This dissertation consists of six essays in health economics.The first essay, “Economic evaluations in health care: Basic principles and special topics”, serves as an introduction to economic evaluations in health care, including estimations of costs, health effects, and the discount rate. Special topics of interest for the rest of the studies are also discussed, e.g. the role of modelling in cost-effectiveness analysis, and methods for dealing with incomplete observations in clinical trial data. The main theme of the second essay, “Consumption and production by age in Sweden: Basic facts and health economic implications”, is a fairly detailed compilation of consumption and production figures by age in Sweden. The purpose of this is to use the difference between consumption and production in each age group as a measure of the average costs of added years of life in the general population. In economic evaluations of health care interventions, only future costs for related ill­nesses have typically been included in the analysis. However, the health economist David Meltzer has argued that future costs for un­related illnesses and general consumption should also be in­cluded in eco­nomic evaluations. Otherwise, the analysis will not be consistent with expected utility maximiza­tion. The third essay is entitled “The possibility of predicting health care costs in the future from predicted changes in age structure and age specific mortality: The case of Sweden”. Changes in the age structure, especially the growing number of elderly people, have raised concerns about increasing costs for health and elderly care in the future. However, the number of elderly per se is not the main problem, since the growing number of elderly people is a result of better health and hence lower morta­lity. The main purpose of the study is to investigate if future health care costs can be predicted based on forecasts of future changes in age structure and mortality rates. It is shown here that at least in Sweden and in the U.S., there is a linear relationship between age-specific mortality and age-specific health care costs. When these relationships are applied retrospectively to old data, however, the predictions are underestimates of the actual costs. These results are in line with earlier studies, which show that the future age structure is not likely to have a great impact on the future health care costs. The fourth essay is called “Cost effectiveness of bisoprolol in the treatment of chronic congestive heart failure in Sweden: Analysis using data from the Cardiac Insufficiency Bisoprolol Study II” (with Niklas Zethraeus and Bengt Jönsson). Treatment of heart failure with beta blockers was introduced in Sweden already in the 1970s, but it was not until the 1990s that large-scale clinical trials established the efficacy of beta blockers in reducing heart failure mortality. The study consists of an economic evaluation of the beta blocker bisoprolol added to standard treatment of chronic heart failure, compared with placebo added to the same standard treatment. The study raises a number of methodological issues. At the forefront are the inclusion of costs of added years of life, and the question of how to model health effects that extend beyond the clinical trial on which the economic evaluation is based. The results indi­cate that treatment with bisoprolol is cost-effective. A drawback of the analysis in the fourth study was that the expected survival after the end of follow-up was modelled deterministically. This makes it impossible to assess the uncertainty of the cost-effectiveness estimate in a realistic way. The fifth essay is entitled “Assessing uncertainty in cost-effectiveness analysis by combining resampling of clinical trial data with stochastic modelling: The economic evaluation of bisoprolol for heart failure revisited”. Here, the drawback with the fourth study that was mentioned above is addressed by using resamp­ling of the clinical trial data in combination with stochastic modelling of the expected survival after the end of follow-up in the clinical trial. The methodology is inspired by the bootstrap method, which is a simulation technique whereby various statistics, like the mean and variance, can be estimated through repeated resampling from the original sample. The difference from the traditional boot­strap method is that resampling of observations from the clinical trial data is combined with stochastic modelling of the expected remaining lifetime of the patients who were alive at the end of the clinical trial. Cost-effectiveness acceptability curves for treatment of heart failure with bisoprolol were obtained as a result of the analysis. The sixth essay, “Survival analysis techniques for estimating the costs attributable to head and neck cancer in Sweden”, concerns the estimation of average treatment cost attri­butable to a disease when the data contain censored, i.e. incomplete, observations. For various reasons, censored observations are common in medical and epidemiological studies. As a result, the length of the survival time or the size of the costs for those who are alive at the end of follow-up are not exactly known. This is of course problematic if we want to estimate the average survival time or the average cost for all patients, both survivors and non-survivors included. In this study, the Kaplan-Meier sample-average estimator is used for overcoming the problem with censored observations. It is a method that has been proposed specifically for handling censored cost data. / Diss. Stockholm: Handelshögsk., 2002

Diss. Stockholm: Handelshögsk., 2002.

