DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH NATIONAL ADVISORY NEUROLOGICAL DISORDERS AND STROKE COUNCIL Summary of Meeting1 February 11-12, 1999
The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 144th meeting on February 11,
1999, in Building 31, Conference Room 6, National Institutes of Health, Bethesda, Maryland. Dr. Gerald Fischbach, Director
of the National Institute of Neurological Disorders and Stroke (NINDS), served as Chairperson.
In accordance with Public Law 92-463, the meeting was:
Open: February 11, 1999 -- 8:40 a.m. to 5:05 p.m.
for the review and discussion of program development, needs, and policy; and
Closed: |
February 11, 1999 - 5:05 p.m. to 6:05 p.m. |
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February 12, 1999 - 8:35 a.m. to 11:50 a.m. |
for the review of the Board of Scientific Counselors' Reports and discussion and consideration of individual grant applications.
Council members present were:
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Mr. Robert V. Abendroth Dr. Dennis Choi Ms. Alicia Conill Dr. Mahlon DeLong Dr. Martha Denckla Dr. Darryl DeVivo Dr. Uta Francke Dr. Julian Hoff Ms. Kathleen Hunter |
Ms. Martha Keys Mr. Morton Kondracke (absent 2/12) Dr. Masakazu Konishi Dr. John Mazziotta Mr. Henry Morris, Jr. (absent 2/11) Dr. George Ojemann Dr. Jerome Posner Dr. Richard Tsien (absent 2/12)
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Council members absent were:
Dr. Carla Shatz
Council Roster (Attachment 1)
Ex Officio Members present:
Dr. John Booss, Department of Veterans Affairs Dr. Andrew Dutka, Department of Defense
Members of the public present for portions of the open meeting included:
Ms. Raychel Bartek, Friedreich's Ataxia Parent Ms. Andrea Castrogiovanni, The American Speech and Hearing Association Mr. Tom Hogan, The Blue Sheet Ms. Margaret Calvano, Epilepsy Foundation R. D. Broadwell, Brain Injury Association
NINDS employees present for portions of the meeting included:
Dr. Audrey S. Penn Dr. Constance Atwell Dr. Gerald Fischbach Ms. Brenda Kibler Mr. Edward Donohue Dr. Cheryl Kitt Dr. F. J. Brinley Dr. Al Kerza Dr. Giovanna Spinella Dr. Michael Walker Dr. William Heetderks Dr. Paul Nichols Ms. Margaret Jacobs Ms. Marian Emr Dr. Katherine Woodbury Dr. Philip Sheridan Mr. Jim Stoneman Dr. Joseph Drage Dr. F. Terry Hambrecht Dr. Robert Baughman Dr. Eugene Oliver Dr. Sally Broman Mr. Phillip Wiethorn Dr. Charlotte McCutchen Ms. Mary Miers Ms. Shirley Broderick Ms. Irene Fong Ms. Carole Kirby Ms. Gladys Bohler Dr. Alan Willard Ms. Dianna Jessee Dr. Arlene Chiu Ms. Kimberly Pendleton Ms. Tina Carlisle Mr. Gahan Briethaupt Mr. Paul Myers Ms. Karen Shields Ms. Jean Hoffman Ms. Pam Jones
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Dr. John Marler Dr. Paul Sheehy Dr. Lillian Pubols Ms. Shannon Garnett Ms. Margo Warren Mr. Levon Parker Dr. Emanuel Stadlan Mr. Larry Salas Ms. Nena Wells Ms. Paula Walker Dr. Gabrielle Leblanc Mr. Kenny Bond Dr. Thomas Jacobs Ms. Natalie Larsen Ms. Maureen Volz Ms. Ruth Linn Mr. Andy Baldus Ms. Pat Turner Ms. Janice Solomon Dr. Claudia Blair Dr. Robert Zalutsky Ms. Lorraine Fitzsimmons Ms. Carol Rowan Ms. Angela Eldridge Ms. Kathleen Howe Mr. Kevin Kirby Dr. Alfred Gordon Ms. Rita Rollins-Hickey Ms. Sheila Simmons Dr. Paul Scott Ms. Marvene Horwitz Ms. Mary Graham Ms. Jennifer Gorman Dr. Deborah Hirtz Ms. Diane Drew Ms. Susan Free Mr. Kirk Davis Dr. Story Landis Ms. Sandy Walter Ms. Denise Chatman
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Other Federal employees present for portions of the meeting included:
Dr. Joe Marwah, CSR Dr. David Simpson, CSR Dr. John Bishop, CSR Dr. Brent Stanfield, NIMH Dr. Joanne Fujii, CSR Dr. Michael Lang, CSR Dr. Rochelle Small, NIDCD Dr. Elliott Postow, CSR Dr. Carl Banner, CSR Dr. Daniel Kenshalo, CSR Dr. Bernard Driscoll, CSR Dr. Jay Joshi, CSR Ms. Kristina Borror, OD Dr. Emmeline Edwards, NSF
I. CALL TO ORDER AND OPENING REMARKS
