Depuis le début des années 2000, les traitements anticancéreux oraux (TAO) sont en développement croissant, notamment dans le cancer du sein. Ils permettent aux patients la prise de comprimés par voie orale à domicile améliorant la qualité de vie. On estime que 10 à 34% des tumeurs du sein sur-expriment la protéine HER2 (HER2+) qui augmente le risque de métastases. Deux thérapies ciblées anti-HER2 sont actuellement disponibles : le trastuzumab, anticorps monoclonal administré par voie intraveineuse et le lapatinib, inhibiteur de tyrosine kinase administré par voie orale. D’après les recommandations de l’Agence Nationale d’Accréditation et d’Evaluation en Santé (ANAES, 2003), les TAO devraient être privilégiées par rapport aux formes intraveineuses prises à l’hôpital lorsque leur efficacité est équivalente. Dans la pratique courante des oncologues, les TAO semblent néanmoins sous-utilisées dans certains cas. En plus des freins médicaux connus (adhésion thérapeutique, gestion des effets indésirables), les TAO induisent une consommation de ressources hopitalières supplémentaires qui n’est pas valorisée dans le modèle de tarification à l’activité (T2A) des établissements hospitaliers, lequel repose sur la nature et la quantité d’activité médicale réalisée. Nous supposons que le modèle de T2A représente un frein économique à l’utilisation des TAO entrainant une disparité d’accès entre les traitements anticancéreux oraux et intraveineux. L’objectif de ce travail de thèse était donc de déterminer le rôle de la T2A dans l’accès des patients aux TAO au moyen d’une évaluation médico- économique de l’impact économique et organisationnel des TAO sur le système de soins. Une revue de littérature a permis de mettre en évidence le rôle du mode de financement des soins sur l’accès aux TAO en France et aux Etats-Unis. L’analyse des bases de données nationales hospitalières du Programme Médicalisé des Systèmes d’Information (PMSI) a permis de quantifier l’enjeu économique de la chimiothérapie pour les établissements de soins et qui représente la deuxième activité des hôpitaux en volume après l’hémodialyse. Le bénéfice lié aux séances de chimiothérapie a ainsi été estimé à 108 millions d’Euros en 2010 pour l’ensemble des établissements publics et privés en France. L’analyse a également permis de simuler le transfert d’allocation de ressources de l’hôpital vers les soins de ville induit par la substitution des séances de chimiothérapie par l’utilisation des TAO. Un modèle comparant le coût du traitement intraveineux (trastuzumab) aux TAO (lapatinib et capécitabine) dans le cancer du sein métastatique HER2+ a confirmé des coûts moindres pour les TAO (17 165€ versus 36 077€ par an et par patient) liés à une économie sur les transports médicalisés mais surtout sur les consommations hospitalières et ce, malgré un coût d’acquisition plus élevé des TAO. Malgré cet impact budgétaire négatif pour les hôpitaux, une étude de préférences (Méthode des Choix Discrets) conduite auprès d’un échantillon de 203 médecins hospitaliers et libéraux a montré que l’efficacité d’un traitement anticancéreux restait le déterminant principal de la décision thérapeutique (β=2,214, p<0,0001). L’étude a toutefois révélé que, aux stades avancés du cancer, la voie d’administration et son coût étaient également associés au choix du traitement (β=0,612, p=0,035 ;β=0,506, p<0,0001). Les résultats montrent donc que le modèle de financement de l’activité hospitalière influence le choix des modalités de traitement même si les critères d’ordre médicaux et environnementaux du patient demeurent des déterminants essentiels dans le choix du recours aux TAO (profil clinique du patient, adhésion thérapeutique, préférences du patient, environnement familial et socio-économique, conditions d’accès à l’offre de soins) / Since the early 2000’s, oral anticancer drugs (OADs) are increasingly available especially for the treatment of breast cancer. This route of chemotherapy administration allows patients to take oral tablets at home improving their quality-of-life. We estimate that 10 to 34% of breast tumors over-express the HER2 protein (HER2+) that increases the risk of developing metastasis. Two anti-HER2 targeted therapies are currently available: trastuzumab, a monoclonal antibody administered intravenously and lapatinib, a tyrosine kinase inhibitor administered orally. According to the recommendations of the National Agency for Accreditation and Evaluation in Health (ANAES, 2003), OADs should be administered when their efficacy is equivalent to the one of intravenous forms taken at hospital. In the current practice of oncologists, OADs seem to be underused in some cases. The medical brakes to the use of OADs (i.e. adherence, management of side effects) are well known. Nonetheless, OADs induce additional hospital healthcare resources which are not taken into account in the hospital payment system that is based on the nature and the quantity of medical activities performed (i.e. per-case