A judicialização da fosfoetanolamina sintética no Brasil / The judicialization of synthetic phosphoethanolamine in Brazil

Este artigo analisou a judicialização da fosfoetanolamina sintética no Brasil, a partir de estudo exploratório das decisões judiciais da vara de fazenda pública da comarca de São Carlos, em São Paulo, após a interrupção do fornecimento da substância pela Universidade de São Paulo. O estudo catalogou os argumentos constantes da Ação Direta de Inconstitucionalidade 5.501/DF, que julgou inconstitucional a Lei n. 13.269/2016, que autorizou a produção e a prescrição da fosfoetanolamina sintética para quaisquer tipos de câncer (neoplasia maligna) enquanto os estudos clínicos não fossem concluídos. As sentenças de primeira instância concederam a fosfoetanolamina com base no testemunho dos pacientes sobre impactos positivos do uso da substância em sua saúde e pela ausência de registro de efeitos colaterais. Juízes que concederam acesso à fosfoetanolamina tinham ciência da carência de evidências científicas de segurança e eficácia, bem como do necessário registro da substância como medicamento no órgão  regulador, nos termos da legislação sanitária. No Supremo Tribunal Federal, a ausência de evidências científicas e a utilização de legislação para criar exceção casuísta levaram à declaração de inconstitucionalidade da norma pela maioria dos votos. O estudo registra, todavia, certa indisposição do Poder Judiciário em incorporar no processo decisório a avaliação das autoridades de regulação e fiscalização em saúde como fonte da correta avaliação da segurança e eficácia de medicamentos. Em conclusão, o testemunho dos pacientes sobre as perspectivas de cura ou redução do sofrimento, somado à ausência de provas nos processos judiciais sobre os riscos do consumo da fosfoetanolamina, foram cruciais para tais decisões.

This article analyzed the judicialization of phosphoethanolamine in Brazil, based on an exploratory study of court decisions in the district of São Carlos/SP after the supply of the substance was interrupted by the University of São Paulo. The study cataloged the arguments contained in the Direct Action of Unconstitutionality 5,501/DF that deemed Law 13,269/2016, which authorized the production and prescription of synthetic phosphoethanolamine for any type of câncer (malignant neoplasm) unconstitutional, while the clinical studies were not completed. The results indicated that the judges authorized the use of the substance based on the patients' testimony about the positive impacts of the use of phosphoethanolamine on their health and the absence of side effects. The judges were aware of the lack of scientific evidence of safety and efficacy, as well as the obligation to register the substance as a medicine by the regulatory agency, according to health legislation. In the Supreme Court, the mentioned lack of scientific evidence and the strategic use of legislation to create a case-by-case exception led to the declaration of unconstitutionality of the Law by a majority of Ministers votes. The study registers, however, a certain unwillingness of the Judiciary to incorporate in the decision-making process the evaluation of the health regulatory agency as a source of the correct evaluation of medicines. In conclusion, the convinced patients' testimony about the perspectives of cure or reduction of suffering added to the absence of evidence in the legal proceedings regarding the risks of the consumption of phosphoethanolamine was crucial to the judicial decisions.

Reforming the regulatory reform: general law on independent agencies in Brazil / Reformando la reforma regulatoria: Ley General de Organismos Independientes en Brasil / Reformando a reforma regulatória: Lei Geral das Agências Independentes no Brasil

Abstract This paper addresses the effects of the new general law on independent agencies in Brazil. This regulatory reform sought to increase transparency and accountability, strengthen ex-ante evaluation, and improve decision-making. The research objective was to evaluate the possible organizational and institutional consequences of these changes. The study compared data collected from key actors in the 11 agencies referring to the period before the law with the regulatory scenario one year after the law was enacted. The results allow an unprecedented panoramic view of the agencies' instruments under the inspiration of better regulation, and the new scenario can positively impact these structures' credibility and trust. The study indicates an advance in the Brazilian regulatory governance model and opens space for future research.

Resumen Este artículo investiga los efectos de la nueva Ley General de Organismos Independientes en Brasil. Esta reforma de la reforma regulatoria intentó aumentar la transparencia y la rendición de cuentas, fortalecer la evaluación ex ante y mejorar la toma de decisiones. El objetivo de la investigación fue evaluar las posibles consecuencias organizacionales e institucionales de estos cambios. A partir de la recolección de datos con actores clave de los 11 organismos, se realizó una comparación entre el período previo a la Ley y el escenario regulatorio a un año de su vigencia. Los resultados permiten una panorámica inédita de los instrumentos de los organismos, bajo la inspiración de la better regulation. Este nuevo escenario puede tener un impacto positivo en la credibilidad y confianza de estas estructuras. El estudio indica un avance en el modelo brasileño de gobernanza regulatoria y abre espacio para futuras investigaciones.

