O objetivo da pesquisa foi analisar a experiência financeira de famílias no cuidado de crianças e adolescentes com câncer. Estudo descritivo que utilizou o método misto para analisar os custos diretos e indiretos do câncer infantojuvenil, no sistema familiar. Após aprovação ética, a pesquisa foi realizada com pais e cuidador principal de crianças e adolescentes com câncer, em seguimento em um hospital público do interior paulista. A coleta de dados foi realizada entre junho de 2013 e fevereiro de 2014, por meio da aplicação do questionário \"Custos do Cuidado da Criança com Câncer\" de forma concomitante à realização de entrevistas semiestruturadas, audiogravadas em gravador digital. Integraram o estudo 62 participantes, dentre os quais 17 também participaram da entrevista semiestruturada. Os dados provenientes dos questionários foram analisados e reportados, utilizando-se a estatística descritiva, e os discursos das entrevistas foram analisados conforme orientação para análise temática dedutiva e indutiva. A caracterização dos participantes demonstra que a maioria (88%) eram mães, casadas ou que viviam com um companheiro e que acompanhavam o filho, durante o tratamento. Os resultados foram apresentados e discutidos a partir das unidades de sentido: 1) Repercussão do câncer infantojuvenil na situação financeira das famílias; 2) Custos diretos e indiretos do câncer infantojuvenil para as famílias; e 3) Redes de apoio e apoio social às famílias de crianças e adolescentes com câncer. Com base nessas unidades, elaboramos dois temas, que explica a experiência financeira das famílias, no cuidado de crianças e adolescentes com câncer: \"Custe o que custar, nosso filho adoecido em primeiro lugar\" e \"Toda ajuda é bem-vinda\". Após o câncer, o déficit econômico foi inevitável a essas famílias e foi ainda mais contundente naquelas em que o principal cuidador era o provedor principal da renda familiar. Os custos diretos corresponderam aos gastos com alimentação; transporte; reformas da casa; artefatos para o cuidado e com presentes e doces para o filho doente e seus irmãos saudáveis. O custo indireto correspondeu à perda da atividade laboral do principal cuidador, devido à impossibilidade de conciliar sua carreira com os cuidados do filho adoecido. A condição do câncer infantojuvenil impôs uma situação de vulnerabilidade social às famílias, sendo imprescindível o suporte social. No entanto, apesar das dificuldades, as famílias não medem esforços para atender às necessidades do filho adoecido, o qual está acima de qualquer prioridade do sistema familiar. Os resultados desta pesquisa têm potencial para subsidiar as intervenções de enfermagem e de outros profissionais de saúde, para planejar e elaborar políticas públicas que possam minimizar as repercussões do diagnóstico do câncer infantojuvenil no sistema familiar e para orientar pesquisas futuras. / This research aimed to analyze the financial experience of families in the care of children and adolescents with cancer. It is a descriptive study which used a mixed method to analyze direct and indirect costs of children and youth cancer in the family system. After ethical approval, the research was conducted with parents and primary caregiver of children and adolescents in cancer follow up at a public hospital in the interior of São Paulo state. Data collection was carried out between June 2013 and February 2014 through the questionnaire \"Care Costs of Children with Cancer\", concomitant to performing semi-structured interviews which were recorded on a digital recorder. Study participants were 62, of whom 17 also participated in semi-structured interviews. Data from the questionnaires were analyzed and reported using descriptive statistics, and the speeches were analyzed according to guidelines for deductive and inductive thematic analysis. The characterization of the participants shows that the majority (88%) were mothers, married or living with a partner and who accompanied the child during treatment. The results were presented and discussed from the meaning units: 1) impact of children and youth cancer and its consequence on the financial situation of families; 2) direct and indirect costs of children and youth cancer for families; and 3) support network and social support for families of children and adolescents with cancer. Based on these units, two themes were developed, which explains the financial experience of families in the care of children and adolescents with cancer: \"No matter the cost, our ill child in the first place\" and \"All help is welcome\". After cancer, the economic deficit was inevitable for these families and was even more decisive in those in which the primary caregiver was the family´s main provider. Direct costs corresponded to spending on food; transport; reforms of the house; artifacts for the care; and gifts and candies for the sick child and their healthy siblings. Indirect cost corresponded to the loss of labor activity of the primary caregiver, due to the impossibility of conciliating his/her career with the care of the ill son/daughter. The condition of children and youth cancer imposed a socially vulnerable condition to the families, and the social support was vital. However, despite the difficulties, the families go to great lengths to meet the needs of the ill child, which is above any priority of the family system. The results of this research have the potential to support nursing interventions and other health professionals to plan and develop public policies that may minimize the repercussions of the diagnosis of children and youth cancer in the family system and to guide future researches.

