NINDS Advisory Council Meeting Minutes, February 10-11, 2005

1. Call to Order and Opening Remarks
2. Report of the Director, Division of Extramural Research
3. Report of the Director, NINDS
4. Identification of Topics for Future Council Discussion
5. Revisit Currrent Policy Phohibiting a Second Javits Neuroscience Award
6. Council Subcommittee Reports
7. Burden of Illness
8. Concept Approval for Fiscal Year 2006 Proposed Initative
9. New NIH Conflict of Interest Regulations
10. Overview of the Division of Intramural Research
11. Scientific Presentation: "Malignant Gliomas: From Bedside to Bench and Back"
12. Review of the Division of Intramural Research Board of Scientific Counselors' Reports
13. Council Review of Pending Applications
14. Adjournment

DEPARTMENT OF HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NATIONAL INSTITUTES OF HEALTH
NATIONAL ADVISORY NEUROLOGICAL DISORDERS AND STROKE COUNCIL

Summary of Meeting ¹
February 10-11, 2005

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 162nd meeting on February 10-11, 2005, at Building 31, Conference Room 10, Bethesda, Maryland. Dr. Story Landis, 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 10, 2005 --8:30 a.m. to 4:15 p.m.
for the review and discussion of program development, needs, and policy; and
Closed:		February 10, 2005 - 4:15 p.m. to 5:00 p.m. February 11, 2005 - 8:10 a.m. to 11:20 a.m.
for the consideration of individual grant applications.

Council members present were:

Mr. Ronald Bartek
Dr. Bruce Bean
Dr. Alicia Conill
Dr. Raymond Dingledine
Dr. J. Donald Easton
Dr. Francisco Gonzalez-Scarano
Dr. John Loeser
Mr. Jeffrey Martin
Ms. Prisca Chen Marvin
Dr. William Mobley
Ms. Ellyn Phillips
Dr. Patrick Pullicino
Dr. Sally Shaywitz
Dr. Ira Shoulson
Dr. David Van Essen
Mr. Robert Waterman
Dr. Huda Zoghbi

Council Roster (Attachment 1)

Ex Officio Members present:

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

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

Dr. Masahiro Sato, Japan Science and Technology Agency
Dr. Serge Przedborski, Columbia University
Dr. Patrick Mantyh, University of Minnesota
Dr. Bruce Coull, University of Arizona
Mr. Robi Blumenstein, High Q Foundation
Ms. Linda Gough, Constella Group, Inc.
Ms. Christina Clark, ALS Association
Dr. Viviana Simon, Society for Women's Health Research
Ms. Patricia Kobor, American Psychological Association
Ms. Patti Stanco, North American Brain Tumor Coalition
Ms. Hollie Stephenson, NPRCs
Mr. Jeffrey Young, The Blue Sheet
Ms. Beth Roy, Scientific Social Sciences
Ms. Karla Price, Epilepsy Foundation
Mr. Robert Balkam, Restless Leg Syndrome Foundation
Ms. Michelle Rodrigues, SRI
Mr. Mark Scheidler, Independent

NINDS employees present for portions of the meeting included:

Dr. Alan Willard
Ms. Ruth Linn
Dr. John Marler
Dr. Scott Janis
Dr. Barbara Radziszewska
Dr. Frances Yee
Dr. Merrill Mitler
Dr. Claudia Moy
Dr. Robin Conwit
Mr. Michael Loewe
Dr. Melinda Kelley
Dr. Meena Hiremath
Dr. Raul Saavedra
Dr. Katrina Gwinn-Hardy
Ms. Nena Wells
Dr. Story Landis
Dr. Brandy Fureman
Dr. Linda Porter
Ms. Marian Emr
Dr. Dan Tagle
Dr. Tom Jacobs
Dr. Yuan Liu
Dr. Alfred Gordon
Dr. Emmeline Edwards
Dr. Ernie Lyons
Dr. Eugene Oliver
Dr. Diane Murphy
Ms. Quandra Scudder
Dr. Laura Mamounas
Dr. Robert Baughman
Ms. Diane Howden
Dr. Robert Finkelstein
Ms. Stephanie Clipper
Ms. Stephanie Fertig
Dr. Ursula Utz
Dr. Kenneth Fischbeck
Mr. Mark Salo
Ms. Carol Rowan
Ms. Liz Elliott
Dr. Lorenzo Refolo
Ms. Michelle Johnson
Dr. Jonathan Horsford
Dr. John Porter
Ms. Margaret Jacobs
Dr. Andrea Sawczuk
Dr. JoAnn McConnell
Dr. David Jett
Dr. Michael Nunn
Dr. Tom Miller
Dr. Naomi Kleitman
Dr. Audrey Penn
Dr. Yejun He
Dr. Christina Vert
Ms. Maureen Hambrecht
Dr. Daofen Chen
Dr. Paul Scott
Mr. Paul Girolami
Dr. Gabrielle LeBlanc
Mr. Paul Myers
Mr. Andy Baldus
Dr. Karen Bateman
Dr. Richard Crosland
Dr. Randall Stewart
Ms. Cikena Reid
Ms. Lynn Morin
Ms. Joellen Austin
Dr. Robert Zalutsky
Dr. Katie Woodbury-Harris
Dr. Debra Hirtz
Dr. Shanta Rajaram
Ms. Margo Warren
Ms. Rebecca Farkas
Dr. Lauren Murphree
Ms. Stacey Chambers
Dr. Richard Benson
Ms. Deborah McNeill
Ms. Natalie Frazin
Dr. Nora Gardner
Mr. Jeff Domanski
Ms. Lynn Rundhaugen
Ms. Nancy Hart
Ms. Shannon Garnett
Dr. Audrey Kalehua
Mr. Ray Chaudhuri

