Evaluating Drugs for Rare Diseases (DRDs) for the purpose of reimbursement and beyond represents a tremendous challenge for most health care priorities. A consensus is set about the irrelevance of cost e ectiveness analysis to evaluate such drugs. The appeal for multi criteria decision aid models seems reasonable as the evaluation of DRDs is indeed multifaceted. However, the application of MCDA for the purpose of evaluating DRDs is yet primitive and simplistic. The present work tries to tackle the issue of evaluating DRDs from a decision maker angle by adopting an innovative robust ordinal regression MCDA method, UTADIS-GMS, that helps the decision maker discern between the DRDs based on their multi criteria value.

My thesis is focused on Czech Association for Rare Diseases funding. Primary objective was to create fundraising strategy for this organization. This strategy is now financed mainly by pharmaceutical companies, which causes conflict of interests. Secondary objective was to propose suitable marketing communication strategy. To achieve these goals, it was neccessary to clarify theoretical knowledge of nonprofit institutions first. In practical part of my thesis I select companies, which, I believe, could profit from cooperation with Czech Association for Rare Diseases most. There are also few ideas stated about communications and PR improvement of Czech Association for Rare Diseases.

Approximately 7000 rare disorders exist, affecting 2 percent of Canadians and millions of people worldwide. Given that for many rare diseases only one allele is mutated, we hypothesize inducing expression of the remaining wild-type allele may have a therapeutic effect. SMAD3 heterozygosity results in Aneurysms-Osteoarthritis Syndrome (AOS) – an aortic aneurysm disorder also known as Loeys-Dietz Syndrome Type 3. We conducted a screen of FDA-approved compounds and found that 13-cis-retinoic acid (13-CRA) induces SMAD3 in normal human fibroblast cultures. Treatment with therapeutic concentrations of 13-CRA increased SMAD3 mRNA in normal human fibroblasts, patient fibroblasts, wild-type murine vascular smooth muscle cells and Smad3+/- murine vascular smooth muscle cells. Increases in SMAD3 protein were also observed in normal human fibroblasts, patient fibroblasts, and wild-type murine vascular smooth muscle cells. Immunofluorescent imaging revealed the primary site of protein induction to be nuclear. We report here the in vitro induction of SMAD3 mRNA and protein by therapeutic levels of 13-CRA and suggest further investigation of this modality for the treatment of AOS.

