Bakgrund: Strategier för att upprätta ett system för finansiering av särläkemedel, d.v.s. läkemedel för behandling av sällsynta sjukdomar, pågår. Målet är att individer med störst behov ska prioriteras utan att resurser till större individgrupper minskas. Problem föreligger dock vid fördelning av resurserna, då dessa redan är begränsade, och att särläkemedel medför mycket höga kostnader. Syfte: Syftet med detta examensarbete är att redovisa hur olika intressenter i Sverige bedömer i vilken omfattning särläkemedel skall användas, vem som skall bära kostnaderna, och hur prioriteringar bör göras för att skapa ett ekonomiskt utrymme för deras användning. Som modelläkemedel har Cerezyme® (ett läkemedel mot Gaucher’s sjukdom) använts. Metod: För att finna svar på min frågeställning gjordes datainsamling genom sökningar i följande databaser: Tandvård- och läkemedelsverket, Fass, Google och PubMed. För att studera prioritering exemplifierades arbetet genom en fallstudie av Cerezyme®. Resultat: Undersökningarna visade att prioriteringar sker genom kostnadsberäkningar av QALY (quality-adjusted life year) tillsammans med människovärdesprincipen, kostnadseffektivitetsprincipen, samt behovs- och solidaritetsprincipen. Utifrån dessa grunder handlägger TLV (Tandvård- och läkemedelsförmånsverket) för innefattande av läkemedelsförmån. TLV valde den 8 mars, 2012, att utesluta Cerezyme® ur läkemedelsförmånen på grund av för höga kostnader per patient och år. Detta överklagades av tillverkaren, Genzyme, men förvaltningsrätten avslog överklagandet den 30 april, 2012. Genzyme valde att överklaga domen, vilket kammarrätten sedan beviljade genom inhibering av TLV:s beslut tills en slutgiltig dom för Cerezyme® fastslagits. TLV överklagade återigen, vilket också avslogs. Cerezyme® finns inom förmån tills vidare. Slutsats: Det råder idag stora olikheter kring rätten att få behandling gällande särläkemedel beroende på patientens geografiska lokalisering, är det synnerligen viktigt att se över finansiering och prioritering av dessa behandlingar. / The choice of my thesis is based on orphan drugs, which individuals with rare diseases use as treatment, diagnostics or to prevent the progress of the disease. In order to get a classification as an orphan drug, the drug must be used for a condition that affects 5 or less of 10 000 individuals, based on the European classification. The clinical trials for this type of medicines are as every medical trial, expensive and orphan drugs have the smallest patient groups. Therefore there is no justification to the pharmaceutical companies in development in orphan drugs. This project is made by a case study and answer survey, and the literature research was based on articles written in English or Swedish, and articles older than 2000 were excluded.The purpose of this thesis is to evaluate how priorities of resources are made, to fund expensive drugs, in Sweden. Tandvårds- och läkemedelsförmånsverket (TLV) has the authority to decide whether different kind of medicines are subjects to the Swedish pharmaceutical benefits, which are funding a great amount of medicines. The thesis is based on evaluations from various stakeholder, Swedish laws and previous research in priority.Sweden is financing the orphan drugs in three ways. Orphan drugs included in Swedish pharmaceutical benefits are funded by customs fee to 2200 SEK, and the rest of the costs are financed by the state through the council counties. Orphan drugs in hospitalization are financed by the hospital, clinic or the county where the patient is registered. The orphan drugs which are prescribed but still excluded from the benefits are financed either by the patient, county or the hospital. The investigation of pricing and financial proposition of orphan drugs in Sweden is delayed but still in progress, and are expected to be presented in April, 2014.TLV make the decisions regarding pharmaceutical benefits through calculations of QALY’s and by three ethical grounds or principles. The principles stand for human dignity, cost-effectiveness, solidarity and needs. TLV could either approve the drug, which makes the drug included to pharmaceutical benefits, or disapprove the drug and makes it unavailable through state funding. TLV decided to exclude Cerezyme® from the Swedish pharmaceutical benefits. The decisions were made of calculations of QALY’s, which was calculated much higher costs than previously approved by TLV. The manufacturers of Cerezyme® did not agree with TLV’s decision, and went to higher courts. The recent decision of higher courts was to re-include Cerezyme® from pharmaceutical benefits, which makes the drug available to patients in desperate need again.Processes of different kinds of orphan drugs to include these to pharmaceutical benefits are not treated equally. Depending of the state of the disease, prevalence and geographic location, are patients treated variously. This is a major problem in management of orphan drugs, and should be prevented as soon as possible. All citizens should on equal terms, have access to same health care, this through Swedish Health Care laws.

