Dissertations / Theses on the topic 'Pharmacoeconomic evaluation'

Magister Scientiae - MSc (Pharmacy Administration and Policy Regulation)
Aim: The purpose of this research was to assess the validity of pharmacoeconomic evaluation in Egypt three years after the guideline was issued and analyse challenges and opportunities for improvement. Objectives: To conduct a literature review of pricing, medicine reimbursement, and pharmacoeconomic evaluation. Examine, in conjunction with relevant stakeholders, the progress of the pharmacoeconomic evaluation. To present examples of pharmacoeconomic evaluation deployment. To propose recommendations on how to optimize the pharmacoeconomic implementation. Methods: A literature review and a qualitative research method that was conducted using a semi-structured interview with stakeholders of the reimbursement process in Egypt. In addition, examples were analysed to determine the impact of pharmacoeconomic methods on medicine reimbursement in Egypt. Results: The Egyptian Pharmacoeconomic Evaluation Unit was established in 2013, it supports various reimbursement decisions, especially for new technologies. The unit evaluations depended mainly on the available international data. However, fragmentation of the health care system in Egypt is a major obstacle to progress. The guidelines are still non-compulsory for implementation, and accordingly some reimbursement committees do not consider its evaluation in its decision making. Conclusion and Recommendations: The pharmacoeconomic evaluation has demonstrated a good start in Egypt. To gain the full benefit of pharmacoeconomic evaluation, authorities need to consider reducing the complexity of health care system, setting clear strategies, building capabilities to improve pharmacoeconomic awareness; endorsing risk sharing strategy and building a proper health related information system along with creation of full Health Technology Assessment program. The above-mentioned recommendations could be associated together under the Universal Health Coverage road map that Egypt committed to achieve by 2030.

Given financial constraints, drug manufacturers are required to provide pharmacoeconomic evaluations to demonstrate the value for money of their drug compared to current treatment when requesting reimbursement by publicly funded health care systems. This thesis is a retrospective examination of pharmacoeconomic evaluations submitted for review to the Common Drug Review process. Its purpose was to determine the pattern of adherence to guidelines, trends in methodological quality, and transparency, changes in the adoption and practice of sensitivity analysis and probabilistic methods, use of indirect treatment comparison, and identify methodological factors−determinants of recommendations. Using an instrument that was developed and tested, information from 201 pharmacoeconomic evaluations was collected and analysed. Pharmacoeconomic evaluations may have improved over time in terms of adherence, methodological quality, transparency, use of probabilistic sensitivity analysis and indirect treatment comparison. However, such improvements have been minimal and further efforts are needed to better improve pharmacoeconomic evaluations in the future.

This study aimed to investigate the effect of incorporating adverse drug reactions in economic analyses of drug therapies. Subsequently, the impact of this information on prescribing in primary care is explored. In order to achieve the aims of the study, three main studies were conducted. In the first study, an economic analysis was conducted to estimate the comparative costs of a large UK population (N = 98 887) given nonsteroidal anti-inflammatory drug (NSAID) therapy alone and in combination of gastrointestinal (GI) protective agents including concomitant prescriptions of H2 blockers, omeprazole and misoprostol. The second study was a pharmacoeconomic analysis, using data from the literature and local expert opinion, of three commonly prescribed classes of drugs in primary care – NSAIDs, selective serotonin reuptake inhibitors (SSRIs) and angiotensin converting enzyme (ACE) inhibitors for the treatment of rheumatoid arthritis, depression and hypertension respectively. Finally, the results from the pharmacoeconomic analysis were disseminated to GPs in a local Health Board to explore the impact on influencing primary care prescribing. Economic analyses based on various data sources have shown that the total cost of drug therapies are often much higher than the purchasing cost alone. There is much value in taking into account the clinical and economic impact of drug-induced ADRs when conducting pharmacoeconomic evaluations. However, this is often restricted by the availability of some of the data that are required to complete the economic model. The necessary data do exist, but linked clinical data for this type of analysis are not readily available for research purposes. General practitioners were generally supportive of economic evaluations and the exploratory study on disseminating pharmacoeconomic information. However, the dissemination exercise had failed to demonstrate a positive relationship. In addition to the barriers highlighted in the literature, it was found that GPs do not feel that there is a role for the implementation of economic information in primary care.

