Introdução O Transtorno de Déficit de Atenção/hiperatividade (TDAH) tem sido muito estudado, mas informações econômicas referentes ao seu tratamento com o metilfenidato de liberação imediata (MFD-LI) ainda necessitam ser exploradas. Grande parte da população mundial, principalmente aqueles que vivem em países em desenvolvimento, utiliza essa formulação como principal escolha para o tratamento do TDAH. Esses países, por sua condição financeira, necessitam informações de análises econômicas para administrar de forma eficiente os recursos públicos destinados aos setores da saúde. Objetivos Avaliar a eficácia do MFD-LI através de estudos com tempo superior a 12 semanas, e realizar uma análise econômica para o tratamento do TDAH com MFD-LI para crianças e adolescentes brasileiros. Método O estudo foi planejado em cinco etapas: 1) estimativa de custo do não tratamento do TDAH para o Brasil, e estimativa de economia com tratamento com MFD-LI; 2) revisão sistemática da literatura nas principais bases de dados internacionais onde se buscaram estudos abertos com tratamento do TDAH com MFD-LI por tempo igual ou superior a 12 semanas; também foram feitas metanálises e uma metaregressão 3) estudo naturalístico para obterem-se dados de uma amostra brasileira referentes a probabilidades de uso e sucesso com tratamento com MFD-LI por 12 semanas, e estimar os utilities desses indivíduos; 4) painel Delphi com especialistas em TDAH no Brasil; 5) estudo de custo-efetividade para o tratamento do TDAH com MFD-LI no Brasil, utilizando um Modelo de Markov. A perspectiva adotada será a do sistema público de saúde brasileiro como pagador. Resultados Os resultados principais encontrados para cada uma das etapas foram: 1) a estimativa de custos anuais com o TDAH não tratado no Brasil foi de R$ 1.594 bilhões/ano, e da quantia que poderia ser economizada se tratado, R$ 1 bilhão/ano. 2) na revisão sistemática da literatura, de 4.498 resumos, sete foram incluídos para compor a metanálise. O tempo de tratamento variou entre 13 e 104 semanas. O efeito agregado para desatenção e hiperatividade medida pelos pais, respectivamente, foi 0.96 (95%CI 0.60 - 1.32) e 1.12 (95%CI 0.85 - 1.39), e pelos professores 0.98 (95%CI 0.09 - 1.86) e 1.25 (95% CI 0.7 - 1.81). A metaregressão não mostrou associação entre as variáveis idade, qualidade do artigo e tempo de tratamento com heterogeneidade. 3) no estudo naturalístico, de 171 pacientes avaliados, 73 forneceram informações para o baseline, e 56 para a 12a semana de tratamento com MFD-LI. Os utilities para um paciente com TDAH não tratado (baseline) foram 0.69 (crianças) e 0.66 (adolescentes), e estimaram-se ganhos entre 0.09 a 0.10 utilities/mês, se tratados adequadamente. 4) no painel Delphi, de 26 especialistas, 14 responderam o questionário online, e foi estimado que a probabilidade dos pacientes não tratados se manterem sintomáticos na 12a semana seria de 91%, e 9% a probabilidade de melhora espontânea; 5) no estudo de custo-efetividade, para o caso base, estimou-se que o Incremental Cost Effectiveness Ratio (ICER) seja I$9,103/QALY (Quality Adjusted Life Years) para crianças e I$11,883/QALY para adolescentes em um horizonte temporal de 06 anos. Para os cenários mais desfavoráveis, os ICERS mais elevados foram I$95,164/QALY para 50% de sucesso com o tratamento, e I$15,000/QALY para 70% de adesão em um horizonte temporal de 06 anos. Conclusões O MFD-LI é um tratamento eficaz para crianças e adolescentes, por um período superior a 12 semanas. Entretanto, o Brasil pode estar aumentando os custos referentes à saúde por não estar fornecendo um tratamento eficaz e economicamente acessível para o TDAH. O tratamento mostrou ser uma opção custo-efetiva para crianças e adolescentes brasileiros, mesmo em cenários desfavoráveis para o tratamento. / Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) is a well-known psychiatric disorder, but some economical aspects of the treatment with Methylphenidate Immediate-release (MPH -IR) still need to be explored. A large number of people around the world, most living in Low-Middle Income Countries (LMIC), use this formulation as the first choice for ADHD treatment. These countries, due to their financial condition, need information from health economic analyzes to efficiently manage the public resources allocated to the health sector. Objective To study the efficacy of MPH-IR reviewing studies conducted for more than 12 weeks long, and to perform an economic analysis for the treatment of ADHD with MPH-IR for Brazilian children. Method The study was planned in a five stages process: 1) to estimate the cost of untreated ADHD for Brazil, and to estimate the savings if MPH-IR were adequately provided; 2) systematic review of the literature to identify papers published where young patients with ADHD were treated with MPH-IR for more than 12 weeks, and to perform a meta-analysis and a meta-regression; 3) to conduct a naturalistic study with a Brazilian sample to collect the probabilities of use and success with the MPH-IR treatment for 12 weeks, and to estimate the utilities; 4) to perform a Delphi panel with ADHD Brazilian experts; 5) to conduct a cost-effectiveness analysis for the treatment of ADHD with MPH-IR in Brazil, using a Markov model. The perspective is the one of the Brazilian public health system as the payer. Results The main findings for each step were: 1) the estimated annual expenditures with untreated ADHD in Brazil were R$1.594billon/year, and the estimated amount that could be saved was R$1billion/year; 2) in the systematic review, from 4,498 abstracts, 7 studies were selected. The length of treatment ranged from 13 to 104 weeks. The aggregate effects for inattention and hyperactivity, according to parents evaluations were respectively 0.96 (95%CI 0.60 - 1.32) and 1.12 (95%CI 0.85 - 1.39), and for teachers 0.98 (95%CI 0.09 - 1.86) e 1.25 (95% CI 0.7 - 1.81). There was no evidence of association between heterogeneity and the variables, age, paper quality and length of treatment; 3) in the naturalistic study, from 171 patients assessed, 73 provided information in the baseline, and 56 in the 12th week of MPH-IR treatment. Utilities for an untreated ADHD patient (baseline) were 0.69 (children) and 0.66 (adolescents), and it was estimated a gain ranging from 0.09 to 0.10 utilities/month if subjects were properly treated; 4) in the Delphi Panel, 26 experts were addressed and 14 filled in the online questionnaire. It was estimated the probability of untreated patients to remain symptomatic on the 12th week to be 91%, and the probability of spontaneous improvement, 9%; 5) in the cost-effectiveness analysis, for the base case, it was estimated an Incremental Cost Effectiveness Ratio (ICER) of I$9,103/QALY (Quality Adjusted Life Years) for children and I$11,883/QALY for adolescents, in a time horizon of 6 years. The worst case scenarios were also tested, and the highest ICER were I$95,164/QALY when patient reached 50 % of success with the treatment, and I$15,000/QALY if only 70% of use was observed in a time horizon of 6 years. Conclusions MPH-IR is an efficacious treatment for ADHD children and adolescents for periods longer than 12 weeks. However, Brazil may be probably wasting money due to not provide an efficient and affordable treatment for ADHD such as the MPH-IR. The treatment proved to be cost-effective for children and adolescents living in Brazil, even when the worst case scenarios were tested.

