RESUMEN
The Sentinel System is a national electronic postmarketing resource established by the US Food and Drug Administration to support assessment of the safety and effectiveness of marketed medical products. It has built a large, multi-institutional, distributed data network that contains comprehensive electronic health data, covering about 700 million person-years of longitudinal observation time nationwide. With its sophisticated infrastructure and a large selection of flexible analytic tools, the Sentinel System permits rapid and secure analyses, while preserving patient privacy and health-system autonomy. The Sentinel System also offers enhanced capabilities, including accessing full-text medical records, supporting randomized clinical trials embedded in healthcare delivery systems, and facilitating effective collection of patient-reported data using mobile devices, among many other research programs. The nephrology research community can use the infrastructure, tools, and data that this national resource offers for evidence generation. This review summarizes the Sentinel System and its ability to rapidly generate high-quality, real-world evidence; discusses the program's experience in, and potential for, addressing gaps in kidney care; and outlines avenues for conducting research, leveraging this national resource in collaboration with Sentinel investigators.
Asunto(s)
Bases de Datos Farmacéuticas , Vigilancia de Productos Comercializados , Insuficiencia Renal Crónica/terapia , Investigación Biomédica , Sistemas de Información en Salud , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
The National Institutes of Health (NIH) oversight of human gene transfer research, which is defined as the deliberate transfer of recombinant and/or synthetic nucleic acid molecules to humans, originates with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). The NIH Guidelines, which were first published in the Federal Register almost 40 years ago, have been amended numerous times to remain responsive to scientific progress and to clearly define the responsibilities of NIH, the Recombinant DNA Advisory Committee (RAC), investigators, and institutions. Human gene transfer trials conducted at clinical sites in the United States (USA) are subject to the NIH Guidelines if they are conducted at, or sponsored by, an institution that receives any support for recombinant or synthetic nucleic acid research from the NIH. Human gene transfer trials conducted either in the USA or abroad are also subject to the NIH Guidelines if the investigational agent was developed with NIH funds and the institution that developed the investigational materials sponsors or participates in these projects. Trials are registered with the NIH Office Biotechnology Activities (OBA) and there are ongoing reporting requirements. Each new trial is reviewed by the RAC, and those that are novel or raise unique ethical or social issues are selected for review at quarterly public RAC meetings. The RAC also advises the NIH on policy and other matters relating to clinical gene transfer research and biosafety.
Asunto(s)
ADN Recombinante/uso terapéutico , Control de Medicamentos y Narcóticos/legislación & jurisprudencia , Terapia Genética/legislación & jurisprudencia , Vectores Genéticos/uso terapéutico , Investigación Biomédica Traslacional/legislación & jurisprudencia , Animales , Ensayos Clínicos como Asunto , Terapia Genética/ética , Humanos , Consentimiento Informado/ética , Consentimiento Informado/legislación & jurisprudencia , National Institutes of Health (U.S.) , Seguridad del Paciente/legislación & jurisprudencia , Guías de Práctica Clínica como Asunto , Proyectos de Investigación , Investigación Biomédica Traslacional/ética , Estados UnidosAsunto(s)
Investigación Biomédica , Conjuntos de Datos como Asunto , Aprobación de Drogas/métodos , Medicina Basada en la Evidencia , Investigación Biomédica/métodos , Aprobación de Drogas/legislación & jurisprudencia , Registros Electrónicos de Salud , Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Importance: Only about half of patients with atrial fibrillation (AF) who are at increased risk for stroke are treated with an oral anticoagulant (OAC), despite guideline recommendations for their use. Educating patients with AF about prevention of stroke with OACs may enable them as agents of change to initiate OAC treatment. Objective: To determine whether an educational intervention directed to patients and their clinicians stimulates the use of OACs in patients with AF who are not receiving OACs. Design, Setting, and Participants: The Implementation of a Randomized Controlled Trial to Improve Treatment With Oral Anticoagulants in Patients With Atrial Fibrillation (IMPACT-AFib) trial was a prospective, multicenter, open-label, pragmatic randomized clinical trial conducted from September 25, 2017, to May 1, 2019, embedded in health plans that participate in the US Food and Drug Administration's Sentinel System. It used the distributed database comprising health plan members to identify eligible patients, their clinicians, and outcomes. IMPACT-AFib enrolled patients with AF, a CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score of 2 or more, no evidence of OAC prescription dispensing in the preceding 12 months, and no hospitalization-related bleeding event within the prior 6 months. Interventions: Randomization to a single mailing of patient and/or clinician educational materials vs control. Main Outcomes and Measures: Analysis was performed on a modified intention-to-treat basis. The primary end point was the proportion of patients with at least 1 OAC prescription dispensed or at least 4 international normalized ratio test results within 1 year of the intervention. Results: Among 47â¯333 patients, there were 24â¯909 men (52.6%), the mean (SD) age was 77.9 (9.7) years, mean (SD) CHA2DS2-VASc score was 4.5 (1.7), 22â¯404 patients (47.3%) had an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more, and 8890 patients (18.8%) had a history of hospitalization for bleeding. There were 2328 of 23â¯546 patients (9.9%) in the intervention group with initiation of OAC at 1 year compared with 2330 of 23â¯787 patients (9.8%) in the control group (adjusted OR, 1.01 [95% CI, 0.95-1.07]; P = .79). Conclusions and Relevance: Among a large population with AF with a guideline indication for OACs for stroke prevention who were randomized to a mailed educational intervention or to usual care, there was no clinically meaningful, numerical, or statistically significant difference in rates of OAC initiation. More-intensive interventions are needed to try and address the public health issue of underuse of anticoagulation for stroke prevention among patients with AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03259373.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Tromboembolia , Anciano , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Estudios Prospectivos , Medición de Riesgo/métodos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Tromboembolia/epidemiologíaAsunto(s)
