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.Fil: Lopes, Luciane C.. University Of Sorocaba; BrasilFil: Salas, Daiana Maribel. University of Pennsylvania; Estados UnidosFil: Osorio de Castro, Claudia Garcia Serpa. Fundación Oswaldo Cruz; BrasilFil: Freitas Leal, Lisiane. McGill University; CanadáFil: Doubova, Svetlana V.. Mexican Institute of Social Security; MéxicoFil: Cañás, Martín. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; ArgentinaFil: Dreser, Anahi. Instituto Nacional de Salud Pública; MéxicoFil: Acosta, Angela. Universidad ICESI; ColombiaFil: Oliveira Baldoni, Andre. Federal University of São João Del-Rei; BrasilFil: de Cássia Bergamaschi, Cristiane. University of Sorocaba; BrasilFil: Marques Mota, Daniel. Brazilian Health Regulatory Agency; BrasilFil: Gómez Galicia, Diana L.. Universidad Autónoma del Estado de Morelos; MéxicoFil: Sepúlveda Viveros, Dino. Universidad de Chile; ChileFil: Narvaez Delgado, Edgard. No especifíca;Fil: da Costa Lima, Elisangela. Universidade Federal do Rio de Janeiro; BrasilFil: Chandia, Felipe Vera. Pontificia Universidad Católica de Chile; ChileFil: Ferre, Felipe. Universidade Federal de Minas Gerais; BrasilFil: Marin, Gustavo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Olmos, Ismael. State Health Services Administration; UruguayFil: Zimmermann, Ivan R.. Universidade do Brasília; BrasilFil: Fulone, Izabela. University of Sorocaba; BrasilFil: Roldán Saelzer, Juan. Instituto de Salud Pública; ChileFil: Sánchez Salgado, Juan Carlos. No especifíca;Fil: Castro Pastrana, Lucila I.. Universidad de Las Américas de Puebla; MéxicoFil: de Souza, Luiz Jupiter Carneiro. Fundación Oswaldo Cruz; BrasilFil: Machado Beltrán, Manuel. Universidad Nacional de Colombia; ColombiaFil: Tolentino Silva, Marcus. University of Sorocaba; BrasilFil: Mena, María Belén. Universidad Central del Ecuador; EcuadorFil: de França Fonteles, Marta Maria. Universidade Federal do Ceara; BrasilFil: Urtasun, Martín Alejandro. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; Argentin

Estrés oxidativo e inflamación en la ocurrencia de fibrilación auricular post-cirugía coronaria

Doctor en Ciencias FarmacéuticasLa fibrilación auricular postoperatoria es la complicación más frecuente luego de una cirugía cardiaca y afecta a una alta proporción de pacientes después de ser sometidos a una cirugía coronaria. Su aparición eleva la morbilidad y mortalidad en estos pacientes, y prolonga las hospitalizaciones con un aumento en la utilización de recursos clínicos y farmacológicos. Actualmente no se dispone de terapias efectivas y seguras para su prevención o manejo. Los mecanismos que condicionan su aparición aún son en gran medida desconocidos, pero actualmente se sabe que los procesos de inflamación y estrés oxidativo se encuentran involucrados, probablemente condicionando transformaciones estructurales y funcionales de la aurícula conocidas como remodelado cardiaco, o incluso actuando como factores desencadenantes para la fibrilación auricular. Particularmente, se conoce que los pacientes que presentan niveles plasmáticos más elevados del marcador inflamatorio proteína C reactiva, tienen una mayor probabilidad de experimentar una fibrilación auricular postoperatoria. El polimorfismo +219 G>A en el gen de proteína C reactiva ha sido relacionado previamente con niveles plasmáticos más elevados de proteína C reactiva en individuos sanos sometidos a una situación fisiológica de estrés. Los objetivos de este estudio consistieron en determinar si el aumento del estrés oxidativo y la presencia de un proceso inflamatorio sistémico determinan la ocurrencia de fibrilación auricular en pacientes sometidos a cirugía cardiaca, y a la vez determinar si la presencia del polimorfismo +219 G>A en el gen de proteína C reactiva (PCR) se asocia a niveles más elevados de proteina C en estos pacientes y a una mayor incidencia de fibrilación auricular postoperatoria. Para ello se reclutaron 194 pacientes en ritmo sinusal y con indicación de cirugía de revascularización miocárdica en los hospitales Clínico de la Universidad