Anualmente, surgem cerca de 500.000 novos casos de câncer cérvico-uterino e perto de 230.000 mulheres morrem, em todo mundo, acometidas por esta neoplasia, com especial destaque para os países em desenvolvimento. A infecção persistente pelo vírus HPV é condição necessária para a ocorrência desta doença e os tipos oncogênicos HPV 16 e HPV 18 são os responsáveis por cerca de 70% dos casos de câncer cérvico-uterino. Na última década, vacinas profiláticas contra o HPV foram desenvolvidas, objetivando reduzir a incidência do câncer cérvico-uterino, sendo indicadas prioritariamente a meninas adolescentes na faixa etária de 9 a 15 anos de idade. Atualmente, encontram-se disponíveis para comercialização e uso duas vacinas: Bivalente (para o HPV 16 e 18) e Quadrivalente (para os tipos 6, 11, 16, 18). Este trabalho objetivou realizar uma revisão sistemática da literatura sobre a eficácia, em mulheres, das vacinas comercialmente disponíveis contra o HPV, com foco na avaliação da eficácia vacinal estratificada por grupos etários e desfechos. Dos 378 estudos identificados nas bases MEDLINE, LILACS e Cochrane Colaboration, 6 estudos clínicos controlados randomizados foram selecionados, correspondendo a 41.750 mulheres. As vacinas Quadrivalente e Bivalente reduziram significativamente o risco da ocorrência de lesões precursoras do câncer cérvico-uterino como o NIC2 em 96,9% (IC 95%, 90,299,0) e NIC3 em 96,2% (IC 95%, 89,098,7) nas análises por protocolo quando comparadas ao grupo controle. Somente um estudo MUÑOZ et al (2009) trazia os resultados de eficácia da vacina para o HPV por subgrupo etário, mas sua população de estudo foi de 3.819 mulheres de 24-45 anos, sem história prévia de infecção pelos subtipos vacinais (6, 11, 16 e 18), arroladas em um estudo multicêntrico randomizado com a vacina Quadrivalente controlado por placebo, com tempo de seguimento médio de 26 meses. Usando um desfecho que combinava infecção persistente por no mínimo 6 meses de duração, neoplasia intra-epitelial cervical e lesões genitais externas, encontrou uma eficácia de 91,8% (IC 95%, 67,199,1) para a faixa etária de 2434 anos e de 88,6% (IC 95%, 51,998,7) para a faixa etária de 3545 anos. A vacinação profilática pode prevenir a infecção pelo HPV em mulheres de 15 a 45 anos sem infecção prévia pelos subtipos virais cobertos pela vacina por pelo menos 5 anos, correspondendo ao tempo máximo de seguimento dos estudos incluídos nesta revisão. Para a avaliação da eficácia da vacina na incidência e mortalidade do câncer cervical será necessário, contudo, tempo maior de seguimento dos estudos / Annually, about 500,000 new cases of cervical cancer occur and nearly 230,000 women die worldwide affected by this cancer, with particular emphasis on developing countries. Persistent HPV infection is a necessary condition for the occurrence of this disease and the oncogenic types HPV 16 and HPV 18 are responsible for approximately 70% of cervical cancer cases. In the last decade, prophylactic HPV vaccines have been developed, aimed at reducing the incidence of cervical cancer, with priority given to adolescent girls aged 9 to 15 years old. Currently, there are two commercially available HPV vaccines: Bivalent (HPV 16 and 18) and Quadrivalent (types 6, 11, 16, 18). This study aimed to perform a systematic review on commercially available HPV vaccine efficacy in women, with a focus on evaluation of vaccine efficacy stratified by age groups and outcomes. Six randomized controlled trials were selected of the 378 studies identified in MEDLINE, LILACS and Cochrane Collaboration, corresponding to 41,750 women. The Bivalent and Quadrivalent vaccine significantly reduced the risk of occurrence of precursor lesions of cervical cancer presenting efficacy of 96.9% (95% CI, 90.2-99.0) for CIN2 and 96.2% (CI 95%, 89.0- 98.7) for CIN3 in the per protocol population analysis when compared to the control group. Only one study - MUÑOZ et al (2009) - brought results of HPV vaccine efficacy by age subgroup. Involving 3,819 women of 24-45 years without previous history of infection with the vaccine subtypes (6, 11, 16, 18) on the baseline, enrolled in a randomized multicenter study with the Quadrivalent vaccine, placebo controlled with follow-up period about 26 months. A combined outcome of persistent infection for at least 6 months duration, cervical intraepithelial neoplasia and external genital lesions was used. For the age group of 24-34 years, vaccine efficacy was 91.8% (95% CI, 67.1-99.1) and age 35-45 years was 88.6% (CI 95%, 51.9-98.7). Vaccine efficacy of the entire population enrolled in the protocol was 90.5% (CI 95%, 73.7-97.5). The prophylactic vaccination can prevent HPV infection in women from 15 to 45 years not previously infected with the HPV subtypes covered by the vaccines by at least 5 years, corresponding to the maximum time of follow-up studies included in this review. For evaluation of vaccine efficacy on the incidence and mortality of cervical cancer will be necessary, however, longer follow up studies