Introdução: As morbidades e mortalidade relacionadas ao uso de medicamentos (MRM) representam um desafio para a saúde pública e são consequências da utilização não efetiva e insegura dos medicamentos. Estudos internacionais mostram como as MRM afetam pacientes internados no hospital e como podem ser evitadas na maioria dos casos. Entretanto, pouco é conhecido sobre as MRM na prática ambulatorial. Estas pesquisas têm abordado as consequências clínicas negativas para os usuários de medicamentos e sugerem que vultosas somas de recursos financeiros são utilizadas para manejar e resolver estas morbidades ao redor do mundo. Já no Brasil, o conhecimento sobre as MRM é escasso em ambas perspectivas e o seu impacto econômico é desconhecido. Objetivo: O propósito desta Tese foi obter uma estimativa sobre os gastos com morbidade e mortalidade associadas ao uso de medicamentos no Brasil, utilizando modelos farmacoeconômicos (teórico e empírico). Métodos: Foram considerados como morbidades relacionadas a medicamentos os novos problemas de saúde advindos da utilização de uma farmacoterapia (por exemplo, reações adversas, dependência a medicamentos e intoxicação por overdose) e as falhas terapêuticas (por exemplo, efeito insuficiente dos medicamentos e problemas de saúde não tratados). Foram conduzidos dois estudos utilizando abordagens distintas (bottom up e top down) na coleta de dados sobre custos. O primeiro estimou, por meio da análise do tipo microcosting, os custos para resolução de Morbidades Relacionadas a Medicamentos em casos identificados no serviço de emergência de um hospital universitário. Resultados: O custo médio para tratar cada um desses pacientes é de aproximadamente R$ 2.200. Reações adversas a medicamentos, falta de adesão à farmacoterapia e problemas resultantes da administração de doses incorretas foram as causas mais prevalentes das morbidades. No segundo estudo, um modelo do tipo cost-of-illness foi traduzido e adaptado para a realidade brasileira, e então um painel com especialistas (farmacêuticos e médicos) foi realizado para estimar a proporção de pacientes que experimentam uma MRM, a proporção de MRM evitáveis e as consequências clínicas resultantes desta morbidade. A partir disto, o custo das MRM para o sistema de saúde brasileiro foi modelado, baseado em estatísticas nacionais sobre o consumo de serviços de saúde. Os especialistas julgaram as morbidades relacionadas a medicamentos como um evento bastante frequente. De acordo com esta estimativa central, as MRM seriam responsáveis por um uso considerável de recursos, podendo chegar a 23% do orçamento público anual total destinado à saúde no Brasil. Para cada real gasto com medicamentos, pelo Ministério da Saúde no Brasil, cinco reais seriam gastos para resolver as MRM. Da mesma forma foi verificado que mais da metade dos casos seriam evitáveis. Conclusão: As MRM são, de fato, um problema de ordem econômica-orçamentária, clínica e humanística para os usuários de medicamentos e para o sistema de saúde brasileiro, e que é imperiosa a criação de políticas públicas e ações capazes de evitar os danos gerados pelo uso não racional de medicamentos, garantir a segurança dos pacientes, bem como uma melhor alocação de recursos em saúde. / Introduction: Drug related morbidities and mortality (DRM) is a challenge to public health due to the consequences of ineffective and unsafe medicines use. It is well known that the DRM are common among hospitalized patients, and are preventable to some extent, but little is known about DRM outside the hospital. In Brazil, the knowledge on the subject is scarce and its economic impact is unknown. However, international studies suggest that DRM result in considerable amounts of financial resources to manage and resolve these morbidities around the world and the negative clinical consequences for those who use medicines. Aim: In this thesis, the drug related morbidities include: new medical problems arising from the pharmacotherapy (adverse effects, addiction to drugs and intoxication by overdose) and therapeutic failure (e.g. insufficient drug effect and untreated health problems). Methods: Two studies were conducted using different methodologies. The first study was a cross-sectional study, based on a microcosting analysis, where patients admitted to a teaching hospital emergency were identified in order to determine the proportion of people seeking health services due to a DRM, and, consequently, to obtain the cost for manage these patients. Results: It was observed that 14.6% of patients visiting an emergency service, do so because of a DRM and the average cost to treat each of these patients is approximately R$ 2,000. Adverse drug reactions, lack of adherence to pharmacotherapy and problems resulting from the administration of incorrect doses were the most prevalent causes of morbidity. In the second study, a cost-of-illness model was translated to portuguese and adapted, and then a panel of experts (pharmacists and physicians) was conducted to estimate the proportion of patients experiencing DRM, the proportion of preventable DRM, and the negative outcomes resulting from this morbidity. From this, the DRM cost for the Brazilian Health System was modeled, based on national statistics on the consumption of health services. Experts have judged drug-related morbidities to be a fairly frequent event. According to central estimate, the DRM would be responsible for a considerable use of resources, being able to reach 23% of the total annual public health budget in Brazil. For each real (R$ 1,00) spending on medicines, by the Brazilian Ministry of Health, five reais (R$ 5,00) would be spent to manage the DRM. Likewise, in this study it was also verified that more than half of the cases would be avoidable. In the second, a panel of experts (pharmacists and physicians) was performed to estimate the proportion of patients experiencing an DRM, DRM preventable ratio and the clinical consequences of this morbidity. From this, the cost of DRM for the Brazilian health system was modeled, based on national statistics on the consumption of health services. Conclusion: Based on these and many other results presented in this thesis, it is concluded that the DRM are indeed, an economic, clinical and humanistic issue for those who use medicines and to the Brazilian health system, and that is overriding the establishment of public policies and actions to prevent the damage caused by the non-rational use of medicines to ensure patient safety and to the best allocation of health resources.