This thesis is composed of two economic evaluations: one trial-based study and one model-based study. In a recent study published in Clinical Infectious Diseases in 2011, a team of OUCRU investigators found that immediate antiretroviral therapy (ART) was not associated with improved 9-month survival in HIV-associated TBM patients (HR, 1.12; 95% CI, .81 to–1.55; P = .50). An economic evaluation of this clinical trial was conducted to examine the cost-effectiveness of immediate ART (initiate ART within 1 week of study entry) versus deferred ART (initiate ART after 2 months of TB treatment) in HIV-associated TBM patients. Over 9 months, immediate ART was not different from deferred ART in terms of costs and QALYs gained. Late initiation of ART during TB and HIV treatment for HIV-positive TBM patients proved to be the most cost-effective strategy. Increasing resistance of Plasmodium falciparum malaria to artemisinin is posing a major threat to the global effort to eliminate malaria. Artesmisinin combination therapies (ACT) are currently known as the most efficacious first-line therapies to treat uncomplicated malaria. However, resistance to both artemisinin and partner drugs is developing and this could result in increasing morbidity, mortality, and economic costs. One strategy advocated for delaying the development of resistance to the ACTs is the wide-scale deployment of multiple first-line therapies. A previous modeling study examined that the use of multiple first-line therapies (MFT) reduced the long-term treatment failures compared with strategies in which a single first-line ACT was recommended. Motivated by observed results of the published modelling study in the Lancet, the cost-effectiveness of the MFT versus the single first-line therapies was assessed in settings of different transmission intensities, treatment coverages and fitness cost of resistance using a previously developed model of the dynamics of malaria and a literature –based cost estimate of changing antimalarial drug policy at national level. This study demonstrates that the MFT strategies outperform the single first-line strategies in terms of costs and benefits across the wide range of epidemiological and economic scenarios considered. The second analysis of the thesis is not only internationally relevant but also with a focus towards healthcare practice in Vietnam. These two studies add significant new cost-effectiveness evidence in Vietnam. This thesis presents the first trial-based economic evaluation in Vietnam considers patient-health outcome measures as the participants have cognitive limitations (tuberculous meningitis), dealing with missing data along with the potential ways to handle this common problem by the use of multiple imputation, and the issues of censored costs data. Having identified these issues would support the decision makers or stakeholders including the pharmaceutical industry to devise a new guideline on how to implement a well-design trial-based economic evaluation in Vietnam in the future. Another novelty of this thesis is the introduction of the detailed of costing of drug regimens change in which the economic evaluations considering the drug policy change often do not include. This cost could be substantial to the healthcare system for retraining the staff and publishing the new guidelines. This thesis will document the costs incurred by the Vietnamese government by changing the first-line treatment of malaria, from single first-line therapy (ACT) to multiple first-line therapies.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-22T12:05:16Z No. of bitstreams: 1 ricardoaugustopalettaguedes.pdf: 29477997 bytes, checksum: 211b12a02f343517656d1362450971d3 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-22T15:41:53Z (GMT) No. of bitstreams: 1 ricardoaugustopalettaguedes.pdf: 29477997 bytes, checksum: 211b12a02f343517656d1362450971d3 (MD5) / Made available in DSpace on 2016-07-22T15:41:53Z (GMT). No. of bitstreams: 1 ricardoaugustopalettaguedes.pdf: 29477997 bytes, checksum: 211b12a02f343517656d1362450971d3 (MD5) Previous issue date: 2016-04-29 / O glaucoma é considerado pela Organização Mundial de Saúde como a principal causa de cegueira irreversível no Brasil e no mundo. A forma mais comum, o glaucoma primário de ângulo aberto, tem bases genéticas, portanto sua prevenção primária ainda é inviável do ponto de vista prático. As principais ações para evitar a progressão para cegueira estão voltadas para sua prevenção secundária (diagnóstico precoce e tratamento eficaz). O principal fator de risco para a progressão da doença é a hipertensão ocular. Nos pacientes glaucomatosos, a pressão intraocular se eleva por uma obstrução gradativa da via de escoamento do humor aquoso no olho, chamada trabeculado. O tratamento do glaucoma pode ser realizado através de colírios, laser ou cirurgia. O envelhecimento da população mundial requer uma alocação custo-efetiva de recursos no tratamento e no controle do glaucoma primário de ângulo aberto. Com a previsão do