Nombre de « scandales éthiques » ont émaillé l’actualité de la recherche clinique dans les pays du Sud. Face à ce constat, il semble que les principes fondateurs de l’éthique de la recherche biomédicale admis et promulgués par les déclarations et les conférences de consensus internationales ne suffisent pas à protéger au Sud les volontaires participant à des essais cliniques. Nécessitant une adaptation hors du contexte qui a permis leur consolidation, bien que soit donné à voir à chaque nouveau scandale à quel point tout infléchissement des cadres normatifs peut être porteur de dérives inadmissibles, ces principes s’avèrent pour partie remis en question par la situation économique, sanitaire, sociétale des pays du Sud.Le concept de « double standard éthique » décrivant le double écueil auquel l’éthique de la recherche doit faire face, celle-ci s’avère captive d’une forme d’impérialisme des principes et des valeurs ou bien vouée au relativisme moral. La première alternative semble devoir conduire inexorablement à l’arrêt des recherches cliniques dans les pays ne permettant pas l’application stricte des normes qui les encadrent au Nord. La deuxième semble quant à elle mener à l’acceptation d’une réalisation irresponsable,dérégulée, d’essais cliniques aux finalités variables. Face à ce constat, se pose la question de savoir si cette alternative entre absolutisation de la norme et dérégulation peut être dépassée afin de penser une éthique de la recherche au Sud à la fois universelle et singulière.L’exploration de cette question permettra de redéfinir l’éthique comme processus de discussion et de priorisation des principes universels guidé par une compréhension de situations toujours singulières. De ce point de vue, l’adaptation des « conceptions internationalistes » de l’éthique de la recherche à la singularité des contextes apparaîtra non comme une nécessité externe, provoquée par un élément extérieur,mais comme un devoir inhérent à la nature même de la visée éthique. Plus encore, les questions posées par les contextes des pays du Sud à l’éthique de la recherche clinique serviront de révélateur en contribuant à montrer le bien fondé d’une remise encause des interprétations normatives de ses principes, au Nord y compris.7 / Number of “ethical scandals” have punctuated the news of clinical research in developing countries. Given this fact, it seems that the founding principles of the ethics’ biomedical research accepted and promulgated by declarations and international conferences are not enough to protect the volunteers participating in clinical trials in South’s countries. Out of context enabling their strengthening, ethical principles require adaptation. If each new scandal shows how any shift in regulatory frameworks may carry unacceptable abuses, these principles are nevertheless found challenged by South’s economic, state of health and social organizations. The concept of “double standard ethics” describes the twin dangers to which the biomedical research ethics faces. Indeed, biomedical research is captive to a form of imperialism of principles and values, or devoted to moral relativism. The first alternative seems to lead inexorably to the cessation of clinical research in developing countries do not allow the strict application of the standards that govern the North. The second appears to lead to the acceptance of irresponsible and unregulated clinical trials.Given this situation, the question arises whether this alternative may be exceeded in order to assume a research ethics in the South at once universal and unique. The exploration of this issue will redefine ethics as a process of discussion and priorization of universal principles guided by an understanding of situations always singular. From this point of view, the adaptation of “internationalist conceptions” of research ethics to unique contexts appear not as an external necessity but as a duty inherent in the nature of the ethical aim. Moreover, questions asked by the contexts of the South’s countries to the ethics’ clinical research will serve as a contributing developer to show the merits of a challenge to normative interpretations of its principles, including in North’s countries.