Introdução: As morbidades e mortalidade relacionadas ao uso de medicamentos (MRM) representam um desafio para a saúde pública e são consequências da utilização não efetiva e insegura dos medicamentos. Estudos internacionais mostram como as MRM afetam pacientes internados no hospital e como podem ser evitadas na maioria dos casos. Entretanto, pouco é conhecido sobre as MRM na prática ambulatorial. Estas pesquisas têm abordado as consequências clínicas negativas para os usuários de medicamentos e sugerem que vultosas somas de recursos financeiros são utilizadas para manejar e resolver estas morbidades ao redor do mundo. Já no Brasil, o conhecimento sobre as MRM é escasso em ambas perspectivas e o seu impacto econômico é desconhecido. Objetivo: O propósito desta Tese foi obter uma estimativa sobre os gastos com morbidade e mortalidade associadas ao uso de medicamentos no Brasil, utilizando modelos farmacoeconômicos (teórico e empírico). Métodos: Foram considerados como morbidades relacionadas a medicamentos os novos problemas de saúde advindos da utilização de uma farmacoterapia (por exemplo, reações adversas, dependência a medicamentos e intoxicação por overdose) e as falhas terapêuticas (por exemplo, efeito insuficiente dos medicamentos e problemas de saúde não tratados). Foram conduzidos dois estudos utilizando abordagens distintas (bottom up e top down) na coleta de dados sobre custos. O primeiro estimou, por meio da análise do tipo microcosting, os custos para resolução de Morbidades Relacionadas a Medicamentos em casos identificados no serviço de emergência de um hospital universitário. Resultados: O custo médio para tratar cada um desses pacientes é de aproximadamente R$ 2.200. Reações adversas a medicamentos, falta de adesão à farmacoterapia e problemas resultantes da administração de doses incorretas foram as causas mais prevalentes das morbidades. No segundo estudo, um modelo do tipo cost-of-illness foi traduzido e adaptado para a realidade brasileira, e então um painel com especialistas (farmacêuticos e médicos) foi realizado para estimar a proporção de pacientes que experimentam uma MRM, a proporção de MRM evitáveis e as consequências clínicas resultantes desta morbidade. A partir disto, o custo das MRM para o sistema de saúde brasileiro foi modelado, baseado em estatísticas nacionais sobre o consumo de serviços de saúde. Os especialistas julgaram as morbidades relacionadas a medicamentos como um evento bastante frequente. De acordo com esta estimativa central, as MRM seriam responsáveis por um uso considerável de recursos, podendo chegar a 23% do orçamento público anual total destinado à saúde no Brasil. Para cada real gasto com medicamentos, pelo Ministério da Saúde no Brasil, cinco reais seriam gastos para resolver as MRM. Da mesma forma foi verificado que mais da metade dos casos seriam evitáveis. Conclusão: As MRM são, de fato, um problema de ordem econômica-orçamentária, clínica e humanística para os usuários de medicamentos e para o sistema de saúde brasileiro, e que é imperiosa a criação de políticas públicas e ações capazes de evitar os danos gerados pelo uso não racional de medicamentos, garantir a segurança dos pacientes, bem como uma melhor alocação de recursos em saúde. / Introduction: Drug related morbidities and mortality (DRM) is a challenge to public health due to the consequences of ineffective and unsafe medicines use. It is well known that the DRM are common among hospitalized patients, and are preventable to some extent, but little is known about DRM outside the hospital. In Brazil, the knowledge on the subject is scarce and its economic impact is unknown. However, international studies suggest that DRM result in considerable amounts of financial resources to manage and resolve these morbidities around the world and the negative clinical consequences for those who use medicines. Aim: In this thesis, the drug related morbidities include: new medical problems arising from the pharmacotherapy (adverse effects, addiction to drugs and intoxication by overdose) and therapeutic failure (e.g. insufficient drug effect and untreated health problems). Methods: Two studies were conducted using different methodologies. The first study was a cross-sectional study, based on a microcosting analysis, where patients admitted to a teaching hospital emergency were identified in order to determine the proportion of people seeking health services due to a DRM, and, consequently, to obtain the cost for manage these patients. Results: It was observed that 14.6% of patients visiting an emergency service, do so because of a DRM and the average cost to treat each of these patients is approximately R$ 2,000. Adverse drug reactions, lack of adherence to pharmacotherapy and problems resulting from the administration of incorrect doses were the most prevalent causes of morbidity. In the second study, a cost-of-illness model was translated to portuguese and adapted, and then a panel of experts (pharmacists and physicians) was conducted to estimate the proportion of patients experiencing DRM, the proportion of preventable DRM, and the negative outcomes resulting from this morbidity. From this, the DRM cost for the Brazilian Health System was modeled, based on national statistics on the consumption of health services. Experts have judged drug-related morbidities to be a fairly frequent event. According to central estimate, the DRM would be responsible for a considerable use of resources, being able to reach 23% of the total annual public health budget in Brazil. For each real (R$ 1,00) spending on medicines, by the Brazilian Ministry of Health, five reais (R$ 5,00) would be spent to manage the DRM. Likewise, in this study it was also verified that more than half of the cases would be avoidable. In the second, a panel of experts (pharmacists and physicians) was performed to estimate the proportion of patients experiencing an DRM, DRM preventable ratio and the clinical consequences of this morbidity. From this, the cost of DRM for the Brazilian health system was modeled, based on national statistics on the consumption of health services. Conclusion: Based on these and many other results presented in this thesis, it is concluded that the DRM are indeed, an economic, clinical and humanistic issue for those who use medicines and to the Brazilian health system, and that is overriding the establishment of public policies and actions to prevent the damage caused by the non-rational use of medicines to ensure patient safety and to the best allocation of health resources.

