Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison.

Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.

Molecular Detection of Leishmania (Leishmania) mexicana in Sandflies from the State of Yucatan, Mexico.

Background: Leishmaniases are a group of vector-borne zoonotic diseases of public health relevance within the tropical and subtropical regions of the world. The state of Yucatan is a vulnerable and receptive area to localized cutaneous leishmaniasis (LCL) due to its proximity to the high-transmission endemic states of Campeche and Quintana Roo. Autochthonous cases of LCL caused by Leishmania (Leishmania) mexicana have been documented in the state, showing a geographical expansion of the disease. Materials and Methods: Using CO2-supplemented Centers for Disease Control and Prevention light traps and Shannon traps, we captured anthropophilic sandflies in the surroundings of a locality with recent records of autochthonous cases of LCL. Sandflies carrying Leishmania DNA were evidenced using PCR. Results: A total of 140 Phlebotominae (Diptera: Psychodidae) females of four species were captured: Lutzomyia (Tricholateralis) cruciata (Coquillett), Psathyromyia (Psathyromyia) shannoni (Dyar), Lutzomyia (Lutzomyia) longipalpis (Lutz and Neiva), and Dampfomyia (Coromyia) deleoni (Fairchild and Hertig). Molecular results showed that 6.1% (95% confidence interval [CI] = 2.3-12.9%) of Lu. cruciata and 43.8% (95% CI = 19.8-70.1%) of Pa. shannoni showed evidence of carrying L. (L.) mexicana DNA. Conclusion: We provide evidence of anthropophilic sandflies carrying L. mexicana DNA in a municipality with recorded autochthonous cases of LCL caused by this parasite species in the state of Yucatan, suggesting the emergence of new focus of LCL in Mexico.

Transparency of data on the value chain of medicines in Argentina, Brazil, and Colombia.

Introduction: The transparency of data on the value chain of medicines is crucial for the study and monitoring of the pharmaceutical system. These data may impact medicine pricing negotiations, contribute to patient access to pharmaceutical products, and strengthen health systems. Objective: This study analyzed the national strategies to ensure the transparency of data from medicine cost development to marketing in Argentina, Brazil, and Colombia. Method: A descriptive study was carried out by searching databases, reports, documents, and scientific articles published between January and August 2022 related to rules on transparency and databases, including 1) marketing authorization; 2) pricing; 3) intellectual property; 4) clinical trials; 5) research and development (R&D); and 6) health technology assessment (HTA) of selected biopharmaceuticals. Results: Transparency data, rules, and information are not uniform. The infostructures (organizational capacity for collecting and distributing information) regarding the pharmaceutical value chain in these three countries face limitations in appropriate measures to publicly share data and evidence, including pre-clinical data, clinical data, and costs. None of the countries require transparency about data on research and development costs. All three countries present similar publicization of data on marketing authorization and intellectual property, with some differences. The significant limitations in Argentina include the absence of formal price regulation and data on the volume of medicine purchased and respective amounts paid. Among the three countries, Brazil showed a higher degree of information transparency, perhaps due to the legal regulation that guarantees citizens access to information of public interest. Brazil also stands out in terms of the public availability of HTA reports and pricing, in addition to the highest volume of information. In contrast, Colombia has in place a decree that allows 5 years of trial data exclusivity for new medicines, an act contrary to data transparency. Despite the different stages of transparency, no country has evidenced a robust use of these data in public policy decision-making. Conclusion: The results reinforce the presence of information asymmetry between stakeholders, data fragmentation, data gaps and overlap, and difficulty in comparing available data across the three countries and the use of these data nationally to produce evidence.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Judicialización del acceso a medicamentos en el contexto Suramericano / Judicialization of access to medicines in the South American context

