NINDS Advisory Council Meeting Minutes, September 18, 2003

• I. Call to Order and Opening Remarks
• II. Report of the Associate Director for Extramural Research
• III. Report of the Director, NINDS
• IV. The NIH Roadmap Process
• V. Update on Funding Strategy for Fiscal Year 2004
• VI. Scientific Presentation: "The Future of Human Genetics in Neurology"
• VII. National Research Council and Institute of Medicine Report
• VIII. Concept Approval for Fiscal Year 2005 Proposed Initiatives
• IX. Council Subcommittee Reports
• X. Council Review of Pending Applications
• XI. Adjournment

Department of Health and Human Services
Public Health Service
National Institutes of Health
National Advisory Neurological Disorders and Stroke Council

Summary of Meeting¹
September 18, 2003

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 158th meeting on September 18, 2003, at the Hyatt Regency Bethesda, Bethesda, Maryland. Dr. Story Landis, Director of the National Institute of Neurological Disorders and Stroke (NINDS), served as Chairperson. Because of the Federal government closure on September 18-19 due to Hurricane Isabel, the meeting was held at the Hyatt Regency Bethesda and business was conducted in one day.

In accordance with Public Law 92-463, the meeting was:

Open: September 18, 2003 --10:30 a.m. to 3:30 p.m.

for the review and discussion of program development, needs, and policy; and

Closed: Closed: September 18, 2003 - 3:30 p.m. to 6:00 p.m.

for the consideration of individual grant applications and other business.

Council members present were:

Mr. Ronald Bartek
Dr. Bruce Bean
Dr. Alicia Conill
Dr. Raymond Dingledine
Dr. Daniel Lowenstein
Mr. Bradley Margus
Mr. Jeffrey Martin
Dr. William Mobley
Ms. Ellyn Phillips
Dr. Patrick Pullicino
Dr. Sally Shaywitz
Dr. Ira Shoulson
Mr. Robert Waterman

Council Roster (Attachment 1)

Council members absent were:

Dr. Keith Black
Dr. J. Donald Easton
Dr. Susan Hockfield
Dr. Lydia Villa-Komaroff
Dr. Huda Zoghbi

Ex Officio Members absent:

Dr. Paul Hoffman, Department of Veterans Affairs
Dr. Geoffrey Ling, Department of Defense

Council Ad Hoc Consultant

Dr. Apostolos Georgopoulos, University of Minnesota

Members of the public present for portions of the open meeting included:

Dr. Louis Ptacek, University of California, San Francisco

NINDS employees present for portions of the meeting included:

Dr. Constance Atwell Dr. Robert Baughman Mr. Andy Baldus Dr. Maureen Beanan Mr. Gahan Breithaupt Dr. Daofen Chen Dr. Arlene Chiu Dr. Robin Conwit Dr. Robert Finkelstein Dr. Alfred Gordon Dr. Katrina Gwinn-Hardy Dr. Robert Hart Dr. Jill Heemskerk Dr. Deborah Hirtz Dr. Henry Khachaturian Dr. Naomi Kleitman Ms. Margaret Jacobs Dr. Scott Janis Dr. Story Landis Dr. Yuan Liu Mr. Michael Loewe Dr. Ernest Lyons

Dr. John R. Marler Dr. Laura Mamounous Dr. Cynthia McCormick Dr. Mary Ellen Michel Dr. Merrill Mitler Dr. Claudia Moy Dr. Diane Murphy Dr. Paul Nichols Dr. Michael Nunn Dr. Eugene Oliver Ms. Sylvia Parsons Dr. Audrey S. Penn Dr. Barbara Radziszewska Dr. Raul Saavedra Dr. Paul Sheehy Dr. Randall Stewart Dr. Danilo Tagle Dr. Ursula Utz Dr. Alan Willard Dr. Frances Yee

I. Call to Order and Opening Remarks

Dr. Story Landis, Director, NINDS, welcomed Council members, guests, and staff to the 158th Council meeting. The following new Council members were introduced: Dr. Alicia Conill, Dr. Raymond Dingledine, Dr. William Mobley, and Dr. Patrick Pullicino. Mr. Robert Waterman was welcomed back to the Council for a full term following an interim appointment. New Council member, Dr. Huda Zoghbi, was unable to attend this meeting.

