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Stay-at-home mom Rebecca McDonald’s life was saved when she participated in a thrombolytic therapy research study. A devout runner, she developed a pulmonary embolism when she resumed the sport after her youngest child Jordan was born. Dad Robert MCDonald and baby Jordan paid a visit to mom on 7 east. The McDondalds are from Boise, Idaho.
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Standards for Clinical Research
The Standards for Clinical Research, established in 2001, set forth some essential principles and processes for the conduct of clinical research in the NIH intramural research programs. Achieving patient safety, efficient protocol implementation and effective quality assurance requires adequate training of clinical investigators and sufficient infrastructure to support their endeavors. A clinical standards review process using these standards was initiated in the summer of 2000. Using a peer review approach, NIH institutes review one another. Initial reviews of five NIH institutes were conducted with the intent to develop a baseline compliance with the Standards for Clinical Research and to identify best practices in the organizations. A long-standing Clinical Center goal is for this type of standards framework to serve as a model for research institutions across the country.
Bench-to-Bedside Program
The purpose of the Bench-to-Bedside Program is encouragement of new collaborations between basic and clinical investigators across the NIH institutes. In this program intramural researchers translate scientific findings into clinical applications. Since its inception in 1998 more than 175 proposals have been submitted and 32 projects have been funded. The awards were supported by Clinical Center carry-over funds for the first two competitive cycles, after which the institutes agreed to continue the program with their own funds. In 2003 the institutes are again providing funding for one-to-two year projects of up to $100,000 a year. In addition to institute resources, a new source of funding has been identified.The NIH Office of Rare Diseases will be supporting five projects at $100,000 per award per year for two years. The projects must focus on an area of science/research directly related to a rare disease. An orphan or rare disease is generally considered to have a prevalence of less than 200,000 affected individuals in the United States. Certain diseases with more than 200,000 affected individuals are included but subpopulations of these conditions may be less than the prevalence standard for rare disease.
Protocol Services
A newly designed Office of Protocol Services was established in 2002. Formerly known as the Protocol Coordination Center, the purpose of the specialized unit is to better facilitate clinical research during the protocol phases of development, approval, implementation, and evaluation/monitoring and to provide principal investigators with tools and applications that help simplify the entire protocol process. One such effort, ProtoType, is the first step in the protocol services migration toward better use of information technology and paperless systems, standardization of systems with built-in flexibility and enhanced patient care and safety. ProtoType, a web-based clinical protocol-writing application, will simplify the protocol writing process by providing recommended language cassettes for protocol and consent form use. The application will assure that regulatory requirements are met by providing help on relevant parts of the protocol and by linking to NIH Clinical Center policies. Ultimately, it will provide links to other clinical and research databases. Protocol Services, in conjunction with the Medical Executive Committee information technology subcommittee, has been conducting iterative testing of the new application. The first version of ProtoType is expected to be released in the summer of 2003.
Clinical Bioethics International Research Ethics
Perceptions of Benefits and Risks of Biomedical Research in a Developing Country
The Department of Clinical Bioethics is studying how people involved in research in a developing country perceive the benefits and risks of biomedical research. NIH bioethics researchers and others will survey several groups of research participants as well as people in the community that are not involved in a large HIV-based research program in the Rakai district of Uganda. The Rakai Project is an ongoing study in southwestern Uganda with an intensive research program in 46 communities. The bioethics investigators are exploring the Ugandans’ perceptions of the benefits and burdens of research for themselves as individuals, for their communities and in general. No study of this magnitude has ever addressed this question. The empirical data resulting from this study will inform the deliberation and resolution of ethical issues related to biomedical research in developing countries.