aumento da incidência e da prevalência do glaucoma no futuro, o impacto econômico aumentará significativamente. O objetivo deste estudo é avaliar a eficiência comparativa do tratamento do glaucoma primário de ângulo aberto no Brasil, através de uma avaliação de custo-utilidade de diferentes estratégias de tratamento. O estudo de custo-utilidade foi realizado através de modelagem de Markov. Os dados (custos, efetividades e probabilidades de transição) para a construção do modelo foram obtidos na literatura e através da análise de um banco de dados de pacientes portadores de glaucoma primário de ângulo aberto em tratamento e cadastrados pelo pesquisador. A perspectiva utilizada foi a do Sistema Único de Saúde financiador e o horizonte temporal foi o da expectativa de vida média da população brasileira. As alternativas de tratamento testadas nos modelos foram observação, tratamento clínico com colírios, tratamento com laser e tratamento com cirurgia. Construíram-se 3 modelos de Markov de acordo com o estágio evolutivo da doença: Modelo 1 para glaucoma inicial, Modelo 2 para glaucoma moderado e Modelo 3 para glaucoma avançado. As medidas de desfecho analisadas foram os custos (em reais), o ganho em qualidade de vida (utilidades) e a razão de custo-utilidade incremental. Encontrou-se que no Modelo 1, a razão de custo-utilidade incremental do tratamento inicial com laser e do tratamento inicial com colírios, em relação à observação, foi R$2.811,39/QALY (Quality-adjusted life year) e R$3.450,47/QALY, respectivamente. Ambas as estratégias foram custo-efetivas, proporcionando ganhos significativos de qualidade de vida (em torno de 2,5 QALYs para o tratamento a laser e 5,0 QALYs para o tratamento com colírios). No Modelo 2, tanto o laser quanto a cirurgia foram bastante custo-efetivos. O tratamento inicial com colírios apresentou custos elevados e quase ultrapassou o limiar de custoefetividade sugerido pela organização Mundial de Saúde. Para o Modelo 3, tanto o tratamento inicial com colírios quanto o com cirurgia foram custo-efetivos. Em todos os modelos, a idade de entrada teve um impacto grande nos resultados. Quanto mais jovem o paciente, mais custo-efetivos eram os tratamentos iniciais com laser e com cirurgia. Concluiu-se, portanto, que todas as estratégias de tratamento do glaucoma primário de ângulo aberto foram custo-efetivas e proporcionaram ganhos reais na qualidade de vida. Os resultados sugerem quais as estratégias mais custoefetivas de acordo com o estágio evolutivo do glaucoma primário de ângulo aberto. / Glaucoma is the main cause of irreversible blindness in the world and in Brazil. The most common type, primary open-angle glaucoma, has genetic basis, therefore primary prevention (avoiding occurrence of the disease) is difficult to perform. Main actions to prevent glaucoma blindness target secondary prevention (early diagnosis and effective treatment). The most important risk factor for glaucoma is ocular hypertension. In glaucomatous patients, intra-ocular pressure elevates as aqueous humor outflow pathways (trabecular meshwork) are progressively obstructed. Glaucoma treatment involves medications, laser or surgery. As world population grows and becomes older, both incidence and prevalence of primary open-angle glaucoma tend to be higher in the future. Hence, there is an urgent need for a costeffective resource allocation in order to reducing its economic impact. The purpose of this study is to determine the most cost-effective strategy for the treatment of primary open-angle glaucoma in Brazil. Participants were a hypothetical cohort of primary open-angle glaucoma patients, separated into early, moderate and advanced stages. We developed 3 Markov models (one for each glaucoma stage), from the perspective of the Brazilian Public Health System and a horizon of the average life expectancy of the Brazilian population. We tested different strategies for each model. Main outcome measures were incremental cost-utility ratio, medical direct costs and quality-adjusted life year. The results show that in early glaucoma, incremental cost-utility ratio of initial laser and initial medical treatment over observation only, were R$2.811,39/QALY (Quality-adjusted life year) and R$3.450,47/QALY, respectively. Both strategies were cost-effective. The two alternatives have provided significant gains in quality of life over no treatment. In moderate glaucoma, both laser and surgery were highly cost-effective. Initial medical therapy in this group led to higher costs and was marginally cost-effective. For advanced glaucoma patients, both surgery and medications were cost-effective. In all models, starting age had a great impact on results. Both laser and surgery were more cost-effective, the younger the patient. In conclusion, from early to advanced glaucoma, all tested treatment strategies were cost-effective and provided real gains in quality of life. We suggest different strategies for different glaucoma stages, according to a cost-effectiveness ratio ranking.

