NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

MEETING MINUTES
September 16, 2005

I. CALL TO ORDER AND OPENING REMARKS - Dr. Elizabeth G. Nabel

Dr. Elizabeth G. Nabel, Director of the National, Heart, Lung, and Blood Institute opened the meeting and welcomed the Council members to the 219th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC).

Guests

Dr. Nabel welcomed Dr. Philip Smith and Dr. Jeffrey Friedman.

Hurricane Katrina

NIH mobilized the Commissioned Corps and set up a field hospital in Meridian, Mississippi, staffed by 30 physicians from NIH. After it was apparent that it would not be used, staff were sent to other field hospitals.

HLBI has created a Katrina page that can be accessed via its public website. The Katrina page contains a link to a message from the Director that highlights key guidance and resources available from the NHLBI and the NIH.

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II. REVIEW OF CONFIDENTIALITY & CONFLICT OF INTEREST - Dr. Elizabeth G. Nabel

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 the meeting was published in the Federal Register indicating that it would start at 8:30 a.m. and remain open until approximately 2:00 p.m. Dr. Nabel also reminded the Council members that they are special government employees and are subject to departmental conduct regulations.

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III. DIRECTOR’S REPORT - Dr. Elizabeth G. Nabel

Dr. Nabel has begun a series of journal editorials in order to enhance communication between the Institute and its constituency groups, grantees, and public advocacy groups. The first editorial is entitled “A Vision for the Future of the NHLBI,” and was published in early July in four journals: The American Journal of Respiratory and Critical Care Medicine, Blood, Circulation, and Sleep. Dr. Nabel plans to write four editorials a year that will cover timely topics that are of concern to NHLBI constituencies. The second editorial will be “New Investigator: Fostering Independence”. It will describe new Institute policies to help the new investigator that have been developed by an NHLBI committee led by Dr. Helena Mishoe. New investigators will be funded 5 percentile points beyond the R01 pay line. Furthermore, new investigators who are within the 6 to 10 percentile points above the pay line will be asked to provide further information addressing issues noted in the summary statements. The responses will be reviewed by staff and reported to Council. Dr. Nabel welcomes comments on her editorials from members of the Council.

The NHLBI held a Working Group meeting on Genome Wide Association in NHLBI Cohorts the first of a series of expert working groups to translate our understanding of the genetics of complex cardiovascular, pulmonary and blood diseases into diagnostic tools and therapeutics for the practice of clinical medicine. The group was asked to develop recommendations to establish a transparent process for Genome Wide Association Study selection, determination of technology platforms, and procedures for data sharing and analysis. NHLBI will provide a report of the group’s work at the October Council meeting.

New initiatives will include several related to cell therapy. The Lung Division held a workshop during the summer that will result in an initiative. DHVD has released the cardiovascular cell therapy network RFA which was published in the Guide August 16, 2005 with a receipt date of March 10, 2006 and a start date of December 6, 2006. In an effort to expand its portfolio of genome-wide association studies, the Institute developed two initiatives, Large-Scale Genotyping of NHLBI Cohorts and Design and Analysis of Genome-wide Association Studies. Responses to both were due in July 2005.

NHLBI is starting to develop process for generating a Strategic Plan for the Institute. A formal report will be provided at the October meeting of the Council. The plan will be community based with involvement by the extramural community throughout its development primarily via a series of workshop-like meetings. It will focus on areas where the Institute is uniquely positioned and critical to the advancement of innovative, cutting edge, and high impact research and will include concrete implementation steps along with a provision for ongoing assessment to track and update activities over time. The final plan will be presented to Council in early 2006.

Budget

NHBLI is closing out the fiscal year; a report on the FY 05, 06 and 07 budgets will be provided at October Council meeting.

Copies of press releases on NHLBI funded studies and activities since the last Council meeting were provided in the briefing books. Dr. Nabel highlighted three of thm:

• High Blood Pressure Not Well Controlled Among Older Men and Women (Framingham Heart Study, Journal of the American Medical Association, July 27, 2005) ).
• Decline in Physical Activity Plays Key Role in Weight Gain Among Adolescent Girls (10 Year Health and Growth Study, Lancet, July 23, 2005 ).
• Women’s Health Study Finds Vitamin E does not Protect Women from Heart Attack, Stroke, or Cancer (Women’s Health Study Journal of the American Medical Association, July 6, 2005 ).

