Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Saúde Coletiva, Florianópolis, 2014. / Made available in DSpace on 2015-04-29T21:01:07Z (GMT). No. of bitstreams: 1 333075.pdf: 1774661 bytes, checksum: e5fa9c30aaaf6ff60cf50832b788a2df (MD5) Previous issue date: 2014 / Ao final do século XX, o debate acerca da universalidade dos princípios éticos para pesquisas envolvendo seres humanos emanados pela Declaração de Helsinque, documento promulgado pela Associação Médica Mundial, foi iniciado. O pano de fundo das discussões consistiu nas pesquisas médicas, patrocinadas por instituições de nações ricas, as quais sendo moralmente inaceitáveis de serem conduzidas em seus países, foram conduzidas em países periféricos transformando populações pobres como cobaias de ensaios clínicos placebo controlados, mesmo com a existência de terapias eficazes para as doenças em estudo. Tais estudos são exemplos de intervenções biopolíticas, caracterizadas pelo filósofo francês Michel Foucault (2000; 2008a), como táticas existentes nos Estados modernos que fazem da dimensão biológica humana um recurso para atingir determinados fins, em geral, a maximização da vida do coletivo. Contudo, o poder de maximizar a vida na biopolítica é acompanhado de um poder de morte, em que, para se fazer viver, será necessário deixar morrer uma parcela da população. Este estudo versa sobre a ética em pesquisa médica envolvendo seres humanos no panorama internacional, mais especificamente, no desamparo dos participantes em ensaios clínicos nos países em desenvolvimento por conta do duplo standard, ou seja, da adoção de critérios de proteção diferentes dos países centrais quando um mesmo desenho metodológico de ensaios clínicos seja realizado em países de poucos recursos. O objetivo foi analisar a emergência e o desenvolvimento do princípio do uso do placebo expresso na Declaração de Helsinque como processo de formação de uma estratégia biopolítica. Defende-se a tese de que a Declaração de Helsinque configura-se como uma estratégia biopolítica na medida em que o princípio do uso do placebo, emendado em 2013, instaurou o duplo standard para ensaios clínicos nos países em desenvolvimento. Para tanto, foi realizada uma análise genealógica, conforme preconizado por Foucault (2004a; 2000; 1996), do princípio do uso do placebo na Declaração de Helsinque tendo como fonte de dados principais os documentos da Associação Médica Mundial norteadores dos processos de discussão e revisão da Declaração de Helsinque e suas sete versões oficiais, no período compreendido entre 1953 e 2013. Os resultados dos processos de análise e discussão são apresentados em dois artigos. O primeiro artigo discute os bastidores da história da Declaração de Helsinque, desde sua gênese aos processos de revisão. O segundo analisa a gênese e o desenvolvimento do14princípio referente ao uso do placebo na Declaração de Helsinque até a legitimação do duplo standard ético para ensaios clínicos randomizados nos países em desenvolvimento em 2013. A partir das análises, foi possível considerar que a Declaração de Helsinque coloca em evidência a existência de uma verdadeira estratégia biopolítica, segundo o qual, por conta das desigualdades socioeconômicas no panorama global, corpos sem direitos passam a ser instrumentalizados no campo da experimentação médica. Desse modo, um desvio de conduta ética em pesquisa envolvendo seres humanos se transformou erroneamente em uma prática aceitável. Nesse sentido, o presente estudo buscou contribuir como forma de resistência ao imperialismo moral e aos interesses privados que minimizam a proteção dos participantes de pesquisa nos países em desenvolvimento e aponta para a necessidade de justiça social no campo da experimentação humana.<br> / Abstract : At the end of the twentieth century started the debate about ethical principles universality for research involving human subjects issued by the Declaration of Helsinki, a document promulgated by the World Medical Association. Discussions background was medical research sponsored by wealthy nations? institutions, which would not be morally acceptable in their countries. Thus, they used poor populations from periphery countries as guinea pigs in clinical trials of controlled placebos, even with the existence of efficient therapies for diseases under study. Such studies are examples of biopolitical interventions characterized by the French philosopher Michel Foucault (2008a; 2000) as existing tactics in modern states that turn human biological dimension into a resource in order to achieve individual goals, in general, collective life maximization. However, the power to maximize the life, in biopolitics, is accompanied by a death power. Therefore, in order to live it will be necessary to let die a population?s portion. The present study focuses on medical research ethics involving human subjects in the international arena, specifically on participants? helplessness of clinical trials because of a double standard, in developing countries. In other words, the adoption of different protection criteria of developed countries when the same methodological design on clinical trials is conducted in countries with poor resources. The aim was to analyze the emergence and development of placebo use principle expressed in the Declaration of Helsinki as a training process of a biopolitical estrategy. It is possible to defend the thesis that the Declaration of Helsinki configures a biopolitical strategy to the extent that placebo-use principle, amended in 2013, established the double standard for clinical trials in developing countries. Thereby, there was a genealogical analysis according to Foucault?s recommendation (2004a, 2000, 1996) on the placebo-use principle, in the Declaration of Helsinki, having as main data source the World Medical Association?s documents. They guided discussion processes and revision of the Declaration of Helsinki, and also, their seven official versions in the period between 1953 and 2013. Two