RESUMO - O cancro do colo útero representa um importante problema de saúde pública em Portugal: é o terceiro cancro mais frequente nas mulheres entre os 15 e os 44 anos, originando a morte de 346 mulheres anualmente. Contudo, esta patologia é altamente evitável, nomeadamente, através da imunização contra a infeção HPV, que é a causa necessária para o desenvolvimento do cancro. A elevada prevalência da infeção em mulheres mais velhas sugere que a vacinação poderá ser uma estratégia custo-efetiva mesmo numa faixa etária superior. Para que seja racionalmente ponderada a comparticipação da vacina nestas mulheres é necessária a realização de um estudo fármaco-económico que comprove o custo-efetividade desta intervenção, já que o seu financiamento atual prevê apenas as mulheres não abrangidas pelo Programa Nacional de Vacinação, dos 18 aos 25 anos. Os objetivos do trabalho são realizar uma revisão da literatura sobre estudos de avaliação económica relativos à prevenção do CCU e avaliar a relação de custo-efetividade de vacinar mulheres contra o HPV entre os 26 e os 55 anos em comparação com a prática clínica corrente, em Portugal. É utilizado o Modelo Global Cervarix® e realiza-se uma análise de custo-utilidade e de custo-efetividade. Os resultados demonstraram que a vacinação em mulheres dos 26 aos 45 anos poderá ser uma opção custo-efetiva, permitindo um aumento de anos de vida, uma diminuição dos casos e mortes por CCU e um incremento de QALYs. O RCEI variou entre 7.914€/QALY e 29.049€/QALY com a vacinação aos 26 e aos 45 anos, respetivamente, para a alternativa de vacinação mais rastreio versus a situação atual de rastreio organizado e oportunístico, em Portugal.
ABSTRACT - Cervical cancer represents an important public health problem in Portugal: it is the third most frequent cancer in women between 15 and 44 years, leading to the death of 346 women annually. However, this disease is largely avoidable, namely, through the immunization against HPV infection, which is necessary to cause the development of cancer. The high prevalence of infection in older women suggests that vaccination may be a cost-effective strategy even in an older age group. If public reimbursement of the vaccine in these women is to be considered, it is necessary to perform a pharmacoeconomic study examining the cost-effectiveness of this intervention, since current arrangements permit only women between 18 to 25, not covered by Portuguese National Vaccination Programme, to be reimbursed. The objectives of this study are to review the literature on economic evaluation studies about the prevention of cervical cancer and to assess the cost-effectiveness of vaccinating women against HPV between 26 and 55 years old compared with current clinical practice in Portugal. The study uses the Global Cervarix® Model and carries out cost-utility and cost-effectiveness analyses. The results demonstrated that vaccination in women 26 to 45 years can be a cost-effective option, allowing an increase in life years, a reduction in cervical cancer cases and deaths and an increase in QALYs. The ICER ranged from 7.914€/QALY and 29.049€/QALY with vaccination at 26 and 45 years, respectively, for the alternative of vaccination plus screening versus the current situation of organized and opportunistic screening in Portugal.

A gestão do processo saúde/doença tem requerido somas cada vez maiores de recursos especialmente àqueles destinados à aquisição de medicamentos em hospitais de porte especial, devido à complexidade dos procedimentos, incorporação de novas tecnologias, visando não só o acesso, mas, também a qualidade de vida da população assistida. Uma das estratégias possíveis para a minimização dos custos hospitalares com a aquisição de medicamentos é instalação de farmácia semi-industrial para a produção dos mesmos, após rigoroso estudo de viabilidade econômica. Neste contexto esta investigação teve como objetivo estabelecer estratégia de estudo farmacoeconômico para avaliar a viabilidade de implantação de farmácia semi-industrial para produção de medicamentos em hospital de porte especial da rede pública. Para tanto foi realizado um estudo do consumo e dos gastos hospitalares com medicamentos nos anos 2006/2007, visando conhecer as classes que aliassem maior consumo e valor monetário e seus requisitos para a manufatura. As formas farmacêuticas que despertaram maior expectativa de produção foram os medicamentos na forma sólida (comprimidos simples e revestidos), os injetáveis de pequeno volume e os pós liofilos injetáveis. Para estes foram planejadas as instalações (área física e equipamentos), matérias-primas e recursos humanos necessários para a produção. A análise de viabilidade farmacoeconômica foi realizada considerando valores médios para as formulações, incluindo excipiente e fármaco, custos de implantação e implementação. O estudo demonstrou que a produção hospitalar de medicamentos é viável sob o ponto de vista farmacoeconômico, pois o investimento se paga no primeiro mês e a partir deste passa a reduzir os gastos hospitalares com medicamentos, ou seja, começa a dar lucro e gerar benefícios para a sociedade.