Remarks by the Director, NIH

Dr. Elias Zerhouni welcomed and congratulated Dr. Nabel for her expert guidance since she was appointed Director of NHLBI. Dr. Zerhouni also emphasized Dr. Nabel’s efforts to promote new investigators.

Dr. Zerhouni reiterated his goal of breaking down unnecessary barriers to science by reducing the rigidity of the research enterprise. He also noted the growing importance of interdisciplinary science.

In response to questions from Council members, Dr. Zerhouni elaborated on his views about resource allocation, the future of the NIH Roadmap, the changing role of physician scientists, and the complexity of institutional regulatory issues. He emphasized that the NIH Roadmap is designed to be an "innovation" fund, neither static nor rigid, this is administered with continuous assessment of scientific priorities. He also noted NIH efforts at "harmonizing" the regulatory environment to simplify conducting translational research.

Gene Therapy Resource Initiative

Dr. Sonia Skarlatos, Deputy Director of the Division of Heart and Vascular Diseases, presented an initiative for the gene therapy resource program, a major translational effort to move gene therapy from the bench to the bedside by providing critical resources for research in the area. The Program will comprise a Clinical Coordinating Center to coordinate all core laboratories and provide regulatory assistance for clinical trials, a preclinical grade vector production core laboratory, two clinical grade vector production core laboratories, and a pharmacology/toxicology core laboratory. The Program is expected to support two phase I/II gene transfer clinical trials per year that have met all regulatory requirements and are ready to enroll patients. Council members were enthusiastic about the initiative.

Management Status

Dr. Nabel announced that the Institute is currently seeking applicants for the Deputy Director position as well as for the Special Assistant for Clinical Research which was previously held by Dr. Lawrence Friedman . The Special Assistant position entails responsibility for oversight of all aspects of Institute-supported clinical research, including oversight of data and safety monitoring recommendations, monitoring of adverse event reporting, and review of conflicts of interest. Both position announcements closed on October 21, 2005.

Dr. Nabel introduced Dr. Rae Ellen Kavey who will serve as Senior Medical Officer in the Pediatric Cardiovascular Risk Reduction Program, Office of Prevention, Education, and Control (OPEC), NHLBI.

Dr. Nabel also introduced Commander Richard T. Mahon, Division Head, Operational and Undersea Medicine, Naval Medical Research Center, Silver Spring, Maryland, who will serve as an ex officio member of the NHLBI.

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IV. NIH OBESITY ACTIVITIES – Dr. Elizabeth G. Nabel

Dr. Nabel discussed the Trans-NIH Obesity Task Force which is very active in coordinating and expanding the obesity research supported by NIH. Dr. Alan Spiegel, Director NIDDK and Dr. Nabel, Co-Chair serve on the Task Force. They have been asked to represent NIH and the Department at a September 22 White House meeting of the Committee on Science to Coordinate obesity activities throughout the Federal government.

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V. THE OBESITY PROBLEM AND APPROACHES TO IDENTIFYING SOLUTIONS – Dr. Denise Simon-Morton

Dr. Denise Simons-Morton, Director of the Clinical Applications and Prevention Program, Division of Epidemiology and Clinical Applications, NHLBI, summarized trends in overweight/obesity in the U.S. over the past 25 years. In 2003, the NHLBI convened a Think Tank on Enhancing Obesity Research at NHLBI to suggest research recommendations for confronting the public health challenge of obesity (Executive Summary published January 2004). The NIH Obesity Research Task Force was also established in 2003 (see description above). NIH currently supports a sizeable portfolio of obesity-related research, including basic research, epidemiologic studies, randomized clinical trials, and studies of intervention effectiveness in "real world" settings.