INTRODUÇÃO: Aproximadamente 170 milhões de pessoas são portadores de hepatite C crônica, sendo esta atualmente a principal causa de transplantes hepáticos no mundo. Os pacientes com hepatite crônica C são atualmente tratados com interferon e ribavirina (IFN/RBV). Estudos de associação do genoma associaram à resposta ao tratamento com IFN/RBV a um polimorfismo de nucleotídeo único (SNP) nas proximidades do gene da Interleucina 28B, que codifica a interferona-?. OBJETIVOS: Padronizar nova metodologia de baixo custo e menor tempo de execução para a genotipagem do polimorfismo rs12979860. Investigar a frequência do polimorfismo rs12979860, em uma coorte de pacientes com hepatite crônica C e sua associação com a resposta ao tratamento no Hospital das Clínicas da Universidade de São Paulo. MÉTODOS: A genotipagem foi realizada, por novo método diagnóstico, PCR multiplex CTPP (confronto de dois pares de iniciadores) e validado através de sequenciamento direto e PCR em tempo real. Um estudo retrospectivo foi realizado em 248 portadores de hepatite C crônica, tratados com interferon e ribavirina; 138 portadores de hepatite C crônica, virgens de tratamento e 240 doadores de sangue. Foi analisado o DNA, dados clínicos e demográficos, juntamente com dados sobre a resposta ao tratamento. RESULTADOS: O método de PCR CTPP foi padronizado e mostrou-se mais rápido e de menor custo comparado ao sequenciamento e PCR em tempo real. Pacientes com resposta virológica sustentada (RVS) apresentaram uma frequência de 33/61 (54,1%) para o genótipo C/C, de 21/61 (34,4%) para o genótipo C/T e 7/61 (11,5%) para o genótipo T/T. Pacientes que não tiveram RVS (Não RVS) apresentam uma frequência de 44/185 (23,8%) para o genótipo C/C, de 102/185 (55,1%) para o genótipo C/T e de 39/185 (21,1%) para o genótipo T/T. Os Não RVS estão associados ao genótipo C/T (p=0,002) e ao genótipo T/T (p=0,001) quanto comparados com o grupo de RVS. CONCLUSÕES: Esta dissertação descreve um método inovador, rápido e de baixo custo, o PCR CTPP, que detecta o polimorfismo rs12979860. O ensaio é internamente controlado e não requer a utilização de endonucleases de restrição ou equipamento especial. O polimorfismo rs12979860 é um preditor significativo da resposta ao tratamento com IFN/RBV em pacientes com infecção crônica pelo vírus da hepatite C. A genotipagem deste, em conjunto com os indicadores já existentes, pode identificar prováveis não respondedores ao tratamento / INTRODUCTION: Approximately 170 million people are chronic carriers of hepatitis C virus (HCV). Chronic HCV patients are currently treated with pegylated interferon and ribavirin (PEG- IFN/RBV). A genome-wide association with PEG-IFN/RBV treatment response and a single nucleotide polymorphism (rs12979860) has been identified near the interleukin 28B gene that encodes interferon-?-3. AIM: Describe an innovative, fast, and low-cost multiplex polymerase chain reaction with confronting two-pair primers that detects the rs12979860 polymorphism. Investigate the frequency of polymorphism rs12979860, among patients with chronic hepatitis C and association with to response treatment at the Hospital das Clínicas da Universidade de São Paulo. METHODS: Genotyping was performed by new diagnostic method, multiplex PCR CTPP (confronting two-pairprimers) and validated by direct sequencing and real time PCR. Retrospective study was conductedin 248 patients with hepatitis C chronic treated with interferon and ribavirin, 138 patients with chronic hepatitis C treatment-naïve and 240 blood donors. We analyzed DNA, clinical and demographic data, along with data onthe response to treatment. RESULTS AND CONCLUSIONS: The CTPP method was standardized and proved faster and lower cost compared to sequencing andreal time PCR. Patients with sustained virologic response (SVR) showed a frequency of 33/61 (54.1%) for the genotype C/C of 21/61 (34.4%) for the genotype C/T and 7/61 (11.5%) for genotype T/T. Patients with out sustained virologic response (Non SVR) have a frequency of 44/185 (23.8%) for the genotype C/C,102/185 (55.1%) for the genotype C/T and 39/185 (21.1%) for genotype T/T.The Non SVR are associated with genotype C/T (p = 0.002) and T/T genotype (p= 0.001) as compared with the group of SVR. Today, the IL28B genotyping is recomended by in the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines. As a result, physicians should consider testing IL28B in patients with hepatitis C; however, the implementation of routine genotyping has been halted in tertiary care hospitals because of the need for molecular biology tools that are expensive and highly complex. The CTPP multiplex assay described here detects in a single reaction the genotypes C/C, C/T, and T/T. This method allows rapid genotyping of the polymorphism rs12979860, which is reproducible in minimally equipped laboratories; it does not require any special equipment and is a relatively low-cost procedure. The PCR-CTPP method can be used for large testing arrays and is also suitable for genotyping a small number of samples

O objetivo principal da presente pesquisa foi estimar o valor monetário de visitação do Parque “PHILLIPE WESTIN CABRAL DE VASCONCELOS” e adjacências da ESALQ/ USP localizado no Município de Piracicaba do Estado de São Paulo. Para tanto, foi aplicado o método de valoração contingente, adotando-se o modelo de referendo com distribuição de probabilidade logística. O levantamento de dados foi efetuado no período de agosto a setembro de 2004, realizando-se 207 entrevistas, extraindo-se uma amostra para aproveitamento de 202 observações. O valor médio da disposição a pagar foi estimado em R$ 14,53 por mês. O beneficio econômico total foi estimado em R$ 37.487,40 por mês, considerando o numero total estimado de 2.580 visitantes mensais. Tais valores demonstram o considerável beneficio econômico que os atributos do Parque da ESALQ/ USP geram para toda a população local. Tais resultados podem ser utilizados para auxiliar no planejamento de políticas de visitação ordenada do lugar, além de auxiliar na