<p>The global HIV/AIDS pandemic has emerged alongside a changing world order marked by the growing power and authority of business, new constraints on public authority and policy autonomy, and new global hierarchies, inequalities, and contradictory tendencies. These conditions have helped midwife new configurations of public and private power, authority, and relations and shaped normative and operating environments for global health governance. In these contexts, public-private partnerships emerged as an institutional experiment, ostensibly to address health governance gaps and failures, including access to HIV and AIDS medicines in the global South. This study investigates the growth and roles of private authority in health governance through the lens of four case studies of public-private partnerships intended to enhance access to HIV and AIDS medicines in the global South. The study reveals that public-private partnerships in health emerged from this history as institutional experiments, yet not convincingly as functionalist responses to governance gaps and failures. The history demonstrates that private business actors opted to engage in partnerships in the contexts of a convergence of social, political, and commercial pressures, and normative and structural transformations in the world order. The case study partnerships emerged as accommodation or <em>trasformismo </em>strategies which offered concessions in an attempt to neutralise and co-opt social contestation around treatment access, without succumbing to demands for deeper structural and legislative reforms. These strategies offer bilateral, narrow, and tactical contributions in a framework of poor design, governance, accountability, and equity considerations and obligations, and are ultimately unconvincing in their commitment or capacity to expand access to HIV and AIDS medicines. Ultimately, public-private partnerships in health present practical, strategic, and normative consequences that necessitate new approaches to reform and/or serious reconsideration of their role and prospects in global health governance.</p> / Doctor of Philosophy (PhD)

There are numerous threats to medication safety at care transitions, which are heightened for older people, because they live with multiple long-term conditions as well as polypharmacy, and have frequent hospital admissions. Whilst evidence of the severity and scale of these medicines-related problems exists, there is insufficient detail about the lived experience of post-discharge medicines management, in particular what helps or what hinders, and how better support could be enabled. This thesis, underpinned by the Medicines Research Council framework for complex intervention design, aimed to find acceptable intervention components, which would enhance patient experience. This research followed a sequential, mixed method design to: establish the evidence base through critical literature review, develop theory using an interview study grounded in behaviour change theory, and finally to model potential intervention components by expert consensus. Interviews revealed that there were gaps in current service provision, which impacted on participants’ knowledge of and capabilities with their medicines. Despite these challenges, some participants took actions to safeguard from problems after discharge. The literature review found that effective components of trialled interventions were self-management advice, post-discharge telephone follow up and medicines reconciliation. Further behaviour change techniques from the literature, alongside expert consensus and theory-driven analysis of interview findings resulted in final selection of eight potential components. Real-world implementation of these must be coupled with key changes to current healthcare practices and policy, including better engagement with patients and carers, as well as pro-active post-discharge follow-up. Future work must carefully explore how these components can be tested pragmatically.

Yes / Three dimensional printing (3DP) was used to engineer novel oral drug delivery devices, with specialised design configurations loaded with multiple actives, with applications in personalised medicine. A filament extruder was used to obtain drug-loaded - paracetamol (acetaminophen) or caffeine - filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3D printing. A multi-nozzle 3D printer enabled fabrication of capsule-shaped solid devices, containing paracetamol and caffeine, with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different from the drug in the adjacent layers; and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least squares component matching to produce false colour representations of distribution of the drugs showed clearly the areas that contain paracetamol and caffeine, and that there is a definitive separation between the drug layers. Drug release tests in biorelevant media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both drugs was simultaneous and independent of drug solubility. With the DuoCaplet design it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device, and the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods. / The full-text of this article will be released for public view at the end of the publisher embargo on 10 Oct 2016.

No / OBJECTIVES: The aims of this study were to conduct the proof of concept study and to develop and evaluate an educational intervention that promotes the evidence-based supply of non-prescription medicines (NPMs). METHOD: An educational intervention was delivered to pharmacy assistants and pharmacists in three pharmacies in England. The intervention included the provision of summaries of evidence for the treatment of four minor ailments and resulted in the preparation of evidence-based portfolios for the treatment of the following ailments: athlete's foot, cough, nasal congestion and period pain. The effect of the intervention was evaluated using a combination of direct overt observation, vignettes, self-reported behaviour and interviews. KEY FINDINGS: Evaluation data were collected from the three pharmacies. Data were derived from 3 pharmacists and 13 assistants, of whom 10 (3 pharmacists; 7 assistants) attended the training event. Comparing pre- and post-intervention practice, 8/11 (pre-) versus 5/6 (post-) observed, 46/80 versus 62/80 vignette and 25/30 versus 39/40 self-reported recommendations were evidence based. Prior to the intervention, 3/16 participants understood the role of evidence regarding the supply of NPMs compared with 16/16 post-intervention. Participants reported relying upon experiential knowledge to inform their decision making prior to the educational intervention. Thereafter, the participants reported using evidence to a greater extent. Barriers and facilitators for evidence-based practice were also identified. CONCLUSION: A one-off educational intervention increased participants' self-reported awareness and potential application of evidence to inform their supply of NPMs. Further research is needed to assess the effectiveness, long-term impact, generalisability and cost-effectiveness of this intervention for a wider range of common conditions.

