och resultatet i undersökningen visar att företagen uppvisar  en ärlighet i marknadsföringen. Då ärlighet kopplas samman med trovärdighet  och hänsyn tas till den informationstillgång som marknadsföringen erbjuder,  visar även detta på ett moraliskt rättfärdigat agerande. Vid utförandet av annonser  för receptbelagda läkemedel visade det sig att mer resurser läggs på att  skapa en informativ reklam än vad det görs vid utformandet av reklam för de receptfria  läkemedlen. I den marknadsföring som bedrivs för receptfria läkemedel  skulle en mer informativ och saklig marknadsföring öka företagens moraliska  anseende.</p> / <p><em>Aims</em>: Overall aims of this thesis are to bring a broader and deeper understanding, from  a moral point of view, of marketing of pharmaceuticals, and to consider whether  there is a reason for separating advertising from information in the sector.</p><p><em>Methods</em>: A qualitative approach to the subject was used. Methods for data compilation  were semi-structured interviews with representatives for The Swedish Association  of the Pharmaceutical Industry (Läkemedelsindustriföreningen), and studies  of advertisements in The Journal of the Swedish Medical Association (Läkartidningen)  and commercials on a TV channel (TV4). A customised, self-made,  grid was utilised for coding and compiling data from the observations of commercial  material. Following that, the empirical material from interviews as well  as observations has been analysed, using the theory of counter productivity as a  model for ethical audit.</p><p><em>Results</em>: The authors judge marketing activities of the pharmaceutical industry to be morally  justified. One reason for this judgement is, that the pharmaceutical industry  contributes to an increased well-being among citizens by providing research, research  activities being financed by revenues, which – in turn – are enhanced by  marketing. Another reason is that companies show responsible in the dissemination  of information and that the results of the study indicate sincerity in marketing.  When responsibility is linked to trustworthiness and when availability of information  provided by marketing activities is taken into consideration, there is  also evidence of a morally justifiable behaviour. Advertisements for drugs on  prescription showed more informatively designed than those for over-the-counter  drugs. A more informative and appropriate marketing of non-prescription pharmaceuticals  would enhance the moral reputation of the companies.</p>

Syfte: Det övergripande syftet med denna uppsats är att ur ett moraliskt perspektiv ge  en vidare och mer ingående förståelse för marknadsföringen av läkemedel samt  att utforska om det finns anledning att skilja mellan reklam och information i läkemedelsbranschen. Metod: Problemet i denna studie belyses via en kvalitativ ansats. De metoder som använts  för datainsamlingen har varit semistrukturerade intervjuer med representanter  från Läkemedelsindustriföreningen samt observationer av annonser i Läkartidningen  och reklamfilmer på TV4. I arbetet har det använts en egenframställd  mall för att koda och sammanställa datamaterialet från reklamobservationerna.  Det empiriska materialet från både intervjuer och observationer har sedan  analyserats via kontraproduktivitetsteorin samt en modell för etisk revision. Resultat: Marknadsföring av läkemedel bedöms av författarna till denna studie vara en  moraliskt rättfärdigad handling. En av anledningarna till detta är att läkemedelsföretagen  genom sin forskning bidrar till ett ökat välbefinnande för samhällets  medborgare. Forskningen finansieras till viss del av försäljningsintäkter, vilka i  sin tur har större chans att öka då marknadsföring bedrivs. En annan anledning är  att företagen genom sin marknadsföring tar sitt ansvar vad gäller informationsspridning  om läkemedlen och resultatet i undersökningen visar att företagen uppvisar  en ärlighet i marknadsföringen. Då ärlighet kopplas samman med trovärdighet  och hänsyn tas till den informationstillgång som marknadsföringen erbjuder,  visar även detta på ett moraliskt rättfärdigat agerande. Vid utförandet av annonser  för receptbelagda läkemedel visade det sig att mer resurser läggs på att  skapa en informativ reklam än vad det görs vid utformandet av reklam för de receptfria  läkemedlen. I den marknadsföring som bedrivs för receptfria läkemedel  skulle en mer informativ och saklig marknadsföring öka företagens moraliska  anseende. / Aims: Overall aims of this thesis are to bring a broader and deeper understanding, from  a moral point of view, of marketing of pharmaceuticals, and to consider whether  there is a reason for separating advertising from information in the sector. Methods: A qualitative approach to the subject was used. Methods for data compilation  were semi-structured interviews with representatives for The Swedish Association  of the Pharmaceutical Industry (Läkemedelsindustriföreningen), and studies  of advertisements in The Journal of the Swedish Medical Association (Läkartidningen)  and commercials on a TV channel (TV4). A customised, self-made,  grid was utilised for coding and compiling data from the observations of commercial  material. Following that, the empirical material from interviews as well  as observations has been analysed, using the theory of counter productivity as a  model for ethical audit. Results: The authors judge marketing activities of the pharmaceutical industry to be morally  justified. One reason for this judgement is, that the pharmaceutical industry  contributes to an increased well-being among citizens by providing research, research  activities being financed by revenues, which – in turn – are enhanced by  marketing. Another reason is that companies show responsible in the dissemination  of information and that the results of the study indicate sincerity in marketing.  When responsibility is linked to trustworthiness and when availability of information  provided by marketing activities is taken into consideration, there is  also evidence of a morally justifiable behaviour. Advertisements for drugs on  prescription showed more informatively designed than those for over-the-counter  drugs. A more informative and appropriate marketing of non-prescription pharmaceuticals  would enhance the moral reputation of the companies.