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.

Abstract : Rare diseases are debilitating conditions often leading to severe clinical manifestations for affected patients. Orphan drugs have been developed to treat these rare diseases affecting a small number of individuals. Incentives in the legal framework aimed to recoup the research and development cost of orphan drugs for pharmaceutical companies have been implemented in the United States and the European Union. At the present time, Canada is still lacking a legal and policy framework for orphan drugs. Several problems at the federal and provincial levels remain: lack of research funds for rare diseases, discrepancies on orphan drug policies between provinces, difficulties to access and reimburse these high price drugs. Recommendations and measures are proposed, such as a pan-Canadian (national) scientific committee to establish evidence-based guidelines for patients to access orphan drugs uniformly in all provinces with a disease specific registry, a formal agreement for a centralized Canadian public funding reimbursement procedure, and increasing the role of “guardian” for prices by the Patented Medicines Review Board in Canada. These recommendations and measures will be beneficial for the implementation of a policy framework for orphan drugs in Canada. / Résumé : Les maladies rares sont des maladies sérieuses pouvant causer des manifestations cliniques sévères chez les patients atteints. Les médicaments orphelins ont été développés pour le traitement de ces maladies rares qui touchent un petit nombre d’individus. Un cadre légal permettant des incitatifs pour les compagnies pharmaceutiques aux États-Unis et au niveau de l’Union Européenne a favorisé la recherche et le développement desdits médicaments. Présentement, il n’existe pas de cadre juridique et de politiques spécifiques au Canada entourant les médicaments orphelins. Ceci a mené à plusieurs problèmes tant au niveau fédéral que provincial dont: un manque de support financier consacré à la recherche pour les maladies rares, des disparités entre les provinces concernant les politiques pour les médicaments orphelins, des difficultés d’accès et de remboursement desdits médicaments dont les coûts sont élevés. Des recommandations et mesures sont proposées, telles l’implantation d’un comité scientifique pancanadien (national) afin d’établir des lignes directrices fondées sur des données probantes pour faciliter un accès uniforme aux médicaments orphelins pour les patients, y compris un registre spécifique élaboré pour chaque maladie, établir une entente formelle centralisée pour tout le Canada pour un financement public de remboursement des médicaments orphelins, augmenter le rôle de « gardien » des prix par le Conseil d’examen du prix des médicaments brevetés au Canada. Ces recommandations et mesures serviront à l’implantation d’un cadre de politiques pour les médicaments orphelins au Canada.

Pharmaceutical industry is today struggling with its productivity as products keep failing after long and expensive development programs. The protability is further threatened by erce competition from cheaper product copies. As an attempt to increase the pipeline output, pharmaceutical companies have lately turned to the strategy of drug repositioning. By applying an already developed drug in new disease areas the lifetime of the product is prolonged and return time on already made investments elongated.  Such development is imbued by less risk than a de novo development and has proven to be a faster and cheaper way to meet the medical demand. With limited company budgets and the often many repositioning possibilities, an informed repositioning selection must be made. As such theoretical model is not publicly available this thesis takes on the task to determine which parameters to take into consideration and how these should be weighted in relation to each other in order to evaluate di erent drug repositioning possibilities. Six main topics are identied to a ect the repositioning success, these are: medical need, economic return, scientic support, timing, life cycle extenders and external relations. These ndings are derived from empirics collected during interviews with employees from ve di erent competence areas involved in repositioning initiatives, na mely: research & development, clinical studies, regulatory a airs, pricing, and commercial. By further support from literature within the elds of drug repositioning and R&D project selection a three-step repositioning model was developed. The first step in the three-step repositioning model consists of primary parameters, these are essential parameters that have to be fullled in order to perform a repositioning strategy. If any of the primary parameters are not fullled, the repositioning opportunity should be killed in a go/no-go decision. In a second step, the secondary parameters are evaluated in a scoring model in order to determine the economical outlook of each repositioning opportunity. The opportunities showing greatest economical outlook should further be evaluated in the third and nal step in the three-step repositioning model. In this nal step the di erent repositioning opportunities are evaluated by their coherence with an overall corporate strategy. By applying this repositioning model to a repositioning selection scarce company resources  ay be focused on the repositioning opportunities showing best future prospect. Evaluating the potential of repositioning opportunities in a structured way should also increase chances to succeed. If successful, a repositioning initiative may a ect both company and society as the company improves return on earlier investments, while more patients in need of treatment will receive access to it. However, the three-step repositioning model presented in this thesis should be tested for more cases and perhaps be complemented with additional parameters or di erent gradings in order to optimize the selection.

