Recent advances in molecular biology suggest that in vivo manipulation of gene products may favorably alter clinical outcome in patients with congestive heart failure or vascular disease. As part of the University of Pittsburgh's specific genes that play a pathophysiologic role in myocardial failure and failure of arteriovenous shunts. While it is hypothesized that these novel therapies will alter the phenotypic expression of specific target cells (e.g., failing cardiac myocytes, vascular cells in arteriovenous shunts), the effects of these genes on other non- targeted cells are unknown. Accordingly, it is mandatory that closely supervised evaluation of enrolled patients be performed to not only assess the anticipated favorable outcome but to ensure that there are no unexpected side effects that may outweigh the benefits of these therapies. The primary goal of the clinical research core of this RFA is to provide independent oversight of both of the proposed clinical trials to ensure that potential adverse events are identified and appropriately reported to the study's independent Data and Safety Monitoring, the University of Pittsburgh Biomedical IRB, the National Institutes of Health and, when appropriate, the US Food and Drug Administration.
The specific aims of the core are: 1. To ensure that clinical gene interventions in this project adhere to all local and federally-mandated scientific and bioethic agencies. 2. To audit and investigate all adverse and significant adverse event associated with the proposed trials for quality assurance. 3. To form an independent data and safety monitoring board which will be responsible for interim analysis of safety and outcome parameters to ensure that adverse events do not compromise patient safety. To ensure patient safety, which is the highest priority of these studies, the clinical core will be responsible for (1) oversight of reporting of adverse events, (2) quality assurance, (3) interim analysis of adverse events and patient outcome, and (4) formation of an independent data and safety monitoring board which will evaluate the incidence of adverse events and patient outcomes to determine whether the studies meet pre-specified safety criteria. To perform these functions, the clinical core staff will be administratively, financially, and scientifically independent of the investigators and staff of the molecular biology and clinical trial projects. The independence of the clinical core has been ensured by the PI of the overall project (Dr. Joe Glorioso) and the Dean of the University of Pittsburgh Medical School (Dr. Arthur Levine) who have granted the clinical core PI (Dr. Steven Reis) complete autonomy and have empowered him with the right to withdraw active therapy form specific patients and to terminate the clinical studies should they meet pre- specified safety criteria.
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