Essential Medicine Lists (EMLs) are important for the prioritization and availability of medicines around the world. Since the first Model List of Essential Medicines (MLEM) from the World Health Organization in 1977, the list has expanded from 208 to 479 medicines. The availability of essential medicines is a key priority under the World Health Organization’s Universal Health Coverage agenda & the United Nation’s Sustainable Development Goals (in particular goal 3.8 Coverage of Essential Health Services). EMLs are an important tool to inform health decisions at a country-level and at least 137 countries now have their own national EML. Despite this, there is wide variability in the methods used to develop them, and the certainty of evidence of medicines included on WHO’s MLEM and national EMLs. Additionally, a lack of coordination may result in time delays in updating EMLs or unnecessary duplication of efforts between EMLs and other evidence synthesis and health decision-making paradigms, such as health guidelines. In this thesis, we seek to understand the decision-making process for EMLs with particular focus on WHO’s MLEM, and to identify and advance opportunities to coordinate their development with health guidelines. This is accomplished through three papers, which build upon each other in this sandwich thesis. Paper 1 is a qualitative interview study with EML and guideline stakeholders to better understand decision-criteria and processes in EMLs. Paper 2 evaluates, using user-experience testing, a framework for the connection of guidelines and EMLs using an Evidence-to-Decision (EtD) framework for EMLs. Paper 3 presents a stakeholder-driven Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group concept paper exploring the conceptual challenges and opportunities of linking guidelines and EMLs using case studies on real-world implementation of this connection. / Thesis / Doctor of Philosophy (PhD) / Medicines are important for treating health conditions, and the most important medicines are called essential medicines. Essential Medicine Lists (EMLs) are created to determine what should be considered an essential medicine around the world, and also to ensure people have access to them. The number of medicines on the World Health Organization’s Model List of Essential Medicines (MLEM) has grown since it was first released, but these medicines aren’t always available to treat people who need them. Sometimes medicines that are not the most important are included on national essential medicine lists. The way that the WHO EML and national EMLs are made has been under review and criticized. Health guidelines tell people how medicines should be used, however, the connection between EMLs and health guidelines is not always consistent. Sometimes they may say different things about the same medicine. Additionally, there are differences in how EMLs and guidelines are established, and those involved do not always work with each other. In this thesis, I try to understand how decisions about which medicines are included in EMLs are made, and how they connect to health guidelines. Chapter 1 is an introduction to the topic. Chapter 2 asks experts about the decision-making process for EMLs. In chapter 3, we change a tool for guidelines to help connect guideline and EML decisions and ask for feedback regarding improvements. Chapter 4 presents the work with a group of guideline experts to present problems and suggest ways to overcome them to make EMLs and health guidelines better connected.

Yes / Medicines are often suboptimally managed for heart failure patients across the transition from hospital to home, potentially leading to poor patient outcomes. The Improving the Safety and Continuity Of Medicines management at Transitions of care programme included: understanding the problems faced by patients and healthcare professionals; developing and co-designing the Medicines at Transitions of care Intervention (MaTI); a cluster randomized controlled trial testing the effectiveness of a complex behavioural MaTI aimed at improving medicines management at the interface between hospitals discharge and community care for patients with heart failure; and a process evaluation. The MaTI included a patient-held My Medicines Toolkit; enhanced communication between the hospital and the patient's community pharmacist and increased engagement of the community pharmacist postdischarge. This paper reports on the patients' experiences of the MaTI and its implementation from the process evaluation. Twenty one-to-one semi-structured patient interviews from six intervention sites were conducted between November 2018 and January 2020. Data were analysed using the Framework method, involving patients as co-analysts. Interview data were triangulated with routine trial data, the Consolidated Framework for Implementation Research and a logic model. Within the hospital setting patients engaged with the toolkit according to whether staff raised awareness of the My Medicines Toolkit's importance and the time and place of its introduction. Patients' engagement with community pharmacy depended on their awareness of the community pharmacist's role, support sources and perceptions of involvement in medicines management. The toolkit's impact on patients' medicines management at home included reassurance during gaps in care, increased knowledge of medicines, enhanced ability to monitor health and seek support and supporting sharing medicines management between formal and informal care networks. Many patients perceived that the MaTI offered them support in their medicines management when transitioning from hospital into the community. Importantly, it can be incorporated into and built upon patients' lived experiences of heart failure. Key to its successful implementation is the quality of engagement of healthcare professionals in introducing the intervention. Patients were involved in the study design, as qualitative data co-analysts and as co-authors. / Programme Grants for Applied Research. Grant Number: RP-PG-0514-20009.