justificativa do investimento na manutenção e preservação do lugar. O estudo constatou os motivos para não aceitação do valor de pagamento mensal. O valor sugerido, a restrição orçamentária e a imputação de que a manutenção e preservação de áreas naturais publicas é responsabilidade do governo, são algumas das principais razões. / The main objective of the present research was to estimate the monetary value of visitation of Park "PHILLIPE WESTIN CABRAL OF VASCONCELOS" and adjacencies of ESALQ/USP located in the City of Piracicaba, State of São Paulo. For which, the method of contingent valuation was applied, adopting the model countersignature with distribution of logistic probability. The data-collected was over the period between August and September 2004. The sample totaled 207 interviews, out of which, 202 were used in the estimation procedures. The average value of the willingness to pay was estimated to be R$ 14,53 per month. The total economic benefit was calculated to be R$ 37.487,40 per month considering a total monthly visitation of 2.580. Such values demonstrate a considerable economic benefit that Park of ESALQ/USP generates for all its visitors. Such results can be used to assist in the planning of visitation policies and to justify the investment in the Park’s maintenance and preservation. Also, the main reasons for payment refusal were: suggested value; the income restriction; and the perception that the maintenance and preservation of public natural areas are responsibility of the government.

Introdução: As avaliações econômicas completas do tipo custo-utilidade, suportadas por dados de efetividade do mundo real, permitem uma perspectiva diferenciada da avaliação de tecnologia em saúde. Objetivo: Realizar uma análise de custo-utilidade do uso de estatinas para a prevenção secundária de eventos cardiovasculares em portadores de doença cardiovascular isquêmica, e avaliar a variabilidade da efetividade e da razão de custo-efetividade incremental com diferentes classificações de usuários de estatina (incidentes e prevalentes). Método: Um modelo de microssimulação de Markov com 5 estados, ciclos anuais e horizonte temporal de 20 anos, com taxas de desconto de 5% foi desenvolvido. As probabilidades de transição para mortalidade por todas as causas foram extraídas após pareamento por escore de propensão dos dados e tratamento de dados ausentes de uma base secundária de registro assistencial com linkage determinístico com a base de mortalidade do Ministério da Saúde. As probabilidades dos desfechos não-fatais foram obtidas na literatura. As medidas de efetividade (QALY) foram calculadas com dados publicados dos domínios do SF-36 de um estudo realizado com a população do mesmo hospital, no mesmo período e com as mesmas condições clínicas e transformados em medidas de utilidade por modelo validado. Somente custos diretos na perspectiva do reembolso do SUS foram considerados. Resultados: 3.150 pacientes foram pareados após o escore de propensão, 1.050 não usuários de estatina, 1.050 usuários de estatinas classificados como prevalentes e 1.050 usuários de estatinas classificados como incidentes, com diagnóstico de doença cardiovascular isquêmica prévia, com seguimento médio de 5,1 anos. A efetividade das estatinas quando considerados todos os usuários em relação aos não usuários resultou em um HR para mortalidade de 0,992 (IC 95% 0,85; 0,96) e de 0,90 (IC 95% 0,85; 0,96) para os usuários incidentes. A RCEI comparando todos os usuários de estatinas versus não usuários foi de R$5.846,10/QALY e de R$7.275,61/QALY para os usuários incidentes. Conclusão: As estatinas diminuíram a mortalidade por todas as causas, e a análise incluindo usuários prevalentes diminui o tamanho do efeito. O tratamento possui custo-efetividade favorável dentro do limiar de disponibilidade a pagar definido, sendo modificado pela forma de extração do dado de efetividade / Background: The complete economic evaluations, such as cost-utility analysis, supported by real world data of effectiveness lead to a more realistic perspective of a health technology assessment. Objective: Perform a cost-utility analysis of statins for secondary prevention in ischemic cardiovascular disease patients based on effectiveness from real world data and evaluate the variability of effectiveness and incremental cost-effectiveness ratio (ICER) considering prevalent and incident users. Methods: A Markov microssimulation model with five states, annual cycle and time horizon (TH) of 20 years, with discount rate of 5% was developed. Transition probabilities for all cause mortality was derived from a secondary database of a teaching hospital after record linkage with national registry of mortality database and an analysis of propensity score matching and multiple imputation analysis for missing data. Non-fatal endpoints were derived from a published meta-analysis. Utility measures was calculated with a validated model to derive values from published domains of SF-36 QoL questionnaire, domains was measured for a published RCT in the same teaching hospital, over the same period, with similar age and diagnostic characteristics. Only direct costs were analyzed from the Brazilian public health reimbursement perspective. Results: 3150 patients were matched, 1050 non-statins users (CG), 1050 prevalent statins users (PSU) and 1050 incident statins users (ISU) with previous cardiovascular disease, with mean follow-up of 5,1 years. Treatment effects on the treatment group considering all statins users for all cause mortality had a hazard ratio of HR:0,992 (IC 95% 0,85 - 0,96) and HR: 0,90 (IC 95% 0,85 - 0,96) only for ISU. The ICER comparing all users with non-users was R$5.846,10 per QALY and for ISU was R$7.275,61 per QALY. Conclusion: Real world evidence demonstrated that statins are an effective treatment to reduce all cause mortality in secondary prevention and are a cost-effective strategy considering the willingness to pay established, but the prevalent users resulted in less effectiveness of the drug when included in the analysis and influenced the ICER

