Use of antimicrobials in pediatric wards of five Brazilian hospitals.

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Marketing authorisation and pricing of FDA-approved cancer drugs in Brazil: a retrospective analysis.

Background: Most cancer drugs enter the US market first. US Food and Drug Administration (FDA) approvals of new cancer drugs may influence regulatory decisions in other settings. The study examined whether characteristics of available evidence at FDA approval influenced time-to-marketing authorisation (MA) in Brazil, and price differences between the two countries. Methods: All new FDA-approved cancer drugs from 2010 to 2019 were matched to drugs with MA and prices approved in Brazil by December 2020. Characteristics of main studies, availability of randomised controlled trials (RCTs), overall survival (OS) benefit, added therapeutic benefit, and prices were compared. Findings: Fifty-six FDA-approved cancer drugs with matching indications received a MA at the Brazilian Health Regulatory Agency (Anvisa) after a median of 522 days following US approval (IQR: 351-932). Earlier authorisation in Brazil was associated with availability of RCT (median: 506 vs 760 days, p = 0.031) and evidence of OS benefit (390 vs 543 days, p = 0.019) at FDA approval. At Brazilian marketing authorisation, a greater proportion of cancer drugs had main RCTs (75% vs 60.7%) and OS benefit (42.9% vs 21.4%) than that in the US. Twenty-eight (50%) drugs did not demonstrate added therapeutic benefit over drugs for the same indication in Brazil. Median approved prices of new cancer drugs were 12.9% lower in Brazil compared to the US (adjusted by Purchasing Power Parity). However, for drugs with added therapeutic benefit median prices were 5.9% higher in Brazil compared to the US, while 17.9% lower for those without added benefit. Interpretation: High-quality clinical evidence accelerated the availability of cancer medicines in Brazil. The combination of marketing and pricing authorisation in Brazil may favour the approval of cancer drugs with better supporting evidence, and more meaningful clinical benefit albeit with variable degree of success in achieving lower prices compared to the US. Funding: None.

Adverse Drug Reactions to Anti-infectives in Hospitalized Children: A Multicenter Study in Brazil.

INTRODUCTION: Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. OBJECTIVE: To assess ADRs associated with anti-infective use in Brazilian hospitalized children. METHODS: A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0-11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. RESULTS: A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001). CONCLUSION: Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.

The High "Cost" of Experimental Drugs Obtained Through Health Litigation in Brazil.

BACKGROUND: Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use programs, obtained by patients though health litigation. METHODS: A descriptive study using secondary data investigated unlicensed medicines obtained through lawsuits from 2010 to 2017, costing more than 1 million Brazilian reais (BRL), adjusted by the Brazilian Consumer Index to July 2017. Data sources were the Brazilian Health Surveillance Agency Registry (DATAVISA) and Adverse Events in Clinical Studies (NotivisaEC) Databases. Medicines were categorized by the Anatomical Therapeutic Chemical classification to level 03 and events by the WHO Adverse Drug Reaction Terminology. The study received ethical approval by the University of Brasilia Institutional Research Board. RESULTS: In the period, 812 drugs were obtained through litigation, and of these, 78 exceeded cost of 1 million BRL; 44 of them presented reports of 1,248 serious adverse events. Total Brazilian Government expenditure with these drugs was 3.2 billion BRL. Class L04A (n=7) showed greater expenditures (over 1.8 billion BRL). One hundred ninety-six deaths occurred and L01X was the most involved category (49.5%). Most other serious events (n=419) and sequelae (n=10) were related to L01X. CONCLUSION: Very high-cost drugs paid for by the government and obtained through health litigation presented deaths and serious adverse events in expanded access and compassionate use programs in Brazil.

Policy Change and the National Essential Medicines List Development Process in Brazil between 2000 and 2014: Has the Essential Medicine Concept been Abandoned?

Brazil has had a National Essential Medicines List (EML) since 1964. From 2000 to 2010, five consecutive evidence-based editions were produced, building on the essential medicine concept. In 2012, the government changed course to establish a new paradigm, introducing adoption of new medicines as the main aim within the recommendation process. The objective of the article was to report efforts to develop Brazil's national EML, policy changes from 2000 to 2014, discussing results, challenges and perspectives. Brazilian EML history and development process were collected from legislation, minutes, reports and legal ordinances, from 2000 to 2014. The Brazilian EML and the WHO Model Lists were compared using the Anatomical Therapeutic Chemical system. Overlap between lists was verified, and linear trends were produced. Type of membership, inclusion criteria, procedures, flow and listed medicines varied greatly between the selection committees acting before and after 2012. Paradigm-changing legislation aiming at linking list compliance to public financing in 2012 produced (i) greater importance given to political and administrative stakeholders, (ii) increasing trends in number of medicines over the years, (iii) decrease in use of WHO Model List as a reference and (iv) substitution of an essential medicines list review and update process by an adoption decision output. Other issues remained unchanged. Insufficient efforts for list implementation, such as lack of physician education, presented consequences to the health system. Substantial efforts were made to produce and update the list from 2000 to 2014. However, continuous and intense health litigation disproves process outcome effectiveness.