Other Federal employees present for portions of the meeting included:

Dr. Lynn Hudson, OD
Ms. Shana Stepp, NIBIB
Dr. Arlene Chiu, NIBIB
Dr. William Benzing, CSR
Dr. Robert Riddle, NIDA
Dr. Biao Tian, CSR
Dr. Rossana Berti, CSR
Dr. David Thurman, CDC

1. Call to Order and Opening Remarks

   Dr. Story Landis, Director, NINDS, welcomed Council members, guests, and staff to the 162nd Council meeting. In keeping with the Institute's policy of inviting chairpersons of review committees, Dr. Serge Przedborski (Chair of NSD-B) from Columbia University; Dr. Patrick Mantyh (Chair of NSD-C) from the University of Minnesota; and Dr. Bruce Coull (Chair of NSD-K) from the University of Arizona attended the open session of the Council meeting. Dr. Landis announced that Dr. Robert Finkelstein was selected to be the Director of the Division of Extramural Research (DER). She is grateful to the Chief of the Scientific Review Branch, Dr. Alan Willard, for filling in as Acting Director in the interim period. Dr. Emmeline Edwards will continue as Acting Deputy Director, DER, until the conclusion of the search. Mr. Andrew Baldus, the NINDS Budget Officer for the last 15 years, has accepted the position of Assistant Budget Director for NIH. The acting budget officer position will rotate between the two senior budget analysts until the position is filled. Mr. Jeff Domanski, Section Chief of the Grants Management Branch, has been asked to take the Acting Deputy Executive Officer position; and Dr. Paul Scott has recently been named Chief of the Office of Science Policy and Planning. Dr. Paul Hoffman, the Veteran's Affairs ex officio Council member, has recently relocated to Gainesville, Florida, with the Office of the Assistant CRADO for Neuroscience Research. He will hold the positions of Director of the Translational Neuroscience Research Program as well as Research Professor in the Neuroscience Department of the University of Florida and will work closely with Dennis Steindler, the newly named Director of University of Florida's McKnight Brain Institute. Dr. Hoffman will continue to represent the VA on Council through 2005.

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2. Report of the Director, Division of Extramural Research

   Dr. Finkelstein, Director, Division of Extramural Research, thanked Dr. Alan Willard and Dr. Emmeline Edwards for their Acting positions and their assistance to him in the transition period. Dr. Finkelstein explained that the philosophy he brings to the position is that NINDS is a large and complex institute and that it is critical that NINDS not become complacent. It is important that staff continue to actively, creatively, critically, and flexibly think about what the Institute is doing and stay focused on the mission. There are lives at stake. Dr. Landis has modeled this kind of behavior since the beginning, as has the equally dedicated staff.

   Government in the Sunshine Act and the Federal Advisory Committee Act

   Dr. Finkelstein 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 the Board of Scientific Counselors' Reports and 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 had not been involved in any conflict of interest situations during the review of grant applications. 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, an authorization may be granted by the Institute.

   Confidentiality

   During the closed session, any information that is discussed and the outcome of any recommendation are considered privileged information. They may not be discussed outside of the closed session. If an applicant requests support for his or her application from a Council member, the Council member must respond that he/she is not permitted to discuss the application. Any inquiry should be referred to Dr. Robert Finkelstein as the Council Executive Secretary, who will then refer the questions to the appropriate staff member for response.

   Consideration of Minutes of Previous Council Meeting

   The minutes of the Council meeting of September 9-10, 2004, were considered and accepted as written.