Dr. Fischbach welcomed the Council members, guests, and staff to the 144th Council meeting. He introduced the following new
Council members: Dr. Uta Francke, Professor of Genetics, Howard Hughes Medical Institute and Stanford University School of
Medicine; Ms. Kathleen Hunter, Chief Executive Officer, International Rett Syndrome Association; Dr. Julian Hoff, Professor
and Head, Section of Neurosurgery, Department of Surgery, University of Michigan; Mr. Morton Kondracke, Executive Editor and
Columnist of Roll Call, and Dr. Richard Tsien, George D. Smith Professor, Department of Molecular and Cellular Physiology, Stanford University School
of Medicine. He also introduced Dr. David Pleasure, Professor of Pediatrics, Children's Hospital of Philadelphia, as a special
visitor to the Council meeting.
With regard to NINDS personnel news, Dr. Fischbach reported that Mr. Edward Donohue is the new Director, Division of Extramural
Activities, Dr. John Marler is the Acting Director, Division of Clinical Trials and Experimental Therapeutics, and Dr. Alfred
Gordon, Acting Director, Office of Special Programs in Neuroscience.
II. REPORT OF THE ASSOCIATE DIRECTOR FOR EXTRAMURAL RESEARCH
Dr. Constance Atwell, Associate Director for Extramural Research, NINDS, introduced the Grants Management Specialists who
have recently joined the Grants Management Branch: Ms. Tina Carlisle, Ms. Denise Chatman, Ms. Angela Eldridge, Mr. Jerome
Lofton, Ms. Kimberly Pendleton, Ms. Rita Rollins-Hickey, and Ms. Sheila Simons.
A. Council Procedures
Government in the Sunshine Act and Federal Advisory Committee Act:
These Acts require the DHHS to open to public observation as many advisory committee meetings as possible, including the meetings
of the National Advisory Councils. The Council meeting, therefore, was open to public observation except when grant applications
were being reviewed, at the times previously specified in these minutes. Notice of the date and place of the Council meeting
was published in the Federal Register thirty days prior to the meeting.
Conflict of Interest:
The regulations concerning conflict of interest were reviewed, and Council members were reminded that materials furnished
for review purposes and discussion during the closed portions of the meeting are considered privileged information. All Council
members present signed a statement certifying that they did not participate in the discussion of, or vote on, an application
from any organization, institution, or any part of a university system, except for those which have multi-campus institution
waivers or are specifically designated as separate organizations under 18 U.S.C. 208(a), of which they are an employee, consultant,
officer, director or trustee, or in which they have a financial interest.
B. Consideration of Minutes of Previous Meeting
The minutes of the Council meeting of September 17-18, 1998, were considered and accepted as written.
C. Consideration of Dates for Future Council Meetings
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May 20-21, 1999 September 23-24, 1999 February 10-11, 2000 May 25-26, 2000 September 14-15, 2000 |
(Thursday and Friday) (Thursday and Friday) (Thursday and Friday) (Thursday and Friday) (Thursday and Friday) |
D. Program Announcements
Dr. Atwell mentioned the Program Announcements (PAs) and Requests for Applications (RFAs) that NINDS published in the NIH Guide and mailed to members of the Council since their last meeting. The relatively large number of PAs and RFAs is one indication
of the increasing amount of responsibility that NIH, including NINDS particularly, is accepting for leading biomedicine to
needed discoveries and applications.
E. Reports Book
Dr. Atwell reminded the members of Council that the Reports Book was available. The Reports Book for this meeting included
a list of all funding actions since the previous Council meeting, the annual summary of interim actions taken by staff in
Fiscal Year 98, and the list of applications designated High Program Priority in Fiscal Year 98 and the status of each.