Los gobiernos suramericanos reconocen el acceso a medicamentos como parte del derecho de sus poblaciones a la salud y al bienestar. Tanto la vida como la salud entendidas como derechos sociales implican esfuerzos de los sistemas de salud para garantizar las mejores condiciones de manera equitativa y colectiva, sin restricciones de acceso, y manteniendo su sostenibilidad. El fenómeno, conocido como "judicialización del acceso a los medicamentos" se ha tornado una vía alternativa a los mecanismos establecidos por el sistema de salud en la región, generando preocupaciones relacionadas con la contradicción entre los esfuerzos de los sistemas de salud y las determinaciones judiciales. Este artículo presenta una revisión sistemática el tema en la región, a partir de las bases de datos Scopus, PubMed y Lilacs. Muchos de los casos informados describen demandas individuales sin que se hayan generado rutas colectivas, cuyas sentencias pudieran involucrar a grupos más numerosos de personas, generar jurisprudencia para próximos abordajes similares, e impactar en el diseño o implementación de políticas públicas. Según el principio de universalidad, la judicialización de medicamentos es una estrategia útil en tanto mantenga el equilibrio entre la garantía del derecho a la salud, el bienestar colectivo y la mejor disposición de los recursos en salud. Desde la perspectiva jurídica queda una gran inquietud sin resolver en cuanto al rol de las diversas instancias con las que cuentan los países para garantizar derechos fundamentales y su articulación con otras instancias como tribunales y autoridades administrativas.

South American governments recognize access to medicines as part of the right of their popu-lations to health and welfare. Both, life and health understood as social rights imply efforts of the health systems to guarantee the best conditions in an equitable and collective way, without restrictions to access, and maintaining their sustainability. The so-called "judiciali-zation of access to medicines" has become an alternative path to the mechanisms established by the health systems in the region, generating concerns related to the contradiction between the efforts of health systems and judicial determinations. This article presents a systematic review on the subject in the region, based on Scopus, PubMed and Lilacs databases. Many of the cases reported describe individual claims that have not generated collective routes, whose sentences could involve more numerous groups of people; generate jurisprudence for similar approaches, and impact on the design and implementation of public policies. Under the principle of universality, the judicialization of medicines is a useful strategy insofar as it maintains the balance between the guarantees of the right to health, collective welfare and the best disposition of the health resources. From a legal perspective, there is still an unresolved concern regarding the role of the various entities that are available to countries to guarantee fundamental rights and its articulation with other bodies such as courts and administrative authorities.

Medicine Shortages: Gaps Between Countries and Global Perspectives.

Introduction: Over the last decade, global health policies and different research areas have focused on the relevance and impact of medicine shortages. Published studies suggest there have been difficulties with access to medicines since the beginning of the 20th century, and there have been advances in our understanding and management of the problem since then. However, in view of global and regional health care concerns with shortages, we believe this phenomenon needs to be characterized and described more fully regarding the types of medicines affected, possible causes, and potential strategies to address these. The aim of this scoping review was to identify, compare if possible, and characterize the recent literature regarding the situation of medicines shortages between countries, and provide different perspectives, including a global context and national approaches. Methodology: A scoping study presented as a narrative review of the situation and findings principally based on published articles. Results: Based on the reported cases in the literature, a typology of medicines shortage and supply interruption episodes and their causes were proposed; national approaches to notify and manage the medicines shortages cases were described and classified by update frequency; principal differences between market and supply chain management perspectives of the situation were identified and global and countries' perspectives were described. Conclusion: Policy makers require solutions that prevent those cases in which the population's health is affected by episodes of medicine shortages and/or interruption in the supply chain. There is also a need to generate a glossary related to logistics management and the availability of medicines which will be useful to understand and overcome shortages. In addition, recognize that potential solutions are not only related with actions linked to research, development and innovation, but much wider. Overall, we believe this article can act as a basis for future discussions in this important area.

