Compounded drugs as an alternative to the therapeutical gaps of inborn errors of metabolism

Abstract Inborn errors of metabolism are rare disorders with few therapeutic options for their treatments, which can make patients suffer with complications. Therefore, compounded drugs might be a promising option given that they have the ability of meeting the patient's specific needs, (i) identification of the main drugs described in the literature; (ii) proposal of compounding systems and (iii) calculation of the budgetary addition for the inclusion of these drugs into the Brazilian Unified Health System. The research conducted a literature review and used management data as well as data obtained from official Federal District government websites. The study identified 31 drugs for the treatment of inborn errors of metabolism. Fifty eight percent (58%) (18) of the medicines had their current demand identified, which are currently unmet by the local Health System. The estimated budget for the production of compounded drugs was of R$363,16.98 per year for approximately 300 patients. This estimated cost represents a budgetary addition of only 0.17% from the total of expenditures planned for drug acquirement. There is a therapeutic gap for inborn errors of metabolism and compounding pharmacies show potential in ensuring access to medicine therapy with a low-cost investment.

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, identified, among the medicines considered essential to the Brazilian health context, those unavailable, for which strategies were evaluated to mitigate the identified unavailability, which is conventionally called therapeutic gaps. For 57% (n = 235) of pharmaceutical presentations identified as therapeutic gaps in SUS, manipulation was identified as the best strategy to promote access. Of these presentations, 30% (n = 70) were identified as priorities in the context of patient care and were mainly related to the demands of the pediatric public and those affected by poverty-related diseases. Concerning poverty-related diseases, the absence of evidence on the development of a standard formula for drugs with indication for such diseases was demonstrated. The need for an annual investment of approximately US$74.75 per capita was estimated to offer treatments in adequate presentations to SUS users, which should reflect in the improvement of the quality of life of about 26 thousand people. It was observed that this investment amount corresponds to only 3% of the budget for the purchase of medicines financed exclusively by the Ministry of Health thorugh the Strategic Component of Pharmaceutical Assistance (CESAF) approved for 2021.

The different clinical guideline standards in Brazil: High cost treatment diseases versus poverty-related diseases.

Each year, evidence-based clinical guidelines gain more space in the health professionals' practice and in services organization. Due to the scarcity of scientific publications focused on diseases of poverty, the development of well-founded clinical guidelines becomes more and more important. In view of that, this paper aims to evaluate the quality of Brazilian guidelines for those diseases. The AGREE II method was used to evaluate 16 guidelines for poverty-related diseases (PRD) and 16 guidelines for global diseases whose treatment require high-cost technologies (HCD), with the ultimate aim of comparing the results. It was found that, in general, the guideline development quality standard is higher for the HCD guidelines than for the PRD guidelines, with emphasis on the "rigour of development" (48% and 7%) and "editorial independence" (43% and 1%) domains, respectively, which had the greatest discrepancies. The HCD guidelines showed results close to or above international averages, whereas the PRD guidelines showed lower results in the 6 domains evaluated. It can be concluded that clinical protocol development priorities need some redirecting in order to qualify the guidelines that define the healthcare organization and the care of vulnerable populations.

The regulation and adoption of health technologies under Brazil's Unified Health System: barriers to access to medicines for diseases of poverty? / Registro e incorporação de tecnologias no SUS: barreiras de acesso a medicamentos para doenças da pobreza?

The study aimed to examine the regulation and adoption of health technologies for the diseases of poverty in the Brazil's Unified Health System (SUS). An exploratory, descriptive study was conducted between January and May 2016 consisting of the search and analysis of relevant documents on the websites of Brazil's National Health Surveillance Agency, the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the National Commission for the Adoption of Technologies by the SUS, and Saúde Legis (the Ministry of Health's Legislation System). The 2014 version of the Brazilian National List of Essential Medicines (RENAME, acronym in Portuguese) contained 132 medicines for diseases of poverty. Over one-third of these (49) had only one national producer, while 24 were not registered in the country. The number of medicines contained in the RENAME dedicated to this group of diseases increased by 46% between 2006 and 2014. Despite advances in the regulation and incorporation of technologies by the SUS, given the lack of market interest and neglect of diseases of poverty, the government has a vital role to play in ensuring access to the best available therapies in order to reduce health inequalities. It therefore follows that Brazil needs to improve the regulation of medicines that do not attract market interest.