O câncer do colo do útero é o quarto tipo de câncer mais frequente em mulheres em todo mundo. No Brasil, estima-se que cerca de 16 mil novos casos ocorrem por ano. A redução deste tipo de câncer ao longo dos anos deve-se ao rastreamento das lesões intraepiteliais cervicais por meio do exame citológico de Papanicolaou. Em 2014, o Programa Nacional de Imunização (PNI) introduziu a vacina contra o papilomavírus humano (HPV) como prevenção primária deste câncer, uma vez que este vírus é uma causa necessária para o surgimento desta malignidade. A vacinação não substitui o rastreamento, visto que não há proteção contra todos os tipos de HPV de alto risco e nem imunização de toda a população. A incorporação do programa de vacinação interfere nos resultados do programa de rastreamento, pois leva a diminuição dos casos de câncer e lesões precursoras. Desta forma, existe a necessidade de explorar novas estratégias de rastreamento, considerando também outras tecnologias existentes. Objetivo: desenvolver um modelo do tipo Markov para realizar uma análise de custo-efetividade de estratégias de rastreamento do câncer do colo do útero para hipotéticas coortes imunizadas e não imunizadas contra o vírus do HPV no Brasil na perspectiva do Sistema Único de Saúde (SUS). Métodos: A primeira parte é a exploração e avaliação qualitativa de estudos de avaliação econômica sobre estratégias de rastreamento para prevenção do câncer do colo do útero que utilizaram um modelo do tipo Markov feita por meio de uma revisão sistemática. A reunião das várias abordagens utilizadas e das principais características destes modelos poderá auxiliar a construção de um modelo em cenários onde há poucos profissionais capacitados com esta técnica. Baseando-se nesta revisão e nas consultas a especialistas das áreas de ginecologia, virologia e epidemiologia, foi desenvolvido um modelo matemático de análise de decisão estático do tipo Markov que simula a história natural do câncer do colo do útero considerando a imunização contra o HPV. Este modelo simula o seguimento de uma coorte de mulheres, dos 10 anos até o óbito, cujos parâmetros foram estimados a partir de dados secundários (revisão da literatura, sistemas de informação em saúde e inquéritos populacionais) nacionais específicos do rastreamento e calibrados de forma a refletir as condições reais de rastreamento encontradas no Brasil. Resultados: A revisão dos modelos de Markov para avaliação econômica de estratégias de rastreamento do câncer do colo do útero mostrou que a declaração do problema e a descrição das estratégias a serem comparadas foram muito bem relatados. Em contrapartida, os itens de avaliação da incerteza e consistência do modelo e a consistência precisam melhorar o relato. Os resultados obtidos por meio da calibração do modelo se mostraram satisfatórios, pois alcançaram uma boa concordância com os dados empíricos. A análise do caso base sugeriu que a melhor estratégia foi o Teste HPV-DNA como triagem para o encaminhamento da citologia ou da colposcopia, com repetição a cada 5 anos, para mulheres entre 30 e 70 anos. Esta estratégia promove um ganho de 9,5 dias ao longo dos anos e detecta, a cada 100 mil mulheres, 6 casos a mais de câncer e 16 de NIC II/III. A razão de custo-efetividade incremental (RCEI) foi de R$16.056,94 por ano de vida ganho, na perspectiva do sistema de saúde. Conclusão: Estudos futuros devem considerar metodologias que levem em conta a incerteza, a heterogeneidade e a consistência no modelo de decisão e utilizar diretrizes validadas para o relato do estudo / Cervical cancer is the fourth most common cancer in women worldwide. In Brazil, it is estimated that around 16,000 new cases occur per year. The reduction of this type of cancer over the years owes to cervical intraepithelial lesions screening through pap smears. In 2014, the National Immunization Program (NIP) introduced a vaccine against human papillomavirus (HPV) as the primary prevention of this cancer, since this virus is a necessary cause for the onset of this malignancy. Vaccination does not replace screening because there is no protection against all types of high risk HPV nor immunization of the entire population. Incorporation of the vaccination program interferes with the results of the screening program, leading to a decreased number of cancer cases and precursor lesions. In this way, there is a need to explore new screening strategies, also considering other existing technologies. Objective: Determining a Markov based model to perform a cost-effectiveness analysis of cervical cancer screening strategies for hypothetical immunized and non-immunized cohorts against the HPV in Brazil from the perspective of the Unified Health System (UHS). Methods: The first part is a qualitative appraisal and assessment of economic evaluation studies on screening strategies for cervical cancer prevention using a Markov based model done through a systematic review. The combination of different approaches and of the main features of these models can be auxiliary in the construction of a model in scenarios where there are few professionals trained with this technique. Based on this review and consultations with specialists in the areas of gynecology, virology and epidemiology, a Markov model for decision analysis was developed, which simulates the natural history of cervical cancer considering immunization against HPV. This model simulates the follow-up of a cohort of women, from 10 years-old to death, whose parameters were estimated from secondary data, particular to screening and calibrated in order to reflect real screening conditions found in Brazil. Results: A review of Markov models for economic evaluation of cervical cancer screening strategies showed that the report of the problem statement and the description of the compared strategies were well conducted. In contrast, the uncertainties of the model and the consistency were the worst items. The results obtained by calibration of the model were satisfactory, since a good agreement with empirical data was achieved. The baseline case analysis suggested that the best strategy was the HPV-DNA Test as triage for cytology or colposcopy referral, repeated every 5 years, for women between 30 and 70 years-old. This strategy promotes a gain of 9.5 days over the years and detects, every 100,000 women, 6 cases of cancer and 16 of CIN 2/3. The incremental cost-effectiveness ratio (ICER) was R$16,056.94 per life years gained from the health system perspective. Conclusion: Future studies should consider methodologies that take into account uncertainty, heterogeneity and consistency in the decision model and use validated guidelines for the study report

