A pesquisa clínica é considerada um método inovador em medicina clínica e essencial para o desenvolvimento de novas drogas. No Brasil, a pesquisa clínica teve um grande avanço após a publicação da Resolução 196/96 pelo Conselho Nacional de Saúde e Ministério da Saúde, que foi baseada na Declaração Helsinque e Organização Mundial de Saúde. Desta forma, a realização de estudos clínicos dentro dos padrões éticos exigidos requer infra-estrutura adequada e equipe treinada. O objetivo deste estudo foi avaliar os grupos que realizam pesquisa clínica no Brasil em relação a: qualificação profissional, conhecimento regulatório e curso em Boas Práticas Clínicas (BPC). Trata-se de um estudo transversal com investigadores (PI) e sub-investigadores (SI) que foram identificados inicialmente pelo Currículo Lattes do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). A busca utilizou palavras-chave específicas que discriminam apenas aqueles que têm experiência com ensaios clínicos. Após consentimento informado, os voluntários foram submetidos a um questionário composto de questões qualitativas e quantitativas. Foram entrevistados 100 PI e SI. As regiões brasileiras mais representativas foram Sudeste (68%) e Sul (18%). As principais instituições envolvidas foram do complexo HCFMUSP, UNIFESP e outras instituições federais. Os centros foram classificados como públicos e universitário (54%) e instituições acadêmicas e privadas (23%). Com relação aos pesquisadores, 56% dedicam até 10hrs semanais para pesquisa clínica e 73% deles exercem atividades acadêmicas. No ano passado, 35% dos entrevistados tiveram 1 ou 2 artigos científicos internacionais publicados. No que diz respeito à experiência em ensaios clínicos, 57% e 77% tinham experiência na fase II e III respectivamente. Pós graduação foi observada em 86%, sendo Doutor (62%)a maior titulação observada. Sobre conhecimento BPC, 91% alegaram conhecer, embora apenas 74% tivessem curso formal. Todas as equipes de pesquisa clínica são multidisciplinares com maior participação de enfermeiros e farmacêuticos. Com relação à equipe, 88% tinham conhecimento em BPC, embora apenas 77% tivessem cursos formais. Com relação aos estudos clínicos realizados 36%, 60% e 44% são fases II, III e IV respectivamente. O tempo para aprovação dos protocolos clínicos é de um mês em 45% dos centros. A maior dificuldade em contratar profissionais nesta área foi a falta de recursos humanos qualificados (45,3%). Os benefícios da pesquisa clínica identificados foram: intercâmbio de conhecimento (35%), benefícios dos voluntários (17,8%) e melhoria na qualidade do cuidado á saúde (5,7% ). A expectativa da pesquisa clínica no Brasil citada pelos pesquisadores foi considerada boa (60,5%), mas é deficiente em incentivo e recursos. Em conclusão, os investigadores possuem qualificação e conhecimento adequado para realizar estudos clínicos, porém, existe a necessidade de maior treinamento. Os centros em que os investigadores atuam, possuem equipe treinada e infra-estrutura adequada para realização de ensaios clínicos fase II, III e IV. A pesquisa clínica possibilita ganho de conhecimento científico, atualização sobre novas condutas terapêuticas, intercâmbio de conhecimento com outras Instituições, tanto nacionais como internacionais. / Clinical trial is considered a breakthrough method in medicine and essential to the development of new drugs. In Brazil, clinical trials increased after the publication of the resolution 196/96 by the Health National Cabinet and Health Ministry, that was based on Helsinki declaration and WHO, among other relevant clinical trial documents. Clinical trials that comply with those regulations require an appropriate infrastructure and team qualification. The goal of this study was to evaluate general clinical trial groups in Brazil: professional qualification, regulatory knowledge and Good Clinical Practice. This is a transversal study with investigators (PI) and sub investigator (SI). PI and SI data were initially obtained from Curriculum Lattes from National Advice of Scientific and Technological Development (CNPq). The selection was made by using specific keywords which would discriminate those who in fact have clinical trial experience. After informed consent, the volunteers were submitted to a questionnaire which was composed of qualitative and quantitative questions. A hundred PI and SI were interviewed. The most representative Brazilian regions were Southeast (68%) and South (18%). The main institutions involved were HCFMUSP complex, UNIFESP and others federal institutions. The centers were classified in academic public institutions (54%) and private academic institutions (23%). With regard to the investigators 56% of them dedicated 10hrs per week for clinical trial and 73% have academic activities. Last year, 35% had 1 or 2 international scientific article published. Concerning the experience in trials, 57% and 77% had experience phase II and III, respectively. Academic graduation is observed in 86% of them and the higher titrations is Doctor (62%). 91% had GCP knowledge although only 74% had a formal training. About the team, all of them are multidisciplinary with majority of nurses and pharmaceuticals. 88% had GCP knowledge although only 77% had formal training. 36%, 60% and 44% of clinical trials were in phase II, III and IV. The time for approval of clinical protocols is one month in 45%. The major difficult detected was recruitment of professionals with suitable training and knowledge (45%). The benefits cited by the investigators were: improving exchange of knowledge (35%), volunteers benefits (18%) and improvement in quality of care (6%). The expectation of clinical trials in Brazil cited by the investigators was good and increasing (60%) but is deficient in incentive and resource. In conclusion, researchers have appropriate skills and knowledge to perform clinical studies however there is still a need for training. The centers where the researches work, have trained staff and adequate infrastructure for conducting clinical trials phase II, III and IV. Clinical research provides gain of scientific knowledge, update on new therapeutic conducts, sharing knowledge with other institutions, both national and international.

