A tuberculose (TB) é uma doença infecto contagiosa causada pelo Bacilo de Koch (Mycobacterium tuberculosis), sua forma mais frequente é a tuberculose pulmonar, e tem cura quando o tratamento é realizado corretamente. É uma das importantes causas de mortalidade no mundo, e apresenta alta prevalência e incidência no Brasil, o qual se encontra entre os países com maiores números de casos da doença. O objetivo desse trabalho foi efetuar um estudo sobre custo-efetividade do tratamento para tuberculose (abordando as estratégias de tratamento supervisionado e autoadministrado), buscando evidencias para estimar custos diretos (no distrito oeste de Ribeirão Preto-SP) e custos indiretos (para algumas regiões deste município). Por ser uma doença associada às condições sociais e econômicas (nelas incluídas o Brasil), buscou-se observar as deficiências das organizações e gestão do sistema de saúde, através da análise dos custos gerados pela TB. Foi efetuado um estudo epidemiológico, descritivo, pesquisa avaliativa, visando coletar dados sócio-demográficos, e características sobre acompanhamento e evolução do tratamento através dos prontuários dos doentes de TB para estimativa de custos diretos, e também estimar os custos indiretos através de entrevista com os pacientes. A fim de efetuarmos a análise de custo-efetividade do tratamento diretamente observado (TDO) e autoadministrado (TAA) da TB. Foram amplamente discutidos a qualidade dos dados, e realizadas as estimativas dos custos: direto, resultando em R$ 1075,39 (para estratégia TDO) e R$806,98 (estratégia TAA); e indireto, resultando em R$2001,39 (para TDO) e R$974,53 (para TAA). Encontrou-se uma Razão de Custo-efetividade Incremental (RCEI) negativo de 8.0562 por tratamento concluído da estratégia TDO em relação ao TAA. Palavras / Tuberculosis (TB) is an infectious disease caused by Kochs bacillus (Mycobacterium tuberculosis), most frequently presented as pulmonary tuberculosis. It is fully curable with the right treatment. TB is an important cause of death worldwide and presents high prevalence and incidence in Brazil, one of the countries with the highest number of cases. The aim of this study was to evaluate the cost-effectiveness of tuberculosis treatment (directly observed treatment DOT, and self-administered treatment SAT), searching evidence in order to estimate direct (in the Western district of Ribeirão Preto-SP) and indirect (for some regions of this city) costs. Due to the fact TB is associated with social and economical conditions (including in Brazil), an analysis of costs generated by TB was carried out, by observing the deficiencies of organizations and management of the health system. A descriptive epidemiological study of an evaluative research was carried out to collect socio-demographic data and characteristics of evolution and follow-up of TB treatment, to estimate the direct costs through the analysis of medical forms of patients, and indirect costs through interviews with patients. In order to evaluate the cost-effectiveness of DOT and SAT strategies for TB treatment, the quality of data was analyzed and estimates of direct and indirect costs were calculated. The results show a negative incremental cost-effectiveness ratio (ICER) of 8,0562 for DOTS strategy compared to SAT strategy.