Yes / Three-dimensional printing (3DP) has demonstrated great potential for multi-material fabrication because of its capability for printing bespoke and spatially separated material conformations. Such a concept could revolutionise the pharmaceutical industry, enabling the production of personalised, multi-layered drug products on demand. Here, we developed a novel stereolithographic (SLA) 3D printing method that, for the first time, can be used to fabricate multi-layer constructs (polypills) with variable drug content and/or shape. Using this technique, six drugs, including paracetamol, cffeine, naproxen, chloramphenicol, prednisolone and aspirin, were printed with dfferent geometries and material compositions. Drug distribution was visualised using Raman microscopy, which showed that whilst separate layers were successfully printed, several of the drugs diffused across the layers depending on their amorphous or crystalline phase. The printed constructs demonstrated excellent physical properties and the different material inclusions enabled distinct drug release profiles of the six actives within dissolution tests. For the first time, this paper demonstrates the feasibility of SLA printing as an innovative platform for multi-drug therapy production, facilitating a new era of personalised polypills.

Yes / Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate …

This research, with the main focus on HIV/AIDS, tuberculosis and malaria, was based on data from the literature, and on questionnaire and interview surveys with the main stakeholders: authorities, drug-developers and NGOs/foundations. It revealed the following determinants, which contributed to the occurrence of drug pricing conflicts in Brazil, Thailand and South Africa: governmental constitutional commitments to supply medicines to poor people, the existence of a local pharmaceutical industry capable of producing generic versions of patented medicines and long histories of disease treatment programmes. The research documented the preferred approaches to increase global access to life-saving medicines for the next decade, which were found to be: public-private-partnerships, prevention measures, dedication of >0.5% of GNP to poor countries, and improvement of national healthcare/insurance systems. Those approaches were integrated into a conceptual framework, which could enable country-level organizations to move beyond the conflict mentality via a 'Public-Private-Partnership for gradual Self-Sufficiency and Sustainability Model,' (P3S3). Within this framework, rich countries should invest >0.5% of their GNP to help to alleviate poverty in poor countries. With these funds, national governments should implement programmes to expand implementation of disease prevention measures and improve national - 4 - healthcare/insurance systems and the quality of the medicines involved. Public-private-partnerships should act as 'steering-and-controlling' organizations to guide the process and to minimise corruption. As a positive message to all who currently lack access to these medicines, the thesis author's conclusion is that the use of this model could help to turn the current unsustainable development policies into sustainable ones, and as a consequence, it would contribute to improvements in the quality of life of millions of people in poor countries.