Para a condução de um estudo clínico hoje é necessária colaboração e participação de um diverso grupo de partes interessadas, incluindo patrocinadores do estudo, governo, agencias regulatórias, comitês de ética, pacientes, investigadores clínicos. Os centros de pesquisa clínica, local onde estudos clínicos são realizados, devem conseguir gerenciar tudo isso para que possam conduzir os estudos clínicos de forma a garantir a acurácia e qualidade dos dados, bem como a segurança dos sujeitos de pesquisa. Na busca da melhoria contínua do desempenho de uma organização, a Teoria das Restrições atua por meio de ações gerenciais sobre os gargalos, apresentando ferramentas que podem auxiliar na compreensão de um problema complexo, entre elas está a Árvore da Realidade Atual (ARA). É importante realizar um diagnóstico do ambiente interno da organização, sendo predecessor às mudanças e intervenções nas organizações de forma eficaz. O encontro de um problema leva a identificação de uma oportunidade de melhoria dos processos. Assim, o objetivo deste trabalho é verificar se a ARA pode auxiliar a gestão de uma unidade de pesquisa clínica, já que se trata de um problema complexo, apontando oportunidades de melhoria. Para isso, foi realizado um estudo de caso na Unidade de Pesquisa Clínica (UPC) do HCFMRP-USP, sendo realizadas todas as etapas para construção da ARA. Como resultado, foi construída a ARA, sendo identificados 257 Efeitos Indesejáveis (EIs) e 04 causas raízes desses efeitos, que juntas constituem os problemas centrais do centro. Para cada uma das causas raízes foi proposto um plano de ação. Conclui-se que a utilização da ARA mostrou-se eficiente no âmbito de pesquisa clínica, uma vez que conseguiu sintetizar as principais oportunidades de melhoria de um centro de pesquisa, e direcionar os esforços dos gestores em ações específicas e estratégicas. / Cooperation among a diverse group of stakeholders, including: research, sponsors industry, academia, government, nonprofit organizations, clinical investigators, patients, physicians, and regulators is necessary in conducting a clinical trial today. The investigators and sites where clinical studies are conducted, should be able to manage it all those things, so they can conduct clinical studies to ensure the accuracy and quality of data as well the safety of research subjects. In pursuit of continuous improvement of an organization\'s performance, Theory of Constraints operates through management actions on bottlenecks, with tools that can assist in the understanding of a complex problem, among them is the Current Reality Tree (CRT). It is important to make a diagnosis of the organization\'s internal environment, and before the changes and effectively interventions in organizations. Finding a problem leads to the identification of an opportunity to improve process. The aim of this study is to verify if the Current Reality Tree can assist the management of a clinical research site, since it is a complex problem, pointing out opportunities for improvement. For this, we conducted a study case in the Clinical Research Unit (UPC) HCFMRP-USP, being applied all steps from CRT methodology. As a result, it was built ARA, identified 257 Undesirable Effects (EIs) and 04 root causes of these effects, which together are the core problems. For each of the root causes was proposed a plan of action. With this it has been concluded that the use of the ARA was efficient under clinical research, one could summarize the main opportunities for improvement of a site, and direct the efforts of managers in specific and strategic actions.