O objetivo da pesquisa foi analisar a experiência financeira de famílias no cuidado de crianças e adolescentes com câncer. Estudo descritivo que utilizou o método misto para analisar os custos diretos e indiretos do câncer infantojuvenil, no sistema familiar. Após aprovação ética, a pesquisa foi realizada com pais e cuidador principal de crianças e adolescentes com câncer, em seguimento em um hospital público do interior paulista. A coleta de dados foi realizada entre junho de 2013 e fevereiro de 2014, por meio da aplicação do questionário \"Custos do Cuidado da Criança com Câncer\" de forma concomitante à realização de entrevistas semiestruturadas, audiogravadas em gravador digital. Integraram o estudo 62 participantes, dentre os quais 17 também participaram da entrevista semiestruturada. Os dados provenientes dos questionários foram analisados e reportados, utilizando-se a estatística descritiva, e os discursos das entrevistas foram analisados conforme orientação para análise temática dedutiva e indutiva. A caracterização dos participantes demonstra que a maioria (88%) eram mães, casadas ou que viviam com um companheiro e que acompanhavam o filho, durante o tratamento. Os resultados foram apresentados e discutidos a partir das unidades de sentido: 1) Repercussão do câncer infantojuvenil na situação financeira das famílias; 2) Custos diretos e indiretos do câncer infantojuvenil para as famílias; e 3) Redes de apoio e apoio social às famílias de crianças e adolescentes com câncer. Com base nessas unidades, elaboramos dois temas, que explica a experiência financeira das famílias, no cuidado de crianças e adolescentes com câncer: \"Custe o que custar, nosso filho adoecido em primeiro lugar\" e \"Toda ajuda é bem-vinda\". Após o câncer, o déficit econômico foi inevitável a essas famílias e foi ainda mais contundente naquelas em que o principal cuidador era o provedor principal da renda familiar. Os custos diretos corresponderam aos gastos com alimentação; transporte; reformas da casa; artefatos para o cuidado e com presentes e doces para o filho doente e seus irmãos saudáveis. O custo indireto correspondeu à perda da atividade laboral do principal cuidador, devido à impossibilidade de conciliar sua carreira com os cuidados do filho adoecido. A condição do câncer infantojuvenil impôs uma situação de vulnerabilidade social às famílias, sendo imprescindível o suporte social. No entanto, apesar das dificuldades, as famílias não medem esforços para atender às necessidades do filho adoecido, o qual está acima de qualquer prioridade do sistema familiar. Os resultados desta pesquisa têm potencial para subsidiar as intervenções de enfermagem e de outros profissionais de saúde, para planejar e elaborar políticas públicas que possam minimizar as repercussões do diagnóstico do câncer infantojuvenil no sistema familiar e para orientar pesquisas futuras. / This research aimed to analyze the financial experience of families in the care of children and adolescents with cancer. It is a descriptive study which used a mixed method to analyze direct and indirect costs of children and youth cancer in the family system. After ethical approval, the research was conducted with parents and primary caregiver of children and adolescents in cancer follow up at a public hospital in the interior of São Paulo state. Data collection was carried out between June 2013 and February 2014 through the questionnaire \"Care Costs of Children with Cancer\", concomitant to performing semi-structured interviews which were recorded on a digital recorder. Study participants were 62, of whom 17 also participated in semi-structured interviews. Data from the questionnaires were analyzed and reported using descriptive statistics, and the speeches were analyzed according to guidelines for deductive and inductive thematic analysis. The characterization of the participants shows that the majority (88%) were mothers, married or living with a partner and who accompanied the child during treatment. The results were presented and discussed from the meaning units: 1) impact of children and youth cancer and its consequence on the financial situation of families; 2) direct and indirect costs of children and youth cancer for families; and 3) support network and social support for families of children and adolescents with cancer. Based on these units, two themes were developed, which explains the financial experience of families in the care of children and adolescents with cancer: \"No matter the cost, our ill child in the first place\" and \"All help is welcome\". After cancer, the economic deficit was inevitable for these families and was even more decisive in those in which the primary caregiver was the family´s main provider. Direct costs corresponded to spending on food; transport; reforms of the house; artifacts for the care; and gifts and candies for the sick child and their healthy siblings. Indirect cost corresponded to the loss of labor activity of the primary caregiver, due to the impossibility of conciliating his/her career with the care of the ill son/daughter. The condition of children and youth cancer imposed a socially vulnerable condition to the families, and the social support was vital. However, despite the difficulties, the families go to great lengths to meet the needs of the ill child, which is above any priority of the family system. The results of this research have the potential to support nursing interventions and other health professionals to plan and develop public policies that may minimize the repercussions of the diagnosis of children and youth cancer in the family system and to guide future researches.