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VI. MAXIMIZING THE IMPACT OF BASIC RESEARCH IN OBESITY- Dr. Philip Smith

Dr. Philip F. Smith, Deputy Director of the Division of Diabetes, Endocrinology, and Metabolic Diseases and Co-Director of the Office of Obesity Research, NIDDK, reviewed important findings from recent NIH-supported basic research in obesity. The NIH currently supports obesity research in such areas as neurobiology on obesity, pathophysiologic mechanisms of obesity-associated cardiovascular disease, heterogeneity of fat deposits, non-mammalian models of obesity, diet and body composition, and measuring energy intake and expenditure.

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VII. LEPTIN AND THE BIOLOGICAL BASIS OF OBESITY- Dr. Jeffrey Friedman

Dr. Jeffrey M. Friedman, Howard Hughes Medical Investigator, The Rockefeller University, explained that the answer to the obesity problem is not simply "eat less and exercise more" because obesity is caused by three factors—lack of willpower, lifestyle/environment, and biology/genes. The public usually focuses on the first two factors. Dr. Friedman emphasized the importance of an individual's genetic makeup in the development of obesity.

In the mid-1990s, Dr. Friedman's lab identified leptin, a hormone secreted by fat cells that balances food intake and energy expenditure. Dr. Friedman presented a case report of a young boy of normal birth weight whose morbid obesity began in infancy and who exhibited marked over-eating and very high insulin levels. Leptin replacement therapy greatly reduced the boy's obesity, and after 5 years of leptin treatment, his weight was normal. But most overweight individuals are leptin resistant, rather than leptin deficient. Dr. Friedman's research currently includes identifying genetic mutations in the leptin pathways and finding differences in the pathways between lean and obese individuals. His lab is also currently studying residents of the Pacific Island of Kosrae where there is a high incidence of obesity, the cause of which is not understood, to increase understanding about the genetic basis of obesity and obesity-related diseases.

Dr. Friedman proposed the following steps for addressing the obesity problem:

• define molecular components of the pathways that regulate body weight
• define molecular defects in abnormal states/obesity
• identify effects of environmental factors (e.g., diet, lifestyle, hormones) on these pathways
• develop rational therapies

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VIII. OBESITY AS A MODIFIABLE RISK FACTOR FOR CHRONIC DISEASE – Dr. Denise Simons-Morton

Dr. Simons-Morton presented evidence, based on results of NHLBI supported research, of the effects of obesity on several risk factors for cardiovascular disease (CVD)—dyslipidemia, hypertension, and diabetes—and how they are affected by weight loss. Studies have shown, for example, that moderate amounts of weight loss can lower lipid levels and blood pressure and prevent the development of diabetes. The NHLBI continues to study such issues as the effect of intentional weight loss on CVD events; the most beneficial macronutrient diet composition (i.e., percentages of carbohydrate, protein, and fat) for weight loss; and the most effective approaches for reaching minority and underserved populations.

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IX. RESEARCH TO APPLICATION: THE NHLBI OBESITY EDUCATION INITIATIVE - Ms. Karen Donato

“WE CAN” is a national education program to help prevent overweight and obesity among children ages 8-13 years, was launched June 1st. A collaborative effort of the NHLBI, the NIDDK, the National Institute of Child Health and Human Development, and the National Cancer Institute, We Can! provides resources and community-based programs for parents, caregivers, and youth that focus on behaviors to encourage healthy eating, increase physical activity, and reduce sedentary time. We Can! is off to a good start; since June, 42 communities in 22 states have begun implementing We Can! programs.

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X. CLOSED PORTION

This portion of the meeting was closed to the public in accordance with the determination that it was concerned with 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).

There was 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 that presented there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to that effect.

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XI. REVIEW OF APPLICATIONS

The Council considered 138 applications requesting $318,646,119 in total direct costs. The Council recommended 138 applications with total direct costs of $317,116,660. A summary of applications by activity code may be found in Attachment B.

ADJOURNMENT

The meeting was adjourned at 3:30 p.m. on September 16, 2005.

CERTIFICATION

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

Elizaberh G. Nabel, , M.D.
Chairperson
National Heart, Lung, and Blood Advisory Council

Deborah Beebe, Ph.D.
Executive Secretary
National Heart, Lung, and Blood Advisory Council

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