Summary of Meeting1
September 18-19, 2008
The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 173rd meeting on September 18-19, 2008, 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: September 18, 2008: 10:35 a.m. to 5:15 p.m.
for the review and discussion of program development, needs, and policy; and
Closed: September 19, 2008: 8:10 a.m. to 9:55 a.m.
for the consideration of individual grant applications.
Council members present were:
Ms. Susan Axelrod
Mr. Robi Blumenstein
Dr. Emery Brown
Dr. Lucie Bruijn
Dr. Ralph Dacey
Dr. Robert Friedlander
Ms. Katherine Hood
Dr. Edgar Kenton
Dr. Helen Mayberg
Dr. Laura Ment
Dr. Luis Parada
Ms. Cindy Parseghian
Dr. Timothy Pedley
Dr. John Povlishock
Dr. Louis Ptacek
Dr. Caroline Tanner
Dr. Gary Westbrook
Dr. Vicky Holets Whittemore
Council Roster (Attachment 1)
Ex Officio Members present:
Dr. Robert Ruff, Department of Veterans Affairs
Dr. Geoffrey Ling, Department of Defense
Members of the public present for portions of the open meeting included:
Dr. Ellen Hess, Emory University
Greg Strylewicz, Social and Scientific Systems, Inc.
Mr. Ronald Bartek, Friedreich's Ataxia Research Alliance
Branka Sekis, Social and Scientific Systems, Inc.
Angela Ostrow, Epilepsy Foundation
NINDS employees present for portions of the meeting include:
Dr. Alan Willard
Ms. Margaret Jacobs
Other Federal employees present for portions of the meeting included:
Dr. George McKie, CSR
Dr. Pat Manos, CSR
Dr. Alexander Yakovlev, CSR
Dr. Rene Etcheberrigaray, CSR
Dr. Peter Guthrie, CSR
Dr. Boris Sokolov, CSR
Dr. Jay Joshi, CSR
Dr. Seetha Bhagavan, CSR
Dr. Suzan Nadi, CSR
Dr. Jerry Taylor, CSR
Mr. Kenneth Frushour, NEI
I. Call to Order and Opening Remarks
Dr. Landis welcomed Council members, visitors, and staff to the 173rd meeting of the National Advisory Neurological Disorders and Stroke Council meeting. Dr. Landis introduced the following four new Council members:
Dr. Emery Brown is Professor of Health Sciences and Technology and a Professor of Computational Neuroscience at Massachusetts Institute of Technology; and the Massachusetts General Hospital Professor of Anaesthesia at Harvard Medical School.
Dr. Robert Friedlander is Vice Chairman of the Department of Neurosurgery at Brigham and Women's Hospital in Boston. He is also an Associate Professor in Surgery (Neurosurgery) at Harvard Medical School, Brigham and Women's Hospital.
Ms. Katherine Hood is Chief Executive Officer of The Michael J. Fox Foundation for Parkinson's Research Foundation.
Dr. Louis Ptacek is Director of the Division of Neurogenetics at the University of California, San Francisco School of Medicine, where he holds the John C. Coleman Distinguished Professorship in Neurodegenerative Diseases. He is also an investigator with the Howard Hughes Medical Institute.
Council members will be contacted in the near future for suggestions for Council nominees to replace the four members rotating off of Council next July.
In keeping with the Institute's policy of inviting chairs of CSR review committees, Dr. Landis introduced Dr. Ellen Hess, Chair of the NINDS NSD-C Committee, who is attending the open session of the Council meeting. Dr. Hess recently moved from Johns Hopkins to the Department of Pharmacology and Neurology, Emory University.
Dr. Landis introduced new OD staff: Mr. Ken Frushour (new budget officer to start on September 28), Dr. Susan Marino, a Program Analyst working with Drs. Landis and Koroshetz, Dr. Giovanni Guerrera, Health Science Policy Analyst, Office of Science Policy and Planning, and Dr. Lisa Gough, a 2008 AAAS Science and Technology Policy Fellow, who has started a rotation with the NINDS Office of Communications and Public Liaison.
II. Report of the Associate Director for Extramural Research, NINDS
Dr. Robert Finkelstein, Associate Director for Extramural Research, NINDS, informed the Council that they would be in open session today and in closed session to the public tomorrow when individual grants are discussed.
Approval of Council Minutes - Dr. Finkelstein requested, and the Council voted approval, for the May 29-30, 2008, Council meeting minutes.