Análise de custo-benefício (CBA) é um instrumento de avaliação de políticas que auxilia na tomada de decisão, empregada principalmente por gestores públicos. A CBA foi utilizada com o intuito de alcançar o objetivo principal desse estudo: verificar se a exportação de água virtual - água incorporada em um produto durante seu processo produtivo - embutida em 10 produtos do setor agropecuário brasileiro, no período de 2002 a 2016, está sendo benéfica ao Brasil. Os produtos estudados foram agrupados em 5 grupos, Açúcar, Café, Milho, Soja e Boi que, somados, desde o ano de 2012 têm representado mais de 20% do total das exportações brasileiras, em termos monetários, US$. Para qualquer análise custo-benefício é necessário que todos os impactos (custos e benefícios) sejam monetizados para se apurar o benefício líquido (BL), que é alcançado diminuindo-se os custos (C) dos benefícios (B), (BL=B-C). O estudo admitiu como custo os custos de produção, dos produtos estudados; a tarifa de armazenagem portuária; e, o valor da água virtual exportada pelo Brasil. Como benefício está sendo considerado o valor recebido com a exportação desses produtos, convertido em moeda nacional. Dessa forma, para alcançar o objetivo principal do estudo, foi necessário precificar a água virtual, um dos objetivos específicos do estudo. Ademais, o estudo apresenta ainda os principais parceiros importadores do Brasil, com relação aos produtos estudados; a importância brasileira como país exportador para esses parceiros importadores; a diferença no volume de água utilizado para produção, tanto no Brasil quanto nesses importadores; e, o volume e o valor total da água virtual exportada no período analisado. A hipótese central que norteou esse trabalho é que o Brasil obteve mais benefícios do que custos ao exportar água virtual, embutida na cesta de produtos agropecuários escolhida. Inclusive, essa hipótese pôde ser confirmada, uma vez que se identificou, por meio da CBA, benefícios totais líquidos positivos, no período de 2002 a 2016, isto é, os benefícios (valor das exportações) superaram os custos (custo de produção, tarifa portuária e valor da água virtual). No que tange aos benefícios líquidos por grupo de produto estudado, os mesmos apresentaram resultado negativo em alguns anos do período analisado. Como exemplo, para o grupo Milho, nos anos de 2005, 2006 e 2009 os benefícios líquidos foram negativos. Quanto aos benefícios totais líquidos, os mesmos foram de R$ 216.342.482.411,98 no período de 2002 a 2016. Em relação ao volume total de água virtual exportada, incorporada nos produtos abordados pelo estudo, no período analisado, o mesmo foi de 2.514.850,651 milhões de m3 de água. Em termos de valor monetário, o total apurado para esse volume de água foi de R$ 27.166.366.824,47. / Cost-benefit analysis (CBA) is a policy evaluation tool that assists in decision-making, used primarily by public managers. CBA was used in order to reach the main objective of this study: to verify if the export of virtual water - water contained in a product during its production process - embedded in 10 products of the Brazilian agricultural sector, from 2002 to 2016, is being beneficial to Brazil. The products studied were grouped into 5 groups: Sugar, Coffee, Corn, Soybean and Bovine, which, since the year of 2012, represented more than 20% of total Brazilian exports, in monetary terms, US$. For any cost-benefit analysis it is necessary that all impacts (costs and benefits) are monetized to determine the net benefit (NB), which is achieved by decreasing the costs (C) of the benefits (B), (NB = B-C). The study admitted as cost the costs of production, of the products studied; the port storage tariff; and, the value of virtual water exported by Brazil. As a benefit is being considered the value received with the export of these products, converted into national currency. Thus, to reach the main objective of the study, it was necessary to value the virtual water, one of the main objectives of the study. In addition, the study also analyses the main importing partners of Brazil, in relation to the products studied; the importance of Brazil as a leading agricultural exporting country for these importing partners; the difference in the volume of water used for production, both in Brazil and in the importing partners; and, the volume and total value of the virtual water exported in the analyzed period. The central hypothesis that guided this work is that Brazil obtained more benefits than costs when exporting virtual water embedded in the chosen basket of agricultural products. This hypothesis could even be confirmed, since the CBA identified positive total net benefits from 2002 to 2016, i.e., benefits (value of exports) exceeded costs (production cost, tariff port value and virtual water value). Regarding the net benefits per product group studied, they presented negative results in some years of the analyzed period, for example, for the Corn group, in the years 2005, 2006 and 2009 the net benefits were negative. As for the total net benefits, they were R$ 216,342,482,411.98 in the period from 2002 to 2016. In relation to the total volume of virtual exported water, incorporated in the products addressed by the study, during the analyzed period, it was 2,514,850,651 million m3 of water. In terms of monetary value, the total amount for this volume of water was R$ 27,166,366,824.47.