This diploma thesis focuses on drug approval efficiency. It is obvious that the drug approval process is lengthy and expensive. The question that arises is whether the length of the drug approval process, as well as associated costs, leads to better safety. The first part briefly summarizes the history of the drug regulation and the drug legislative in the Czech Republic. Also focuses on the theory of economic regulation and the theory of bureaucracy. The second part deals with the drug approval process for new drugs, describes preclinical and clinical testing in relation to the analysis of Sam Peltzman. The third part compares drug approval process in different markets. The last part summarizes off-label prescribing, especially in pediatric.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-06-20T12:21:13Z No. of bitstreams: 1 Ana Catarina dos Santos Holtz.pdf: 26567764 bytes, checksum: a64dbe08b35339d1978a3394c0a08985 (MD5) / Made available in DSpace on 2017-06-20T12:21:13Z (GMT). No. of bitstreams: 1 Ana Catarina dos Santos Holtz.pdf: 26567764 bytes, checksum: a64dbe08b35339d1978a3394c0a08985 (MD5) Previous issue date: 2017-06-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The research seeks to analyze how the pharmaceutical industry builds the discourse on rare diseases and their patients. Taking the Orphan Drug Act, which guarantees benefits for medicines for such diseases, also called orphan drugs, the first chapter seeks to understand the creation of this market and to base the concepts of power, life, speech and governmentality, based on a documental and bibliographical research. The second chapter aims to reflect on the biopolitical strategies that operate in the discursive construction of the concepts of health and patient in the contemporary neoliberal scenario, while the third analyze the discourse of pharmaceutical company Novartis, the sales leader of the orphan drug segment, to understand how the laboratory establishes its institutional and commercial communication regarding rare diseases and their patients. The laboratory discourse exposes the vulnerability of the untreated patient and seeks to create a model of behavior for their rare disease patients. The theoretical foundation is formed by: Michel Foucault; Nikolas Rose; Giorgio Agamben; Didier Fassin; Peter Miller; Carlos Novas; Adriana Petryna; Paul Rabinow; Adele Clarke; Aidar Prado; Peter Pàl Pelbart; Paulo Vaz; Kátia Lerner; Paula Sibilia and Rogério da Costa / A pesquisa busca analisar de que maneira a indústria farmacêutica constrói o discurso sobre as doenças raras e os seus portadores. Tendo como ponto de partida o decreto norte-americano Orphan Drug Act, que garante benefícios para os medicamentos destinados a tais doenças, também denominados medicamentos órfãos, o primeiro capítulo procura compreender a criação deste mercado e fundamentar os conceitos de poder, vida, discurso e governamentalidade, a partir de uma pesquisa documental e bibliográfica. O segundo capítulo tem como objetivo refletir sobre as estratégias biopolíticas que operam na construção discursiva dos conceitos de saúde e paciente diante do cenário neoliberal contemporâneo, enquanto o terceiro consiste em analisar o discurso do laboratório farmacêutico Novartis, líder de vendas do segmento de medicamentos órfãos, para entender como o laboratório estabelece a sua comunicação institucional e comercial em relação às doenças raras e seus portadores. O discurso do laboratório expõe a vulnerabilidade do paciente sem tratamento e procura criar um modelo de conduta para os seus pacientes de doenças raras. A fundamentação teórica é formada por: Michel Foucault; Nikolas Rose; Giorgio Agamben; Didier Fassin; Peter Miller; Carlos Novas; Adriana Petryna; Paul Rabinow; Adele Clarke; Aidar Prado; Peter Pàl Pelbart; Paulo Vaz; Kátia Lerner; Paula Sibilia e Rogério da Costa

Esta dissertação é composta por dois ensaios sobre economia da saúde. O primeiro ensaio tem como objetivo analisar o ambiente regulatório no mercado de medicamentos para doenças raras. Essas doenças são caracterizadas por afetar um pequeno número de indivíduos em uma determinada população e por serem crônicas, progressivas, degenerativas, 80% são de origem genética, 50% afetam as crianças, das quais 30% morrem antes dos 5 anos de idade. Elas representam risco de morte e um custo socioeconômico alto para o paciente e sua família. Devido à raridade, a indústria farmacêutica tem não demonstra interesse em desenvolver novos medicamentos órfãos. Apesar de individualmente raras, estima-se