Dispensing and determinants of non-adherence to treatment for non complicated malaria caused by Plasmodium vivax and Plasmodium falciparum in high-risk municipalities in the Brazilian Amazon.

BACKGROUND: In Brazil, 99.7 % of malaria cases occur in the Amazon region. Although the number of cases is decreasing, the country accounted for almost 60 % of cases in the Americas Region, in 2013. Novel approaches for malaria treatment open the possibility of eliminating the disease, but suboptimal dispensing and lack of adherence influence treatment outcomes. The aim of this paper is to show the results on dispensing practices, non-adherence and determinants of non-adherence to treatment of non-complicated malaria. METHODS: The study was conducted in six high-risk municipalities with Plasmodium vivax and Plasmodium falciparum transmission in the Brazilian Amazon and based on the theoretical framework of the Mafalda Project, which included investigation of dispensing and adherence. The World Health Organization Rapid Evaluation Method has been used to estimate sample size. Individuals over 15 years of age with malaria were approached at health facilities and invited to participate through informed consent. Data was collected in chart review forms focusing on diagnosis, Plasmodium type, prescribing, and dispensing (kind, quantity, labelling and procedures). Follow-up household interviews complemented data collection at health facility. Non-adherence was measured during the implementation phase, by self-reports and pill-counts. Analysis was descriptive and statistical tests were carried out. Determinants of non-adherence and quality of dispensing were assessed according to the literature. RESULTS: The study involved 165 patients. Dispensing was done according to the national guidelines. Labelling was adequate for P. vivax but inadequate for P. falciparum medicines. Non-adherent patients were 12.1 % according to self-reports and 21.8 % according to pill-counts. Results point to greater non-adherence among all P. falciparum patients and among malaria non-naîve patients. More patients informed understanding adverse effects than 'how to use' anti-malarials. CONCLUSIONS: Non-adherent patients were mostly those with a P. falciparum diagnosis and those in their second or more malaria episode. New taxonomies and concepts on adherence stress the importance of focusing on the individual patient. Interventions targeted to and tailored for malaria patients must be addressed by health policy and implemented by managers and clinicians.

Hospital preparedness in advance of the 2014 FIFA World Cup in Brazil.

INTRODUCTION: Regardless of the capacity of the health care system of the host nation, mass gatherings require special planning and preparedness efforts within the health system. Brazil will host the 2014 Fédération Internationale de Football Association (FIFA) World Cup and the 2016 Olympics. This paper represents the first results from Project "Prepara Brasil," which is investigating the preparedness of the health sector and pharmaceutical services for these events. Hypothesis/Problem This study was designed to identify the efforts engaged in to prepare the health sector in Brazil for the FIFA World Cup 2014 event, as well as the 2016 Summer Olympics. METHODS: Key informant interviews were conducted with representatives of both the municipality and hospital sectors in each of the 12 host cities where matches will be played. A semi-structured key informant interview guide was developed, with sections for each type of participant. One of each municipality's reference hospitals was identified and seven additional general hospitals were randomly selected from all of the inpatient facilities in each municipality. The interviewers were instructed to contact a reference hospital, and two of the other hospitals, in the jurisdiction for participation in the study. Questions were asked about plans for mass-gathering events, the interaction between hospitals and government officials in preparation for the World Cup, and their perceptions of their surge capacity to meet the potential demands generated by the presence of the World Cup events in their municipalities. RESULTS: In all, 11 representatives of the sampled reference hospitals, and 24 representatives of other general private and public hospitals in the municipalities, were interviewed. Most of the hospitals had some interaction with government officials in preparation for the World Cup 2014. Approximately one-third (34%) received training activities from the government. Fifty-four percent (54%) of hospitals had no specific plans for communicating with the government or other agencies during the World Cup. Approximately half (51%) had plans for surge capacity during the event, but only 27% had any surge capacity for isolation of potentially infectious patients. CONCLUSION: Overall, although there has been mention of a great deal of planning on the part of the government officials for the World Cup 2014, hospital surge to meet the potential increase in demand still falls short.

Antiretroviral drug expenditure, pricing and judicial demand: an analysis of federal procurement data in Brazil from 2004-2011.