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II. Report of the Associate Director for Extramural Research

Government in the Sunshine Act and the Federal Advisory Committee Act

Dr. Constance Atwell, Associate Director for Extramural Research, NINDS, reviewed the Government in the Sunshine Act and the Federal Advisory Committee Act, which require the Department of Health and Human Services to open to public observation as many advisory committee meetings as possible, including the National Advisory Councils. The NANDS Council meeting was open to the public, except during the review of grant applications. Notice of the date and place for 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. 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, of which they are an employee, consultant, officer, director or trustee, or in which they have a financial interest. Institutions or organizations which have multi-campus institution waivers, or are specifically designated as separate organizations under 18 U.S.C. 208(a), are exempt from this provision. Council members were also reminded that they need to remove themselves from discussions of applications from any institution from which they have received an honorarium for one year from the time the honorarium was received. If the Council member's participation is deemed critical to the discussion, however, a waiver may be granted by the Institute.

Consideration of Minutes of Previous Council Meeting

The minutes of the Council meeting of May 22-23, 2003, were considered and accepted as written.

Consideration of Dates for Future Council Meetings

The following dates for future Council meetings were reconfirmed:

February 12-13, 2004 (Thursday and Friday)

May 27-28, 2004 (Thursday and Friday)

September 9-10, 2004 (Thursday and Friday)

February 10-11, 2005 (Thursday and Friday)

May 26-27, 2005 (Thursday and Friday)

September 15-16, 2005 (Thursday and Friday)

Other Items

Reports Book--The Reports Book consists of applications that have been designated for funding since the last Council meeting. It includes interim actions that have been taken and the status of applications that were identified for High Program Priority.

Expedited Review Process--Dr. Atwell reported that 160 out of 196 expedited applications were ready to be awarded.

Loan Repayment Program--Dr. Atwell reported on the extramural Loan Repayment Program (LRP). The purpose is to recruit and retain highly qualified health professionals to biomedical and behavioral research careers by countering the growing economic disincentives to embark on such careers, using as an incentive the repayment of educational loans. The allocation of funds is determined by the Office of the Director, NIH, and is related to each IC's proportion of its clinical research portfolio to all of the clinical research being funded at the NIH.

The NINDS received 79 applications for the LRP (compared to 32 applications for FY 2002) and will pay 48 (32 clinical and 16 pediatric). Other I/Cs are paying some of the grants assigned to NINDS. The Scientific Review Branch conducted the review. Dr. Atwell reported that the success rate was 58 percent for clinical applications and 67 percent for pediatric applications. The Loan Repayment Program is widely advertised in professional journals, on the NIH website, and in e-mail distribution notices.

NIMH-NINDS Data Sharing Plan for Genetics--Dr. Atwell gave a brief history of the data sharing plan and thanked Dr. Katrina Gwinn-Hardy for her work on this effort. The plan is now in the NIH Director's office for approval. The plan requires investigators to make their data available to the research community after a certain time period within award of the grant.

Special Considerations List--Dr. Atwell called attention to the Special Considerations list, which will be reviewed in closed session, and reminded Council that the information was provided to them on the Council website before today's meeting.

Staff Actions--The following new staff were introduced: Dr. Janet He, program analyst for the System and Cognitive Neuroscience Cluster; and Karen Dunlap, Grants Management Specialist. In other staff news, Dr. Atwell announced that Dr. Paul Nichols, program director in the Systems and Cognitive Neuroscience Cluster, is retiring at the end of the year, after 32 years of service. He has covered neuromuscular disorders, diabetes, and many other areas throughout his tenure at NINDS. Dr. Atwell expressed appreciation for his service and wished him well in his retirement. Dr. Toby Behar, program director in the Neural Environment Cluster, is moving to the NIH Center for Scientific Review, where she will maintain her focus on glial research. Dr. Atwell thanked her for her service to NINDS.