   Consideration of Dates for Future Council Meetings

   The following dates for future Council meetings were reconfirmed:

   May 26-27, 2005		(Thursday and Friday)
   September 15-16, 2005		(Thursday and Friday)
   February 9-10, 2006		(Thursday and Friday)
   May 25-26, 2006		(Thursday and Friday)
   September 14-15, 2006		(Thursday and Friday)
   New Dates
   February 15-16, 2007		(Thursday and Friday)
   May 24-25, 2007		(Thursday and Friday)
   September 20-21, 2007		(Thursday and Friday)

   Other Items

   Expedited Review Process--Dr. Finkelstein reported that the Grants Management Branch has succeeded in expediting 105 applications for award. A total of 202 applications had received Council concurrence for expedited review.

   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 during FY 2004, the status of applications that were identified for High Program Priority for October 2004 Council, as well as an HPP status report for FY 2004. Council had received the Reports Book in a mailing as well as a copy of the report "NIH Roadmap for Medical Research."

   Council Operating Procedures--Once a year, Council is required to endorse the Council Operating Procedures, which includes the Council Delegated Authorities. Council moved to approve the Operating Procedures.

   NINDS Activities to Include Women and Minorities in Clinical Research--Every two years, Council is required to submit a report to NIH verifying that the Institute is in compliance with women and minority inclusion requirements. Dr. Frances Yee, program analyst in the Clinical Trials group, has conducted the analysis and has prepared the report for submission. Dr. Yee gave a report to the Clinical Trials Subcommittee that morning. More on this topic is summarized in the Council Subcommittee Report section of these minutes.

   Materials Produced by the Office of Communications and Public Liaison--Dr. Finkelstein called attention to the materials produced by OCPL for the public on stroke and other disorders, and he encouraged the Council members to review them.

   Staff Action--Dr. Paul Sheehy, formerly with the Neurodegeneration Cluster, has accepted the position of Associate Director for the Division of Extramural Research at NIGMS. New staff with NINDS include Dr. Ray Chaudhuri, program analyst with the Neurogenetics Cluster; Ms. LaShell Gaskins, program specialist with Technology Development; Ms. Michelle Johnson, program analyst with the Neurodegeneration Cluster; Dr. Jonathan Horsford, on detail to the Neurogenetics Cluster; Dr. Audrey Kalehua, program analyst in Repair and Plasticity; Ms. Lynn Rundhaugen, program analyst in Channels, Synapses and Circuits; Dr. John Porter, program director in Channels, Synapses and Circuits; Dr. Lorenzo Refolo, program director in Neurodegeneration; and Mr. Edward Myrbeck, program specialist in the Grants Management Branch.

   Dr. Masahiro Sato, Deputy Manager, Department of Research Project, Japan Science and Technology Agency is attending today's Council meeting as a visitor.

3. Report of the Director, NINDS

   Conflict of Interest at NIH--At Dr. Sally Shaywitz' request, Dr. Michael Gottesman, NIH Deputy Director for Intramural Research, will speak to Council on the new NIH Conflict of Interest policies and their implications for both the Intramural program and on recruitment of senior staff at NIH. Included in these new policies are regulations about stock holdings, which are in addition to consulting restrictions. The press has raised the question of whether similar policies should apply to NIH-funded researchers in the extramural community.

   The President's Budget, FY 2006--The President requested a .7 percent increase in the NINDS budget in FY 2006; however, the budget process has just begun, and the final numbers may differ from the President's initial request.

   Blueprint--For over a year, an NIH process that has involved 15 Institutes/Centers (I/Cs) and representatives from the broader neuroscience community has been underway to plan, synergize, and expedite research across the neuroscience portfolio. The "Blueprint" vision will be publicly presented to the research community in October. The neuroscience-related I/Cs have a history of cooperation. Over the last five years, NIH I/Cs have funded over 60 cooperative programs in neuroscience, including joint predoctoral training programs, a mouse mutagenesis and phenotyping project, and the Gene Expression Nervous System Atlas (GENSAT): the Blueprint I/Cs are seeking ways to build on this foundation. A Blueprint Consortium (http://neuroscienceblueprint.nih.gov) was put together to coordinating planning. The Consortium has met to discuss how to work together to develop the tools and other resources needed to advance research specifically on three linked nervous system processes: Development, Plasticity, and Degeneration. Implementation of the Neuroscience Blueprint has included establishing a collaborative infrastructure, securing a commitment for funds by the interested I/Cs, and an agreement to expand GENSAT to include research on eyes, ears, and sensory data. Looking forward, in FY 2006 the plans are to provide support for core facilities and to support training in neuroimaging, computational neuroscience, and neurobiology of disease. Other government agencies such as the Departments of Energy and Defense will be contacted to learn what they are doing in the same areas, for coordination and planning purposes. Funding for Blueprint activities will increase from a beginning percentage of 0.15 percent of neuroscience budgets in FY 2005 to 0.60 percent in FY 2008 and will likely total $100 million over the first five years. The President's budget includes $12 million for Blueprint projects. The Blueprint is also intended to act as a catalyst for disease-specific planning, sharing best practices, and finding opportunities for co-funding among the I/Cs. It can help provide a framework for priority-setting at NIH and help shape NIH policies, as well. Dr. Landis will continue to report the progress of Blueprint planning to Council. In response to a question from Council, Dr. Landis described the mechanisms for funding Blueprint projects and how a project gets accepted into the Blueprint.