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Yes / Poor medicines management places patients at risk, particularly during care transitions. For patients with heart failure (HF), optimal medicines management is crucial to control symptoms and prevent hospital readmission. This study explored the concept of resilience using HF as an example condition to understand how the system compensates for known and unknown weaknesses. We explored resilience using a mixed-methods approach in four healthcare economies in the north of England. Data from hospital site observations, healthcare staff and patient interviews, and documentary analysis were collected between June 2016 and March 2017. Data were synthesised and analysed using framework analysis. Interviews were conducted with 45 healthcare professionals, with 20 patients at three timepoints and 189 hours of observation were undertaken. We identified four primary inter-related themes concerning organisational resilience. These were named as gaps, traps, bridges and props. Gaps were discontinuities in processes that had the potential to result in poorly optimised medicines. Traps were features of the system that could produce errors or unintended adverse medication events. ‘Bridges’ were features of the medicines management system that promoted safety and continuity which ensured that, despite varying conditions, care could be delivered successfully. ‘Props’ were informal, temporary or impromptu actions taken by patients or healthcare staff to avoid potential adverse events. The numerous opportunities for HF patient safety to be compromised and sub-optimal medicines management during this common care transition are mitigated by system resilience. Cross-organisational bridges and temporary fixes or ‘props’ put in place by patients and carers, healthcare teams and organisations are critical for safe and optimal care to be delivered in the face of continued system pressures.

This thesis explores how decentralisation of basic pharmaceutical assistance was introduced in Brazil. Decentralisation aimed to improve access to basic medicines. Nevertheless, the inconsistency in the availability of medicines in the Brazilian public health system (SUS - Unified Health System) justified the development of two seemingly contradictory, yet co-existing, approaches: decentralisation and recentralisation. The central question of my thesis was how the simultaneous processes of decentralisation and recentralisation, which took place between 1998 and 2011, have affected access to medicines distributed by SUS. My second aim was to explore how political and power dynamics impacted the implementation of decentralisation policies. I carried out semi-structured interviews with key actors in policy-making for pharmaceutical assistance; interviewees were selected from among the health secretaries and Ministry of Health officials that participated in interfederative boards of agreement. The Grounded Theory approach, as well as documentary analysis, informed my data collection and analysis. My findings suggest that decentralisation was important for improving the availability of medicines, although levels of improvement varied across the country. Decentralisation in itself was not sufficient to improve the availability of medicines largely due to the regional differences. Federative relationships involved in the decentralised management of pharmaceutical assistance are seen as important by health secretaries, but are considered laborious and time-consuming by Ministry of Health officials. Lack of compliance with agreements at state level was mentioned as one of the main barriers to further improving access to medicines. In this context of struggle, the Popular Pharmacy programme, controlled by the federal government, was created in 2004. The initiative, which can be regarded as a recentralisation process, rapidly improved the availability of basic medicines. There is no clear indication of which is the best approach for improving access to basic medicines in Brazil. Both decentralisation and centralisation worked well in some contexts but failed in others.

