Today, Real World Data (RWD) is a popular topic in many studies. In particular, it is anticipated to be a significant resource for addressing issues brought on by drug development costs, lengthy development times, and safety concerns. The Swedish healthcare Quality Registries (QR) are studied to contribute to the improvement of health care with individual-based clinical data. Recorded data is used for quality improvement, guidance compliance monitoring, and research. However, the workflow for such a framework that applies RWD which is patient-related data that came from various sources to the new drug development field is currently not well-defined. Thus the main aim of this project is to establish a strategy for integrating RWD with pharmaceutical modeling. To achieve this aim, QRs were examined through an ontological approach. The data and procedures necessary for modeling the development of new drugs, as well as the correspondence of the pieces offered by QR, were studied to assess the feasibility. The modeling of new drug development was studied for three applications: Adverse Drug Event (ADE), Computer-based Simulation (CBS), and drug repurposing, and the analysis of QRs was conducted on seven diseases. After in-depth analysis, although there were differences between the registries, it showed enough feasibility in terms of how much the data provided in the studies on drug repurposing and computer-based simulation satisfied the items required for new drug development. However, in the case of rare diseases, given the lack of an automated method, the ethical ambiguity, and the speed of the process, there still seems to be potential for improvement.  Many registries have begun to support research on the development of novel medications, such as by independently recording the features of drugs. These initiatives could enable the future potential of new Real World Evidence (RWE) such as in the field of proteomics and genomics discovery. / Idag är Real World Data (RWD) ett populärt ämne i många studier. I synnerhet förväntas det vara en betydande resurs för att ta itu med problem som orsakas av kostnader för läkemedelsutveckling, långa utvecklingstider och säkerhetsproblem. Kvalitetsregistren studeras för att bidra till att förbättra hälso- och sjukvården med individbaserade kliniska data. Registrerade data används för kvalitetsförbättring, övervakning av efterlevnad av riktlinjer och forskning. Arbetsflödet för ett sådant ramverk som tillämpar RWD som är patientrelaterad data som kom från olika källor till det nya läkemedelsutvecklingsområdet är dock för närvarande inte väldefinierat. Därför är huvudsyftet med detta projekt att upprätta en strategi för att integrera RWD med läkemedelsmodellering. För att uppnå detta mål undersöktes kvalitetsregister genom ett ontologiskt tillvägagångssätt. De data och procedurer som krävs för att modellera utvecklingen av nya läkemedel, såväl som överensstämmelsen mellan de bitar som erbjuds av kvalitetsregister, studerades för att bedöma genomförbarheten. Modelleringen av utvecklingen av nya läkemedel studerades för tre tillämpningar: skadlig läkemedelseffekt, datorbaserad simulering och återanvändning av läkemedel, och analys av kvalitetsregister genomfördes på sju sjukdomar. Efter en djupgående analys, även om det fanns skillnader mellan registren, visade den tillräcklig genomförbarhet när det gäller hur mycket data som tillhandahållits i studierna om läkemedelsåteranvändning och datorbaserad simulering uppfyllde de krav som krävdes för utveckling av nya läkemedel. Men när det gäller sällsynta sjukdomar, med tanke på avsaknaden av en automatiserad metod, den etiska oklarheten och processens snabbhet, verkar det fortfarande finnas potential för förbättringar. Många register har börjat stödja forskning om utveckling av nya mediciner, till exempel genom att oberoende registrera drogens egenskaper. Dessa initiative skulle kunna möjliggöra den framtida potentialen för nya verkliga bevis, såsom inom området för proteomik och genomik.