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III. Report of the Director, NINDS

In her introductory remarks, Dr. Story Landis stated that she felt honored by having been chosen to lead NINDS. She thanked everyone who had worked so hard to keep NINDS on course and moving ahead since Dr. Gerald Fischbach left, particularly Dr. Audrey Penn who served as Acting Director, Dr. Gene Major who served as Acting Deputy Director and Dr. Constance Atwell. Dr. Landis briefly outlined her long-standing relationship with NINDS including a postdoctoral NRSA, R01support with two sequential Javits awards, directorship of an NINDS training grant, study service in CSR, service on the NINDS Intramural Board of Scientific Counselors, and an eight year term as Scientific Director of the NINDS Intramural Program. Dr. Landis stated that she felt that while working at the NIH for eight years while serving as Scientific Director has provided some preparation for serving as Director, she recognizes that there will be many new responsibilities and duties that will require a steep learning curve. She plans to spend the first several months meeting with other institute directors, program staff, health voluntary and advocacy groups, and professional organizations.

NINDS will recruit a new Scientific Director to run the Intramural program. In the interim, Dr. Gene Major will serve as Acting Director for the Basic Neuroscience Program. Dr. Henry McFarland already serves as Clinical Director. Both will report to Dr. Landis. The first phase of the Porter Neuroscience Building will open June 1. Funds have not yet been obtained for its completion.

NINDS plans a number of recruitments in the extramural program for the coming year. These include a replacement for Dr. Constance Atwell, who will be retiring, as well as a number of program directors. Council members were encouraged to nominate candidates for such positions.

The coming year will be challenging for the institute as NINDS balances the opportunities for investing in basic, translational, and clinical neurosciences, in hypothesis driven and hypothesis generating science, and in big versus small science. Additional factors include Congressional disease-specific mandates and Roadmap activities

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IV. The NIH Roadmap Process

Dr. Lana Skirboll, Associate Director, Office of Science Policy, Office of the Director, NIH, reported that soon after becoming the Director of NIH, Dr. Zerhouni convened a series of meetings to chart a "Roadmap" for medical research in the 21st century. The purpose was to identify major opportunities and gaps in biomedical research that no single institute at NIH could tackle alone but that the agency as a whole must address to make the biggest impact on the progress of medical research. The opportunities for discoveries have never been greater, but the complexity of biology remains a daunting challenge. NIH is uniquely positioned to catalyze changes that must be made to transform our new scientific knowledge into tangible benefits for people. Developed with input from meetings with more than 300 nationally-recognized leaders in academia, industry, government, and the public, the NIH Roadmap provides a framework of the priorities the NIH as a whole must address in order to optimize its entire research portfolio. It lays out a vision for a more efficient and productive system of medical research. It identifies the most compelling opportunities in three main areas: new pathways to discovery, research teams of the future, and re-engineering the clinical research enterprise.

Initiatives under the NIH Roadmap will help enable the agency to sustain its historic record of cutting-edge contributions that are central to extending the quality of healthy life for people in this country and around the world. A complete description of the NIH Roadmap can be found at http://nihroadmap.nih.gov/index.asp

In Council discussion, Congress's interest in the Roadmap project was discussed. It was noted that Congress appropriated funds for the project, and the NIH Director has met with congressional committees to discuss it. The House has asked NIH to emphasize degenerative diseases and translational research. Dr. Penn explained that no specific diseases are targeted by the Roadmap plan; rather, it is a broad, in-depth guide for research needs. Dr. Landis informed Council that each institute is to identify how Roadmap goals apply to the goals of the institute. One third of one percent of every I/C's budget will go to the Roadmap fund, which will support the first year costs of the Roadmap projects. They should add value to the individual institute's efforts.