Fair Benefits for Research in Developing Countries
Increasingly debated is the claim that ethical international research requires that products proven effective through research be made “reasonably available” to inhabitants of the host community. At a 2001 conference held by the Department of Clinical Bioethics on the Ethical Aspects of Research in Developing Countries in Blantyre, Malawi, participants comprised of clinical researchers from at least 8 different African countries reached a consensus that would greatly inform the debate and resolution of the issue. Department of Clinical Bioethics chief Dr. Ezekial Emanuel and representatives from the African nations in attendance at the conference coauthored an article published in the December 2002 issue of Science magazine, the first such multi-national article of its kind. The authors claim that the requirement to make a proven intervention reasonably available to the inhabitants of the host community or country at the end of a clinical research trial is “vague and seriously flawed.” The bioethicists claim that this requirement, although thought necessary to avoid exploitation in developing countries, confuses a particular “type of benefit with the need to provide a fair share of benefits to avoid exploitation” and further that it only “applies to a narrow range of research (i.e., successful Phase III studies).” They propose a framework of fair benefits to research participants instead of a requirement for reasonable availability.
Imaging Sciences
Intraoperative Imaging
This initiative will provide a real-time magnetic resonance imaging capability in the surgical suite. Display of current and pre-operative imaging data will be performed using state-of-the-art 3D and virtual reality technology. Under the direction of King Li, M.D., M.B.A., Associate Director for Imaging Sciences, the project continues to move toward implementation. This is a collaborative effort between the Clinical Center, the National Cancer Institute and the National Institute of Neurological Disorders and Stroke.
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Bennie Wilson jokes with his wife Karen, a kidney transplant recipient, on patient care unit 11 east. The Wilsons are from San Antonio, Texas.
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Picture Archiving and Communication System/Radiology Information System (PACS/RIS)
A multi-year, multi-million dollar effort to initiate filmless radiology services and automated radiology operations began in 2000. An enterprise-wide version was released in the summer of 2002. The system can display radiology images and reports on workstations and desktop computers across NIH. An upgraded version that provides more versatility in displaying the image data will be released in the spring of 2003. With this service, clinicians can order state-of-the-art image processing procedures such as virtual endoscopy, 3D angiography, 3D skeletal studies, brain perfusion studies, and functional tumor studies. The processed study images are then available to the clinicians via the PAC system.
Molecular Imaging
The new Molecular Imaging Laboratory is now fully functional. Scientists who have a background in physics, engineering, molecular biology, chemistry, genomics, proteomics, and image analysis work together as a team to explore new ways of imaging molecular events in vivo and to develop new targeted imaging and therapeutic agents. This translational research program will provide new clinical research tools that allow the Imaging Sciences Program in the Clinical Center to move boldly into the post-genomic era.
State-of-the-Art Imaging Equipment Procurement
To continually provide cutting-edge imaging technologies for clinical research, a number of state-of-the-art imaging equipment purchases are being made: a PET/CT scanner with a 16-slice CT scanner combined with a top-of-the-line PET scanner; a 3T MRI; a 16-slice CT scanner; a 3D ultrasound unit; and a combined CT-angiography unit. The configuration of much of this equipment is not commercially available and will provide the Imaging Sciences Program with some unique capabilities.
Clinical Research Information System (CRIS)
CRIS, the Clinical Center’s next-generation clinical information infrastructure, is a $60 million project that will link and support patient care, research and management. A vendor has been selected to build the largest component of CRIS, the core that comprises the patient-care aspects of the information system. These patient-care aspects include the electronic medical record and housing data such as lab results, pharmacy orders and multidisciplinary care documentation. This phase of the CRIS project replaces and expands the Clinical Center’s current hospital information system known as the Medical Information System, or MIS. MIS has been in operation for about a quarter century. Another 2002 milestone was selection of a system integrator to ensure that the many information systems that comprise CRIS are developed and deployed efficiently and effectively. Once complete, at least 24 distinct information systems will feed into two CRIS hubs, the Clinical Data Repository and the Clinical Data Warehouse.
Transfusion Medicine
Immune Cell Harvesting
The use of donor natural killer (NK) cells in the setting of genetically different blood cell transplantation is being investigated. Evidence suggests that NK cells may have anti-leukemia or anti-tumor properties and do not appear to cause graft-versus-host disease. This means there may be a role for NK cells as part of the transplant regimen. Work is being conducted to develop methods for isolating, manipulating, storing, and assaying the NK cells. This project is being done in collaboration with the National Heart, Lung, and Blood Institute.