O presente trabalho pretende explorar o conceito de circuito superior marginal, proposto por Milton Santos em 1975. Esse conceito faz referência a um subsistema econômico presente nas cidades dos países do Terceiro Mundo. Nesse subsistema, encontramos ações que são, a um só tempo, ligadas às lógicas da modernização e dotadas de menor conteúdo em técnica, ciência e informação. Com isso, formam-se ações híbridas, que expressam tanto as racionalidades globais, instrumentais, como as racionalidades locais, comunicacionais. Para a realização desse estudo, cuidamos da produção de medicamentos no território brasileiro. Embora atentando para as novas condições de hegemonia dos laboratórios multinacionais, enfatizamos a situação dos pequenos laboratórios. Estes se dedicam a produções menos complexas e empregam técnicas e informações menos sofisticadas. Além disso, ficam submetidos ao controle político que os agentes hegemônicos passam a realizar, sobretudo em função dos aparelhos normativos que regulam as ações no território. Nessa medida, os pequenos produtores de medicamentos conformam, para a atividade farmacêutica, um circuito superior marginal. Nosso estudo quer entender as integrações desse circuito com o meio construído em várias situações urbanas brasileiras. / This work aims to explore the concept of marginal superior system, proposed by Milton Santos in 1975. This concept does reference to an economic subsystem that is presented in cities of Third World. In this subsystem we can find actions that are at the same time linked to the rationalities of the modernization and endowed with small contents in terms of technique, science, and information. Thus, hybrid actions emerge, expressing as global and instrumental rationalities as local and communicational rationalities. In order to develop this study, we are concerned about the production of medicines in the Brazilian territory. Though we consider the new conditions of hegemony from the multinational laboratories, we focused the situation of small laboratories. These latter ones develop less complex productions and employ less sophisticated techniques and information. Besides, they are submitted to the political control of the hegemonic actors, especially based on the normative tools that rule the actions in the territory. Thus, the small laboratories constitute, for the pharmaceutical activity, a marginal superior system. Our study aims to understand the linkages between this system and the built environment in several Brazilian urban situations.

O aumento do consumo de medicamentos pela população idosa brasileira e mundial no século XXI, somado ao envelhecimento populacional e relevante transição epidemiológica, apontam para a necessidade de mais estudos epidemiológicos por serem úteis ao planejamento de intervenções em saúde no âmbito coletivo. Os Estudos de Utilização de Medicamentos representam uma importante estratégia nesse sentido, por permitir a obtenção de informações sobre padrões de prescrição e uso de medicamentos, representando, desta forma, etapa de grande importância das investigações epidemiológicas. Este estudo visa estimar a prevalência e caracterizar o perfil de utilização de medicamentos na população idosa atendida pelas farmácias básicas do município de Uberaba-MG, bem como identificar os fatores mais implicados no acesso a esses medicamentos. Tratou-se de um estudo transversal, pelo qual uma amostra casual de 384 usuários de medicamentos foi entrevistada após a retirada seus medicamentos nas farmácias básicas municipais, entre março e julho de 2015, sendo utilizado um instrumento de coleta de dados, previamente padronizado e aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (CEP-FCFRP-USP). O pesquisador coletou informações sociodemográficas e relativas à saúde dos indivíduos, fotocopiou as prescrições, perguntou sobre o acesso aos medicamentos, e aplicou os testes de Batalla (TB), Med-Take (MT), Morisky-Green (MG) e o Índice da Complexidade da Farmacoterapia (ICFT). A idade média foi de 68,8 anos, sendo 70,0% do sexo feminino, renda per capita média de R$ 862,7, com predomínio de pardos (44,0%), casados (58%), com ensino fundamental incompleto (43,15%); a morbidade de maior prevalência foi a Hipertensão Arterial Sistêmica (71,95%). Dos 384 participantes, 95 (24,7%) afirmaram não recorrer à farmácia básica mais próxima de sua residência e as principais justificativas foram: fácil acesso devido às linhas de ônibus (40%) e consulta na unidade (31,6%). O perfil farmacoepidemiológico apresentou um intervalo de um a dez fármacos utilizados por paciente, com média de três fármacos/paciente; a maior prevalência foi dos medicamentos do aparelho cardiovascular (40,9%); 55,5% realizam automedicação. Conhecimento satisfatório sobre a farmacoterapia foi observado em 49,7% dos participantes; os resultados dos testes TB e MG foram de 13% e 57% de aderentes à farmacoterapia, respectivamente, não havendo correlação linear entre os resultados destes testes. O valor médio do ICFT foi de 7,3, sendo que 32,8% dos participantes possuíam terapias de alta complexidade; este índice apresentou correlação linear negativa em relação ao teste MT. A polifarmácia (uso de seis ou mais princípios ativos) esteve presente em 25,5% dos idosos, a qual não apresentou associação estatística com as variáveis sexo, estado civil, idade, renda per capita e escolaridade. 