Le cancer du foie est la deuxième cause de mortalité due au cancer dans le monde, avec près de 83% des cas et 84% des décès ayant lieu dans les pays en voie de développement. Le type histologique de cancer du foie le plus fréquemment répandu est le carcinome hépatocellulaire (HCC). Selon la littérature disponible, le HCC affecte électivement des sujets masculins de plus de 50 ans ayant développé préalablement une cirrhose hépatique. Nos objectifs étaient donc i) de confirmer au niveau moléculaire la singularité du HCC chez les patients péruviens, ii) d'évaluer les stratégies d'intervention chirurgicale dans le contexte clinique iii) d'étudier les pratiques de médecine traditionnelle, complémentaire et alternative (TCAM) chez les patients iv) d'étendre cette étude à d'autres pays en développement afin d'obtenir une vision plus globale de la problématique liée au cancer du foie. Nous avons montré que le HCC péruvien présentait un spectre de mutations unique. De plus, nous avons démontré que les arbres décisionnels thérapeutiques développés jusqu'alors ne sont pas adaptés au contexte clinique rencontré au Pérou, et qu'ils sont susceptibles d'être réévalués afin d'augmenter la proportion de patients pouvant être candidats à une intervention chirurgicale. Nous avons caractérisé le fait que la majorité des patients avec un HCC a recours à la phytothérapie de manière complémentaire et alternative. Enfin, nous avons réalisé une étude d'épidémiologie clinique préliminaire sur le cancer du foie au Cambodge. Nous avons décrit une situation clinique distincte de celle rencontrée au Pérou, mais qui nécessite également des recherches scientifiques et cliniques plus approfondies. / Liver cancer is the second leading cause of cancer related death in the world. About 83% of liver cancer cases occur in the developing world. The preeminent histotype of liver cancer is hepatocellular carcinoma (HCC). According to the relevant literature, HCC is defined by patient profile corresponding grossly to cirrhotic males over 50 years old. The aims of the present work were thus to i) confirm at the molecular level the pecularity of Peruvian HCC; ii) evaluate the surgical intervention strategies for HCC in the clinical context encountered in Peru; iii) study the practices of traditional, complementary and alternative medicine ( TCAM) among patients; iv) widen the study to other low- and middle income countries in order to provide deeper insights on liver cancer. We found that Peruvian HCC displayed a unique mutation spectrum. Furthermore, we demonstrated that current therapeutic algorithms for liver cancer are not suited to the clinical context found in Peru. These therapeutic algorithms should be reevaluated in order to increase the number of patients who could be eligible for surgical intervention. Moreover, we characterized the fact that the majority of Peruvian HCC patients rely on phytotherapy in a complementary and alternative way. Finally, we undertook a preliminary clinical, epidemiological study on liver cancer in Cambodia. We delineated a clinical context distinct from the one described in Peru that also requires further clinical and scientific investigation.

Early diagnosis is a promising strategy to reduce premature mortalities and for optimal use of resources. But the absence of mathematical models specific to the data settings in LMIC’s impedes the construction of economic analysis necessary for decision-makers in the development of cancer control programs. This thesis presents a new methodology for parameterizing the natural history model of breast cancer based on data availabilities in low and middle income countries, and formulation of a control optimization problem to find the optimal screening schedule for mammography screening, solved using dynamic programming. As harms and benefits are known to increase with the increase in the number of lifetime screens, the trade-off was modeled by formulating the immediate reward as a function of false positives and life-years saved. The method presented in thesis will provide optimal screening schedules for multiple scenarios of Willingness to Pay (numeric value assigned for each life-year lived), including the resulting total number of lifetime screens per person, which can help decision-makers evaluate current resource availabilities or plan future resource needs for implementation.