Resumo Este trabalho investiga os efeitos da nova Lei Geral das Agências Independentes no Brasil. Essa reforma da reforma regulatória buscou aumentar a transparência e a responsabilidade, fortalecer a avaliação ex ante e melhorar a tomada de decisões. O objetivo da pesquisa foi avaliar possíveis consequências organizacionais e institucionais dessas mudanças. A partir da coleta de dados com atores-chave nas 11 agências, foi feita uma comparação entre o período anterior à Lei e o cenário regulatório após um ano de sua vigência. Os resultados permitem uma visão panorâmica inédita dos instrumentos das agências, sob a inspiração da better regulation. Esse novo cenário pode impactar positivamente na credibilidade e confiança dessas estruturas. O estudo indica um avanço no modelo de governança regulatória brasileiro e abre espaço para futuras pesquisas.

Severe iron-deficiency anemia as initial manifestation of pulmonary hemosiderosis in a child.

Idiopathic pulmonary hemosiderosis is a potentially fatal disease that results from episodes of alveolar hemorrhage of unknown origin. The clinical spectrum is varied, and anemia may constitute the only manifestation of illness, preceding other signs and symptoms by several months. We present the case of a 4 year-old child presenting with fever, vomiting and prostration, associated with pallor. He had microcytic and hypochromic anemia refractory to iron therapy. Gastrointestinal bleeding was ruled out after negative extensive etiological investigation. Subsequently, pulmonary infiltrates suggestive of alveolar hemorrhage were observed in the chest radiography. The cytological exam of the bronchoalveolar lavage showed hemosiderin-laden macrophages. After the etiological study, the diagnosis of idiopathic pulmonary hemosiderosis was made by exclusion. He was initiated on corticosteroid therapy, later associated to an immunosuppressive agent, with subsequent correction of anemia and of the radiological pattern. The patient is currently asymptomatic.

Severe iron-deficiency anemia as initial manifestation of pulmonary hemosiderosis in a child / Anemia ferropriva grave como manifestaçao inicial de hemossiderose pulmonar em criança

ABSTRACT Idiopathic pulmonary hemosiderosis is a potentially fatal disease that results from episodes of alveolar hemorrhage of unknown origin. The clinical spectrum is varied, and anemia may constitute the only manifestation of illness, preceding other signs and symptoms by several months. We present the case of a 4 year-old child presenting with fever, vomiting and prostration, associated with pallor. He had microcytic and hypochromic anemia refractory to iron therapy. Gastrointestinal bleeding was ruled out after negative extensive etiological investigation. Subsequently, pulmonary infiltrates suggestive of alveolar hemorrhage were observed in the chest radiography. The cytological exam of the bronchoalveolar lavage showed hemosiderin-laden macrophages. After the etiological study, the diagnosis of idiopathic pulmonary hemosiderosis was made by exclusion. He was initiated on corticosteroid therapy, later associated to an immunosuppressive agent, with subsequent correction of anemia and of the radiological pattern. The patient is currently asymptomatic.

RESUMO A hemossiderose pulmonar idiopática é uma doença potencialmente fatal que cursa com episódios de hemorragia alveolar de etiologia desconhecida. As manifestações clínicas são variadas, e a anemia pode constituir o único sinal de doença, precedendo em vários meses os outros sinais e sintomas. Apresenta-se o caso de criança de 4 anos, com febre, vômitos e prostração, associados à palidez. Apresentava anemia microcítica e hipocrômica, refratária à terapêutica com ferro. A hipótese diagnóstica de sangramento gastrintestinal foi excluída, após investigação etiológica extensa, inconclusiva. Posteriormente, em radiografia torácica, foram observados infiltrados sugestivos de hemorragia alveolar. O exame citológico do lavado broncoalveolar mostrou macrófagos com depósitos de hemossiderina. Após estudo etiológico, assumiu-se, por exclusão, o diagnóstico de hemossiderose pulmonar idiopática. Foi iniciada terapêutica com corticoides, associada posteriormente a imunossupressor, com correção subsequente da anemia e do padrão radiológico, encontrando-se, atualmente, assintomático.

Sharing regulatory data as tools for strengthening health systems in the Region of the Americas.

Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as tools for strengthening health systems. Based on a narrative (nonsystematic) review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data) and data- and work-sharing (inter-agency data). The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1) the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics) and 2) the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

Sharing regulatory data as tools for strengthening health systems in the Region of the Americas / El intercambio de datos sobre reglamentación para fortalecer los sistemas de salud en la Región de las Américas

Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as tools for strengthening health systems. Based on a narrative (nonsystematic) review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data) and data- and work-sharing (inter-agency data). The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1) the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics) and 2) the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

La transparencia normativa es una característica indispensable de las autoridades de registro sanitario fidedignas. En la Región de las Américas, el proceso de crear un gobierno transparente sigue siendo frágil y fragmentado en distintos organismos de reglamentación sanitaria (ORS) y organismos de referencia regionales (ORR). En el presente estudio se examinó la transparencia de los ORR mediante el escrutinio de diferentes documentos con datos relativos al ciclo vital de los medicamentos (el expediente farmacológico, el informe de los ensayos clínicos y el informe de las inspecciones) como instrumentos para fortalecer los sistemas de salud. Sobre la base de una revisión narrativa (es decir, no sistemática) de la transparencia reglamentaria en los ORR, la situación relativa a la transparencia se clasificó en dos tipos: la divulgación pública de información (datos intrainstitucionales) y el intercambio de datos y la colaboración (datos interinstitucionales). Se evaluaron los riesgos y beneficios de la divulgación pública de información sobre medicamentos teniendo en cuenta (1) la participación y las funciones de los distintos interesados directos (profesionales de la salud, el sector industrial, la comunidad y el sector académico) y (2) la protección de los datos comerciales y personales de carácter confidencial. El intercambio de datos y la colaboración entre agencias se evaluaron en el contexto de diversos proyectos de armonización y cooperación dirigidos a lograr la convergencia reglamentaria. Se propone la toma de medidas técnicas y prácticas para establecer una directiva en pro de la transparencia en el medio reglamentario farmacéutico a fin de mejorar y fortalecer los sistemas de salud en las Américas. Hacer frente a estas dificultades exige el liderazgo de entidades como la Organización Panamericana de la Salud en la dirección y el respaldo de alianzas de colaboración regionales que fomenten el desarrollo y establecimiento de un entorno reglamentario fidedigno y de un sistema de salud pública sostenible en las Américas, usando como punto de partida las iniciativas internacionales que hayan dado buenos resultados y teniendo en cuenta las características internas y las experiencias de cada país.

A tool for a comprehensive assessment of treated wastewater quality.

The main goal of a wastewater treatment plant (WWTP) is to comply with the treated wastewater (TWW) quality requirements. However, the assessment of this compliance is a rather complex process for WWTPs in the EU Member States, since it requires the integration of a large volume of data and several criteria according to EU Directives 91/271/EEC and 2000/60/EC. A tool for a comprehensive assessment of TWW quality in this context is herein presented. The tool's novelty relies on an integrated analysis of performance indicators (PIs) and new performance indices (PXs). PIs integrate the several compliance criteria into a single framework, supported by flowcharts for a straightforward assessment of TWW compliance by practitioners. PXs are obtained by applying a performance function to the concentration values analysed in the TWW for discharge or reuse. PXs are dimensionless and the scale adopted (0-300) defines three performance levels: unsatisfactory, acceptable and good performance. The reference values proposed for these levels and for the PIs were based on the EU legislation. The PXs complement the information provided by the PIs. While the latter assess the plant effectiveness in a given year (i.e. the TWW compliance with the requirements), PXs tackle the plant reliability, i.e. they allow to easily compare the performance of different parameters over the time and to identify when the performance did satisfy or fail the pre-established objectives and the distance that remains to achieve these targets. The tool was tested in 17 WWTPs and the most representative results are herein illustrated.

Translating removal efficiencies into operational performance indices of wastewater treatment plants.

Removal efficiencies are often used to assess the performance of a single or a group of unit operations/processes (UOPs) of a wastewater treatment plant (WWTP). However, depending on the influent concentration (Cin), the same efficiency of removal (Er) may be insufficient or excessive to achieve the UOP or WWTP effluent quality requirements, expressed by concentration limit values (LVs). This paper proposes performance indices (PXs), Er-based, as new metrics for benchmarking, i.e. for assessing and improving the performance of each UOP or treatment step and ultimately of the WWTP as a multi-barrier system, and comprehensively describes the stepwise method of translating Ers into PXs. PXs are dimensionless and vary between 0 and 300 to define three performance levels: unsatisfactory (0-100), acceptable (100-200) and good (200-300) performance. The method developed takes into consideration Cin and LV, and the reference values for judging the performance are given from Er-Cin typical ranges and Er vs. Cin model curves, LV based and field data based. The general equations of the Er model curves are derived. A set of six curves is calibrated for TSS (Total Suspended Solids) and COD (Chemical Oxygen Demand) removal by primary sedimentation and activated sludge systems (carbon or combined carbon and nutrients removal), using 5-year (2006-2010) field data from five Portuguese WWTPs. A statistical analysis of the PX results is additionally proposed to assess treatment reliability. The new method is applied in two WWTPs and the PX results are compared with those of conventional measures - Er and performance indicators (PIs). The results demonstrate that, whereas a simplistic Er-driven or PI-driven management of the WWTPs shows limitations, the developed PXs are adequate measures for benchmarking removal efficiencies towards WWTP reliability and sustainability.