A promoção do business process managment (BPM) tem o potencial de trazer diversos benefícios para organizações de diferentes tamanhos, setores de atuação, regiões geográficas ou níveis de maturidade em gerenciamento de processos. Um dos fatores críticos de sucesso para a promoção de BPM é o seu alinhamento com o planejamento estratégico da organização. Este trabalho procura explorar o potencial de facilitação da promoção de BPM em uma unidade de pesquisa clínica (UPC) por meio do alinhamento com o planejamento estratégico. A pergunta de pesquisa que se pretende responder é: quais são os benefícios de um diagnóstico e planejamento estratégico prévios à promoção de um programa de BPM em uma unidade de pesquisa clínica (UPC)? Assim, o objetivo é definir as etapas e auxiliar na condução de um planejamento estratégico em uma unidade de pesquisa clínica, identificando posteriormente os benefícios decorrentes desta prática para a promoção de um programa de BPM. O método utilizado no trabalho foi a pesquisa-ação. Concluiu-se que a análise e estruturação inicial do processo de planejamento estratégico foi adequado como preparação para um primeiro ciclo de promoção de BPM na organização focal. Com base nas lições aprendidas durante o desenvolvimento foi proposto um modelo de planejamento estratégico orientado à promoção de BPM. / Business process management (BPM) has the potential to enhance performance for organizations of different sizes, industries, geographical locations or maturity levels of process management. One critical success factor for the promotion of BPM is its alignment with strategic planning. This research aims to explore the potential benefits of aligning the strategic planning process with a BPM program. Thus, the research question is defined as: what are the benefits of executing a diagnosis and strategic planning before a BPM program in a clinical research center (CRC)? The objective of the research is to define and execute steps of a strategic planning process in a clinical research center, identifying the benefits of these activities for a subsequent BPM program. Action-research was the method applied. The main findings were that the initial diagnosis of the organization in focus\' management practices and structuring of the strategic planning process ware adequate to prepare for the first cycle of a BPM program. Based on lessons learned along the research, a model was proposed for the strategic planning process oriented towards the promotion of BPM.

Magister Artium (Development Studies) - MA(DVS) / This study is interested in understanding and describing the everyday reality of clinical researchers from the perspective of those who operate on the grassroots level –in this case, the field staff working under the guidance of the study coordinator and principal investigators.

Les dispositifs médicaux (DM) sont des produits de santé qui représentent un ensemblehétérogène de plus de 500 000 technologies, allant de la plus simple à la plus complexe.Contrairement au médicament, il n’existe pas de démarche formelle quant aux étapes dudéveloppement clinique des DM, notamment pour ceux les plus à risque.L’objectif de ce travail de thèse était de décrire les données cliniques disponibles en Francelorsqu’un DM accède au marché, et de proposer des solutions pour améliorer la quantité etla qualité des études cliniques réalisées. Pour cela, nous avons exploré deux voies :l’accompagnement des industriels pour la mise en place d’études cliniques qui répondentaux attentes des différents acteurs ; et l’utilisation de registres pour améliorer le niveau depreuve disponible, en générant des données cliniques complémentaires dès la diffusion.L’évaluation clinique des DM est complexe et difficile ; elle nécessite un apprentissage desindustriels et des interactions avec les autorités de santé. Toutefois, le niveau des donnéescliniques disponibles pour évaluer les DM doit et peut être amélioré, notamment par laspécialisation de méthodologistes et l’accompagnement des industriels par des plateformesproches du terrain clinique. / Medical devices are health products representing a heterogeneous set of more than 500 000technologies, from the simplest to the most complex ones. Unlike drugs, there is no formalframework for the stages of clinical development of medical devices, especially those with ahigher degree of risk.The objective of this thesis was to describe clinical data available in France when a medicaldevice is launched, and suggest some options to improve the quality and quantity of clinicalstudies performed. To this end, we explored two ways: supporting enterprises for theimplementation of clinical studies that meet the expectations of all stakeholders; and usingregistries to improve the level of available evidence by generating additional post-marketingclinical data.The clinical evaluation of medical devices is complex and difficult, and must go through thelearning of industrials and interactions with health authorities. However, the level of clinicalevidence should and can be improved, including the specialization of methodologists and theaccompaniment of enterprises through platforms close to the clinical field.

