NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

MEETING MINUTES
September 5, 2002

I.  CALL TO ORDER AND OPENING REMARKS - Dr. Claude Lenfant

Dr. Claude Lenfant opened the meeting and welcomed the Council members to the 207th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC). Dr. Lenfant reminded Council that September is Cholesterol Education Month.  For cholesterol education, the theme is a continuation of the past year’s theme which was "know your cholesterol numbers and know your risk.  " The Institute will be providing materials and tools for the public to encourage and help people to know their cholesterol numbers and know their risks and ultimately help them to lead healthier and longer lives.  The Institute is also celebrating the thirtieth anniversary of the sickle cell disease program and Dr. Charles Peterson would describe those activities. 

Member Updates

Secretary Thompson has invited the replacements for Council’s retiring members but their names could not be shared until all of the clearances had been completed.  The proposed members have been invited to attend the October Council meeting.

Dr. Alcalay and Dr. Toy were not present for the Council meeting.

Guests

Dr. Lenfant announced that there would be two guest speakers on asthma: Dr. George Rust, Director of the National Center for Primary Care at Morehouse School of Medicine and Dr. Homer Boushey, Chief of the Asthma Clinical Research Center and Division of Allergy and Immunology at the University of California, San Francisco.

Board of Extramural Advisors (BEA) Working Group Meeting

Dr. Lenfant reminded the Council that they were invited to the meeting of the BEA Working Group. The report from that meeting would be presented to the October Council meeting.

October Meeting and Retirement Dinner

Dr. Lenfant announced that the October Council meeting scheduled for October 24-25 would be the last meeting for five Council members who are retiring (Drs. Cowley, Douglass, Ramirez, Rosenberg, and Spragg). A dinner has been scheduled for the evening of October 24. The NHLBI Intramural Research Program and the BEA initiatives will be reviewed at the October meeting.  An NIH Conference to discuss Hormone Replacement Therapy on October 23-24 will overlap with the October Council meeting.

Personnel Announcements

Dr. Lenfant announced that the Institute recently established the Office of Minority Health Affairs and that     Dr. Helena Mishoe has been appointed as its Associate Director.  Dr. Mishoe has had a long and distinguished career with the Institute.  In addition, Dr. Liana Harvath has been selected as the Deputy Director of the Division of Blood Diseases and Resources.  She has been the Program Director of the Blood Resources Program and has been actively assisting Dr. Peterson in the Division leadership duties since he became Division Director.  Dr. Elias Zerhouni was appointed as the new Director of NIH. He was previously the Martin Donner Professor of Radiology in the Department of Radiology at Johns Hopkins University and Executive Vice Dean of the Johns Hopkins School of Medicine.

Dr. Lenfant announced the passing of Dr. Donald S. Fredrickson on June 7, 2002. Dr. Fredrickson joined what was then the National Heart Institute in 1953 as the Chief of the Metabolic Diseases Branch in the Intramural Program.  He was the Director of the Institute from 1966-1968 and Director of the NIH from 1975 to 1981.  He was best known for his work on lipid metabolism and for his support of recombinant DNA research.

Loan Repayment Program

The Loan Repayment Program was initiated this year in response to the Public Health Improvement Act of November 2000.  Dr. Lenfant announced that NHLBI received 106 applications and awarded approximately 70% of them. Next year, applicants will be eligible if they have support from any source of funding as long as they do not receive money directly from for-profit organizations.

New Publications

Council members were given copies of the "FYI from the NHLBI," the public interest newsletter from the Institute, the reports entitled "Sickle Cell Research for Treatment and Cure" and "Management of Sickle Cell Disease," and a quick reference of the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report on Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics for 2002. 

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II.  REVIEW OF CONFIDENTIALITY & CONFLICT OF INTEREST - Dr. Claude Lenfant

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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 the meeting was published in the Federal Register indicating that it would start at 8:00 a.m. and remain open until approximately 12:00 p.m. Dr. Lenfant also reminded the Council members that they are Special Government Employees and are subject to departmental conduct regulations. 

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III.  REPORT OF THE DIRECTOR 

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Dr. Lenfant made a presentation on the Fiscal Year 2003 budget. The President’s budget request for the FY 2003 Labor, Health and Human Services, and Education Appropriation Bill includes $2,798,200,000 for the NHLBI.  The Senate Appropriations Committee recommended that the NHLBI receive a somewhat higher amount.  The House Appropriations Committee’s recommendations are expected to be announced this month. Dr. Lenfant noted that the largest number of K awards is at the NHLBI.  He also noted that the number of FTEs has not risen with the increase in budget.  In response to Council questions about the budget in future years, Dr. Lenfant noted that the NHLBI had accomplished very significant public health activities and the budget would be predicated on what had been done in the past fiscal year.

