This thesis consists of three chapters. The first chapter explores the effects of prenatal nutritional deficiency on depression in adulthood. It is well established that maternal behaviour during pregnancy has a lasting effect on the child for years to come. Studies show that in utero nutritional shocks can have prolonged effects on health and labour market outcomes later in life of the offspring. In this paper I investigate whether such nutritional deficiencies during gestation can have an extended impact on mental health in adulthood. Using the fourth wave of Indonesian Family Life Survey (IFLS), I find that Muslim individuals who were potentially exposed to Ramadan in the first and third trimester have significantly higher scores on the depression scale than those who were not exposed. This effect is particularly significant among Muslim males who were exposed in the first trimester and Muslim females who were exposed in the third trimester. Similar effects of exposure are also found on the probability of being depressed in the Muslim population. The absence of such impact of exposure in the non-Muslim population suggests that nutritional deficiencies during the gestation period can have lasting effects on mental health and may increase the possibility of developing depression later in life. Next, the literature on socioeconomic health inequality uses individuals' socioeconomic rank (p) to develop the concentration index. In the second chapter of the thesis, I construct an alternative framework by directly using individuals' income level (y) to rank them and develop stochastic dominance conditions to investigate whether this method leads to the same conclusion as using the socioeconomic ranks (p). Using World Health Survey data for five South Asian countries, I conclude that using the socioeconomic ranks (p) and income levels (y) to rank individuals lead to different results in dominance tests adjusted for different equivalence scales. Lastly, to address the arbitrariness problem of the health concentration index's value caused by assuming the existence of a ratio-scaled variable, Makdissi and Yazbeck (2014) adopted a counting approach to measure health inequality. In the third chapter of the thesis, I apply this counting approach in a two-fold way. Firstly, I estimate the values of population health status and health inequality in United States using the National Health Interview Survey (2010) data. Then, assuming increased government expenditure on health awareness, I simulate the effects such policy interventions and see what improvements in the public health can be achieved. Also, I propose the count-approach incremental cost effectiveness ratio (C-ICER) which is a simple measure to assess the cost effectiveness of public health awareness campaigns.

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.

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.

Introdução: Dados de custo necessários na Análise de Custo-Efetividade (CEA) são, muitas vezes, obtidos de estudos longitudinais primários. Neste contexto, é comum a presença de censura caracterizada por não se ter os dados de custo a partir de certo momento, devido ao fato de que indivíduos saem do estudo sem esse estar finalizado. A ideia da Ponderação pela Probabilidade Inversa (IPW – do inglês, Inverse Probability Weighting) vem sendo bastante estudada na literatura relacionada a esse problema, mas é desconhecida a disponibilidade de ferramentas computacionais para esse contexto. Objetivo: Construir ferramentas computacionais em software Excel e R, para estimação de custos pelo método IPW conforme proposto por Bang e Tsiatis (2000), com o objetivo de lidar com o problema da censura em dados de custos. Métodos: Através da criação de planilhas eletrônicas em software Excel e programação em software R, e utilizando-se bancos de dados hipotéticos com situações diversas, busca-se propiciar ao pesquisador maior entendimento do uso desse estimador bem como a interpretação dos seus resultados. Resultados: As ferramentas desenvolvidas, ao proporcionarem a aplicação do método IPW de modo intuitivo, se mostraram como facilitadoras para a estimação de custos na presença de censura, possibilitando calcular a ICER a partir de dados de custo. Conclusão: As ferramentas desenvolvidas permitem ao pesquisador, além de uma compreensão prática do método, a sua aplicabilidade em maior escala, podendo ser considerada como alternativa satisfatória às dificuldades postas pelo problema da censura na CEA. / Introduction: Cost data needed in Cost-Effectiveness Analysis (CEA) are often obtained from longitudinal primary studies. In this context, it is common the presence of censoring characterized by not having cost data after a certain point, due to the fact that individuals leave the study without this being finalized. The idea of Inverse Probability Weighting (IPW) has been extensively studied in the literature related to this problem, but is unknown the availability of computational tools for this context. Objective: To develop computational tools in software Excel and software R, to estimate costs by IPW method, as proposed by Bang and Tsiatis (2000), in order to deal with the problem of censorship in cost data. Methods: By creating spreadsheets in Excel software and programming in R software, and using hypothetical database with different situations, we seek to provide to the researcher most understanding of the use of IPW estimator and the interpretation of its results. Results: The developed tools, affording the application of IPW method in an intuitive way, showed themselves as facilitators for the cost estimation in the presence of censorship, allowing to calculate the ICER from more accurate cost data. Conclusion: The developed tools allow the researcher, besides a practical understanding of the method, its applicability on a larger scale, and may be considered a satisfactory alternative to the difficulties posed by the problem of censorship in CEA.

