September 2, 2004


Dr. Barbara Alving, Acting Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed members to the 215th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC).

Dr. Alving reminded everyone that two NHLBI programs are recognized officially in September: the Sickle Cell Disease Program and the Cholesterol Education Program. She reported that recent findings show declining stroke rates in children with sickle cell disease in California, largely due to results of the NHLBI-supported Stroke Prevention in Sickle Cell Anemia (STOP1) trial. Cholesterol Month 2004 emphasizes the importance of having one's cholesterol measured and knowing one's risk of developing heart disease. A web-based Cholesterol Month Kit contains materials to instruct individuals about how to improve their cholesterol numbers. Dr. Alving recommended that everyone read about the recently updated recommendations for cholesterol treatment, which are available from the Cholesterol Month Kit.

Staff Updates

Dr. Alving informed the Council that the search for a new NHLBI director is continuing. She also announced that Dr. Eser Tolunay is now the Director of the Vascular Biology Research Program in the Institute's Division of Heart and Vascular Diseases. In addition, Dr. Sonia Skarlatos has been appointed the Deputy Director of the Division of Heart and Vascular Diseases.

Member Updates

Drs. Austin, Costanzo, Drazen and Thomas as well as Ms. Byrnes were unable to attend September Council. In addition, the Institute is searching for a replacement for Mary H. Deer, R.N., who recently found it necessary to step down from the Council. The replacements for the retiring council members have been invited and we are in the process of receiving their acceptances. Their appointments officially begin November 1, 2004 but they will be invited to attend October Council.

Guest Speakers:

  • Dr. Charles Peterson, Director, Division of Blood Diseases and Resources, NHLBI.
  • Dr. Elizabeth Nabel, Director, Clinical Research Program, Division of Intramural Research, NHLBI.
  • Dr. Robert Balaban, Scientific Director of Laboratory Research, Division of Intramural Research, NHLBI.
  • Dr. Warren Leonard, Chief of the Laboratory of Molecular Immunology, Division of Intramural Research, NHLBI.
  • Dr. James Kiley, Director of the Lung Diseases Division, NHLBI.
  • Dr. Robert Lemanske, Jr., Council member and Professor of Pediatrics and Medicine at the University of Wisconsin Hospital in Madison , Wisconsin .


In addition to the Council Briefing Book there were the following publications:

  • a copy of the September FYI Newsletter,
  • Bi-Lingual Facts Sheets on Blood Pressure and Healthy Heart Tips for Filipino and Vietnamese Communities,
  • a pamphlet entitled “NIH Improving Health Through Discovery” which highlights major accomplishments from NIH-supported research.

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The Council was reminded that according to Public Law 92-463, the Federal Advisory Committee Act, the meeting of the NHLBAC would be open to the public except during consideration of grant applications. A notice of this meeting was published in the Federal Register indicating that it would start at 8:30 a.m. and remain open until approximately 12:00 p.m. Dr. Alving also reminded the Council members that they are Special Government Employees and are subject to Departmental conduct regulations.

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The NIH budget for FY 2005 has not yet been approved. In the current period of "budget flattening", the Institute is trying to maintain its funding line for traditional research grants (R01s). In FY 2004 the Institute has funded R01s through the 25.0 percentile. The Institute expects to issue fewer initiatives in the coming year and will be investigating how to increase efficiency in its clinical trials.

Dr. Alving asked the Council members whether September 8 would be better for the September 2005 Council instead of September 1 and the Council unanimously agreed.

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Dr. Charles Peterson, Director, Division of Blood Diseases and Resources, NHLBI, presented an overview of the Institute’s sickle cell disease research program. Dr. Peterson described progress in treating sickle cell disease patients since the early 1970s, when the NHLBI established the first comprehensive sickle cell centers. Since then, the life expectancy for sickle cell disease patients has risen from the teen years to the forties and fifties. There are a number of programs including a strategic plan for a gene based cure of the hemoglobinopathies, a pulmonary initiative, intervention protocols in collaboration with intramural in the area of pulmonary disease, hydroxyurea programs, initiatives in rare diseases, and networks (hemostasis and thrombosis, bone marrow transplant, sickle cell disease, and thalassemia), as well as important training programs to attract the best clinicians. Dr. Peterson also discussed remaining challenges and steps the NHLBI is taking to meet them; for example, looking for other research areas that offer synergies with sickle cell disease such as thalassemia research in order to increase efficiency of research efforts, and partnering with other institutes and agencies. Improving quality of life and the management of individuals with sickle cell disease are also important priorities. Finally, the U.S. Postal Service plans to issue a stamp in late September to raise public awareness of the disease.