The health/sickness process management has required greater sums of resources specially those destinated to medicines acquisition in special port hospital, due to complexity of proceeding, incorporation of new technology, having in view not only the access but, also the assisted population quality of life. One of the possible strategies for hospital cost minimization with medicines acquisition is the installation of a semi industrial pharmacy, to product these medicines, after an accurate of economic viability. In this context, this investigation aimed establish pharmacoeconomics study strategy to evaluate the implantation of semi industrial pharmacy for medicine production in special port hospital of the public service. For this a study of the consumption and the hospital expenses with medicine was realized in 2006/2007, having a view to know the classes that ally a greater consumption and monetary value and its requisite for manufacture. The pharmaceutic forms that excit a greater production expectative were the solid form medicines (simple and coated tablets), the injectables of small volumes, and injectable liofile powder. For this the necessary installations (physical area and equipments), raw material and human resources were planned for the production. The pharmacoeconomics viability analysis was realized considering medium values for the formulations including excipients and drug, implantation and implementation costs. The study has showed that the medicine hospital productions is viable under the pharmacoeconomics point of view because the investment is paid in a month and after that the hospital expenses with medicines are reduced, so its begins to give profit and benefits for the society.

Introduction: Prescription drug monitoring programs (PDMPs) are one strategy established to curb the prescription opioid abuse epidemic. Prescriber use mandates has emerged as a promising practice to increase PDMPs impact on prescription opioid abuse; however, evidence of its effectiveness has not yet been established. Kentucky was the first state to implement comprehensive prescriber use mandates in July 2012. Objective: To assess the relationship between prescriber use mandates policy and emergency department (ED) visits related to prescription opioid poisoning among adults in Kentucky and North Carolina. Secondary aim: to evaluate the economic impact of prescriber use mandates in Kentucky. Methods: A controlled, pre-post study design. Data from the State Emergency Department Databases (SEDD) and the State Inpatient databases (SID) were used to identify prescription opioid poisoning ED visits among those ≥ 12 years old. Prevalence rate were estimated. Prescription opioid poisoning ED visits were characterized based on sociodemographic and clinical characteristics. Logistic regression was applied to compare occurrences of prescription opioid poisoning ED visits pre and post prescriber use mandates in Kentucky, and between Kentucky and North Carolina for the period 2011 to 2014. A cost of illness framework was applied to estimate direct medical costs associated with prescription opioid poisoning ED visits. The economic impact of prescriber use mandates was quantified based on logistic regression coefficient for the interaction term (state*time to implementation). Results: There were 7,419 and 12,598 prescription opioid poisoning -related ED visits in Kentucky and North Carolina, respectively. Young and Middle age, male gender, white, having one or more chronic conditions, and psychiatric conditions (such as depression and drug abuse) were significantly associated with prescription opioid poisoning ED visits (p-value<0.05). The odds of having a prescription opioid poisoning ED visit in Kentucky were significantly lower compared to North Carolina in 2012, 2013, and 2014 compared to 2011 (OR = 0.9, 0.7, and 0.7 respectively). The total estimated direct medical costs were $13.77 and $24.37 million in Kentucky and North Carolina, respectively. In Kentucky, the economic impact of prescriber use mandates was estimated at - $2.3 million. Conclusion: Prescriber use mandates is effective in reducing prescription opioid poisoning ED visits, and its economic impact is considerable.

A albumina humana (AH) é um medicamento de ampla utilização e de custo elevado que integra o elenco de procedimentos especiais do Ministério da Saúde no Brasil. Em 2004, a ANVISA publicou uma resolução que estabelece diretrizes para o uso terapêutico deste medicamento. Apesar dos dados da literatura sugerirem conclusões não definitivas sobre os reais benefícios do uso de albumina no tratamento de pacientes com síndrome nefrótica (SN), a diretriz recomenda o uso nos casos de edemas refratários ao uso de diuréticos. O objetivo deste estudo foi avaliar através de análises econômicas a indicação clinica da diretriz para uso de Albumina Humana da ANVISA, em pacientes com Síndrome Nefrótica. A partir de uma coorte concorrente foram realizadas análises econômicas dos tipos custo-efetividade e custoutilidade. A população do estudo foi constituída por pacientes adultos e pediátricos internados com síndrome nefrótica em quatro grandes hospitais do SUS do Estado da Bahia. Os pacientes incluídos foram divididos em dois grupos comparativos conforme o seguimento ou não das orientações de uso de albumina humana da diretriz da ANVISA. A perspectiva da análise econômica foi sobre o provedor de atenção à saúde, o SUS. Os dados de qualidade de vida dos pacientes foram obtidos através de aplicação dos questionários genéricos SF36 e CHQ-PF50. O índice QALY (anos de vida ajustados à qualidade de vida) foi utilizado para a avaliação de custo-utilidade da comparação. Ao final do estudo foram selecionados 109 pacientes, com 60% de adultos, 56% do gênero feminino, mais de 90% de negros e pardos tendo 41,3% seguido as diretrizes da ANVISA. O custo médio global por internação (média de 22 dias) para o SUS foi de R$ 2.360/paciente. Os parâmetros de efetividade analisados, peso, diurese e balanço hídrico foram mais efetivos em termos de custo para os pacientes que seguiram a diretriz. A RCEI para dias de internação evitados evidenciou um custo adicional de R$55,33/dia evitado. A análise de qualidade de vida demonstrou que seguir a diretriz dominou o não seguimento propiciando um acréscimo de 8% de qualidade de vida e gerando uma economia de R$ 3.458,13 por QALY ganho. As análises de sensibilidade das RCEI e RCUI evidenciaram a robustez dos resultados, principalmente na variação do QALY, que mesmo após 60% de variabilidade garantiu economia para o sistema. Os resultados deste estudo forneceram informações sobre o uso de albumina humana em pacientes com síndrome nefrótica que podem juntamente com outros dados nortear as práticas de saúde no SUS do ponto de vista clinico e econômico. As análises econômicas indicaram que apresentam melhores relações de custo-efetividade e custo utilidade os tratamentos dos pacientes que seguiram as orientações da diretriz da ANVISA.