A tuberculose (TB) é uma doença infecto contagiosa causada pelo Bacilo de Koch (Mycobacterium tuberculosis), sua forma mais frequente é a tuberculose pulmonar, e tem cura quando o tratamento é realizado corretamente. É uma das importantes causas de mortalidade no mundo, e apresenta alta prevalência e incidência no Brasil, o qual se encontra entre os países com maiores números de casos da doença. O objetivo desse trabalho foi efetuar um estudo sobre custo-efetividade do tratamento para tuberculose (abordando as estratégias de tratamento supervisionado e autoadministrado), buscando evidencias para estimar custos diretos (no distrito oeste de Ribeirão Preto-SP) e custos indiretos (para algumas regiões deste município). Por ser uma doença associada às condições sociais e econômicas (nelas incluídas o Brasil), buscou-se observar as deficiências das organizações e gestão do sistema de saúde, através da análise dos custos gerados pela TB. Foi efetuado um estudo epidemiológico, descritivo, pesquisa avaliativa, visando coletar dados sócio-demográficos, e características sobre acompanhamento e evolução do tratamento através dos prontuários dos doentes de TB para estimativa de custos diretos, e também estimar os custos indiretos através de entrevista com os pacientes. A fim de efetuarmos a análise de custo-efetividade do tratamento diretamente observado (TDO) e autoadministrado (TAA) da TB. Foram amplamente discutidos a qualidade dos dados, e realizadas as estimativas dos custos: direto, resultando em R$ 1075,39 (para estratégia TDO) e R$806,98 (estratégia TAA); e indireto, resultando em R$2001,39 (para TDO) e R$974,53 (para TAA). Encontrou-se uma Razão de Custo-efetividade Incremental (RCEI) negativo de 8.0562 por tratamento concluído da estratégia TDO em relação ao TAA. Palavras / Tuberculosis (TB) is an infectious disease caused by Kochs bacillus (Mycobacterium tuberculosis), most frequently presented as pulmonary tuberculosis. It is fully curable with the right treatment. TB is an important cause of death worldwide and presents high prevalence and incidence in Brazil, one of the countries with the highest number of cases. The aim of this study was to evaluate the cost-effectiveness of tuberculosis treatment (directly observed treatment DOT, and self-administered treatment SAT), searching evidence in order to estimate direct (in the Western district of Ribeirão Preto-SP) and indirect (for some regions of this city) costs. Due to the fact TB is associated with social and economical conditions (including in Brazil), an analysis of costs generated by TB was carried out, by observing the deficiencies of organizations and management of the health system. A descriptive epidemiological study of an evaluative research was carried out to collect socio-demographic data and characteristics of evolution and follow-up of TB treatment, to estimate the direct costs through the analysis of medical forms of patients, and indirect costs through interviews with patients. In order to evaluate the cost-effectiveness of DOT and SAT strategies for TB treatment, the quality of data was analyzed and estimates of direct and indirect costs were calculated. The results show a negative incremental cost-effectiveness ratio (ICER) of 8,0562 for DOTS strategy compared to SAT strategy.

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The study uses Cost Effectiveness Analysis (CEA) as a method to analyse the economicand environmental impact of carbon dioxide (CO2e) emission abatement projects in theCanadian residential sector. It includes the more traditional environmental andeconomic criteria, yet it incorporates a behavioural component to the analysis. Adetailed account of the environmental specifications, emission reductions, and economicconsiderations of 11 abatement projects are used as input for the CEA. In addition,behavioural variables, such as disposable income, home ownership, and home repairskills, are taken into account to complement the study.The results indicate that the implementation of several of these carbon abatementprojects, such as insulating hot water pipes, replacing incandescent light bulbs,installing a programmable thermostat, etc. can bring about large emission reductionstogether with a net economic benefit, and in most cases, without altering the levels ofcomfort. This method can serve as a template for the evaluation of other related projectswithin the climate change mitigation context in Canada and in other countries, in anattempt to increase adoption rates of such projects.

This dissertation aims at developing and testing a new method that can better capture preferences for multistate health profiles. The motivation arose from the failure of the QALY (Quality-Adjusted Life Year) model in adequately capturing preferences in multistate health profiles. The current QALY-based technique captures preferences for multistate health profiles by evaluating each health state in the profile independently of other states. As the past literature showed, this additive independence condition does not hold in practice and hence such approach is inadequate. To address this issue, this study proposes a novel approach to measure preferences for multistate health profiles by looking at two consecutive health states at a time. It hypothesizes that an evaluation of the future health state is dependent or "conditioned" on the level of the preceding, or current, health state. Characteristics of the current health state that are suspected to impact the resulting conditional preference scores for future health state are systematically explored in a carefully designed empirical study. The interested factors include duration of the current health state, direction of change and amplitude of change between the current and future health states. A 2