Registro e incorporação de tecnologias no SUS: barreiras de acesso a medicamentos para doenças da pobreza? / The regulation and adoption of health technologies under Brazil´s Unified Health System: barriers to access to medicines for diseases of poverty?

Resumo O presente trabalho buscou verificar os aspectos relacionados ao registro sanitário e à incorporação de tecnologias no SUS para as doenças da pobreza. Trata-se de estudo exploratório, descritivo, desenvolvido entre janeiro e maio de 2016, em que foram realizados levantamentos e análises de documentos nos sítios eletrônicos da Anvisa, FDA, EMA, Conitec e Sistema Saúde Legis. Verificou-se um total de 132 medicamentos elencados na Rename 2014 para atendimento específico das doenças da pobreza, sendo que mais de um terço (49) possuem apenas um produtor nacional e outros 24 não possuem registro no país. No período de 2006 a 2014 houve crescimento de 46% do número de medicamentos na Rename para tais doenças. Apesar dos avanços do SUS nos campos da regulação e incorporação de tecnologias, dado o desinteresse de mercado e a condição de negligência para as doenças da pobreza, a atuação do Estado é imprescindível para garantir o acesso às melhores terapias disponíveis, visando à redução das iniquidades em saúde. Infere-se que o Brasil precisa avançar na regulação e incorporação de medicamentos sem interesse mercadológico, agenda inconclusa que pode gerar barreiras de acesso às tecnologias para as populações vulneráveis.

Abstract The study aimed to examine the regulation and adoption of health technologies for the diseases of poverty in the Brazil’s Unified Health System (SUS). An exploratory, descriptive study was conducted between January and May 2016 consisting of the search and analysis of relevant documents on the websites of Brazil’s National Health Surveillance Agency, the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the National Commission for the Adoption of Technologies by the SUS, and Saúde Legis (the Ministry of Health’s Legislation System). The 2014 version of the Brazilian National List of Essential Medicines (RENAME, acronym in Portuguese) contained 132 medicines for diseases of poverty. Over one-third of these (49) had only one national producer, while 24 were not registered in the country. The number of medicines contained in the RENAME dedicated to this group of diseases increased by 46% between 2006 and 2014. Despite advances in the regulation and incorporation of technologies by the SUS, given the lack of market interest and neglect of diseases of poverty, the government has a vital role to play in ensuring access to the best available therapies in order to reduce health inequalities. It therefore follows that Brazil needs to improve the regulation of medicines that do not attract market interest.

Prioridades da pesquisa clínica com medicamentos no Brasil e as doenças da pobreza / Priorities of clinical drug trials in Brazil and neglected diseases of poverty

Objetivo. Identificar os ensaios clínicos com medicamentos realizados no Brasil entre 2012 e 2015, com destaque para os que envolvem doenças da pobreza. Método. Foram pesquisados os repositórios de ensaios clínicos ReBEC e ClinicalTrials.gov. Verificou-se a distribuição dos ensaios clínicos identificados em relação à carga de doenças do país e em relação ao grau de iniquidade (doenças da pobreza vs. doenças não vinculadas à pobreza). Também foram investigadas as fases dos ensaios clínicos, as instituições que conduziram os ensaios e o tipo de financiamento (privado, público ou misto). Resultados. Foram incluídos 866 ensaios clínicos, 88 identificados no ReBEC e 778 no ClinicalTrials.gov; 73 (8,5%) eram de fase I, 610 (70,5%) de fases II e III e 183 (21%) de fase IV. Foram identificados 38 ensaios (4%) enfocando as doenças relacionadas à pobreza. Quanto à carga de doenças, 734 (84,8%) ensaios abordaram as doenças não transmissíveis, que de fato representam a maior carga de doença no Brasil. A indústria farmacêutica foi a grande responsável pelo desenvolvimento de ensaios clínicos de medicamentos (55,3%). O financiamento privado predominou (57,1%); entretanto, considerando-se apenas os estudos com doenças da pobreza, 63,1% foram financiados por recursos públicos. Conclusões. Os ensaios clínicos com medicamentos realizados no Brasil nos últimos anos possuem relativa conformidade com a proporção de carga de doenças. Porém, as doenças da pobreza não foram prioritárias. São necessárias ações mais efetivas para redirecionar a pesquisa clínica com medicamentos ao atendimento das necessidades nacionais.