In vitro fertilization (IVF) is used to help infertile couples achieve a live birth. Clinical studies have suggested that multiple, consecutive cycles of IVF can increase live birth rate significantly. Others have documented improved live birth rates from the use of new laboratory techniques for preimplantation genetic screening (PGS). This genetic screening technique seeks to determine the ploidy of the embryo prior to implantation into the woman. To date, no study has examined the cost-effectiveness of using IVF in conjunction with PGS compared to that of IVF alone for 3 consecutive cycles in achieving a live birth. This study compared the incremental cost-effectiveness ratios (ICER) from each intervention arm based on the clinical probabilities for each outcome and this study was grounded in the protection motivation theory. Costs were obtained from secondary sources, such as the literature and government databases. The model was constructed using a decision-analytical approach that allowed for z test statistical analysis of the outcomes, where the ICER is the dependent variable and the independent variables are the 2 interventions. The robustness of the model was tested through univariate and probabilistic sensitivity analysis and stratified by age groups. The results showed that PGS with IVF was cost-effective for women aged under 40 and women aged 40-42, but not for women over 42. Based on a willingness-to-pay threshold of $100,000, IVF with PGS was the most cost-effective strategy in all age groups. The positive social change implication of this study is such that understanding the costs associated with a new technology to achieve a live birth is significant for society to help guide clinical treatment of these patients.

Cost-effectiveness analysis is widely conducted in the economic evaluation of new treatment options. In many clinical and observational studies of costs, data are often censored. Censoring brings challenges to both medical cost estimation and cost-effectiveness analysis. Although methods have been proposed for estimating the mean costs with censored data, they are often derived from theory and it is not always easy to understand how these methods work. We provide an alternative method for estimating the mean cost more efficiently based on a replace-from-the-right algorithm, and show that this estimator is equivalent to an existing estimator based on the inverse probability weighting principle and semiparametric efficiency theory. Therefore, we provide an intuitive explanation to a theoretically derived mean cost estimator. In many applications, it is also important to estimate the survival function of costs. We propose a generalized redistribute-to-the right algorithm for estimating the survival function of costs with censored data, and show that it is equivalent to a simple weighted survival estimator of costs based on inverse probability weighting techniques. Motivated by this redistribute-to-the-right principle, we also develop a more efficient survival estimator for costs, which has the desirable property of being monotone, and more efficient, although not always consistent. We conduct simulation to compare our method with some existing survival estimators for costs, and find the bias seems quite small. Thus, it may be considered as a candidate for survival estimator for costs in a real setting when the censoring is heavy and cost history information is available. Finally, we consider one special situation in conducting cost-effectiveness analysis, when the terminating events for survival time and costs are different. Traditional methods for statistical inference cannot deal with such data. We propose a new method for deriving the confidence interval for the incremental cost-effectiveness ratio under this situation, based on counting process and the general theory for missing data process. The simulation studies show that our method performs very well for some practical settings. Our proposed method has a great potential of being applied to a real setting when different terminating events exist for survival time and costs.