Ce travail porte sur les processus migratoires et identitaires de la population coréenne installée en France ou au Québec. Son objectif premier est de comprendre l’influence du contexte socioculturel sur la façon dont les migrants s’adaptent et s’intègrent dans les pays d’accueil dont les modèles d’intégration diffèrent. Considérant que la langue constitue un élément principal dans le processus d’adaptation ainsi que dans les stratégies identitaires, la dynamique langagière des familles migrantes a été analysée avec une attention particulière. 17 familles coréennes composées du père, de la mère et de leur enfant âgé de 11-15 ans ont été rencontrées en France ou au Québec, à travers essentiellement l’entretien semi-dirigé et le questionnaire sociolinguistique. Les résultats de notre recherche révèlent que le modèle républicain assimilationniste français favorise l’intégration linguistique et culturelle des immigrants coréens alors que le modèle interculturel québécois promeut l’intégration socioprofessionnelle, civique et communautaire. Les enfants dits « de la deuxième génération de l’immigration » intègrent de manière spontanée la culture et la langue du pays d’accueil de leurs parents par la scolarisation ainsi que celles d’origine dans le cadre intrafamilial. Nos analyses qualitatives montrent que les processus adaptatifs et identitaires des migrants coréens s’élaborent en lien étroit avec le contexte socioculturel mais aussi par un travail de symbolisation de l’interculturalité sur le plan personnel et groupal. / This work concerns the migratory and identical processes of the Korean population installed in France or in Quebec. Its first purpose is to understand the influence of the socio-cultural context on the way that the immigrants adapt themselves and become integrated into the host countries whose models of integration differ. Considering that the language establishes a main element in the process of adaptation as well as in the identical strategies, the linguistic dynamics of the immigrant families was analyzed with a particular attention. 17 Korean families consisted of the father, the mother and their 11-15-year-old child were met in France or in Quebec, through essentially the semi-structured interview and the sociolinguistic questionnaire. The results of our search reveal that the French republican model promotes the linguistic and cultural integration of the Korean immigrants while the Quebec’s intercultural model promotes the socio-professional, civic and community integration. The second-generation immigrants integrate in a spontaneous way the culture and the language of the host country of their parents with the schooling as well as those of the origin into the interfamily context. Our qualitative analyses show that the adaptive and identical processes of the Korean immigrants develop in narrow relation with the socio-cultural context but also with a work of symbolization of the interculturality on the personal and group plan.

This study examines tools and practices involved in a large scale and multi-sited clinical trial of a potential drug against obesity. Two tools are in focus: a clinical research protocol and a computer control system. The analysis is based on there being different ways in which the tools are localized in order for the work to flow smoothly and to produce reliable data. It does this through delineating different types of work performed: production tasks, classical managerial work, compliance work and the work of coordinating beliefs and goals. The study is based on interviews, observations and documentary analysis. Through describing these types of work and how it is organized, the study emphasizes the trial as being part of an industrial production process. Hence, the tools are used not only to produce reliable data, but also to manage the work of the tools’ users in order to enable a smooth production process. In line with such a description, the protocol and computer control system are seen as objects that discipline practice, something that also resonates in the way staff talk about their work. The dissertation shows how the tools, despite this, leave room for aspects of clinical trial work that are both rational/technical and experiential/contingent. The dissertation also shows that obesity is enacted in different ways in the practices performed in the trial. Making sense of these somewhat contradictory enactments requires work referred to as coordination of beliefs about what obesity is, as well as of the different goals of the trial. By such a focus on invisible work, the dissertation shows that those nurses, dieticians and doctors involved in the everyday follow-through of the trial have a strategic position in mediating between pharmaceutical companies and their potential market for the drug under study, namely the trial participants.

L'imagerie par tomographie en cohérence optique (OCT) est prometteuse comme support de la prise de décision au cours des procédures d'interventions coronariennes percutanées (PCI), pou évaluer les lésions athéromateuses, juger de la bonne implantation du stent, et dépister les lésions vasculaires dues au stent. L'OCT représente donc bien une aide potentielle pour le cardiologue interventionnel tout au long de la procédure de stenting, avec un impact certain sur la stratégie interventionnelle initialement programmée. De plus, l'OCT se révèle comme un nouvel outil pour prédire la dissection des bords de stent chez les patient avec ACS sans élévation du segment ST, rendant possible une stratification des patients quant à ce risque. Des essais cliniques randomisés sont maintenant nécessaires pour savoir si l'assistance par l'OCT pendant la procédure améliore le pronostic à long terme des patients après PCI / Optical Coherence Tomography (OCT) imaging is promising in decision making during Percutaneus Coronary Interventions {PCI) procedures, including evaluating controversial plaque lesions, assessing stent implantation, and surveying stent-related vascular injury. Thus, OCT has potential to guide interventional cardiologists throughout the stent implantation procedure, impacting on planned interventional strategy. In addition, OCT is the most novel image technology to predict stent edge dissection for patients with non-ST-segment elevation ACS, enabling risk stratification of patients who are at a higher risk of this complication. Large-scale randomized trials are now warranted to assess whether OCT results and guidance during de procedure improve long-term clinical outcomes of PCis.