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4. Identification of Topics for Future Council Discussion

   Dr. Finkelstein stated that staff's primary goal is to make optimal use of Council's knowledge and expertise in Institute planning. The Council members confirmed their strong interest in supporting the Director and sharing their expertise. They would like to help address such questions as: what are the problems and where are the opportunities to bring new tools and concepts to neuroscience research, what areas are ripe for investment that would result in substantial progress in understanding the nervous system and that would make a difference in the lives of people with neurological disorders, and what new kinds of collaborations are needed to move research forward. Council members emphasized the importance of three points: 1) team-building between Council and staff, 2) creating a mechanism for dialogue regarding new plans, programs, and problems, and 3) establishing a regular review of initiatives that NINDS has undertaken, for Council input. Dr. Mobley stated that the Council believes that opportunities exist that are not necessarily reflected in surveys of burden of disease, and therefore Council would like to help define the priorities for research. Mechanisms for dialogue and participation were presented as topics of future discussion by Council. An example of an opportunity for Council review is for Council to see the Parkinson's Working Group five-year report, which is due to be released in the summer of 2005. Dr. Landis suggested identifying formal Council liaisons to disease-related groups with which staff are involved, such as the Parkinson's Working Group. Another idea is to invite Council to the Extramural Division's annual planning retreat. Council could also be consulted for topics for workshops and on workshop plans. Council members pointed out that although the Council Operating Procedures state that Council's primary responsibility is to review and approve grant applications, Council can also provide concept clearance for new funding programs and can review Institute's objectives, priorities, and accomplishments. Council members are prepared to assist in all of these areas, and they are keenly interested in receiving more information from the Institute; however, preferably not as it is currently supplied, i.e. all of the information they do receive is sent two weeks before Council. Mr. Waterman summarized his concerns with three points: 1) Council members are eager to be involved in the Institute's plans, 2) they would welcome a discussion of identifying areas for funding within the framework of disease burden versus where research is ripe for progress, and 3) they would like to get together more often and perhaps brainstorm about the major issues and opportunities in neuroscience research. The venue and format for these sessions are important.

   Dr. Finkelstein proposed several possible topics for discussion at future Council meetings that would more closely engage Council in Institute decisions, and he suggested a subset of Council members could work with staff to lay the groundwork for each topic. He presented three main categories (Planning, Prioritizing, and Funding), each of which had several subtopics. There was a discussion about the Institute's range of flexibility for priority-setting and funding parameters. This is a possible area for future Council discussion. One suggestion was to create ad hoc subcommittees to address specific topics and issues, not necessarily disease-focused. Dr. Zoghbi made the following suggestions: 1) Council discuss trans-NIH initiatives, such as the Roadmap, before it becomes too late to have an influence on the initiatives, 2) invite Dr. Francis Collins to speak to Council and discuss areas of mutual concern, and 3) have the Institute conduct an analysis to determine the success of past initiatives. There was additional support for the Planning topic: "How can NINDS determine if a program has been successful or unsuccessful, and who should be involved in making that judgment?" There was support for formulating benchmarks for success, as well. Council would like more communication with the program directors, in order to have the opportunity to share their expertise and ideas about future projects.

   Dr. Finkelstein suggested establishing a working group to define the topic clearly. The majority of Council voted for the topic stated above regarding determining the success of NINDS programs. Dr. Landis summarized Council's interest in analyzing: 1) the mechanism by which a chosen program was generated; 2) the program itself, which could be comprised of several initiatives; and 3) identifying the outcomes and how the Institute could then learn from that process. Drs. Conill, Gonzalez-Scarano, Loeser, Mobley, Shaywitz, Shoulson, Zoghbi and Mr. Waterman volunteered to participate in the working group.

   Dr. Landis will ask the Training Subcommittee to think about recommendations for the Institute to recruit and train new neuroscience investigators.