Human albumin (HA) is a drug widely used and of high cost that integrates the cast of special procedures of the Ministry of Health in Brazil. In 2004, ANVISA issued a resolution establishing guidelines for the therapeutic use of this drug. Although data from the literature suggest no definite conclusions about the real benefits of the use of albumin in the treatment of patients with nephrotic syndrome (NS), the guideline recommends the use in cases of edema refractory to diuretics. The aim of this study was to evaluate economic analyzes through the clinical indication of guideline for use of Human Albumin ANVISA, in patients with nephrotic syndrome. Economic analyzes of both cost-effectiveness and cost-utility types were performed from a concurrent cohort. The study population was composed of adult and pediatric patients hospitalized with nephrotic syndrome in four major public hospitals in the State of Bahia. The included patients were divided into two distinct groups according to whether ANVISA’s guidelines for use of human albumin were followed by them or not. The economic perspective of the analysis regarded the health care provider, the NHS. The quality of life data of the patients were obtained through application of generic questionnaires SF36 and CHQ - PF50. The QALY index (quality-adjusted life year) was used to assess cost-utility comparison. At the end of the study 109 patients were selected, consisting of 60% adults, 56 % females, over 80 % blacks and dark-skinned, where 41.3 % followed the guidelines of ANVISA. The overall average cost per hospitalization (22 days average) to the NHS was R$ 2.360/patient. The analyzed parameters, weight, urine volume, and fluid balance were more effective in terms of cost for patients who followed the guidelines. The ICER for days of hospitalization avoided showed an additional cost of R$55.33/avoided day. The quality of life analysis showed that the majority followed the guidelines providing an increase of 8 % for quality of life and generating savings of R$ 3,458.13 per QALY gained. Sensitivity analyzes of the ICER and ICUR showed the robustness of the results, especially the variation of the QALY, which even after 60% of variability guaranteed savings for the system. The results of this study provided information on the use of human albumin in patients with nephrotic syndrome that can, along with other data, guide health care practices in the NHS from both clinical and financial standpoints. The economic analyzes that show better the costeffectiveness and cost utility of treatment patients who followed the recommendations the guideline of ANVISA.

博士
高雄醫學大學
藥學研究所
98
Objective: To evaluate the usage for stress-related upper gastrointestinal bleeding prophylaxis in a medical center in Taiwan and examine the efficacy and safety of proton pump inhibitors (PPIs) in comparison with histamine-2 receptor antagonists (H2RAs) for stress-related upper gastrointestinal (UGI) bleeding prophylaxis among critical care patients. To perform a pharmacoeconomic evaluation to explore the most costeffectiveness agent for stress-related gastrointestinal bleeding prophylaxis. Methods: A retrospective drug usage evaluation, systematic review and meta-analysis of comparing histamine-2 receptors to proton pump inhibitors for stress ulcer prophylaxis in critically ill patients were performed. And then a decision tree analysis was performed to calculate the incremental cost-effectiveness ratio to explore the most cost-effectiveness agent for stress ulcer prophylaxis. Results and discussions: All patients with risk for stress ulcer evaluated were all prescribed PPIs and the risk of gastrointestinal bleeding was decreased when comparing to without prophylaxis. We identified 7 randomized controlled trials with a total of 936 patients for systematic review and meta-analysis. The overall pooled risk deference (95% confidence interval, p value; I2 statistics) of stress-related UGI bleeding comparing PPIs versus H2RAs was -0.04 (-0.09, 0.01, p=.08; I2=66%). In the sensitivity analysis, removing Levy study significantly reduced the heterogeneity (from I2=66% to 26%) and shifted the overall risk difference closer to the null (pooled risk difference –0.02, 95% CI –0.05 to 0.01, p=.19). There was no difference between PPIs and H2RAs therapy in the risk of pneumonia and ICU mortality with pooled risk differences of 0.00 (-0.04, 0.05, p=.86; I2=0%) and 0.02 (-0.04, 0.08, p=.50; I2=0%) respectively. In the pharmacoeconomic analysis, enteral PPIs were the most cost-effectiveness agents for stress ulcer prophylaxis. Conclusions: This study did not find strong evidence that PPIs were different from H2RAs in terms of stress-related UGI bleeding prophylaxis, pneumonia, and mortality among patients admitted to ICUs. Due to limited trial data, future well-designed and powerful randomized clinical trials are warranted. From the point of decision maker, enteral PPIs may be the best choice for prophylaxis.