570 interações medicamentosas potenciais foram verificadas, estando 47,4% dos participantes sujeitos a pelo menos uma interação; 54,7% utilizam medicamentos considerados inapropriados ao idoso. Tais evidências reforçam a necessidade da adoção de estratégias a fim de melhorar a farmacoterapia e a assistência prestada à saúde do paciente idoso. / The increased consumption of medicines by Brazilian elderly population and world in the twenty-first century, coupled with the aging population and relevant epidemiological transition point to the need for more epidemiological studies to be useful to health interventions planning in a community basis. The Drug Use Studies represent an important strategy accordingly, to allow obtaining information on patterns of prescription and use of drugs, representing thus step of great importance of epidemiological investigations. This study aims to estimate the prevalence and characterize the profile of use of drugs in the elderly population served by basic pharmacies in the city of Uberaba-MG, and identify more factors involved in access to these drugs. It was a cross-sectional study, whereby a random sample of 384 users of drugs was interviewed after that it was withdrawing its medicines on the basic pharmacies in the city, between March and July 2015, using a previously standardized and approved data collection instrument by Ethics Committee in Research of the Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (CEP-FCFRP-USP). The researcher collected socio-demographic and health information from individuals, photocopied the prescriptions, asked about access to medicines, and applied the tests of Batalla (TB), Med-Take (MT), Morisky-Green (MG) and the Complexity Index of the Pharmacotherapy (ICFT). The average age was 68.8 years, 70.0% female, average per capita income of R$ 862.7, with a predominance of browns (44.0%), married (58%), with education incomplete elementary (43.15%); the most prevalent morbidity was Arterial Hypertension (71,95%). Of the 384 participants, 95 (24.7%) said they did not resort to basic pharmacy closest to your residence and the main reasons were: easy access due to bus lines (40%) and in consultation Unit (31.6%). The pharmacoepidemiological profile presented a range of one to ten drugs used per patient with average of three drugs/patient; the highest prevalence was among the drugs of the cardiovascular system (40.9%); 55.5% performed self-medication. Satisfactory knowledge on pharmacotherapy was observed in 49.7% of participants; the results of the TB and MG tests were 13% and 57% adherent to the pharmacotherapy, respectively, and there was no linear correlation between the results of these tests. The mean value of ICFT was 7.3, with 32.8% of participants having high complexity; this index presented a negative linear correlation in relation to the MT test. Polypharmacy (use of six or more active principles) was present in 25.5% of the elderly, which did not present statistic association with the variables gender, marital status, age, per capita income and schooling. 570 potential drug interactions were verified, with 47.4% of participants being subject to at least one interaction; 54.7% use drugs considered inappropriate to the elderly. Such evidences reinforce the need to adopt strategies to improve pharmacotherapy and health care for elderly patients.

Charles University, Faculty of Pharmacy in Hradec Kralove Department of Social and Clinical Pharmacy Author Barbora Boltnarová Supervisor PharmDr. Jan Kostriba, Ph.D. Title of Diploma Thesis Analysis of Counterfeit Medicines from the Perspective of Medicines Policy Objectives: The aim of the theoretical part of this diploma thesis was the analysis of the counterfeiting of medicinal products and a summary of the most critical topics and issues related to this illegal activity. Another purpose of the theoretical part was the mapping of trends in counterfeiting of medicinal products on the domestic and world scale and to compile a summary of the instruments used to combat counterfeiting of medicinal products. The aim of the practical part was the analysis of the reports of falsified medicinal products and to compare the obtained results with hypotheses based on theoretical knowledge. Methods: The data was obtained by analyzing the reports of counterfeit medicinal products published by State Institute for Drug Control in the period from 2nd March 2006 to 14th November 2017. Altogether, 115 reports from the Czech Republic and from abroad were analyzed. Results: The results of the analysis show that the situation regarding counterfeiting of medicinal products in the Czech Republic is relatively safe...