que o número de casos de alcançar 420 a 560 milhões de pessoas. Para a referida análise foi utilizado o modelo econômico desenvolvido por DeBrock (1985), que consiste na determinação simultânea de esforço de inovação e extensão de patentes, estabelecendo a trajetória ótima de proteção como resultado de um jogo não cooperativo entre o regulador e a empresa inovadora. Foram identificados individualmente os principais incentivos e instrumentos de regulação econômica. Eles são compostos por assistência à protocolos, procedimento centralizado de análise, reduções de taxas, o acesso de pesquisa financiado e exclusividade de mercado. Conclui-se que o instrumento regulatório mais importante foi a exclusividade de mercado, pois garante lucros extraordinários para a empresa inovadora, tornando o desenvolvimento de novas drogas tornou-se economicamente viável. No entanto, ressalta-se que todos os mecanismos tem um papel importante no sistema de incentivos e que cada um deles deve ser considerado para o desenvolvimento de políticas públicas para doenças raras. O segundo ensaio tem como objetivo medir o impacto do Diabete Melito nos rendimentos dos trabalhadores brasileiros no ano de 2008. Essa doença é caracterizada pelo elevado nível de glicose no sangue, problema que pode desencadear desencadeia má cicatrização, ataque cardíaco, acidente vascular cerebral, insuficiência renal, problemas de visão e amputação de membros. Dados do Ministério da Saúde indicam que, no Brasil, em 2010, havia cerca de 10 milhões de casos da doença, sendo a quarta principal causa de morte no país. Dados da WHO estimam que a prevalência da doença no Brasil é de 10,2% da população, cerca de 20 milhões de pessoas. A hipótese a ser testada é que o estado de saúde interfere nos rendimentos por meio de três mecanismos distintos: (i) na decisão de participar no mercado de trabalho, mensurado por meio de um Probit binário, (ii) na quantidade de horas trabalhadas e (iii) a produtividade por hora, ambos mensurados por meio do método de dois estágios de Heckman. Cada modelo é estimado separadamente para indivíduos com e sem doenças, sendo tomada a diferença do valor esperado de ambos para capturar o efeito contrafactual. Os resultados obtidos indicaram a existência de perdas progressivas, que incidem com maior intensidade entre a população feminina e que, no agregado, podem chegar ao valor de R$ 8.064.408.441.99 (USD 3.450.709.518,02 e EUR 2.490.436.905,56), correspondendo a cerca de 0,54% dos rendimentos totais e 0,20% do PIB do referido ano. Concluiu-se que o Diabete Melito gera perdas significativas na renda dos trabalhadores brasileiros, especialmente em relação à sua participação no mercado de trabalho. Os resultados indicam que as políticas públicas devem ser direcionadas para a prevenção da doença, uma vez que o desenvolvimento de comorbidades amplifica o efeito de perdas. Por fim, visando a manter a inter-relação entre os temas e a estabelecer a unidade do trabalho, foram abordadas na última seção as conclusões a respeito da dissertação. / This dissertation consists of two essays on health economics. The aim of the first essay is to analyze the regulatory environment for medicinal products for rare diseases. These diseases are characterized by to affect a small number of individuals in a given population and to be chronic, progressive, degenerative, 80% are genetic in origin, 50% affect children, of which 30% die before the age of 5. They represent death risk and a high socioeconomic cost to the patient and his family. Due to the rarity, pharmaceutical industry has not shown interest in developing new orphan drugs. Although individually rare, estimatives show that the number of cases to reach 420 million to 560 million people. For this analysis the economic model developed by DeBrock (1985), which consists of the simultaneous determination of innovation effort and extension of patents, establishing the optimal path protection as a result of a non-cooperative game between the regulator and the innovator was used. The main incentives and instruments of economic regulation were individually identified. They are protocols assistance, centralized analysis procedure, fee reductions, access to funded research and market exclusivity. We conclude that the most important regulatory tool was market exclusivity, because it ensures extraordinary profits for the innovator, making the development of new drugs become economically viable. However, it is noteworthy that all the mechanisms have an important role in the incentive system and that each