Introdução: O Núcleo de Ensaios Clínicos da Bahia conta com estrutura física implantada, potenciais pesquisadores em diversas especialidades e equipe capacitada para execução de protocolos de pesquisa. Apesar disso, possui reduzido número de projetos em andamento e consequentemente, sub-utilização da capacidade instalada. Objetivo: Diagnosticar a situação atual da pesquisa clínica no Hospital Universitário Professor Edgard Santos, identificar os fatores que viabilizam o efetivo desenvolvimento das atividades de pesquisa e elaborar um plano de gestão para reestruturação do Núcleo. Métodos: Estudo observacional e descritivo realizado no Hospital Universitário Professor Edgard santos, em três fases: revisão documental; observação direta da estrutura física e situação de recursos humanos e, entrevista com pesquisadores líderes de grupos de pesquisa clínica do hospital. Resultados: Foram identificados documentos relativos aos Procedimentos Operacionais Padrão das atividades de pesquisa, documento normativo da pesquisa clínica e fluxogramas de processos prioritários. Foram registradas no hospital 109 pesquisas clínicas em 2016 e 90, em 2017 Foram executados 16 protocolos de pesquisa clínica no Núcleo de Ensaios Clínicos em 2017, grande parte do grupo da Hepatologia e com patrocínio da indústria farmacêutica. Estruturalmente o Núcleo está dividido em área administrativa e clínica compartilhada com serviços assistenciais e conta com equipe composta por 8 profissionais. Foram identificados 14 pesquisadores líderes de grupo de pesquisa clínica no hospital e entrevistados 9 desses pesquisadores. A partir das entrevistas, foi elaborada a Matriz SWOT e construído o Mapa Estratégico do Núcleo de Ensaios Clínicos da Bahia, baseado no Balanced Scorecard, com 12 objetivos estratégicos, acompanhados de um Plano de Ação com 12 metas e 35 iniciativas para alcance dos objetivos traçados.Conclusão: O desenvolvimento do planejamento estratégico do Núcleo, pelo mapeamento da pesquisa na instituição poderá auxiliar a alavancar a execução de protocolos clínicos no hospital, permitindo o acesso de pacientes às novas tecnologias não disponíveis no mercado. / Introduction: The Center for Clinical Trials in Bahia has an implanted physical structure, potential researchers in several specialties and a team capable of carrying out research protocols. Despite this, it has a small number of projects in progress and, consequently, underutilization of installed capacity. Objective: To diagnose the current situation of clinical research at the University Hospital Professor Edgard Santos, to identify the factors that make feasible the effective development of research activities and to elaborate a management plan for the restructuring of the Nucleus. Methods: Observational and descriptive study conducted at the University Hospital Professor Edgard santos, in three phases: documentary review; direct observation of the physical structure and human resources situation, and interview with leading researchers from the hospital's clinical research groups. Results: Documents related to the Standard Operational Procedures of the research activities, normative document of clinical research and priority process flowcharts were identified. A total of 109 clinical trials were registered in the hospital in 2016 and 90 in 2017 Sixteen clinical research protocols were performed in the Clinical Trials Nucleus in 2017, a large part of the Hepatology group and sponsored by the pharmaceutical industry. Structurally the Nucleus is divided into administrative and clinical area shared with care services and has a team composed of 8 professionals. We identified 14 leading researchers from the clinical research group at the hospital and interviewed 9 of these researchers. Based on the interviews, the SWOT Matrix was elaborated and the Strategic Map of the Clinical Trials Nucleus of Bahia, based on the Balanced Scorecard, was constructed, with 12 strategic objectives, accompanied by an Action Plan with 12 goals and 35 initiatives to reach the objectives outlined . Conclusion: The development of the Center's strategic planning, by mapping the research in the institution, can help to leverage the execution of clinical protocols in the hospital, allowing patients access to new technologies not available in the market.

