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NINDS Advisory Council Meeting Minutes, February 5-6 2009


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 5-6, 2009

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 174th meeting on February 5-6, 2009, 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 5, 2009:  10:30 a.m. to 4:50 p.m.

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

Closed:            February 6, 2009:  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 (2/6/09 only)

Members of the public present for portions of the open meeting included:
Mr. Ronald Bartek, Friedreich's Ataxia Research Alliance
Dr. Anne Rutkowski, CURE CMD
Beth Roy, Social and Scientific Systems, Inc.
Donna Meltzer, Epilepsy Foundation
Rick Hansen, Digicon Corporation
Ms. Michelle Rodriguez, SRI
Dr. Merit Cudkowicz, Massachusetts General Hospital
Dr. Howard Federoff, Georgetown University

NINDS employees present for portions of the meeting included:

Dr. Alan Willard
Ms. Ruth Linn
Dr. Scott Janis
Dr. Merrill Mitler
Dr. Claudia Moy
Dr. Deborah Hirtz
Dr. Raul Saavedra
Ms. Nena Wells
Dr. Story Landis
Dr. Brandy Fureman
Dr. Linda Porter
Dr. Dan Tagle
Dr. Tom Jacobs
Dr. Yuan Liu
Dr. Emmeline Edwards
Dr. Ernie Lyons
Dr. Laura Mamounas
Dr. Robert Finkelstein
Dr. John Porter
Dr. Jill Heemskerk
Dr. David Owens
Dr. Eugene Golanov
Dr. Jane Fountain
Ms. Lydia Munger-Little
Ms. Lynn Rundhaugen
Ms. Maureen Hambrecht
Dr. Margaret Sutherland
Dr. Amelie Gubitz
Dr. David Jett
Ms. Joellen Harper-Austin
Dr. Beth-Anne Sieber
Dr. May Wong
Dr. Stephen Korn
Dr. Wendy Galpern
Ms. Tracy Chen
Mr. Taek Oh
Mr. Scott Prince
Mr. Daniel Stimson
Ms. Lisa Gough
Mr. James Stables
Ms. Margo Warren
Ms. Lisa Joliet
Dr. Rebecca Farkas
Dr. Timothy Lavaute
Mr. Ken Frushour
Dr. Ned Talley
Dr. Jennifer Antelman
Dr. Ursula Utz
Ms. Nancy Hart
Dr. Steve Markowski
Dr. Alan Koretsky
Ms. Vanessa Mahon
Dr. Robert Riddle
Mr. Aaron Kinchen

Ms. Margaret Jacobs
Dr. JoAnn McConnell
Dr. Naomi Kleitman
Dr. Audrey Penn
Dr. Daofen Chen
Dr. Randall Stewart
Dr. Robert Zalutsky
Dr. Shanta Rajaram
Mr. Paul Girolami
Dr. Shai Silberberg
Dr. Ned Talley
Dr. Joe Pancrazio
Mr. Phil Wiethorn
Dr. Michelle Jones-London
Dr. Mark Scheideler
Dr. Ramona Hicks
Dr. Debra Babcock
Ms. Christina Vert
Mr. Peter Gilbert
Ms. Pamela Mayer
Dr. Ran Zhang
Dr. William Benzing
Dr. Walter Koroshetz
Ms. Tijuanna Decoster
Ms. Marian Emr
Dr. David Yeung
Ms. Preeti Hans
Dr. Ti Lin
Dr. Paul Scott
Ms. Shannon Garnett
Dr. Alexander Runko
Dr. Yolanda Vallejo
Dr. Anna Taylor
Dr. Cara Allen
Ms. Joanne Odenkirchen
Dr. Laurie Gutmann
Dr. Miriam Leenders
Ms. Stacey Chambers
Dr. Richard Crosland
Ms. Natalie Frazin
Dr. Janet He
Dr. Giovanna Guerrero
Ms. Louise Ritz
Dr. Gary Murray
Ms. Lynn Morin
Ms. Janice Cordell
Dr. Jim Gnadt
Ms. Pam Pearson-Green
Dr. Salida Waddy
Dr. Robin Conwit
Dr. Rebecca Desrocher
Dr. Unni Jensen
Dr. Melinda Kelley
Ms. Maxine Davis-Vanlue
Dr. Al Gordon

Other Federal employees present for portions of the meeting included:

Dr. Mary Affeldt, NIDA
Dr. Stefano Bertuzzi, OD
Dr. Jacob Hoots, OD
Dr. Daphne Robinson, NIAID
Dr. Malcolm Smith, NCI
Dr. Jonathan Ivins, CSR
Dr. Seetha Bhagavan, CSR
Dr. Aftab Ansari, CSR
Dr. ReneEtcheberrigaray, CSR
Dr. Mary Custer, CSR
Dr. Jay Joshi, CSR
Dr. Laurent Taupenot, CSR
Dr. Joy Gibson, CSR
Dr. Pat Manos, CSR
Dr. Deborah Lewis, CSR
Dr. Geoffrey Schofield, CSR
Dr. Carol Hamelink, CSR
Dr. Peter Guthrie, CSR
Dr. Aiden Hampson, CSR

I.  Call to Order and Opening Remarks

Dr. Landis welcomed Council members, visitors, and staff to the 174th meeting of the National Advisory Neurological Disorders and Stroke Council meeting.  Dr. Landis announced that effective on January 1 Dr. Audrey Penn has an emeritus appointment in the Office of the Director in NINDS.  Among departures, Dr. Landis mentioned that Dr. John Marler, who had been on sabbatical from his position as Associate Director for Clinical Research, had taken a position with the FDA and that Dr. Melinda Kelley with the Office of Science Policy and Planning will be leaving NINDS for a position with NHLBI. 

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 September 18-19, 2008, Council meeting minutes.

The following future Council meeting dates were confirmed

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)

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 136 applications eligible to be expedited for payment, and 100 awards have been issued.  

DER Staff Updates—Dr. Finkelstein reported on Margaret Jacobs’ retirement at the end of February thanking her for her enormous contributions to epilepsy research.  Dr. Finkelstein introduced the following new DER staff:  Dr. Salina Waddy, Program Director, Office of Minority Health and Research; Ms. Jennifer Antelman, Health Program Specialist, Office of Clinical Research; Dr. James Gnadt, Program Director, Systems and Cognitive Neuroscience Cluster; Dr. Miriam Leenders who is on detail from the intramural program as a Health Program Specialist working with Dr. Ned Talley in the Channels, Synapses, and Circuits Cluster; and Dr. Anna Taylor, Health Program Specialist, Office of the Associate Director for Extramural Research. 

III.  Report of the Director, NINDS

FY 2009 Budget

Since Congress has not yet passed an omnibus appropriations bill for FY 2009, NIH is operating at FY 2008 budget levels on a Continuing Resolution [Public Law 110-329: Consolidated Security, Disaster Assistance, and Continuing Appropriations Act, 2009].  The CR expires on March 6, 2009, but will probably be extended, since an omnibus bill is unlikely to be passed by then.  The CR means that NINDS will probably maintain its payline at the 10th percentile for most grant applications.  Most R01 applications from new investigators will be paid to the 20th percentile.

Bills under consideration in the House and Senate would increase the NIH budget by 2.9-3.5 percent.  For a budget increase within this range, NINDS will probably be able to increase its payline to the 11th percentile.

Economic Stimulus Package and its Potential Impact on NINDS

There are House and Senate versions of proposed legislation [The American Recovery and Reinvestment Act of 2009] to stimulate the U.S. economy.  Each of these bills would provide a two-year increase in the NIH budget.  Although the stimulus funds are temporary, they represent a tremendous opportunity for NIH.

The House version of the Recovery Act has passed [H.R.1.EH] and would provide:

  • $1.5 billion for the ICs, including $40 million for NINDS
  • $1.5 billion for renovations at non-Federal research facilities (NCRR)
  • $500 million for renovations and construction on the NIH campus – would likely include completion of the Porter Neuroscience Building for intramural neuroscience.
  • $400 million transferred from the Agency for Healthcare Research and Quality (AHRQ) to NIH to fund comparative effectiveness research.

The Senate version [H.R.1.AS2] would provide:

  • $8 billion for ICs, because of an amendment by Sens. Harkin and Specter
  • $1.35 billion for the NIH Common Fund
  • $300 million for NCRR
  • $500 million for the NIH campus
  • $400 million transferred from AHRQ to fund comparative effectiveness research.

If the Act called for an increase in the NIH base budget, NINDS could increase its payline for R01 grants.  However, because the Act calls for temporary stimulus funds, a payline increase is not feasible.  As currently written, the legislation requires NIH to spend the stimulus funds within two years, but a typical R01 grant spans four to five years.

In addition to the timing of the stimulus, NINDS must also consider its intent.  Two primary goals of the stimulus are "to preserve and create jobs" and to "spur… technological advances in science and health."  In keeping with those goals, 2-year grants could be made available to scientists whose labs are in danger of closing.

Once the Recovery Act has passed and the stimulus has been implemented, allocation of the funds will be reported at www.recovery.gov.  (Note: On February 17, 2009, the President signed The American Recovery and Reinvestment Act into law.  The final version provides: $7.4 billion to the ICs, $800 million to the NIH Common Fund, $1.3 billion to NCRR, $500 million for the NIH campus, and $400 million transferred from AHRQ to fund comparative effectiveness research.)