The following future Council meeting dates were confirmed:
February 5-6, 2009 (Thursday and Friday)
May 28-29, 2009 (Thursday and Friday)
September 17-18, 2009 (Thursday and Friday)
February 4-5, 2010 (Thursday and Friday)
May 27-28, 2010 (Thursday and Friday)
September 23-24, 2010 (Thursday and Friday)-rescheduled from September 16-17
Expedited Review Process-A subset of Council members, prior to the meeting, approve applications within the payline for which there are no unresolved issues. For this round, there were 115 applications eligible to be expedited for payment, and 46 awards have been issued.
Loan Repayment Program -The Program began seven years ago. The purpose is to make it easier for well-qualified clinicians to go into biomedical or behavioral research. There were 114 applications for clinical and pediatric research loan repayment. The budget of $2.6 million allowed NINDS to make 58 awards; 40 were for clinical research and 18 for pediatric research. Fifty one were to M.D. or M.D./Ph.D.s, five were to Ph.D.s., and two were to DOs.
DER Staff Updates- Dr. Finkelstein introduced the following new DER staff: Dr. Timothy LaVaute, Program Analyst, in the Neural Environment Cluster, and Louise Ritz, Clinical Research Project Manager, in the Clinical Trials Cluster. Dr. Finkelstein also reported on the upcoming departure of Cikena Reid who will be taking a position with the National Institute on Drug Abuse.
III. Report of the Director, NINDS
Transition to a New Administration - With the general presidential election coming on November 4, 2008, and inauguration of the President-elect on January 20, 2008, changes in leadership are also likely at NIH. Because the Directors of NIH and NCI are presidential appointees, in principle, they will leave their offices before the President leaves office. Other Institute and Center directors will likely remain in place.
NINDS Strategic Planning Effort - This is an Institute-wide review intended to help identify the strengths and weaknesses of our current activities and to suggest new strategies to facilitate the Institute's mission to reduce the burden of neurological diseases. Four planning modules, each consisting of an external advisory panel and an internal NINDS working group, are in the process of reviewing the Institute's activities and priorities in four areas of neuroscience research:
The review is iterative, with the external groups formulating questions, and the internal groups providing data relevant to the questions. This process will lead to a set of recommendations that will help guide NINDS' investment in basic and clinical neuroscience research over the next ten years. All four modules are on track to complete their reports by the next Council meeting in February 2009. The Institute has identified the need for a fifth planning module to review NINDS' diversity efforts, from enhancing diversity in the workforce to reducing racial and gender disparities in public health. The internal and external working groups for this module will be assembled by the beginning of the calendar year.
Comparative Effectiveness Health Research - Motivated by rising health care costs, lawmakers are considering legislation that would establish a non-profit institute to support research comparing the effectiveness of various healthcare interventions. Senators Max Baucas (D., Montana.) and Kent Conrad (D., North Dakota.) introduced the Comparative Effectiveness Health Research Act (S. 3408) in the Senate on July 31, 2008, and it has been referred to the Senate Finance Committee. The Act defines comparative effectiveness research (CER) as "research evaluating and comparing the implications and outcomes of two or more health care strategies to address a particular medical condition." If established, the CER institute would support new research and systematic reviews of previous research through contracts with federal agencies and private entities. NIH has a history of supporting CER studies, including but not limited to:
NIH Roadmap Update -The NIH established the Roadmap in 2004 to support cross-cutting research that is beyond the scope and resources of individual Institutes and Centers. The Roadmap is now supported by a line-item appropriation, known as the NIH Common Fund, mandated by Congress through the 2006 NIH Reform Act. Grants awarded through Roadmap are supported by equal contributions from the Common Fund and from a lead Institute or Center assigned to the grant.
Through the summer and fall of 2006, NIH solicited ideas for new "Roadmap 1.5" initiatives, and two of these ideas were approved as five-year programs. The Human Microbiome Project will characterize the bacteria and other microbes that live within the healthy human body, and examine whether changes in this microbiome are related to disease. At present, there are no plans to support the analysis of microbes in cerebrospinal fluid, so this project may not have immediate relevance to neurological diseases. The Epigenome Project will enhance the understanding of how health and disease are influenced by epigenetics (changes in gene expression and function without a corresponding alteration in DNA sequence). An active RFA "Epigenomics of Human Health and Disease" calls for projects that will correlate epigenetic changes in human cells (or under limited circumstances, cells from non-human mammals) with disease, aging, or environmental exposures. Applications may have relevance to neurological disease, and may come under review at the next Council meeting in February.
Topics for Roadmap 2.0 projects were submitted and reviewed in 2008. Based on feedback during the "review of peer review," the funds available for new Roadmap Projects will be used for transformative research. Launched this year, the NIH Transformative R01 Program is designed to support high-risk research with the potential to create or overturn scientific paradigms. While the program is open to all scientific areas relevant to NIH, areas of particular need have been identified, and many of those have special relevance to the NINDS mission.