This thesis assesses UK banking liquidity regulation and supervision and the Basel liquidity requirements, and models banks' liquidity risk. The study reveals that the FSA's risk-assessment framework before 2008 was too general without specifically considering banks' liquidity risk (as well as its failures on Northern Rock). The study also lists the limitations of the FSA's banking liquidity regimes before 2008. The thesis reviews whether the FSA's new liquidity regimes after 2008 would have coped with UK banks' liquidity risks if they have been applied properly. The fundamental changes in the FSA's liquidity supervision reflect three considerations. First, it introduces a systemic control requirement by measuring individual fifirm's liquidity risk with a market-wide stress or combination of idiosyncratic and market-wide stresses. Second, it emphasizes the monitoring of business model risks and the capability of senior managers. Third, it allows both internal and external managers to access more information by increasing the liquidity reporting frequencies. The thesis also comments on the Basel Liquidity Principles of 2008 and the two Liquidity Standards. The Principles of 2008 represents a substantial revision of the Principles of 2000 and reflect the lessons of the fifinancial market turmoil since 2007. The study argues that the implementation of the sound principles by banks and supervisors should be fexible, but also need to be consistent to make sure they understand banks' liquidity positions quite well. The study also explains the composition of the Basel liquidity ratios as well as the side effect of Basel liquidity standards; for example, it will reshape interbank deposit markets and bond markets as a result of the increase in demand for `liquid assets' and `stable funding'. This thesis uses quantitative balance sheet liquidity analysis, based upon modified versions of the BCBS (2010b) and Moody's (2001) models, to estimate eight UK banks' short and long-term liquidity positions from 2005 to 2010 respectively. The study shows that only Barclays Bank remained liquid on a short-term basis throughout the sample period (2005-2010); while the HSBC Bank also proved liquid on a short-term basis, although not in 2008 and 2010. On a long-term basis, RBS has remained liquid since 2008 after receiving government support; while Santander UK also proved liquid, except in 2009. The other banks,especially Natwest, are shown to have faced challenging conditions, on both a short-term and long-term basis, over the sample period. This thesis also uses the Exposure-Based Cash-Flow-at-Risk (CFaR) model to forecast UK banks' liquidity risk. Based on annual data over the period 1997 to 2010, the study predicts that by the end of 2011, the (102) UK banks' average CFaR at the 95% confidence level will be -£5.76 billion, Barclays Bank's (Barclays') CFaR will be -£0.34 billion, the Royal Bank of Scotland's (RBS's) CFaR will be -£40.29 billion, HSBC Bank's (HSBC's) CFaR will be £0.67 billion, Lloyds TSB Bank's (Lloyds TSB's) CFaR will be -£4.90 billion, National Westminister Bank's (Natwest's) CFaR will be -£10.38 billion, and Nationwide Building Society's (Nationwide's) CFaR will be -£0.72 billion. Moreover, it is clear that Lloyds TSB and Natwest are associated with the largest risk, according to the biggest percentage difference between downside cash flow and expected cash flow (3600% and 816% respectively). Since I summarize a bank's liquidity risk exposure in a single number (CFaR), which is the maximum shortfall given the targeted probability level, it can be directly compared to the bank's risk tolerance and used to guide corporate risk management decisions. Finally, this thesis estimates the long-term United Kingdom economic impact of the Basel III capital and liquidity requirements. Using quarterly data over the period 1997:q1 to 2010:q2, the study employs a non-linear-in-factor probit model to show increases in bank capital and liquidity would reduce the probability of a bank crisis significantly. The study estimates the long-run cost of the Basel III requirements with a Vector Error Correction Model (VECM), which shows holding higher capital and liquidity would reduce output by a small amount but increase bank profitability in the long run. The maximum temporary net benefit and permanent net benefit is shown to be 1.284% and 35.484% of pre-crisis GDP respectively when the tangible common equity ratio stays at 10%. Assuming all UK banks also meet the Basel III long-term liquidity requirements, the temporary net benefit and permanent net benefit will be 0.347% and 14.318% of pre-crisis GDP respectively. Therefore, the results suggest that, in terms of the impact on output, there is considerable room to further tighten capital and liquidity requirements, while still providing positive effects for the United Kingdom economy.