Pacientes portadores de comunicação oronasal necessitam de dispositivo protético obturador, para o restabelecimento da sua função, estética e qualidade de vida perdida, devido à remoção ou ausência da maxila. Esta tecnologia reabilitadora vem se desenvolvendo há alguns séculos, com aprimoramentos das técnicas de confecção e materiais odontológicos que auxiliem na elaboração de obturadores cada vez mais eficientes, principalmente no que se refere a sua adaptação. Esta tecnologia é fortemente dependente tanto do domínio das técnicas laboratoriais, quanto de habilidades específicas na arte da reconstrução da face (manuais, sensitivas e tácitas), pois sua confecção é artesanal, personalizada e individualizada, determinando que a disponibilidade e distribuição dos recursos humanos qualificados para a sua elaboração constituam-se em obstáculo significativo para um acesso mais amplo e equânime. O trabalho em tela teve por objetivo examinar o estado da arte relativo às diferentes técnicas de moldagens e confecção das próteses obturadoras utilizadas no cuidado reabilitador de pacientes maxilarectomizados, buscando subsidiar proposições para o seu aprimoramento. Este estudo teórico-exploratório utilizou dois caminhos metodológicos complementares. O primeiro tomou por base uma revisão de literatura científica nacional e internacional e acadêmica, publicada sob a forma de artigos, teses e dissertações, utilizando as bases bibliográficas MEDLINE, BBO, LILACS, SCIELO, Biblioteca Virtual de Saúde e Colaboração Cochrane, e as bases de dissertações e teses da CAPES Banco de Teses; Base Thesis e Biblioteca Digital de Teses e Dissertações (BDTD), do Instituto Brasileiro de Informação em Ciência e Tecnologia (IBICT). O segundo caminho teve por foco a exploração de um dos principais limitadores ao acesso e utilização dos dispositivos obturadores do país a escassez de recursos humanos especializados buscando-se identificar os centros formadores de capacitação nesta área específica, a partir da Coordenação de Aperfeiçoamento de Pessoal Nível Superior (CAPES) do Ministério da Educação e do Conselho Federal de Odontologia, bem como o número de profissionais Protesistas Bucomaxilofaciais e Técnicos em Prótese Dentárias disponíveis em território Nacional para confecção dos obturadores, a partir de consulta ao Conselho Federal de Odontologia (CFO). Os resultados permitiram traçar um panorama histórico de desenvolvimento tecnológico destas próteses desde os primeiros dispositivos utilizando materiais da natureza. São apresentados e discutidos vários tipos de obturadores, bem como as diversas técnicas e materiais envolvidos, sendo também explorados seus benefícios para reabilitação, em particular os impactos na qualidade de vida associados ao seu uso, e alguns obstáculos técnicos a serem ultrapassados para melhoria da tecnologia reabilitadora. O exame do quantitativo e distribuição regional dos diversos profissionais envolvidos na sua confecção sinaliza uma grande escassez destes recursos humanos, bem como sua grande concentração na região Sudeste, em particular no eixo Rio - São Paulo. Além disto, o numero de centros formadores em termos técnicos de nível médio e de pós- graduação é insignificante e ainda vem ocorrendo à desativação de cursos, pela falta de procura. Esses dados apontam para significativas dificuldades no acesso a tecnologia, proveniente, sobretudo da falta e má distribuição regional de profissionais capacitados em prótese bucomaxilofacial em território nacional, dos escassos centros formadores de recursos humanos e do baixo incentivo ao ensino e pesquisa / Patients with oral-nasal connection due to the absence or extirpation of the maxilla need a prosthetic obturator for esthetical reasons, to restore function, and to partially regain the lost quality of life. This technology has evolved in the course of many centuries in conjunction with the improvement in manufacturing techniques and odontological materials that play a role in the elaboration and design of more efficient obturators, especially regarding their adaptation. This technology is exceedingly dependent on the mastery of laboratorial methods as well as specific skills in the art of facial reconstruction because its confection is artisanal, personalized, and customized. The existence and distribution of suitable human resources are an evident obstacle to the evenly access to this technology. The aim of this work was to scrutinize the state of the art regarding different moulding and manufacturing techniques of prosthetic obturators employed in the rehabilitation process of maxillectomized patients, intending to make a contribution for its improvement. This theoretical-exploratory study used two complementary methodological instruments. One was a broad review of the national and international scientific literature published as articles, doctoral thesis and dissertations, utilizing different bibliographical databases: MEDLINE, BBO, LILACS, SCIELO, Biblioteca Virtual de Saúde (Virtual Health Library), and The Cochrane Collaboration, as well as the doctoral thesis and dissertations included in