To facilitate the identification of high-risk projects, the program will pilot novel peer review methods. Differences from the traditional R01 grant include a shorter application, a review process that emphasizes innovation and potential impact over methodology, and a second level of review by the NIH Council of Councils. A funding opportunity, RFA RM08-029, is open through January 29, 2009, and will be reissued annually for five years. Total funding available for fiscal year 2009 is $25 million.
Protecting Early-Stage Investigators - Between 1980 and 2006, the mean age of NIH-funded investigators increased dramatically. By 2020, it is estimated that NIH-funded investigators over age 70 will outnumber those under age 45. In 2007, NIH set a goal of supporting a minimum of 1500 new (or first-time) investigators - defined as a principal investigator who has not previously competed successfully for a significant NIH independent research award. However, an analysis of 2007 award data later showed that about half of new investigators (as defined above) were over age 42, and that many had previously received major funding from other government agencies in the U.S. and abroad. A revised policy therefore focuses on increasing support for early-stage investigators (ESIs) - defined as individuals who receive an R01, had not previously held a significant NIH grant, and who are within ten years of completing a terminal degree or residency training. It is estimated that 55 percent of new investigators are presently ESIs. Many Institutes and Centers now set a more generous payline for ESIs.
The challenge is to implement changes to the peer review process that correct the tendency for reviewers to penalize ESIs for lack of experience and reputation. Reviewers may also be scoring new investigators and ESIs lower than established investigators because they recognize that the funding process increases the former group's likelihood of success. There are data to support that idea: In the past decade, the odds that a new investigator will receive a good percentile score relative to an established investigator have worsened. Following the recommendations of the NIH Peer Review Self-Study, which took place June 2007 to June 2008, NIH will cluster ESI applications for review, so that they are discussed and scored separately from established investigator applications. NIH leadership is also considering the possibility that an equal percentage of ESI applications and established investigator applications should be scored, and that an equal percentage of applications from the two groups should be funded.
Finally, data show that since 1998, new investigator applications for research project grants (RPGs) other than R01-equivalents have increased, but there has not been a corresponding increase in non-R01 awards to new investigators. In particular, there has been an increase in applications for R21s (Exploratory/Developmental Research Grants) - which are limited to $275,000 over a two-year period - perhaps because there is a misconception that having an R21 improves the likelihood of receiving an R01. NINDS could take a number of actions to discourage R21 applications from new investigators, such as making new investigators ineligible for the R21 or eliminating the unsolicited R21 altogether (which some Institutes have done). Council members commented that the latter option would deny all investigators a mechanism to pursue high-risk projects, and that the best solution is to educate investigators that the R01, not the R21, is an ideal first grant.
IV. Clinical and Translational Science Awards (CTSAs): Building Connections
Dr. Landis and Dr. Barbara Alving, Director, NCRR, said that the neuroscience community will benefit from engagement by NINDS with the CTSA program (www.ctsaweb.org). This program, funded by NCRR, creates a definable home for clinical and translational science at 38 academic institutions across the country. Major goals include speeding the translation of basic discoveries into clinical applications, engaging communities in clinical research, and training the next generation of clinical and translational researchers. Dr. Alving reported that 24 CTSA sites were established in 2006-2007, and 14 were established in 2008. The plan is to fund 60 CTSA sites by 2012. The CTSA philosophy emphasizes team science and partnerships that link academic institutions to federal, state and local governments, and to industry, she said. CTSAs have enabled the recipient institutions to forge collaborations between their medical schools and business schools, in order to develop business plans, training programs, cost analyses and public-private partnerships, and to facilitate intellectual property protection and commercialization of new inventions. Dr. Alving noted that within the 2007 CTSA cohort, there are 63 NINDS grants represented and 4 CTSA sites that offer neurology training opportunities.
Dr. Jeffrey Rothstein, Professor, Department of Neurology, Johns Hopkins University, described a CTSA-funded program at Hopkins - the Institute for Clinical and Translational Research (ICTR). Under the direction of Dr. Daniel Ford, Vice Dean for Clinical Investigation at Hopkins, ICTR began offering milestone-driven, translational research grants to Hopkins faculty earlier this year. Dr. Rothstein is Co-Director of the Neuro-Translational Program at the Hopkins Brain Science Institute. This program facilitates drug development for neurological diseases, and will become coupled to the CTSA program, he said.