Dr. Penn, who has worked closely with the NIH Director's office on the Roadmap, thanked the program staff involved in the Roadmap committees and noted that NINDS is taking the lead on the Molecular Libraries Roadmap.

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V. Update on Funding Strategy for Fiscal Year 2004

Dr. Atwell explained that at the last Council meeting, it was decided that making efforts to maintain a 21 percentile payline should be the institute's foremost goal. To that end, Council advised that the institute change the percentage cuts from IRG-recommended levels, to 7 ½ percent for modular grants and 12 ½ percent for non-modular grants. The NIH budget has not been signed by the President, and the projected budget for FY 04 has not changed from the last Council presentation. It is estimated that there will be $298 million available for competing grants in FY04, assuming the Senate budget is passed. There is a $22 million difference between the House and Senate budgets. In estimating the FY 04 budget, staff had to consider several factors: 1) The new contribution to the Roadmap fund, 2) The increase in the number of applications since the last Council. The new rate of increase was projected into FY 04. 3) The increase in the average cost of a grant is higher than what was projected at the last Council budget presentation. 4) The new average percentage cut in grants requested by Council at the last meeting. Applying these factors to the competing budget estimate, the resulting payline percentile is 19.0. Although this is less than last year, it is higher than most of the other institutes at NIH. Dr. Atwell presented a table of all of the applications received in FY 03 by activity, by Council, and by percentage. Eighty one percent of the applications were R01s. Mr. Martin asked if the staff have performed a portfolio analysis to find the areas where more support is needed. Dr. Landis explained that the institute has been asked to submit a five-year plan to the NIH Director, and support for research needs will be included in that plan.

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VI. Scientific Presentation: "The Future of Human Genetics in Neurology"

Dr. Louis Ptacek, Investigator, Howard Hughes Medical Institute, Professor of Neurology, University of California, San Francisco, reported that there has been an explosion in the application of molecular human genetics to neurological diseases over the last 20 years, beginning with the implementation of the first human genetic maps. The mapping of the genome allowed first localization and then positional cloning of human disease genes and culminated with sequencing of the human genome. Some have argued that the accelerating pace of disease-gene discovery has meant that this field would be short-lived and that much of the work in the molecular basis of inherited human diseases would soon be completed. In part, because of the nature of this field and because of the accelerating pace of discovery, our definition of human genetics is evolving rapidly. Identification of many genes causing human neurological diseases has radically changed our understanding of disease pathogenesis in many areas. What changes can we expect over the next decade? Using specific examples in the genetics of human neurological diseases, the opportunities for a new era in human genetics were discussed. Molecular dissection of Mendelian neurological diseases will evolve into new possibilities for understanding complex inheritance of disease predisposition and will also yield new tools for development of better treatments for patients with neurological diseases. Development of new therapies and understanding of complex disease lags behind the discovery of Mendelian disease genes, but we can also expect acceleration of the pace of discovery in these areas in the decade to come.

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VII. National Research Council and Institute of Medicine Report

Council member, Mr. Robert Waterman, described a Congressional concern that with 27 institutes and centers, NIH may have become too unwieldy and unmanageable to carry out its mission. Congress asked the Institute of Medicine and National Research Council to conduct a review of NIH's organization. They began with the major assumptions that NIH has been highly successful in fulfilling its mandate and that any potential reorganization would involve taking into account strategic priorities, the existing culture, systems and processes, and NIH's multiple constituent relationships. After over a year of study and consultation with the current and former NIH directors, institute directors and staff, and members of the research community and public, the IOM and NRC produced 14 recommendations:

1. Assure that centralization of management functions will not undermine NIH's ability to identify, fund, and manage the best research and training.
2. Create a public process for considering proposed changes in the number of NIH institutions or centers.
3. Strengthen the overall NIH clinical research effort through consolidation of programs and creation of a new leadership position.
4. Enhance and increase trans-NIH strategic planning and funding.
5. Strengthen the Office of the NIH Director.
6. Establish a process for creating new OD offices and programs.
7. Create a Director's Special Projects Program to support high-risk, high-potential payoff research.
8. Promote innovation and risk-taking in intramural research.
9. Standardize level-of-investment data and information management systems.
10. Set terms and conditions for IC Director appointments and improve IC Director review process.
11. Set terms and conditions for the NIH Director appointment.
12. Reconsider the special status of the National Cancer Institute.
13. Retain integrity in appointments to advisory councils and reform advisory council activity and membership criteria.
14. Increase funding for Research Management and Support.