Implementation of Changes to Enhance Peer Review

Dr. Alan Willard, Chief, Scientific Review Branch, gave an update on the phased implementation of changes to peer review.  These changes are the product of the NIH Peer Review Self-Study, an effort launched in June 2007 to evaluate the efficiency and fairness of peer review.  The changes follow the recommendations of four working groups that were tasked with meeting four goals:  (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) Conduct Continuous Review of Peer Review.

Changes Already in Place

  • Revised Applications – The Self-Study working groups found that there has been a decrease in the number of awards made in response to new applications, and a relative increase in awards made after first or second revised applications (A1s or A2s).  To streamline the time to an award, the A2 has been eliminated, beginning with new applications that were due January 25, 2009.  Under a grandfather clause, A2s are allowed for applications submitted prior to January 25, 2009.  For these grandfathered applications, A2s will not be accepted after January 7, 2011.
  • Early-Stage Investigators – The Self-Study working groups recommended special consideration of early-stage investigators (ESIs), defined as individuals who have not previously held a significant NIH grant, and who are within ten years of completing a terminal degree or residency training.  Starting with R01 grant applications received for February 5, 2009, submission dates, NIH now identifies ESI applications, and where possible, will cluster them for review beginning with May 2009 review meetings.

Other Changes to be Implemented at May 2009 Review Meetings

  • New Priority Scoring System – Rather than the 41-point scale that is currently used to assign priority (overall) scores to applications, reviewers will use a 9-point scale designed to fit the way people bin information.
  • Scoring of Individual Core Criteria – Reviewers will also use the 9-point scale to score the core criteria (significance, investigator(s), innovation, approach, and environment).  These criterion scores will inform the overall score, but will not be used in a formulaic calculation.  Even applications that are not discussed during review will receive criterion scores.
  • Template for Reviewer Critiques – Reviewers' written critiques will follow a template that contains distinct sections for:  the core review criteria, the application's overall impact, and other criteria/additional considerations.  Comments will be written as bullet points and short narratives.
  • New Emphasis on Impact and Career Status – Review criteria will be enhanced to reflect the potential impact of the application and the career status of the investigator, including ESI status and the track record of established investigators.

Changes for January 2010 Due Dates and Later

  • The research plan in R01 applications will be limited to 12 (rather than 25) pages.
  • R01 applications will be restructured so that the application sections correspond to the enhanced review criteria.

IV.  Reports of the NINDS Planning Modules

Introduction

Dr. Paul Scott, Director, Office of Science Policy and Planning, summarized the status of the Institute-wide strategic planning effort.  The primary goal is to evaluate how well NINDS is carrying out its mission to reduce the burden of neurological disease, and to generate a set of concrete recommendations where gaps or weaknesses are identified.  Four planning modules, each consisting of an external advisory panel and an internal NINDS working group, were established to evaluate four areas of investment:

  • Diseases
    Advisory Panel Chairs:  Drs. Tim Pedley and Henry Paulson
    NINDS working group leaders:  Drs. Deborah Hirtz and Joe Pancrazio

  • Translational Science
    Advisory Panel Chairs:  Drs. Howard Federoff and John McCall
    NINDS working group leaders:  Drs. Joe Pancrazio and Rebecca Farkas

  • Clinical Science
    Advisory Panel Chairs:  Drs. Dan Lowenstein and Merit Cudkowicz
    NINDS working group leaders:  Drs. Shanta Rajaram and Melinda Kelley

  • Basic Science
    Advisory Panel Chair: Dr. Gary Westbrook
    NINDS working group leaders:  Drs. Ned Talley, Heather Rieff, and Giovanna Guerrero

The modules engaged in an iterative process, with the external panels formulating questions and the internal groups providing relevant data.  Multiple opportunities were provided for public input, including a Request for Information that was posted on the NINDS web site and sent to patient advocacy groups.  During the planning effort, there was an evident 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. This module has been assembled but has not yet met.  Today, the original four modules presented their preliminary findings and recommendations.  These will be incorporated into a draft plan, which will be posted for public comment and finalized by spring 2009.

Diseases Module – Summary presented by Dr. Pedley

Task and Procedures

This group was charged with evaluating how NINDS should invest in research across the spectrum of neurological disorders, taking into account factors such as disease burden and scientific opportunity.  The group identified five major areas of need, and formed five working groups to articulate specific recommendations.

Key Findings and Recommendations

  • Develop a publicly accessible database of neurological diseases in which the diseases can be related and clustered according to disease mechanism and other information.  Current methods for tracking NINDS investment across the disease spectrum are outdated, and largely do not account for shared mechanisms.  The new database should reflect current science, change readily and dynamically in response to new advances, and capture in digital, searchable form the main categories of disease mechanisms and burden.  The database will be intended primarily for use by investigators, but might eventually serve a larger audience. 