The purpose of this research is to conduct an evaluation of the return on investment value of Employee Assistance Programmes within the South African context. Assistance to employees originated from the 19th century. The term Employee Assistance Programmes was however formulated in the 1970’s in the United States. The Employee Assistance field has since seen a paradigm shift in its focus, significant growth in its market value (amount of corporate clients internationally investing in EAPs for their employees), the establishment of a regulatory and ethical body through EAPA and its formalization as an academic discipline. This study takes the concept of return on investment value of EAPs further than the ratio of benefit-to-cost. The utilization of different data sources, inclusive of quantitative and qualitative instruments creates an opportunity to explore areas of value perception of different role players in the field. It furthermore maps the subjective and objective experience of behaviour change resulting from personal problems and the journey of change as a result of focused interventions. The consistency of views across different datasources as well as between different industries strengthens the value add claims of EAPs as contributing to the financial bottom line of companies. This study advocates for the importance of programme evaluation as a central part of EAP contracting. It furthermore also highlights the importance of documentation of employee performance for evaluation purposes. It illustrates a journey that can be complicated by the failure to agree to evaluative terms at program inception as well as unstructured data-capturing within companies. Employee behaviour consists of both computable and incomputable elements. Generally the focus of a return on investment study would be the computable components of human behaviour. This investigation however highlights significant elements of risk relating to employee performance challenges that is not easy to include in a ROI but holds significant financial and reputational risks for corporate clients. The influence of individual performance challenges on teams and the challenges it holds for line managers is also highlighted through the qualitative journey of this study. Employee behaviour seems vulnerable to internal and external forces and as a result companies’ productivity can be affected by how individual employees respond to these forces. It could be accepted that interventions that is aimed at stabilising and improving employee behaviour, will inevitably impact work performance and as a result the financial bottom-line of the company. Employee Assistance Programmes often operates in an arena where other programmes aimed at impacting employee behaviour are also present. It is thus difficult to isolate it’s intervention as being one of the main behaviour changing facilitators of the company. This study acknowledges this challenge and changes focus to different data-sources reporting on employee behaviour before and after EAP intervention. The consistency of data across these different data-sources becomes one of the main reporting areas for this study. Eventually the challenges encountered in this study guides the advocacy in the recommendations for a thorough agreement of programme evaluation at inception, the areas that will be included in such evaluations, the availability of Human Resource data to ensure effective evaluation inclusive of ROI assessments, targeted assessments at service provider level with effective software support. / Thesis (DPhil)--University of Pretoria, 2010. / Social Work and Criminology / unrestricted

Estudo comparativo entre os custos dos tratamentos clínico, cirúrgico ou percutâneo em portadores de doença multiarterial coronária estável - 5 anos de seguimento [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo, 2013. INTRODUÇÃO: As principais opções terapêuticas para a doença multiarterial coronária incluem cirurgia de revascularização miocárdica (CRM), intervenção coronária percutânea (ICP) e tratamento clínico (TC). Essas três estratégias terapêuticas apresentam eficácia similar em determinados subgrupos de pacientes. No presente momento, estudos direcionados à análise econômica são escassos, e contemplam, principalmente, os custos comparativos entre as intervenções cirúrgica e percutânea. OBJETIVOS: Analisar, prospectivamente, o custo comparativo das três formas terapêuticas da doença multiarterial coronária estável, durante cinco anos de seguimento. MÉTODOS: Foi computado o custo terapêutico global de 611 pacientes do ensaio clínico The Second Medicine, Angioplasty, or Surgery Study (MASS II), baseado na remuneração provida pelo sistema de saúde suplementar do Instituto do Coração do HC/FMUSP, tomando-se os valores em moeda nacional corrente. Realizou-se, posteriormente, análise de custo-efetividade para o tempo livre de eventos clínicos e o tempo livre de eventos acrescido de tempo livre de angina. RESULTADOS: O TC apresentou 3.79 e 2.07 QALY (quality-adjusted lifeyears); o ICP apresentou 3.59 e 2.77 QALY; e o CRM apresentou 4.4 e 2.81 QALY, respectivamente, para sobrevida livre de eventos e sobrevida livre de eventos e angina. Os custos para sobrevida livre de eventos foram R$ 16.327,80 para TC, R$ 35.940,60 para ICP e R$ 32.873,40 para CRM. A análise pareada dos custos para sobrevida livre de eventos mostrou que houve diferença significante favorecendo TC contra ICP (P < 0,01), e em comparação com CRM (P < 0,01); e CRM versus ICP (P = 0,01). Os custos para sobrevida livre de eventos e angina foram R$ 29.795,40, R$ 46.495,80 e R$ 44.305,20, respectivamente. A comparação pareada dos custos livres de eventos mais livres de angina demonstrou que houve diferença significante favorecendo TC contra ICP (P = 0,04), e em comparação com CRM (P < 0,001). Não houve diferença entre CRM e ICP (P > 0,05). CONCLUSÃO: A análise comparativa entre as diferentes opções terapêuticas desta amostra revelou que TC foi mais custo-efetivo que CRM, e esta, por sua vez, mais custo-efetivo que ICP / BACKGROUND: The therapeutic options for multivessel coronary artery disease are coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), or medical