of them should be considered for the development of public policies for rare diseases. The second essay aims to measure the impact of diabetes mellitus on the income of Brazilian workers in 2008. The main disease characteristic is high blood glucose, a problem that can trigger scarring troubles, heart attack, stroke, failure kidney, vision problems and limbs amputation. Ministry of Health data indicate that, in Brazil, in 2010, there were about 10 million cases of the disease, making it the fourth leading cause of death in the country. WHO data estimate that the disease prevalence is 10.2% of the Brazilian population, about 20 million people. The hypothesis to be tested is that the health status interfere in worker income through three distinct mechanisms: (i) in the decision to participate in the labor market, measured by means of a binary Probit, (ii) in the amount of hours worked and (iii) in the productivity per hour, both measured by the Heckman two-stage method. Each model is estimated separately for individuals with and without disease, and taking the difference of the expected value of both to capture the counterfactual effect. The results indicated the existence of progressive losses, which focus more strongly among women and that, in the aggregate, may reach R$ 8.064.408.441.99 (3,450,709,518.02 USD and EUR 2,490,436,905, 56), corresponding to about 0.54% of the total income and 0.20% of GDP in that year. It was concluded that diabetes mellitus causes significant losses in Brazilian workers income, especially in relation to their participation in the labor market. The results indicate that public policies should be directed to the prevention of disease, since the development of comorbidities amplifies the losses effect. Finally, to keep the inter-relationship between the issues and to establish the unity of the work, have been addressed in the last section the conclusions regarding the dissertation.

Esta dissertação é composta por dois ensaios sobre economia da saúde. O primeiro ensaio tem como objetivo analisar o ambiente regulatório no mercado de medicamentos para doenças raras. Essas doenças são caracterizadas por afetar um pequeno número de indivíduos em uma determinada população e por serem crônicas, progressivas, degenerativas, 80% são de origem genética, 50% afetam as crianças, das quais 30% morrem antes dos 5 anos de idade. Elas representam risco de morte e um custo socioeconômico alto para o paciente e sua família. Devido à raridade, a indústria farmacêutica tem não demonstra interesse em desenvolver novos medicamentos órfãos. Apesar de individualmente raras, estima-se que o número de casos de alcançar 420 a 560 milhões de pessoas. Para a referida análise foi utilizado o modelo econômico desenvolvido por DeBrock (1985), que consiste na determinação simultânea de esforço de inovação e extensão de patentes, estabelecendo a trajetória ótima de proteção como resultado de um jogo não cooperativo entre o regulador e a empresa inovadora. Foram identificados individualmente os principais incentivos e instrumentos de regulação econômica. Eles são compostos por assistência à protocolos, procedimento centralizado de análise, reduções de taxas, o acesso de pesquisa financiado e exclusividade de mercado. Conclui-se que o instrumento regulatório mais importante foi a exclusividade de mercado, pois garante lucros extraordinários para a empresa inovadora, tornando o desenvolvimento de novas drogas tornou-se economicamente viável. No entanto, ressalta-se que todos os mecanismos tem um papel importante no sistema de incentivos e que cada um deles deve ser considerado para o desenvolvimento de políticas públicas para doenças raras. O segundo ensaio tem como objetivo medir o impacto do Diabete Melito nos rendimentos dos trabalhadores brasileiros no ano de 2008. Essa doença é caracterizada pelo elevado nível de glicose no sangue, problema que pode desencadear desencadeia má cicatrização, ataque cardíaco, acidente vascular cerebral, insuficiência renal, problemas de visão e amputação de membros. Dados do Ministério da Saúde indicam que, no Brasil, em 2010, havia cerca de 10 milhões de casos da doença, sendo a quarta principal causa de morte no país. Dados da WHO estimam que a prevalência da doença no Brasil é de 10,2% da população, cerca de 20 milhões de pessoas. A hipótese a ser testada é que o estado de saúde interfere nos rendimentos por meio de três mecanismos distintos: (i) na decisão de participar no mercado de trabalho, mensurado por meio de um Probit binário, (ii) na quantidade de horas