articles present the analysis and discussion processes? results. The first one develops the inside story of the Declaration of Helsinki, from its genesis to the revision processes. The second one examines the principle?s genesis and development regarding the use of placebo in the Declaration of Helsinki until the legitimation of ethical double standard16for randomized clinical trials in developing countries, in 2013. From the analysis, it was possible to consider that the Declaration of Helsinki highlights the existence of a valid biopolitical strategy. According to that and because of socioeconomic inequalities, in the global picture, human bodies with no rights are being exploited in the medical experimentation field. Thus, an ethical conduct deviation in research involving humans mistakenly turned into an acceptable practice. The research seeks to contribute as a resistance form to moral imperialism and private interests that minimize research participants? protection, in developing countries. Also, it points out the need for social justice in the field of human experimentation.

O presente trabalho busca revisar fatores metodológicos e relativos aos pacientes associados com a resposta ao placebo em ensaios clínicos randomizados de antidepressivos em crianças e adolescentes através de uma atualização da revisão sistemática Placebo Response in Randomized Controlled Trials of Antidepressants for Pediatric Major Depressive Disorder de Bridge et al., publicada em 2009 com dados referentes ao período de 1997 a 2006. Este estudo analisou preditores relacionados ao indivíduo, como gênero, proporção de caucasianos, primeiro episódio depressivo, idade, tempo de doença e gravidade de sintomas depressivos. Quanto a possíveis preditores metodológicos, foram analisados ano de publicação, número de locais de estudo, número de pacientes randomizados, tempo de estudo, local (nos Estados Unidos ou não), se houve placebo run in period, o uso de placebo para todos os participantes anteriormente à randomização e a média de participantes randomizados por local de estudo. Esta revisão identificou como preditor mais importante para resposta ao placebo a variável número de locais de estudo, mesmo com controle para gravidade de doença. Publicado em 2009, este estudo foi o único ao investigar efeito placebo primariamente a analisar dados referentes apenas aos transtornos depressivos na infância e na adolescência e exclusivamente antidepressivos de segunda geração, não incluindo antidepressivos tricíclicos. Tendo em vista que mais de uma década se passou desde a publicação do estudo mais recente incluído, nesta dissertação buscou-se atualizar esses resultados, utilizando os mesmos critérios de busca de estudos e de inclusão e de exclusão, também fazendo uso das mesmas variáveis e análises estatísticas. A análise compreendeu o período de 2006 a 2015, com a inclusão de 4 novos estudos publicados e não publicados, que preencheram os mesmos critérios descritos em 2009. A amostra de pacientes aumentou cerca de 26%, com o número de pacientes randomizados aumentando de 2.862 para 3.608. As características de estudo que tiveram associação estatisticamente significativa com a resposta ao placebo foram número de pacientes randomizados e número de locais de estudo. Após análise por regressão múltipla, o único preditor de resposta ao placebo foi o número de locais de estudo. Diferentemente do estudo anterior não houve associação entre a proporção de respondedores ao placebo e o ano de publicação. Utilizando a estratégia de investigação mais semelhante possível e com a inclusão dos últimos dez anos em estudos, o principal achado do estudo original pôde ser replicado, e o conhecimento sobre o tema atualizado. / This study aims to review methodological and patient characteristics associated with placebo response in randomized clinical trials of antidepressants in children and adolescents with major depressive disorder. We aim to update the study Placebo Response in Randomized Controlled Trials of Antidepressants for Pediatric Major Depressive disorder. Bridge et al. published this study in 2009 with data comprehending 1997 to 2006. The authors examined patient characteristics such as gender, proportion of Caucasian, recurrent depression, age, duration of illness and severity of depressive symptoms. Also possible clinical trial predictors were publication year, number of study sites, number of randomized patients, study duration, location (USA and non-USA), placebo run-in period, and mean number of participants per study site. The strongest predictor of placebo response found was number of study sites, even controlling for severity of illness. Furthermore placebo response has increased over the years in the studies analyzed. This review was the only study to investigate primarily placebo response in depressive disorder in childhood and adolescence and second-generation antidepressants, not including tricyclic antidepressants. The article presented here sought to update these results using the same search syntax, as well as inclusion and exclusion criteria, performing analysis with the same variables and statistical strategy. The update included research from 2006 to December 2015, with the inclusion of 4 published and unpublished studies that met the same criteria described in 2009. The sample increased around 26%: the number of patients randomized was 2,862 in the 2009 review, reaching to 3,608 in 2016. Number of patients randomized and number of study sites were the only variables that were significantly correlated with placebo response. Severity of depressive symptoms was not associated with placebo response in this update. After multiple regression analyses, the only predictor of placebo response was number of study sites. Unlike the previous study, there was no correlation between response to placebo and year of publication. Using the most similar research strategy with a larger sample the main finding of the original study could be replicated.

Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2016-02-19T17:40:04Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO Amanda Araujo da Silva.pdf: 1118936 bytes, checksum: 6bd8bc17d5acd18170a03c0868d86bce (MD5) / Made available in DSpace on 2016-02-19T17:40:04Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO Amanda Araujo da Silva.pdf: 1118936 bytes, checksum: 6bd8bc17d5acd18170a03c0868d86bce (MD5) Previous issue date: 2015-03-05 / CNPQ / O uso das plantas medicinais é a forma mais antiga de medicação. Muitos dos medicamentos que conhecemos hoje são oriundos de fontes animais e vegetais, porém apenas recentemente sua eficácia foi comprovada, através de comprovações científicas, fundamentando os Programas de assistência a saúde complementar da Organização Mundial de Saúde. É comprovado que diversas plantas contêm ingredientes biodinâmicos medicinalmente benéficos que foram testados clinicamente através de processos laboratoriais; outras plantas estão sendo testadas até os dias atuais. Contudo, ainda há uma lacuna quanto a toxidade das plantas e ao mal conhecimento desse mecanismo. O principal objetivo é elucidar as plantas medicinais que são utilizadas na Região Metropolitana do Recife para o tratamento das cefaleias e verificar se há associação entre o conhecimento popular e o conhecimento científico. O estudo foi observacional e descritivo, em duas fases: 1) entrevistas semiestruturadas realizadas com os vendedores dos Mercados Públicos; 2) revisão narrativa através das bases de dados PUBMED e SCIENCEDIRECT. As principais plantas mencionadas foram: colônia (Alpinia speciosa), anis estrelado (Illicium verum) anador ou chambá (Justicia pectoralis) e babatenon ou barbatimão (Stryphnodendron), as quais, através da revisão, foram identificadas como portadoras de substâncias anti-inflamatórias e analgésicas que são capazes de melhorar a condição de saúde do indivíduo. / The use of medicinal plants is the oldest form of medication. Many of the medications we know today are of origin animal and vegetable sources, but only recently its effectiveness has been proven through scientific evidence, basing assistance programs complement the health of the World Health Organization. It is proven that many plants contain biodynamic ingredients medicinally beneficial that have been clinically tested by laboratory processes; other plants are being tested to the present day. However, there is still a gap as the toxicity of plants and evil knowledge of this mechanism. The main objective is to elucidate the medicinal plants that are used in the Metropolitan Region of Recife for the treatment of headache and check for association between the popular knowledge and scientific knowledge. The study was observational and descriptive, in two phases: 1) semi-structured interviews with the sellers of the Public Markets; 2) narrative review through PubMed and SCIENCEDIRECT databases. The main plants mentioned were: Colony (Alpinia speciosa), star anise (Illicium verum) Anador or Chamba (Justicia pectoralis) and babatenon or barbatimão (Stryphnodendron), which, through the review, were identified as having anti-inflammatory substances and analgesic that are able to improve the health condition of the individual.

Class of 2015 Abstract / Objectives: To retrieve data from RCTs for lorcaserin and phentermine and topiramate combination on weight loss, BMI reduction, and other factors from the placebo groups and to determine if there is a difference in weight loss between those groups. Methods: Design: Meta-analysis Inclusion criteria: RCTs that compared lorcaserin or phentermine/topiramate to placebo as submitted to the FDA and posted to the FDA website. The studies needed to report weight loss or BMI values at baseline and post-treatment. Measures: The primary dependent variables were weight lost in kilograms, change in BMI, and percent who achieved 5% weight loss in the placebo arm. Data Collection: A standardized data collection form was used to extract data from the selected trials. Data was independently extracted by 3 researchers and discrepancies were resolved by consensus. Data Analysis: Data was analyzed by constructing a forest plot of the amount of weight lost in the placebo arm stratified by type of drug. A funnel plot and Kendall’s tau were used to assess publication bias. Heterogeneity was assessed with I2. The a priori alpha level was 0.05. Results: Statistically significant weight loss was achieved in the placebo arm in all 6 RCTs Weight loss was consistent across type of study Lorcaserin studies, mean = 2.42 kg Phentermine/topiramate studies, mean = 2.14 kg Overall rate of 5% weight loss was 0.32 No data was reported on actual caloric intake or actual quantity of exercise Funnel plot and Kendall’s tau (p = 0.85) indicated there was no publication bias There was heterogeneity in the lorcaserin studies resulting from one study reporting a large effect Conclusions: Participants in the placebo arm lost weight with monthly counseling on calorie intake and exercise, however, actual caloric intake or quantity of exercise that resulted in the weight loss is unknown.