the CAPES database - Base Thesis and Digital Library of thesis and dissertations, from the Brazilian Institute of Information in Science and Technology. The other methodological instrument focused on the investigation of the main reasons for the restricted access of patients to prosthetic obturators in our country the lack of expert human resources trying to identify the centers of excellence and development in this specific area using the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) of the Ministry of Education and of the Federal Council of Odontology, as well as the number of dedicated technicians making bucomaxillofacial prosthesis and dental prosthesis in our national territory by consulting the Federal Council of Odontology. The results allowed the construction of a historical frame of the technological development of these prosthesis from the very first obturators manufactured with natural materials. Different types of obturators are presented and discussed, along with the many techniques and the various materials employed. Their specific benefits for the rehabilitation process are also discussed, in particular the impact in quality of life associated with its specific use. Obstacles to the further development and implementation of the rehabilitation technology are also examined. The availability and regional distribution of qualified personnel reveal a remarkable shortage of human resources and its overwhelming concentration to the Southeast region, particularly the Rio de Janeiro - São Paulo area. There are a negligible number of centers for preparing technicians and offering post graduation opportunities. Furthermore, there are centers being deactivated due to the lack of demand. This data demonstrates the striking difficulties in making this technology more evenly available throughout the national territory as a result of the lack of incentive for education and research

Anualmente, surgem cerca de 500.000 novos casos de câncer cérvico-uterino e perto de 230.000 mulheres morrem, em todo mundo, acometidas por esta neoplasia, com especial destaque para os países em desenvolvimento. A infecção persistente pelo vírus HPV é condição necessária para a ocorrência desta doença e os tipos oncogênicos HPV 16 e HPV 18 são os responsáveis por cerca de 70% dos casos de câncer cérvico-uterino. Na última década, vacinas profiláticas contra o HPV foram desenvolvidas, objetivando reduzir a incidência do câncer cérvico-uterino, sendo indicadas prioritariamente a meninas adolescentes na faixa etária de 9 a 15 anos de idade. Atualmente, encontram-se disponíveis para comercialização e uso duas vacinas: Bivalente (para o HPV 16 e 18) e Quadrivalente (para os tipos 6, 11, 16, 18). Este trabalho objetivou realizar uma revisão sistemática da literatura sobre a eficácia, em mulheres, das vacinas comercialmente disponíveis contra o HPV, com foco na avaliação da eficácia vacinal estratificada por grupos etários e desfechos. Dos 378 estudos identificados nas bases MEDLINE, LILACS e Cochrane Colaboration, 6 estudos clínicos controlados randomizados foram selecionados, correspondendo a 41.750 mulheres. As vacinas Quadrivalente e Bivalente reduziram significativamente o risco da ocorrência de lesões precursoras do câncer cérvico-uterino como o NIC2 em 96,9% (IC 95%, 90,299,0) e NIC3 em 96,2% (IC 95%, 89,098,7) nas análises por protocolo quando comparadas ao grupo controle. Somente um estudo MUÑOZ et al (2009) trazia os resultados de eficácia da vacina para o HPV por subgrupo etário, mas sua população de estudo foi de 3.819 mulheres de 24-45 anos, sem história prévia de infecção pelos subtipos vacinais (6, 11, 16 e 18), arroladas em um estudo multicêntrico randomizado com a vacina Quadrivalente controlado por placebo, com tempo de seguimento médio de 26 meses. Usando um desfecho que combinava infecção persistente por no mínimo 6 meses de duração, neoplasia intra-epitelial cervical e lesões genitais externas, encontrou uma eficácia de 91,8% (IC 95%, 67,199,1) para a faixa etária de 2434 anos e de 88,6% (IC 95%, 51,998,7) para a faixa etária de 3545 anos. A vacinação profilática pode prevenir a infecção pelo HPV em mulheres de 15 a 45 anos sem infecção prévia pelos subtipos virais cobertos pela vacina por pelo menos 5 anos, correspondendo ao tempo máximo de seguimento dos estudos incluídos nesta revisão. Para a avaliação da eficácia da vacina na incidência e mortalidade do câncer cervical será necessário, contudo, tempo maior de seguimento dos estudos / Annually, about 500,000 new cases of cervical cancer occur and nearly 230,000 women die worldwide affected by this cancer, with particular emphasis on developing countries. Persistent HPV infection is a necessary condition for the occurrence of this disease and the oncogenic types HPV 16 and HPV 18 are responsible for approximately 70% of cervical cancer cases. In the last decade, prophylactic HPV vaccines have been developed, aimed at reducing the incidence of cervical cancer, with priority given to adolescent girls aged 9 to 15 years old. Currently, there are two