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5. Revisit Current Policy Prohibiting a Second Javits Neuroscience Award

   Dr. Landis asked Council to make two changes in the Javits Awards policy. Javits awards are conditional, seven-year awards given to distinguished investigators with a record of substantial contributions on the cutting edge. The investigators are expected to be highly productive. The applications can be competitive renewals or new applications. The program began at NINDS in 1983 and is similar to other I/Cs' Merit awards, except those are ten-year awards and these are seven. NINDS has funded 476 Javits awards to date, and the numbers in any given year have ranged from 47 in the first year to 3 in one year. In 1995, Council recommended that there be the set number of 12 Javits awards per year, and that a PI could only ever have one Javits. Dr. Landis asked Council to consider making two changes: 1. Increase the maximum number of Javits awards possible in any one year from 12 to 15. The rationale for this request is twofold: there has been a substantial increase in high-quality R01 applications, and Council has actually funded more than 12 in five of the last six fiscal years. A special vote has been needed each year to permit the Institute to go over the limit. Increasing the maximum number of awards will eliminate the need for the annual, special voting requirement. 2. Allow an investigator to receive more than one Javits award. It is possible that a small subset of Javits awardees could be doing such outstanding research that they could merit a second Javits award. The criteria for the second award would be more rigorous than the first, and the awards could not be given in consecutive years.

   Council voted to leave to the Director's discretion the number of Javits Awards recommended for funding and to permit a second Javits award to a principal investigator.

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6. Council Subcommittee Reports

   Training and Career Development Subcommittee

   Dr. Bruce Bean summarized four main issues:

   1. A progress report of the NINDS/NIMH/NIDA task force by Nora Gardner of the NINDS Office of Science Policy and Planning that evaluated the effectiveness of particular training programs. The final report will be compiled at the end of April and will be a topic of discussion by the full Council at a future meeting.

   2. Margaret Jacobs and Lynn Rundhaugen gave a report on the NINDS T32 training program. The analysis focused on the distribution of the grants among institutions and the distribution of funded slots between programs funding broad areas of research versus sharply-focused areas. The subcommittee agreed that the distribution was approximately equal and did not need addressing.

   3. Consideration of K24 Awards. There have been very few K24 awards made by NINDS. Dr. Willard and Dr. Saavedra conducted an analysis and found that there was not a problem with the review. How can the Institute encourage more candidates to apply? Some suggestions made by the subcommittee were to advertise the program more extensively at scientific meetings and for the Institute to notify K23 awardees of the program as they approach the end of their grants. In response to a question about changing the associate professor requirement of applicants, Dr. Bean explained that the requirements come from NIH and so the Subcommittee would like to try advertising the program more aggressively before we approach NIH to change the associate professor requirement.

   4. How to provide more support to new investigators? One suggestion was to shorten the review cycle for K awards, possibly by moving the review date to a month earlier than done currently. Council would include these awards in their delegated authority for expedited approval. Council voted to include K awards to the expedited review process.

   5. Another suggestion for helping young investigators was to extend the NRSA F32 program to individuals finishing or who have recently finished a residency in neurology, child neurology, or neurosurgery. The new F32 would be issued as a PAR, and the review would be conducted by NINDS rather than CSR. The Training Subcommittee will determine criteria for measuring success of the program. Council voted to expanding the F32 and having NINDS review the applications on an experimental basis.

   Three new issues were discussed:

   1. Dr. Hoffman raised the question of whether the Institute has an adequate mechanism for supporting mentoring besides the K24 program. The mechanism would bring researchers from various areas to focus on one disease, both clinicians and basic scientists, from different perspectives.

   2. Dr. Zoghbi suggested collecting data regarding the time the K awardee applies for an R01. Some grantees may think that because the K award pays their salaries, they can't apply for an R01 in their third year. It would be helpful to analyze who is successful, who is not, and when they applied for the R01. Dr. Landis said the Institute has some of these data, but they need to be updated. The Institute will make it a priority.

   3. In response to the comment about the length of time some IRBs take to issue their approval, Dr. Landis noted that part of the NIH Roadmap Re-engineering the Clinical Enterprise includes working toward the goal of reducing time spent by reporting structures and on other requirements. She will update Council on this Roadmap project as part of the Director's report at the next Council meeting.

   Clinical Trials Subcommittee

   Dr. Ira Shoulson summarized the Subcommittee meeting. He requested that the Clinical Trials Subcommittee meet in the morning before the full Council meeting and if possible avoid having the subcommittees meet concurrently so that Council members interested in attending both of the meetings can do so. Dr. Landis will adjust the next subcommittee schedule as requested.