生技新藥產業是指使用於人類及動植物用之新藥及高風險醫療器材之產業。而生技新藥產業與醫藥產業，在目的上均與人類及動植物用藥或醫療儀器相關；差異之處在於目前的生技醫藥產業相較於20餘年前的醫藥產業，多了生物技術的應用，產業結構由大型藥廠垂直整合演變為非營利組織、生物技術公司、大型藥廠分工的形態。總結來說，生物技術是生技新藥產業的重要組成要素，而生物技術的興起，則改變了過去醫藥產業產品與技術的組成，也改變了產業結構。 生物技術產業或醫藥產業是全球各國競相發展的產業類別，我國亦不例外；其中，美國無論於生物技術或醫藥產業的發展，均居於全球領先的地位，其成功必然有可以提供我們討論或學習之處。而在知識價值鏈的體系中，美國大學更扮演著提供創新以及產學合作的重要角色，對於全球生技新藥產業的進步有重要的貢獻。從而本研究以美國為標的，研究產業的發展歷程，並進一步以產業之觀點，探討大學產學合作的模式以及智慧財產管理，希望能供我國大學與產業實務發展的參考。 從美國生物技術與醫藥產業發展的歷史與經驗，本研究歸納出生物技術產業興起的因素，與1980年代發生的基礎科學上的突破性發展、拜杜法案的通過、專利法將生物技術的發明納入保護範圍，三項因素有關。另外，由大學所提供的創新，透過密切的產學合作、授權與技術移轉、企業間的策略聯盟等方式，於知識的價值鏈中流動並增加價值，而大學提供創新的人才，往往也是創業者和重要的經營者。 本研究認為，美國大學對生物技術發展具有重要性的貢獻，其中，大學內部創業與大學智慧財產的管理特別值得討論。在大學內部創業方面，美國大學不但鼓勵創業，並制定股權政策，允許新創公司以股權取代部分的授權報酬，給予新創公司實際的協助。透過限制大學持股比例與禁止大學擔任董事或參與董事投票活動之原則，則可兼顧大學避免利益衝突與公司專業經營的需求。 在大學智慧財產管理的部份，本研究認為加州大學系統的智慧財產管理方式，採用網路式的授權與技術移轉組織，將各校區共同的需求如政策、法務、資訊技術與通訊等活動統籌處理，而將需與發明人和企業密切交流的活動如授權與技術移轉的活動交由各校區的授權與技術移轉中心負責。透過此種統籌與分工管理的方式，能夠兼顧減少營運成本與增加授權效率的功能。 經由本研究節果，建議我國的大學可採用網路式的授權與技術移轉組織之概念，除各校之授權與技轉中心外，聯合設一統籌政策、法務、智慧財產資料庫之管理機構，並對大學持有公司股份、鼓勵創業、避免利益迴避等議題制定一致的政策，方能有效利用資源並發揮大學創新的價值。 / Biotech and new drug development industry are targeted toward the development of drugs for human, animal, or plant use. This also includes the high-risk industry in medical devices. Although the pharmaceutical industry shares common objectives, the biotech and new drug industry emphasizes on applications in biotechnology and its industrial structure is composed by non-profit organizations and biotech dedicated firms. While biotechnology forms the basis to the biotech and new drug industry, the improvement of biotechnology also changed the interaction between the pharmaceutical products and technologies as well as its industrial structure. Biotechnology and pharmaceutical industry have received considerable attention around the world, including Taiwan. Since U.S. has been the leading country in the development of biotechnology and pharmaceutical industry, we can surely learn from its success. In particular, universities in the U.S. have played a crucial role in providing innovation and promoting university-industry cooperation and resulted in significant contributions to the progress of global biotech and new drug industry. Thus, this study will investigate the development of the industry within the U.S. by dissecting the various university-industry cooperation models and the management of intellectual property rights. Results from this study will hopefully shed some light on bridging our university with industry for further practice operation. By examining the U.S. biotech and pharmaceutical industry, this study has concluded that breakthroughs in fundamental, the passage of Bayh-Dole Act, and the inclusion of biotechnology into patent law science in 1980s are responsible for the rise of biotechnology industry. In addition, active university-industry cooperation along with licensing, technology transfer, strategic alliance among enterprises and information flowing in the knowledge value chain added the value of the innovation provided by universities. In many cases, the university has not only provided innovation, but also a source for future leaders that would take on role of the founders or head of project management. The U.S. universities have made significant contributions to the development of biotechnology by establishing entrepreneurship programs, intellectual property rights management, and often providing substantial assistance in business start-up. One type of assistance is rendered through regulating policies on equity that allows start-up companies to provide equity in place of part of license fee. In order to avoid a “conflict of interest”, universities should be limited of their possession of industry equity, which can prevents them from taking part in the company as the board director or members. In terms of the management of intellectual property rights, the measures of management of the University of California system can help diminish operation cost and enhance licensing efficiency. University of California system resorts to Technology transfer in a distributed institutional network that feed the common needs from each campus such as patent policies, general counsel, and information technology and communications. A licensing and technology transfer center (OTT) on each campus will follow a system wide license and technology transfer process between the inventor and the enterprise. In conclusion, it is recommended that our university could adopt the concept of network licensing and technology transfer. Through an overall arrangement, a management institute can be established to regulate the planning of policies, provide general counseling, and build a database of intellectual property rights aside from the existing licensing and technology center of each university. In the best interest of the developing biotech and new drug industry, universities should initiate policies with regard to equity holding limitation, encouragement of start-up business, and the avoidance in the “conflict of interest” so the industry may effectively utilize university resources and demonstrate its innovative values.