Les maladies cardiovasculaires (MCV) ont une prévalence élevée dans le monde et sont considérées comme la deuxième cause de mortalité chez la population canadienne. Les statines sont reconnues comme le traitement par excellence dans la prévention des MCV. Toutefois, les statines ne conviennent pas à tous les patients, potentiellement, en raison de la survenue d’effets secondaires et du manque d’efficacité. Avec l’avancement de la science, de nouvelles thérapies voient le jour dans le milieu cardiovasculaire. Les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9 PCSK9 (iPCSK9) constituent un traitement efficace pour réduire les évènements cardiovasculaires. Cependant, ces thérapies sont dispendieuses pour le système de santé. Cette thèse a pour but d’explorer la pharmacoéconomie des thérapies dispendieuses ayant démontrées une efficacité clinique importante dans le traitement préventif des MCV. La pharmacoéconomie est un outil d’évaluation destiné aux décideurs ayant comme objectif d’optimiser l’utilisation des ressources humaines et financières. Tout d’abord, dans un premier article, nous avons évalué l’efficacité maximale d’une thérapie hypolipémiante à partir des grilles de risque cardiovasculaires. Selon les résultats obtenus, l’efficacité maximale qu’il est raisonnable d’espérer a correspondu à une diminution du risque relatif variant entre 0,46 et 0,66. Ensuite, dans un deuxième article, nous avons estimé l’efficacité d’une thérapie dispendieuse dans un contexte différent puisque les études cliniques étaient en cours. Avec l’aide d’un modèle de Markov, la propension à payer a été fixée à deux seuils distincts, alors que le coût d’acquisition de la thérapie est demeuré fixe. Nos résultats ont estimé que pour atteindre les seuils de propension à payer de 50 000 $ et 100 000 $ par année de vie ajustée pour la qualité, l’efficacité devrait être de 0,58 et 0,78 respectivement. Finalement, l’étude randomisée contrôlée établissant l’efficacité clinique des iPCSK9 a été publiée. Nous avons donc pu évaluer le coût-utilité réel des iPCSK9 avec une nouvelle méthode de simulation, nommée Conditions et évènements discrètement intégrés. Cette étude est l’objet 2 de mon troisième article. Les résultats de cet article ont estimé que l’iPCSK9 n’est pas coût-efficace selon l’efficacité obtenue dans les études cliniques. En conclusion, suite aux résultats présentés dans cette thèse rédigée par articles, il serait envisageable d’intégrer dans le modèle pharmacoéconomique l’option d’un test génétique afin d’individualiser le traitement de chaque patient.
Cardiovascular diseases (CVD) have a high prevalence worldwide and are considered the second leading cause of death in the Canadian population. Statins are recognized to be the gold standard treatment in the prevention of CVD. However, statins are not suitable for all patients, potentially because of side effects and lack of efficacy. With the advancement of science, new therapies are emerging in the cardiovascular field. Inhibitors of proprotein convertase subtilisin-kexin type 9 (iPCSK9) have been shown to be effective in reducing cardiovascular events. However, these therapies are expensive. This article-based thesis aims to explore the pharmacoeconomics of expensive therapies that have demonstrated significant clinical efficacy in the preventive treatment of CVD. Pharmacoeconomics is an evaluation tool for decision-makers with the objective of optimizing the use of human and financial resources. In the first publication, we evaluated the maximum effectiveness of lipid-lowering therapy from cardiovascular risk grids. According to our results, this maximum expected benefit fluctuates between 0.46 and 0.66. In the second publication, we estimated the effectiveness of an expensive therapy. At the time of our second publication, the results of the randomized controlled trial evaluating the clinical efficacy of iPCSK9 had not been published yet. Therefore, we used a Markov model to estimate the necessary clinical efficacy of PCSK9 inhibitors to reach two arbitrarily selected willingness-to-pay (WTP) thresholds. Our results showed that an efficacy of 0.58 and 0.78 were necessary to reach WTP thresholds of $50,000 and $100,000 per quality-adjusted life years respectively. Once the clinical efficacy of iPCSK9 was published, we evaluated their cost-utility. This was the object of our third article and a new simulation method named Discretely Integrated Condition was used. Our results suggested that at the current price, the PCSK9 inhibitors were not cost-effective. Following the results presented in this article-based thesis, it would be of interest to integrate the option of a hypothetical genetic test into the pharmacoeconomic model. This genetic test would be able to identify good responders in order to optimize the treatment of each individual patient.