Terapia Genética , Vectores Genéticos , Trasplante de Células Madre Hematopoyéticas , Retroviridae/genética , Técnicas de Transferencia de Gen , Terapia Genética/efectos adversos , Terapia Genética/ética , Terapia Genética/legislación & jurisprudencia , Vectores Genéticos/efectos adversos , Vectores Genéticos/genética , Humanos , Proyectos de InvestigaciónRESUMEN
Institutions that receive National Institutes of Health (NIH) funding for research involving recombinant or synthetic nucleic acid molecules are required, as a term and condition of their funding, to comply with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) (NIH, 2013). Under the NIH Guidelines, institutions must establish and register an Institutional Biosafety Committee (IBC) with the NIH. The IBC is then responsible for reviewing and approving research projects subject to the NIH Guidelines. The IBC review of projects involving recombinant or synthetic nucleic acid molecules is critical to ensuring that such research is conducted in a safe and responsible manner. In 2006, staff from NIH began conducting educational site visits to institutions that had an IBC registered with NIH. The purpose of these site visits is to assist IBCs with their institutional programs of oversight for recombinant or synthetic nucleic molecules. Based on our findings, the site visit program has been beneficial to institutional biosafety programs. The information gathered during the site visits has allowed NIH to tailor its educational materials to help institutions address their oversight challenges. Additionally, since NIH's visits are primarily educational in nature, we have been able to foster a positive environment in which IBC members and staff feel comfortable reaching out to NIH for advice and assistance.
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Investigación Biomédica/organización & administración , Vigilancia de Productos Comercializados/métodos , Evaluación de la Tecnología Biomédica/organización & administración , United States Food and Drug Administration/organización & administración , Investigación Biomédica/normas , Recolección de Datos/métodos , Humanos , Vigilancia de Productos Comercializados/normas , Evaluación de la Tecnología Biomédica/normas , Estados Unidos , United States Food and Drug Administration/normasRESUMEN
Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances.
Asunto(s)
Terapia Genética/ética , Animales , Educación Continua , Investigación Genética , Terapia Genética/economía , Terapia Genética/legislación & jurisprudencia , Vectores Genéticos , Humanos , National Institutes of Health (U.S.) , Investigación con Células Madre , Trasplante de Células Madre , Transducción Genética , Estados UnidosRESUMEN
Gene therapy has shown clinical efficacy for several rare diseases, using different approaches and vectors. The Gene Therapy for Rare Diseases workshop, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities and Office of Rare Diseases Research, brought together investigators from different disciplines to discuss the challenges and opportunities for advancing the field including means for enhancing data sharing for preclinical and clinical studies, development and utilization of available NIH resources, and interactions with the U.S. Food and Drug Administration.
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Enfermedades Raras/genética , Enfermedades Raras/terapia , Ensayos Clínicos como Asunto , Terapia Genética , Humanos , National Institutes of Health (U.S.) , Investigación Biomédica Traslacional , Estados Unidos , United States Food and Drug AdministrationRESUMEN
In response to public and scientific concerns regarding human gene transfer research, the National Institutes of Health (NIH) developed a transparent oversight system that extends to human gene transfer protocols that are either conducted with NIH funding or conducted at institutions that receive NIH funding for recombinant DNA research. The NIH Recombinant DNA Advisory Committee (RAC) has been the primary advisory body to NIH regarding the conduct of this research. Human gene transfer research proposals that are subject to the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) must be submitted to the NIH Office of Biotechnology Activities (OBA), and protocols that raise novel scientific, safety, medical, ethical, or social issues are publicly discussed at the RAC's quarterly public meetings. OBA also convenes gene transfer safety symposia and policy conferences to provide a public forum for scientific experts to discuss emerging issues in the field. This transparent system of review promotes the rapid exchange of important scientific information and dissemination of data. The goal is to optimize the conduct of individual research protocols and to advance gene transfer research generally. This process has fostered the development of retroviral, lentiviral, and adeno-associated viral vector mediated gene delivery.
Asunto(s)
Comités Consultivos , ADN Recombinante/genética , Terapia Genética/normas , National Institutes of Health (U.S.) , Comités Consultivos/estadística & datos numéricos , Animales , Ensayos Clínicos como Asunto , Dependovirus/genética , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Vectores Genéticos , Humanos , Guías de Práctica Clínica como Asunto , Retroviridae/genética , Estados UnidosRESUMEN
There have been several recent scientific advances in gene-based and cell-based therapies that might translate into novel therapeutic approaches for neurodegenerative disorders. Such therapies might need to be directly delivered into the CNS, and complex scientific and ethical assessment will be needed to determine whether a sham neurosurgical arm should be included in clinical trials assessing these agents. We have developed a framework of points for investigators to consider when designing trials that involve direct delivery of a therapeutic agent to the CNS. The inclusion of a sham neurosurgical arm will be guided in part by the objectives of the clinical study (preliminary safety, optimisation, and feasibility vs preliminary efficacy vs confirmatory efficacy) and the need to minimise bias and confounds. Throughout the clinical development process, the perspectives of researchers, ethicists, and patients must be considered, and risks should be minimised whenever possible in a manner that is consistent with good trial design.