trabalhadas e (iii) a produtividade por hora, ambos mensurados por meio do método de dois estágios de Heckman. Cada modelo é estimado separadamente para indivíduos com e sem doenças, sendo tomada a diferença do valor esperado de ambos para capturar o efeito contrafactual. Os resultados obtidos indicaram a existência de perdas progressivas, que incidem com maior intensidade entre a população feminina e que, no agregado, podem chegar ao valor de R$ 8.064.408.441.99 (USD 3.450.709.518,02 e EUR 2.490.436.905,56), correspondendo a cerca de 0,54% dos rendimentos totais e 0,20% do PIB do referido ano. Concluiu-se que o Diabete Melito gera perdas significativas na renda dos trabalhadores brasileiros, especialmente em relação à sua participação no mercado de trabalho. Os resultados indicam que as políticas públicas devem ser direcionadas para a prevenção da doença, uma vez que o desenvolvimento de comorbidades amplifica o efeito de perdas. Por fim, visando a manter a inter-relação entre os temas e a estabelecer a unidade do trabalho, foram abordadas na última seção as conclusões a respeito da dissertação. / This dissertation consists of two essays on health economics. The aim of the first essay is to analyze the regulatory environment for medicinal products for rare diseases. These diseases are characterized by to affect a small number of individuals in a given population and to be chronic, progressive, degenerative, 80% are genetic in origin, 50% affect children, of which 30% die before the age of 5. They represent death risk and a high socioeconomic cost to the patient and his family. Due to the rarity, pharmaceutical industry has not shown interest in developing new orphan drugs. Although individually rare, estimatives show that the number of cases to reach 420 million to 560 million people. For this analysis the economic model developed by DeBrock (1985), which consists of the simultaneous determination of innovation effort and extension of patents, establishing the optimal path protection as a result of a non-cooperative game between the regulator and the innovator was used. The main incentives and instruments of economic regulation were individually identified. They are protocols assistance, centralized analysis procedure, fee reductions, access to funded research and market exclusivity. We conclude that the most important regulatory tool was market exclusivity, because it ensures extraordinary profits for the innovator, making the development of new drugs become economically viable. However, it is noteworthy that all the mechanisms have an important role in the incentive system and that each of them should be considered for the development of public policies for rare diseases. The second essay aims to measure the impact of diabetes mellitus on the income of Brazilian workers in 2008. The main disease characteristic is high blood glucose, a problem that can trigger scarring troubles, heart attack, stroke, failure kidney, vision problems and limbs amputation. Ministry of Health data indicate that, in Brazil, in 2010, there were about 10 million cases of the disease, making it the fourth leading cause of death in the country. WHO data estimate that the disease prevalence is 10.2% of the Brazilian population, about 20 million people. The hypothesis to be tested is that the health status interfere in worker income through three distinct mechanisms: (i) in the decision to participate in the labor market, measured by means of a binary Probit, (ii) in the amount of hours worked and (iii) in the productivity per hour, both measured by the Heckman two-stage method. Each model is estimated separately for individuals with and without disease, and taking the difference of the expected value of both to capture the counterfactual effect. The results indicated the existence of progressive losses, which focus more strongly among women and that, in the aggregate, may reach R$ 8.064.408.441.99 (3,450,709,518.02 USD and EUR 2,490,436,905, 56), corresponding to about 0.54% of the total income and 0.20% of GDP in that year. It was concluded that diabetes mellitus causes significant losses in Brazilian workers income, especially in relation to their participation in the labor market. The results indicate that public policies should be directed to the prevention of disease, since the development of comorbidities amplifies the losses effect. Finally, to keep the inter-relationship between the issues and to establish the unity of the work, have been addressed in the last section the conclusions regarding the dissertation.