treatment alone (MT). These three therapeutic strategies present similar efficacy for specific subgroups. At the present moment, economic outcome trials are scant, and contemplate comparative cost between surgical or percutaneous intervention. OBJECTIVE: To analyze, prospectively, the comparative cost from three therapeutic strategies in multivessel coronary artery disease, at 5-year of follow-up. METHODS: We analyzed cumulative costs of 611 patients from clinical trial The Second Medicine, Angioplasty, or Surgery Study (MASS II). The economic analysis is based on remuneration provided by the supplementary health system of the Heart Institute of the Clinical Hospital of FMUSP, expressing these values in Brazilian currency. It was compared to the cumulative costs of each therapeutic strategy in the 5-year follow-up period. A cost-effectiveness analysis was then conducted for event-free survival and event plus angina-free survival. Cost-effectiveness analysis was performed by quality-adjusted life- year (QALY) analysis. RESULTS: Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years (QALY) and 2.07 QALY; PCI presented 3.59 and 2.77 QALY; and CABG demonstrated 4.4 and 2.81 QALY. The event-free costs were R$ 16327.80 for MT; R$ 35940.60 for PCI; and R$ 32873.40 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P < 0.01) and versus CABG (P < 0.01) and CABG versus PCI (P =0.01). The event-free plus angina-free costs were R$ 29795.40, R$ 46495.80 e R$ 44305.20, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P =0.04), and versus CABG (P < 0.001); there was no difference between CABG and PCI (P > 0.05). CONCLUSION: The comparative analysis among the different therapeutic strategies demonstrated that MT was more cost-effective than CABG, and this than PCI

Le bénéfice de survie restreint à un horizon temporel donné a été proposé comme mesure alternative aux mesures relatives de l’effet d’un traitement notamment dans le cas de non proportionnalité des risques de décès. Le bénéfice de survie restreint correspond à la différence des survies moyennes entre deux bras de traitement et s’exprime en nombre d’années de vie gagnées. Dans la littérature, cette mesure est présentée comme plus intuitive que le hazard ratio et plusieurs auteurs ont proposé son utilisation pour le design et l’analyse d’un essai clinique. Toutefois, ce n’est pas actuellement la mesure qui est utilisée de manière courante dans les essais randomisés. Cette mesure s’applique quelle que soit la distribution des temps de survie et est adaptée si l’hypothèse des risques proportionnels n’est pas respectée. De plus, le bénéfice de survie restreint peut être utilisé en évaluation médico-économique où la mesure d’un effet absolu est nécessaire (nombre d’années de vie gagnées pondérées ou non par la qualité de vie). Si l’on souhaite estimer le bénéfice de survie restreint à partir d’une méta-analyse sur données individuelles, se pose alors la question de prendre en compte l’effet essai dû à la structure hiérarchique des données. L’objectif de cette thèse était de comparer des méthodes statistiques d’estimation du bénéfice de survie restreint à partir de données individuelles d’une méta-analyse d’essais cliniques randomisés. Le point de départ a été une étude de cas (étude coût-efficacité) réalisée à partir des données de la Meta-Analysis of Radiotherapy in Lung Cancer. Cette étude a montré que les cinq méthodes d’estimation étudiées conduisaient à des estimations différentes du bénéfice de survie et de son intervalle de confiance. Le choix de la méthode d’estimation avait également un impact sur les résultats de l’analyse coût-efficacité. Un second travail a consisté à mener une étude de simulation pour mieux comprendre les propriétés des méthodes d’estimation considérées en termes de biais moyen et d’erreur-type. Enfin, la dernière partie de la thèse a mis en application les enseignements de cette étude de simulation au travers de trois méta-analyses sur données individuelles dans le cancer du nasopharynx et dans le cancer du poumon à petites cellules. / The survival benefit restricted up to a certain time horizon has been suggested as an alternative measure to the common relative measures used to estimate the treatment effect, especially in case of non-proportional hazards of death. The restricted survival benefit corresponds to the difference of the two restricted mean survival times estimated for each treatment arm, and is expressed in terms of life years gained. In the literature, this measure is considered as more intuitive than the hazard ratio and many authors have suggested its use for the design and the analysis of clinical trials. However, it is not currently the most used measure in randomized trials. This measure is valid under any distribution of the survival times and is adapted if the proportional hazards assumption does not hold. In addition, the restricted survival benefit can be used in medico-economic evaluation where an absolute measure of the treatment effect is needed (number of [quality adjusted] life years gained). If one wants to estimate the restricted survival benefit from an individual participant data meta-analysis, there is a need to take into account the trial effect due to the hierarchical structure of the data. The aim of this thesis was to compare statistical methods to estimate the restricted survival benefit from an individual participant data meta-analysis of randomized trials. The starting point was a case study (cost-effectiveness analysis) using data from the Meta-Analysis of Radiotherapy in Lung Cancer. This study showed that the five investigated methods yielded different estimates for the restricted survival benefit and its confidence interval. The choice of a method to estimate the survival benefit also impacted on cost-effectiveness results. Our second project consisted in a simulation study to have a better understanding of the properties of the investigated methods in terms of bias and standard error. Finally, the last part of the thesis illustrated the lessons learned from the simulation study through three examples of individual participant data meta-analysis in nasopharynx cancer and in small cell lung cancer.

Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen. / Hintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

[EN] Adaptation to the multiple facets of global change challenges the conventional means of sustainably planning and managing water resources at the river basin scale. Numerous demand or supply management options are available, from which adaptation measures need to be selected in a context of high uncertainty of future conditions. Given the interdependency of water users, agreements need to be found at the local level to implement the most effective adaptation measures. Therefore, this thesis develops an approach combining economics and water resources engineering to select a cost-effective programme of adaptation measures in the context of climate change uncertainty, and to define an equitable allocation of the cost of the adaptation plan between the stakeholders involved. A framework is developed to integrate inputs from the two main approaches commonly used to plan for adaptation. The first, referred to as "top-down", consists of a modelling chain going from global greenhouse gases emission scenarios to local hydrological models used to assess the impact of climate change on water resources. Conversely, the second approach, called "bottom-up", starts from assessing vulnerability at the local level to then identify adaptation measures used to face an uncertain future. Outcomes from these two approaches are integrated to select a cost-effective combination of adaptation measures through a least-cost optimization model developed at the river basin scale. The model is then used to investigate the trade-offs between different planning objectives defined in terms of environmental flow requirements, irrigated agriculture development, and the cost of the programme of measures. The performances of a programme of measures are finally assessed under different climate projections to identify robust and least-regret adaptation measures. The issue of allocating the cost of the adaptation plan is considered through two complementary perspectives. The outcome of a negotiation process between the stakeholders is modelled through the implementation of cooperative game theory to define cost allocation scenarios. These results are compared with cost allocation rules based on social justice principles to provide contrasted insights into a negotiation process. This innovative framework has been applied in a Mediterranean case study in the Orb River basin (France). Mid-term climate projections, downscaled from 9 General Climate Models, are used to assess the uncertainty associated with climate projections. Demand evolution scenarios have been developed to project agricultural and urban water demands on the 2030 time horizon. The least-cost river basin optimization model developed in GAMS allows the cost-effective selection of a programme of measures from a catalogue of 462 supply and demand management measures. Nine cost allocation scenarios based on different social justice principles have been discussed through face-to-face semi-structured interviews with 15 key informants and compared with solution concepts from cooperative game theory for a 3-player game defined at the river basin scale. The interdisciplinary framework developed in this thesis combines economics and water resources engineering methods, establishing a promising means of bridging the gap between bottom-up and top-down approaches and supporting the creation of cost-effective and equitable adaptation plans at the local level. / [ES] La adaptación a los múltiples aspectos del cambio global supone un reto para los enfoques convencionales de planificación y gestión sostenible de los recursos hídricos a escala de cuenca. Numerosas opciones de gestión de la demanda o de la oferta están disponibles, de entre las cuales es necesario seleccionar medidas de adaptación en un contexto de elevada incertidumbre sobre las condiciones futuras. Dadas las interdependencias existentes entre los usuarios del agua a nivel local, hace falta buscar acuerdos a escala de cuenca para implementar las medidas de adaptación más eficaces. Por este motivo, esta tesis desarrolla una metodología que, combinando economía e ingeniería de los recursos hídricos, busca seleccionar un programa de medidas coste-eficaz frente a las incertidumbres del cambio climático, y asimismo definir un reparto justo del coste de la adaptación entre los actores implicados. El marco metodológico ha sido desarrollado para integrar contribuciones de los dos principales enfoques utilizados para la planificación de la adaptación. El primero, denominado descendente ("top-down"), consiste en una cadena de modelación que va desde los escenarios de emisiones de gases efecto invernadero a nivel global hasta los modelos hidrológicos utilizados a nivel local para evaluar así el impacto del cambio climático sobre los recursos hídricos. Por el contrario, el segundo enfoque denominado ascendente ("bottom-up") empieza por evaluar la vulnerabilidad del sistema a nivel local para después identificar medidas de adaptación frente a un futuro incierto. Los resultados de los métodos mencionados previamente se han integrado con el fin de seleccionar una combinación coste-eficaz de medidas de adaptación a través de un modelo de optimización a menor coste a escala de cuenca. El modelo se utiliza para investigar las soluciones de compromiso ("trade-offs") entre diversos objetivos de planificación como son los caudales ecológicos necesarios, el