F. Council General Recommendations
Each January/February, the Council considers the general guidelines for administrative actions that may be taken by Program
staff without prior approval by Council. One addition in the Council General Recommendations was suggested by staff. Staff
is proposing to initiate a one-year pilot to issue expedited awards using a small group of Council members. Following discussion,
Council concurred with this recommendation. A copy of the amended Council General Recommendations is attached as Appendix
1.
G. Modular Grants
Dr. Atwell discussed the new modular grant application and award process which was announced in the December 15, 1998, NIH Guide, as a means to allow the investigators and reviewers to focus more on their science and less on budgetary details. The NIH
invites comments from investigators, reviewers, applicant organizations, and NIH staff during the first year of implementation
(address comments to modulargrants@nih.gov). Based on the comments, the NIH may refine the process, and later, will formally
assess the modular processes.
Applicants must configure budget requests for annual direct costs up to $250,000 in multiples of $25,000. The modular format
for applications will be required NIH-wide, as follows:
- April 1999 receipt dates for Small Business Technology Transfer grants, Phase I (R41) and Small Business Innovation Research
grants, Phase I (R43).
- May 25, 1999, receipt date for Academic Research Enhancement Awards (R15).
- June 1, 1999, receipt date for new and competing-renewal research project grants (R01), small grants (R03), and exploratory/developmental
grants (R21).
Applications that request more than $250,000 direct costs for any budget year and applications for any activity code not in
the list above will continue to use standard application procedures.
H. Jacob Javits Neuroscience Investigator Award
At its October 1998 meeting, the NANDS Council approved a change in the administration of the Jacob Javits Neuroscience Investigator
Award. (The award has consisted of a seven-year project period.) The award would be an initial project period of four years,
after which, based on an administrative review, NINDS staff may award an additional project period of three years. Dr. Atwell
reported that the Council Review Committee concurred with the implementation plan prepared by NINDS staff. A copy of the revised
NINDS policy on Javits Investigator Awards is attached as Appendix 2.
I. Clinical Trials Planning Grants
The rapid rate of discovery in basic and translational research has increased the NINDS' opportunity to support soundly designed
and well-executed clinical trials. The NINDS is a steward of public funds that the United States Congress appropriated to
support the research that ultimately might have the most positive impact on maintaining and/or restoring the health of the
nervous system. Therefore, in addition to more opportunity, the NINDS has a greater responsibility to choose wisely in which
clinical trials of which therapeutic approaches to invest. The NINDS considers scientific merit and program priority when
making all types of awards. However, the investment of time and money in a clinical trial is usually much more than for other
types of research. Thus, the amount of wisdom, knowledge, and commitment that the NINDS brings to deciding which clinical
trials to support (and in the land of a finite budget, which clinical trials will not receive NINDS funding), can hasten or
sabotage the medical advancements that the NINDS wants to foster.
The Council Review Committee, at its meeting the evening before, discussed processes by which the NINDS could make decisions
about which applications for planning a clinical trial and which applications for a full-scale clinical trial to fund. Dr.
Atwell presented the recommendations developed by the Council Review Committee:
- The Council should examine every application for a clinical trial planning grant, regardless of the priority score/percentile
that the Initial Review Group (IRG) assigned.
- The Council should recommend the relative priority for funding of each application for a clinical trial planning grant. In
that process, the Council may recommend lower priority to specific applications with scores within the 'payline' than to other
applications with scores beyond the 'payline.'
Funding of an application for a planning grant carries with it the commitment of the NINDS to fund the ensuing competitive
renewal application for the full clinical trial, if the IRG concludes that the research proposed in that application is technically
meritorious.
J. Women and Minorities as Subjects in Clinical Research
Council is required every two years to review the NIH and NINDS part of the report for tracking the inclusion of women and
minorities as subjects in clinical research. The Council members had received in advance of the meeting the report for NIH
prepared by the Office of Research on Women's Health and the report of the Recruitment Data for NINDS Clinical Studies for
Fiscal Years 1995 and 1996. Dr. Atwell pointed out that the studies funded by the NINDS are recruiting appropriately diverse
populations of subjects successfully. Council concurred with this report.
III. REPORT OF THE DIRECTOR, NINDS
Dr. Fischbach opened by describing the meeting of the Council Review Committee. The group consisting of Mr. Abendroth, Dr.