This thesis addresses the extraction of medical knowledge from clinical text using deep learning techniques. In particular, the proposed methods focus on cancer clinical trial protocols and chest x-rays reports. The main results are a proof of concept of the capability of machine learning methods to discern which are regarded as inclusion or exclusion criteria in short free-text clinical notes, and a large scale chest x-ray image dataset labeled with radiological findings, diagnoses and anatomic locations. Clinical trials provide the evidence needed to determine the safety and effectiveness of new medical treatments. These trials are the basis employed for clinical practice guidelines and greatly assist clinicians in their daily practice when making decisions regarding treatment. However, the eligibility criteria used in oncology trials are too restrictive. Patients are often excluded on the basis of comorbidity, past or concomitant treatments and the fact they are over a certain age, and those patients that are selected do not, therefore, mimic clinical practice. This signifies that the results obtained in clinical trials cannot be extrapolated to patients if their clinical profiles were excluded from the clinical trial protocols. The efficacy and safety of new treatments for patients with these characteristics are not, therefore, defined. Given the clinical characteristics of particular patients, their type of cancer and the intended treatment, discovering whether or not they are represented in the corpus of available clinical trials requires the manual review of numerous eligibility criteria, which is impracticable for clinicians on a daily basis. In this thesis, a large medical corpora comprising all cancer clinical trials protocols in the last 18 years published by competent authorities was used to extract medical knowledge in order to help automatically learn patient’s eligibility in these trials. For this, a model is built to automatically predict whether short clinical statements were considered inclusion or exclusion criteria. A method based on deep neural networks is trained on a dataset of 6 million short free-texts to classify them between elegible or not elegible. For this, pretrained word embeddings were used as inputs in order to predict whether or not short free-text statements describing clinical information were considered eligible. The semantic reasoning of the word-embedding representations obtained was also analyzed, being able to identify equivalent treatments for a type of tumor in an analogy with the drugs used to treat other tumors. Results show that representation learning using deep neural networks can be successfully leveraged to extract the medical knowledge from clinical trial protocols and potentially assist practitioners when prescribing treatments. The second main task addressed in this thesis is related to knowledge extraction from medical reports associated with radiographs. Conventional radiology remains the most performed technique in radiodiagnosis services, with a percentage close to 75% (Radiología Médica, 2010). In particular, chest x-ray is the most common medical imaging exam with over 35 million taken every year in the US alone (Kamel et al., 2017). They allow for inexpensive screening of several pathologies including masses, pulmonary nodules, effusions, cardiac abnormalities and pneumothorax. For this task, all the chest-x rays that had been interpreted and reported by radiologists at the Hospital Universitario de San Juan (Alicante) from Jan 2009 to Dec 2017 were used to build a novel large-scale dataset in which each high-resolution radiograph is labeled with its corresponding metadata, radiological findings and pathologies. This dataset, named PadChest, includes more than 160,000 images obtained from 67,000 patients, covering six different position views and additional information on image acquisition and patient demography. The free text reports written in Spanish by radiologists were labeled with 174 different radiographic findings, 19 differential diagnoses and 104 anatomic locations organized as a hierarchical taxonomy and mapped onto standard Unified Medical Language System (UMLS) terminology. For this, a subset of the reports (a 27%) were manually annotated by trained physicians, whereas the remaining set was automatically labeled with deep supervised learning methods using attention mechanisms and fed with the text reports. The labels generated were then validated in an independent test set achieving a 0.93 Micro-F1 score. To the best of our knowledge, this is one of the largest public chest x-ray databases suitable for training supervised models concerning radiographs, and also the first to contain radiographic reports in Spanish. The PadChest dataset can be downloaded on request from http://bimcv.cipf.es/bimcv-projects/padchest/. PadChest is intended for training image classifiers based on deep learning techniques to extract medical knowledge from chest x-rays. It is essential that automatic radiology reporting methods could be integrated in a clinically validated manner in radiologists’ workflow in order to help specialists to improve their efficiency and enable safer and actionable reporting. Computer vision methods capable of identifying both the large spectrum of thoracic abnormalities (and also the normality) need to be trained on large-scale comprehensively labeled large-scale x-ray datasets such as PadChest. The development of these computer vision tools, once clinically validated, could serve to fulfill a broad range of unmet needs. Beyond implementing and obtaining results for both clinical trials and chest x-rays, this thesis studies the nature of the health data, the novelty of applying deep learning methods to obtain large-scale labeled medical datasets, and the relevance of its applications in medical research, which have contributed to its extramural diffusion and worldwide reach. This thesis describes this journey so that the reader is navigated across multiple disciplines, from engineering to medicine up to ethical considerations in artificial intelligence applied to medicine.