Católica, Clínico de la Universidad de Chile, y del Instituto Nacional del Tórax, a los que, luego de firmado el consentimiento informado correspondiente, se les tomó muestras sanguíneas previo y con posterioridad a la cirugía, para determinar parámetros de inflamación (PCRus, molécula-1 de adhesión vascular celular y recuento de blancos), estrés oxidativo (sustancias reactivas al ácido tiobarbitúrico y actividad enzimática de catalasa, superóxido dismutasa y glutatión peroxidasa) y remodelado auricular (metaloproteinasas 2 y 9), y una muestra adicional previo a la cirugía para determinar el polimorfismo +219G/A del gen de proteína C reactiva. Posteriormente se hizo un seguimiento clínico al paciente a través de la revisión de la ficha clínica, con el fin de identificar a los pacientes que experimentaron fibrilación auricular postoperatoria. Un 16,5% de los pacientes, es decir, 32 de ellos, experimentaron fibrilación auricular postoperatoria. La edad resultó ser un predictor para dicho evento. La cirugía provocó una clara respuesta inflamatoria reflejada en todos los parámetros considerados, especialmente en la proteína C reactiva, mientras que la respuesta oxidativa fue menos clara. Los marcadores inflamatorios sistémicos y de estrés oxidativo no resultaron diferentes entre los pacientes con o sin fibrilación auricular post-operatoria, excepto en el caso de VCAM-1, cuyos niveles plasmáticos preoperatorios fueron significativamente mayores en los pacientes que desarrollaron fibrilación auricular post-operatoria. La determinación del polimorfismo +219G/A del gen de proteína C reactiva arrojó una frecuencia alélica de 0,443 para el alelo A y 0,557 para el alelo G, y una frecuencia genotípica de 0,191 para AA, 0,505 para AG y 0,304 para GG. No hubo relación entre el polimorfismo y la incidencia de fibrilación auricular postoperatoria, pero sí se registró niveles de proteína C reactiva un 100% más elevados en pacientes con genotipo GG. En conclusión, niveles elevados de VCAM-1 en pacientes sometidos a cirugía de revascularización coronaria predicen un mayor riesgo para fibrilación auricular postoperatoria. El genotipo GG del polimorfismo +219G/A del gen de proteína C reactiva determina niveles más elevados de proteína C reactiva, pero estos mayores niveles no guardan relación con una mayor incidencia de fibrilación auricular postoperatoria. La edad es un claro predictor de fibrilación auricular postoperatoriaPostoperative atrial fibrillation is the most common complication after cardiac surgery and affects a high proportion of patients undergoing coronary surgery. Its appearance raises morbidity and mortality in these patients, prolongs hospitalizations, and increases clinical and pharmacological resources utilization. Currently there are no safe and effective therapies available for its prevention or management. The mechanisms that determine their apparition are still largely unknown, but now it is known that the processes of inflammation and oxidative stress are involved, probably conditioning structural and functional changes of the atrium known as cardiac remodeling, or even acting as triggers for atrial fibrillation. Particularly, it is known that patients with higher plasmatic levels of inflammatory marker C-reactive protein, are more likely to experience postoperative atrial fibrillation. +219 G> A polymorphism in the CRP gene has been previously associated with higher plasma levels of CRP in healthy individuals undergoing a physiological stress. The aim of this study is to determine whether increased oxidative stress and presence of a systemic inflammatory process determine the occurrence of atrial fibrillation in patients undergoing cardiac surgery, while determining whether the presence of +219 G> A polymorphism in the CRP gene is associated with higher levels of CRP and a higher incidence of postoperative atrial fibrillation. This study recruited 194 patients in sinus rhythm and with indication of myocardial revascularization surgery in hospitals Clínico de la Universidad Católica, Clínico de la Universidad de Chile, and