Esta dissertação é composta por dois ensaios sobre economia da saúde. O primeiro ensaio tem como objetivo analisar o ambiente regulatório no mercado de medicamentos para doenças raras. Essas doenças são caracterizadas por afetar um pequeno número de indivíduos em uma determinada população e por serem crônicas, progressivas, degenerativas, 80% são de origem genética, 50% afetam as crianças, das quais 30% morrem antes dos 5 anos de idade. Elas representam risco de morte e um custo socioeconômico alto para o paciente e sua família. Devido à raridade, a indústria farmacêutica tem não demonstra interesse em desenvolver novos medicamentos órfãos. Apesar de individualmente raras, estima-se que o número de casos de alcançar 420 a 560 milhões de pessoas. Para a referida análise foi utilizado o modelo econômico desenvolvido por DeBrock (1985), que consiste na determinação simultânea de esforço de inovação e extensão de patentes, estabelecendo a trajetória ótima de proteção como resultado de um jogo não cooperativo entre o regulador e a empresa inovadora. Foram identificados individualmente os principais incentivos e instrumentos de regulação econômica. Eles são compostos por assistência à protocolos, procedimento centralizado de análise, reduções de taxas, o acesso de pesquisa financiado e exclusividade de mercado. Conclui-se que o instrumento regulatório mais importante foi a exclusividade de mercado, pois garante lucros extraordinários para a empresa inovadora, tornando o desenvolvimento de novas drogas tornou-se economicamente viável. No entanto, ressalta-se que todos os mecanismos tem um papel importante no sistema de incentivos e que cada um deles deve ser considerado para o desenvolvimento de políticas públicas para doenças raras. O segundo ensaio tem como objetivo medir o impacto do Diabete Melito nos rendimentos dos trabalhadores brasileiros no ano de 2008. Essa doença é caracterizada pelo elevado nível de glicose no sangue, problema que pode desencadear desencadeia má cicatrização, ataque cardíaco, acidente vascular cerebral, insuficiência renal, problemas de visão e amputação de membros. Dados do Ministério da Saúde indicam que, no Brasil, em 2010, havia cerca de 10 milhões de casos da doença, sendo a quarta principal causa de morte no país. Dados da WHO estimam que a prevalência da doença no Brasil é de 10,2% da população, cerca de 20 milhões de pessoas. A hipótese a ser testada é que o estado de saúde interfere nos rendimentos por meio de três mecanismos distintos: (i) na decisão de participar no mercado de trabalho, mensurado por meio de um Probit binário, (ii) na quantidade de horas trabalhadas e (iii) a produtividade por hora, ambos mensurados por meio do método de dois estágios de Heckman. Cada modelo é estimado separadamente para indivíduos com e sem doenças, sendo tomada a diferença do valor esperado de ambos para capturar o efeito contrafactual. Os resultados obtidos indicaram a existência de perdas progressivas, que incidem com maior intensidade entre a população feminina e que, no agregado, podem chegar ao valor de R$ 8.064.408.441.99 (USD 3.450.709.518,02 e EUR 2.490.436.905,56), correspondendo a cerca de 0,54% dos rendimentos totais e 0,20% do PIB do referido ano. Concluiu-se que o Diabete Melito gera perdas significativas na renda dos trabalhadores brasileiros, especialmente em relação à sua participação no mercado de trabalho. Os resultados indicam que as políticas públicas devem ser direcionadas para a prevenção da doença, uma vez que o desenvolvimento de comorbidades amplifica o efeito de perdas. Por fim, visando a manter a inter-relação entre os temas e a estabelecer a unidade do trabalho, foram abordadas na última seção as conclusões a respeito da dissertação. / This dissertation consists of two essays on health economics. The aim of the first essay is to analyze the regulatory environment for medicinal products for rare diseases. These diseases are characterized by to affect a small number of individuals in a given population and to be chronic, progressive, degenerative, 80% are genetic in origin, 50% affect children, of which 30% die before the age of 5. They represent death risk and a high socioeconomic cost to the patient and his family. Due to the rarity, pharmaceutical industry has not shown interest in developing new orphan drugs. Although individually rare, estimatives show that the number of cases to reach 420 million to 560 million people. For this analysis the economic model developed by DeBrock (1985), which consists of the simultaneous determination of innovation effort and extension of patents, establishing the optimal path protection as a result of a non-cooperative game between the