Choi, Dr. DeLong, Dr. DeVivo, Dr. Ojemann, and Dr. Tsien, meets the evening before the Council meeting to discuss selected
issues in order to more succinctly present these to the full Council.The NINDS budget for Fiscal Year 1999 increased 16 percent
over the Fiscal Year 1998 budget, which equates to a $120 to $125 million increase. Most of this will be for centers, program
projects and R01 grants. The Institute funded three Parkinson's Disease Centers of Excellence in Fiscal Year 1998 as mandated
by the Udall Act. An RFA for additional Centers has been reissued. There will be an increase in the training budget, mostly
allocated to stipend increases. The Division of Intramural Research will also get increased funds, but its budget will remain
about the same percentage of the total Institute budget. The NINDS Research Management and Support budget, which includesstaff
support and salaries, is less than 3 percent of our total budget, which is too little, Dr. Fischbach believes. NINDS has fewer
program directors relative to other Institutes, so in the coming year the Institute will recruit eight to ten new program
directors. It is expected that the success rate for grants will rise from 29 percent to as high as 35 percent. The downward
negotiation for grant awards will be reduced from 10 percent to 5 percent. For the first time, $10 million has been set aside
for grantee equipment and infrastructure needs.
Stimulated by Dr. Varmus' announcement on areas of emphasis, the NIH issued a record number of RFAs last year. Mindful of
supporting only the best research, NINDS has been selective in cosponsoring new RFAs.
Dr. Choi asked about budget prospects for Fiscal Year 2000 if the NIH funding reverts to the 2.4 percent increase proposed
in the President's budget. Dr. Fischbach indicated that there will be a drop in the number of new grants, and a resulting
fall in the payline.
The large budget increase in Fiscal Year 1999 has prompted Congressional interest in how the funds will be used. This underscores
the importance of the Institute's recently undertaken planning process.
Dr. Fischbach then presented an update on the strategic planning process. He emphasized that the process will help guide the
future of neuroscience research, particularly in neurological diseases.
To review, seven planning groups were formed in the areas of: Neurodegeneration; Neurogenetics; Channels, Synapses, and Circuits;
Neurodevelopment, Plasticity, and Repair; Cognition and Behavior; Glia and other Non-neuronal Cells; and Experimental Therapeutics
and Clinical Trials. These topics were formulated at a meeting at Woods Hole this past summer, and approved by Council in
September 1998. The topics of these panels were intentionally broad to provide a starting point to address all 600 diseases
under the aegis of NINDS.
Council members raised a general question about the change in the mission statement found in the draft document - and the
replacement of the word "disorders" with the word "disease." A discussion ensued, with some members arguing for retaining
the change and others members arguing to revert back to the original statement. Another suggestion was to use both terms in
the statement.
Dr. Fischbach informed the Council that the draft report they were provided with at the meeting is not a final report, but
an outline of the panel reports.
The subsequent planning process timeline includes sending out a summary of the report to public advocacy groups and the neuroscience
community for comment and presenting the summary to Congress at the annual appropriations hearings (March 1999). The first
full report, to be published in May, will be about 40 pages in length and will include color photographs. This report will
be the first step in an on-going process of Institute planning. The initial plan is viewed as helping shape priorities over
the next two to three years.
The title of the planning draft is "Neuroscience at the New Millennium." Dr. Fischbach related to Council the sense of exhilaration
that was a part of the planning panel meetings - panel members seemed genuinely honored to be taking part in this process,
and were very interested in continuing to participate in the process as it evolved. In addition, program staff will be intensely
involved in the process of implementation.
The planning process identified seven initial goals. They are:
- to attack neurodegenerative disorders over the lifespan. A lifespan view is important, as is identifying common mechanisms
of degeneration.
- define brain communication and organization. This includes all levels from channels and synapses on up to cognition and behavior.
- promote nervous system development and repair.
- analyze glia and other non-neuronal cells.
- support infrastructure and resources. This is a key recommendation, and will need careful consideration, as it may require
the need for tradeoffs with other important initiatives.
- create a premier intramural national neuroscience center.
- expand clinical trials and therapeutics.
Each of these goals had subtopics, which Dr. Fischbach reviewed with Council.
Concerning neurodegeneration, he emphasized that NINDS wanted to be ambitious, and cure Parkinson's disease within ten years.
Council members inquired what was meant by "cure," and Dr. Fischbach defined it as stopping or reversing the course of the
disorder. Several Council members questioned whether it was a good idea to be so definitive about this. This led to discussion
about the importance of not overstating what can be done and thereby raising expectations that may not be met. This could
then lead to a backlash from the voluntary groups. Most members thought that it was important to be optimistic, and have the
overall goal be a cure, but to not be specific in terms of promising a specific date when this will occur.