En Haïti, la sécurité routière est un problème de santé publique important, causant plus de blessés et de morts que le système de santé du pays ne peut prendre en charge. Afin d’améliorer la sécurité routière, des stratégies de transfert de connaissances (TC) sont nécessaires pour promouvoir l’élaboration de politiques basées sur les connaissances issues de la recherche (CIR). Une stratégie de TC a été élaborée pour partager avec des acteurs clés les résultats de trois récentes études sur la sécurité routière en Haïti. L’objectif de la présente recherche était d’évaluer l’appréciation, le contenu et l’impact sur l’utilisation des connaissances de cette stratégie. L’étude a utilisé un devis mixte, employant deux questionnaires quantitatifs (n = 13/16) deux à trois mois après un atelier délibératif au coeur de la stratégie et des entretiens qualitatifs (n = 12/16) ont été menés sept à neuf mois post-atelier. L’atelier a généralement été apprécié par les participants, notamment pour la qualité des données présentées et pour son approche multidisciplinaire. Cependant, ils ont été déçus par l’absence de décideurs, et par le nombre et la variété limités de parties prenantes présentes. Même si les participants ont rapporté une forte volonté d’utiliser les connaissances présentées, l’atelier a eu un effet limité sur leur utilisation. Cette étude met en évidence le potentiel des ateliers délibératifs intégrés à une stratégie de TC dans les pays à revenu faible et intermédiaire, ainsi que l’importance d’inclure les décideurs dans le processus. Cette recherche aboutie à une série de recommandations pour de futurs ateliers, afin d’augmenter leur impact sur l’utilisation des connaissances et de promouvoir la prise de décision basée sur des CIR. / In Haiti, road safety is an important public health issue, causing more deaths and injuries that the country’s health system can provide for. Knowledge transfer (KT) strategies are needed to promote evidence-based policy-making (EBDM) to improve road safety. A KT strategy was developed to share with key actors the results of three recent studies about road safety in Haiti. The present research’s purpose was to evaluate the appreciation, the content, and the impact on knowledge use by key actors of this KT strategy. This research used a mixed-method design, using quantitative questionnaires (n = 13/16) two to three months following the workshop at the center of this strategy, and qualitative interviews (n = 12/16) seven to nine months post-workshop. The workshop was generally appreciated by participants, especially for the quality of the data presented and its multidisciplinary approach. However, they were disappointed by the absence of decision-makers and by the limited number and variety of stakeholders present. Even though the participants reported a strong will to do so, the workshop had limited effect on knowledge use. This study highlighted the potential of deliberative workshops as a knowledge transfer strategy in LMICs, as well as the importance to include policy-makers in the process. This research also resulted in certain recommendations for future workshops, in the objective of increasing knowledge use and of promoting evidence-based decision-making.

Aim: The aim of this work was to broaden the understating of the role of parental engagement and learning materials at home, in promoting high cognitive and social emotional development. The study assessed the connection between maternal and paternal engagement, having 3 or more books and 2 or more types of playthings, towards the cognitive and social-emotional development of children. Methods: Data from the Multiple Indicator Cluster Surveys (MICS) was used, involving 2517 children in Zimbabwe. Unadjusted logistic regression was conducted to assess the possible confounders. Logistic regression was performed between parental engagement, children having 3 or more books and 2 or more types of playthings, towards the outcome of interest. Results: The results indicate that 91% of the children acquired high cognitive development and 63.4% social emotional. There has not been a significant association between maternal engagement and children’s cognitive or social-emotional development. Similarly, no correlation was found between paternal engagement and children’s development. Nevertheless, households having 3 or more books, reported increased odds of children having high cognitive development and lower odds of social-emotional development. Similarly, children with 2 or more types of playthings, depicted a positive association for social-emotional growth, whereas cognitive development decreased further. Conclusion: The association between having 3 or more books and 2 or more types of playthings remained significant, although parental engagement was insignificant. Future research on parenting practices in different cultural contexts is suggested, concerning the developmental status of children. In addition, more developmental, age-related assessment items are needed.