Tese de mestrado, Ciências Biofarmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2018
A farmacoeconomia é uma disciplina que avalia o uso de medicamentos em termos de recursos na maximização da saúde da população. Dado que os recursos para os cuidados de saúde são finitos, a avaliação económica envolve a estimativa do custo de oportunidade, i.e., os benefícios marginais perdidos como resultado do deslocamento de tratamentos ou serviços existentes para financiar novos medicamentos. A farmacocinética é a ciência que visa o estudo do movimento de fármacos no organismo, o que inclui a absorção, distribuição, metabolismo e eliminação destes e seus metabolitos. Com o advento da química analítica e métodos de quantificação sofisticados, bem como de um aumento do poder de computação, a farmacocinética como ciência tem tido um desenvolvimento exponencial. Uma das áreas da farmacocinética que se tem desenvolvido mais é a farmacocinética populacional: apesar da farmacocinética de um fármaco poder ser estudada individualmente em cada indivíduo, a abordagem populacional é benéfica para o estudo de grupos de pacientes que são difíceis de investigar, como a população de bebés prematuros, pacientes com insuficiência hepática ou renal. Na farmacocinética populacional, cada indivíduo é avaliado simultaneamente com o modelo de efeitos mistos não-lineares (parametrização). Não linear significa que a variável dependente dessa concentração está relacionada não linearmente à associação de variáveis independentes e parâmetros do modelo. Efeitos fixos refere-se aos parâmetros que não se alteram em indivíduos, enquanto o efeito aleatório se refere àqueles parâmetros que se alteram através dos indivíduos. O principal objetivo das estimativas de modelação farmacocinética populacional é o de procurar os parâmetros de farmacocinética populacional e fonte de variabilidade. Os objetivos restantes consistem em concentrações observadas da dose administrada pela deteção das covariáveis preditivas na população avaliada. Em farmacocinética populacional, os indivíduos poderão apenas fornecer dados de concentração plasmática escassos. As cinco principais partes fundamentais para a construção de um modelo farmacocinético populacional incluem: dados, modelo estrutural, modelo estatístico, modelo de covariáveis e software de modelação. Os modelos estruturais definem o perfil de concentração plasmática ao longo do tempo nos indivíduos. Os modelos estatísticos descrevem a variabilidade aleatória na população que não é explicável (como a variabilidade entre as ocasiões), entre a variabilidade do indivíduo ou a variabilidade residual. Os modelos de covariável demonstram a variabilidade estimada pelas características da população, como covariáveis. O software de modelação, como o software de modelação de efeitos mistos não linear, permite a combinação de dados e modelos e aplica o método de estimativa para avaliar parâmetros para os modelos estatísticos, estruturais e de covariáveis que definem os dados. Na modelação farmacocinética populacional, o software possui um algoritmo de minimização do valor da função objetivo, praticando a estimativa de máxima verossimilhança. No momento da adaptação dos dados populacionais, a concentração estimada para cada indivíduo é influenciada pela variância dos parâmetros populacionais e de cada parâmetro individual, e pela variação em cada valor das concentrações previstas e observadas. A avaliação da probabilidade marginal depende dos parâmetros de efeito aleatório (η) e efeito fixo da população. Não há existência de solução analítica para verossimilhança marginal. Enquanto buscava a máxima verossimilhança, inúmeras abordagens foram aplicadas para a aproximação da verossimilhança marginal. O FOCE e o LAPLACE são as abordagens mais antigas que estimam a verdadeira verossimilhança com uma função adicional simplificada. O trabalho de dissertação no âmbito do Mestrado em Ciências Biofarmacêuticas teve por objetivo o estabelecimento de ferramentas baseadas em simulação de dados com base em modelos farmacocinéticos populacionais para uma posterior análise farmacoeconómica. Neste trabalho utilizou-se a informação disponível para a combinação fixa de Glecaprevir e Pibrentasvir (Mavyret®), medicamento usado no tratamento do vírus da hepatite C crónica. As simulações foram realizadas utilizando o software R e seu pacote Shiny. O R é uma linguagem para análise de dados de computação estatística e gráfica. A população simulada no modelo foi agrupada de acordo com as covariáveis similares, sendo simulados 1000 indivíduos por cenário. O relatório de submissão da FDA do Mavyret® foi usado como referência na modelação farmacocinética populacional. Neste relatório encontra-se descrito o modelo farmacocinético populacional desenvolvido, com base nos estudos clínicos realizados para o medicamento. No modelo descrito, foram identificadas diferentes covariáveis. O modelo descrito foi então