commercially available HPV vaccines: Bivalent (HPV 16 and 18) and Quadrivalent (types 6, 11, 16, 18). This study aimed to perform a systematic review on commercially available HPV vaccine efficacy in women, with a focus on evaluation of vaccine efficacy stratified by age groups and outcomes. Six randomized controlled trials were selected of the 378 studies identified in MEDLINE, LILACS and Cochrane Collaboration, corresponding to 41,750 women. The Bivalent and Quadrivalent vaccine significantly reduced the risk of occurrence of precursor lesions of cervical cancer presenting efficacy of 96.9% (95% CI, 90.2-99.0) for CIN2 and 96.2% (CI 95%, 89.0- 98.7) for CIN3 in the per protocol population analysis when compared to the control group. Only one study - MUÑOZ et al (2009) - brought results of HPV vaccine efficacy by age subgroup. Involving 3,819 women of 24-45 years without previous history of infection with the vaccine subtypes (6, 11, 16, 18) on the baseline, enrolled in a randomized multicenter study with the Quadrivalent vaccine, placebo controlled with follow-up period about 26 months. A combined outcome of persistent infection for at least 6 months duration, cervical intraepithelial neoplasia and external genital lesions was used. For the age group of 24-34 years, vaccine efficacy was 91.8% (95% CI, 67.1-99.1) and age 35-45 years was 88.6% (CI 95%, 51.9-98.7). Vaccine efficacy of the entire population enrolled in the protocol was 90.5% (CI 95%, 73.7-97.5). The prophylactic vaccination can prevent HPV infection in women from 15 to 45 years not previously infected with the HPV subtypes covered by the vaccines by at least 5 years, corresponding to the maximum time of follow-up studies included in this review. For evaluation of vaccine efficacy on the incidence and mortality of cervical cancer will be necessary, however, longer follow up studies

A Estratégia de Saúde da Família foi implantada pelo Ministério da Saúde, em 1994, para orientar o sistema de saúde brasileiro em direção a Atenção Primária à Saúde. A partir de então, a ampliação da cobertura de equipes de ESF tem estado entre as metas de governo. Para consecução deste propósito, o perfil dos profissionais e a formação se caracterizam como um grande diferencial, com papel determinante em uma reorientação desta magnitude e abrangência. A Residência Multiprofissional em Saúde foi uma das políticas criadas neste sentido. O Grupo Hospitalar Conceição oferece esta modalidade de formação desde 2004. Objetivo: Avaliar a adequação do Programa da Residência Integrada em Saúde, na ênfase Saúde da Família e Comunidade, do GHC, como uma tecnologia de formação de profissionais em APS para o SUS, através de dados coletados junto aos seus egressos. Métodos: O delineamento é um estudo de caso descritivo com associação da metodologia quantitativa e qualitativa, orientado pela avaliação de inferência causal proposta por Habicht et al. A coleta das informações se deu de maneira virtual através de um questionário semiestruturado em formato autoaplicável. A população pesquisada foram 74 profissionais egressos do Programa formados entre os anos de 2005 e de 2008. Resultados: O estudo contou com a participação de 77% dos egressos do Programa. Os dados encontrados revelam uma população de profissionais jovens, predominantemente, do sexo feminino. Estes profissionais exercem suas atividades em 19 cidades, sendo que, na cidade de Porto Alegre se concentram mais de metade deles. 76% dos egressos estão vinculados ao setor público e 49% atuam diretamente na APS. A maioria dos participantes afirma que a formação alterou a forma de perceber a realidade em APS, melhorou suas habilidades e aumentou os conhecimentos. Conclusões: As evidências produzidas no estudo fornecem subsídios para considerar o Programa como uma tecnologia adequada à formação de profissionais de saúde em APS para o SUS. / The Family Health Strategy, an initiative from the Ministry of Health, started in 1994, providing guidelines to the Brazilian Health System towards Primary Health Care. Since then, there was a remarkable increase in the strategy coverage. To pursue this objective, the professional profiles and their formation are characterized as great differentials, with a pivotal role in a reorientation of such magnitude. The Health Interprofessional Residency was one of these government policies created with this scope, and the Grupo Hospitalar Conceição has been offering this continuum education course since 2004. Objective: To evaluate the fitting adequation of The Health Interprofessional Residency, emphasis in Family and Community Health, as a good technology to train health professionals in Primary Health Care in the context of Brazilian Health System, using data collected from professionals graduated in the Residency program. Methods: The design is based on a descriptive study case, associating quantitative and qualitative methodologies, relying on the evaluation of causal inference proposed by Habicht et al. The information was collected by a virtual mode with a semi structured and