BACKGROUND: Previous studies have described expenditures for antiretroviral (ARV) medicines in Brazil through 2005. While prior studies examined overall expenditures, they have not have analyzed drug procurement data in order to describe the role of court litigation on access and pricing. METHODS: ARV drug procurement from private sector sources for the years 2004-2011 was obtained through the general procurement database of the Brazilian Federal Government (SIASG). Procurement was measured in Defined Daily Doses (DDD) per 1000 persons-under-treatment per day. Expenditures and price per DDD were calculated and expressed in U.S. Dollars. Justifications for ARV purchases were examined in order to determine the relationship between health litigation and incorporation into Brazil's national treatment guidelines. RESULTS: Drug procurement of ARVs from private sources underwent marked expansion in 2005, peaked in 2009, and stabilized to 2008 levels by 2011. Expenditures followed procurement curves. Medications which were procured for the first time after 2007 cost more than medicines which were introduced before 2007. Judicial actions initially resulted in purchases of newer medications for a select number of patients in Brazil but ultimately expanded availability to a larger population through incorporation into the national treatment guidelines. CONCLUSIONS: Drug procurement and expenditures for ARVs in Brazil varied between 2004-2011. The procurement of some drugs from the private sector ceased after public manufacturers started producing them locally. Judicial demand has resulted in the incorporation of newer drugs into the national treatment guidelines. In order for the AIDS treatment program to remain sustainable, efforts should be pursued to reduce prices through generic drugs, price negotiation and other public health flexibilities such as compulsory licensing.

A methodological approach for the evaluation of preparedness of pharmaceutical services / Un enfoque metodológico para evaluar el estado de preparación de los servicios farmacéuticos

OBJECTIVE: The aim of this article is to provide an outcome evaluation model for preparedness of pharmaceutical services (PS) in disaster situations. METHODS: A five-step evaluation model development was conducted. The first step was a search of disaster preparedness and PS literature. The second step consisted of a description of the political and organizational aspects, external context, implementation, and performance of PS in disaster preparedness. A theoretical model on PS preparedness in disaster situations, encompassing pharmaceutical services variables and measures of preparedness, was developed as the third step. The fourth step produced a comprehensive theoretical model for evaluating PS preparedness, combining the two approaches used in steps two and three. The fifth and final step examined the development of the indicator framework. RESULTS: The results of this methodological approach are presented in the logic model of PS preparedness and the indicator framework, both of which were developed based on the disaster preparedness and PS literature and organized to provide a structured evaluation approach. CONCLUSIONS: PS was conceptualized as a program that can be evaluated by measurable effects. These effects can only be measured based on documented, on-site conditions before and after an event recognized as a disaster situation. This conceptual approach is context-modulated and therefore only applicable where the logistic cycle has been adopted as the rationale for PS.

OBJETIVO: Proporcionar un modelo de evaluación de resultados relativos al estado de preparación de los servicios farmacéuticos (SF) para situaciones de desastre. MÉTODOS: Se elaboró un modelo de evaluación en cinco pasos. El primer paso fue una búsqueda bibliográfica sobre preparativos para situaciones de desastre y SF. El segundo consistió en una descripción de los aspectos políticos y técnicos, el contexto externo, la implementación y el desempeño de los SF en la preparación para situaciones de desastre. El tercer paso fue la elaboración de un modelo teórico sobre el estado de preparación de los SF para situaciones de desastre, que comprendía variables relativas a los SF y medidas del estado de preparación. El cuarto paso consistió en la creación de un modelo teórico integral para evaluar el estado de preparación de los SF, mediante la combinación de los enfoques usados en los pasos dos y tres. El quinto y último paso fue el análisis de la elaboración del marco de indicadores. RESULTADOS: Se presentan los resultados de este enfoque metodológico en el modelo lógico del estado de preparación de los SF y el marco de indicadores, ambos elaborados con base en la bibliografía sobre preparativos para casos de desastre y SF, y organizados para poder proporcionar un método estructurado de evaluación. CONCLUSIONES: A efectos de la elaboración de este marco conceptual se consideró a los SF como un programa que podría ser evaluado a partir de sus efectos cuantificables. Estos efectos solo pueden ser medidos sobre la base de condiciones documentadas en el lugar de los hechos antes y después del evento considerado una situación de desastre. Este enfoque conceptual está modulado en función del contexto y por lo tanto se considera aplicable solamente donde se haya adoptado el ciclo logístico como fundamento de los SF.

A methodological approach for the evaluation of preparedness of pharmaceutical services.

OBJECTIVE: The aim of this article is to provide an outcome evaluation model for preparedness of pharmaceutical services (PS) in disaster situations. METHODS: A five-step evaluation model development was conducted. The first step was a search of disaster preparedness and PS literature. The second step consisted of a description of the political and organizational aspects, external context, implementation, and performance of PS in disaster preparedness. A theoretical model on PS preparedness in disaster situations, encompassing pharmaceutical services variables and measures of preparedness, was developed as the third step. The fourth step produced a comprehensive theoretical model for evaluating PS preparedness, combining the two approaches used in steps two and three. The fifth and final step examined the development of the indicator framework. RESULTS: The results of this methodological approach are presented in the logic model of PS preparedness and the indicator framework, both of which were developed based on the disaster preparedness and PS literature and organized to provide a structured evaluation approach. CONCLUSIONS: PS was conceptualized as a program that can be evaluated by measurable effects. These effects can only be measured based on documented, on-site conditions before and after an event recognized as a disaster situation. This conceptual approach is context-modulated and therefore only applicable where the logistic cycle has been adopted as the rationale for PS.