In terms of development, Dr. Fischbach pointed out that before we can repair neural circuits, we need to understand them.
The best example of a circuit ripe for more analysis is the spinal cord.
Regarding glia, he pointed out that there is much we don't know about them, and that this panel was extremely happy to have
the importance of this topic.
In terms of clinical trials, he reminded Council that NINDS has adopted new planning and pilot grant mechanisms. He also indicated
that the process will include making choices of selected areas to emphasize. One topic would be better delivery of agents
to the brain, and it will be important to collaborate with industry on this.
Council members pointed out that the attitude of the neuroscience community needs to be changed from viewing industry as only
profit-motivated to being seen as valuable partners. Neuroscience needs to harness the energy of industry, find areas where
academia and industry can work together, and give industry incentives to do so. One way would be to collaborate with the private
sector early in the process - this might help industry get drug approval from the FDA - a strong incentive for collaboration.
Dr. Fischbach pointed out that providing specialized resources and support for collaborative endeavors was discussed by all
the panels. However, putting more funds toward resources may result in reductions in other areas.
In terms of the intramural program, Dr. Fischbach updated Council on plans to construct a new building complex in collaboration
with NIMH to house neuroscience research at NIH. He showed architectural drawings of the proposed new complex.
Copies of the slides used in Dr. Fischbach's presentation are attached as Appendix 3.
IV. UPDATE ON REVIEW AND NEUROSCIENCE STUDY SECTIONS
Following introductory remarks by Dr. Atwell, Dr. Lillian Pubols, Chief of the NINDS Scientific Review Branch, presented an
overview of the review process, focusing on some frequently asked questions. The Center for Scientific Review (CSR) referral
office assigns grants to institutes by a multi-stage process, with extensive written guidelines. Applications are subsequently
assigned for review to an institute's review branch or CSR's Initial Review Group (IRG) and study section. The Scientific
Review Administrator (SRA) is critical before, during and after the review process. One particularly important aspect of the
SRA's job is the need to balance many factors in selecting and evaluating reviewers.
Dr. Elliot Postow, Director of the CSR Division of Molecular and Cellular Mechanisms, reviewed the neuroscience study section
reorganization process. Reviewers' philosophy had to change somewhat to cope with the additional grant mechanisms added after
integration. The success rates and score distributions from the first two rounds of review indicate that NINDS grants appear
to be succeeding about as expected. Median success rates were perhaps slightly better than other institutes, but with no dramatic
deviations. Likewise, score distributions, though variable, were perhaps slightly better on average than other CSR study sections
in approaching the goal of a 300 median score.
Dr. Postow then addressed the issue of evaluation, which was promised as an integral part of the reorganization. CSR obtained
a grant from the NIH evaluation fund and appointed an external advisory committee, but that committee focused almost exclusively
on psychometric issues. CSR is forming a second committee with more stakeholder involvement, including participation of Institute
staff and extramural scientists. However, several factors confound attempts to evaluate the effects of the reorganization
per se. These include simultaneous changes in scoring practices and new review criteria, as well as SRA vacancies and the temporary
appointment of reviewers.
Dr. David Pleasure, Professor of Pediatrics at the Children's Hospital of Philadelphia, described his impressions as a chair
of a new neuroscience study section. Although he supported the idea of the reorganization, he noted some problems in execution.
One problem is the mixing of R01 and postdoctoral applications in the same study sections. While some study sections handle
the different criteria for review well, others do not, and assignment of postdoctoral applications to a subset of review groups
might be more effective. The review groups are also struggling with the new criteria regarding innovation. There is one very
serious problem: the review process cannot work well without very good SRAs who have adequate support, and there are too few
SRAs, with too little support.
The extensive Council discussion focused mainly on two issues. First, there was general agreement that recruiting and supporting
good people to be SRAs is critical to the NINDS mission, especially given the Institute's emphasis on investigator-initiated
grants. Second, the Council agreed that not only the fairness of review of clinical research, but also the perception of the
review process among young people considering a career path in research is critical. The reorganization has moved toward one
goal of the NIH Director's Panel on Clinical Research, that is assigning clinical grants to study sections that see a reasonable
proportion of clinical grants. However, it is not yet clear whether clinical and translational research is being fairly evaluated.