Luftverkehrsprognosen stellen ein wichtiges Instrument dar, die Luftverkehrsinfrastruktur zu beeinflussen. Hinter vielen der Projekte, die von Luftverkehrsprognosen begleitet werden, stehen Interessen. Dies gilt insbesondere für Ausbauvorhaben von Flughäfen, die von eindeutigen Zielen und Wünschen getragen werden. Die Gutachter, die im Rahmen solcher Ausbauvorhaben tätig werden, sind der Gefahr ausgesetzt, beeinflusste Prognosen zu erstellen. Die Art und Intensität dieser Beeinflussung sowie die Methodik dieser Analysen sind Gegenstand dieses Aufsatzes. Zunächst wurden neuere Ergebnisse der OECD und EU erarbeitet und denen der Flughafenstudien gegenübergestellt. Nachfolgend wurde die Intensität der Beeinflussung auf Grundlage einer eigenen Untersuchung analysiert. Dabei wurden politische Entscheidungsträger im Rhein-Main-Gebiet nach Ihrer Verwendung von Studien und deren Ergebnisse befragt. Die Impact Study, als häufigste Forschungsmethodik, wurde in ihre Bestandteile zerlegt und mit der Full Cost-Benefit-Analyse, welche die durch die FAA empfohlene Methode ist, verglichen. Grundsätzlich sind solche Gutachten meist externe Analysen aus privatwirtschaftlicher Hand, die einerseits im Auftrag von regionalen Entscheidungsträgern, aber andererseits auch im Auftrag von Flughafen- und Fluggesellschaften angefertigt wurden. Die Unabhängigkeit der Prognosen ist damit gefährdet. Auf Grundlage der (neutralen) OECD- und EU-Ergebnisse zeigte sich, dass etwaige regionale Wirtschaftsimpulse und damit einhergehendes Beschäftigungswachstum durch erhöhten Flugverkehr nicht zu finden sind. Die kritische Analyse von „bezahlten Studien“ ist demnach von Bedeutung. Die Mehrzahl der politischen Amts- und Entscheidungsträger in Deutschland trifft allerdings Entscheidungen auf Basis keiner oder ausschließlich nicht-neutraler, bezahlter Auftragsstudien. Historisch betrachtet ist dies kein Novum. Bereits in den 60er Jahren kann man solche Studien und Entscheidungen nachweisen. Bezüglich des Forschungsdesign zeigte sich, dass Impact-Studien kaum für zur Beurteilung des Luftverkehrs geeignet sind. Sie beziehen die relevanten Effekte nur teilweise in ihre Berechnungen ein. Es wurde eine Reihe von systematischen Fehlern identifiziert. Die FAA-Richtlinien in den USA für methodisch korrekte Studien greifen nur wenig. Für weitere Forschung sehen wir die wichtige Aufgabe, die Methodik der Full Cost-Benefit-Analyse für die Prognose möglicher Effekte zur Anwendung zu bringen. / Aviation traffic forecasts and airport analyses are important instruments which influence decisions on aviation related infrastructure. Behind many of such infrastructure projects, which are supported by forecast analyses, one finds political interests. This is especially the case for aviation projects, such as infrastructure enlargement projects of airports, which are motivated by distinct goals and desires. Referees who act within this framework are exposed to the risk of producing biased results. The form and degree of intensity of such influence and manipulation, as well as the methodology of such forecast analyses, are the subject of this working paper. To begin with, newer research results by the OECD and the EU have been formulated and further compared to results of studies commissioned by airport operators. Subsequently, the degree of intensity of such influence has been analysed on the basis of our own research. A survey was thereby produced, investigating the application of neutral and non-neutral studies in the decision-making processes of the public administration in the Rhein-Main-area. Impact studies, which are currently the most used method, have been segmented and compared with studies using full cost-benefit-analysis, the recommended method by the FAA. With regard to these results, it can be argued that most forecast analyses are produced by private consultancies, by order of public entities but also by order of airport operators. The independence of such research and its results is therefore endangered. Recent OECD and EU research results have shown that eventual effects, such as regional economic stimulus and employment growth, are absent. Thus, care in the application of study results in this field is necessary. However, the majority of policy makers (in Germany) unfortunately base their decisions mostly on non-neutral studies. Historically seen, this is not a novelty. Regarding the research design, impact studies are hardly suitable for airport studies. Further, it can be shown that impact studies incorporate mostly only non-negative items in their cash flow calculations, compared to full cost-benefit-analyses which incorporate all relevant items. A number of systematic flaws are further identified. The regulation-guidelines by the FAA, which demand to incorporate all items, have had little impact on the research design of airport studies in the US so far. The promotion and fostering of full cost-benefit-analyses is necessary to lift the quality of airport studies.

Dans un contexte d’augmentation constante des dépenses de santé, la création et l'utilisation des technologies innovantes en chirurgie mini-invasive est de plus en plus tributaire de notre capacité à démontrer leur efficacité et évaluer leurs impacts. À ce jour, comme nous le montrons tout au long de cette thèse, la littérature en sciences économiques ne fournit pas aux décideurs et aux évaluateurs les outils adéquats pour réaliser de telles évaluations.Notre travail combine les meilleurs aspects de l'économie de la santé et de l'économie de l'innovation afin d’établir un cadre méthodologique commun pour l'évaluation des innovations chirurgicales hybrides. En utilisant l'institut de chirurgie guidée par l'image (IHU Strasbourg) comme fondation pour nos analyses, nous créons les bases pour une évaluation coût-bénéfice globale couvrant aussi bien ses activités de soin que de R\&D.L'utilisation des outils développés dans cette thèse permettra à l'IHU, ou tout autre institut chirurgical, de justifier l’intérêt de ces types d'activités en démontrant que les impacts socio-économiques d'une innovation chirurgicale peuvent, éventuellement, compenser le coût supplémentaire qu'elle génère pour le système de santé. / With constant rises in healthcare expenditures, the creation and use of innovative technologies in Minimally Invasive Surgery (MIS) is increasingly dependent on our ability to demonstrate their efficiency and evaluate their impacts. To date, as we show throughout this thesis, the economic literature has not provided decision makers and analysts with the adequate tools to perform such evaluations.Our work combines the best aspects of health economics and economics of innovation to establish a common methodological framework for the evaluation of hybrid innovations in MIS. Using the Institute of Image Guided Surgery (IHU Strasbourg) as a base for our investigations, we create the groundwork for a comprehensive cost-benefit evaluation covering the institute’s patient care and R\&D activities.The use of the tools developed in this thesis will allow the IHU, or any other surgical institute, to provide advocacy for these types of activities by demonstrating that the socio-economic impacts of a surgical innovation can possibly outweigh the additional cost it incurs to the healthcare system.