payment system (PPS)). We assume that the current model of PPS represents an economic barrier to the use of OADs and which induces a disparity of access between oral and intravenous cancer treatments. The objective of this thesis was to determine the role of the PPS on the patient access to OADs based on a medico-economic evaluation of the economical and organizational impacts of OADs on the health care system. A literature review has highlighted the role of the funding of care on the access to OADs in the French and US healthcare systems. From an analysis of the national hospital database (PMSI database), we have quantified the economic implications of chemotherapy administration that is the second hospital activity in volume after hemodialysis. Earnings associated with chemotherapy sessions have been estimated at 108 million Euros in 2010 for all private and public institutions in France. This analysis also allowed us to simulate the transfer of resources allocation from hospital to community setting induced by the substitution of chemotherapy sessions by the use of OADs. A model comparing the cost of intravenous anticancer drug (trastuzumab) to OADs (lapatinib and capecitabine) in the treatment of HER2+ metastatic breast cancer confirmed the lower costs for OADs (€ 17,165 versus € 36,077 per year per patient). The higher acquisition cost of OADs was offset by the cost savings in terms of medical transportation and hospital resources. Despite this negative budget impact for hospitals, a preference study (Discrete Choice Experiment) conducted among 203 physicians showed that the efficacy of cancer treatment remained the main determinant of the therapeutic decision (β=2.214, p<0.0001). The study has also revealed that, in the advanced stages of cancer, the route of administration and its associated cost was also associated with the treatment choice (β=0.612, p= 0.035; =β0.506, p<0.0001). Overall, the results show that the hospital payment system influences the choice of treatment modalities. Nonetheless, medical criterions related to the patient remain essential in the choice of using OADs (clinical profile of the patient, adherence, patient preferences, familial and socio-economic environment, and conditions of access to health care)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O aumento exponencial dos gastos em saúde demanda estudos econômicos que subsidiem as decisões de agentes públicos ou privados quanto à incorporação de novas tecnologias aos sistemas de saúde. A tomografia de emissão de pósitrons (PET) é uma tecnologia de imagem da área de medicina nuclear, de alto custo e difusão ainda recente no país. O nível de evidência científica acumulada em relação a seu uso no câncer pulmonar de células não pequenas (CPCNP) é significativo, com a tecnologia mostrando acurácia superior às técnicas de imagem convencionais no estadiamento mediastinal e à distância. Avaliação econômica realizada em 2013 aponta para seu custo-efetividade no estadiamento do CPCNP em comparação à estratégia atual de manejo baseada no uso da tomografia computadorizada, na perspectiva do SUS. Sua incorporação ao rol de procedimentos disponibilizados pelo SUS pelo Ministério da Saúde (MS) ocorreu em abril de 2014, mas ainda se desconhecem os impactos econômico-financeiros decorrentes desta decisão. Este estudo buscou estimar o impacto orçamentário (IO) da incorporação da tecnologia PET no estadiamento do CPCNP para os anos de 2014 a 2018, a partir da perspectiva do SUS como financiador da assistência à saúde. As estimativas foram calculadas pelo método epidemiológico e usaram como base modelo de decisão do estudo de custo-efetividade previamente realizado. Foram utilizados dados nacionais de incidência; de distribuição de doença e acurácia das tecnologias procedentes da literatura e de custos, de estudo de microcustos e das bases de dados do SUS. Duas estratégias de uso da nova tecnologia foram analisadas: (a) oferta da PET-TC a todos os pacientes; e (b) oferta restrita àqueles que apresentem resultados de TC prévia negativos. Adicionalmente, foram realizadas análises de sensibilidade univariadas e por cenários extremos, para avaliar a influência nos resultados de possíveis fontes de incertezas nos parâmetros utilizados. A incorporação da PET-TC ao SUS implicaria a necessidade de recursos adicionais de R$ 158,1 (oferta restrita) a 202,7 milhões (oferta abrangente) em cinco anos, e a diferença entre as duas estratégias de oferta é de R$ 44,6 milhões no período. Em termos absolutos, o IO total seria de R$ 555 milhões (PET-TC para TC negativa) e R$ 600 milhões (PET-TC para todos) no período. O custo do procedimento PET-TC foi o parâmetro de maior influência sobre as estimativas de gastos relacionados à nova tecnologia, seguido da proporção de pacientes submetidos à mediastinoscopia. No cenário por extremos mais otimista, os IOs incrementais reduzir-se-iam para R$ 86,9 (PET-TC para TC negativa) e R$ 103,9 milhões (PET-TC para todos), enquanto no mais