   Dr. John Marler and Dr. Scott Janis reviewed the activities of the Clinical Trials Working Group, the clinical research collaboration project, and efforts to develop cognitive and functional scales common to all NINDS funded clinical trials. Three recently-held workshops were reviewed: 1) "Measuring Cognitive Functioning Outcomes in Neurology Research," planned by Dr. Claudia Moy, 2) "Towards the Development of Pediatric Stroke Trials," planned by Dr. Deborah Hirtz, and 3) "Clinical Trials in Spinal Muscular Atrophy," planned by Dr. Deborah Hirtz. Some, such as the Neuroimaging Workshop, have resulted in publications. The workshops present opportunities for collaboration among researchers interested in a particular disease and he hopes staff will continue to encourage those collaborations. At the last Clinical Trials Subcommittee meeting the group began a discussion about the length of time it takes for clinical trials to get started focusing in particular on issues of recruitment and enrollment. In order to help address potential problems it was recommended that NINDS require PI's to submit data indicating the feasibility of recruitment, especially of women and minorities. For example, the PI's could be asked to conduct a chart review to be able to support the feasibility of their project. Reviewers should look at the track record of the PI and the other groups involved. Other rate-limiting factors that should be discussed in the future are delays that commonly result from the supply of the drug for the trial and in forming the DSMBs.

   The Clinical Trials Subcommittee reviewed the NINDS Plan to Recruit Women and Minorities in Clinical Research, prepared by Dr. Frances Yee. There was an NIH mandate to prepare this report every two years. There is a slight decrease in the recruitment of minorities from 2003 to 2004 but this likely is a statistical anomaly. The Subcommittee recommended approval of the report but made note of their concern in the drop in minority recruitment. Council voted to approve the Subcommittee report.

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7. Burden of Illness

   Dr. Deborah Hirtz, Program Director, Clinical Trials Cluster, reviewed a number of ways burden of illness (BOI) can be measured and what measures may be important to NINDS. BOI is one factor used to help the Institute with priority-setting. In projecting BOI, the Institute can consider how research will change the BOI and can compare projections of future burden with or without a change in investment. One component of determining BOI is measurement of incidence and prevalence. A study by Gross et al was published in the New England Journal of Medicine in 1999 that compared 29 estimates of NIH 1996 disease-specific funding to data on 6 measures: total mortality, years of life lost, number of hospital days, incidence, prevalence, and disability adjusted life years. Dr. Hirtz presented data on the five neurological conditions studied. The analysis concluded that there was no relationship between NIH funding and incidence, prevalence or number of hospital days of the patients; the number of deaths and years of life lost were somewhat associated; and that the disability-adjusted life-years (DALYs) was the data point most predictive of funding. Disability-adjusted life years combines several dimensions of burden into a single summary measure and is the sum of life-years lost due to premature death plus life-year equivalents lost to disability. The limits to DALYs are that many of the parameters used in calculating DALYs have substantial uncertainties; there are no data for many conditions; the disability scores are fixed, not a range; weighting for age has been variable; and there are inconsistencies in accounting for co-morbidity. Consequently, there are incomplete and inadequate data for most conditions, and comparisons of disease-specific burden are not straight-forward.

   Dr. Hirtz, Dr. Katrina Gwinn-Hardy, and Dr. Robert Zalutsky, in collaboration with Dr. David Thurman of the CDC, are conducting a study to determine incidence and prevalence of twelve of the most common neurological disorders. They are identifying and classifying the relevant literature according to a scheme that indicates the likelihood of accuracy and generalizability of the data,, Several examples were presented. To be meaningful and accurate, incidence and prevalence data need to be carefully scrutinized.

   In subsequent Council discussion it was clear that BOI estimates depend on a number of variables which are inconsistently measured; comparison of BOI numbers across diseases is inaccurate; and BOI may be one of many considerations in setting NINDS priorities. Staff routinely consider BOI when making decisions, but some BOI data are better than others for specific diseases. Council made several recommendations regarding the value and use of BOI data, including: taking what incidence and prevalence data are available into consideration, staff should think about what other BOI and other measures should be used to set priorities; suggesting dividing diseases by classes and using the data from those groupings; and that NINDS take the lead in surveying non-NIH agencies for other BOI data. They noted that prevalence, incidence, and definitions of diseases are constantly changing, so the data are only good for a limited amount of time. The Institute needs to be mindful that BOI is a sensitive issue to voluntaries, and so it needs to be calculated with care; addressing BOI is an opportunity to partner with other I/Cs. BOI needs to be balanced with opportunity when setting priorities.

   It was agreed that it would be prohibitive to determine BOI for all 600 disorders in the NINDS portfolio. Dr. Landis informed Council that Dr. Zerhouni has sent a proposal to the Office of Strategic Planning Steering Committee which included a study of BOI and priority-setting. It proposes involving several I/Cs for the neurological disorders. Dr. Zoghbi suggested it may be preferable to divide diseases by classes and use the data from those groupings. NINDS can also take the lead in surveying non-NIH agencies for other BOI data.