在各大藥廠明星藥品專利到期、新藥開發數量銳減的當下，全球首例植物新藥MediGene Veregen™ 的核准上市為製藥產業帶來新的希望，雖然製藥價值鏈與商品化模式已為人所熟知，但針對植物新藥特殊性所架構之商品化模式還是一個全新的議題，為了架構一個適合台灣中小型藥廠的植物新藥開發模式，本研究嘗試以技術層面為根基，從法規面、產品面與產業面深入探討MediGene Veregen™ 關鍵的成功因素，從中獲取值得台灣藥廠參考的經驗，同時考量台灣植物新藥開發的大環境限制因素，包括法規與健保，給予台灣藥廠一些植物新藥商品化策略建議。 本研究之架構以實務觀點出發，首先整理參考文獻以探討植物新藥包含的範圍與藥品開發流程，幫助藥廠了解植物新藥商品化需要具備的條件與資訊；接著針對台灣與美國在植物新藥方面審查上市之法規、流程與審核成果進行研究，結果顯示目前台灣有兩種植物新藥審查系統「中藥新藥」與「植物抽取新藥」，對廠商而言並不如美國單一系統來得便利；再者藉由探討植物新藥的價值鏈結構、法規結構、產品結構與產業結構，試圖架構植物新藥商品化模式；接下來以兩家新藥開發廠商為例進行實際個案研究，一家為成功推出植物新藥商品的德國藥廠MediGene AG，一家為台灣藥廠中天生技/合一生技，主要藉由分析MediGene Veregen™ 商品化過程的關鍵成功因素，比較中天生技/合一生技WH-1商品化模式的異同，探討是否有足以借鏡與改進之處。最後，歸納整理上述的研究做出結論，並且對於台灣藥廠提出策略建議，希望能對於台灣新藥開發公司有實質上的幫助。 / While the star drug patents of each big pharmaceutical company are expired one after another and the quantity of their newly developed drugs sharply declines in these years, MediGene Veregen™, the first botanical new drug in the world, enters the market and therefore brings a new hope for the pharmaceutical industry. Although the value chain and the commercialization model of pharmaceutical industry have been known and researched a lot, the specific construction of commercialization model for botanical drugs is still a brand new subject. In older to construct the model that is suitable for Taiwanese middle and small pharmaceutical companies for the process from development to commercialization of botanical new drugs, this research, based on the technical analysis, attempts to discuss the key success factors of MediGene Veregen™ through analyzing the aspects of the laws, regulations, industry and product itself. With the case study about the environmental limited factors of new drug development in Taiwan, including the laws and regulations as well as the health insurance, this research tries to offer Taiwan pharmaceutical companies some strategic suggestions for the development and commercialization of botanical new drugs. The structure of this research is based on the practical viewpoints. First, we reorganize the reference in order to define the scope of botanical new drugs and the processes of drug development. It can help pharmaceutical companies understand the conditions and information needed for botanical new drug commercialization. Then, our studies focus on the laws and regulations in Taiwan and the United States, as well as the application processes and approvals for botanical new drugs. The results show that there are two evaluation systems in Taiwan for botanical new drug applications. For those pharmaceutical companies, the dual system is not as convenient as the sole evaluation system in the States. Furthermore; based on the discussion on the structure of the value chain, laws, regulations, product and industry, this paper makes an attempt to construct a better commercialization model of botanical new drugs. Next, two pharmaceutical companies are chosen as case study in this paper. One is a German pharmaceutical company, MediGene AG, which launched the first botanical new drug. The other is a Taiwan pharmaceutical company, MicroBio Co., Ltd/Oneness Bio-Tech Co., Ltd. By analyzing the key success factors in the commercialization process of MediGene Veregen™ and comparing its commercialization model with MicroBio Co., Ltd/Oneness Bio-Tech Co. WH-1, we try to get any valuable idea and insight. Finally, our conclusion and strategic suggestions may have solid help for Taiwan botanical new drug pharmaceutical companies.