Drug utilization study of two generic antibiotics in a tertiary hospital in Bogotá

Introduction: The Colombian national pharmaceutical policy establishes as a strategy the generation of greater pharmaco-epidemiological research at the national level, especially in the case of antibiotic drugs. Objective: To provide local pharmaco-epidemiological evidence regarding the effectiveness, conditions of use and safety of generic meropenem and cefepime in a tertiary hospital in Bogotá. Materials and methods: We conducted a descriptive, longitudinal and retrospective drug utilization study. The data were collected from the medical histories of all the patients who had cefepime or meropenem prescribed. Results: We included 82 patients treated with cefepime and 91 treated with meropenem in the study. Most of the patients were in services different from the intensive care unit (taking cefepime: 59.8%, and meropenem: 52.7%). Only 21.9% of the patients treated with cefepime and 49% of those treated with meropenem were seen by an infectious disease specialist. The antibiogram was performed for 47% and 60% of the patients treated with cefepime and meropenem, respectively. The most frequent indication for cefepime were respiratory infections and for meropenem, genitourinary ones. Therapeutic success rates were 61.7% for cefepime and 63.0% for meropenem. Conclusions: This study contributes evidence regarding the therapeutic performance of two generic antibiotics used in tertiary hospitals. There were no reports of therapeutic failure during the study period. In the cases of non-response, pharmacokinetic alterations, unfavorable clinical conditions, and inappropriate choice of antimicrobial treatment were identified as frequent factors.

Utilización de dos antibióticos genéricos en un hospital de tercer nivel en Bogotá / Drug utilization study of two generic antibiotics in a tertiary hospital in Bogotá

Resumen Introducción. La política farmacéutica de Colombia establece la necesidad de intensificar la investigación en farmacoepidemiología a nivel nacional, especialmente en el caso de los antibióticos. Objetivo. Aportar información farmacoepidemiológica en cuanto a la efectividad, las condiciones de uso y la seguridad de la cefepima y el meropenem genéricos en un hospital de alta complejidad en Bogotá. Materiales y métodos. Se hizo un estudio descriptivo, longitudinal y retrospectivo sobre la utilización de estos medicamentos. Los datos se recolectaron de todas las historias clínicas en las cuales se registraba el uso de cefepima y meropenem. Resultados. Se incluyeron 82 pacientes tratados con cefepima y 91 con meropenem. La mayoría de ellos había estado internada en servicios diferentes a la unidad de cuidados intensivos (59,8 % con cefepima y 52,7 % con meropenem). El 21,9 % de los tratados con cefepima y el 49 % de los tratados con meropenem, tuvieron consulta con un infectólogo, en tanto que en 47 % de los primeros y en 78 % de los segundos, se hizo cultivo o antibiograma. Las condiciones más frecuentemente tratadas con cefepima fueron las infecciones de vías respiratorias (32,5 %) y, con meropenem, las infecciones genitourinarias (34,8 %). Las tasas de éxito terapéutico fueron de 61,7 % para la cefepima y de 63,0 % para el meropenem. Conclusiones. Este estudio aporta información sobre el desempeño terapéutico de dos antibióticos genéricos de uso hospitalario. No hubo reportes de falla terapéutica durante el periodo de estudio. En los casos en que no hubo respuesta al tratamiento, las causas frecuentes fueron las alteraciones farmacocinéticas, las condiciones clínicas desfavorables y la elección inadecuada del tratamiento antimicrobiano.

Abstract Introduction: The Colombian national pharmaceutical policy establishes as a strategy the generation of greater pharmaco-epidemiological research at the national level, especially in the case of antibiotic drugs. Objective: To provide local pharmaco-epidemiological evidence regarding the effectiveness, conditions of use and safety of generic meropenem and cefepime in a tertiary hospital in Bogotá. Materials and methods: We conducted a descriptive, longitudinal and retrospective drug utilization study. The data were collected from the medical histories of all the patients who had cefepime or meropenem prescribed. Results: We included 82 patients treated with cefepime and 91 treated with meropenem in the study. Most of the patients were in services different from the intensive care unit (taking cefepime: 59.8%, and meropenem: 52.7%). Only 21.9% of the patients treated with cefepime and 49% of those treated with meropenem were seen by an infectious disease specialist. The antibiogram was performed for 47% and 60% of the patients treated with cefepime and meropenem, respectively. The most frequent indication for cefepime were respiratory infections and for meropenem, genitourinary ones. Therapeutic success rates were 61.7% for cefepime and 63.0% for meropenem. Conclusions: This study contributes evidence regarding the therapeutic performance of two generic antibiotics used in tertiary hospitals. There were no reports of therapeutic failure during the study period. In the cases of non-response, pharmacokinetic alterations, unfavorable clinical conditions, and inappropriate choice of antimicrobial treatment were identified as frequent factors.

