Drugs for treating rare diseases had been neglected by the pharmaceutical industry for a long time, due to the complex and costly drug R&D process as well as a small unprofitable market. Since its introduction in 1983, the Orphan Drug Act (ODA) has sought to prompt the innovation of drugs for minority diseases by reducing the regulatory and economic barriers. The incentives of the ODA have been effected through market protection, tax credit, fee waiver and grants to increase the accessibility of orphan products for the public. The number of orphan drugs available in the market has risen sharply from just ten in the decade before 1983 to over 400 since 1983. This increase implies a substantial improvement of the healthcare of patients suffering rare diseases and a success of the orphan drug legislation with the aim to motivate the development and manufacture of products that have low commercial potentials. Although it is evident that the ODA has successfully stimulated drug companies to develop numerous orphan products, treatments are very expensive. The sales of blockbuster orphan drugs have provided drug companies with unusually highprofit margins and limited patient access to treatments. The dilemma presented by the ODA reflects many of the issues currently faced by policymakers. In this thesis, we have analyzed the long-term evolution of the biopharmaceutical industry. In particular, we have examined drug discovery in the period of random screening, rational design and network collaboration, and explored the influence of the ODA. We have taken the theory of the sectoral system of innovation, and combined it with the complex adaptive model of innovation, and found that the complex version of that theory is capable of explaining the comprehensive drug innovation system. A Multi-agent Based Model has been introduced to identify and analyze the dynamics of bio-pharmaceutical innovation. The model has explored the roles of the main players in the sector and the influence of their relationships embedded in the process of orphan drug innovation. Through this model, we have investigated the mechanisms of how the incentives stimulate orphan drug innovation during the period from 1983- 2012. Moreover, the model has been applied to solve the dilemma of the ODA through analyzing how to achieve the best trade-off between orphan drug developments. Drawing upon the results of the simulation, we provide a sound basis for adjusting the ODA incentives to strikes an appropriate balance between stimulating orphan drug innovation and providing benefits to society, propose some resolutions to the ODA, while also to motivate orphan drug development in a financial way. The Advice for other countries planning to enact the orphan drug legislation and directions for further research suggested by this model have been put forward.

The aim of the "Shared Board" project is to design and implement an application that will allow a real-time collaboration on workgroup projects in a network environment. The communication can be accomplished using Instant Messaging or multimedia whiteboard with a possibility of drawing, attaching interactive objects and combined with voice and video communication. The term project part solves utilization of interactive whiteboards, design of communication protocol and grafical user interface. Implementation is solved as masters thesis part.

La thèse est une recherche action ; l'action s'articule autour d'une plateforme de télémédecine, évaluée en matière de processus et de résultats dans des publications scientifiques et en matière éthique dans le présent manuscrit. La plateforme de télé-expertise a été crée sur le modèle développé par le collegium telemedicus (https://collegiumtelemedicus.org) et implantée sur les terrains d'intervention de Médecins Sans Frontières (MSF), organisation non gouvernementale humanitaire. Le système donne accès à un réseau de spécialistes capables de répondre sous quelques heures aux demandes d'avis spécialisés des soignants en situation d'isolement géographique et / ou dans des zones à faibles ressources. Plus de 4000 cas ont été traités à travers la plateforme confirmant le besoin et l'intérêt du service par les soignants présents sur le terrain. Les évaluations scientifiques montrent que le système est fiable et performant. La majorité des utilisateurs juge le service utile et adapté aux besoins du terrain avec un effet positif sur la prise en charge des patients. L'accès à un spécialiste réduit en outre le sentiment d'isolement des praticiens en leur permettant une gestion collégiale des cas et participe à son éducation dans des domaines spécialisés. Un certains nombre de limites existent toutefois, comme les difficultés de suivi des patients ou l'absence de retour adressé à l'expert impliqué sur l'évolution du cas après son avis. L'action est née sous la double impulsion d'un constat d'une perte de chance en l'absence d'accès aux spécialistes et de l'injustice d'accès aux soins spécialisés en situation d'isolement géographique et dans des zones à faibles ressources. Bien que le droit international plaide pour le meilleur soin pour tous, il le conditionne aux ressources disponibles des populations concernées, signant par là même le constat de son impuissance à faire appliquer le droit qu'il proclame. L'action mise en œuvre grâce au soutien opérationnel de MSF (connaissance du terrain, recrutement des spécialistes volontaires...) apporte une réponse concrète et immédiate à cette injustice. L'évaluation rigoureuse du système relève d'une démarche éthique qui vise à s'assurer d'une utilisation efficiente des ressources dans un contexte où leur allocation est un enjeu éthique majeur. L'analyse a permis d'établir dans quelle mesure l'action respecte les principes éthiques de bienfaisance et de non-malfaisance et comment le principe d'autonomie se trouve renforcé par l'accès aux avis spécialisés en améliorant les « capabilités » individuelles. Enfin, l'action interroge nos pratiques de pays à haut revenus, notamment la place et l'organisation de la médecine spécialisée. Les solutions développées dans les zones à faibles revenus constituent des modèles efficaces et économes, susceptibles de faire évoluer la façon de penser la santé et le modèle de soin dans les pays à haut revenus. / The thesis is an action research; the action is based on a telemedicine platform, evaluated in terms of process and results in scientific publications and ethics issues raised in this manuscript. The tele-expertise platform was created on the model developed by the collegium telemedicus (https://collegiumtelemedicus.org) and implemented on the intervention fields of Médecins Sans Frontières (MSF), a humanitarian non-governmental organization. The system provides access to a network of specialists able to respond within a few hours to requests for expert advice to healthcare providers in situations of geographic isolation and / or in low-resource settings. More than 4000 cases were processed through the platform, confirming the need for and interest in the service by healthcare providers working in difficult environments. The scientific assessments show that the system is reliable and efficient. The majority of users judge the service to be useful and well adapted to the needs in the field with a positive impact on patient management and outcomes. Access to specialists also reduces the sense of isolation of practitioners, allowing them collegial case management and assisting in their education in specialized areas. However, a certain number of limitations exist, such as monitoring patient follow-up or lack of feedback sent to the expert involved on the evolution of the case following the provision of expert advice. The action is born from the loss of opportunity caused by the absence of access to specialists, and the injustice represented by restricted access to specialized care in a situation of geographic isolation or in low-resource settings. International law advocates the best possible care for all, but acknowledges that it depends on the available resources of the targeted populations.Thus international law acknowledges its inability to apply the law that it proclaims. The action was implemented thanks to the operational support of MSF (field experience, volunteer specialists recruitment ...). It provides a concrete and immediate response to the injustice of restricted access to expertise from the field. Rigorous evaluation of the system comes within an ethical approach designed to ensure an efficient use of resources in a context where their allocation is a major ethical issue. The analysis helped to establish the extent to which the action respects the ethical principles of beneficence and non-maleficence, and how the principle of autonomy is reinforced by access to expert advice by improving the "capabilities" of the individual. Finally, the action questions existing high-income country practices, including the establishment and organization of specialized medicine. The solutions developed in low-resources areas are effective and efficient models, likely to change the way of thinking about health and care model in high income countries.