Abstract Knee osteoarthritis (OA) is one of the main causes of chronic disability in elderly people. In end-stage knee OA, patients experience both short- and long-term benefits from total knee arthroplasty (TKA). All the significant deficiencies in functional capacity and health-related quality of life (HRQOL) are not spontaneously resolved after surgery. Therefore, it is essential that patients receive effective rehabilitation. So far, there are no gold standards in terms of outcome measurements of TKA and rehabilitation in connection with surgery. The present series of studies was designed for the purpose of examining the effectiveness and cost-effectiveness of a multidisciplinary rehabilitation program compared with conventional orthopedic care, the attributes of disability in elderly knee OA patients waiting for primary TKA, and the impact of patient-relevant factors on the outcome of TKA one year after surgery. Special emphasis was placed on self-reported functional capacity, HRQOL, and objectively measured functional capacity. Objective and subjective physical function and HRQOL were investigated with a battery of physical function tests and questionnaires (WOMAC, 15D, and RAND-36) during a one-year follow-up. Pain, body mass index (BMI), and antero-posterior laxity of the affected knee were the main attributes of self-reported disability in the patients waiting for primary TKA. The multidisciplinary rehabilitation program did not yield faster attainment of recovery than did conventional orthopedic care. Equal, significant improvement in HRQOL and functional capacity was found in both groups, but conventional care was clearly cost-saving. A preoperative score below the general population level on the 15D, the presence of pain, higher age, and the presence of pulmonary disease preoperatively decreased the possibility of reaching the HRQOL level of the general population. More severe pain preoperatively was associated with a higher degree of functional recovery. The presence of osteoporosis, male gender, impaired function of the opposite knee, and higher age were associated with a lower degree of improvement in self-reported function. The results highlight the multifactorial nature of health status in TKA. Further intervention studies are needed to identify patients who would benefit most from intensive rehabilitation interventions after TKA and to create standards for outcome tools after joint replacement surgery and rehabilitation interventions. / Tiivistelmä Polvinivelrikko on merkittävimpiä niistä sairauksista, jotka rajoittavat ikääntyneiden toimintakykyä. Vaikka tekonivelleikkauksella voidaan sekä välittömästi että pidemmän ajan kuluessa kohentaa merkittävästi polvinivelrikosta kärsivien elämänlaatua ja toimintakykyä, osa potilaista ei leikkauksen jälkeenkään selviydy hyvin arjestaan. Siksi on tärkeää, että potilasta kuntoutetaan tekonivelleikkauksen jälkeen asianmukaisesti ja tehokkaasti. Leikkauksen ja kuntoutuksen tuloksellisuutta arvioivien mittareiden käytöstä ei ole olemassa standardoituja suosituksia. Tämän väitöskirjan päätavoitteena oli selvittää 2–4 kuukautta leikkauksen jälkeen toteutetun, moniammatillisen, polikliinisen kuntoutuksen kustannustehokkuutta sekä sen vaikuttavuutta elämänlaatuun ja toimintakykyyn verrattuna perinteiseen ortopediseen hoitokäytäntöön. Lisäksi selvitettiin tekijöitä, jotka heikentävät potilaan toimintakykyä pitkälle edenneessä polvinivelrikossa, sekä potilaslähtöisiä tekijöitä, jotka vaikuttavat leikkaustulokseen vuosi leikkauksen jälkeen. Itsearvioitua toimintakykyä sekä elämänlaatua arvioitiin kyselykaavakkeiden (WOMAC, 15D ja RAND-36) avulla ja fyysistä toimintakykyä mitattiin testipatteristolla. Tutkimuksen seuranta-aika oli yksi vuosi. Painoindeksi, kipu ja leikattavan polven etu-takasuuntainen väljyys selittivät eniten tekonivelleikkausta odottavien potilaiden toimintakyvyn rajoitteita. Potilaiden elämänlaatu ja toimintakyky kohenivat merkittävästi tekonivelleikkauksen jälkeen. Moniammatillisesti toteutettu kuntoutus ei tehostanut leikkauksesta toipumista verrattaessa sitä perinteiseen ortopediseen hoitokäytäntöön, joka vertailussa myös säästi selkeästi kustannuksia. Väestökeskiarvoa huonommaksi koettu elämänlaatu jo ennen leikkausta, kivuliaisuus, korkea ikä ja keuhkosairaudet heikensivät mahdollisuutta saavuttaa väestökeskiarvon tasoinen koettu elämänlaatu vuosi leikkauksen jälkeen. Leikkausta edeltävä vaikea-asteinen kivuliaisuus assosioitui merkittävään toimintakyvyn parantumiseen. Osteoporoosi, miessukupuoli, vastakkaisen polvinivelen epänormaali toiminta ja korkea ikä taas liittyivät vaatimattomampana koettuun toimintakyvyn parantumiseen. Tekonivelleikattujen potilaiden terveydentilan monitekijäisyys heijastuu tutkimustuloksiin. Jatkossa tarvitaan interventiotutkimuksia, jotta voitaisiin paremmin tunnistaa ne potilaat, jotka hyötyisivät eniten tehostetusta leikkauksen jälkeisestä kuntoutuksesta. Lisäksi olisi tärkeää tutkia, miten kuntoutuksen tuloksellisuutta arvioivia mittareita voitaisiin yhtenäistää.