pessimista os mesmos aumentariam para R$ 194,0 e R$ 242,2 milhões, respectivamente. Resultados sobre IO, aliados às evidências de custo-efetividade da tecnologia, conferem maior racionalidade às decisões finais dos gestores. A incorporação da PET no estadiamento clínico do CPCNP parece ser financeiramente factível frente à magnitude do orçamento do MS, e potencial redução no número de cirurgias desnecessárias pode levar à maior eficiência na alocação dos recursos disponíveis e melhores desfechos para os pacientes com estratégias terapêuticas mais bem indicadas. / The exponential increase in health spending requires economic studies, in order to support decisions of public or private agents related to the incorporation of new technologies to health systems. Positron emission tomography (PET) is an imaging technology in the field of nuclear medicine, of high cost and still recent in the country. Scientific evidence accumulated in relation to its use in non-small cell lung cancer (NSCLC) is significant, and technology proves to be of higher accuracy than conventional imaging techniques in mediastinal and distance staging. Economic evaluation conducted in 2013 indicates its cost-effectiveness in NSCLC staging compared to current management strategy based on the use of computed tomography (CT) in the perspective of the Brazilian Health System (SUS). It was incorporated to the list of procedures available through SUS by Ministry of Health (MoH) in April, 2014; however, the economic and financial impacts of this decision are still unknown. This study aimed to estimate the budgetary impact (BI) of the incorporation of PET in NSCLC staging for 2014 to 2018 from the perspective of SUS as the financier of health care. Estimates were calculated by the epidemiological method, and used as basis decision model from previous cost-effectiveness study. National data on incidence of the disease; distribution of prevalence of the disease and technologies accuracy from literature; and costs from microcosting study and SUS database were used. Two strategies of use of the new technology were analyzed: offer (a) to all patients, and (b) restricted to those with negative result of CT. Additionally, univariate and extreme scenarios sensitivity analysis were performed to assess the influence on the results of possible sources of uncertainty in the parameters used. The incorporation of PET-CT to SUS implies the need of additional resources from R$ 158.1 (limited offer) to 202.7 million (comprehensive offer) in five years, and the difference between the two strategies is R$ 44.6 million in the period. In absolute terms, the total BI would be of R$ 555 million (PET-CT for negative CT) and R$ 600 million (PET-CT for all) in the period. The cost of the procedure PET-CT was the most influential parameter on the expenditures estimates related to new technology, followed by the proportion of patients undergoing mediastinoscopy. In the most optimistic extreme scenario, incremental BI would drop to R$ 86.9 (PET-CT for negative CT) and R$ 103.9 million (PET-CT for all), while in the most pessimistic scenario it would increase to R$ 194.0 and R$ 242.2 million, respectively. Results of BI, combined with evidence of cost-effectiveness of the technology gives greater rationality to the final decisions of policymakers. The incorporation of PET in NSCLC staging seems financially feasible when faced to the magnitude of the MoH budget, and potential reduction in the number of unnecessary surgeries can lead to more efficient allocation of resources and better outcomes for patients with better indicated therapeutic strategies.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O aumento exponencial dos gastos em saúde demanda estudos econômicos que subsidiem as decisões de agentes públicos ou privados quanto à incorporação de novas tecnologias aos sistemas de saúde. A tomografia de emissão de pósitrons (PET) é uma tecnologia de imagem da área de medicina nuclear, de alto custo e difusão ainda recente no país. O nível de evidência científica acumulada em relação a seu uso no câncer pulmonar de células não pequenas (CPCNP) é significativo, com a tecnologia mostrando acurácia superior às técnicas de imagem convencionais no estadiamento mediastinal e à distância. Avaliação econômica realizada em 2013 aponta para seu custo-efetividade no estadiamento do CPCNP em comparação à estratégia atual de manejo baseada no uso da tomografia computadorizada, na perspectiva do SUS. Sua incorporação ao rol de procedimentos disponibilizados pelo SUS pelo Ministério da Saúde (MS) ocorreu em abril de 2014, mas ainda se desconhecem os impactos econômico-financeiros decorrentes desta decisão. Este estudo buscou estimar o impacto orçamentário (IO) da incorporação da tecnologia PET no estadiamento do CPCNP para os anos de 2014 a 2018, a partir da perspectiva do SUS como financiador da assistência à saúde. As estimativas foram calculadas pelo método epidemiológico e usaram como base modelo de decisão