Objective. To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. Method. Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). Results. The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. Conclusions. The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

[Priorities of clinical drug trials in Brazil and neglected diseases of poverty]. / Prioridades da pesquisa clínica com medicamentos no Brasil e as doenças da pobreza.

OBJECTIVE: To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. METHOD: Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). RESULTS: The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. CONCLUSIONS: The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

The cost of excessive postoperative use of antimicrobials: the context of a public hospital.

OBJECTIVE: To evaluate the improper use of antimicrobials during the postoperative period and its economic impact. METHODS: We conducted a prospective cohort study by collecting data from medical records of 237 patients operated on between 01/11/08 and 31/12/08. RESULTS: from the 237 patients with the information collected, 217 (91.56%) received antimicrobials. During the postoperative period, 125 (57.7%) patients received more than two antimicrobials. On average, 1.7 ± 0.6 antimicrobials were prescribed to patients, the most commonly prescribed antibiotic being cephalothin, in 41.5% (154) of cases. The direct cost of antimicrobial therapy accounted for 63.78% of all drug therapy, this large percentage being attributed in part to the extended antimicrobial prophylaxis. In the case of clean operations, where there was a mean duration of 5.2 days of antibiotics, antimicrobials represented 44.3% of the total therapy cost. CONCLUSION: The data illustrate the impact of overuse of antimicrobials, with questionable indications, creating situations that compromise patient safety and increasing costs in the assessed hospital.

The cost of excessive postoperative use of antimicrobials: the context of a public hospital / Consequências do uso excessivo de antimicrobianos no pós-operatório: o contexto de um hospital público

OBJECTIVE: To evaluate the improper use of antimicrobials during the postoperative period and its economic impact. METHODS: We conducted a prospective cohort study by collecting data from medical records of 237 patients operated on between 01/11/08 and 31/12/08. RESULTS: from the 237 patients with the information collected, 217 (91.56%) received antimicrobials. During the postoperative period, 125 (57.7%) patients received more than two antimicrobials. On average, 1.7 ± 0.6 antimicrobials were prescribed to patients, the most commonly prescribed antibiotic being cephalothin, in 41.5% (154) of cases. The direct cost of antimicrobial therapy accounted for 63.78% of all drug therapy, this large percentage being attributed in part to the extended antimicrobial prophylaxis. In the case of clean operations, where there was a mean duration of 5.2 days of antibiotics, antimicrobials represented 44.3% of the total therapy cost. CONCLUSION: The data illustrate the impact of overuse of antimicrobials, with questionable indications, creating situations that compromise patient safety and increasing costs in the assessed hospital. .

OBJETIVO: avaliar o emprego de antimicrobianos relacionado ao seu uso inadequado e impacto econômico durante o período pós-operatório. MÉTODOS: foi desenvolvido um estudo de coorte prospectivo por meio da coleta de dados de 237 prontuários de pacientes operados entre 01/11/08 e 31/12/08. RESULTADOS: dos 237 pacientes com informações coletadas no estudo 217 (91,56%) fizeram uso de antimicrobianos. Durante o pós-operatório, 125 (57,7%) pacientes utilizaram mais de dois antimicrobianos. Foi prescrito, em média, 1,7 ± 0,6 antimicrobianos por paciente, sendo o antimicrobiano mais prescrito a cefalotina, em 41,5% (154) dos casos. O custo direto da terapia antimicrobiana representou 63,78% de toda a terapia farmacológica, sendo esta grande porcentagem atribuída em parte ao prolongamento da profilaxia antimicrobiana. No caso das operações limpas, onde houve um tempo médio de uso de antimicrobianos de 5,2 dias, os gastos com antimicrobianos representaram 44,3% do custo total da terapia. . CONCLUSÃO: os dados exemplificam o impacto do uso excessivo de antimicrobianos, com indicações questionáveis e criando situações que comprometem a segurança dos pacientes e aumento os custos no hospital avaliado. .