Background: Multiple sclerosis (MS) is a chronic, incurable disease of the central nervous system (CNS) and a potentially severe cause of neurological disability throughout adult life. Typically diagnosed between the ages of 20 and 40, the disease is associated with a severely impaired health-related quality of life and a high societal economic impact. About 85% of patients are initially diagnosed with relapsing-remitting MS (RRMS), which is characterized by the unpredictable occurrence of relapses. Clinically, a relapse is defined as a worsening or appearance of new neurological symptoms followed by a period of partial or complete recovery (relapse without worsening, RWW). Up to 80% of patients transit to the secondary progressive course (SPMS) within 20 years. SPMS is marked by an accumulation of irreversible disability either resulting from relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). Even though health economic assessments are well established in MS, implications of relapses and disability worsening on societal economic costs have scarcely been studied. Regarding disability worsening it is known that annual costs increase with increasing disability from 21,174–28,200€ (EDSS 0–3) to 39,923–44,000€ (EDSS 4–6.5) (in 2015 values). However, the impact of PIRA and RAW on societal costs remains not well understood. Research to date has shown that the societal economic burden of MS increases in periods of relapses with most recent estimates at 2468€ per relapse (in 2015 values). The results of relapse cost analyses are inconsistent between studies since relapses and associated costs can vary across and within individuals depending on disease severity, disease duration, age, gender or therapy. However, a comprehensive test of this hypothesis is still needed. Research aims: I investigated the societal economic costs of disability worsening and relapses in patients with MS. First, I determined the societal economic costs of patients achieving disease activity free status (DAF, neither relapses nor disability worsening) and compared them with those having PIRA and RAW events. Second, I estimated direct and indirect relapse costs and determined differences in costs related to patient characteristics. Furthermore, I described the pharmacoeconomic impact during the relapse follow-up. Methods: Two-year clinical and pharmacoeconomic data were derived from two single arm, prospective, multicenter, non-interventional long term studies conducted in Germany applying the Multiple Sclerosis Health Resource Survey (MS-HRS). The MS-HRS estimates the MS-associated direct and indirect costs from a societal perspective using the most accurate form of bottom-up microcosting. Costs are presented per quarter in 2011 Euros. PIRA and RAW events were indicated through a roving confirmed disability worsening (CDW) measure and corresponding relapse assessments. CDW is based on a predefined increase on the Expanded Disability Status Scale (EDSS) sustained over at least 6 months. The effects of PIRA and RAW on total, direct medical, direct non-medical and indirect societal economic costs are adjusted for age, gender and EDSS. Due to the right skewness of cost data, I applied a Generalized Linear Mixed Model (GLMM) with a negative binomial distribution. Patients achieving DAF were assigned as the reference group. I calculated relapse costs as the difference in quarterly costs between propensity score (PS) matched patients with and without relapses (1:1 ratio). Statistical differences in relapse costs between patient and disease strata were derived from a Generalized Linear Model (GLM) with a negative binomial distribution. For relapse active patients, I additionally calculated the difference between quarterly costs prior- and during relapse and determined costs in the post-relapse quarter. Results: Overall, 1959 patients were analyzed with typical patient characteristics for a clinical RRMS population. Patients reported an average age of 41.62±10.04 years and were mostly female (73%). The mean disease duration was 7.30±5.95 with a mean baseline EDSS value of 2.26±1.37. Total mean quarterly societal economic costs including disease-modifying therapies (DMTs) were 6929€±2886€ per patient averaged over two years. Excluding DMTs, patients achieving DAF status had total mean quarterly costs of 1703€±2489€. PIRA caused 29% (IRR: 1.29; 95% CI 1.06–1.50, p<0.05) higher total costs compared to DAF. On the contrary, RAW increased total costs by factor 1.56 (95% CI 1.30–1.87, p<0.001). The effect of PIRA and RAW was striking for direct medical costs which increased by factor 1.48 (95% CI 1.13–1.95, p<0.01) and 2.25 (95% CI 1.72–2.94, p<0.001), respectively. In the relapse cost analyses, a total of 1882 patients were included encompassing 607 (32%) relapse-active patients. After PS-matching, 597 active and inactive patients were retained. Relapse costs ranged between 690€ (age: 50+ years) and 1729€ (disease du-ration: <5 years). In mildly disabled and recently diagnosed patients, indirect relapse costs (range: 971€-1093€) constantly outweighed direct costs (range: 535€-636€). The increase from prior- to relapse quarter was strongest for inpatient stays (+364%, 390€; p<0.001), day admissions (+241%, 53€; p<0.001) and absenteeism (+127%, 419€; p<0.001). In the post-relapse quarter direct costs and costs of absenteeism remained elevated for patients with relapse associated worsening. Conclusion: For the case of MS, disease activity should be a focus in medical research to reduce the societal economic burden of the disease. Disability worsening is associated with significantly higher societal economic costs compared to DAF status in patients with MS. Accordingly, it is highly important from a societal perspective to delay or even prevent transition into the progressive phase of MS. That is another argument for treating MS patients early with appropriate DMTs. Furthermore, relapses significantly increase the societal economic burden of MS. From a health economic societal perspective, the prevention of relapses in young patients and those with a recent diagnosis should be a particular focus.