Compared to the relative wealth of information surrounding design in the context of system-of-systems there has been little research surrounding policy making in system-of-systems. While the adoption of a formal approach and lexicon for system-of-systems problems has been proposed by researchers, the specific inclusion of regulatory policies in system-of-systems is still largely absent or underdeveloped. Typically, there is no distinction between internal policies of an organization and exogenous policies coming through regulatory channels. Further, researchers have yet to formally employ a standardized framework to regulatory policy problems in the context of a system-of-systems. As international regulatory bodies are calling on world States to identify and select “baskets of measures” to address CO2 emissions from civil aviation, there is a growing recognition that doing so will require a framework for policy identification and selection. Despite this recognition, such a framework has yet to be established. This research develops a formal lexicon for public policy as a part of system-of-systems, and employs a formalized process to explore multiple established, planned, and potential policies in the context of the global civil aviation system. Existing architectures and lexicons will be expanded to include regulatory policies that have often been treated as exogenous forcing functions in system-of-systems problems. Ultimately, a process for informed quantitative decision making to support concurrent CO2 regulatory policy analysis and design in the civil aviation system-of-systems is established. The developed methodology will allow policy makers to systematically identify effective policy space, while maintaining the objectivity of the analyst.

Preventative interventions often demand that resources be consumed in the present in exchange for future benefits. Understanding these trade-offs, in a context of resource constraints, is essential for policy makers. Cost-effectiveness analysis is one tool to inform decision-making. Targeted testing and treatment (TTT) for latent tuberculosis infection (LTBI) consists in identifying people at high risk for LTBI for preventive treatment to decrease the risk that they will develop active tuberculosis disease (ATBD). The state of Tennessee began conducting TTT statewide in 2001. This study uses a decision tree to evaluate the cost and outcomes of TTT for LTBI in Tennessee, compared to passive ATBD case finding (PACF). Key event probabilities were obtained from the Tennessee TTT program and from the literature. Outcomes are measured in terms of Quality Adjusted Life Years (QALY). The cost-effectiveness threshold was set at $100,000/QALY saved. One-way sensitivity analyses around factors related to study design (exclusion of patient costs, secondary transmission, discount rate and analytical horizon), the program’s environment (prevalence of LTBI and drug resistance, ATBD treatment costs) and program performance (program maturity, treatment initiation and completion rate, testing in low-risk group, test characteristics, screening costs) were conducted, as was probabilistic sensitivity analysis (PSA) which takes into account the uncertainty in multiple parameters simultaneously. The base case, with a 25-year time horizon and 3% discount rate, shows that TTT prevents 47 ATBD cases, and saves 31 QALYs per 100,000 patients screened for LTBI at a societal cost of $12,579 (2011 US$) per QALY saved. Sensitivity analyses identified value thresholds that would trigger a change in preferred policy. PSA shows that the likelihood that TTT would be cost-effective is low. Decision makers interested in implementing TTT should carefully assess the characteristics of the local TB epidemic and expected program performance to determine whether TTT is preferable over PACF from a cost-effectiveness viewpoint.

This dissertation is motivated by two of the health-related Millennium Development Goals (MDGs): MDG 4, focused on reducing child mortality, and MDG 5, which aims to improve maternal health. My three papers evaluate the health and economic impact, and cost-effectiveness, of interventions to improve maternal and child health in three areas of the developing world using methods from decision sciences and statistics. In paper 1, I use a decision-analytic model that simulates the natural history of pregnancy and pregnancy-related complications to assess the expected health outcomes, costs, and cost-effectiveness of strategies to reduce maternal mortality in Afghanistan. Increasing family planning was found to be the most effective single intervention to reduce maternal mortality. Further findings suggest that a stepwise approach that couples increased family planning with incremental improvements in access to appropriate intrapartum care could prevent 3 out of 4 maternal deaths and would be cost-effective. Paper 2 explores the value of community-based disease management programs for reducing mortality from childhood pneumonia and malaria in 24 countries of sub-Saharan Africa. I use a model-based framework that combines symptom patterns, care-seeking behavior, and treatment coverage from an empirical assessment of household survey data with information on diagnostic algorithms and disease progression from the literature. Results indicate that a community health worker program modeled on currently-existing programs could avert over 100,000 under-five deaths combined across the 24 countries and would be regarded as cost-effective compared to the status quo under typical benchmarks for international cost-effectiveness analysis. My third paper evaluates the effect of Janani Suraksha Yojana (JSY), a conditional cash transfer program intended to promote the use of reproductive health services in India, on childhood immunizations and other reproductive and child health indicators. Using observational data from the most recent district-level household survey, I conduct a matching analysis with logistic regression to assess the associations of interest. Results show that receipt of financial assistance from JSY led to a significant increase in childhood immunizations rates, post-partum check-ups, and some healthy breastfeeding practices, but no impact was found on exclusive breastfeeding and care-seeking behaviors.