Introdução: O orçamento financeiro de estudos clínicos constitui um dos itens que compõem o projeto de pesquisa incluído nos objetivos do modelo de gestão do EPECSUS. A análise criteriosa desse documento, a fim de verificar se os valores oferecidos pelo patrocinador satisfazem os custos institucionais para a realização do estudo, deve ser uma prática comum às instituições que conduzem pesquisa clínica. A análise orçamentária deve ser baseada no fluxograma do estudo e nos valores cobrados na instituição em que o estudo será desenvolvido. Saber defender os direitos da instituição no que tange aos custos de estudos clínicos demonstra bom preparo da Instituição e certamente é apreciado pelos patrocinadores, além de ser parte fundamental na estratégia de manutenção da sustentabilidade dos centros de pesquisa. Métodos: Para desenvolvimento da proposta para cálculo do orçamento de projetos de pesquisa acadêmicos, foram utilizadas técnicas de microcusteio considerando-se valores individuais de insumos e serviços, baseados em valores de aquisição do Hospital Universitário Lauro Wanderley – PB. Foram contempladas as categorizações de custos diretos e indiretos na criação de planilhas em programa Excel, como ferramenta voltada para a execução orçamentária de projetos de pesquisa. Resultados: Chegou-se a um aplicativo em Excel para ser preenchimento pelo pesquisador e gerar um orçamento acurado do estudo, de forma amigável. É constituído por tabelas customizadas para os diferentes itens envolvidos, gerando, ao final, o orçamento consolidado. Desenvolveu-se, ainda, o manual do usuário para orientar o seu preenchimento. As planilhas poderão ser adaptadas às necessidades de cada instituição. Conclusão: O uso da técnica de microcusteio para orçamento de projetos de pesquisa, por meio de planilhas voltadas para este fim, pode determinar de forma mais precisa a viabilidade financeira de cada projeto de pesquisa, bem como melhorar a adequação financeira institucional com o seu implemento no centro de pesquisa, podendo melhorar a adequação financeira institucional. / Introduction: The financial budget for clinical trials is one of the items that make up the research project included in the objectives of the EPECSUS management model. The careful analysis of this document intending to verify if the costs offered by the sponsor satisfy the institutional costs to carry out the study should be a common practice for the institutions conducting clinical research. The budget analysis should be based on the study flow chart and the amounts charged at the institution where the study will be conducted. Knowing how to defend the institution's rights regarding the costs of clinical studies demonstrates the institution's good preparedness and it is certainly appreciated by the sponsors, as well as being a fundamental part of the strategy of maintaining the sustainability of the research centers. Methods: Microcountment techniques were used for the budgeting of research projects based on individual values of inputs and services, based on acquisition values of the Lauro Wanderley University Hospital - PB, as well as the categorization of direct and indirect costs through the creation of Excel spreadsheets as a tool for budget execution of research projects. Results: An application in Excel was reached to be completed by the researcher and generate an accurate study budget, in a friendly way. It is made up of custom tables for the different items involved, generating, in the end, the consolidated budget. The user manual was also developed to guide its completion. The worksheets can be adapted to the needs of each institution. Conclusion: The use of the micro-budgeting technique for budgeting research projects, through spreadsheets designed for this purpose, can determine more precisely the financial viability of each research project, as well as improve the financial adequacy institution with its implementation in the research center.

La surveillance des infections sur prothèses ostéo-articulaires (IPOA) est une cible de la surveillance des infections nosocomiales, calcul d'incidence difficile et peu robuste (données manquantes, pas de suivi à long terme), sur cette chirurgie à faible incidence d'infection du site opératoire (ISO). Le PMSI est une base exhaustive de données médico-administratives, permettant de suivre la trajectoire des patients (chainage). L'objectif de la thèse était d'évaluer la validité du PMSI pour la surveillance des IPOA et d'estimer son utilisation en routine sur une cohorte régionale. Une cohorte rétrospective régionale de patients avec première arthroplastie de hanche ou de genou a été constituée en utilisant la base PMSI. La définition d'IPOA était basée sur un algorithme PMSI utilisant les codes CIM-10 et les actes CCAM. Une étude de sensibilité sur 1 000 dossiers médicaux était réalisée par une enquête cas-témoin nichée dans la cohorte. L'application de la définition validée (Se 97%, Spe 95%, VPP 87%, VPN 98%) dans la cohorte a permis le calcul du taux d'IPOA, 2,2/100 pers-année [IC 95% 2,0- 2,6] et d'estimer les facteurs de risque : sexe masculin, dénutrition, obésité, maladies chroniques. La médiane de survenue de l'IPOA était 71 jours (1 à 1 650 j) mais un tiers des IPOA survenait plus d'un an après la pose. Ce travail a démontré le potentiel de l'outil PMSI (fiabilité, facilité d'utilisation, moindre coût) pour la surveillance des ISO, sous conditions d'un algorithme approprié de sélection des cas. / One target of surgical site infections (SSI) surveillance is hip or knee arthroplasty infections (HKAI), however, HKAI incidence estimations are considered to be poorly effective, especially regarding data collection and patient follow-up. In France, each hospital discharge must be registered in the National Hospital Discharge Database (HDD), convenient and permanent medico-administrative database that can be mined for epidemiological studies and evaluation. This study aims to assess performance criteria of using the HDD as an additional tool to survey SSI occurring after HKA and to study its use in routine. A cohort study was conducted using retrospectively collected regional data from the French HDD. Surveillance of HKAI occurrence was performed based on various algorithms using the ICD-10, and the classification of procedures in a case-control study nested in the cohort. The HKAI case definition was validated by checking 1,000 medical charts as the gold standard, giving performance criteria as Se 97%, Spe 95%, PPV 87%, PNV 98%. The HKAI incidence density was 2.2/100 pers-year [CI95% 2.0- 2.6] and risk factors were male gender, undernutrition, obesity, chronic diseases. The median time for HKAI occurrence was 71 days (1-1,650 d), but 1/3 of HKAI occurred more than one year after arthroplasty. The HDD potential for routine SSI surveillance in low risk surgery was demonstrated, under conditions of having appropriate algorithm for selecting infections.