Si hier les guérisseurs revendiquaient uniquement le besoin de reconnaissance, aujourd’hui, ils se battent plutôt pour que la reconnaissance qui leur a été accordée par l’État soit capable d’intégrer les conceptions africaines de la maladie et des thérapies ; de les protéger au même titre que les biomédecins dans l’exercice de leur profession ; de protéger les malades en cas de préjudices moral et physique. Ils craignent que la reconnaissance [accordée] ne soit pas reconnue juridiquement par une loi camerounaise qui régule leurs pratiques de soins. Dans la mesure où, sans une reconnaissance juridique et institutionnelle, il leur est impossible de se maintenir dans l’espace [public] de sociabilité thérapeutique ; de changer, à partir de la position illégitime, leurs conditions de praticiens précaires, et surtout leur relation aux usagers de soins [les mères] et aux biomédecins. Dans cette perspective, on se demande quelles sont les modalités d’intéressement ou de désintéressement mutuel qui permettent aux guérisseurs – affaiblis institutionnellement – et aux biomédecins – fortement reconnus – d’évoluer vers une réciprocité de perspectives. L’étude cherche à identifier les modes d’arrachement à l’affaiblissement institutionnel, en s’intéressant, d’un côté, aux processus de capacitation et de renforcement de la légitimité ; et de l’autre, à l’impact de ce renforcement, d’abord, sur la redéfinition des objets et figures de la rencontre et de la reconnaissance, et ensuite, sur la reconfiguration de l’espace de soins et du profil du thérapeute camerounais contemporain. Pour répondre à cet objectif, nous avons sollicité le cadre théorique de la sociologie des épreuves d’inspiration pragmatiste [Thévenot, Boltanski, Gennard et Cantelli] et de l’anthropologie capacitaire [Ricœur]. Les observations de consultations en Maisons de Soins [chez les guérisseurs] et au Centre Mère et Enfant [Hôpital pédiatrique] et les entretiens individuels effectués à Yaoundé [Cameroun] ont engendré une réflexion sur le sens que donnent les mères, guérisseurs et biomédecins au fait de rencontrer ou de refuser de rencontrer un soignant. L’analyse des données recueillies inscrit la rencontre dans l’axe de la reconnaissance capacitaire [des compétences], permettant ainsi d’envisager une pluralité de figures de la reconnaissance et de la rencontre. Elle indique aussi que si la formation à l’identité professionnelle biomédicale constitue pour les guérisseurs une tactique de renforcement de leur légitimité, l’inscription en médecines africaines de certains biomédecins [résistants ou non conformistes] les prédisposent à une résistance institutionnelle aux normes biomédicales ; ce qui permet de nuancer, au regard de la pluralisation et de la diversification des rationalités en jeu, la compréhension du caractère monolithique des institutions. Il en résulte une réflexion sur le brouillage des frontières entre les médecines africaines et la biomédecine, ce brouillage ayant alors comme conséquences, entre autres, une possible fragmentation ou morcellement de ces médecines en termes de «biomodernisation» des médecines africaines et de «traditionalisation» de la biomédecine en contexte africain. / If yesterday the need for recognition was the core claim among traditional health practitioners, today, their quest resides in the recognition not only of their practice but also of the African conceptions of diseases and therapies; in their protection as profesionnals (such as biomedical health practictioners); in the protection of patients in case of moral or physical prejudices. The traditional health practitioners fear that their recognition will not extend to or be sanctioned by Cameroonian law, which regulates their care practices. Without legal and institutional recognition, it is impossible for these practitioners to remain in the social care space; to change, from their illegitimate position, their condition of precarious practitioners, and especially their relationship to biomedical health practitioners. Thus, what are the modalities of mutual interestedness or disinterestedness that allow traditional [institutionally weakened] and biomedical practitioners [strongly recognized] to evolve towards reciprocity of perspectives? The study is seeking to identify modes of wrenching from the institutional weakening, focusing, on one hand, on empowerment and reinforcing processes of healers’ legitimacy; and on the other hand, to the impact of empowerment on the redefinition of objects and figures of encounter and of recognition, on the reconfiguration of social care space and the profile of the therapist. To achieve this objective, we have sought the reference framework of sociology of proofs and the anthropology of capacity of Ricœur. The observations of consultations in «Maisons de Soins» and to the «Centre Mère et Enfant» and interviews have led to a reflection on the interpretation associated by mothers, traditional and biomedical health practitioners to what it means to consult or refuse to consult traditional healer or biomedical practitioner. The analysis of data situates the encounter in the axis of capacity of recognition, allowing us to consider multiple figures of recognition and of encounter. It shows that if the adoption of the biomedical professional identity constitutes for traditional health practitioners a tactic of reinforcement of their legitimacy, the integration in African medicines of some biomedical health practitioners predispose them to an institutional resistance to biomedical norms; making it possible to nuance the comprehension of the monolithic character of institutions, given pluralization and diversification of rationalities at stake. This results in a reflection on blurring of frontiers of African medicines and biomedicine, thus giving place to a possible fragmentation of these medicines in terms in terms of biomodernization of African medicines and traditionalization of biomedicine.