À l’instar des autres disciplines de la santé, la profession chiropratique doit poursuivre ses efforts pour maintenir sa crédibilité et sa reconnaissance. À cette fin, il est essentiel de renforcer les bases scientifiques de la chiropratique par une meilleure compréhension des mécanismes et une validation de l’efficacité de l’intervention chiropratique. Cependant, plusieurs obstacles compliquent la recherche clinique en chiropratique. Le recrutement de cliniciens et d’un grand nombre de patients représente un défi de taille. Un réseau de recherche basée sur la pratique (RRBP) pourrait permettre de relever ces défis. Les RRBP sont des réseaux où les chiropraticiens collaborent avec les patients et les chercheurs. Ce projet vise à développer le premier réseau de recherche clinique chiropratique au Québec. Pour y parvenir, nous avons invité les 1323 chiropraticiens de l’Ordre des chiropraticiens du Québec (OCQ) à se joindre au Réseau québécois de recherche clinique en chiropratique (RQRCC) en 2015. Près de 200 chiropraticiens ont accepté d’en devenir membres. La structure du RQRCC a été établie en incluant un comité exécutif de quatre chercheurs et deux étudiants et un comité consultatif de neuf membres représentant différents groupes d’intérêt. Ce dernier contribue à assurer que les projets sont pertinents pour l’avancement de la pratique clinique. Cette infrastructure de recherche permettra la mise en œuvre d’études cliniques à grande échelle sur les troubles musculo-squelettiques et sur d’autres thèmes utiles pour la profession chiropratique. Le RQRCC facilitera également l'implantation des lignes directrices cliniques, le transfert des connaissances et l’évaluation de l’impact des stratégies entourant ce transfert de connaissances. Au bout du compte, ces efforts collectifs contribueront à l’amélioration de la pratique et, ultimement, de la santé des patients. Le RQRCC fait aussi partie d’un méta-réseau canadien. Il est donc attendu que cette initiative nationale mène des études de plus grande envergure afin de généraliser les résultats à l’ensemble de la population et de contribuer à l’amélioration de la santé des Canadiens. / Like all other health disciplines, the chiropractic profession needs to continue its efforts to improve its credibility and recognition. For this purpose, it is important to develop its scientific basis. Chiropractic needs to understand and validate the mechanism and effectiveness of its treatment approach. However, several challenges complicate chiropractic clinical research, such as the recruitment of qualified clinicians with interest for research, and the recruitment of patients. The Practice-Based Research Network (PBRN) approach could be a way to circumvent many of these challenges. PBRNs are networks where health professionals collaborate with patients and researchers. This project aims to develop the first chiropractic clinical research network in Quebec. For this purpose, in 2015, we invited the 1323 chiropractors of the Quebec Chiropractic licensing body to join the Réseau québécois de recherche clinique en chiropratique (Quebec Chiropractic Clinical Research Network (RQRCC)). Nearly 200 chiropractors have agreed to become members. The RQRCC is composed of an executive committee of four researchers and two students, and an advisory committee, of nine members representing different interest groups whose role is to ensure that projects are relevant to the advancement of chiropractic science. This research infrastructure, which is still under development, will enable the implementation of large-scale clinical studies on musculoskeletal disorders and other themes relevant to the chiropractic profession. This network will evaluate the impact of knowledge transfer strategies and facilitate the implementation of clinical guidelines. We believe that these actions will contribute to the improvement of patients’ health. In summary, this clinical research network will create, make accessible and transmit the best scientific evidence to its members and eventually to the entire chiropractic community. The network is also part of a Canadian meta-network. This national initiative is expected to conduct larger studies in order to generalize results to the entire population and to contribute to improving the health of Canadians.

No description available.