O presente estudo teve por objetivo observar os níveis de concordância entre a avaliação clínica e fotográfica digital no diagnóstico de desempenho de restaurações posteriores (Classe I e Classe II) em resina composta. As avaliações clínicas foram feitas por dois examinadores (C1 e C2) calibrados (e-calib) usando critérios da Fédération Dentaire Internationale (FDI) considerando propriedades estéticas, funcionais e biológicas. Em cada momento de avaliação clínica, uma fotografia digital padronizada de cada restauração foi realizada. Dois examinadores digitais (D1 e D2), igualmente calibrados e usando os mesmos critérios avaliaram todas as imagens obtidas nas avaliações clínicas. Os dados foram analisados com Coeficiente de Cohen Kappa e teste não paramétrico de Kruskal-Wallis e o teste de Dunn de comparação múltipla, com nível de significância de 5%. Comparações intra (mesmo método) e inter (métodos diferentes) examinadores foram feitas. Os resultados revelaram que os níveis de concordância variaram de \"Perfeito\" a \"Justo\". Houve diferença significante (p < 0.05) intra-examinadores; entre C1 e C2 para o manchamento marginal; entre D1 e D2 para brilho superficial, estabilidade de cor e translucidez, forma anatômica, e fratura do material e retenção; inter-examinadores foram encontradas diferenças significantes em todas as propriedades estéticas (brilho superficial, manchamento marginal, estabilidade de cor e translucidez e forma anatômica) e funcionais (fratura do material e retenção e adaptação marginal) observadas. A associação entre a imagem digital e o exame clínico pode ser uma ferramenta promissora para detecção de falhas precoces em restaurações de resina composta, necessitando de mais estudos que investiguem o método digital. / The present study aimed to evaluate the agreement levels between clinical and digital photographic assessments on the performance of posterior composite resin restorations (Class I and Class II). The clinical assessments were made by two examiners (C1 and C2) calibrated through e-calib with the Fédération Dentaire Internationale (FDI) criteria considering esthetic, functional and biological properties. In each moment of clinical assessment, standard digital photographs of each restoration were obtained. Two digital examiners (D1 and D2), equally calibrated and using the same criteria, evaluated all the images obtained in the clinical assessment. The data were analyzed with the calculation of Cohen Kappa coefficient, Kruskal-Wallis non-parametric test and Dunn\'s multiple shared test, with significance of 5%. Intra (same method) and inter (different methods) comparisons were realized. The results showed that agreement levels varied from \"Perfect\" to \"Fair\". There was a significant difference (p < 0.05) intra-examiners; between C1 and C2 to the marginal staining parameter; between D1 and D2 in the parameters surface luster, colour match and translucency, esthetic anatomical form and fracture of material and retention; inter-examiners was noticed significant difference in all the esthetic (surface luster, colour match and translucency, marginal staining, esthetic anatomical form) and functional properties (fracture of material and retention and marginal adaptation) observed. The association between the digital image to the clinical exam may be a promising tool associated with the clinical method to detect early failures in composite resin restorations, requiring further studies investigating the digital method.