A aprovação da Estratégia Global e do Plano de Ação sobre Saúde Pública, Inovação e Propriedade Intelectual (GSPOA), no âmbito da Organização Mundial da Saúde (OMS), está baseada na percepção da necessidade de melhoria nas condições de acesso dos países em desenvolvimento a medicamentos e outros produtos que atendam às suas necessidades específicas de saúde pública. Para tanto, a GSPOA está dividida em 8 elementos principais, 25 subitens, distribuídos por 108 pontos de ação, que visam aumentar a eficácia na promoção da inovação dentro dos países, através do desenvolvimento institucional, investimento e coordenação de áreas relevantes para a inovação em saúde. Nesse contexto, o escopo da presente investigação doutoral consiste em perscrutar os desafios para a plena implementação da referida política internacional no Brasil. Trata-se de estudo de caso - enquanto método de investigação qualitativa - que tem sua aplicação quando o pesquisador busca uma compreensão extensiva e com mais objetividade e validade conceitual, do que propriamente estatística. Perquiriu-se, destarte, políticas públicas nacionais, observando racionalmente se promoveram alguma alteração efetiva no âmbito interno, relacionadas com a pesquisa e desenvolvimento e ao acesso a medicamentos seguros, eficazes, de qualidade, e, principalmente, a preços acessíveis. Partindo de uma perspectiva crítica, e marcos teóricos consagrados, buscou-se situar a GSPOA num contexto de saúde transnacional em uma era de globalização, e os desafios para implementar mais completamente um direito à saúde, que transcenda medicamentos e exigências individuais, e que promova a reconsideração da relação sistêmica entre pesquisa farmacêutica, interesse comercial e assistência à saúde pública. Observamos que, para o período de 2008-2015, houve um processo de recrudescimento das políticas de inovação na seara da saúde, bem como êxito na promoção de iniciativas relativas à identificação de lacunas, e na formulação de estratégias que priorizam explicitamente a pesquisa e desenvolvimento em doenças negligenciadas de maior incidência no país. No entanto, verificou-se que tais ferramentas ainda são insuficientes para a efetiva superação do hiato tecnológico, e do déficit público referente às importações de insumos para o setor saúde. Um dos principais desafios relacionados com a inovação em saúde seria justamente colocar o sistema universal de saúde em posição de centralidade no âmbito das políticas do Estado. Em suma, tem-se que tais desafios têm origem orçamentário-financeira, normativa e institucional. Orçamentário-financeira porque o subfinanciamento do SUS é histórico, impactando nas demandas de pesquisa e desenvolvimento na seara sanitária. Quanto ao aspecto normativo, contata-se que opções equivocadas, especialmente quando da promulgação da Lei de Propriedade Industrial (nº 9.279/1996), comprometem a instrumentalização de políticas progressistas para que a propriedade intelectual responda melhor às reais necessidades de saúde pública. Em relação ao marco institucional, constatou-se que o diálogo entre os órgãos da Administração Pública, envolvidos na seara do acesso a medicamentos, em suas mais diversas interfaces, tem sua ação prejudicada diante da sobreposição dos interesses econômicos frente à segurança sanitária. A superação de tais entraves, para a plena implementação da GSPOA no Brasil, é deveras imprescindível, numa ação positiva no contexto do direito social à saúde e ao acesso universal a medicamentos / The approval of the Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPOA) within the framework of the World Health Organization (WHO) is based on the perception of the need to improve the access conditions of developing countries to medicines and other products that meet your specific public health needs. To this end, GSPOA is divided into 8 main elements, 25 sub-items, distributed by 108 action points, aimed at increasing efficiency in promoting innovation within countries, through institutional development, investment and coordination of areas relevant to innovation in health. In this context, the scope of this doctoral research consists of examining the challenges for the full implementation of this international policy in Brazil. It is a case study - as a method of qualitative research - that has its application when the researcher seeks an extensive understanding and with more objectivity and conceptual validity, than properly statistical. National public policies have been sought, rationally observing whether they have promoted any effective changes at the internal level related to research and development and access to safe, effective, quality and, above all, affordable medicines. From a critical perspective, and with established theoretical frameworks, the aim was to situate the GSPOA in a transnational health context in an era of globalization, and the challenges to more fully implement a right to health, which transcends medicines and individual demands, and promotes the reconsideration of the systemic relationship between pharmaceutical research, commercial interest and public health assistance. We note that, for the period 2008-2015, there was a process of strengthening innovation policies in health, as well as successful initiatives to identify gaps, and the formulation of strategies that explicitly prioritize research and development in neglected diseases of greater incidence in the country. However, it was verified that such tools are still insufficient for the effective overcoming of the technological gap, and of the public deficit regarding imports of inputs for the health sector. One of the main challenges related to health innovation would be precisely to place the universal health system in a position of centrality within the scope of State policies. In summary, these challenges have a budgetary-financial, normative and institutional origin. Budgetary-financial because SUS underfunding is historical, impacting the demands of research and development in the sanitary seara. Regarding the normative aspect, it is suggested that misguided options, especially when promulgating the Industrial Property Law (No. 9.279 / 1996), compromise the use of progressive policies so that intellectual property responds better to the real needs of public health. In relation to the institutional framework, it was found that the dialogue between the Public Administration organs, involved in the area of access to medicines, in its most diverse interfaces, is affected by the overlapping of economic interests in relation to health security. The overcoming of such obstacles, for the full implementation of the GSPOA in Brazil, is indeed essential, in a positive action in the context of the social right to health and universal access to medicines