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V. INTRAMURAL PRESENTATION- Drs. Elizabeth Nabel and Robert Balaban

Dr. Elizabeth Nabel, Director, Clinical Research Program, Division of Intramural Research, NHLBI, previewed the presentation she plans to make to Council next month. She highlighted three clinical research areas of major growth at the NIH: stem cell research; sickle cell anemia and pulmonary complications; and cardiothoracic surgery. The Clinical Research Program is also hosting a two-day symposium September 13-14 entitled “Cardiovascular Regenerative Medicine” focusing on basic aspects of stem cell biology and their potential application to the cardiovascular system. Dr. Mark Gladwin has been recruited to join NHLBI from the Critical Care Medicine Department of the Clinical Center. Dr. Keith Horvath has recently joined NHLBI from Northwestern University to develop the cardiothoracic surgery program.

Dr. Robert Balaban, Director, Laboratory Research Program, Division of Intramural Research, NHLBI, discussed the challenge over the next several decades in making the transition from understanding individual molecular machines to understanding how these work and function together in whole organisms to being able to unravel the complexity of disease. A new field of research referred to as systems biology has evolved to deal with this complexity. Dr. Balaban described discovery-based tools such as gene sequencing, gene expression, proteomics, and metabolomics which are necessary for the systems biology approach. Dr. Balaban described three ongoing intramural projects in cardiac developmental biology, including RNAi screening, mutagenesis screening, and screening for post translation or modifications of protein function with respect to cardiac development. Dr. Balaban emphasized that the tools and information developed so far in his laboratory have been posted on their website. He also emphasized the importance of collaborations with the extramural community which are always welcomed.

Dr. Warren Leonard, Chief, Laboratory of Molecular Immunology, Division of Intramural Research, NHLBI, reported on research undertaken in his lab on the role of defective cytokine signaling in severe combined immunodeficiency diseases (SCID). Cytokines are molecules produced by one cell that act on the same or another cell. Cytokines include interleukins, hematopoietic factors, growth hormones and interferons. Dr. Leonard presented several findings about a family of cytokines (Type I cytokines) including their structure and their role in SCID.

At the conclusion of the presentations, Dr. Alving and several NHLBI staff members summarized ways in which the NHLBI fosters interaction between research communities within and outside the NIH; for example, through Material Transfer Agreements (MTAs) with industry, Cooperative Research and Development Agreements (CRADAs) and programs like the Programs for Genomic Applications (PGAs). Many resources developed in the PGAs are now available to the extramural research community (e.g., microarray tools and data; animal models, and mutagenesis phenotyping). NHLBI policy requires that all information and tools developed in the PGAs be made freely available in a timely manner to the research community through the NHLBI website.

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VI. ROADMAP UPDATE - Dr. Lawrence Friedman

Dr. Lawrence Friedman, Acting Deputy Director, NHLBI, updated Council members on the NIH Roadmap. The Roadmap identifies major opportunities and gaps in biomedical research that no single NIH Institute or Center can address alone and encourages cross-Institute activities. Opportunities have been identified in three main areas: new pathways to discovery; research teams of the future; and re-engineering the clinical research enterprise. Over 25 initiatives were released this year. The NHLBI is the lead Institute for two related to clinical research networks: Inventory and Evaluation of Clinical Research Networks, and Feasibility of Integrating and Expanding Clinical Research Networks. In addition, Dr. Balaban added that the Institute’s Division of Intramural Research is taking the lead on a project to construct an Imaging Probe Development Center to produce probes that are not readily available from a commercial supplier. In response to queries, Dr. Friedman emphasized that the Roadmap accounts for less than one percent of the NIH budget and is meant to be a stimulant for capitalizing on available research resources, not to replace current research activities or priorities.

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VII. NHLBI CLINICAL REASEARCH NETWORKS- Dr. James Kiley and Dr. Robert Lemanske

Dr. James Kiley, Director, Division of Lung Diseases, NHLBI, presented an overview of the Institute’s Clinical Research Networks. He described their structure and organization and the manner in whichclinical trials are developed and monitored. Dr. Kiley estimated that the process of moving from protocol concept review to implementation is at least 7 months shorter for clinical research networks than for trials performed through investigator-initiated R01 applications. The NHLBI currently supports nine clinical research networks ($60 million in Fiscal Year 2004) that address a range of biomedical areas; the Institute plans to start three additional networks in FYs 2005-2006. The Institute has an internal network coordinating committee which is developing best practices for networks and promoting exchange of information. Topics discussed include informed consent, recruitment strategies, conflict of interest, private sector interactions, fiscal management, and data sharing.

