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NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

MEETING MINUTES
February 10, 2000

The 197th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Thursday, February 10, 2000, in Conference Room 10, Building 31, National Institutes of Health (NIH), Bethesda, Maryland. The meeting was open to the public from 8:30 a.m. to 1:45 p.m. The meeting was closed to the public from 2:00 p.m., to adjournment on February 10, 4:15 p.m. Dr. Claude Lenfant, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

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

Dr. Claude Lenfant opened the meeting at 8:30 a.m. and welcomed everyone to the 197th meeting of the National Heart, Lung, and Blood Advisory Council. He reintroduced the new and reappointed members who were present at the prior meeting, Dr. Rena Alcalay and Mr. Alan Meisel, and introduced the other new Council members.

Dr. Mary Lipscomb is Professor and Chair of the Department of Pathology and Director of the Medical Laboratory Science Program at the School of Medicine at the University of New Mexico. Her research interests involve the immunoregulation of the lung. She is a member of a number of professional organizations and has served on numerous NIH committees.

Dr. Roberta Williams is Professor and Chair of the Department of Pediatrics at the University of North Carolina. She is a Pediatric Cardiologist who has published extensively and lectured internationally. She has served on a number of national committees and has had a long association with the American College of Cardiology.

Ms. Paula Polite is President of the Sarcoidosis Research Institute, an organization that provides educational information concerning this disease. She has served on committees of the American Lung Association and has worked to establish programs in sarcoidosis. Ms. Polite's training is in information systems, and she currently works for the City of Memphis. She will be fulfilling the remainder of the term for Dr. Lopez who resigned in the fall.

There have also been some changes in the professional activities of Council members. Dr. Shiriki Kumanyika who relocated last year to the University of Pennsylvania, has been officially appointed Professor of Epidemiology and Associate Dean for Health Promotion and Disease Prevention. Dr. Paul Whelton has been appointed Senior Vice President for the Health Sciences at Tulane University School of Medicine.

Personnel Announcements

NIH

Dr. Harold Varmus has left the NIH to direct the Sloan Kettering Institute in New York City. Dr. Ruth Kirschstein has become Acting Director of the NIH. She had asked to meet with all Councils, and planned to come to the Council meeting at 1:00 p.m. Dr. Yvonne Maddox, Deputy Director of the National Institute of Child Health and Development, will serve as Acting Deputy Director of the NIH.

NHLBI

Dr. Suzanne Hurd, Director of the Division of Lung Diseases, has retired. Dr. James Kiley has been appointed Director of the Division of Lung Diseases (DLD). Dr. Kiley was previously Program Director for Airway Biology and Diseases in the Division as well as Director of the National Center for Sleep Disorders Research. The Airway Biology and Diseases Program will be directed by Dr. Gail Weinmann, and Dr. Michael Twery will be Acting Director of the Sleep Center until a permanent Director is chosen.

Dr. Steven Mockrin has been appointed Director of the Division of Heart and Vascular Diseases (DHVD). Dr. Lawrence Friedman has moved from the Division of Epidemiology and Clinical Applications (DECA) to the Office of the Director to work on special projects. Dr. Peter Savage, who was Deputy Director of DECA, is now the Acting Director of that Division.

Finally, Dr. Robert Balaban was chosen as the Scientific Director for Laboratory Research Programs in the NHLBI Intramural Program, joining Dr. Elizabeth Nabel who is the Scientific Director for Clinical Research Programs.

II. REVIEW OF CONFIDENTIALITY AND CONFLICT OF INTEREST PROCEDURES - Dr. Claude Lenfant

Dr. Lenfant reminded the Council 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 2:00 p.m. He also reminded the Council members that they are Special Government Employees and are subject to Departmental Conduct Regulations.

III. REPORT OF THE DIRECTOR - Dr. Claude Lenfant

Budget Update

Dr. Lenfant presented a series of slides showing the NHLBI budget for fiscal years (FY) 1999 and 2000. The FY1999 budget was $1.7 billion, and the FY2000 budget is slightly greater than $2 billion. The FY2001 president's budget is $2,137,000,000, an increase of about $110 million or 5.4 percent over the current budget. This percentage increase ranks 16th among NIH Institutes but is a very large dollar amount. The NHLBI ranks second in overall funding within the NIH.