<p>Scaphoid fracture is most common in young individuals of working age. Without adequate diagnosis and treatment, long-term results are poor. Operative treatment is being recommended increasingly often instead of a long time in cast, although there is no evidence-based support for its superiority.</p><p>The present thesis focuses on diagnostic problems and therapeutic consequences of acute scaphoid fractures and of scaphoid reconstruction when other treatments have failed.</p><p>Simultaneous plain radiographs and computed tomography were done in 97 injured wrists. Structural assessments of plain radiography images were highly predictive with respect to the risk of having a displaced or comminute fracture as diagnosed on computed tomography. Any finding of a gap or step-off > 0.5 mm, the presence of an intermediate fragment or a dorsal lunate tilt of ≥ 15° identified 81 % of fractures that were displaced or comminuted when investigated with computed tomography.</p><p>Eighty-three patients were randomly allocated to and received either nonoperative treatment in cast or operative treatment with the aim of assessing long-term outcome of the two treatment options. Fifty-two of the patients were occupationally active. From an occupational perspective with an early return to work, surgical treatment was superior in individuals with manual employment, and from a health economic perspective conservative treatment was superior in non-manual workers.</p><p>Patients treated for scaphoid fractures generally do well up to 13 years after the injury based on limb-specific outcome scores. No benefits were identified with operative treatment compared to non-operative treatment in cast. On the contrary, there was an increased risk for osteoarthritis in the scaphotrapezial joint in those who were operated.</p><p>The patient-rated long-term results of silicone implant arthroplasty were good, with pain relief and reasonable hand function in many patients up to 20 years after surgery.</p>

L’endométriose est devenue un problème de santé important du fait de sa prévalence (près d'une femme sur dix), des multiples complications engendrant un coût notable pour la société. Le coût de la maladie est aussi le coût de ses conséquences : traitements de l'infertilité mais aussi perte de productivité des femmes et de leur entourage, et ne sont encore pas clairement identifiés. Ces conséquences sont d'autant plus importantes qu'il existe un retard diagnostique (délai diagnostique moyen supérieur à 6 ans), or plus celui-ci est long, plus la maladie est découverte à un stade sévère et les patientes à un stade sévère ont davantage de complications, nécessitent une prise en charge plus lourde et plus coûteuse, ce à quoi il faut ajouter l’errance médicale et les traitements inadéquats. La volonté d'une meilleure connaissance et reconnaissance de la maladie a abouti à des actions du monde associatif, relayées. L’évaluation économique des prises en charge, à partir d’études de cas, est un outil important d’optimisation les choix pour améliorer le sort des patientes. Cette thèse se décompose en cinq chapitres : dans le premier chapitre nous nous intéressons aux aspects théoriques de l’évaluation économique en santé et méthodologiques de l’évaluation de coût social de la maladie. Le second chapitre traite de la maladie de l’endométriose en détails et de la méthodologie adoptée dans les études de cas qui sont présentés dans les chapitres trois, quatre et cinq. Le troisième chapitre présente une étude multicentrique sur les coûts et la qualité de vie des femmes souffrant des symptômes associés à l’endométriose en Europe. Le quatrième chapitre étudie prospectivement le coût sociétal de l’endométriose en France. Enfin, le cinquième chapitre est consacré à une étude rétrospective sur la persistance des coûts associés à l’endométriose dans le temps.Cette thèse montre l’importance de l’endométriose sur le système de soins en termes de coût (€ 10,6 milliards par an en France) et illustre la nécessité d'améliorer la prise en charge en direction d’interventions plus précoces et de recours plus rapides à des centres de compétence. A une efficacité constante, il est possible d’estimer la réduction de coûts liés à une politique plus productive. Améliorer la qualité des diagnostics et des prises en charge permette aussi de maximiser l’utilité affectée aux femmes en termes de qualité de vie. / Endometriosis becomes an increasingly major health problem because of its prevalence (nearly one woman out of ten), multiple complications leading to a significant cost on the society. The cost of the disease is also the cost of its consequences which are the treatments of infertility and also the loss of productivity of women and their entourage that are not yet clearly identified. These consequences are more important when there is a delay in the diagnosis (the average delay of diagnosis is longer than 6 years), but the longer the period of diagnosis is, the more the disease will be detected in a more severe stage. The patients at this severe stage have more complications, requiring more expensive care, to which must be added the medical wandering and the inadequate treatment.The desire for a better knowledge and recognition of the disease has resulted in associative actions all around the world. The economic evaluation of health care, based on case studies, is an important tool to optimize the choices to improve the situation of the patients. This thesis is divided into five chapters : the first chapter attempts to elucidate framework of health economic evaluation and the evaluation of the social cost of illness. The second chapter focuses on the endometriosis disease in detail and the methodology used in the case studies presented in Chapter Three, Four and Five. The third chapter presents a multicenter study on the costs and quality of life of women suffering from symptoms associated with endometriosis in Europe. The fourth chapter is concerned with a prospective study on the societal cost of endometriosis in France. The fifth chapter is devoted to a retrospective study on the persistence of costs associated with endometriosis over time.This thesis shows the importance of endometriosis on the health care system in terms of cost (€ 10.6 billion per year) and illustrates the need to improve care in favor of earlier interventions and an earlier refer to competence centers. With constant efficiency, it is possible to estimate the cost reduction linked to a more productive policy. Improving the quality of diagnosis and management also maximizes the affected usefulness of women in terms of quality of life.