O constante crescimento mundial da Pesquisa Clínica no desenvolvimento de novas drogas foi responsável pelo aumento do interesse em traçar as atividades desenvolvidas pelas Autoridades Regulatórias. Os dados foram obtidos através de revisão bibliográfica sistemática, destacando o tempo de aprovação dos protocolos clínicos e as normatizações vigentes: no Brasil, Estados Unidos da América, União Europeia, Canadá e Japão. Além disso, observou-se a atuação de profissionais experientes na realização de atividades no Comitê de Ética para Análise de Projetos de Pesquisa (CAPPesq) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Com isso, foi possível identificar as diferenças significantes em relação à legislação e ao sistema regulatório dos países em questão. Deficiências no sistema regulatório brasileiro responsáveis pela demora no tempo de aprovação foram constatadas. Com a identificação destes fatores, foram elaboradas sugestões relacionadas à qualificação dos profissionais atuantes, organização das atividades desempenhadas pelas Autoridades Regulatórias e possíveis alterações administrativas. A diferente atuação das autoridades analisadas pode servir como fonte de aprimoramento do sistema regulatório nacional e, consequentemente, aprimorar o processo para aprovação e realização de protocolos clínicos com medicamentos testados no Brasil. / The world-wide Clinical Research for new drug development growth was responsible for the increase of interest in following the regulatory authorities activities. Data were collected through a systematic literature review.The main facts observed were clinical protocols time approval and guidelines in Brazil, United States of America, European Union, Canada and Japan. In addition, it was observed the activities realized by experienced professionals of the IRB of the University of São Paulo School of Medicine. Significant legislation and regulatory system differences between the countries were identified. Some deficiencies at Brazilian regulatory system, suggestions regarding the acting professionals qualification, organization of the regulatory authorities activities and possible administrative changes were discussed. The different performance of the regulatory authorities can serve as a source to upgrade the national regulatory system and consequently lead to improvements in process of approval and realization of clinical protocol with drugs tested in Brazil.

Nos anos 90 era comum que a distinção entre o traficante e o usuário estivesse baseada nos artigos da antiga lei de drogas, ou seja, em criminalizar alguém por drogas por meio dos artigos 16 ou 12. Eram os próprios números dos artigos das leis que representavam socialmente e distinguiam um usuário (16) de um traficante de drogas (12) e, claro, o modo como à polícia poderia ou não incriminar alguém dentro do sistema de justiça criminal no Brasil. Após o ano de 2006, o Estado Brasileiro promulga a chamada Nova Lei de Drogas com o objetivo de deslocar o usuário de drogas para o sistema de saúde ao mesmo tempo em que aumenta a punição para os traficantes. Assim, este trabalho analisa as principais implicações da chamada nova lei de drogas lei 11.343 de 2006 desde a sua formulação no sistema político até a sua aplicação no sistema de justiça criminal tendo como problemática empírica geral o fenômeno da intensificação do encarceramento por tráfico de drogas no Brasil, sobretudo, após o advento da nova lei. Para tanto, a análise parte da formulação que o novo dispositivo de drogas no Congresso Nacional teve, dentre os seus principais objetivos, dispor: i) o fim da pena de prisão para o usuário de drogas; ii) o advento de um tratamento médico para o usuário; iii) o aumento da punição para o traficante mediante a expansão de grupos criminosos no início dos anos 2000, sobretudo, em