A series of slides was shown indicating the breakdown of the budget into various categories, including both AIDS and non-AIDS research. The total obligation for research project grants is anticipated to be $1.3 billion in FY2000. The President's FY2001 budget requests $1.339 billion, an increase of 6.5 percent. It was noted that in FY1999, the base commitment for research project grants was $735 million, moving to $859 million in FY2000, and jumping to slightly more than $1 billion in the FY2001 President's budget. This is the amount of money committed to grants already funded.

Over the last two years, the number of new awards has risen from 800 to 950, and is projected to be almost 1,100 this year. This is both good news and bad news. The concern is that without an equivalent increase in the budget, the 1,100 grants funded this year will generate a base commitment which will erode the Institute's ability to fund new grants. This happened several years ago and was extremely damaging to the equilibrium in the scientific community. The proposed President's budget request would lead to a decrease in the number of new grants in FY2001 by 23 percent due to the total increase of 20 percent for noncompeting research project grants.

The Council noted that a 23 percent decrease in funded applications would have a depressing effect on applicants, and would provide widely different prospects of funding depending on the time an application is submitted. Dr. Lenfant noted that there are many additional steps prior to the finalization of the NIH budget. In addition, it should be remembered that this is an election year which may result in a dynamic which is currently unpredictable. An issue which does need to be considered is that of the average cost of grants. One needs to consider whether research is becoming more expensive or whether there are other forces driving the increase.

Council asked the size of a budget increase necessary to maintain the level of funding in FY2001 at its current rate. The answer was greater than 12 percent. Council also noted that under the current budget, there would be a 79 percent decrease in competing AIDS grants if the President's budget is approved. They asked whether there were strategies to be used to influence the budget. It was noted that the role of the NIH in the congressional hearings is to support the President's budget.

Council raised an issue about indirect cost rates. It was noted that indirect costs are negotiated by a separate organization and are not within the control of the NIH.

Average Cost of Grants

The average cost of a grant for next year is projected to be $385,000. That figure is obtained by averaging all Institute grants, both large and small. Five years ago, the average cost of a grant was approximately $250,000, and the average cost of a grant has increased from the time of the last Council meeting to the current one by $20,000; that is a $5 million increase from the projected level three months ago. Furthermore, the number of grants supported by the Institute has risen from approximately 2,800 only a few years ago to the current level of 3,400, a consequence of the increased budgetary support.

The Institute has a current commitment of $55 million to pay for about 55 research grants requesting more than $500,000 in any one year. Additional grants in this category that have been received, but are not yet reviewed, are requesting $40 million. Were all these applications to be funded, it would cost $95 million, which would use up of the entire anticipated increase in our budget next year. This is a significant outlay for a limited number of grants.

Dr. Lenfant noted that many of these large studies are based on translational research, primarily clinical studies. These are studies in which the Congress has tremendous interest. The Institute obviously cannot eliminate this type of research both because it is important to do, and because it is part of the mandate of the NHLBI. It is important, however, that each of these applications is examined to see where they fit within the priorities of the Institute.

Council suggested that savings could be achieved by the centralization of services and equipment. The Institute noted that Council would need to be involved in such decisions because of its substantial impact upon the research community. Some members of the Council suggested, that a task force should be set up to look at issues of centralization. It was noted that the Institute and the scientific community need to be involved in any such discussions. The Institute was cautioned about micromanagement within universities. The Council raised the possibility of multi-year funding to level out future commitments; the Institute noted that it receives only one-year funds from the Congress.

Council commented that some agencies deal with renewing the infrastructure rather than committing all their resources to recurring costs. There are three or four NIH Institutes which have construction authority; NHLBI is one of them. However, Congress has chosen to allocate funds for construction only to the National Center for Research Resources.

IV. UPDATE ON THE PUBLIC INTEREST GROUP - Council Members

Council members were asked to comment on the meeting with public groups held the previous day. Council expressed appreciation to Dr. Roth for organizing the meeting. Although many of the attendees came with single-item agendas, there were many positive comments about the meeting. There were many good suggestions from participants, and hopefully a dialog will continue. It is critical that the NHLBI continues to get its message out. Other Council members agreed that the meeting was a positive experience.