Die vorliegende kumulative Promotion umfasst drei veröffentlichte Publikationen, die im Rahmen der Berliner Borderline Versorgungsstudie (BBV-Studie) durchgeführt wurden. In Studie 1 wurde die effectiveness der ambulanten Dialektisch-Behavioralen Therapie (DBT) an N = 47 Patienten mit einer Borderline Persönlichkeitsstörung (BPS), die das DBT-Behandlungsjahr vollständig durchlaufen haben, untersucht. Im Prä-Post-Vergleich zeigten sich für die untersuchten Symptombereiche signifikante Veränderungen und die Effektstärken lagen überwiegend im mittleren Bereich. 77% der Patienten erfüllten nach einem Jahr DBT nicht mehr die diagnostischen Kriterien für eine BPS. In Studie 2 wurden die Krankheitskosten von N = 55 BPS-Patienten in dem Jahr vor der ambulanten DBT umfassend aus einer gesellschaftlichen Perspektive erhoben. Die durchschnittlichen Kosten lagen bei €26.882 (SD = €32.275). Davon gingen mit €17.976 (SD = €23.867) etwa 66% auf die direkten, mit €8.906 (SD = €15.518) knapp 34% auf die indirekten Kosten zurück. In Studie 3 wurden für die N = 47 DBT- compleater die Krankheitskosten im Jahr vor der Therapie mit denen während des DBT-Behandlungsjahres und mit denen während des ersten Katamnesejahres (N = 33) verglichen. Die durchschnittlichen Krankheitskosten lagen im Jahr vor der DBT bei €28.026 (SD = €33.081), während des DBT-Jahres bei €18.758 (SD = €19.450) und sanken innerhalb des Katamnesejahres weiter auf €14.750 (SD = €18.592). Die deutlichsten Kostenreduktionen zeigten sich im stationären Bereich. Hingegen konnten die indirekten Kosten kaum gesenkt werden. Insgesamt weist die vorliegende Promotion darauf hin, dass die ambulante DBT auch unter Versorgungsbedingungen in Berlin wirksam ist. Zudem besitzt die BPS auch in Deutschland eine hohe gesellschaftliche Relevanz. Die Krankheitskosten können deutlich gesenkt werden, wenn BPS-Patienten in einem DBT-Netzwerk behandelt werden. Hieraus ergeben sich erste Hinweise auf die Effizienz der ambulanten DBT. / This thesis includes three publications that were conducted as part of a Berlin wide treatment study (“Berliner Borderline Versorgungsstudie“). In study 1, we examined the effectiveness of dialectical behavior therapy (DBT) for borderline personality disorder (BPD) under the routine health care situation in Berlin. N = 47 patients completed the one-year treatment and provided data. Our findings demonstrate significant improvements on all measures with medium effect sizes. Moreover, at the end of the first treatment year, 77% of the patients no longer met the criteria for a BPD diagnosis. In Study 2, BPD-related cost-of-illness 12 months prior to outpatient DBT was assessed in a sample of N = 55 BPD-patients from a societal perspective. Total cost-of-illness was €26882 (SD = €32275) per patient. €17976 (SD = €23867; 66%) were direct costs and €8906 (SD = €15518; 34%) were calculated as indirect costs. In study 3, societal cost-of-illness of the N = 47 DBT completers was calculated for 12 months prior to DBT and further investigated during DBT-treatment year and during the following year. Total mean annual cost-of-illness was €28026 (SD = €33081) during pre-treatment, €18758 (SD = €19450) during the DBT treatment year and €14750 (SD = €18592) during the follow-up year for the N = 33 patients who participated in the final assessment. Cost savings were mainly due to marked reductions of inpatient treatment costs, while indirect costs barely decreased. In sum, the present thesis shows that outpatient DBT under routine mental health care conditions in Berlin leads to positive results. Furthermore, mean annual cost-of-illness of German BPD-patients exceed those of many other mental disorders meaning that BPD poses a high economic burden. Importantly, treatment of BPD patients with an outpatient DBT program is associated with substantial overall cost savings. Correspondingly, outpatient DBT has the potential to be an efficient treatment.

Très peu de travaux ont été publiés sur l’évaluation du fardeau des patients atteints de la maladie de Huntington (MH) et de leur famille. Les objectifs de cette thèse étaient: 1/le développement d’un instrument mesurant les caractéristiques de la MH; 2/la validation de cet instrument; 3/la mise en place d’une étude observationnelle; 4/le développement d’un modèle d’évaluation de la trajectoire des patients. Un instrument auto-administré de qualité de vie liée à la santé (QVLS) et un instrument auto-administré clinique spécifiques aux patients ont été développé. Ils présentaient de bonnes propriétés psychométriques et ont été validés dans plusieurs langues. Les coûts de la MH dans cinq pays (France, Italie, Espagne, Etats Unis, Pologne) ont été évalués. La QVLS des patients et des aidants et ses déterminants ont été décrites. Aussi, un modèle mathématique qui modélise l’évolution des patients a été développé pour pouvoir évaluer l’efficience de nouvelles thérapies dans la prise en charge de la MH. Une comparaison entre un traitement fictif et les soins standards actuels a été faite qui a permis de démontrer qu’une thérapie qui améliore le score total TMS de l’instrument d’autoévaluation H-CSRI de 3,3 points ne sera pas coût efficace. Aussi des travaux sur la QVLS chez des patients atteints de troubles de la consommation d’alcool, et des patients ayant des symptômes associées à l'hyperplasie bénigne de la prostate ont été réalisés ainsi que des travaux sur les trajectoires des patients atteints d’AVC. Ces travaux apportent des informations originales qui répondent à des besoins pour l’évaluation des interventions thérapeutiques dans chacun des domaines considérés. / Few studies have been done on the evaluation of the burden of patients suffering from Huntington’s disease (HD) and their family. The objectives of this thesis were: 1/development of an instrument evaluating HD characteristics; 2/validation of this instrument; 3/implementation of an observational study; 4/development of a model evaluating patients’ pathways. A self-administered instrument of quality of life related to health (HRQoL) and a self-administered clinical instrument specific for patients were developed. Both instruments showed good psychometric properties and were validated in several languages. The costs of HD in five countries (France, Italy, Spain, USA, Poland) were assessed. HRQoL of patients and caregivers and their determinants have been described. Also, a mathematical model that models the evolution of patients was developed to assess the cost-effectiveness of new therapies in HD. A comparison between a mock treatment and current standard care showed that a therapy that improves the total score of the self-assessment TMS (H-CSRI) by 3.3 points would not be cost effective. Also, studies on HRQoL in patients with alcohol use disorders, and in patients with lower urinary tract symptoms were made as well as studies on stroke patients pathways. These studies bring original information that meets needs for evaluation of therapeutic interventions in each of the considered areas.

