ABSTRACT
El paradigma tradicional de la investigación clínica farmacológica comprende la realización de estudios de fase 1, 2 y 3. Sin embargo, el reciente avance de lo que se ha dado en llamar "medicina de precisión" ha impulsado el surgimiento de innovaciones en el diseño de ensayos clínicos, en especial en el área de la oncología. Este artículo tiene como propósito describir y caracterizar los estudios de farmacología clínica de oncología autorizados por la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) durante el período comprendido entre agosto de 2018 y julio de 2022; analizar el estado de situación de los diseños de los ensayos clínicos en oncología, las fases de investigación, los productos en investigación y el sitio de localización tumoral en relación con el avance de la medicina de precisión y los diseños innovadores.
The traditional paradigm of pharmacological clinical research involves carrying out phase 1, 2, and 3 studies. However, the recent advance of what has been called "precision medicine" has promoted the emergence of innovations in the design of clinical trials, especially in the area of oncology. The purpose of this article is to describe and characterize oncology clinical pharmacology studies authorized by the National Administration of Drugs, Food and Medical Devices (ANMAT) during the period from August 2018 to July 2022, and analyze the status of the clinical trial designs, research phases, investigational products and tumor site locations concerning the advancement of precision medicine and innovative designs
Subject(s)
Clinical Trial , Study Characteristics , Medical OncologyABSTRACT
El avance de la ciencia y tecnología en los últimos años dio lugar a la necesidad de dar respuesta a una mayor cantidad de preguntas en investigación de forma más eficiente. Esto ha provocado la generación de nuevos diseños en investigación, dando origen a los "protocolos maestros". A diferencia de los diseños tradicionales en los que en cada ensayo clínico se prueba habitualmente un solo fármaco, en una única población, con una patología determinada, los protocolos maestros utilizan una estructura con un diseño de ensayo clínico y un protocolo para evaluar simultáneamente múltiples fármacos y/o enfermedades, en múltiples sub-estudios. Entre estos novedosos diseños se pueden mencionar tres tipos: canasta (basket), paraguas (umbrella) y plataforma (platform) los cuales serán analizados en este artículo. Debido a su complejidad, el abordaje de estos nuevos modelos de ensayo clínico requiere la revisión y actualización permanente de los estándares vigentes y una constante discusión por parte de las diferentes agencias regulatorias a nivel mundial. Estos diseños no deben considerarse a priori como medios para reducir la rigurosidad de la planificación de los ensayos clínicos ni disminuir los estándares regulatorios, sino como herramientas para gestionar situaciones experimentales complejas. Desde el punto de vista regulatorio, para poder analizar y dar respuesta a estos desafíos, ANMAT cuenta, actualmente, con espacios de intercambio que permiten crear el ámbito apropiado de discusión científica-regulatoria que aliente el desarrollo de nuevos medicamentos, pero manteniendo estrictos estándares de calidad éticos y científicos. En esta revisión se plantea la necesidad de conocer en detalle estos nuevos diseños analizando sus potenciales beneficios y limitaciones
The need to answer a greater number of questions more efficiently has led to the generation of new designs in research, giving rise to the "master protocols". This term refers to a clinical trial design created to evaluate multiple hypotheses through substudies that are developed simultaneously and that may contain an adaptive design. Among these novel designs, three types can be mentioned: basket, umbrella and platform which will be analyzed in this article. Due to their complexity, the approach of these new clinical trial designs requires the continuing revision and updating of the current standards and a constant discussion by the different regulatory agencies worldwide. From the regulatory point of view, in order to analyze and satisfy these challenges, ANMAT currently has exchange spaces that allow the creation of the appropriate field of scientific-regulatory discussions that encourage the development of new medicines, while maintaining strict standards of ethical and scientific quality. This revision raises the need to know in detail these new designs analyzing their potential benefits and limitations.
Subject(s)
Social Change , Clinical Protocols , Clinical TrialABSTRACT
Purpose. The main purpose is to define more accurately the epileptogenic zone (EZ) with noninvasive methods in those patients with MRI diagnosis of focal cortical dysplasia (FCD) and epilepsy who are candidates of epilepsy surgery. Methods. Twenty patients were evaluated prospectively between 2007 and 2010 with comprehensive clinical evaluation, video-electroencephalography, diffusion tensor imaging (DTI), and high-resolution EEG to localize the equivalent current dipole (ECD). Key Findings. In 11 cases with white matter asymmetries in DTI the ECDs were located next to lesion on MRI with mean distance of 14.63 millimeters with topographical correlation with the EZ. Significance. We could establish a hypothesis of EZ based on Video-EEG, high-resolution EEG, ECD method, MRI, and DTI. These results are consistent with the hypothesis that the EZ in the FCD is complex and is often larger than visible lesion in MRI.
ABSTRACT
The issue of psychotic disorders in epilepsy has given rise to great controversy among professionals; however, there are not many studies in this area and the physiopathological mechanisms remain unknown. The aim of this study was to describe the spectrum of psychotic disorders in an Argentine population with refractory temporal lobe epilepsy (RTLE) and to determine the risk factors associated with psychotic disorders. Clinical variables of the epileptic syndrome were compared among a selected population with RTLE with and without psychotic disorders (DSM-IV/Ictal Classification of psychoses). Logistic regression was performed. Sixty-three patients with psychotic disorders (Psychotic Group, PG) and 60 controls (Control Group, CG) were included. The most frequent psychotic disorders were brief psychotic episodes (35%) (DSM-IV) and interictal psychosis (50%) (Ictal Classification). Risk factors for psychotic disorders were bilateral hippocampal sclerosis, history of status epilepticus, and duration of epilepsy greater than 20 years.
Subject(s)
Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/epidemiology , Psychotic Disorders , Adolescent , Adult , Aged , Aged, 80 and over , Argentina/epidemiology , Case-Control Studies , Diagnostic and Statistical Manual of Mental Disorders , Electroencephalography , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Psychometrics , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Psychotic Disorders/etiology , Retrospective Studies , Risk Factors , Statistics, Nonparametric , Young AdultABSTRACT
We describe a patient who showed cystic lesions in the midbrain and obstructive hydrocephalus. MR imaging features corresponded to abnormal dilatation of perivascular spaces. Similar clinical and MR imaging findings were described in previous reports of patients presenting with mesencephalo-thalamic expanding lacunae; the diagnosis of some of those cases was confirmed at postmortem examination This condition is extremely rare but should be part of a differential diagnosis when evaluating cystic abnormalities in this area of the brain.