O objetivo do estudo foi construir o perfil dos indicados pelos Comitês de Ética em Pesquisa - CEPs - para membros da Comissão Nacional de Ética em Pesquisa - CONEP, líderes no sistema de controle da ética em pesquisa no Brasil, quanto à representação de grupos sociais, formação e experiência profissional e experiência e conhecimento em ética na pesquisa. Enquanto informantes-chave, buscou-se conhecer práticas correntes no sistema, e compreensão da regulamentação. Foram aplicados questionários, via correio ou via eletrônica, aos 188 componentes da lista de 2003, obtendo-se 94 respostas válidas, que representaram 80% dos CEPs. O questionário constou de 4 partes - a parte I, de caracterização pessoal, mostrou proporção semelhante de gênero, alta qualificação acadêmica, participação em cursos de pequena duração sobre ética em pesquisa/ bioética, e sensibilidade social. Dos respondentes, 50% tinham cargos de gestão na instituição, 18% deles ligados diretamente à pesquisa, apenas 4% eram representantes de usuários, 90% participaram de pesquisas nos últimos 10 anos, sendo um terço em pesquisa clínica. A parte II correspondeu a uma auto-avaliação de sua participação como membros de CEPs, que mostrou satisfação com a relevância do trabalho, valorização de qualidades como responsabilidade, compromisso, habilidade para trabalho em equipe, sendo que 89% e 85% consideraram-se preparados e competentes respectivamente, apesar de percepção variada da representatividade e compreensão política de sua atuação. Identificaram-se áreas de maior dificuldade na análise de projetos, e encontros, seminários e discussão de casos como formas preferenciais de preparação. A parte III identificou as percepções sobre o funcionamento do sistema de avaliação ética das pesquisas no Brasil, evidenciando a utilização das diretrizes e normas do CNS na análise dos projetos. A mais efetiva participação dos representantes de usuários e o monitoramento das pesquisas são dificuldades freqüentes. Sugestões de melhoria do sistema referiram a abordagem dos projetos da área de ciências humanas, pré-requisitos e preparação para membros de CEPs, integração e melhoria da comunicação entre CEPs e com a Comissão Nacional. A parte IV foram estudos de casos, que evidenciaram convergência de posicionamentos na grande maioria das situações apresentadas. Conclui-se que o reconhecimento da liderança desses indicados nos CEPs institucionais tem reflexos da cultura institucional, mais comumente universidades, e que a indicação de membros reconhecidos pelos seus pares, pode conformar um perfil favorável à atuação na Comissão Nacional. / The objective of the study was to analyze the profile of the persons indicated by the research ethics institutional review boards to become members of the National Commission of Research Ethics (Comissão Nacional de Ética em Pesquisa/CONEP), considered as leaders in the research ethics evaluation system in Brazil, as to their social group representation, professional experience, experience in research ethics, views about current practices in the system and relations to formal regulations. Questionnaires were sent by mail and electronically to the 188 members of IRBs indicated as candidates in 2003 for nomination as member of CONEP, with 94 answers, representing 80% of the IRB universe at that time. The questionnaire was composed of 4 parts, with part 1 dedicated to personal characterization. The results indicated equal gender proportions, high academic qualification, and frequent participation in short courses about research and bioethics. About 50% occupied institutional positions, 18% directly related to research, and only 4% were representatives of the patients. About 90% had involvement with research in the last 10 years, a third with clinical research. Part II was dedicated to their self-evaluation as members of IRBs, revealing feelings of satisfaction and gratification with their work, and valorization of attributes such as responsibility, compromise, team work capabilities, and 89% and 85% considered themselves prepared and competent for their functions, although with differing perceptions regarding representation and political understandings about their work. Some areas present more difficulties in the analysis of the projects and meetings, seminars and case discussions were mentioned as preferential mechanisms for development. Part III identified perceptions about the functioning of the national research ethics evaluation system, and the utilization of official regulations in project analysis. A more effective participation of the patient representatives and the monitoring of projects are major problems. Areas of necessary investment: how to deal with social sciences research projects, pre-requisites and preparation of IRB members and improved communication of IRBs with each other and the National Commission. Part IV consisted of case studies dedicated to frequent ethical dilemmas in research and the majority had convergent positions as to how to deal with them. The profile of these members as leaders in their IRBs reflects also very strong institutional cultures.