O aumento do consumo de medicamentos pela população idosa brasileira e mundial no século XXI, somado ao envelhecimento populacional e relevante transição epidemiológica, apontam para a necessidade de mais estudos epidemiológicos por serem úteis ao planejamento de intervenções em saúde no âmbito coletivo. Os Estudos de Utilização de Medicamentos representam uma importante estratégia nesse sentido, por permitir a obtenção de informações sobre padrões de prescrição e uso de medicamentos, representando, desta forma, etapa de grande importância das investigações epidemiológicas. Este estudo visa estimar a prevalência e caracterizar o perfil de utilização de medicamentos na população idosa atendida pelas farmácias básicas do município de Uberaba-MG, bem como identificar os fatores mais implicados no acesso a esses medicamentos. Tratou-se de um estudo transversal, pelo qual uma amostra casual de 384 usuários de medicamentos foi entrevistada após a retirada seus medicamentos nas farmácias básicas municipais, entre março e julho de 2015, sendo utilizado um instrumento de coleta de dados, previamente padronizado e aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (CEP-FCFRP-USP). O pesquisador coletou informações sociodemográficas e relativas à saúde dos indivíduos, fotocopiou as prescrições, perguntou sobre o acesso aos medicamentos, e aplicou os testes de Batalla (TB), Med-Take (MT), Morisky-Green (MG) e o Índice da Complexidade da Farmacoterapia (ICFT). A idade média foi de 68,8 anos, sendo 70,0% do sexo feminino, renda per capita média de R$ 862,7, com predomínio de pardos (44,0%), casados (58%), com ensino fundamental incompleto (43,15%); a morbidade de maior prevalência foi a Hipertensão Arterial Sistêmica (71,95%). Dos 384 participantes, 95 (24,7%) afirmaram não recorrer à farmácia básica mais próxima de sua residência e as principais justificativas foram: fácil acesso devido às linhas de ônibus (40%) e consulta na unidade (31,6%). O perfil farmacoepidemiológico apresentou um intervalo de um a dez fármacos utilizados por paciente, com média de três fármacos/paciente; a maior prevalência foi dos medicamentos do aparelho cardiovascular (40,9%); 55,5% realizam automedicação. Conhecimento satisfatório sobre a farmacoterapia foi observado em 49,7% dos participantes; os resultados dos testes TB e MG foram de 13% e 57% de aderentes à farmacoterapia, respectivamente, não havendo correlação linear entre os resultados destes testes. O valor médio do ICFT foi de 7,3, sendo que 32,8% dos participantes possuíam terapias de alta complexidade; este índice apresentou correlação linear negativa em relação ao teste MT. A polifarmácia (uso de seis ou mais princípios ativos) esteve presente em 25,5% dos idosos, a qual não apresentou associação estatística com as variáveis sexo, estado civil, idade, renda per capita e escolaridade. 570 interações medicamentosas potenciais foram verificadas, estando 47,4% dos participantes sujeitos a pelo menos uma interação; 54,7% utilizam medicamentos considerados inapropriados ao idoso. Tais evidências reforçam a necessidade da adoção de estratégias a fim de melhorar a farmacoterapia e a assistência prestada à saúde do paciente idoso. / The increased consumption of medicines by Brazilian elderly population and world in the twenty-first century, coupled with the aging population and relevant epidemiological transition point to the need for more epidemiological studies to be useful to health interventions planning in a community basis. The Drug Use Studies represent an important strategy accordingly, to allow obtaining information on patterns of prescription and use of drugs, representing thus step of great importance of epidemiological investigations. This study aims to estimate the prevalence and characterize the profile of use of drugs in the elderly population served by basic pharmacies in the city of Uberaba-MG, and identify more factors involved in access to these drugs. It was a cross-sectional study, whereby a random sample of 384 users of drugs was interviewed after that it was withdrawing its medicines on the basic pharmacies in the city, between March and July 2015, using a previously standardized and approved data collection instrument by Ethics Committee in Research of the Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (CEP-FCFRP-USP). The researcher collected socio-demographic and health information from individuals, photocopied the prescriptions, asked about access to