Proposed methodology for monitoring antiretroviral drugs price negotiations in Latin America and the Caribbean.

OBJECTIVES: The spread of HIV/AIDS challenges governments to provide antiretroviral (ARV) treatment at affordable prices, and various initiatives have been developed with that intent. In Latin America and the Caribbean, four subregional negotiations were conducted during 2002-2005 to reduce drug prices and thus broaden access to ARVs. Studies were carried out to monitor the negotiations, and the development of a monitoring methodology was recommended. The objective of the current study was to develop and describe a potential methodology for monitoring ARV price negotiations. METHODS: The study, carried out in 2006-2007, consisted of a design phase and validation phase. The design phase included an extensive literature review and development of a theoretical framework. Validation was performed using health professional consensus and pilot studies in three countries-Barbados, Honduras, and Peru-representing the Caribbean, Central American, and Andean subregions. RESULTS: The results included a detailed logic model and a 40-indicator framework. Both were tested in the field. Indicators were evaluated for feasibility, pertinence, and sensitivity, based on the outcome of the pilot study. CONCLUSIONS: This monitoring methodology is designed to help countries self-evaluate progress toward implementation of ARV price negotiations. The results of the pilot study indicate that its implementation in the field helped elucidate the ARV price negotiation process by identifying local conditions and indirectly measuring countries' negotiating capacities.

Proposed methodology for monitoring antiretroviral drugs price negotiations in Latin America and the Caribbean / Propuesta de metodología para monitorear la negociación de precios de los medicamentos antirretrovirales en América Latina y el Caribe

OBJECTIVES: The spread of HIV/AIDS challenges governments to provide antiretroviral (ARV) treatment at affordable prices, and various initiatives have been developed with that intent. In Latin America and the Caribbean, four subregional negotiations were conducted during 2002-2005 to reduce drug prices and thus broaden access to ARVs. Studies were carried out to monitor the negotiations, and the development of a monitoring methodology was recommended. The objective of the current study was to develop and describe a potential methodology for monitoring ARV price negotiations. METHODS: The study, carried out in 2006-2007, consisted of a design phase and validation phase. The design phase included an extensive literature review and development of a theoretical framework. Validation was performed using health professional consensus and pilot studies in three countries-Barbados, Honduras, and Peru-representing the Caribbean, Central American, and Andean subregions. RESULTS: The results included a detailed logic model and a 40-indicator framework. Both were tested in the field. Indicators were evaluated for feasibility, pertinence, and sensitivity, based on the outcome of the pilot study. CONCLUSIONS: This monitoring methodology is designed to help countries self-evaluate progress toward implementation of ARV price negotiations. The results of the pilot study indicate that its implementation in the field helped elucidate the ARV price negotiation process by identifying local conditions and indirectly measuring countries' negotiating capacities.

OBJETIVO: La diseminación del VIH/sida exige de los gobiernos suministrar el tratamiento antirretroviral (ARV) a precios asequibles y se han desarrollado varias iniciativas con ese fin. En América Latina y el Caribe se han realizado cuatro negociaciones subregionales entre 2002 y 2005 para reducir los precios de los medicamentos y así ampliar el acceso a los ARV. Se han realizado estudios para monitorear las negociaciones y se ha propuesto crear una metodología de monitoreo. El objetivo del presente trabajo fue desarrollar y describir una posible metodología para el monitoreo de las negociaciones de los precios de los ARV. MÉTODOS: El estudio, realizado en 2006-2007, constó de las fases de diseño y validación. En la fase de diseño se hizo una extensa revisión de la literatura y se desarrolló un marco teórico. La validación se realizó mediante un análisis de consenso de profesionales de la salud y un estudio piloto en tres países -Barbados, Honduras y Perú- en representación del Caribe, América Central y la subregión andina. RESULTADOS: Se obtuvo un detallado modelo logístico y un marco conceptual de 40 indicadores. Ambos se probaron en el terreno. Se evaluaron la factibilidad, pertinencia y sensibilidad de los indicadores según los resultados del estudio piloto. CONCLUSIONES: Esta metodología de monitoreo se diseñó para ayudar a los países a autoevaluar sus progresos en la implementación de la negociación de precios de los ARV. Los resultados del estudio piloto indican que su implementación en el terreno ayudó a esclarecer el proceso de negociación de los precios de los ARV mediante la identificación de las condiciones locales y la medición indirecta de la capacidad de negociación de los países.