The discussion also explored more broadly the plight of physician-scientists. Dr. Fischbach suggested that a small working
group of Council members collect relevant data and make the case for any recommendations.
V. NATIONAL BIOETHICS ADVISORY COMMISSION REPORT
Ms. Lorraine Fitzsimmons, Program Analyst , Science Policy and Analysis Branch, NINDS, and Dr. John Booss, NANDS Council Member
and Director of Neurology Service, Veterans Administration Medical Center, West Haven, Connecticut, reported on the National
Bioethics Advisory Commission (NBAC) Report: "Research Involving Persons with Mental Disorders That May Affect Decision making
Capacity." This report was produced pursuant to Executive Order 12975 which directs the Commission to consider the protection
of the rights and welfare of human research subjects. In the report NBAC considers how ethically acceptable research can be
conducted with human subjects who suffer from mental disorders that may affect their decision making capacity; whether additional
protections are needed; and, if so, what they should be and how they should be implemented. Although existing Federal regulations
for research involving human subjects have provided special protections for certain populations that are regarded as particularly
vulnerable, persons with mental disorders who may have impaired capacity to make decisions, and therefore to give voluntary
informed consent, have not received special protections. The NBAC proposes a number of recommendations, some in the form of
requirements that would require changes in the language of the Common Rule or changes and additions to the Code of Federal
Regulations.
The implications of the report for clinical neurology and neurosurgery research are extensive. Unfortunately, however, input
was neither invited nor received from researchers and patient groups other than those representing psychiatric disorders.
Other than being included within the "dementia" category of patients, neurological disorders such as Alzheimer's disease and
other neurodegeneration, vascular disease, and traumatic brain injury are not specifically considered in the report. Many
other concerns were discussed, including the categories of risk, the membership requirements of review boards, and capacity
assessment. If the recommendations of the report are implemented, several possible negative effects may result for neuroscience
research. It was suggested that the neuroscience community may be alerted to these concerns at the several national workshops
and conferences to be held in the near future.
VI. ACCESS TO PRIMARY DATA VIA THE FREEDOM OF INFORMATION ACT (FOIA)
Dr. Wendy Baldwin, Director of the Office of Extramural Research, Office of the Director, NIH, reported on the implications
of a notice of proposed rule making from the Office of Management and Budget concerning Freedom of Information Act (FOIA)
provisions as they apply to information produced by a grantee. The Omnibus 1999 Appropriations bill from Congress directed
the Office of Management and Budget (OMB) to amend rules to extend the FOIA to "require Federal awarding agencies to ensure
that all data produced under an award will be made available to the public under the [Act]." Following legislative intent,
the OMB has confined the data release to published data used by the Federal Government in developing policy or rules. The
proposed rule indicates that the awarding agency should make the data available through the procedures established under the
FOIA. However, several important issues remain to be clarified.
We are now in a 60-day public comment period on the Notice of Proposed Rule Making. During this period, individual researchers,
research institutions and Federal agencies have an opportunity to seek clarification of different aspects of this proposed
rule. Some questions that might be asked include: How broad is the definition of data? How would costs of compliance be recouped?
Are protections for privacy under FOIA sufficient? When do data in a publication have to be released, and what "publications"
are included-only formal peer-reviewed publications or notes for a verbal presentation?
VII. SCIENTIFIC PRESENTATION: "THE INTERACTION OF SPIDER TOXINS WITH ION CHANNELS"
Dr. Kenton Swartz, Chief, Molecular Physiology and Biophysics Unit, Division of Intramural Research, NINDS, reported that
the orchestrated activity of ion channel proteins enable the nervous system to generate and propagate the electrical signaling
that ultimately allows us to sense and respond to our environment. Ion channels are integral membrane proteins that when open
allow ions, for example sodium, potassium or calcium, to cross the cell membrane. The goal of his research is to define the
molecular composition of specific ion channels and to understand what they normally do and how they do it. Many drugs used
to treat neurological and psychiatric disorders derive their efficacy from their ability to alter the activity of ion channels.
Their research objectives should, therefore, help to define specific channels as therapeutic targets and to develop drugs
against them.
The identification of genes encoding ion channel proteins has revealed a tremendous diversity of ion channels. Dr. Swartz
is interested in understanding how the specialization of particular ion channels allows them to fulfill specific physiological
functions.