Vitamin K has a negligible effect on bone mineral density (BMD) and a large but uncertain effect on fractures. The three studies in the thesis explored uncertainty about the effect of vitamin K on fractures using the methods of economic evaluation and Bayesian meta-analysis. In study 1, a Markov probabilistic microsimulation model was developed for a hypothetical cohort of 50-year-old postmenopausal women without osteoporosis. This was a fracture incidence-based model, populated with data from the literature. It was used to examine the cost-effectiveness of two supplementation strategies over a lifetime horizon. We compared vitamin K2 (or vitamin K1) concurrent with vitamin D3 and calcium versus vitamin D3 and calcium alone. Study 2 included a systematic review, and classical and Bayesian univariate meta-analyses to determine the efficacies of the K vitamins on BMD or fractures in current and future trials. Study 3 used Bayesian bivariate random-effects meta-analysis to jointly model the treatment effects on two correlated bone outcomes. We compared the estimates from the univariate and bivariate meta-analyses and explored how these results would change the conclusions of the cost-effectiveness analysis. The strategies including vitamin K were highly cost-effective at willingness-to-pay of $50,000/QALY (quality-adjusted life year); however, the results were most sensitive to changes in the efficacy of vitamin K. The univariate meta-analyses showed large uncertainties in the anti-fracture effects of vitamin K2 in current and future trials. The bivariate 95% credible intervals were considerably narrower than those from the univariate meta-analyses. Using future odds ratios from the bivariate meta-analyses, vitamin K2 cost more than $100,000/QALY while vitamin K1 was cost-saving. Our analyses found substantial uncertainty around the estimates of the vitamin K effect on fractures. We recommend against routine use of vitamin K for fracture prevention. Bayesian bivariate meta-analysis accounts for all available information and should be considered when the treatment effects are measured on two correlated outcomes.

Vitamin K has a negligible effect on bone mineral density (BMD) and a large but uncertain effect on fractures. The three studies in the thesis explored uncertainty about the effect of vitamin K on fractures using the methods of economic evaluation and Bayesian meta-analysis. In study 1, a Markov probabilistic microsimulation model was developed for a hypothetical cohort of 50-year-old postmenopausal women without osteoporosis. This was a fracture incidence-based model, populated with data from the literature. It was used to examine the cost-effectiveness of two supplementation strategies over a lifetime horizon. We compared vitamin K2 (or vitamin K1) concurrent with vitamin D3 and calcium versus vitamin D3 and calcium alone. Study 2 included a systematic review, and classical and Bayesian univariate meta-analyses to determine the efficacies of the K vitamins on BMD or fractures in current and future trials. Study 3 used Bayesian bivariate random-effects meta-analysis to jointly model the treatment effects on two correlated bone outcomes. We compared the estimates from the univariate and bivariate meta-analyses and explored how these results would change the conclusions of the cost-effectiveness analysis. The strategies including vitamin K were highly cost-effective at willingness-to-pay of $50,000/QALY (quality-adjusted life year); however, the results were most sensitive to changes in the efficacy of vitamin K. The univariate meta-analyses showed large uncertainties in the anti-fracture effects of vitamin K2 in current and future trials. The bivariate 95% credible intervals were considerably narrower than those from the univariate meta-analyses. Using future odds ratios from the bivariate meta-analyses, vitamin K2 cost more than $100,000/QALY while vitamin K1 was cost-saving. Our analyses found substantial uncertainty around the estimates of the vitamin K effect on fractures. We recommend against routine use of vitamin K for fracture prevention. Bayesian bivariate meta-analysis accounts for all available information and should be considered when the treatment effects are measured on two correlated outcomes.