Leucodepletion, the removal of leucocytes from blood products improves the safety of blood transfusion by reducing adverse events associated with the incidental non-therapeutic transfusion of leucocytes. Leucodepletion has been shown to have clinical benefit for immuno-suppressed patients who require transfusion. The selective leucodepletion of blood products by bed side filtration for these patients has been widely practiced. This study investigated the economic consequences in Queensland of moving from a policy of selective leucodepletion to one of universal leucodepletion, that is providing all transfused patients with blood products leucodepleted during the manufacturing process. Using an analytic decision model a cost-effectiveness analysis was conducted. An ICER of $16.3M per life year gained was derived. Sensitivity analysis found this result to be robust to uncertainty in the parameters used in the model. This result argues against moving to a policy of universal leucodepletion. However during the course of the study the policy decision for universal leucodepletion was made and implemented in Queensland in October 2008. This study has concluded that cost-effectiveness is not an influential factor in policy decisions regarding quality and safety initiatives in the Australian blood sector.

Introdução: Dados de custo necessários na Análise de Custo-Efetividade (CEA) são, muitas vezes, obtidos de estudos longitudinais primários. Neste contexto, é comum a presença de censura caracterizada por não se ter os dados de custo a partir de certo momento, devido ao fato de que indivíduos saem do estudo sem esse estar finalizado. A ideia da Ponderação pela Probabilidade Inversa (IPW – do inglês, Inverse Probability Weighting) vem sendo bastante estudada na literatura relacionada a esse problema, mas é desconhecida a disponibilidade de ferramentas computacionais para esse contexto. Objetivo: Construir ferramentas computacionais em software Excel e R, para estimação de custos pelo método IPW conforme proposto por Bang e Tsiatis (2000), com o objetivo de lidar com o problema da censura em dados de custos. Métodos: Através da criação de planilhas eletrônicas em software Excel e programação em software R, e utilizando-se bancos de dados hipotéticos com situações diversas, busca-se propiciar ao pesquisador maior entendimento do uso desse estimador bem como a interpretação dos seus resultados. Resultados: As ferramentas desenvolvidas, ao proporcionarem a aplicação do método IPW de modo intuitivo, se mostraram como facilitadoras para a estimação de custos na presença de censura, possibilitando calcular a ICER a partir de dados de custo. Conclusão: As ferramentas desenvolvidas permitem ao pesquisador, além de uma compreensão prática do método, a sua aplicabilidade em maior escala, podendo ser considerada como alternativa satisfatória às dificuldades postas pelo problema da censura na CEA. / Introduction: Cost data needed in Cost-Effectiveness Analysis (CEA) are often obtained from longitudinal primary studies. In this context, it is common the presence of censoring characterized by not having cost data after a certain point, due to the fact that individuals leave the study without this being finalized. The idea of Inverse Probability Weighting (IPW) has been extensively studied in the literature related to this problem, but is unknown the availability of computational tools for this context. Objective: To develop computational tools in software Excel and software R, to estimate costs by IPW method, as proposed by Bang and Tsiatis (2000), in order to deal with the problem of censorship in cost data. Methods: By creating spreadsheets in Excel software and programming in R software, and using hypothetical database with different situations, we seek to provide to the researcher most understanding of the use of IPW estimator and the interpretation of its results. Results: The developed tools, affording the application of IPW method in an intuitive way, showed themselves as facilitators for the cost estimation in the presence of censorship, allowing to calculate the ICER from more accurate cost data. Conclusion: The developed tools allow the researcher, besides a practical understanding of the method, its applicability on a larger scale, and may be considered a satisfactory alternative to the difficulties posed by the problem of censorship in CEA.