[Proposed model for managing drugs used for unregistered indications in Colombia]. / Propuesta de un modelo de gestión de medicamentos en indicaciones no registradas en Colombia.

The use of drugs for unregistered indications, known as "off-label" use, is a practice that creates problems of rational use and access when other options are not available. Health systems should address this situation, particularly in connection with decisions concerning coverage, while trying to minimize health risks and clearly define the roles and responsibilities of the parties involved. Colombia's Ministry of Health and Social Protection (MinSalud), together with the National University of Colombia and national experts, developed a proposal for a model for managing drugs being used for unregistered indications (off-label) and their potential reimbursement with public resources, taking into account international practices and country characteristics. The management model is non-punitive and is geared toward promoting the rational use of these drugs so that barriers to access are reduced whenever their use is supported by solid scientific evidence. The model addresses patient safeguards in the bioethical domain and the roles and responsibilities of the prescriber and government entities.

Propuesta de un modelo de gestión de medicamentos en indicaciones no registradas en Colombia / Proposed model for managing drugs used for unregistered indications in Colombia

El uso de medicamentos en indicaciones no registradas (INR), conocido como uso “off-label”, es una práctica que genera problemas de uso racional y de acceso cuando no existen alternativas disponibles. Los sistemas de salud deben gestionar esta realidad, sobre todo cuando se trata de decisiones de cobertura, buscando minimizar los riesgos para la salud y estableciendo de forma clara los papeles y las responsabilidades de los agentes involucrados. El Ministerio de Salud y Protección Social de Colombia (MinSalud), junto con con la Universidad Nacional de Colombia y expertos nacionales, diseñaron una propuesta de modelo de gestión del uso de medicamentos en indicaciones no registradas (off-label) y su potencial reembolso con recursos públicos, teniendo en cuenta prácticas internacionales y la realidad nacional. El modelo de gestión es no punitivo y está orientado a la promoción del uso racional de estos medicamentos, de forma que se reduzcan las barreras al acceso cuando su uso está respaldado por pruebas cientificas de calidad. El modelo incorpora elementos de garantías bioéticas del paciente, los papeles y las responsabilidades del prescriptor y de las entidades de gobierno.

The use of drugs for unregistered indications, known as “off-label” use, is a practice that creates problems of rational use and access when other options are not available. Health systems should address this situation, particularly in connection with decisions concerning coverage, while trying to minimize health risks and clearly define the roles and responsibilities of the parties involved. Colombia's Ministry of Health and Social Protection (MinSalud), together with the National University of Colombia and national experts, developed a proposal for a model for managing drugs being used for unregistered indications (off-label) and their potential reimbursement with public resources, taking into account international practices and country characteristics. The management model is non-punitive and is geared toward promoting the rational use of these drugs so that barriers to access are reduced whenever their use is supported by solid scientific evidence. The model addresses patient safeguards in the bioethical domain and the roles and responsibilities of the prescriber and government entities.

Complicaciones asociadas y análisis de supervivencia de niños con leucemias agudas tratados con el protocolo BFM-95 / Associated complications and survival analysis in children with acute leukemia treated with BFM-95 protocol