Dr. Walter Koroshetz, Deputy Director, NINDS, described ongoing efforts and possibilities for leveraging the CTSA network to enhance translational and clinical neuroscience research and training. Dr. Koroshetz serves on a CTSA operations committee that gives NIH Institutes and Centers a voice within the CTSA network. He is spearheading an effort to establish a neuroscience point person at every CTSA site, and to educate the clinical neuroscience community about CTSAs. As an example, members suggested that the CTSA neuro network might provide the backbone for a rare disease consortium to improve access to patients and patient tissue samples. In addition, the data management systems being developed in the CTSA consortium could facilitate sharing of clinical research data. It was noted that NINDS might consider creating funding opportunities to encourage CTSA consortia to develop neuroscience projects that leverage NCRR resources.
V. FY 2009 Budget Strategy
Dr. Finkelstein reported that the estimated total spending on neuroscience research by NIH in FY 2008 was $4.8 billion. NINDS supported the largest portion of that research, about one-third. NINDS' budget was $1.552 billion, and the payline for unsolicited RPGs was the 10th percentile.
We are now engaged in the FY 2009 budget process. The President has proposed a 0.2 percent decrease in the NIH budget, totaling $29.457 billion, which would result in a budget of $1.546 billion for NINDS. Congress has not announced its FY 2009 budget plan, which means that NIH will likely operate on continuing resolution maintaining FY 2008 budget levels. Despite the flat or slightly decreased budget, NINDS may be able to raise the payline to the 12th percentile, due to a reduction in the commitment base.
Dr. Finkelstein also reported on continuing efforts to protect new and early-stage investigators. Beginning in FY 2007, NIH set a goal of supporting a minimum of 1500 new investigators, and each Institute was given a target number of new investigators to fund, based on the average number of new investigators funded over the last five years. NINDS' goal was 128. This year, 40 new investigators were funded within the payline and an additional 79 were funded up to the 25th percentile. Thirty-four NINDS investigators received NIH Director Bridge Awards, which are available to investigators who are near the payline and who have limited additional support.
VI. Modifying the Payline for A0 Applications
One priority that has emerged from the NIH Peer Review Self-Study is to fund the best science earlier and reduce the need for first and second revised applications (A1s and A2s). Dr. Shai Silberberg, Program Director, Channels, Synapses, and Circuits Cluster, presented a possible interim measure to solve this issue. In 1998, 60 percent of R01-equivalent grants were awarded based on an initial application (A0). In 2007, less than 30 percent of awards went to A0s and there was a complementary increase in awards to A2s, suggesting that meritorious applicants are "waiting in line" to receive their grants. Dr. Silberberg presented an analysis showing that an application that scores within 5 percent of the payline as an A0 has an 88 percent probability of scoring inside the payline as an A1. Moving out to 6 percent of the payline, that probability dropped to 79 percent. (This analysis was based on R01 applications to NINDS in FY 2007-2008, and did not include new investigators.) Therefore, a possible interim measure is to fund A0s up to the 15th percentile this Council round, which would mean funding 11 more grants. Council members commented that while this strategy would fund the nine or ten A0s likely to score within the payline on their next submission, one or two A0s might be getting a free ride. Dr. Landis reassured the Council that she and the appropriate program directors had reviewed the 11 grants, and found them all meritorious.
VII. NIH Plans for Implementation of Recommended Actions to Enhance Peer Review
Dr. Alan Willard, Chief, Scientific Review Branch, described the changes emerging from the NIH Peer Review Self-Study and the phased implementation of those changes, which began this month. A Peer Review Oversight Committee, of which Dr. Landis is a member, has established four working groups charged with carrying out four tasks: (1) Engage the Best Reviewers, (2) Improve the Quality and Transparency of Review, (3) Ensure Balanced and Fair Reviews Across Scientific Fields and Career Stages, and (4) Continuous Review of Peer Review.
Engaging the Best Reviewers
In 2009, new reviewers will be given additional flexibility regarding their tour of duty and other efforts will be undertaken to improve retention of standing review members. A toolkit, incorporating best practices for recruiting reviewers, will be made available to all Institutes and Centers in 2009. In spring 2009, training will be available to reviewers and Scientific Review Officers related to the changes in peer review. Pilots will be conducted in 2009 on the feasibility of virtual review meetings to provide reviewers greater flexibility and alternatives to in-person meetings.
Improving the Quality and Transparency of Review
In May 2009, the current 41-point scale for scoring applications will be replaced with a 7-point integer scale, designed to fit the way people bin information. Reviewers will provide feedback through scores and critiques for each criterion in a structured summary statement. Also in 2009, reviewers will begin giving streamlined (undiscussed) applications a preliminary score. In time for January 2010 receipt dates, R01 applications will be shortened (to a 12-page research plan) and restructured to align with review criteria that focus more on impact, innovation and track record and less on detailed methodology. Council members commented that the 7-point scale is likely to create a higher number of borderline applications that may require greater scrutiny from Council and from program staff.