medicines, and applied the tests of Batalla (TB), Med-Take (MT), Morisky-Green (MG) and the Complexity Index of the Pharmacotherapy (ICFT). The average age was 68.8 years, 70.0% female, average per capita income of R$ 862.7, with a predominance of browns (44.0%), married (58%), with education incomplete elementary (43.15%); the most prevalent morbidity was Arterial Hypertension (71,95%). Of the 384 participants, 95 (24.7%) said they did not resort to basic pharmacy closest to your residence and the main reasons were: easy access due to bus lines (40%) and in consultation Unit (31.6%). The pharmacoepidemiological profile presented a range of one to ten drugs used per patient with average of three drugs/patient; the highest prevalence was among the drugs of the cardiovascular system (40.9%); 55.5% performed self-medication. Satisfactory knowledge on pharmacotherapy was observed in 49.7% of participants; the results of the TB and MG tests were 13% and 57% adherent to the pharmacotherapy, respectively, and there was no linear correlation between the results of these tests. The mean value of ICFT was 7.3, with 32.8% of participants having high complexity; this index presented a negative linear correlation in relation to the MT test. Polypharmacy (use of six or more active principles) was present in 25.5% of the elderly, which did not present statistic association with the variables gender, marital status, age, per capita income and schooling. 570 potential drug interactions were verified, with 47.4% of participants being subject to at least one interaction; 54.7% use drugs considered inappropriate to the elderly. Such evidences reinforce the need to adopt strategies to improve pharmacotherapy and health care for elderly patients.

Este trabalho aborda o problema do consumo desenfreado de produtos naturais no Brasil, especificamente de medicamentos fitoterápicos, com suas consequências, discutindo à luz do Direito de Propriedade Industrial e o Direito Sanitário. Procura relacionar o papel e a responsabilidade do INPI e a ANVISA, órgãos diretamente envolvidos na legislação mencionada, para a melhoria da qualidade de produtos fitoterápicos registrados e lançados no mercado brasileiro. Mostra a necessidade de uma reavaliação dos critérios de concessão de patentes para a área analisada por parte do INPI, bem como uma maior aproximação da ANVISA junto à este órgão, de modo que harmonizem estratégias para que a população tenha acesso a medicamentos fitoterápicos seguros e eficazes. Explicita as estratégias d indústria nacional do setor em alavancar suas vendas no mercado, através de projetos de lei que não traduzem com a realidade preconizada pela OMS, para o uso da Medicina Tradicional/Complementar, contrariando a legislação brasileira para o possível registro dos produtos patenteados. Conclui-se que interesses econômicos, ligados à acirrada concorrência no mercado de fitoterápicos e suplementos nutricionais, induzem à concessão de patentes para tais produtos, em detrimento das diretrizes existentes na Lei de Propriedade Industrial brasileira, em critérios de avaliação. / This work approaches the problem of the wild consumption of natural products in Brazil, specifically herbal medicines, with its consequences, discussing to the light of the Right of Industrial Property and the Sanitary Right. It tries to relate the paper and the responsibility of INPI and ANVISA, organs directly involved in the mentioned legislation, for the improvement of the quality of products registered as herbal medicines and thrown in the Brazilian market. It shows the need of a reevaluation of the approaches of concession of patents for the area analyzed on the part of INPI, as well as larger approach of ANVISA close to this organ, so that they harmonize strategies so that the population has access to medications safe and effective herbal medicines. Explicit the strategies of the national industry of the section in it increases its sales in the market, through bills that dont translate with the strategies suggested by Oms, FOR Complementary/Alternative Medicine use, thwarting the Brazilian legislation for the possible registration on the patented products. It is ended that economic interests, linked to the intransigent competition in the herbal medicines market and nutritional supplements, induce to the concession of patents for such products, in detriment of the existent guidelines in the Law of Brazilian Industrial Property, in evaluation approaches.