implementado no software R e o impacto das covariáveis foi estudado com a aplicação Shiny. A população observada foi categorizada em diferentes grupos, tais como doentes tratados com Glecaprevir / Pibrentasvir com compromisso renal e doentes com compromisso renal e cirrose. Foram criados modelos individuais para cada um dos grupos e a comparação entre cada grupo e seus perfis de concentração-tempo foi realizada pelo uso do navegador R e Shiny, onde a atualização nos resultados pode ser vista automaticamente com a alteração em qualquer da covariável ou da variável. Para os diferentes modelos finais incorporados no software e para a população simulada, foram calculados os parâmetros farmacocinéticos AUC e Cmax para posterior análise estatística descritiva. Apesar da implementação dos modelos farmacocinéticos populacionais ter sido realizada em R e Shiny, e os dados terem sido simulados para os diferentes cenários populacionais, a aplicação de metodologias farmacoeconómicas não foram realizadas.
Pharmacoeconomics is the discipline concerned with optimal allocation of resources to maximize population health from the use of medicines. Given that resources for health care are finite, economic evaluation involves estimation of the opportunity cost, that is, the marginal benefits forgone as a result of displacing existing treatments or services to fund new medicines. The purpose of this study is to use tools in pharmacoeconomic analysis for the examination of the positive and adverse impact of the fixed dose combination of Glecaprevir and Pibrentasvir (Mavyret®), used to treat chronic hepatitis C virus. In order to examine the effects in pharmacoeconomics analysis, a population pharmacokinetic model was developed using R software and its package Shiny, where R is a language for data analysis of statistical computing and graphics. The population simulated in the model was grouped according to the similar covariates with the number (n) of 1000. FDA submission report for Mavyret® was used as reference regarding population pharmacokinetics modelling, developed based on the clinical studies performed for the drug product. In the described model, different covariates were identified. The described model was implemented in the R software and the impact of covariates wwas studied with Shiny application. The population observed was categorized in different groups such as patients treated with Glecaprevir/Pibrentasvir having renal impairment and patients with renal impairment and Cirrhosis. Individual models were created for each of the groups and the comparison between each group and their concentration-time profiles was observed that was made easier by the use of R and Shiny web browser where the update in results can be seen spontaneously with the change in any of the covariate or the variable. Different final models were produced and for the simulated population, the pharmacokinetic parameters AUC and Cmax were calculated for descriptive statistical analysis. Despite the implementation of population pharmacokinetics models has been accomplished in R and Shiny, and data has been simulated for different population scenarios, pharmacoeconomic modelling and application of pharmacoeconomic methodologies was not practised.

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
O desenvolvimento de novas tecnologias na área da saúde tem contribuído para a melhoria do estado de saúde e qualidade de vida da população, porém, nem toda a inovação contribui da mesma forma para o aumento dos ganhos em saúde, portanto é necessário utilizar métodos que permitam medir e avaliar o custo de oportunidade dos bens e serviços de saúde. Para valorizar os custos e benefícios relativos de cada tecnologia são utilizadas metodologias de Avaliação de Tecnologias de Saúde, cujo objetivo é apoiar a decisão de utilização e financiamento das tecnologias de saúde. O processo de financiamento dos medicamentos requer uma detalhada avaliação farmacoterapêutica e farmacoeconómica de forma a garantir racionalidade na comparticipação e aquisição. O presente trabalho pretende ilustrar a avaliação farmacoeconómica de tecnologias de saúde, nomeadamente de medicamentos, em Portugal. Inicialmente, caracteriza a avaliação de tecnologias de saúde, nomeadamente o Sistema Nacional de Avaliação de Tecnologias de Saúde. Focar-se-á na descrição da avaliação farmacoterapêutica e farmacoeconómica, de forma a garantir racionalidade na comparticipação e aquisição das tecnologias de saúde. No seguimento da avaliação farmacoeconómica apresentam-se as orientações para estudos de avaliação económica de medicamentos, dando ênfase às técnicas de avaliação económica. Na parte final referem-se não só as condições de financiamento com dados do seu valor em contexto real garantindo uma avaliação ao longo do ciclo de vida da tecnologia, como também a rede europeia para avaliação de tecnologias de saúde, nomeadamente as orientações EUnetHTA.