Instituto Nacional del Tórax, from who, after signing the appropriate informed consent, blood samples were taken before and after surgery to determine parameters of inflammation (CRP, VCAM-1 and white cell count), oxidative stress (Thiobarbituric acid reactive substances and enzymatic activity of catalase, superoxide dismutase and glutathione peroxidase) and atrial remodeling (matrix metalloproteinases 2 and 9), and an additional blood sample was taken prior to surgery to determine the +219 G/A polymorphism in CRP gene. Subsequently patients evolution were followed through the review of clinical records in order to identify those patients who experienced postoperative atrial fibrillation. 16.5% of patients, ie 32 of them, experienced postoperative atrial fibrillation. Age proved to be a predictor for the event. The surgical procedure caused an inflammatory response clearly reflected in all inflammatory parameters considered, especially in Creactive protein, whereas the oxidative response was less clear. Systemic inflammatory and oxidative stress markers were not different between patients with and without postoperative atrial fibrillation, except in the case of VCAM-1, whose plasma levels were significantly higher in preoperative patients who developed postoperative atrial fibrillation. Determination of the +219 G/A polymorphism in CRP gene showed an allele frequency of 0.443 for A allele and 0.557 for G allele and genotype frequencies of 0.191 for AA, 0.505 for AG and 0.304 for GG. There was no association between polymorphism and the incidence of postoperative atrial fibrillation, but CRP levels were 100% higher in patients with GG genotype. In conclusion, higher levels of VCAM-1 in patients undergoing coronary artery bypass surgery predict an increased risk for postoperative atrial fibrillation. GG genotype on +219 G/A polymorphism in CRP gene determines higher levels of CRP, but they are not related to an increased incidence of postoperative atrial fibrillation. Age is a strong predictor of postoperative atrial fibrillatio

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.Fil: Machado, Fernanda Lacerda da Silva. Universidade Federal do Rio de Janeiro; BrasilFil: Cañás, Martín. Universidad Nacional Arturo Jauretche; ArgentinaFil: Doubova, Svetlana V.. Mexican Institute Of Social Security; MéxicoFil: Urtasun, Martín Alejandro. Universidad Nacional Arturo Jauretche; ArgentinaFil: Marin, Gustavo Horacio. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Osorio de Castro, Claudia Garcia Serpa. Instituto Oswaldo Cruz; BrasilFil: Albuquerque, Flavia Caixeta. Sorocaba University; BrasilFil: Ribeiro, Tatiane Bonfim. Universidade de Sao Paulo; BrasilFil: Pont, Lisa. University of Technology Sydney; AustraliaFil: Crisóstomo Landeros, José. Instituto de Salud Pública de Chile; ChileFil: Roldán Saelzer, Juan. Instituto de Salud Pública de Chile; ChileFil: Sepúlveda Viveros, Dino. Universidad del Desarrollo; Chile. Universidad Autónoma de Chile; ChileFil: Acosta, Angela. Universidad Icesi; ColombiaFil: Machado Beltrán, Manuel A.. Universidad Nacional de Colombia; ColombiaFil: Gordillo Alas, Lily Iracema. Ministry of Public Health and Social Assistance; GuatemalaFil: Orellana Tablas, Lourdes Abigail. Ministry of Public Health and Social Assistance; GuatemalaFil: Benko, Ria. University of Szeged; HungríaFil: Convertino, Irma. University of Pisa; ItaliaFil: Bonaso, Marco. University of Pisa; ItaliaFil: Tuccori, Marco. University of Pisa; ItaliaFil: Kirchmayer, Ursula. Lazio Regional Health Service; ItaliaFil: Contreras Sánchez, Saúl E.. Mexican Institute of Social Security; MéxicoFil: Rodríguez Tanta, L. Yesenia. Universidad Cientifica del Sur;Fil: Gutierrez Aures, Ysabel. Ministry of Health of Peru; PerúFil: Lin, Boya. University of Florida; Estados UnidosFil: Alipour Haris, Golnoosh. University of Florida; Estados UnidosFil: Eworuke, Efe. Real World Solutions; Estados UnidosFil: Lopes, Luciane Cruz. Sorocaba University; Brasi

An overview of 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.Facultad de Ciencias Médica