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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