São Paulo. Ou seja, está em jogo à modificação da representação social do traficante e do usuário que bifurca entre uma nova representação médico-social do usuário agora visto como um doente e objeto das instituições de saúde e assistência social e uma velha representação criminal do traficante como inimigo agora visto como um indivíduo perigoso e organizado. São estas duas figuras que engendram a formulação de um novo dispositivo de drogas com diferentes tipos de punições para a venda e o uso de drogas no Brasil nos anos 2000. Argumento que a introdução desse novo dispositivo chamado aqui de dispositivo médico-criminal de drogas produziu uma nova maneira de governar os usuários e traficantes de drogas e que trouxe, como uma das principais consequências, a intensificação da criminalização por tráfico de drogas e a rejeição do deslocamento do usuário para outro sistema que não o sistema de justiça criminal. Assim, demonstro que há uma nova maneira de administração estatal da droga no Brasil, qual é a sua história e como ela desenvolveu práticas no sistema de justiça criminal: como um copo meio vazio de médico e cheio de prisão. / In the 90s it was common that the distinction between the drug dealer and the user was based on the articles from the old drug law, in other words, criminalize someone for drugs through the articles \"16\" or \"12\". Were the very numbers of these articles that used to represent socially and distinguish a user (16) from a drug dealer (12) and, of course, the way the police could incriminate someone or not within the criminal justice system in Brazil. After 2006, the Brazilian State passed the so called New Drug Law in order to move the drug user to the health system while increasing the punishment for traffickers. Thus, this study analyzes the main implications of the new so called drug law - Law 11.343 of 2006 - since its formulation in the political system to its application in the criminal justice system, assuming as a general empirical problem the phenomenon of imprisonment and its increase for trafficking drugs in Brazil, especially after the advent of the new law. Therefore, the analysis assumes that the new drug device in National Congress had, among its main goals, to dispose: i) the end of a prison sentence for drug users; ii) the advent of a medical treatment for the user; iii) an increasing of the punishment for the trafficker due to the expansion of criminal groups in the early 2000s, especially in São Paulo. Ie, what is at stake is the changing in the social representation of drug dealers and users which leads to a bifurcation between a new medical and social representation of the user - now seen as \"sick\" and subject for health and social care institutions - and an old criminal representation of the dealer as an enemy - now seen as an individual \"dangerous and organized.\" These are the two figures that engender the development of a new drug device with different types of punishments for the sale and use of drugs in Brazil in the 2000s. I argue that the introduction of this new device called here as medical- criminal drug device - has produced a new way to govern users and drug dealers and it brought, as one of the main consequences, the increased criminalization of drug trafficking and the rejection of the user displacement to another system other than the criminal justice system. The research, therefore, seeks to first show how new ideas were developed in the formulation of a new drug device, secondly, what were the main implications of this device within the criminal justice system. Thus, I demonstrate that there is a new way of state administration of drugs in Brazil, what is your story and how it developed new practices in the criminal justice system: as a half empty glass of medicine and full of imprisonment.