Dr. Lenfant also announced that the NHLBI would be initiating a full-scale trial, entitled Action to Control Cardiovascular Risk in Diabetes (ACCORD) to evaluate approaches for preventing myocardial infarctions or strokes in patients who have Type II diabetes.  A vanguard study was previously conducted for two and one-half years.  After consulting with members of the scientific community and following the advice of the Data Safety and Monitoring Board of the study, the Institute made the decision to launch the full scale trial despite the very significant costs.  Dr. Lenfant emphasized that this was an important public health mandate considering the alarming increase in the prevalence of Type II diabetes which is partly due to the increase in obesity in the US. Council had numerous questions and agreed with the importance of this study.  Council commended             Dr. Lenfant on the decision to initiate the trial.

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IV.  30 YEARS OF THE NATIONAL SICKLE CELL DISEASE PROGRAM - Dr. Charles Peterson 

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Although identified through symptoms recognized in Africa for millennia, the first description of Sickle Cell Disease appeared in 1910 when Herrick described his observations over a three-year period on a graduate student at the University of Chicago.  The description of the sickle shape of the red cells and many of the clinical sequelae of the disease is still current.  Although sickle cell studies provided the platform for seminal advances in genetics, molecular biology, chemistry, and physics, no therapies were available for patients with the disease.

In 1972, NHLBI was given responsibility for developing a Sickle Cell Disease Program under the National Sickle Cell Anemia Control Act.  Over the subsequent 30 years, the NHLBI committed more than $923 million resulting in four therapies being developed: penicillin prophylaxis, hydroxyurea, stem cell transplantation, and prophylactic transfusion for those at risk for stroke.  The lifespan of persons with sickle cell disease has increased from approximately fifteen years and now extends to the late forties.  While much has been done, the NHLBI recognizes much more remains to be done and has developed a strategic plan to ease the burden on those with the disease and ultimately to provide a cure.

Council commended the Institute on the progress that has been achieved and on continuing with this important program.

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V.  GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF ASTHMA: & TRANSLATING RESEARCH INTO CLINICAL PRACTICE - Dr. James Kiley, Dr. Homer Boushey, and Dr. George Rust   

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The National Asthma Education and Prevention Program (NAEPP) recently released new Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics 2002. Dr. James Kiley, Director, Division of Lung Diseases, briefly introduced this session by describing how the guidelines can serve as a centerpiece to illustrate how translational research can influence clinical practice.  He briefly described how the NAEPP is working with its members and other groups to disseminate the update.  Dr. Kiley introduced the two speakers for this presentation.

Dr. Homer Boushey, Professor of Medicine, University of California at San Francisco, gave an overview of how research translates into clinical practice.  As an example, he described the process of updating the NAEPP Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma.  When the Guidelines were first published in 1991, preliminary reports had suggested that inhaled corticosteroids may have adverse effects on growth rates in children.  Further, an epidemiological study had indicated that regular use of short acting beta-2 agonists might be harmful.  Recommendations in the 1991 Guidelines cautioned against overuse of beta-2 agonists and recommended that children be started on cromolyn first before introducing inhaled corticosteroids.  To further understand the risks and benefits of the various treatments, however, the NHLBI supported:

• the Childhood Asthma Management Program (CAMP) clinical trial on the long-term effectiveness and safety of inhaled corticosteroids.

• several clinical protocols in the Asthma Clinical Research Network (ACRN) on the daily use of short-acting beta agonists and on the role of long-acting beta agonists in therapy. 

Results from these and other studies contributed significantly to updates in the Guidelines in both 1997 and 2002. For example: 

• the CAMP study's findings that inhaled corticosteroids were safe and effective for children with mild-to-moderate asthma led to a new recommendation in the 2002 update of the Guidelines that inhaled corticosteroids are the preferred therapy for children.

• findings from the ACRN studies demonstrated that regular use of short acting beta agonists without inhaled corticosteroids is neither harmful nor helpful in mild asthma. 

• other studies found that long-acting beta agonists alone were insufficient to control moderate asthma, but they were highly beneficial when combined with inhaled corticosteroids. 

However, in the course of developing the 2002 update, it was emphasized that there is a paucity of data on young children with asthma.  Research is now being supported through NHLBI's Childhood Asthma Research and Education Network on asthma in young children. 

Dr. Boushey ended his presentation by reminding the NHLBAC that translating research results into clinical practice is a continuous process: research provides the foundation for clinical practice recommendations and experience in clinical practice generates new research questions. 

Dr. George Rust, Deputy Director, National Center for Primary Care, Morehouse University School of Medicine, talked about his experience with disseminating guidelines through the Morehouse University's NHLBI-funded program to Improve Asthma Care and Outcomes in Safety Net Health Care Centers.  The Centers treat uninsured patients from underserved communities and provide "real world" settings in which to evaluate guideline use.  He used several examples to illustrate how guidelines alone do not make significant changes to practice. They can be implemented only if: 

• the facility has enough resources (e.g. peak flow meters to give to their uninsured patients). 

• the clinical staff has sufficient training (e.g., understanding of standard services that patients should receive). 

• the physicians have tools to help them implement the guidelines e.g., templates of forms that they can customize for their individual practices). 

The Council had a number of questions and an extended discussion about the pathogenesis of asthma, translational research and applications from the Morehouse guidelines implementation project.