regulator and the innovator was used. The main incentives and instruments of economic regulation were individually identified. They are protocols assistance, centralized analysis procedure, fee reductions, access to funded research and market exclusivity. We conclude that the most important regulatory tool was market exclusivity, because it ensures extraordinary profits for the innovator, making the development of new drugs become economically viable. However, it is noteworthy that all the mechanisms have an important role in the incentive system and that each of them should be considered for the development of public policies for rare diseases. The second essay aims to measure the impact of diabetes mellitus on the income of Brazilian workers in 2008. The main disease characteristic is high blood glucose, a problem that can trigger scarring troubles, heart attack, stroke, failure kidney, vision problems and limbs amputation. Ministry of Health data indicate that, in Brazil, in 2010, there were about 10 million cases of the disease, making it the fourth leading cause of death in the country. WHO data estimate that the disease prevalence is 10.2% of the Brazilian population, about 20 million people. The hypothesis to be tested is that the health status interfere in worker income through three distinct mechanisms: (i) in the decision to participate in the labor market, measured by means of a binary Probit, (ii) in the amount of hours worked and (iii) in the productivity per hour, both measured by the Heckman two-stage method. Each model is estimated separately for individuals with and without disease, and taking the difference of the expected value of both to capture the counterfactual effect. The results indicated the existence of progressive losses, which focus more strongly among women and that, in the aggregate, may reach R$ 8.064.408.441.99 (3,450,709,518.02 USD and EUR 2,490,436,905, 56), corresponding to about 0.54% of the total income and 0.20% of GDP in that year. It was concluded that diabetes mellitus causes significant losses in Brazilian workers income, especially in relation to their participation in the labor market. The results indicate that public policies should be directed to the prevention of disease, since the development of comorbidities amplifies the losses effect. Finally, to keep the inter-relationship between the issues and to establish the unity of the work, have been addressed in the last section the conclusions regarding the dissertation.

Background: Increasing costs and quantities of orphan drugs within the European market has led to much debate in Sweden on how they should be handled within the existing reimbursement system. Previously, there has been little research looking at local and regional handling of and implications of these issues when it comes to decision-making, financing, and access. This study aims to provide insight into these issues through perspectives and experiences obtained in interviews with representatives working for County Councils in Northern Sweden. Methods: A case study comprised of semi-structured interviews following a qualitative methodology with an inductive approach was used for this study. Five informants from three different work groups engaged with the orphan drug introduction process in Northern Sweden were interviewed. A thematic analysis was performed on the data where common themes were identified through several rounds of coding to allow cross-sectional analysis between data obtained from informants. Results: The thematic analysis identified five major themes surrounding the introduction process for orphan drugs; centralization of processes, methods & standardization, ethical considerations, economics & price setting, and challenges & difficulties. Informants provided insights, opinions, and a deeper understanding of these themes within the introduction process for orphan drugs. Conclusion: This study confirms many of the complexities in establishing a clear and fair process for introducing orphan drugs. In line with existing literature, informants highlighted how centralization and the pooling of resources and expertise is vital in ensuring equal quality and access to care for patients suffering from rare diseases. There is broad agreement how orphan drug legislation and processes should develop, but substantial hurdles concerning the specifics as well as issues with external actors on pricing of orphan drugs. Addressing these issues could potentially have important benefits, not only for healthcare budgets and patients suffering from rare diseases, but also in setting precedents for future processes where costs and ethics will again come to a head.