desarrollo del regadío y el coste del programa de medidas. Seguidamente, se han evaluado los programas de adaptación frente a varias condiciones climáticas para definir así un programa de medidas robusto y de arrepentimiento mínimo frente al cambio climático. En la última parte se aborda el problema del reparto justo de los costes del plan de adaptación, entendiendo que esto es una manera de favorecer su implementación. Para ello, se han modelado los resultados de un proceso de negociación entre los diferentes actores mediante escenarios de reparto basados en la teoría de juegos cooperativos. Posteriormente, se han comparado estos resultados con otras reglas de reparto de costes basadas en principios de justicia social, proporcionando así un punto de vista diferente al proceso de negociación. Este novedoso enfoque ha sido aplicado a una cuenca mediterránea, la cuenca del rio Orb (Francia). Para ello, se han empleado proyecciones climáticas a medio-plazo de datos reescalados de 9 Modelos de Circulación Global. Además, se han desarrollado escenarios de evolución de la demanda en los sectores urbano y agrícola para el horizonte de planificación de 2030. El modelo de optimización a menor coste a escala de cuenca desarrollado en GAMS permite seleccionar un programa de medidas, de entre las 462 medidas de gestión de la oferta o de la demanda. Nueve escenarios de reparto de costes basados en diferentes principios de justicia social han sido debatidos con informantes clave mediante entrevistas y comparados con conceptos de solución de la teoría de juegos cooperativos, considerando un juego de 3 jugadores a escala de cuenca. El marco interdisciplinario desarrollado durante esta tesis combina métodos de economía y de ingeniería de los recursos hídricos de manera prometedora y permite integrar los enfoques "top-down" y "bottom-up", contribuyendo a definir un plan de adaptación coste-eficaz y justo a nivel local. / [CA] L'adaptació als múltiples aspectes del canvi global implica un repte per als enfocaments convencionals de planificació i gestió sostenible dels recursos hídrics a escala de conca. Existeixen nombroses opcions de gestió de la demanda y de la oferta. De entre elles, cal seleccionar mesures d'adaptació en un context d'incertesa elevada sobre les condicions futures. Donades les interaccions entre els usuaris de l'aigua a nivell local, és necessari buscar acords a escala de conca per tal d'implementar les mesures d'adaptació més eficaces. Per aquest motiu, la tesi desenvolupa una metodologia que, mitjançant la combinació d'economia i enginyeria dels recursos hídrics, siga adient per seleccionar un programa de mesures cost-eficaç per a fer front a les incerteses del canvi climàtic i, a més a més, definir un repartiment just del cost d'adaptació entre els actors implicats. El marc metodològic ha estat desenvolupat amb el fi de permetre integrar contribucions del principals enfocaments que s'utilitzen per a la planificació de l'adaptació. El primer, que es denomina descendent ("top-down"), consisteix a una cadena de modelació que va des dels escenaris d'emissions de gas d'efecte hivernacle a nivell global fins als models hidrològics a nivell local per avaluar l'impacte del canvi climàtic sobre els recursos hídrics. Per contra, el segon enfocament, que es denomina ascendent ("bottom-up"), comença per avaluar la vulnerabilitat del sistema a nivell local per a tot seguit identificar mesures d'adaptació de cara a un futur incert. Els resultats del mètodes esmentats prèviament, s'han integrat per a seleccionar una combinació de mesures d'adaptació cost-eficaç mitjançant un model d'optimització a menor cost a escala de conca. El model s'utilitza per investigar les solucions de compromís ("trade-offs") entre els diversos objectius de planificació, com són els cabals ecològics necessaris, el desenvolupament del regadiu i el cost del programa de mesures. A continuació, s'avaluen els programes d'adaptació per a varies condicions climàtiques amb el fi de definir un programa de mesures robust i de penediment mínim per a fer front al canvi climàtic. En la darrera part, s'escomet el problema del repartiment just dels costs del pla d'adaptació, considerant que això és una manera de facilitar la implementació del pla. En conseqüència, els resultats d'un procés de negociació entre els diferents actors han estat modelats mitjançant escenaris de repartiment basats en la teoria de jocs cooperatius. Tot seguit, els resultats s'han comparat amb altres regles de repartiment de costos basades en principis de justícia social. Això ha proporcionat un punt de vista diferent al procés de negociació. Aquest enfocament innovador s'ha aplicat a una conca mediterrània, la conca del riu Orb (França). Amb aquesta finalitat s'han utilitzat projeccions climàtiques a mig termini de dades reescalades de 9 Models de Circulació Global (MCG). A més a més, s'han desenvolupat escenaris d'evolució de la demanada en els sectors agrícola i urbà per a l'horitzó de planificació de 2030. El model d'optimització a menor cost a escala de conca desenvolupat en GAMS permet seleccionar un programa de mesures, de entre les 462 mesures de gestió de la oferta o de la demanda. Els nou escenaris de repartiment de costs han estat debatuts amb informants clau, mitjançant entrevistes, i comparats amb conceptes de solució de la teoria de jocs cooperatius, considerant un joc de 3 jugadors a escala de conca. El marc interdisciplinari desenvolupat al llarg de la tesi combina mètodes d'economia i d'enginyeria dels recursos hídrics de manera prometedora i permet la integració d'enfocaments "top-down" i "bottom-up", fet que contribueix a definir un pla d'adaptació cost-eficaç i just a escala local. / Girard, CDP. (2015). Integrating top-down and bottom-up approaches to design a cost-effective and equitable programme of measures for adaptation of a river basin to global change [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/59461 / TESIS / Premios Extraordinarios de tesis doctorales