Introdução. Medicamentos não licenciados e sem indicação são utilizados com grande frequência em pediatria por razões éticas e econômicas. A utilização destes medicamentos não constitui um preceito ilegal, mas pode oferecer risco aos pacientes, sendo responsabilidade do médico e do farmacêutico qualquer evento adverso ocasionado. Alguns estudos nesta população sugerem aumento do risco de reações adversas relacionadas ao uso de medicamentos fora das indicações licenciadas. Objetivo. Analisar a exposição a medicamentos não licenciados e sem indicação em neonatos admitidos em Unidade de Terapia Intensiva (UTINEO) em hospital universitário de média complexidade de São Paulo, Brasil. Método. Estudo descritivo transversal dos medicamentos prescritos nas primeiras 24 horas de internação para 79 pacientes admitidos na Unidade de Terapia Intensiva Neonatal, do Hospital Universitário da Universidade de São Paulo (HU-USP), campus de São Paulo, no período de 12/03/08 a 03/11/08. Os medicamentos foram classificados em não licenciados e sem indicação para utilização por população neonatal de acordo com critérios de registro brasileiros e americanos. Resultados: foram prescritos 346 medicamentos. De acordo com os critérios brasileiros de licenciamento 58% não estavam licenciados, 9,5% não eram indicados, sendo que 66 % dos pacientes foram expostos a ao menos 1 item não licenciado e 18% a pelo menos 1 item sem indicação. A avaliação com base nos critérios americanos demonstrou que 53% dos medicamentos não estavam licenciados, 10,9% não tinham indicação, sendo que 63% dos pacientes foram expostos a ao menos 1 item não licenciado e 20% a pelo menos 1 item sem indicação.Conclusões: Os neonatos brasileiros estão expostos a medicamentos não licenciados e sem indicação nas primeiras 24 horas de internação. Embora esforços tenham sido empregados em diversos países para diminuir tal prática, o problema não foi equacionado. No Brasil, ainda, há informações distintas em bulas de medicamentos licenciados e, em relação, aos medicamentos não licenciados ou sem indicação não há nenhuma política estabelecida. / Introduction. In pediatrics utilization of unlicensed an off-label drugs are a common practice and this account for ethical and economic reasons. The utilization of unlicensed and off label drugs is not illegal, but can expose patients to risk of harm. Physicians and pharmacists have legal responsibility for any adverse event that may result from this use. Some studies in the pediatric field suggest an increased risk to adverse reactions related to unlicensed and off label use. Objective. To assess the exposure to unlicensed and off-label medicines in neonates admitted to the Neonatal Intensive Care Unit (NICU) in a Brazilian medium complexity University Hospital. Materials and Methods. A cross sectional descriptive study was conducted of prescribed medicines in the first 24 hours of admission for 79 patients admitted to the Neonatal Intensive Care Unit (NICU) in the University Hospital of the University of São Paulo (HU-USP), campus of São Paulo in the period of 12/03/08 to 03/11/08. The medicines were classified as unlicensed and off-label for use in neonatal population according to the criteria for licensing of medicines in Brazil and US. Results: There were a total of 346 medicines prescribed and according to the established criteria in Brazil 58% were unlicensed, 9.5% were off-label; 66% of patients were exposed to at least 1 item unlicensed and 18% at least 1 item off-label. In relation to the criteria in USA 53% were not licensed, 10.9% were off-label, and 63% of patients were exposed to at least 1 item unlicensed and 20% at least 1 item off-label. Conclusions: Brazilian neonates are exposed to unlicensed and off-label medicines already in the first 24 hours of hospitalization. Although efforts have been employed in several countries to reduce this practice, the problem was not solved. In Brazil, there is even different information in leaflets for medicines licensed in and, in relation, to unlicensed or off-label medicines there is no established policy.