L’oxaliplatine (OXA) est un anticancéreux couramment employé en oncologie, son efficacité étant reconnue en première ligne dans le traitement de nombreux cancers. Cependant, son utilisation est limitée par l’apparition de neuropathies impactant la qualité de vie du patient. Pour identifier et étudier des marqueurs cliniques, plasmatiques et électrochimiques de neuropathie chronique induite par l’oxaliplatine (NPIO), deux études pilotes (LIPIDOXA et CANALOXA) ont été réalisées. Les patients de l’étude LIPIDOXA ont été inclus avant traitement par OXA et ont été évalués avant traitement, tout au long du traitement et six mois après l’arrêt. Entre mai 2014 et juin 2016, 35 patients ont été inclus. L’apparition d’une hypoesthésie thermique a été mise en évidence six mois après arrêt de l’OXA, révélateur d’un processus neurotoxique qui se poursuit même après l’arrêt du traitement. L’étude des marqueurs plasmatiques a révélé, en fin de traitement, une augmentation de la production de prostaglandines E2, un niveau moins élevé de stress oxydant chez les patients souffrant d’une neuropathie de grade 2 ainsi qu’une diminution de la concentration des triglycérides polyinsaturés associée à une tendance à l’augmentation des acides gras libres polyinsaturés. Les patients de l’étude CANALOXA, tous neuropathiques, ont été inclus en cours de traitement par OXA et évalués une seule fois. Entre avril 2016 et mars 2017, 36 patients ont été inclus. Les valeurs des conductances électrochimiques de la peau (ESC) étaient pathologiques pour un tiers des patients. Les valeurs d’ESC étaient bien corrélées avec le score de douleur neuropathique.Ces marqueurs sont cependant peu spécifiques et semblent d’apparition tardive. Aussi, ils sont difficilement utilisables en pratique clinique pour un éventuel suivi de la tolérance neurologique au traitement. Au-delà de l’apport clinique et thérapeutique modéré, ce travail renforce la compréhension de la physiopathologie de la NPIO dans le domaine de la neuropathie à petites fibres, les processus inflammatoires associés et la perturbation du métabolisme lipidique chez le patient traité par oxaliplatine.La complémentarité et les similarités de ces travaux rappellent que la prise en charge du patient doit être globale et conjuguer des éléments variés au sein desquels le patient doit rester au cœur de la gestion de la NPIO. Ce projet de recherche s’inscrit dans une dynamique d’amélioration continue et les résultats des études pilotes constituent une base pour approfondir les travaux. / Oxaliplatin (OXA) is an anti-cancer drug widely used in oncology, its effectiveness is recognized in first-line chemotherapy regimen in many cancers. However, its use is limited by an onset of a disabling peripheral neuropathy with a negative association with quality of life. To identify and study clinical, plasma and electrochemical markers of oxaliplatin-induced chronic neuropathy (OIPN), two pilot studies (LIPIDOXA and CANALOXA) were conducted.Patients in the LIPIDOXA study were included prior to OXA treatment and were evaluated before treatment, during treatment, and six months after discontinuation. Between May 2014 and June 2016, 35 patients were included. The onset of thermal hypoaesthesia was highlighted six months after OXA completion, revealing a neurotoxic process that extends beyond treatment. The study of plasma markers revealed, at the end of treatment, an increase of prostaglandins E2 release, a lower level of oxidative stress in patients suffering from grade-2 neuropathy as well as a decrease in the concentration of polyunsaturated triglycerides associated with a tendency in polyunsaturated free fatty acids increase. The patients in the CANALOXA study, all neuropathic, were included during treatment with OXA and evaluated once. Between April 2016 and March 2017, 36 patients were included. The values of the electrochemical conductances of the skin (ESC) were pathological for one third of patients. ESC values were well correlated with the neuropathic pain score.However, these markers are sparsely specific and seem to be of late onset. Thus, they are are not suitable for a possible monitoring of the neurological tolerance of the treatment in the current care practice. Beyond the moderate clinical and therapeutic contribution, this work strengthens the understanding of the pathophysiology of OIPN in the field of small-fiber neuropathy, the associated inflammatory processes and the disruption of lipid metabolism in the patient treated with oxaliplatin.The complementarity and similarity of this work remind us that the patient care must be global and combine various elements in which the patient must remain at the heart of the management of the OIPN. This project takes part in a dynamic of continuous improvement and the results of these pilot studies constitute the basis for further research in this field.