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VI.  SPECIALIZED CENTERS OF CLINICALLY ORIENTED RESEARCH (SCCOR) IN CARDIAC DYSFUNCTION AND DISEASE - Dr. John Fakunding  

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The objective of the SCCOR program in Cardiac Dysfunction and Disease will be to support clinical and basic investigations related to cardiac function and diseases of the myocardium.  The SCCOR awards supported by this initiative will be required to fulfill the requirements for more clinically oriented research as specified by the guidelines for the newly designed SCCOR mechanism.  The new NHLBI SCCOR programs are designed to foster multidisciplinary research on clinically relevant questions, enabling basic science findings to be more rapidly and efficiently applied to clinical problems.  It is expected that results from this SCCOR program will have a positive effect on the prevention, diagnosis, and treatment of a variety of diseases affecting the myocardium.

The current SCOR in Ischemic Heart Disease, Heart Failure, and Sudden Cardiac Death was initiated in l995, when the SCOR in Ischemic Heart Disease was expanded.  The program was renewed in 2000 and, at present, comprises nine individual awards, which will end in December 2004.  An evaluation of the current SCOR program was conducted by a panel of extramural experts in January 2002, as required by NHLBI policy.  The rationale for announcing a new competition in the SCCOR program in Cardiac Dysfunction and Disease is based on the recommendations from the SCOR evaluation, past accomplishments, and opportunities for new research directions.

The goal of the SCCOR program in Cardiac Dysfunction and Disease is to stimulate clinically relevant, multidisciplinary collaborations leading to clinical and basic science research efforts on important public health problems of heart disease.  Diseases affecting the myocardium, such as ischemic cardiomyopathy, metabolic abnormalities, rhythm disturbances, and hypertrophy, often present as a continuum that begins with injury to the heart and progresses to overt dysfunction and failure.  Recent advances in understanding the molecular and cellular biology of heart muscle and the pathogenesis of diseases of the myocardium offer new directions for the study of heart disease and the development of diagnostic, preventive, and therapeutic strategies.  Thus, a SCCOR program that focuses on cardiac dysfunction and disease, which allows for a natural and logical integration of disciplines and science, can best serve the needs of the research community and result in advancements in scientific understanding with maximum impact on clinical science and practice.

The translation of knowledge into clinical practice should be a goal of applications submitted in response to this initiative.  Since many heart disease problems disproportionately affect minority individuals, research on health disparities and the translation of this research to clinical practice for affected minority populations will be emphasized.  A unified program of clinical and basic research is needed to address such questions as:

• novel therapeutic approaches for treating diseased and damaged cardiac tissue, including cell-based therapies, tissue engineering, and the development of drug or modulatory targets for prevention or management;

• genotype-phenotype correlations, modifier genes, and genetic variation that influences therapeutic success, as well as the incidence of adverse clinical events, in contractile dysfunction, arrhythmias, and ischemia;

• molecular, cellular and physiologic processes involved in the progression from asymptomatic to overt ventricular dysfunction;

• diagnosis, treatment and underlying pathophysiology of heart failure with preserved systolic function (diastolic heart failure);

• imaging and biomarker tools which can aid in the detection and diagnosis of cardiac diseases.

• mechanisms of initiation of ventricular and atrial arrhythmias and improved approaches to manage their occurrence and sequelea;

• Racial/ethnic differences in pathogenesis of heart failure and response to treatment.

The SCCOR mechanism provides both the incentive and the structure to maintain critical collaborative cores or other resources necessary for translational research.  For example, the SCCOR mechanism affords the ability to establish and maintain a large clinical database, with associated DNA samples, of patients with various forms of heart disease.

The newly developed SCCOR program mechanism requires clinical and basic scientists with a broad range of skills to form collaborative teams focused on a unified theme.  It therefore presents a rich environment for young clinical investigators to be exposed to and develop additional research skills.  The individual centers can be expected to include among their research staffs clinical personnel who are newly trained and relatively inexperienced in research.  Hence, applicants for this SCCOR program will be permitted to request up to $100,000 in direct costs per year for a Clinical Research Skills Development Core.  The objective of the Core will be to support activities to assist new clinical investigators in progressing to more senior status by enhancing their research skills.  This support would be in addition to the usual cap on the SCCOR mechanism.  A Clinical Research Skills Development Core will not be required, however, and its absence will not disadvantage an applicant.

Council enthusiastically endorsed this initiative.

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CLOSED PORTION

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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 in which there was a potential conflict of interest, real or apparent.  Members were asked to sign a statement to this effect.

IX. REVIEW OF APPLICATIONS 

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The Council considered 286 applications requesting $504,916,830 in total direct costs.  The Council recommended 286 applications with total direct costs of $497,357,552. A summary of applications by activity code may be found in Attachment B.

ADJOURNMENT

The meeting was adjourned at 2:30 p.m. on September 5, 2002.

CERTIFICATION

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

Claude Lenfant, M.D.

Chairperson

National Heart, Lung and Blood Advisory Council

on 10/17/02

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