Nos anos 90 era comum que a distinção entre o traficante e o usuário estivesse baseada nos artigos da antiga lei de drogas, ou seja, em criminalizar alguém por drogas por meio dos artigos 16 ou 12. Eram os próprios números dos artigos das leis que representavam socialmente e distinguiam um usuário (16) de um traficante de drogas (12) e, claro, o modo como à polícia poderia ou não incriminar alguém dentro do sistema de justiça criminal no Brasil. Após o ano de 2006, o Estado Brasileiro promulga a chamada Nova Lei de Drogas com o objetivo de deslocar o usuário de drogas para o sistema de saúde ao mesmo tempo em que aumenta a punição para os traficantes. Assim, este trabalho analisa as principais implicações da chamada nova lei de drogas lei 11.343 de 2006 desde a sua formulação no sistema político até a sua aplicação no sistema de justiça criminal tendo como problemática empírica geral o fenômeno da intensificação do encarceramento por tráfico de drogas no Brasil, sobretudo, após o advento da nova lei. Para tanto, a análise parte da formulação que o novo dispositivo de drogas no Congresso Nacional teve, dentre os seus principais objetivos, dispor: i) o fim da pena de prisão para o usuário de drogas; ii) o advento de um tratamento médico para o usuário; iii) o aumento da punição para o traficante mediante a expansão de grupos criminosos no início dos anos 2000, sobretudo, em São Paulo. Ou seja, está em jogo à modificação da representação social do traficante e do usuário que bifurca entre uma nova representação médico-social do usuário agora visto como um doente e objeto das instituições de saúde e assistência social e uma velha representação criminal do traficante como inimigo agora visto como um indivíduo perigoso e organizado. São estas duas figuras que engendram a formulação de um novo dispositivo de drogas com diferentes tipos de punições para a venda e o uso de drogas no Brasil nos anos 2000. Argumento que a introdução desse novo dispositivo chamado aqui de dispositivo médico-criminal de drogas produziu uma nova maneira de governar os usuários e traficantes de drogas e que trouxe, como uma das principais consequências, a intensificação da criminalização por tráfico de drogas e a rejeição do deslocamento do usuário para outro sistema que não o sistema de justiça criminal. Assim, demonstro que há uma nova maneira de administração estatal da droga no Brasil, qual é a sua história e como ela desenvolveu práticas no sistema de justiça criminal: como um copo meio vazio de médico e cheio de prisão. / In the 90s it was common that the distinction between the drug dealer and the user was based on the articles from the old drug law, in other words, criminalize someone for drugs through the articles \"16\" or \"12\". Were the very numbers of these articles that used to represent socially and distinguish a user (16) from a drug dealer (12) and, of course, the way the police could incriminate someone or not within the criminal justice system in Brazil. After 2006, the Brazilian State passed the so called New Drug Law in order to move the drug user to the health system while increasing the punishment for traffickers. Thus, this study analyzes the main implications of the new so called drug law - Law 11.343 of 2006 - since its formulation in the political system to its application in the criminal justice system, assuming as a general empirical problem the phenomenon of imprisonment and its increase for trafficking drugs in Brazil, especially after the advent of the new law. Therefore, the analysis assumes that the new drug device in National Congress had, among its main goals, to dispose: i) the end of a prison sentence for drug users; ii) the advent of a medical treatment for the user; iii) an increasing of the punishment for the trafficker due to the expansion of criminal groups in the early 2000s, especially in São Paulo. Ie, what is at stake is the changing in the social representation of drug dealers and users which leads to a bifurcation between a new medical and social representation of the user - now seen as \"sick\" and subject for health and social care institutions - and an old criminal representation of the dealer as an enemy - now seen as an individual \"dangerous and organized.\" These are the two figures that engender the development of a new drug device with different types of punishments for the sale and use of drugs in Brazil in the 2000s. I argue that the introduction of this new device called here as medical- criminal drug device - has produced a new way to govern users and drug dealers and it brought, as one of the main consequences, the increased criminalization of drug trafficking and the rejection of the user displacement to another system other than the criminal justice system. The research, therefore, seeks to first show how new ideas were developed in the formulation of a new drug device, secondly, what were the main implications of this device within the criminal justice system. Thus, I demonstrate that there is a new way of state administration of drugs in Brazil, what is your story and how it developed new practices in the criminal justice system: as a half empty glass of medicine and full of imprisonment.