self-administered questionnaire. Professionals (74) that concluded the program between 2005 and 2008 were selected to be included in the sample. Results: The response rate was 77%. The population was mainly composed by young individuals, predominantly females. These individuals perform their professional activities in 19 different cities; more than 50% were working in the State capital city (Porto Alegre). From the individuals interviewed, 76% of them were public servants and 49% were working directly in Primary Health Care. Most of the participants stated that the training during Residency had significantly changed their view in relation to the reality in Primary Health Care, improving their skills and increasing their knowledge. Conclusion: The findings from this study show that the Residency Program could be considered a good technology for training Primary Health Care professionals for the Brazilian Health System.

Este estudo exploratório-descritivo tem como objetivo avaliar o desempenho funcional e a qualidade técnica de um registro eletrônico do processo de enfermagem junto a especialistas em informática, enfermeiros docentes e enfermeiros assistenciais. O Hospital Universitário da Universidade de São Paulo em parceria com a Escola de Enfermagem da Universidade de São Paulo, desenvolveu um registro eletrônico denominado Sistema de Documentação Eletrônica do Processo de Enfermagem da Universidade de São Paulo (PROCEnfUSP), para que pudesse ser utilizado na automação das informações do Processo de Enfermagem, visando à adoção de um Sistema de Apoio à Decisão que pudesse contribuir para a melhoria da gestão, da qualidade da assistência e da satisfação dos pacientes. A garantia da qualidade desse sistema é um importante desafio e meta devido à responsabilidade com os usuários e pacientes. Para assegurar essa qualidade foi realizada uma avaliação do sistema PROCEnf-USP utilizando-se do Modelo de Qualidade proposto pela norma ISO/IEC 25010 e do Processo de Avaliação definido na norma ISO/IEC 25040. Na avaliação dos especialistas em informática, adequação funcional obteve 91% de respostas positivas, confiabilidade 76%, usabilidade 62%, eficiência de desempenho 84%, compatibilidade 86%, segurança 89%, manutenibilidade 93% e portabilidade 92%. Os enfermeiros docentes avaliaram positivamente todas as características, adequação funcional obteve 92%, confiabilidade 89%, usabilidade 84%, eficiência de desempenho 81%, compatibilidade 75% e segurança 100%. Os enfermeiros assistenciais das clínicas médica e cirúrgica do hospital avaliaram adequação funcional com 82% de respostas positivas, confiabilidade 69%, usabilidade 85%, eficiência de desempenho 47% compatibilidade 62% e segurança 98%. Os enfermeiros assistenciais de outras unidades avaliaram adequação funcional com 88%, confiabilidade 61%, usabilidade 80%, eficiência de desempenho 46%, compatibilidade 69% e segurança 100%. Conclui-se que o PROCEnf-USP atingiu mais de 70% de respostas positivas na maioria das características de qualidade avaliadas por todos os especialistas. Entretanto, eficiência de desempenho, confiabilidade e compatibilidade obtiveram índices abaixo do parâmetro estabelecido na avaliação dos enfermeiros assistenciais. Os resultados obtidos neste estudo serão utilizados para a realização de melhorias no sistema. Essa pesquisa propiciará a disseminação do conhecimento de uma área emergente, agregando mais uma iniciativa aos crescentes esforços na área de informática em saúde e em enfermagem / This descriptive exploratory study aims to evaluate functional performance and technical quality of an electronic record for the nursing process with technology experts, teaching staff and nurses. The University Hospital in the University of São Paulo in partnership with the School of Nursing of the University of São Paulo, has developed an electronic record called Electronic Documentation System for the Nursing Process of the University of São Paulo (PROCEnf-USP), to be used for the automation of information of the Nursing Process, aimed at the adoption of a Decision Support System that could contribute to the improvement of management, quality of care and patient satisfaction. The quality guarantee of this system is an important challenge and target, due to responsibility with users and patients. To ensure such quality an assessment of the PROCEnf-USP system was carried out using the Quality Model proposed by ISO/IEC 25010 and the Evaluation Process defined in ISO/IEC 25040. In the evaluation of technology experts the characteristic functional suitability had 91% of positive responses, reliability 76%, usability 62%, performance efficiency 84%, compatibility 86%, security 89%, maintainability 93% and portability 92%.The teaching staff positively evaluated all the characteristics, functional suitability had 92%, reliability 89%, usability 84%, performance efficiency 81%, compatibility 75% and security 100%. The nurses from general medical and surgical hospital evaluated functional suitability with 82% of positive responses, reliability 69%, usability 