Le Brésil figure parmi les plus grands marchés consommateurs de médicaments. Cependant, le droit à l'accès aux médicaments, prévu dans sa Constitution Fédérale, ne fait pas partie de sa réalité. Cette situation est attribuable à plusieurs facteurs: le Brésil n'est pas capable de répondre à ses besoins internes et la consommation de médicaments n'est pas équilibrée. En réaction à cette constatation, nous analyserons la situation juridique actuelle du Brésil, afin d'indiquer les lacunes et barrières au plein accès aux médicaments et, surtout, de trouver une solution qui pourrait améliorer cette situation. Les organismes gouvernementaux brésiliens jouant un rôle important dans le développement des nouveaux médicaments sont présentés et, ensuite, l'encadrement juridique applicable à la recherche clinique et à l'autorisation de mise en marché des nouveaux médicaments est analysé; un bref survol de la législation applicable aux médicaments génériques est fait. Dans un deuxième moment de l'étude, la question d'accès aux nouveaux médicaments est mise en lumière: la législation brésilienne relative aux brevets, ainsi que le régime de licence obligatoire sont abordés; de plus, nous évaluons la compatibilité de ce régime avec l'Accord sur les ADPIC et nous évoquons les conflits internationaux qu'il a suscités. En vue de trouver des solutions aux difficultés brésiliennes identifiées, nous concluons notre étude avec l'examen de l'initiative canadienne pour favoriser l'accès aux médicaments aux pays du Sud (RCAN). Nous constatons que l'utilisation du RCAM pourrait, à court terme, favoriser l'accès aux médicaments au Brésil et, à moyen terme, aider à réduire les conflits internationaux. Finalement, à long terme, nous croyons que le Brésil pourrait jouer un rôle de leader international en adoptant une loi semblable à celle du Canada et, ainsi, il serait capable d'aider d'autres pays dans le besoin, qui n'ont aucune capacité de production locale, comme par exemple, plusieurs pays en Afrique. / Brazil is amongst the largest markets for medication and, even though the access to it is guaranteed by Brazilian Federal Constitution, it cannot be taken for granted. This situation is due to several factors: Brazil is not capable of fulfilling its needs and the consumption of drugs does not follow a balanced pattern. Given these facts, we will analyze Brazil's current legal system in order to assess which barriers and gaps prevent the population from gaining full access to medication and, most importantly, what could be done to change this reality. Brazil's government agencies involving in the development of new drugs will be presented, followed by an analysis of the legal norms applicable to clinical research and authorization to market new drugs; also, a brief assessment of the generic drugs legislation will be made. Besides, the access to new drugs issue will be put under light: Brazilian legislation concerning patents and compulsory licensing will be analyzed; as a complement, we will evaluate the compatibility of these rules with the system implemented by the TRIPS Agreement and the international conflicts related to this issue will be shown. Aiming at finding a solution to these issues, this study will focus its final part on the Canadian initiative to improve medication access on the South countries (CAMR). We find that CAMR's initiative could, on the short run, improve medication access in Brazil and, later on, could help to decrease international conflicts. On the long run, we believe Brazil could play a key role in the international scene by adopting a law similar to the Canadian one in order to be able to help countries in need that lack local production capacity, e.g., most of African countries.