Ensuring Balanced and Fair Reviews across Scientific Fields and Career Stages
To fund the best science earlier, NIH is considering separate percentiling of new and resubmitted applications. There is also discussion of permitting only one resubmission (eliminating A2s). In 2009, NIH will evaluate clustering ESI applications for review. The same approach will be considered for clinical research applications.
VIII. Council Subcommittee Reports
Clinical Trials Subcommittee
Dr. Laura Ment, Chair
The subcommittee examined how it handles concept clearance for clinical research grants in excess of $1 million. Current policy defines clinical research as: (1) Patient-oriented research, (2) Epidemiologic and behavioral studies, or (3) Outcomes research and health services research. Additional criteria might address the burden of disease.
Training, Career Development, and Special Programs Subcommittee
Dr. Gary Westbrook, Chair
The subcommittee discussed two possible changes to T32 Institutional Training Grants. One change would increase the maximum number of training slots available from four to eight. Another change would eliminate the distinction between broadly based and highly focused training grants. The subcommittee also discussed new incentives to recruit and retain clinicians in neuroscience research. One possibility is to use a K award to provide 75 percent salary support to clinician-scientists who hold only one R01. Another possibility is to use multi-PI grants that pair a new clinician-scientist with a more established clinician-scientist to jumpstart the new investigator's career.
IX. Concept Clearance for FY 2009 Proposed Initiatives
NINDS asks Council for feedback about initiatives that involve spending new dollars as well as formal concept clearance for these initiatives. Two initiatives were proposed.
Dr. Eugene Golanov, Program Director, Neural Environment Cluster, presented a proposal for a "Stroke Genetics" initiative. This large genome-wide association study (GWAS) in ischemic stroke would utilize data from prior small studies funded by NINDS, and maximize returns on the investment NINDS has already made. Taken together, the small studies generated DNA samples and associated clinical data from some 10,000 ischemic stroke patients. A large GWAS would be possible if the sample data were consolidated into a single genotype-phenotype database. Moreover, this database would be made publicly accessible and would serve as a useful resource for future studies on stroke genetics. Some Council members noted that GWAS studies have searched for genetic risk factors associated with a variety of diseases, and that most of the risk factors identified so far contribute a very small amount of risk - making their clinical utility questionable. Other members pointed out that finding a lack of association between genetics and ischemic stroke would be valuable. Council members also questioned whether the phenotype data collected from prior small GWAS studies is reliable and whether it could be standardized to make useful genotype-phenotype correlations. Dr. Koroshetz emphasized that the proposed GWAS would be milestone-driven, and that the first milestone would be to establish data reliability and harmonization. NINDS will consider Council's comments and re-think this initiative.
Dr. Mark Scheideler, Program Director, Technology Development, presented a proposal for the "Optimization of Molecular Probes for the Nervous System." This initiative would enable the Molecular Libraries Screening Consortium to provide enhanced services to neuroscientists, such as generating molecular probes with better penetration into neural tissue. The key is to refine "hits" from high-throughput screening assays into useful probes via medicinal chemistry. For this purpose, a contract would provide a medicinal chemistry consultant and access to NCI's ChemNavigator - a web-based warehouse of ~50 million chemicals. Council voted to approve this initiative.
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 other applications which needed specific discussion. Prior to the discussion of the grants, Dr. Finkelstein reminded Council regarding conflict of interest and confidentiality as follows:
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.
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, the Council Executive Secretary, who will then refer the questions to the appropriate staff member for response.
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 Project and Center Awards
The Council reviewed a total of 1,945 research project and center applications; of this total, 1,182 applications had primary assignment to NINDS, and 616 of them (52.1 percent) were recommended for support in the amount of $171.3 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 $40.4 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 three investigators as Javits awardees.
Small Business Innovation Research and Small Technology Transfer Award Programs
The Council reviewed a total of 169 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 86 applications had primary assignment to NINDS and 48 of them (55.8 percent) were recommended for support in the amount of $9.9 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 $4.0 million.
The meeting was adjourned at 9:55 a.m. on Friday, September 19.
We certify that, to the best of our knowledge, the foregoing minutes and attachments are accurate and complete.
Robert Finkelstein, Ph.D.
National Advisory Neurological Disorders and Stroke Council
Director, Division of Extramural Research
National Institute of Neurological Disorders and Stroke
Story C. Landis, Ph.D.
National Advisory Neurological Disorders and Stroke Council
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.
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.
Last updated February 8, 2011