85%, performance efficiency 47%, compatibility 62% and security 98%. The nurses from other units evaluated functional suitability with 88%, reliability 61%, usability 80%, performance efficiency 46%, compatibility 69% and security 100%. It is concluded that the PROCEnf-USP reached more than 70% of positive responses in the majority of quality characteristics evaluated by specialists. However, performance efficiency, reliability and compatibility found rates below the parameter established in the assessment of nurses. The results of this survey will be used to implement improvements in the system. Such research will allow the spreading of knowledge in an emerging area, thus adding a further initiative to the growth efforts made in the information technology areas of health and nursing.

Cette thèse aborde les processus nationaux d'Evaluation des Technologies de la Santé (HTA) en Europe, en Australie et au Canada, avec comme point de référence le processus proposé par le National Institute for Health and Care Excellence (NICE) en Angleterre. Une attention particulière est portée sur la façon dont les décisions sont prises dans la gestion des soins de santé, sur quelles considérations ces décisions sont fondées, et sur la valeur des différents éléments d'évidence disponibles pour correctement évaluer les implications d'une mise en oeuvre d'un point de vue pratique. Cette thèse analyse le développement de recommandations dans la gestion des soins de santé afin de permettre l'accès aux traitements les plus efficaces d'un point de vue clinique et économique. Ces recommandations sont réalisées à partir des meilleures évidences disponibles et d'un consensus entre cliniciens, scientifiques, économistes de la santé, gestionnaires des services de soin et patients. La pertinence d'une évaluation en continu des différentes étapes de la gestion d'un problème de santé est également abordée durant cette thèse. L'objectif serait de permettre la production optimale de bénéfices de santé publique en reliant l'évaluation des différents stades d'une maladie. Ainsi, on obtiendrait une appréciation générale qui prendrait en considération que certaines recommandations de soin peuvent appeler à plus de flexibilité ou de contraintes selon les différents stades d'une maladie. Appliquée à la gestion de la dépendance à l'alcool, les abus d'alcool et conséquences attribuables, cette thèse contextualise et analyse le développement optimal d'évidences d'efficacité, d'efficience et d'économie de la santé, le choix de méthodologies appropriées et la manière d'interpréter et d'analyser leurs résultats pour la production optimale de bénéfices de santé publique / The current thesis discusses national processes of Health Technology Assessment (HTA) in Europe, Australia and Canada, with a central reference to the one proposed by the National Institute for Health and Care Excellence (NICE) in England. This is with a focus on the manner decisions about healthcare technologies are taken, based on which considerations and evidence, and with which weight the evidence elements are interlinked with regard to public health implications. The thesis analyses the development of recommendations of care to allow access to the most clinicallyand cost-effective treatments available, based on the best and most up-to-date evidence, and on the consensus from collaboration between clinicians, scientists, health economists, health service managers, as well as patients. Additionally, is discussed the value of covering all components of a disease evolution in assessing in continuum the different steps of disease management. This aims to allow the optimal generation of public health benefits in interlinking appraisals across different stages of disease for a generalist assessment of care, considering that recommendations in some aspects of care can call for more flexibility or constraints in other aspects. With an application to the management of alcohol use disorders, alcohol dependence and attributable harmful consequences, the thesis contextualizes and analyses decisions in the development of health economics and outcomes research evidence, the choice of methodology and directions taken, and their interpretation for optimal generation of public health benefits

The objective of this work is to analyse the possibility of use of micro -- needles technology as the method of drug delivery in the Czech Republic. The characteristics of this product (application, connection with drug, etc.) suggest three possible target groups: patients, health care providers or pharmaceutical companies. One of the goals is to analyse legal requirements on such products, evaluate current market situation and according to this information choose the best group for the product consumption. Also product itself presents a challenge and there are several designs of micro -- needle or needleless drug applicators. Combined together, this study aims to find, whether is the Czech market able to accept new method of drug delivery, in which form and how can patient reach this technology.