   Dr. David Thurman from the Centers for Disease Control and Prevention said that data are being collected by CDC's National Center for Health Statistics, so they can be mined for BOI information. He suggested surveying data from a variety of sources to find gaps in research.

   Dr. Landis summarized the discussion by stating the BOI data need to be considered with caution, that they are most useful when making comparisons within a disease, and that diseases should be grouped in order to have the largest possible impact. BOI is already being integrated into decision-making. NINDS may consider how to analyze the relationship between disease-specific research funding and DALYs. Dr. Finkelstein and Dr. Zalutsky suggested using the data to discover outlying areas with regard to relative neglect or over-funding. Dr. Hirtz's report can be looked at again when Council discusses priority-setting.

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8. Concept Approval for Fiscal Year 2006 Proposed Initiative

   Dr. Finkelstein reviewed the process staff undertakes to develop initiative proposals, which includes workshops; consultation with outside researchers, voluntaries, and other sources; and their own knowledge and creativity. The Institute then conducts a retreat twice a year for staff to present the proposals for the following fiscal year. The NINDS Extramural Science Committee then meets to discuss and rank the proposals. Recently, the Institute has asked Council to provide the concept clearance for the proposals, as a way to increase Council participation in the Institute's decision-making. Those approved to go forward for Council concurrence were:

   1. Cell Biology of Parkinson's Disease
   2. Emergency Neurological Network
   3. Stroke Preclinical Trials Consortia

   Council members expressed support for the concepts brought to them for concurrence but would like more in-depth information about them. Dr. Landis suggested that subgroups of Council members can be created to follow the development of each initiative concept. Likewise, relevant Council members can be involved in the development of NINDS workshops. Dr. Shoulson suggested that the Stroke Preclinical Trials RFA be more precise in terms of discussing the pitfalls in translation and what key elements need to be identified and incorporated into clinical trials. Council voted to concur with the initiative concepts as presented.

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9. New NIH Conflict of Interest Regulations

   Dr. Michael Gottesman, Deputy Director for Intramural Research, NIH, reviewed the general principles behind the Conflict of Interest regulations. Federal employees:

   1. Cannot "serve two masters." They cannot be paid by the federal government and a biotechnology or pharmaceutical company.

   2. Cannot get paid to do the same work in two different places.

   3. Have the right to free speech. That means they are free to engage in paid, outside activities as long as it is on their own time, they are not using government property, and it is not the same work for which they are receiving a government salary.

   The principles have been applied to three main areas; the first of which is related to consulting:

   1. Federal employees cannot receive payment from industries that can be affected by NIH activities. ("Affected industries" has been defined by NIH).

   2. They cannot be paid for work they do with an NIH grantee.

   3. They can be paid by a professional society for work that is not the same as their official duties.

   In many cases, in situations where employees cannot receive outside compensation, employees can perform the functions as part of their official duties.

   The second part of the Conflict of Interest is the issue of awards. NIH staff were allowed to receive honoraria that came with awards given by outside institutions. With the new regulations, senior staff can receive only very limited, highest-level awards. A list of acceptable awards is being prepared for less senior staff, which should be available soon.

   The third category of regulations is related to prohibited holdings. Previously, staff could own stock in industries outside of their research area. However, due to the increased inter-connection between companies and the general concern about NIH staff owning stock in companies they could potentially affect, ownership in those sectors is now prohibited. The new regulations were issued in what is called the "Interim Final Regulations." These remain in force unless changed. The deadline for divesting in prohibited stocks is 150 days from now. The regulations apply to government employees and their spouses (with exceptions) only, and not extramural grantees. In response to a question about the impact of the new regulations on NIH's mission, Dr. Gottesman explained that an evaluation of the impact on current staff and staff interested in working at NIH is part of the new regulations and will be undertaken very soon. Clinical practice by Federal employees is still allowed, but there may be limits imposed on the number of hours.

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10. Overview of the Division of Intramural Research

    Dr. Landis reported that the Intramural program is comprised of a lively and committed group of scientists, physician-scientists, and physicians who are investigating a number of important areas over a very broad range of science, from the structure and function of ion channels to clinical trials on enzyme replacement therapy. Intramural scientists have produced several scientific advances recently, among them were: 1) the use of a fly model for Down Syndrome, which led the investigators to suggest that disregulation of calcineurin plays an important role in causing Down Syndrome, 2) imaging of stroke patients, describing a profile of imaging changes that may reflect early changes in the blood-brain barrier and that people with this profile were more likely to have hemorrhages and do poorly after their stroke, and 3) a small, Phase II clinical trial run by the Neuroimmunology Branch which studied the ability of daclizamab to improve clinical outcomes in multiple sclerosis patients. These patients were getting beta interferon but had not seen significant benefits. There is some interest in going on to a Phase III clinical trial.