Abstract in English and Afrikaans / The clinical research enterprise is an industry in crisis due to the challenges investigators and sites experience to stay viable. Clinical researchers might therefore also become an “endangered species”. The purpose of this study was to gain an understanding of early career research investigators’ experience of clinical research. A generic, exploratory, descriptive and contextual qualitative design was used. Fourteen participants were recruited and interviewed face-to-face from three different clinical research sites in the Gauteng. Data were analysed thematically and cyclically. Findings indicated that early career investigators entered the clinical research “maze” for various reasons and levels of preparedness. As they explored the maze, early career investigators found their way into a labyrinth, all the while making discoveries about the clinical environment and their own desires. They finally reached a point where they needed to move beyond the centre of the labyrinth and ask ‘Quo Vadis’ (where are we going to)? / Die kliniese navorsingsbedryf is ‘n industrie in krises weens die uitdagings wat ondersoekers en navorsingsinstansies beleef om lewensvatbaar te bly. Kliniese navorsers mag daarom ook ‘n ‘bedreigde spesie’ word. Die doel van die studie was om die belewenis van vroeë beroepsnavorsingsondersoekers in kliniese navorsing te verstaan. ‘n Generiese, verkennende, beskrywende en kontekstuele kwalitatiewe ontwerp is gebruik. Veertien deelnemers van drie verskillende kliniese navorsingsinstansies in Gauteng het deelgeneem aan een-tot-een onderhoude. Data is tematies en siklies geanaliseer. Bevindinge het aangedui dat vroeë beroepsnavorsingsondersoekers die kliniese navorsingsdoolhof betree vir verskillende redes en vlakke van gereedheid. Soos wat hulle die doolhof verken het, het vroeë beroepsnavorsingsondersoekers hulle weg in die labirint gevind, terwyl hulle die kliniese omgewing en hul eie wense ontdek het. Hulle het uiteindelik ‘n punt bereik waar hulle verby die middel van die labirint moes beweeg en hulself afvra: “Quo Vadis” (waarheen gaan ons)? / Health Studies / M.A. (Nursing Science)

Le Brésil figure parmi les plus grands marchés consommateurs de médicaments. Cependant, le droit à l'accès aux médicaments, prévu dans sa Constitution Fédérale, ne fait pas partie de sa réalité. Cette situation est attribuable à plusieurs facteurs: le Brésil n'est pas capable de répondre à ses besoins internes et la consommation de médicaments n'est pas équilibrée. En réaction à cette constatation, nous analyserons la situation juridique actuelle du Brésil, afin d'indiquer les lacunes et barrières au plein accès aux médicaments et, surtout, de trouver une solution qui pourrait améliorer cette situation. Les organismes gouvernementaux brésiliens jouant un rôle important dans le développement des nouveaux médicaments sont présentés et, ensuite, l'encadrement juridique applicable à la recherche clinique et à l'autorisation de mise en marché des nouveaux médicaments est analysé; un bref survol de la législation applicable aux médicaments génériques est fait. Dans un deuxième moment de l'étude, la question d'accès aux nouveaux médicaments est mise en lumière: la législation brésilienne relative aux brevets, ainsi que le régime de licence obligatoire sont abordés; de plus, nous évaluons la compatibilité de ce régime avec l'Accord sur les ADPIC et nous évoquons les conflits internationaux qu'il a suscités. En vue de trouver des solutions aux difficultés brésiliennes identifiées, nous concluons notre étude avec l'examen de l'initiative canadienne pour favoriser l'accès aux médicaments aux pays du Sud (RCAN). Nous constatons que l'utilisation du RCAM pourrait, à court terme, favoriser l'accès aux médicaments au Brésil et, à moyen terme, aider à réduire les conflits internationaux. Finalement, à long terme, nous croyons que le Brésil pourrait jouer un rôle de leader international en adoptant une loi semblable à celle du Canada et, ainsi, il serait capable d'aider d'autres pays dans le besoin, qui n'ont aucune capacité de production locale, comme par exemple, plusieurs pays en Afrique. / Brazil is amongst the largest markets for medication and, even though the access to it is guaranteed by Brazilian Federal Constitution, it cannot be taken for granted. This situation is due to several factors: Brazil is not capable of fulfilling its needs and the consumption of drugs does not follow a balanced pattern. Given these facts, we will analyze Brazil's current legal system in order to assess which barriers and gaps prevent the population from gaining full access to medication and, most importantly, what could be done to change this reality. Brazil's government agencies involving in the development of new drugs will be presented, followed by an analysis of the legal norms applicable to clinical research and authorization to market new drugs; also, a brief assessment of the generic drugs legislation will be made. Besides, the access to new drugs issue will be put under light: Brazilian legislation concerning patents and compulsory licensing will be analyzed; as a complement, we will evaluate the compatibility of these rules with the system implemented by the TRIPS Agreement and the international conflicts related to this issue will be shown. Aiming at finding a solution to these issues, this study will focus its final part on the Canadian initiative to improve medication access on the South countries (CAMR). We find that CAMR's initiative could, on the short run, improve medication access in Brazil and, later on, could help to decrease international conflicts. On the long run, we believe Brazil could play a key role in the international scene by adopting a law similar to the Canadian one in order to be able to help countries in need that lack local production capacity, e.g., most of African countries.