While this research addresses fundamental questions about the mechanics of voltage-dependent gating, it also has recently
begun to reveal clinically useful ways to alter the behavior of voltage-gated ion channels. For example, in an attempt to
localize the region of the channel to which one specific toxin binds, they discovered a point mutation that switched the effect
of the toxin from inhibiting channel opening to facilitating channel opening. This is an important result because it suggests
that by interacting with the voltage-sensing domain of voltage-gated ion channels they can modify channel activity in a multidirectional
fashion. Most existing drugs can only 'inhibit' the activity of voltage-gated ion channels. Drugs that open voltage-gated
potassium channels, in particular, could be very useful in a variety of conditions involving hyperexcitibility, including
the brain damage that ensues after a stroke and the aberrant discharging of neurons in epilepsy. Their results suggest specific
ways to design regulatory molecules whose effects on specific channels can be precisely tuned.
VIII. OVERVIEW, DIVISION OF INTRAMURAL RESEARCH
Dr. Story Landis, Director, Division of Intramural Research, NINDS, gave the annual update about the intramural programs.
The Division of Intramural Research receives about 10 percent of the NINDS budget to support the laboratories of 55 independent
investigators. Each independent investigator manages a laboratory that engages other scientific, technical, and administrative
staff, but the variability among the sizes of each laboratory is large.
Some of the research is very basic, such as that of Dr. Ron McKay, who studies features of stem cells that might be useful
for treating certain neuro-degenerative diseases. Other research, such as the work of Dr. Roscoe Brady using enzyme replacement
therapy on Gauchet's Disease and Fabrey's Disease, has more immediate and direct clinical significance. The findings of the
research of Dr. Karen Nelson might significantly reduce the occurrence and/or severity of cerebral palsy. She found that giving
magnesium during the birth process to high-risk, low birth-weight infants decreases the likelihood that cerebral palsy would
occur.
The NIH intramural programs face some very tough competition when trying to recruit the most talented researchers in biomedical
and behavioral research. The NIH has had two rather unique features that are attractive to many researchers. At NIH, a researcher
can gamble on a long-shot, i.e., pursue avenues of research that are very interesting and important, but that might not seem
feasible to the researcher whose laboratory, even job, depends upon obtaining and renewing extramural support from NIH and/or
other sources. For clinical researchers, an attractive feature of the NIH has been the Clinical Center, a hospital that does
not need to generate income from patient care. The Clinical Center admits only research protocol patients, and thus, the Clinical
Center staff and management can focus on the special needs of a research hospital.
The task that the NINDS assigned to Dr. Landis when she was hired three and one-half years ago was to improve the working
environment of the NINDS intramural program. The objectives have been to recruit the most outstanding, creative scientists
and to provide an intellectually stimulating research environment that will foster the ideas and energy that lead to the most
meaningful kinds of productivity. Dr. Landis then described what the NINDS intramural program has accomplished under her leadership.
Innovations: T he Board of Scientific Counselors makes recommendations about the allocation of resources to each laboratory. NINDS management
implements the recommendations with rare modification.
The Marks & Cassell Report mandated changes for all of the NIH intramural programs. Every institute must use open searches
to fill faculty positions. The NINDS has worked hard to ensure that their searches are open and fair, and furthermore, to
ensure that outstanding applicants will be attracted. The NINDS also modified the tenure track system so that the NINDS could
more clearly articulate and more fairly apply the requirements and processes for promotion.
Independent investigators at NIH can be at a disadvantage when competing with a principal investigator of an NIH extramural
grant for an academic position because usually the principal investigator can transfer the grant support to the hiring organization,
but the intramural scientist leaves NIH empty-handed. The NINDS is now making it possible for an intramural researcher who
receives an offer of employment from another organization to take up to two years' salary and their equipment with them to
the new organization.
The NINDS established the "Competitive Fellowship Program" for which postdoctoral fellows within the NINDS can compete. The
fellow must prepare and submit an application for a National Research Service Award fellowship award. A scientific review
group (a.k.a., study section) administered by the Scientific Review Branch, NINDS, reviews the applications. The Competitive
Fellowship Program provides postdoctoral support for only some of the applicants. However, the Competitive Fellowship Program
provides valuable experience in preparing an application for ALL of the applicants.
Creating community: I n the spring of 1998, the NINDS held its scientific retreat which provided an occasion for scientists separated by organizational
component to meet on the basis of common scientific interests.
Dr. Landis wants to foster more communication and collaboration among the laboratories, because such interactions can generate
intellectual vitality and scientific progress. To facilitate such collaboration, she offered approximately $500,000 of support
for a meritorious research project that substantially involved investigators from different disciplines. A few groups of investigators
already have responded to her offer and others are preparing to do so.