The placebo effect represents a fascinating example of how cognition can influence the physiology of the brain and body. The expectation of therapeutic benefit elicited by a placebo given in the guise of active medication has been proposed to be a form of reward expectation, and is associated with activation of brain reward circuitry. Prominent placebo effects occur in Parkinson’s disease (PD), where the expectation of symptom improvement stimulates dopamine release in the striatum. In the work described in this dissertation, positron emission tomography with [¹¹C] raclopride was used to investigate the relationship between the strength of expectation of benefit and the degree of dopamine release in PD, and how this relationship corresponds to current models of dopamine function in reward. Chapter 3 describes a pilot study conducted in patients who had undergone subthalamic nucleus deep-brain stimulation (STN-DBS) in which we examined how awareness of stimulator status (ON or OFF) affected synaptic dopamine levels compared to when subjects were blind. No difference was detected between conditions; however, it proved to be difficult to maintain blinding due to the profound effects of STN-DBS. Chapter 4 describes the development of the methodology for the analysis of high-resolution PET data, in which we utilized the combined efforts of neuroscience and imaging physics to optimize the analysis of [¹¹C] raclopride PET data. In Chapter 5, I describe the use of verbal instructions to manipulate patients’ expectations in order to investigate how the likelihood of receiving levodopa influenced dopamine release when the patients were in fact given placebo. Placebo-induced dopamine release was differentially modulated by expectation in the dorsal and ventral striatum: dopamine release in the putamen was related monotonically to expected reward value, whereas dopamine released in the ventral striatum reflected the uncertainty of benefit or the salience of the expectation. The placebo effect in PD therefore involves at least two related but separate mechanisms: the expectation of benefit itself, which is scaled to reflect the value of the drug to the patient and is mediated by nigrostriatal dopamine, and the uncertainty or salience of benefit that is mediated by mesolimbic dopamine. / Medicine, Faculty of / Graduate

AD/HD medications are shown to be significantly more successful at enhancing attention/concentration performance in individuals with AD/HD than placebo treatments. Few studies, however, have investigated the possibility of a placebo reaction in both medication and placebo groups by comparing placebo treatments to no treatment at all. Using an undergraduate population, I evaluated the effect of expectations about a treatment's efficacy on performance in an attention/concentration task. In addition to cognitive performance outcome measures, I included several physiological measures, such as heart rate variability (HRV) through respiratory sinus arrhythmia (RSA). Contrary to expectations, no differences were observed in performance on attention tasks or physiological measurements as a result of the believed efficacy of an orally administered placebo treatment.

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Introduction Placebos have been used in medical treatments since the dawn of medicine. The placeboeffect is referred to as a beneficial effect of a treatment which cannot be attributed to thepharmacological component of the treatment given. Aim and Method We attempt to understand the current research regarding the placebo effect, its mechanismsand driving factors. We utilize hermeneutics, text-based analytics and argument analysis toanswer our ethical questions regarding the usage of placebo and the placebo effect. Results Classical conditioning and expectation have been accredited as the two most prominentfactors driving a placebo effect. Recent research focuses on identifying minor factorsinfluencing these prominent factors. Through modern imaging techniques researchers haveidentified physiological responses to the placebo effect.We pose four different ways in which a placebo treatment option could be considered ineveryday medicine. We also discuss whether the placebo effect should be used for itsbeneficial effects in all medical treatments, and how this could affect medicine and healthcarepractitioners. Conclusion Current research provides us with substantial evidence that the placebo effect has aphysiological component. It also provides us with explanations as to how this effect can beutilized in every day medical care. The placebo effect can even be utilized without deceivingthe patient which has always been the biggest argument against incorporating it in day to daymedicine. However, there is still lacking evidence of when a placebo effect can be utilized toits full potential which limits its current clinical applications.