It was clear that a number of the representatives represented disease advocacy groups. There was no clear representation of groups interested in prevention. A suggestion was made to identify consumer groups that represent the population at risk for cardiovascular, lung, and blood disease in general, rather than specific diseases. The Council noted that one of the continuing issues was the translation of basic research into clinical treatment and patient education. The media was faulted for misrepresentation of a number of issues concerning the NHLBI. This suggests that an issue may be how to encourage reporters to report accurately the findings of the NIH and the NHLBI.

Council expressed the general feeling that the meeting had been extremely helpful, and the participants had been open and forthright. While there was a wide range of sophistication among the participants, all of them had worthwhile things to say. Dr. Lenfant indicated that now is the time to seize these opportunities. The Institute will provide a summary of Institute programs for broad distribution. This effort will be organized through the Office of Prevention, Education, and Control.

V. UPDATE OF THE STRATEGIC PLAN - Dr. Carl Roth

Dr. Lenfant noted that the draft of the Strategic Plan had been sent to professional societies. The Institute had not received many comments, but those received had been positive. Dr. Roth reminded the Council that the strategic plan activity was recommended as part of the Institute of Medicine report on priority setting at the NIH. Dr. Varmus required that each Institute submit a plan to his office by December 31. After discussion with the Council at the October meeting, the revised report was posted on the website for comment for one month. The document was revised in light of the comments received and submitted to the NIH Office of the Director by December 31.

As suggested by the Council, illustrations were included in order to make the document more user-friendly. Currently the Institute is awaiting clearance for publication of the document through the Government Printing Office. There had been no decision at the NIH level as to whether these reports would be updated annually, but the NHLBI believed that they provide an effective framework to guide planning and to inform the public. There will be an Institute retreat in March of this year to continue the planning process of the Institute.

VI. DELAYED OBLIGATIONS AND IMPACT - Mr. Edward Donohue

Dr. Claude Lenfant introduced Mr. Edward Donohue, Grant Management Officer for the NHLBI. Mr. Donohue discussed with the Council the delayed obligations stipulation in the NIH budget. The Congress required that a portion of the authorized NIH budget be expended on September 29. For the NHLBI the delayed obligation is $361 million or 27 percent of the overall NHLBI budget, exclusive of National Research Service Awards, training grants, and fellowships. Because of the large dollar amount, significant planning is required to manage these obligations successfully.

The NHLBI plan is designed to reduce, to the greatest extent possible, the burden on investigators and institutions, while allowing the NHLBI some internal flexibility. The plan is based on the idea of limiting the impact of end-of-year obligations to the greatest extent possible, in order to limit the impact on competing renewal applications.

The NHLBI plan includes the following actions. A total of $61 million in contract awards will be awarded at the end of the fiscal year; this is part of the normal NHLBI process. The NHLBI also has $80 million in approved RFAs for September starts, which will be awarded on September 29. The NHLBI normally funds the Small Business Innovation Research and Technology Transfer Programs during September. These obligations of about $18 million will be delayed to September 29. The Institute also has $11 million in cooperative agreements that have September 30 start dates. The Institute will reduce their current award period by one day, and then activate the new awards one day early. Finally the Institute has $188 million in noncompeting continuation applications pending for September. All of these figures combined, place the NHLBI within $3 million of its goal for delayed obligations. With the flexibility to delay funding new unsolicited applications and applications for RFAs presented to the May Council meeting until September 29, the Institute expects to be able to meet the goals. The NHLBI will be continually monitoring the process of these actions during the fiscal year.

In response to a question from Council, Mr. Donohue clarified that the intention is to limit delayed obligations to noncompeting continuations with a September 1 start date. In this case there would be a 1/12 award followed by an automatic award for the remainder of the grant on September 29. This would allow for the awards to handle personnel needs and also to purchase new equipment, travel, and other items in an expeditious matter. Mr. Donohue assured the Council that the NHLBI will work with investigators to facilitate this process. He also reminded them that universities have preaward authority of which can be used to be ameliorate any problems.