Dans le but d’améliorer l’accès au traitement pour les patients souffrant des maladies rares, les gouvernements de certains pays ont mis en place une législation ‘orpheline’ dont le but est d’aider à promouvoir la recherche dans ce secteur. En conséquence, le nombre de médicaments orphelins approuvés a significativement augmenté et continue de croître. Cependant, beaucoup de questions restent encore sans réponses. Les coûts par patients élevés, le manque de connaissance sur les maladies, et d’autres spécificités des médicaments orphelins font obstacle à l’utilisation de méthodes d’évaluations standards. L’objectif de cette étude est d’identifier les critères qui permettraient de déterminer la valeur des médicaments orphelins et les préférences de la société vis-à-vis de ces critères.Dans la première phase de l’étude, un état de l’art du marché des médicaments orphelins a été mené. Les défis associés tant à la recherche & développement qu’à l’évaluation des médicaments pour les maladies rares ont été décrits et classifiés. Une revue de toutes les autorisations de mise sur le marché pour les médicaments orphelins en Europe, ainsi que du marché des médicaments orphelins en France, en Italie, en Angleterre et au Pays de Galles a été réalisée. La disponibilité des médicaments orphelins, leur prix et leur remboursement, ainsi que les détails de l’évaluation par les autorités de santé ont été analysés.Dans la seconde phase de l’étude, une revue de littérature a été effectuée afin d’identifier les déterminants potentiels de la valeur des médicaments orphelins. L’impact de certains de ces attributs - dont le choix a été fait en fonction de la disponibilité des données - sur les prix des médicaments orphelins en France, en Italie, en Angleterre et au Pays de Galles a été exploré à l’aide d’une analyse de régression.Enfin, une enquête en ligne a été menée auprès d’un échantillon représentatif de la population française, afin d’étudier ses préférences relatives à certains attributs, sélectionnés au préalable. La liste de déterminants a été développée en se fondant sur un groupe de discussion et des interviews avec des experts. La méthode de l’enquête a suivi la structure d’un questionnaire à choix discrets et a permis d’estimer les poids relatifs des déterminants étudiés.L’étude a permis d’identifier les caractéristiques des médicaments orphelins qui sont le plus appréciées par la société. Ces résultats pourraient être pris en considération dans la méthode d’évaluation des médicaments orphelins, afin de la rendre plus transparente et robuste. / In order to improve the access to treatment for patients suffering from rare diseases, the governments of several countries put in place specific ‘orphan’ legislation aiming at promoting research in the field. In response to these measures, the number of approved orphan drugs has dramatically increased and continues to grow. Nevertheless, a number of issues remain unresolved. Thus, high per-patient costs, poor knowledge of the diseases and other specificities of medicines for rare diseases make it impossible to apply standard methods of health technology assessment to orphan drugs. The objective of the present research was to identify the criteria that determine the value of orphan drugs and study public preferences regarding these criteria.In the first phase of the research, a detailed review was conducted of the current situation on orphan drug market. Challenges related to the development and appraisal of orphan drugs were described and catalogued. A review was carried out of all approvals of orphan drugs in Europe, as well as of orphan drug markets in France, Italy and England and Wales. Orphan drug availability, price and reimbursement status, as well as the details of assessment were analysed.In the second phase, a literature review was conducted to identify potential determinants of orphan drug value. The impact of some of these determinants (choice was based on the availability of data) on orphan drug prices in France, Italy and England and Wales was then explored in a regression analysis.Finally, preferences of French general population in relation to the most relevant determinants of orphan drug value were analysed using an online survey. The list of determinants was developed based on a focus group and expert interviews. The survey was designed as a discrete choice experiment and allowed estimating relative weights of the included determinants.The study allowed identification of orphan drug characteristics that are most valued by the society. Its results may be taken into consideration in drug appraisal process in order to enable a fair assessment and pricing of orphan drugs.