Objetivo: Determinar las complicaciones y porcentaje de supervivencia de niños con leucemia linfoide y mieloide aguda tratados con el protocolo Berlin-Frankfurt-Münster 95 (BFM-95) de Enero de 2008 a Diciembre de 2010 en el Hospital Infantil "Los Ángeles". Materiales y métodos: Una cohorte retrospectiva fue diseñada para evaluar a niños tratados con el protocolo BFM-95 durante tres años en el Hospital Infantil "Los Ángeles". La información fue obtenida de los datos demográficos del paciente, complicaciones asociadas con el protocolo BFM-95 y supervivencia. Los datos fueron recolectados de las historias médicas y los reportes de fallecimiento del hospital. Las variables nominales fueron presentadas como proporciones y las variables continuas fueron expresadas como medias y desviaciones estándares. El análisis de supervivencia fue realizado por el método Kaplan-Meier. Los datos fueron analizados usando el programa Statistical Package for Social Sciences, versión 17,0 (SPSS Inc., Chicago, Illinois, USA). Resultados: Cincuenta y dos niños fueron incluidos en este estudio. De todo el grupo, 47 (90,4%) tuvieron leucemia linfoide aguda y 5 (9,6%) leucemia mieloide aguda. Treinta y cinco (67,3%) presentaron complicaciones. Veintitres niños (65,7%) mostraron complicaciones infecciosas siendo las más frecuentes. El análisis de supervivencia de Kaplan-Meier mostró que los pacientes con complicaciones tuvieron un tiempo más corto de supervivencia comparado a los pacientes sin complicaciones. Conclusiones: La incidencia de complicaciones fue elevada. El análisis Kaplan-Meier reveló diferencias entre la leucemia linfoide aguda y leucemia mieloide aguda de acuerdo a las complicaciones.

Objective: To determine complications and survival percentage in children suffering from acute lymphoid and myeloid leukemia treated with Berlin-Frankfurt-Münster 95 (BFM-95) protocol from January 2008 to December 2010 at Los Ángeles Children Hospital. Materials and methods: A retrospective cohort was designed to evaluate children treated with BFM-95 protocol during three years at Los Ángeles Children Hospital. The Information was obtained from the patient demographics, complications associated with BFM-95 protocol and survival. Data were collected from medical records and hospital decease reports. Nominal variables were presented as proportions and the continuous variables were presented as means and standard deviations. The survival analysis was performed using Kaplan-Meier method. Data were analyzed using the Statistical Package for Social Sciences, 17.0 version software (SPSS Inc., Chicago, Illinois, USA). Results: Fifty two children were included in this study. From the whole group, 47 (90.4%) had acute lymphoid leukemia and 5 (9.6%) had acute myeloid leukemia. Thirty five (67.3%) presented complications. Twenty three children (65.7%) had infectious complications, being the most frequent ones. Kaplan-Meier survival analysis showed that patients with complications have shorter survival time compared to patients with no complications. Conclusions: The incidence of complications was high in children treated with BFM-95 protocol. Kaplan-Meier analysis revealed differences between acute lymphoid leukemia and acute myeloid leukemia according to complications.

[International reference prices and cost minimization analysis for the regulation of medicine prices in Colombia]. / Precios de referencia internacional y análisis de costo minimización para la regulación de precios de medicamentos en Colombia.

OBJECTIVES: To suggest a scheme of decision making on pricing for medicines that are part of Free Regulated Regime, a regulation way of the pharmaceutical pricing policy in Colombia. It includes two regulation tools: international reference prices and a cost minimization analysis methodology. METHODS: Following the current pricing policy, international reference prices were built with data from five countries for selected medicines, which are under Free Regulated Regime. The cost minimization analysis methodology includes selection of those medicines under Free Regulated Regime with possible comparable medicines, selection of comparable medicines, and treatment costs evaluation. RESULTS: As a result of the estimate of International Reference Prices, four medicines showed in the domestic pharmaceutical market a bigger price than the Reference Price. A scheme of decision-making was design containing two possible regulation tools for medicines that are part of Free Regulated Regime: estimate of international reference prices and cost minimization analysis methodology. This diagram would be useful to assist the pricing regulation of Free Regulated Regime in Colombia. CONCLUSIONS: As present results shows, international reference prices make clear when domestic prices are higher than those of reference countries. In the current regulation of pharmaceutical prices in Colombia, the international reference price has been applied for four medicines. Would be suitable to extend this methodology to other medicines of high impact on the pharmaceutical expenditure, in particular those covered by public funding. The availability of primary sources about treatment costs in Colombia needs to be improved as a requirement to develop pharmaco-economic evidence. SISMED is an official database that represents an important primary source of medicines prices in Colombia. Nevertheless, having into account that SISMED represents an important advantage of transparency in medicines prices, it needs to be improved in quality and data availability.