Following Mr. Waterman's presentation, the Council asked: 1) whether the IOM report addressed the IOM's previous recommendations related to NIH's relationship to voluntaries, and 2) what it said about the role of the Intramural program. In response, Mr. Waterman explained that the report started with a "clean slate" and did not revisit previous recommendations. The Intramural program is not as unique as it has been in the past because research in the Extramural community has greatly improved. The report recommends that directors in Intramural review the program and define what its unique role should be. On the question of NIH's budget, IOM stated that it is adequate, but that a higher percentage of the I/Cs' budgets be devoted to the Roadmap. It was noted that the NIH Director's authority to initiate the Roadmap came directly from Congress, which authorized $10 million for the effort. The IOM report recommended that the NIH Director be appointed for one six-year term and be eligible for re-appointment. The Director has said that he will study the IOM recommendations and that they will be implemented. Congressional hearings have been scheduled for the Director to present his plan for implementation.

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VIII. Concept Approval for Fiscal Year 2005 Proposed Initiatives

Dr. Atwell asked the Council to review for concurrence several initiative concepts submitted by staff for FY 2005. Under the Federal Advisory Committee Act, an outside review group must clear all initiatives that involve funding by the Federal Government. Beginning with the 156th Council, the Institute asked that Council conduct the outside review for all new initiatives. Concurrence does not imply a mandate to go forward, as the final decision on the initiatives depends on the availability of funds. A motion was made and passed by Council approving the concepts. Dr. Pullicino requested that the record show he was opposed to the "Collaborative Research in Stem Cell Biology" initiative concept.

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IX. Council Subcommittee Reports

Training and Career Development Subcommittee

Dr. Bruce Bean, Chair of the Training and Career Development Subcommittee, reported that the subcommittee discussed the differences between T32 vs. F32 training experiences. The T32 provides a chance to build a community of trainers/mentors and young trainee scholars. The F32 accelerates the maturation of these young scholars. The Subcommittee explored the question of allowing more training time for F32 fellows as an incentive; however, it cannot be done since the NRSA rules restrict postdoc training to three years total.

The Subcommittee discussed the evaluation of T32 training programs. Currently, the major evaluation is done at the time of peer review. There is a need for a set of guidelines ("best practices") to serve as review criteria. For example, T32 programs should provide a rigorous, well-defined plan for recruitment, appointment, and monitoring of trainees. In addition, T32 programs should have a strong program for training in the responsible conduct of science. A critical element in evaluation of the program should be the involvement of training faculty (mentors) in both the recruitment/appointment, as well as in teaching responsible conduct.

The Subcommittee directed NINDS staff (in particular the Program Directors) to do the following: 1) Begin the work of identifying T32 institutions that do a particularly good job of training and placing their trainees in various academic and industry positions. Important outcome measures include the success of trainees in publishing and in obtaining another position (going beyond the postdoc). 2) In collaboration with other Neuroscience Institutes, begin evaluating the future "manpower" needs for the neurosciences (Are we training adequate numbers of researchers to meet future needs? Do we need new kinds of training experiences for future scientists?) 3) Consider a new workshop at the Society for Neuroscience targeted to T32 postdoc trainees, and possibly also F32 fellows. The objective is to help trainees in career choices and advancement strategies.