O objetivo do estudo foi construir o perfil dos indicados pelos Comitês de Ética em Pesquisa - CEPs - para membros da Comissão Nacional de Ética em Pesquisa - CONEP, líderes no sistema de controle da ética em pesquisa no Brasil, quanto à representação de grupos sociais, formação e experiência profissional e experiência e conhecimento em ética na pesquisa. Enquanto informantes-chave, buscou-se conhecer práticas correntes no sistema, e compreensão da regulamentação. Foram aplicados questionários, via correio ou via eletrônica, aos 188 componentes da lista de 2003, obtendo-se 94 respostas válidas, que representaram 80% dos CEPs. O questionário constou de 4 partes - a parte I, de caracterização pessoal, mostrou proporção semelhante de gênero, alta qualificação acadêmica, participação em cursos de pequena duração sobre ética em pesquisa/ bioética, e sensibilidade social. Dos respondentes, 50% tinham cargos de gestão na instituição, 18% deles ligados diretamente à pesquisa, apenas 4% eram representantes de usuários, 90% participaram de pesquisas nos últimos 10 anos, sendo um terço em pesquisa clínica. A parte II correspondeu a uma auto-avaliação de sua participação como membros de CEPs, que mostrou satisfação com a relevância do trabalho, valorização de qualidades como responsabilidade, compromisso, habilidade para trabalho em equipe, sendo que 89% e 85% consideraram-se preparados e competentes respectivamente, apesar de percepção variada da representatividade e compreensão política de sua atuação. Identificaram-se áreas de maior dificuldade na análise de projetos, e encontros, seminários e discussão de casos como formas preferenciais de preparação. A parte III identificou as percepções sobre o funcionamento do sistema de avaliação ética das pesquisas no Brasil, evidenciando a utilização das diretrizes e normas do CNS na análise dos projetos. A mais efetiva participação dos representantes de usuários e o monitoramento das pesquisas são dificuldades freqüentes. Sugestões de melhoria do sistema referiram a abordagem dos projetos da área de ciências humanas, pré-requisitos e preparação para membros de CEPs, integração e melhoria da comunicação entre CEPs e com a Comissão Nacional. A parte IV foram estudos de casos, que evidenciaram convergência de posicionamentos na grande maioria das situações apresentadas. Conclui-se que o reconhecimento da liderança desses indicados nos CEPs institucionais tem reflexos da cultura institucional, mais comumente universidades, e que a indicação de membros reconhecidos pelos seus pares, pode conformar um perfil favorável à atuação na Comissão Nacional. / The objective of the study was to analyze the profile of the persons indicated by the research ethics institutional review boards to become members of the National Commission of Research Ethics (Comissão Nacional de Ética em Pesquisa/CONEP), considered as leaders in the research ethics evaluation system in Brazil, as to their social group representation, professional experience, experience in research ethics, views about current practices in the system and relations to formal regulations. Questionnaires were sent by mail and electronically to the 188 members of IRBs indicated as candidates in 2003 for nomination as member of CONEP, with 94 answers, representing 80% of the IRB universe at that time. The questionnaire was composed of 4 parts, with part 1 dedicated to personal characterization. The results indicated equal gender proportions, high academic qualification, and frequent participation in short courses about research and bioethics. About 50% occupied institutional positions, 18% directly related to research, and only 4% were representatives of the patients. About 90% had involvement with research in the last 10 years, a third with clinical research. Part II was dedicated to their self-evaluation as members of IRBs, revealing feelings of satisfaction and gratification with their work, and valorization of attributes such as responsibility, compromise, team work capabilities, and 89% and 85% considered themselves prepared and competent for their functions, although with differing perceptions regarding representation and political understandings about their work. Some areas present more difficulties in the analysis of the projects and meetings, seminars and case discussions were mentioned as preferential mechanisms for development. Part III identified perceptions about the functioning of the national research ethics evaluation system, and the utilization of official regulations in project analysis. A more effective participation of the patient representatives and the monitoring of projects are major problems. Areas of necessary investment: how to deal with social sciences research projects, pre-requisites and preparation of IRB members and improved communication of IRBs with each other and the National Commission. Part IV consisted of case studies dedicated to frequent ethical dilemmas in research and the majority had convergent positions as to how to deal with them. The profile of these members as leaders in their IRBs reflects also very strong institutional cultures.