Introdução: As avaliações econômicas em saúde (AES) têm participado como ferramenta de apoio ao processo de decisão no setor de Saúde. No Brasil, seu uso passou a ser amplamente difundido na última década, já sendo obrigatória sua apresentação em processos de incorporações de novas tecnologias no sistema único de saúde. Embora muitas avaliações econômicas de saúde tenham sido conduzidas, nenhum estudo revisou sistematicamente a produção e qualidade das avaliações brasileiras. Objetivo: Revisar sistematicamente e avaliar a qualidade do relato dos estudos publicados de avaliação econômica de tecnologias em saúde desenvolvidos no Brasil. Métodos: Foi conduzida uma revisão sistemática incluindo AES completas e parciais desenvolvidas no Brasil, e publicadas entre 1980 e 2013. Foram utilizadas as bases de dados eletrônicas (Medline, Embase, Lilacs, Scielo, NHS EED, HTA database, Bireme e BVS ECO); os índices de citação (Scopus, Web of science) e Sisrebrats. Resultados: Foram incluídos 535 artigos, dos quais 36,8% foram considerados AES completas, sendo 39,1% análises de custo-efetividade. Quase metade (46,4%) dos estudos não relatou o tipo de análise conduzida, desses 91,9% eram AES parciais. Entre as que informaram, houve concordância entre o relato e o conduzido em 71,4% dos estudos. As modalidades das tecnologias, mais frequentemente, avaliadas foram procedimentos (34,8%) e medicamentos (28,8%) cujo objetivo principal era o de tratamento (72,1%). As três categorias de doenças cujas tecnologias foram, mais frequentemente, avaliadas foram: doenças infecciosas (17,4%), doenças do aparelho circulatório (12,9%) e neoplasia (10,3%). Entre as tecnologias avaliadas pelos estudos incluídos, apenas 64 haviam sido objeto de análise por comissões nacionais de incorporação (CITEC e CONITEC). A maioria dos artigos foi conduzida por autores da academia (65,1%), que se concentram, principalmente, na região Sudeste (73,6%) e Sul (12,5%). O principal veículo de publicação foram as revistas nacionais (72,5%), com escopo médico (55,5%). Apenas 43,5% dos estudos relataram a fonte de financiamento e 36,1% relataram presença de conflito de interesse. Setenta e nove por cento das AES completas obtiveram resultados favoráveis para as tecnologias avaliadas. Com relação à qualidade do relato, apenas 6,6% dos estudos relataram todos os itens avaliados no checklist, mas 47,7% foram considerados em conformidade (relato minimamente satisfatório). Alguns itens como 1) métodos utilizados para mensuração dos dados de custos, 2) taxa de desconto, 3) fontes de financiamento, e 4) conflitos de interesse foram relatados em apenas metade dos estudos. A qualidade do relato apresentou associação estatística significativa (p < 0,001) com o período de publicação (estudos mais recentes apresentaram maior qualidade) e com a presença de conflito de interesse (estudos com conflito de interesse apresentaram maior qualidade). As fontes de dados clínicos, de uso de recursos e de custos foram considerados com melhor nível de evidência quando comparadas às fontes de utilidade. Nos últimos anos, houve um aumento da produção de análises de custo-utilidade, porém a maioria dos estudos utilizou utilidades de outros países validadas por painéis de especialistas brasileiros. Conclusão: Um grande número de AES foi publicado no Brasil entre 1980 e 2013. A qualidade do relato foi considerada satisfatória, principalmente na AES publicadas mais recentemente. Para que as AES possam aumentar sua contribuição nos processos de decisão nacionais, são necessários esforços para melhora da qualidade dos relatos, transparência e padronização da metodologia utilizada e o aperfeiçoamento do sistema de revisão pelos pares nas revistas nacionais não específicas em economia da saúde / Introduction: Health Economic Evaluation (HEE) have participated as a supportive tool to decision-making in health sector. In Brazil, their use has been widespread in the last decade having become mandatory as part of the processes for new technologies in the Brazilian Unified National Health System. Although many Health Economic Evaluation have been conducted, there are no studies that have systematically reviewed the production and quality of Brazilian evaluations. Objective: To systematically review and evaluate the quality of reporting of published studies of health economic evaluation developed in Brazil. Methods: Was conducted a systematic review including full and partial HEE developed in Brazil and published between 1980 and 2013. Electronic databases (Medline, Embase, Lilacs, Scielo, NHS EED, HTA database, Bireme and the BVS ECO); citation indexes (Scopus, Web of science) and Sisrebrats were searched. Results: We included 535 articles, of which 36.8% were considered full HEE, being 39.1% cost-effectiveness analysis. Almost half (46.4%) of the studies did not report the type of analysis conducted, of these 91.9% were partial HEE. Among the reported, there was 71.4% agreement between the reported and conducted in the studies. The most frequent evaluated modalities of technologies were procedures (34.8%) and drugs (28.8%), whose main objective was treatment (72.1%). The three most often evaluated categories of diseases were infectious diseases (17.4%), cardiovascular diseases (12.9%) and cancer (10.3%). Among the technologies evaluated by the included studies, only 64 had been the subject of analysis by incorporating national commissions (CITEC or CONITEC). Most articles were developed by Authors from academia (65.1%), who are mainly concentrated in the Southeast (73.6%) and South (12.5%) regions. The main vehicles for publication were national journals (72.5%), with medical scope (55.5%). Only 43.5% of the studies reported the source of funding and 36.1% reported conflict of interest. Seventy-nine percent of the full HEE obtained favourable results for the evaluated technologies. Regarding the quality of reporting, only 6.6% of the studies had all items evaluated in the checklist, but 47.7% was considered to be in accordance with the reporting requirements (minimally satisfactory reporting). Items such as 1) methods used to measure the cost data, 2) discount rate, 3) funding sources, and 4) conflicts of interest were reported in only half of the studies. The quality of reporting was significantly related (p < 0.001) to the publication period (more recent studies presented higher quality) and the presence of conflict of interest (presence of conflict of interest presented higher quality). Compared to the utilities, the clinical effect size, resources, and costs data were mostly estimated based on high-ranked evidence. In recent years, there has been an increase in production of cost-utility analysis, but most studies used utilities from other countries validated by Brazilian expert panels. Conclusion: A large number of HEE was published in Brazil between 1980 and 2013. The quality of reporting was considered satisfactory, particularly in most recently published HEE. To increase their contribution in national decision-making processes, efforts are needed in order to improve the quality of reports, transparency and standardization of the methodology and the improvement of the peer-review system in national non-specific journals of health economics