Introdução: Dados de custo necessários na Análise de Custo-Efetividade (CEA) são, muitas vezes, obtidos de estudos longitudinais primários. Neste contexto, é comum a presença de censura caracterizada por não se ter os dados de custo a partir de certo momento, devido ao fato de que indivíduos saem do estudo sem esse estar finalizado. A ideia da Ponderação pela Probabilidade Inversa (IPW – do inglês, Inverse Probability Weighting) vem sendo bastante estudada na literatura relacionada a esse problema, mas é desconhecida a disponibilidade de ferramentas computacionais para esse contexto. Objetivo: Construir ferramentas computacionais em software Excel e R, para estimação de custos pelo método IPW conforme proposto por Bang e Tsiatis (2000), com o objetivo de lidar com o problema da censura em dados de custos. Métodos: Através da criação de planilhas eletrônicas em software Excel e programação em software R, e utilizando-se bancos de dados hipotéticos com situações diversas, busca-se propiciar ao pesquisador maior entendimento do uso desse estimador bem como a interpretação dos seus resultados. Resultados: As ferramentas desenvolvidas, ao proporcionarem a aplicação do método IPW de modo intuitivo, se mostraram como facilitadoras para a estimação de custos na presença de censura, possibilitando calcular a ICER a partir de dados de custo. Conclusão: As ferramentas desenvolvidas permitem ao pesquisador, além de uma compreensão prática do método, a sua aplicabilidade em maior escala, podendo ser considerada como alternativa satisfatória às dificuldades postas pelo problema da censura na CEA. / Introduction: Cost data needed in Cost-Effectiveness Analysis (CEA) are often obtained from longitudinal primary studies. In this context, it is common the presence of censoring characterized by not having cost data after a certain point, due to the fact that individuals leave the study without this being finalized. The idea of Inverse Probability Weighting (IPW) has been extensively studied in the literature related to this problem, but is unknown the availability of computational tools for this context. Objective: To develop computational tools in software Excel and software R, to estimate costs by IPW method, as proposed by Bang and Tsiatis (2000), in order to deal with the problem of censorship in cost data. Methods: By creating spreadsheets in Excel software and programming in R software, and using hypothetical database with different situations, we seek to provide to the researcher most understanding of the use of IPW estimator and the interpretation of its results. Results: The developed tools, affording the application of IPW method in an intuitive way, showed themselves as facilitators for the cost estimation in the presence of censorship, allowing to calculate the ICER from more accurate cost data. Conclusion: The developed tools allow the researcher, besides a practical understanding of the method, its applicability on a larger scale, and may be considered a satisfactory alternative to the difficulties posed by the problem of censorship in CEA.

Parkinson's is a chronic, progressive, neurodegenerative disease. The most common treatment is levodopa/carbidopa, which suppresses the symptoms of the disease. In this report, a cost-utility analysis of the MyFID levodopa/carbidopa micro tablet dispenser has been conducted. The method used was a continuous-time Markov chain with states based on the score in MDS-UPDRS II and MDS-UPDRS III. The model was simulated over a time horizon of five years and was started at different disease severity levels. The results obtained from the simulations were a dominant ICER for all model versions except when the simulation was started in the earliest stages of the disease, where it was moderate to high. The conclusion was that the treatment method with the micro / Parkinsons är en kronisk, progressiv, neurodegenerativ sjukdom. Den vanligaste behandlingen är levodopa/carbidopa, som undertrycker symptomen av sjukdomen. I denna rapport har en kostnadsnyttoanalys av MyFID levodopa/ carbidopa-mikrotablettdispensern genomförts. Metoden som användes var en kontinuerlig Markovkedja med tillstånd baserade på poängen i MDS-UPDRS II och MDS-UPDRS III. Modellen simulerades över en tidsperiod av fem år och startades vid olika svårighetsgrader av sjukdomen. Resultaten som erhölls från simuleringarna visade en dominerande ICER för alla modellversioner förutom när simuleringen startades i de tidigaste stadierna av sjukdomen, där den visade en måttligt till hög kostnad. Slutsatsen var att behandlingen med hjälp av mikrotablettdispensern var kostnadseffektiv i de måttliga till senare stadierna av sjukdomen.