Dr. Robert Lemanske, Jr., Council member and Professor of Pediatrics and Medicine at the University of Wisconsin Hospital in Madison, Wisconsin, discussed the work of two asthma-related networks—the Asthma Clinical Research Network (ACRN) and the Childhood Asthma Research and Education (CARE) Network. Dr. Lemanske reviewed some of the trials and studies that were conducted by ACRN, which ran for 10 years starting in 1993, and summarized its major contributions to asthma patient care, including the proper use of beta agonists in clinical practice, new advances in beta receptor pharmacogenetics, efficacy and toxicity of inhaled corticosteroids, and responsiveness to drugs or drug combinations in mild and moderate persistent asthma. He also reviewed several pediatric asthma treatment trials conducted as part of the CARE network.

Council members were supportive of the Institute's clinical research network programs. They were particularly enthusiastic about the time and cost savings afforded by the networks' infrastructure and the contributions the networks have made to the training of clinical investigators. There was also a suggestion to broaden the network concept to pre-clinical and translational studies as well. The point was also made that there is the ability within networks to do research on more than one question in the same patient population at the same time; this cannot be done in other clinical studies. In addition, results are almost instantaneously disseminated across the networks, which in effect, means across the country.

Council indicated a desire to hear how study sections have been reorganized to be more receptive to clinical research and Dr. Alving stated that this would be arranged for October Council. Council also discussed the strengths and weaknesses of the new Specialized Centers of Clinically-Oriented Research. While there is some difficulty in incorporating clinical research with basic research in terms of definition and evaluation, the program is an excellent opportunity for collaboration between basic scientists and clinicians to promote translational research. However, for disease conditions where there are very few patients, networks provide a more feasible approach. Comments were also made on access to FDA databases which are not available to these studies, although there is some contribution to FDA databases through INDs within the network and there are also FDA scientists on protocol review committees. Dr. Kiley also pointed out that there is now an effort to collaborate between the adult and children’s networks to address questions that pertain to both populations and to maximize efficiency.

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Dr. Carl Roth, Associate Director for Scientific Program Operation, NHLBI, updated the Council on recent policy changes regarding program project grants (P01s) and grant applications with direct costs of $500,000 or more in any one year. Both sets of policy changes were posted on the NHLBI Web site during the summer and circulated via the NHLBI Research and Policy update Listserv. One of the most significant P01 policy changes is the removal of restrictions on the number of individual components of a P01 application that can be submitted from organizations other than the applicant organization. Two changes were made to the guidelines for applications with direct costs of $500,000 or more in any one year. One is that all requests made to the NHLBI after July 1, 2004, to accept applications for Phase III clinical trials with direct costs greater than $500,000 in any given year must include plans to submit at least two applications, one of which is for the support of a data coordinating center. The second change is related to financial management, and stipulates that beginning October 1, 2005, requests to submit new applications with direct costs that are greater than the allowable requested direct cost for P01s in any year will be considered by the NHLBI once a year only and the deadline will be November 15. This will allow the Institute to review all requests for very large amounts at one time.


This portion of the meeting was closed to the public in accordance with the determination that it concerned matters exempt from mandatory disclosure under Sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. appendix 2).

The session included a discussion of procedures and policies regarding voting and confidentiality of application materials, committee discussions and recommendations. Members absented themselves from the meeting during discussion of and voting on applications from their own institutions, or other applications in which there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to this effect.


The Council considered 1,181 applications requesting $ 1,833,342,983 in total direct costs. The Council recommended 1,179 applications with total direct costs of $ 1,823,689,661. A summary of applications by activity code may be found in Attachment B.


The meeting was adjourned at 2:30 p.m. on September 2, 2004.


I hereby certify that the foregoing minutes are accurate and complete.

___________________________________ ____________

Barbara Alving, M.D. Date

Acting Chairperson

National Heart, Lung, and Blood Advisory Council

___________________________________ ____________

Deborah Beebe, Ph.D. Date

Executive Secretary

National Heart, Lung, and Blood Advisory Council


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