Introduction: There are no economic evaluations to determine the value of PRSs. The objective of this study was to determine if the addition of a PRS to traditional risk factors to guide statin therapy is a cost-effective intervention for the prevention of primary MI cases in the Ontario healthcare payer perspective. Methods: A PRS cost-effectiveness model was constructed to produce various statin prescription strategies in conjunction with the FRS. Upper PRS thresholds (between 25% to 70%) were set such that individuals falling into them would be eligible for statins while those in lower PRS thresholds (between 1% to 25%) were deemed protected and removed from consideration. The model determined number of incident MIs saved or not saved by statins, costs, quality of life, and the effect of statins on preventing MIs over a 10-year time horizon, discounted at 1.5% annually. One-way sensitivity analysis and a PSA were performed by varying all model parameters. Non-related participants of white British descent from 96,736 participants in the UK Biobank at intermediate risk for cardiovascular disease, determined using the Canadian Cardiovascular Society dyslipidemia guidelines of 2016, were used for the study. Results: The optimal clinical and economic strategy was one whereby the top 70% PRS individuals are eligible for statins, with the lower 5% PRS excluded. A base-case analysis at a PRS cost of $70 produced an ICER of $747,184.10/QALY, ranging from $525,678.90/QALY to $930,144.40/QALY in a one-way sensitivity analysis. In the PSA, the intervention has approximately a 50% probability of being cost-effective at $750,000/QALY. At a genotyping cost of $0, statin strategies guided by PRS dominated standard care when at least 12% of the lower PRS individuals were withheld from statins. When the predictive performance of the PRS is increased, the ICER drops drastically depending on the cost of genotyping and statin strategy. Conclusion: The cost-effectiveness model considers MI cases exclusively and a short, 10-year time horizon which likely overestimate the ICER. However, this study elucidates that the PRS has the potential to be extremely cost-effective in the future. / Thesis / Master of Science (MSc) / Approximately 1 in 3 Canadians live with at least one genetically linked chronic disease. Together, these diseases constitute a large economic burden on the healthcare system and well-being of individuals. Recent advancements in genetics allow risk prediction of developing complex, but common chronic diseases such as cardiovascular disease. Termed as polygenic risk scores, they have the potential to carry beneficial clinical outcomes such as an improved quality of life. However, the economics is not yet understood. This study determined that when targeting heart attacks, approximately $750,000 is required to gain an additional life-year for an adult. Although this may seem high, the result is closer to an upper-limit estimate than the true cost since polygenic risk scores have more benefits than solely for heart attacks. In the future, when accounting for their entire potential, the cost per life-year is likely to be lower, and perhaps even a money-returning investment.

L'introduction de nouvelles biotechnologies dans tout système de soins de santé est un processus complexe qui est étroitement lié aux facteurs économiques, politiques et culturels, et, par conséquent, demande de remettre en cause plusieurs questions sociales et éthiques. Dans la situation particulière de l’Argentine - c’est-à-dire: de grandes inégalités sociales entre les citoyens, la rareté des ressources sanitaires, l’accès limité aux services de base, l’absence de politiques spécifiques - l'introduction de technologies génétiques pose de sérieux défis qui doivent impérativement être abordés par les décideurs politiques. Ce projet examine le cas des tests génétiques prénataux dans le contexte du système de santé argentin pour illustrer comment leur introduction peut être complexe dans une nation où l’accès égale aux services de santé doit encore être amélioré. Il faut également examiner les restrictions légales et les préceptes religieux qui influencent l'utilisation des technologies génétiques, ce qui souligne la nécessite de développer un cadre de référence intégral pour le processus d'évaluation des technologies afin d’appuyer l’élaboration de recommandations pour des politiques cohérentes et novatrices applicables au contexte particulier de l’Argentine. / The introduction of new biotechnologies in any health care system is a complex process that is closely tied to economic, political and cultural factors and thus poses a host of challenging social and ethical issues. In the particular situation of Argentina – that is, a country characterised by significant social inequalities between citizens, a scarcity of resources in health care, limited access to needed services, and a lack of specific health policies – the introduction of new genetic technologies poses serious ethical and policy challenges that need urgent attention by policy-makers. This project examines the case of prenatal genetic tests in the context of the Argentinean health care system with the aim of illustrating how complex their introduction can be in a nation where equal access to health care still needs significant improvements. Attention must also be given to the legal restrictions and religious precepts that strongly shape the use of these technologies. This further highlights the necessity of developing an integrated framework for the process of technology assessment, in order to support coherent and innovative policy recommendations applicable to the particular Argentinean context.