do estudo de custo-efetividade previamente realizado. Foram utilizados dados nacionais de incidência; de distribuição de doença e acurácia das tecnologias procedentes da literatura e de custos, de estudo de microcustos e das bases de dados do SUS. Duas estratégias de uso da nova tecnologia foram analisadas: (a) oferta da PET-TC a todos os pacientes; e (b) oferta restrita àqueles que apresentem resultados de TC prévia negativos. Adicionalmente, foram realizadas análises de sensibilidade univariadas e por cenários extremos, para avaliar a influência nos resultados de possíveis fontes de incertezas nos parâmetros utilizados. A incorporação da PET-TC ao SUS implicaria a necessidade de recursos adicionais de R$ 158,1 (oferta restrita) a 202,7 milhões (oferta abrangente) em cinco anos, e a diferença entre as duas estratégias de oferta é de R$ 44,6 milhões no período. Em termos absolutos, o IO total seria de R$ 555 milhões (PET-TC para TC negativa) e R$ 600 milhões (PET-TC para todos) no período. O custo do procedimento PET-TC foi o parâmetro de maior influência sobre as estimativas de gastos relacionados à nova tecnologia, seguido da proporção de pacientes submetidos à mediastinoscopia. No cenário por extremos mais otimista, os IOs incrementais reduzir-se-iam para R$ 86,9 (PET-TC para TC negativa) e R$ 103,9 milhões (PET-TC para todos), enquanto no mais pessimista os mesmos aumentariam para R$ 194,0 e R$ 242,2 milhões, respectivamente. Resultados sobre IO, aliados às evidências de custo-efetividade da tecnologia, conferem maior racionalidade às decisões finais dos gestores. A incorporação da PET no estadiamento clínico do CPCNP parece ser financeiramente factível frente à magnitude do orçamento do MS, e potencial redução no número de cirurgias desnecessárias pode levar à maior eficiência na alocação dos recursos disponíveis e melhores desfechos para os pacientes com estratégias terapêuticas mais bem indicadas. / The exponential increase in health spending requires economic studies, in order to support decisions of public or private agents related to the incorporation of new technologies to health systems. Positron emission tomography (PET) is an imaging technology in the field of nuclear medicine, of high cost and still recent in the country. Scientific evidence accumulated in relation to its use in non-small cell lung cancer (NSCLC) is significant, and technology proves to be of higher accuracy than conventional imaging techniques in mediastinal and distance staging. Economic evaluation conducted in 2013 indicates its cost-effectiveness in NSCLC staging compared to current management strategy based on the use of computed tomography (CT) in the perspective of the Brazilian Health System (SUS). It was incorporated to the list of procedures available through SUS by Ministry of Health (MoH) in April, 2014; however, the economic and financial impacts of this decision are still unknown. This study aimed to estimate the budgetary impact (BI) of the incorporation of PET in NSCLC staging for 2014 to 2018 from the perspective of SUS as the financier of health care. Estimates were calculated by the epidemiological method, and used as basis decision model from previous cost-effectiveness study. National data on incidence of the disease; distribution of prevalence of the disease and technologies accuracy from literature; and costs from microcosting study and SUS database were used. Two strategies of use of the new technology were analyzed: offer (a) to all patients, and (b) restricted to those with negative result of CT. Additionally, univariate and extreme scenarios sensitivity analysis were performed to assess the influence on the results of possible sources of uncertainty in the parameters used. The incorporation of PET-CT to SUS implies the need of additional resources from R$ 158.1 (limited offer) to 202.7 million (comprehensive offer) in five years, and the difference between the two strategies is R$ 44.6 million in the period. In absolute terms, the total BI would be of R$ 555 million (PET-CT for negative CT) and R$ 600 million (PET-CT for all) in the period. The cost of the procedure PET-CT was the most influential parameter on the expenditures estimates related to new technology, followed by the proportion of patients undergoing mediastinoscopy. In the most optimistic extreme scenario, incremental BI would drop to R$ 86.9 (PET-CT for negative CT) and R$ 103.9 million (PET-CT for all), while in the most pessimistic scenario it would increase to R$ 194.0 and R$ 242.2 million, respectively. Results of BI, combined with evidence of cost-effectiveness of the technology gives greater rationality to the final decisions of policymakers. The incorporation of PET in NSCLC staging seems financially feasible when faced to the magnitude of the MoH budget, and potential reduction in the number of unnecessary surgeries can lead to more efficient allocation of resources and better outcomes for patients with better indicated therapeutic strategies.