FDA decisions and late-stage clinical trial results regarding new pharmaceutical approvals can cause extreme moves in the share price of small biopharmaceutical companies. Throughout the clinical trial process, many potential investors are exposed to market-moving information before such information is made available to the investing public. An investor who wished to profit from advance knowledge about clinical trial results may use the publicly traded options markets in order to increase leverage and maximize profits. This research examined options data surrounding the public release of information pertaining to the efficacy of clinical trials and approval decisions made by the FDA. Events were identified for small pharmaceutical companies with fewer than three currently approved drugs in an attempt to isolate the effect of individual clinical trial and FDA-related events on the share price of the underlying company. Option data were analyzed using logistic regression models in an attempt to predict phase II and III clinical trial outcome results and FDA new drug approval decisions. Implied volatility, open interest, and option contract delta values were the primary independent variables used to predict positive or negative event outcomes. The dichotomized version of a predictor variable designed to estimate total investment exposure incorporating open interest, option contract delta values, and the underlying stock price was a significant predictor of negative pharmaceutical related events. However, none of ii the variables examined in this research were significant predictors of positive drug research related events. The estimated total investment exposure variable used in this research can be applied to the prediction of future clinical trial and FDA decision related events when this predictor variable shows a negative signal. Additional research would help confirm this finding by increasing the sample size of events that potentially follow the same pattern as those examined in this research. / text

Made available in DSpace on 2014-12-17T14:13:35Z (GMT). No. of bitstreams: 1 BolivarPGLD_DISSERT.pdf: 1624811 bytes, checksum: 4e49d5598ae806bbd9ddd7c33b6e903c (MD5) Previous issue date: 2010-06-19 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market / In?meros produtos farmac?uticos v?m sendo desenvolvidos nos ?ltimos anos com a finalidade de incrementar o tratamento de doen?as pelo aumento da efic?cia de f?rmacos. Grande parte destes novos produtos est? baseada nos novos sistemas transportadores de f?rmacos. Entre eles destacamse as microemuls?es, que foram primeiramente estudadas em 1943 por Hoar e Schulman. Microemuls?o pode ser definida como um sistema termodinamicamente est?vel, isotr?pico, transl?cido e transparente de dois l?quidos imisc?veis estabilizados por um filme de tensoativos localizados na interface ?leo/?gua. O objetivo deste trabalho foi incorporar anfotericina B e sinvastatina em um sistema microemulsionado e analisar suas propriedades f?sico-qu?micas e suas a??es terap?uticas ap?s a incorpora??o destes f?rmacos ao sistema. Alguns resultados muito promissores foram alcan?ados como a redu??o da toxicidade e a perman?ncia da efic?cia da anfotericina B incorporada em uma microemuls?o durante o estudo farmacotoxicol?gico in vitro. Quanto ? incorpora??o da sinvastatina na microemuls?o, foi constatada uma melhora significativa no potencial antiinflamat?rio e antiinfeccioso (efeitos pleiotr?picos da sinvastatina) em feridas tratadas com esse sistema. Portanto, podemos concluir que a incorpora??o desses f?rmacos em sistemas microemulsionados faz das microemuls?es uma nova e promissora apresenta??o farmac?utica, habilitando-a a futuros ensaios com a finalidade de torn?-los dispon?veis no mercado farmac?utico

O constante crescimento mundial da Pesquisa Clínica no desenvolvimento de novas drogas foi responsável pelo aumento do interesse em traçar as atividades desenvolvidas pelas Autoridades Regulatórias. Os dados foram obtidos através de revisão bibliográfica sistemática, destacando o tempo de aprovação dos protocolos clínicos e as normatizações vigentes: no Brasil, Estados Unidos da América, União Europeia, Canadá e Japão. Além disso, observou-se a atuação de profissionais experientes na realização de atividades no Comitê de Ética para Análise de Projetos de Pesquisa (CAPPesq) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Com isso, foi possível identificar as diferenças significantes em relação à legislação e ao sistema regulatório dos países em questão. Deficiências no sistema regulatório brasileiro responsáveis pela demora no tempo de aprovação foram constatadas. Com a identificação destes fatores, foram elaboradas sugestões relacionadas à qualificação dos profissionais atuantes, organização das atividades desempenhadas pelas Autoridades Regulatórias e possíveis alterações administrativas. A diferente atuação das autoridades analisadas pode servir como fonte de aprimoramento do sistema regulatório nacional e, consequentemente, aprimorar o processo para aprovação e realização de protocolos clínicos com medicamentos testados no Brasil. / The world-wide Clinical Research for new drug development growth was responsible for the increase of interest in following the regulatory authorities activities. Data were collected through a systematic literature review.The main facts observed were clinical protocols time approval and guidelines in Brazil, United States of America, European Union, Canada and Japan. In addition, it was observed the activities realized by experienced professionals of the IRB of the University of São Paulo School of Medicine. Significant legislation and regulatory system differences between the countries were identified. Some deficiencies at Brazilian regulatory system, suggestions regarding the acting professionals qualification, organization of the regulatory authorities activities and possible administrative changes were discussed. The different performance of the regulatory authorities can serve as a source to upgrade the national regulatory system and consequently lead to improvements in process of approval and realization of clinical protocol with drugs tested in Brazil.