Made available in DSpace on 2016-04-26T20:22:43Z (GMT). No. of bitstreams: 1 Merces da Silva Nunes.pdf: 5147157 bytes, checksum: 007e9a5e0741612e2c3aa1baf4001541 (MD5) Previous issue date: 2014-03-25 / In a Democratic Constitutional State - which elected the human being as the ultimate end of everything and the greatest value of all forms of coexistence, human dignity is the mother principle that inspires, guides and radiates all the legal and social order, is the value that drives and directs the society and its members to commit actions aimed at effecting and promoting the welfare of the human person. Therefore, at the time the Constitution states the dignity of the human being as the founding principle of the Federative Republic of Brazil, it is actually explaining that Brazilian society as a whole has the duty to protect, support and respect the citizen in what the they have as the most sacred and essential to their existence, which is the equality of all human beings in their personal dignity. Recognizing the equality of the human being, in his personal dignity implies that this equality must be respected and observed in all its aspects, especially the political, economic, legal and social conditions regardless of the nature and differences of gender, race, belief, color, language, wealth, birth, national or social origin, as stated in Section II of the Universal Declaration of Human Rights, from 1948. Due to this, the human being must be protected by society and all its members, not only in the sense that this protection has to be a guarantee for them to remain alive, but mainly not to be attacked in their dignity of human people, because their right to live with dignity and the right to a dignified existence is ensured. Regarding the delimitation and scope of the present study, it is crucial to emphasize that when providing the Unified Health System SUS, free of charge, with expensive drugs for rare diseases and treatment of needy people, the pharmaceutical industry gives to the Property a social function - that in a Democratic Constitutional State goes far beyond the payment of taxes and the availability of vacancies, since the hiring of employees and the payment of taxes are prerequisites to the exercise of the economic activity itself without which even the existence of the company would not be considered. In fact, the business activity directed to the exploration of drugs, as in the pharmaceutical industry, should be developed seeking the social interest, to the recovery and improvement of human health . Thus, for the property to meet its social function, as determined by the article 170, III of the Federal Constitution, the pharmaceutical industry has the duty to participate and engage with the state, sharing the responsibility for ensuring the right to health - fundamental social right, and contributing to the achievement of the basic objectives stated in the article 3 of the Federal Constitution / o valor maior de todas as formas de convivência, a dignidade da pessoa humana é o princípio matriz que inspira, norteia e irradia todo o ordenamento jurídico e social, é o valor que move e direciona a sociedade e seus integrantes à prática de ações destinadas à efetivação e promoção do bem estar da pessoa humana. Bem por isso, no momento em que a Constituição Federal explicita a dignidade da pessoa humana como princípio fundante da República Federativa do Brasil, na verdade, está afirmando que a sociedade brasileira, como um todo, tem o dever de proteger, amparar e respeitar o cidadão naquilo que o Homem tem de mais sagrado e essencial à sua existência, que é a igualdade de todo ser humano em sua dignidade de pessoa. Reconhecer a igualdade do ser humano, em sua dignidade de pessoa, implica dizer que essa igualdade deve ser respeitada e observada em todos os seus aspectos, sobretudo, os de natureza política, econômica, jurídica e social independentemente das condições e diferenças de sexo, raça, credo, cor, língua, riqueza, nascimento, origem nacional ou social, tal como explicitado no Artigo II, da Declaração Universal dos Direitos Humanos, de 1948. Por essa razão, o ser humano deve ser protegido pela sociedade e por todos os seus integrantes, não apenas no sentido de essa proteção ser uma garantia de que o ser humano permaneça vivo, mas, principalmente, para que não seja atingido em sua dignidade de pessoa humana, porquanto lhe é assegurado o direito de viver de forma digna, o direito a uma existência digna. No que concerne à delimitação e ao alcance do presente estudo, imperioso destacar que ao destinar, gratuitamente, em favor do Sistema Único de Saúde - SUS- medicamentos de alto custo e doenças raras para tratamento de pessoas carentes, a indústria farmacêutica confere à propriedade uma função social que, num Estado Democrático de Direito, vai muito além do pagamento de tributos e da disposição em oferecer postos de trabalho, uma vez que a contratação de funcionários e/ou colaboradores e o pagamento de tributos são condições indispensáveis ao exercício da própria atividade econômica sem as quais sequer a existência da empresa haveria de ser considerada. Na verdade, a atividade empresarial voltada para a exploração de medicamentos, como é o caso da indústria farmacêutica, deve ser desenvolvida no interesse social, visando a recuperação e a melhoria da saúde humana. Assim, para que a propriedade atenda a sua função social, como determina o artigo 170, III da Constituição Federal, a indústria farmacêutica tem o dever de participar e de agir em conjunto com o Estado, compartilhando a responsabilidade pela efetivação do direito à saúde - direito fundamental social e contribuindo para a consecução dos objetivos fundamentais explicitados no art. 3º da Constituição Federal

In my work, I want to focus on the perceived advantages and disadvantages of membership in the umbrella organization. This topic, I will discuss from the perspectives of the member organizations. This is a specific segment associations - the patient organizations focused to patients with rare diseases. It is clear that cooperation in the umbrella organization brings advantages, but it is probable that it can also bring some disadvantages. For my work I choose the Czech Association for rare diseases. In the Czech Republic is the only organization in the civil sector, focusing exclusively on rare diseases. The goal of the master thesis is to find out the perceived advantages and disadvantages, and how it is related to the level of activity of members of the umbrella organization. Further, I want to compare the data with the theoretical literature in order that differs. Theme of umbrella in the Czech Republic is almost unexplored. There are only a few expert papers in this area. That's why I decided to focus on cooperation in civil sector (organization focus on rare diseases), which is relatively unknown. Keys words: advantages of cooperation, disadvantages of cooperation, rare disease, advocacy function, information function, umbrella organizations, patient organizations, Czech Association for Rare...