The following recommendations were made:

1. Limit the numbers of T32 awards, thus gradually reducing the numbers of trainees. Monitor appointment of more advanced trainees to the T32 program to make sure that they continue to be trained (quality of training is paramount). Make appropriate exceptions for clinical trainees, minorities, women, and underserved scientific areas.
2. While not recommending a specific success rate, the Subcommittee generally endorsed increasing the success rate for the F32 program as an incentive for T32 trainees to apply for their own fellowship grants, and toward achieving the desired balance between trainees and fellows over time.
3. Program staff should analyze the T32 and F32 portfolio of each cluster to assess the strengths and weaknesses of each program, and to increase the quality of career counseling for trainees and fellows.

Clinical Trials Subcommittee

Dr. Ira Shoulson presented the Clinical Trials Subcommittee report in place of the Chair, Dr. Daniel Lowenstein. Dr. Robert Hart, a consultant to NINDS, made a presentation to the Subcommittee on the proposed NINDS-funded Clinical Research Collaboration contract. It will proceed in four steps: 1) information gathering, 2) pilot trials, 3) support for five pilot studies, and 4) full-scale, multi-project operations. The draft Request for Proposal is near completion and, once approved by the Institute Director, will be publicized in mid-December.

Dr. Diane Murphy, program director in the Neurodegeneration cluster, presented a workshop proposal to the Subcommittee entitled, "The Ethics of Genetic Testing in Parkinson's Disease," and discussed the implications for clinical practice. Staff briefed the Subcommittee on three new initiatives: 1) NINDS Neurological Emergency Treatment Trial Network, 2) Clinical Trial Methods in Neurology Training Workshop, and 3) Reducing the Risk of Stroke and Heart Disease Through Improvements in Delivery of Preventive Services.

Infrastructure and Neuroinformatics Subcommittee

Dr. William Mobley reported on the following issues:

1. An announcement will be published that will permit additional applications for Udall Centers. It will lay out the scope of the centers, the research agenda, and the criteria. The Subcommittee recommended that the centers review their programs annually and produce a written report. Institute staff will evaluate the success of the program based on the report. There will be an external review every five years to evaluate the structure and progress toward meeting their goals. Council voted to approve the decision to allow for additional Udall Centers and to approve of the evaluation process.
2. A working group for the SMA project has issued a report describing the goals of the project. Council voted and approved of the Working Group report.
3. The Subcommittee discussed several issues related to the institute's multicomponent mechanisms, including consideration of a separate payline, solicited versus unsolicited applications, encouraging networks rather than centers, and reviewing the related training mechanism. The Subcommittee asked staff to analyze the function of the centers and explore options available. Staff will present their analysis at the next Subcommittee meeting.

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X. Council Review 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 other applications, which needed specific discussion.

Research Training and Career Development Programs

The Council reviewed a total of 92 research career development grant applications; of this total, 65 applications had primary assignment to NINDS, and 45 of them (69.2 percent) were recommended for support in the amount of $6.5 million first-year direct costs. It is anticipated that, of the research career development grant applications competing at this Council, NINDS will be able to pay first-year direct costs of approximately $1.9 million.

Research Grant Awards

The Council reviewed a total of 1,751 research grant applications; of this total, 1,005 applications had primary assignment to NINDS, and 656 of them (65.3 percent) were recommended for support in the amount of $207.3 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 $70.1 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 and selected at each Council meeting. At this meeting, the Council recommended six investigators as Javits awardees.

Small Business Innovation Research and Small Technology Transfer Award Programs

The Council reviewed a total of 184 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 96 applications had primary assignment to NINDS and 53 of them (55.2 percent) were recommended for support in the amount of $8.4 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 $4.6 million.

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XI. Adjournment

The meeting was adjourned at 6:00 p.m. on Thursday, September 18.

We certify that, to the best of our knowledge, the foregoing minutes and attachments are accurate and complete.

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

Story C. Landis, Ph.D.
Chairperson
National Advisory Neurological Disorders
and Stroke Council
Director
National Institute of Neurological Disorders and Stroke

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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