Increasing Red Cell Availability
Under a research protocol, persons with the inherited disorder of iron absorption, hereditary hemochromatosis, are being studied as potential blood donors. Collecting blood from these individuals is the standard treatment for iron overload. However systems to assure safety of this blood for transfusion, and safe and easy methods of following iron depletion have been lacking. The Clinical Center Department of Transfusion Medicine has developed a model system that addresses all of these issues. The first 100 research subjects entered now supply 10 percent of the red blood cells used for transfusion. Applying such a system nationwide should help address blood shortages in the United States.
Islet Cell Harvesting
A laboratory service has been established to isolate pancreatic islets from cadaver organ donors. The process isolates islets, which contain beta cells that produce insulin, and transplants those islets into the livers of patients with Type 1 diabetes. The islet transplant is done through an injection using interventional radiology. The outcome may free Type 1 diabetes patients from being insulin dependent or decrease the amount of insulin they require. This program is led by the National Institute of Diabetes and Digestive and Kidney Diseases and is supported by the Clinical Center.
Platelet Transfusion
More than 30,000 units of platelets for transfusion are collected annually by the Department of Transfusion Medicine in about 4,500 procedures. About 10 percent of these transfusions have limited clinical success, meaning minimal or no increase in platelet count. A molecular complex on the surface of most cells, Human Leukocyte Antigen (HLA), is responsible for rejection of transplants. A genetic analysis study is underway to determine if there is a benefit to platelet survival by increasing the resolution of donor/recipient matching. If so, donors can be selected not only for platelet transfusions but also for other forms of transfusion and transplantation where histocompatibility could be increased through better matching. This study is being undertaken with collaborators at the University of Pittsburgh and the French National Transfusion Service.
Transfusion-transmitted Infections
Blood donors and recipients are being studied to determine the frequency and importance of transfusion-transmitted infections. Specimens from donated blood are tested for a variety of infectious agents and stored long-term for detection of such agents that may emerge in the future. Transfusion recipients will be followed for years to determine whether they have developed infections from transfusions and what impact this might have on their future health. Previous studies conducted by the department of Transfusion Medicine have defined the clinical importance of post-transfusion Hepatitis B and C and HIV.
Critical Care Medicine
Sickle Cell Anemia and Pain
Sickle cell anemia pain occurs when blood vessels are blocked by sickled red blood cells. Researchers from the Clinical Center’s Department of Critical Care Medicine believe this blockage may be exacerbated by an over-abundance of hemoglobin in the blood produced by faulty red blood cells, and they have found a connection between freely-circulating hemoglobin and the pain associated with the disease. In persons with sickle cell anemia, normally disc-shaped red blood cells become crescent-shaped due to an inherited abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a vital protein that carries oxygen from the lungs to the body tissues. For those with the mutation, red blood cells don’t work properly but break down and release large amounts of hemoglobin directly into the blood stream. This study has discovered that the chronic release of cell-free hemoglobin into the blood stream overwhelms the systems in place to remove it by rapidly destroying nitric oxide, a short-lived gas produced by cells lining the blood vessels, and that the excess cell-free hemoglobin reacts with the gas 1,000 times more rapidly than it would if the hemoglobin were in a red blood cell. Destruction of the nitric oxide leads to constricted blood vessels, high blood pressure in the lungs and the restricted flow of oxygen and nutrients to vital tissues and organs. Nitric oxide inhalation therapy and a set of highly sensitive assays were used by the scientists in this study to show that nitric oxide scavenging by the cell-free hemoglobin may play a major role in sickle cell disease. The nitric oxide therapy used in the study inactivated the cell-free hemoglobin, a mechanism that might reduce the severity or duration of pain crisis. The research team includes investigators from the National Institute of Diabetes, Digestive, and Kidney Diseases; the National Heart, Lung, and Blood Institute; and the Medical College of Wisconsin.
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