The development of new health technologies has contributed to improve the health and quality of life of the population. However, not all innovation contributes equally to the increase in health gains. Therefore, it is necessary to use methods to measure and evaluate the opportunity cost of health services. Health Technology Assessment methodologies are used in order to enrich the relative costs and benefits of each technology, whose purpose is to support the decision to use and fund health technologies. The funding process requires a detailed pharmacotherapeutic and pharmacoeconomic evaluation to ensure rationality in the reimbursement and acquisition. This work presents some key points regarding the pharmacoeconomic evaluation, indicating the methodological guidelines for studies of economic evaluation of medicines, namely the analysis techniques. In addition, it illustrates the re-evaluation and the European network for Health Technology Assessment.

Les nouvelles technologies médicales contribuent aux dépenses en santé qui ne cessent de croître, alors que les budgets se trouvent limités. L’évaluation économique des technologies devraient permettre d’identifier quelles sont celles qui sont les plus rentables. Malgré cela, plusieurs technologies dont le rapport coût-efficacité reste plutôt limite ou défavorable sont utilisées en médecine moderne et remboursées par notre système public de santé. Ce mémoire se concentre sur deux technologies en santé cardiovasculaire dont le rapport coût-efficacité est plutôt limite mais qui sont fréquemment utilisées au Canada; les tuteurs médicamentés ou pharmaco-actifs et les défibrillateurs cardiaques implantables (DCI). Nous avons fait une évaluation contingente de ces technologies dans le but d’examiner si ce type d’évaluation économique complémentaire pouvait procurer un point de vue nouveau sur la valeur économique et sociétaire des ces technologies. Les résultats de ces deux évaluations indiquent que les patients accordent une grande importance aux bénéfices que procurent ces deux technologies. Nos résultats soutiennent les politiques de santé actuelles de rembourser de façon libérale ces deux technologies.
Technological innovations have greatly contributed to the rising costs in healthcare, while budgets have remained limited. Economic evaluations of technologies should identify which technologies are cost-effective. However, several technologies used in modern medicine are either borderline cost-effective or even not cost-effective according to many studies. This thesis focuses on two technologies in cardiovascular medicine which are considered borderline cost-effective; drug-eluting stents and implantable cardioverter defibrillators. We conducted a contingent valuation of these technologies in hopes of determining if this alternative type of economic evaluation could give a novel point of view on the economic and societal value of these technologies. Results indicated that patients greatly valued benefits provided by these two technologies. Our result support our public healthcare system policies’ of liberal reimbursement of these two technologies.

Les nouvelles technologies médicales contribuent aux dépenses en santé qui ne cessent de croître, alors que les budgets se trouvent limités. L’évaluation économique des technologies devraient permettre d’identifier quelles sont celles qui sont les plus rentables. Malgré cela, plusieurs technologies dont le rapport coût-efficacité reste plutôt limite ou défavorable sont utilisées en médecine moderne et remboursées par notre système public de santé. Ce mémoire se concentre sur deux technologies en santé cardiovasculaire dont le rapport coût-efficacité est plutôt limite mais qui sont fréquemment utilisées au Canada; les tuteurs médicamentés ou pharmaco-actifs et les défibrillateurs cardiaques implantables (DCI). Nous avons fait une évaluation contingente de ces technologies dans le but d’examiner si ce type d’évaluation économique complémentaire pouvait procurer un point de vue nouveau sur la valeur économique et sociétaire des ces technologies. Les résultats de ces deux évaluations indiquent que les patients accordent une grande importance aux bénéfices que procurent ces deux technologies. Nos résultats soutiennent les politiques de santé actuelles de rembourser de façon libérale ces deux technologies.
Technological innovations have greatly contributed to the rising costs in healthcare, while budgets have remained limited. Economic evaluations of technologies should identify which technologies are cost-effective. However, several technologies used in modern medicine are either borderline cost-effective or even not cost-effective according to many studies. This thesis focuses on two technologies in cardiovascular medicine which are considered borderline cost-effective; drug-eluting stents and implantable cardioverter defibrillators. We conducted a contingent valuation of these technologies in hopes of determining if this alternative type of economic evaluation could give a novel point of view on the economic and societal value of these technologies. Results indicated that patients greatly valued benefits provided by these two technologies. Our result support our public healthcare system policies’ of liberal reimbursement of these two technologies.