In 2001 the Declaration on the TRIPS Agreement and Public Health (‘Doha Declaration’), affirmed the right of member states of the World Trade Organisation (‘WTO’) to interpret and implement the TRIPS Agreement as supportive of the protection of public health and, in particular, access to medicines. While initially well-received, consternation soon arose over the interpretation of a specific paragraph in the Doha Declaration dealing with compulsory licensing. After a further two years of deliberation, the WTO Decision on the Interpretation of Paragraph 6 (‘Paragraph-6 Decision’) was announced in August 2003 specifying when countries can import drugs produced elsewhere under compulsory licence. With one third of the world's population is still denied access to essential medicines - a figure which rises to over 50 per cent in Asia and Africa - the problems facing the public health community are two-fold. The first is the capacity of developing countries (‘DCs’) actually to use the flexibilities afforded under the TRIPS Agreement, the Doha Declaration, and the Paragraph- 6 Decision amid stark inequalities in health resources and the world trading system as a whole. These include provisions for compulsory licensing, parallel importation, and addressing imbalances in research and development (‘R&D’). The pending ratification of the Paragraph-6 Decision, from an interim solution to a permanent amendment, is accompanied by considerable uncertainty: will the protections be accessible under the system currently proposed? The second problem concerns the undermining of the above hard-won flexibilities by provisions adopted under various bilateral and regional trade agreements. Known as ‘TRIPS-plus’- or ‘WTO-plus’- measures, the level of intellectual property rights (‘IPRs’) rights protection being negotiated and even adopted under other trade agreements are more restrictive as regards public health protection. These two sources of concern have led to an increase in rather than a lessening of tensions between the public health and trade policy communities. The thesis opens with a brief analysis of the interplay between patents and medicines. This includes an overview of the human rights framework and the right of access to medicines as a manifestation of human rights. The historical development of the TRIPS Agreement, its legitimacy, and the effect of the introduction of patents for pharmaceuticals are critically analysed. The terms of the Doha Declaration as it relates to public health, the Paragraph-6 Decision and its system, the December 2005 Amendment, and the progress made to date on the public health protections available under the TRIPS Agreement are reviewed and discussed in detail. The thesis describes how, despite these important clarifications, concerns as to the capacity of DCs to implement specific measures persist. This thesis further addresses the development of compulsory licensing in India and South Africa, and the legal framework for compulsory licensing in these countries. The role of competition law and constraints faced by DCs in implementing the flexibilities offered by the TRIPS Agreement and Doha Declaration are considered before turning to the threat posed by TRIPS-plus measures and calls for their critical reassessment. The thesis considers the role of the Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG), the WHO Commission on IPRs, Innovation and Public Health (CIPIH), Patent Pools, and international and multilateral donors in access to medicines. The thesis concludes by reviewing potential ways forward to ensure that access to medicines by the poor living in DCs is secured in all trade agreements. / Mercantile Law / LL.D.

In 2001 the Declaration on the TRIPS Agreement and Public Health (‘Doha Declaration’), affirmed the right of member states of the World Trade Organisation (‘WTO’) to interpret and implement the TRIPS Agreement as supportive of the protection of public health and, in particular, access to medicines. While initially well-received, consternation soon arose over the interpretation of a specific paragraph in the Doha Declaration dealing with compulsory licensing. After a further two years of deliberation, the WTO Decision on the Interpretation of Paragraph 6 (‘Paragraph-6 Decision’) was announced in August 2003 specifying when countries can import drugs produced elsewhere under compulsory licence. With one third of the world's population is still denied access to essential medicines - a figure which rises to over 50 per cent in Asia and Africa - the problems facing the public health community are two-fold. The first is the capacity of developing countries (‘DCs’) actually to use the flexibilities afforded under the TRIPS Agreement, the Doha Declaration, and the Paragraph- 6 Decision amid stark inequalities in health resources and the world trading system as a whole. These include provisions for compulsory licensing, parallel importation, and addressing imbalances in research and development (‘R&D’). The pending ratification of the Paragraph-6 Decision, from an interim solution to a permanent amendment, is accompanied by considerable uncertainty: will the protections be accessible under the system currently proposed? The second problem concerns the undermining of the above hard-won flexibilities by provisions adopted under various bilateral and regional trade agreements. Known as ‘TRIPS-plus’- or ‘WTO-plus’- measures, the level of intellectual property rights (‘IPRs’) rights protection being negotiated and even adopted under other trade agreements are more restrictive as regards public health protection. These two sources of concern have led to an increase in rather than a lessening of tensions between the public health and trade policy communities. The thesis opens with a brief analysis of the interplay between patents and medicines. This includes an overview of the human rights framework and the right of access to medicines as a manifestation of human rights. The historical development of the TRIPS Agreement, its legitimacy, and the effect of the introduction of patents for pharmaceuticals are critically analysed. The terms of the Doha Declaration as it relates to public health, the Paragraph-6 Decision and its system, the December 2005 Amendment, and the progress made to date on the public health protections available under the TRIPS Agreement are reviewed and discussed in detail. The thesis describes how, despite these important clarifications, concerns as to the capacity of DCs to implement specific measures persist. This thesis further addresses the development of compulsory licensing in India and South Africa, and the legal framework for compulsory licensing in these countries. The role of competition law and constraints faced by DCs in implementing the flexibilities offered by the TRIPS Agreement and Doha Declaration are considered before turning to the threat posed by TRIPS-plus measures and calls for their critical reassessment. The thesis considers the role of the Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG), the WHO Commission on IPRs, Innovation and Public Health (CIPIH), Patent Pools, and international and multilateral donors in access to medicines. The thesis concludes by reviewing potential ways forward to ensure that access to medicines by the poor living in DCs is secured in all trade agreements. / Mercantile Law / LL.D.