Dr. Landis also wants to foster productive interactions between the intramural and extramural programs and staff. She would
like to encourage intramural scientists to take a six to twelve month sabbatical to work within the extramural programs. Similarly,
she would like to welcome extramural scientific staff to the intramural laboratories for a sabbatical.
Faculty. D r. Landis reported that she has hired seven faculty members, four of them for tenure track positions. A recent search to
fill two tenure track positions has recruited two likely selections. Currently vacant is the new Clinical Neuroscience Program
Director position, which reports to the Scientific Director, Dr. Landis.
During the past year, eight positions have become vacant due to retirements and, in one case, death. These vacancies provide
the flexibility needed for revitalization and the initiation of new programs and priorities.
Suburban Hospital is a county trauma center and probably will be designated a county stroke center. The NINDS has established
a contract with them that will enable NINDS to do more research about acute neurological trauma.
IX. REVIEW OF THE DIVISION OF INTRAMURAL RESEARCH BOARD OF SCIENTIFIC COUNSELORS' REVIEWS
In closed session, Dr. Landis presented the findings and recommendations of the Board of Scientific Counselors based on their
review of three laboratories and two branches of the Division of Intramural Research.
X. COUNCIL CONSIDERATION OF PENDING APPLICATIONS
This portion of the meeting, involving specific grant review, was closed to the public. The Council gave special attention
to applications from foreign institutions and applications for which there were concerns about human subjects, including appropriate
representation of women and minority subjects, or laboratory animals.
A. Research Training and Career Development Programs
The Council reviewed a total of 68 training and research career development grant applications; of this total, 57 applications
had primary assignment to NINDS, and 53 of them (93.0 percent) were recommended for support in the amount of $7.4 million
first-year direct costs. It is anticipated that, of the training and research career development grants competing at this
Council, NINDS will be able to pay first-year direct costs of approximately $4.1 million.
B. Research Grant Awards
The Council reviewed a total of 985 research grant applications; of this total, 653 applications had primary assignment to
NINDS, and 431 of them (66.0 percent) were recommended for support in the amount of $94.7 million first-year direct costs.
It is anticipated that, of the research grants competing at this Council, NINDS will be able to pay first-year direct costs
of approximately $39.5 million.
Senator Jacob Javits Neuroscience Investigator Awards
The Senator Jacob Javits Neuroscience Investigator Awards are made to distinguished investigators who have a record of scientific
excellence and productivity, who are actively pursuing an area of research of strategic importance, and who can be expected
to continue to be highly productive for a seven-year period. Candidates are nominated at each Council meeting during the fiscal
year, and from these nominations the awardees are selected at the June Council. At this meeting, the Council nominated three
investigators as potential recipients of this award.
C. Special Program Actions
The Council reviewed a total of 94 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant
applications; of this total, 64 applications had primary assignment to NINDS and 47 of them (73.4 percent) were recommended
for support in the amount of $7.1 million first-year direct costs. It is anticipated that, of the SBIR and STTR applications
competing at this Council, NINDS will be able to pay first-year direct costs of approximately $1.5 million.
The Council reviewed a total of 7 Academic Research Enhancement Awards (AREA) applications; of this total, 7 applications
had primary assignment to NINDS, and 5 of them (71.4 percent) were recommended for support in the amount of $0.4 million direct
costs. It is anticipated that NINDS will be able to pay all $0.4 million of these applications.
XI. ADJOURNMENT
Prior to adjournment, Drs. Fischbach and Atwell were thanked for a very interesting and rewarding meeting. The meeting was
adjourned at 11:50 a.m. on Friday, February 12, 1999. We certify that, to the best of our knowledge, the foregoing minutes and attachments are accurate and complete.
5/10/99
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____________/s/_________________ Constance W. Atwell, Ph.D. Executive Secretary National Advisory Neurological Disorders and Stroke Council Associate Director for Extramural Research National Institute of Neurological Disorders and Stroke |
5/10/99
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____________/s/_________________ Gerald D. Fischbach, M.D. Chairperson National Advisory Neurological Disorders and Stroke Council Director National Institute of Neurological Disorders and Stroke |
Ruth Linn Committee Management Specialist
These minutes will be formally considered by the Council at its next meeting. Corrections or notations will be incorporated
in the minutes of that meeting.
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