Aims: To assess effectiveness and economic benefit of the psychological treatment of anxiety disorders in order to compare them with the consumed resources of the treatment. Methods: Assessment of specific and non-specific symptoms and impairments in N=493 anxiety patients (DSM-IV) receiving cognitive behavior therapy pre, post, and one year after treatment with various measures. Additional analyses of costs of the treatment and the benefits due to reduced work disability and health care utilization after therapy (including a pilot study using a willingness-to-pay approach). The treatment setting can be characterised as clinically typical for everyday practice. Core results: a) effectiveness: Effect sizes ranged from 0.9 to 1.9. All improvements were significant and lasted until 1-year-follow-up. Rates of clinically significant therapy success ranged from 63% to 79% depending on outcome measure and success criteria. b) cost-effectiveness analysis: Cost-effectiveness-indices ranged from DM 8338.- to DM 10456.- for one successful treatment (average costs taking also the costs of unsuccessful treatments into account). c) cost-benefit-analysis: Cost reduction in the year after therapy was remarkable (inpatient costs about 25%, other cost factors 87%-100%), resulting in a benefit of DM 3026.- per patient and a cost-benefit-ratio of 1:0.58 in the first year after treatment. Assuming that the improvements are stable, the cost-benefit-ratio after five years would be estimated as 1:2.63. Discussion: The present study shows exemplarily for CBT of anxiety disorders that modern psychotherapy can produce remarkable results at reasonable costs. Furthermore, clinical-psychological treatment methods show an additional economic benefit. Clinical Psychology can benefit from focusing not only the promising developments in classification, etiology, and treatment but also taking over the cost perspective (which is relatively new in scientific evaluation of psychotherapy). (Appendix: Cost-Benefit-Calculator.htm; 8,97 KB -- Usage: Referat Informationsvermittlung/ SLUB) / Fragestellungen: Ermittlung von Effektivität und monetärem Nutzen psychologischer Behandlung von Angststörungen, die dann den für die Therapie aufgewendeten Ressourcen gegenübergestellt werden. Methoden: N=493 Patienten mit Angststörungen (DSM-IV), die eine ambulante störungsspezifische kognitive Verhaltenstherapie absolviert haben, wurden prä, post und zur 1-Jahres-Katamnese untersucht. Das Spektrum der Erhebungen umfasste störungsspezifische und störungsübergreifende Symptombelastung und Beeinträchtigungen in verschiedenen Lebensbereichen, sowie eine globale Therapieerfolgseinschätzung von Patienten und Therapeuten. In einer zweiten Studie wurden zusätzlich an einer Teilstichprobe Kosten-Nutzen-Aspekte untersucht (Einsparungen durch Reduktion von Gesundheitsleistungen und Arbeitsunfähigkeit; außerdem Pilotstudie zu willingness-to-pay-Ansatz). Das Behandlungssetting der Studie ist charakterisiert durch klinisch relevante Rahmenbedingungen und Praxisnähe. Zentrale Ergebnisse: a) Effektivität: Die Effektstärken reichten in Abhängigkeit von der Meßmethode von 0.9 bis 1.9. Die Verbesserungen waren durchgängig signifikant und blieben bis zur 1-Jahres-Katamnese stabil. Die Raten klinisch bedeutsamer Besserungen betrugen 63% - 79% in Abhängigkeit von Mess- und Auswertungsmethode. b) Kosten-Effektivitäts-Analyse: Die Kosten-Effektivitätivitäts-Indices betrugen DM 8338.- bis DM 10456.- (dieser Index gibt an, was eine erfolgreiche Behandlung durchschnittlich kostet, also unter Einbezug der nicht erfolgreichen Behandlungen in die Gesamtkosten). c) Kosten-Nutzen-Analyse: Im Jahr nach Therapie reduzierten sich die Kostenfaktoren der Störungen vor Therapie beträchtlich (stationäre Kosten um 25%, restliche Kostenfaktoren 87% - 100%). Die dadurch erzielten Einsparungen betrugen durchschnittlich DM 3026.- (Kosten-Nutzen-Verhältnis im ersten Jahr: 1 : 0.58). Unter der Annahme, dass die Auswirkungen der Therapie auch über die 1-Jahres-Katamnese hinaus stabil bleiben, kann man abschätzen, dass sich die Therapie innerhalb des zweiten Jahres amortisiert und das Kosten-Nutzen-Verhältnis nach fünf Jahren (diskontiert) 1 : 2.63 beträgt. Diskussion: Wie in dieser Arbeit anhand der kognitiven Verhaltenstherapie für Angststörungen gezeigt wird, kann moderne Psychotherapie bei vertretbarem Aufwand beachtliche Erfolge verbuchen. Klinisch-psychologische Behandlungsmethoden sind darüber hinaus auch wirtschaftlich, derart, dass sie über den reinen Behandlungserfolg hinaus zu Kosteneinsparungen beitragen könnten. Es ist erstaunlich, dass die Kosten-Perspektive der wissenschaftlichen Bewertung von Psychotherapie noch recht neu ist. Die Klinische Psychologie kann davon profitieren, diese Dimension (neben den beachtlichen Erkenntnisfortschritten in bezug auf Klassifikation, Ätiologie, Verlaufsforschung und Behandlungsverfahren) mehr herauszustellen. (Anlage: Cost-Benefit-Calculator.htm; 8,97 KB -- Nutzung: Referat Informationsvermittlung der SLUB)