After numerous renewals and reignitions since the initiation of the "War on Cancer" more than five decades ago, the recent reignition of "Moonshot to Cure Cancer" points to the systemic persistence of cancer as a major cause of loss of life and livelihood. Literature points to the diminishing returns of cancer research through time, as well as heterogeneities in cancer research centers' innovation strategies. This dissertation focuses on the strategic decision by cancer research centers to invest their resources in conducting early phases of clinical trials on new candidate drugs/treatments (resembling exploration) or late phases of clinical trials that push established candidates towards acquiring FDA approvals (resembling exploitation). The extensive clinical trials data suggests that cancer research centers are not only different in their emphasis on exploratory trials, but also in how their emphasis is changing over time. This research studies the dynamics of this heterogeneity in cancer research centers' innovation strategies, how experiential learning and capability development interact to cause dynamics of divergence among learning agents, and how the heterogeneity among cancer research centers' innovation strategies is affected by the dynamics of learning from experience and capability development. The findings of this dissertation shows that endogenous heterogeneities can arise from the process of learning from experience and accumulation of capabilities. It is also shown that depending on the sensitivity of the outcome of decisions to the accumulated capabilities, such endogenous heterogeneities can be value-creating and thus, justified. Empirical analysis of cancer clinical trials data shows that cancer research centers learn from success and failure of their previous trials to adopt more/less explorative tendencies. It also demonstrates that cancer research centers with a history of preferring exploratory or FDA trials have the tendency to increase their preference and become more specialized in one specific type (endogenous specialization). These behavioral aspects of the cancer research centers' innovation strategies provide some of the tools necessary to model the behavior of the cancer research efforts from a holistic viewpoint. / Doctor of Philosophy / The "Moonshot to Cure Cancer" was renewed most recently in September 2022. However, renewal and reignition of this national collective effort is nothing new; this effort started as "War on Cancer" in 1971 and has been reignited numerous times. After more than 50 years of our collective battle to cure cancer, it claims almost 600,000 lives annually and remains as the second leading cause of death in the US. There are a wide variety of cancer research centers from all around the world contributing to this collective effort and they make considerably different decisions regarding their investment in research. There is evidence suggesting that some of the research centers' investment decisions are not optimal and can be improved. It has been shown that systems such as patent regulations can be revised to encourage such improved decisions among cancer research centers. This dissertation focuses on the process of clinical trials for new drugs/treatments for cancer. New drugs/treatments have to pass different phases of trials to ensure that they are safe and effective before they can acquire FDA approvals. Cancer research centers decide whether to invest in early phases of clinical trials for new drug/treatment candidates or invest in late phases of trials for candidates that have already passed the early phases. The clinical trials data show that there has been a sharp rise in number of early phases of trials on new drugs/treatments; however, the same rise cannot be seen in the late phases of trials resulting in approvals. It can also be seen that different research centers put different levels of emphasis on initiating early phases of trials for new drugs/treatments (exploration). In this dissertation, the hypothesis is that this ongoing dilemma that cancer research centers face to invest on how much emphasis to put on exploration in their clinical trials is affected by learning from experience. To test this hypothesis, a mathematical model is used to show differences in decisions can be causes solely by learning from experience, when the decision maker is learning "what to do" from success/failure of previous efforts and learning "how to do it" from practicing and accumulating the required skills. Then, the hypothesis is formally tested using the clinical trials data. The results show that cancer research centers learn from the success and failure of their previous exploratory trials when deciding on their emphasis on exploration. Also, they accumulate skills, resources, and capabilities relevant to the type of research the conduct more often and specialize in either of late- or early-phases of trials. The findings of this dissertation show that learning from experience can cause in differences in decisions. It also finds evidence that cancer research centers learn to place different levels of emphasis on exploration in their clinical trials. These findings can later be used in models of the cancer research ecosystem to study how funding structures and policies can be changed to improve the outcomes of our collective effort to cure cancer.