    In the search for a new scientific director, six candidates that were highly recommended by the Search Committee have been interviewed. There were detailed discussions with two of them, but neither was brought to closure. Two new candidates have applied recently, and negotiations will begin with one of them soon.

    With regard to the Blue Ribbon Panel to review NIH Intramural programs, each institute has been reviewed except NINDS. As soon as a Scientific Director is in place, the Blue Ribbon Panel will review NINDS's Intramural program. Dr. Landis invited one or two Council members to serve as liaisons to the Panel. In light of tightening budgets, there has been increased scrutiny of the Intramural program, and NINDS has recently answered questions about the special mission of NIH's Intramural program, whether the laboratories should be mission-specific or aimed at outstanding science more generally, etc. That information will be made available to the Blue Ribbon Panel.

    New employees in the Intramural program include: 1) Dr. Alfonso Silva, whose area is developing technology for neuroimaging, will be working on using high-field MRI to study primate brain, 2) Dr. John Isaac, who joins the synaptic function group, and 3) Dr. Edward Giniger, whose research focus is to use the fly as the model to look at molecules that guide axon growth. Departing staff include: 1) Dr. Robert Wild, who went to the Cleveland Clinic and 2) Drs. Maria Spatz and Thomas Chase who have retired.

    Dr. Landis reported that the move to the Porter Neuroscience Building is nearly complete. All reports indicate that the open laboratory structure, and the decision to use questions and research themes to group investigators has proven to be a significant step forward in creating an integrated neuroscience committee. No funding is available yet for the second part of the building, but staff remain hopeful that it will become available in the near future.

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11. Scientific Presentation: "Malignant Gliomas: From Bedside to Bench and Back"

    Dr. John Park, Head, Surgical and Molecular Neuro-Oncology Unit, Surgical Neurology Branch, Division of Intramural Research, NINDS, reported that malignant gliomas are the most common primary brain tumors. They are generally associated with a poor prognosis because of the ineffectiveness of surgery, radiation and chemotherapy in controlling their growth and spread. The median survival of patients with the predominant glioma subtype is less than one year. In contrast, patients with malignant gliomas containing allelic 1p chromosomal losses (1p+/-) are frequently responsive to chemotherapy and have median survivals exceeding ten years. He therefore hypothesized that the partial or complete loss of a chemoresistance mediating protein encoded for on 1p contributes to the chemosensitivity of 1p+/- tumors. Using differential proteomics, he identified stathmin as a 1p36.11 encoded protein that is under expressed in 1p+/- malignant glioma cell lines relative to 1p intact (1p+/+) cell lines. Analysis of clinical brain tumor specimens demonstrates decreased expression of stathmin in 1p+/- tumors relative to 1p+/+ tumors as well. To elucidate a functional role for stathmin in brain tumor chemoresistance, he used RNA interference technology to show that malignant glioma cells with decreased stathmin expression have increased sensitivity to CCNU, a DNA alkylating agent. These results provide a possible underlying molecular mechanism for an empirical clinical observation and suggest that selected conventional chemotherapies may be more efficacious if combined with the inhibition of stathmin.

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12. Review of the Division of Intramural Research Board of Scientific Counselors' Reports

    In closed session, Dr. Landis presented the findings and recommendations of the Board of Scientific Counselors based on their review of specific DIR laboratories/units during 2004. The Council discussed the reports of the Board and accepted them.

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13. 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 151 research career development and institutional training grant applications; of this total, 96 applications had primary assignment to NINDS, and 72 of them (75.0 percent) were recommended for support in the amount of $13.0 million first-year direct costs. It is anticipated that, of the research career development and institutional training grant applications competing at this Council, NINDS will be able to pay first-year direct costs of approximately $6.5 million.

    Research Grant Awards

    The Council reviewed a total of 1,992 research grant applications; of this total, 1,146 applications had primary assignment to NINDS, and 743 of them (64.8 percent) were recommended for support in the amount of $217.1 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 $66.8 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 four investigators as Javits awardees.

    Small Business Innovation Research and Small Technology Transfer Award Programs

    The Council reviewed a total of 210 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 118 applications had primary assignment to NINDS and 73 of them (61.9 percent) were recommended for support in the amount of $13.1 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 $5.5 million.

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14. Adjournment

    The meeting was adjourned at 11:20 a.m. on Friday, February 11.

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

Robert Finkelstein, Ph.D.
Executive Secretary
National Advisory Neurological Disorders and Stroke Council
Director, Division of 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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¹ For the record, it is noted that members absent themselves from the meeting when the Council is discussing applications (a) from their respective institutions or (b) in which a real or apparent conflict of interest might occur.

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