VII. CONCEPT REVIEW OF NEW INITIATIVES

A. Division of Lung Diseases

1. Genetic Aspects of Tuberculosis of the Lung -- Dr. Hannah Peavy

The objective of this initiative is to stimulate research on the genetic aspects of tuberculosis in the lung, exploiting advances in molecular biology and in genomics research. It is important to learn about the interaction between host and microbial genes, and to identify genes, or families of genes, to determine virulence, or latency, reactivation of disease, or resistance to antituberculosis drugs. Areas of particular interest are studies using novel biotechnologies, such as microarrays, molecular beacon technology, or differential signature-tagged mutagenesis and innovative collaborations with computational biologists to identify genes that mediate the pathogenesis of tuberculosis of the lung and to elucidate the mechanisms that are responsible. The RFA would encourage collaborations with computational biologists who work with microbiologists and geneticists who look at interactions between host and the microbacterial genomes.

Council felt that this was a timely initiative and will provide an important focus in advancing our understanding of M. tuberculosis, particularly as it interacts with the lung. It was suggested that the initiative be reviewed to make certain that it facilitates the interaction of cell biology with new information about M. tuberculosis. The Council was supportive of this initiative.

B. Division of Epidemiology and Clinical Applications

1. The Framingham Study Renewal -- Dr. Teri Manolio

This initiative is to support a seven-year extension and expansion of the Framingham Study. The objectives are: 1) To identify genetic and environmental factors related to the development of cardiovascular, lung, and blood diseases in 350 complex pedigrees involving 5,500 individuals in three generations; 2) To identify determinants of the evolution of risk factors, subclinical and clinical manifestations of cardiovascular, lung, and blood diseases utilizing information from the 29 consecutive examinations of the original Framingham cohort and clinical manifestations of cardiovascular, lung, and blood diseases utilizing information from 29 consecutive examinations of the original cohort and eight examinations of their offspring; and 3) To establish and make widely available a resource for genetic and nongenetic studies of disease risk using data, DNA, and transformed cells from Framingham study participants.

Council was very supportive of this initiative, noting its importance in our understanding of cardiovascular disease. The initiative, however, engendered substantial discussion because of its size and scope. Council noted that this study does not have the demographic characteristics of cohorts now being created, either from a racial distribution perspective or from breadth of socioeconomic characteristics. Nonetheless, it has much historical data, and has the ability to provide longitudinal follow-up data. The cross-generational data is particularly noteworthy. The Institute responded that there are extensive measures of socioeconomic status (SES) collected in Framingham although the cohort itself does not represent a broad range of socioeconomic status.

Council noted that a broad representation of the scientific community had been consulted in designing the study. They also noted that a Request for Proposals (RFP) would be issued, and the investigators would propose specific approaches. This response would then be subject to peer review. Council also inquired whether other Institutes were to participate in funding this program. In terms of other Institute support, the investigators have been active in seeking out funding from other Institutes.

Dr. Manolio noted that about one and a half million dollars of the budget go to support the molecular genetics and laboratory genetics, statistical genetics and data sharing costs of the study. Dr. Lenfant reiterated that the Institute is in the process of establishing a genetic material sharing process. Framingham has the potential of becoming a national resource from which people can obtain material, genetic material, and phenotyping information.

Council raised the issue that it is not always easy for outside investigators to obtain data from the Framingham study. This is also an area of some concern to the NHLBI, but efforts have been made to address this issue. In particular, efforts are being made to shorten the window whereby data is restricted to Framingham investigators, and to expedite requests for such data.

2. Chelation Therapy of Angina Pectoris - Dr. Michael Domanski

The purpose of this initiative is to determine the efficacy of ethylene diamine tetra-acetic acid (EDTA) chelation therapy in reducing a combined end point of mortality morbidity in patients with chronic stable angina because of coronary artery disease. Chelation refers to the combining of a metal to another substance, generally termed a chelating agent. Even in the absence of any rigorous scientific study, EDTA has been used for a number of years and continues to be used in hundreds of thousands of patients.

Council expressed serious concern with this initiative. They noted that there are only a few very small studies of EDTA in patients with coronary disease, and that these studies were retrospective and not particularly convincing. There were four randomized studies done in peripheral vascular disease; two were negative and the others did not reach statistical significance. Furthermore, the endpoint proposed is very broad, and includes mortality, non-fatal myocardial infarction (MI), hospitalization for unstable angina, and revascularization. Given the controversial nature of the therapy, a more solid endpoint would be desirable.