A institucionalização da seleção de medicamentos em hospitais públicos por meio do planejamento estratégico situacional / Institutionalization of medicine selection in public hospitals through the situational strategic planning / La institucionalización del proceso de selección de medicamentos en los hospitales públicos a través de planificación estratégica situacional

Desde a publicação da primeira relação de medicamentos essenciais da Organização Mundial da Saúde (OMS), em 1977, essa instituição de saúde e diversas outras em todo o mundo têm fomentado a importância da promoção de políticas de medicamentos essenciais para os serviços de saúde. Apesar da inegável contribuição para a promoção do uso racional de medicamentos, a implantação de comitês que gerenciem a implantação de listas de medicamentos essenciais ainda é um desafio para os gestores do Sistema Único de Saúde (SUS). Este trabalho teve como objetivo utilizar uma ferramenta de gestão, proposta pelo economista Carlos Matus, para a superação das dificuldades de implantação de Comissões de Farmácia e Terapêutica nos serviços hospitalares do estado de Sergipe. Para isso, a equipe de pesquisadores realizou, em conjunto com os atores do serviço, a implantação do Planejamento Estratégico Situacional (PES) por meio dos momentos explicativo, normativo, estratégico e tático-operacional. Por meio deste trabalho, observou-se que o método PES caracteriza-se como uma ferramenta recomendada para a implantação de atividades fundamentais da seleção de medicamentos, agrupadas em três objetivos gerais alcançados: 1) a regulamentação de fluxos e procedimentos para a seleção de medicamentos; 2) a organização de comissões de farmácia e terapêutica e 3) a elaboração de listas de medicamentos essenciais.

Desde la publicación de la primera lista modelo de la Organización Mundial de la Salud (OMS) de medicamentos esenciales en 1977, este órgano y varias instituciones de salud en todo el mundo han promovido la importancia de la promoción de políticas de medicamentos esenciales a los servicios de salud. A pesar de la innegable contribución a la promoción del uso racional de los medicamentos, la implementación de los comités que administran la aplicación de listas de medicamentos esenciales sigue siendo un reto para los gestores en el Sistema Único de Salud de Brasil. Este estudio tuvo como objetivo utilizar una herramienta de gestión, propuesta por el economista Carlos Matus, para superar las dificultades de implantación del comité de farmacia y terapéutica en servicios hospitalarios en el estado de Sergipe. Para ello, el equipo de investigación ante los actores del servicio aplicaron la Planificación Estratégica Situacional (PES) por medio de los momentos explicativo, normativo, estratégico y táctico-operacional. A través de este trabajo, se observó que el método PES se caracteriza por ser una herramienta recomendable para la ejecución de las actividades clave de la selección de medicamentos, en este estudio, agrupadas en tres objetivos generales alcanzados: 1) la regulación de los flujos y procedimientos para selección de medicamentos, 2) la organización de comités de farmacia y terapéutica, y 3) la preparación de las listas de medicamentos esenciales.

Since the publication of the first list of World Health Organization (WHO)’s essential medicines, in 1977, this one and some health institutions around the world have encouraged the importance of promoting policies of essential medicines for health services. Despite the undeniable contribution to the promotion of rational use of medicines, the implementation of committees that manage the deployment of lists ofessential medicines is still a challenge for managers of the Brazilian health system (SUS). This study aimed to use a management tool proposed by economist Carlos Matus to overcome the difficulties of implementing pharmacy and therapeutic committees in hospital services of Sergipe, State of Brazil.To do it, the research team conducted with the stakeholders of the implementation of the SituationalStrategic Planning (PES) through explanatory, normative, strategic and tactical-operational moments. It was observed that the PES method is characterized as a recommended tool for the implementation of fundamental activities of of essential medicines’ selection, in this study, grouped into three general objectives achieved: 1) the regulation of flows and procedures for selecting medication, 2) the organization of pharmacy and therapeutic committees, and 3) the preparation of lists of essential medicines.