Council also worried about the potential long-term toxicity for bone disease, especially in post- menopausal women. On one hand, this therapy is currently being used by half a million people. On the other hand the cost of the study, $24 million, is very high with an uncertain outcome. Other Council members expressed concern about the high cost of the study. It was noted that the Center for Alternative and Complementary Medicine would be a cosponsor of this project.

Also of concern to the Council was the fact that many patients who use alternative therapies may not be subject to a scientific argument of non-efficacy. It is unclear that any outcome would have an impact upon current clinical practice. Council continued to express concern over the paucity of scientific evidence supporting the efficacy of this therapy.

It was noted that although the scientific basis for the study is not substantial, this is an issue of major interest to the public. It was pointed out that there was little reason to believe that any outcome from the study would have an impact on current practice. In contrast, it was pointed out that even when therapies known to be efficacious, such as hypertension control, their utilization is often problematic. A motion was made not to support this trial, which passed with one abstention.

C. TRANS-NHLBI INITIATIVE

Ancillary Studies in Heart, Lung, and Blood Disease Trials - Dr. James Kiley

The overall goal of this initiative is to solicit research grant applications to conduct mechanistic studies in clinical trials related to heart, lung and blood diseases. Specifically, this initiative focuses on the utilization of patients and patient materials from such trials to study the mechanisms underlying the interventions, the mechanisms of disease pathogenesis, surrogate markers or biomarkers of disease activity and therapeutic effect, and mechanisms of human cardiopulmonary and hematologic function. Studies aimed at accelerating the development of new technologies within the context of mechanistic investigations are also encouraged. Mechanistic studies in clinical trials supported by any source (industry, public and private) are eligible. Applications submitted under this program undergo an expedited peer review and award to facilitate the timely conduct of these mechanistic studies.

Council commented that the challenge will lie in the fact that the people most competitive for doing the basic mechanistic studies may not be those who have done the clinical trial. But the people doing the trial may be the only ones who know the problem, know the results of the trial, and can frame the questions. Frequently such studies need to be done before the data is available in the public sector. The challenge is to make sure that the pre-publication data is made widely available to the audience who would be the best applicants for the study. Council suggested that the RFA be clarified so that respondents understand that what is desired is mechanistic, non-clinical studies whose purpose is to clarify the phenomena found in the trial.

VIII. REMARKS BY THE ACTING NIH DIRECTOR - Dr. Ruth Kirschstein

Dr. Ruth Kirschstein addressed the Council to talk specifically on clinical research. There is renewed emphasis on this area and one issue in particular is the disparity between majority and minority populations. Dr. Kirschstein has set up a Committee of the IC Directors to work on this initiative and Drs. Fauci and Maddox are the co-chairs of this committee. The Committee will prepare a strategic plan which will deal with this issue. The report will go to Dr. John Ruffin of the Office of Research on Minority Health (ORMH), the Advisory Committee on Research on Minority Health, as well as others before being finalized and submitted to the Director, NIH.

Council was appreciative of Dr. Kirschstein's visit, and thanked her for her interest.

IX. GENERAL RECOMMENDATION OF COUNCIL - Dr. Claude Lenfant

The General Recommendations of the Council, providing delegations of authority to the NHLBI, were presented. The recommendations were the same as in prior years, except for two minor grammatical changes. The recommendations were unanimously approved by the Council.

Dr. Lenfant inquired of the Council as to further business and hearing none declared the open session completed at 1:45 p.m.

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.

REVIEW OF APPLICATIONS

The Council considered 1,212 applications requesting $1,133,186,431 in total costs. The Council recommended 808 applications with total costs of $814,226,169. A summary of applications by activity code may be found in Attachment B.

ADJOURNMENT

The meeting was adjourned at 4:15 p.m. on February 10.

CERTIFICATION

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

Claude Lenfant, M.D.
Chairperson
National Heart, Lung, and Blood Advisory Council
Director
National Heart, Lung, and Blood Institute
on 04/05/00



Robert R. Carlsen
Executive Secretary
National Heart, Lung and Blood Advisory Council
on 04/04/00


NOTE: A complete set of open portion handouts are available from the Executive Secretary.

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