  • Establish a new priority-setting process that would be systematic, comprehensive, and data-driven.  This would involve a systematic environmental scan of scientific opportunities within and across neurological diseases, taking into account the current state of knowledge and ongoing research supported by NINDS and other entities.  The database described in recommendation (1) would facilitate this process by helping identify common disease mechanisms and overlapping scientific opportunities.  Dr. Koroshetz noted that the NINDS Stroke Progress Review Group engages in a similar process to set the Institute's priorities in stroke research.  However, he questioned whether this model would work for rare diseases, and how to maximize the participation of voluntary groups in the priority-setting process.

  • Develop a prototype for evaluating disease initiatives.  When the Institute plans a new initiative, an evaluation metric should be developed as part of the planning process.  Each initiative should clearly state its intended outcomes so that relevant quantitative and qualitative outcome measures can be established to evaluate success.  Evaluation plans should include mechanisms for providing early feedback, an interim assessment using predetermined benchmarks, and a formal review following completion of the initiative, or within 5-10 years for continuing programs.

  • Establish new initiatives to leverage rapidly occurring gains in technology and information.  NINDS could:

Assume more leadership in organizing disease-specific consortia designed to enhance collaboration and resource/data-sharing among investigators.

Establish an expert panel to monitor changes in technology (e.g., in nanoscience, genomics, neuroimaging and informatics) and advise NINDS on how these could be applied to disease research.

Develop additional programs to help investigators gain rapid access to new technologies.

Provide more support for the application of systems-mathematical-computational approaches to disease research.

  • Invest more heavily in "T2" translational research, which is hypothesis-driven research that identifies and measures barriers to translating the results of clinical trials into widespread practice.

Clinical Science Module – Summary presented by Dr. Cudkowicz

Task and Procedures

This group was tasked with assessing the scope and direction of clinical research supported by NINDS.  The group identified three areas of concern:  (a) How to balance NINDS' priorities in clinical research against its priorities in basic and translational research; (b) How to set priorities within clinical research; and (c) How to plan and implement clinical trials more efficiently.

Key Findings and Recommendations – Balancing Clinical, Basic and Translational Research

  • Increase NINDS' investment in clinical research through more initiatives with a clinical emphasis, increased use of clinical research networks, and separate pooling and funding of clinical versus basic science applications.  The return on investment in NINDS-sponsored clinical research has been high, with substantial gains in public health that easily justify the funds spent on large clinical studies.  Nonetheless, compared to seven other Institutes (NCI, NIAID, NHLBI, NIMH, NICHD, NIA, NIAMS), NINDS ranks last in the fraction of its budget spent on clinical research.  In FY 2007, the median fraction these ICs spent on clinical research was 35 percent, NIMH had the highest fraction at 61 percent, and NINDS was 22 percent – where clinical research is defined as research involving humans or human tissue.  Council members noted that this definition probably inflates the gap between NINDS and other Institutes, as it does not necessarily include disease-focused research but does include social science research.

  • Begin funding T2 research through a specific PA with set-aside funding to make up for the lack of T2 research in the NINDS portfolio.

Key Findings and Recommendations – Setting Priorities within Clinical Research

  • Involve additional outside experts in setting clinical research priorities.  Under current procedures, the Clinical Trials Subcommittee of the NANDS has responsibility for concept clearance and final approval of trials costing more than $1 million.  The subcommittee has a rotating membership of talented individuals, but it is a small group without the broad knowledge or experience necessary to evaluate the wide variety of clinical trial proposals submitted to NINDS.  NINDS should include additional experts on its advisory panels tasked with evaluating clinical trial proposals for their potential impact.

  • Develop a new grant application and 2-tier review system for clinical research that calls for brief proposals with an initial focus on need, potential impact of results and feasibility rather than details of trial design.  Current application and review procedures place too much emphasis on the details of trial design and not enough emphasis on the trial's potential impact.  The first tier of review by expert panels should specifically focus on impact.  At present, only a small pool of investigators has the experience and resources to conduct clinical trials. Therefore, for proposals selected to move forward at tier one, the full research protocol should be developed collaboratively with input from the investigators who proposed the study, and possibly from a steering committee appointed by NINDS staff. Dr. Landis noted that NIH-wide changes in peer review already have resulted in shorter applications with an emphasis on impact.

Key Findings and Recommendations – Implementation of Clinical Trials

  • Require that all clinical studies include study metrics and response action plans from the outset.  Many clinical trials are not completed within their budgeted timelines and others do not produce conclusive results, problems that can be traced to flaws in trial design and execution.  Study metrics – measures to assess the feasibility of a trial and its ongoing progress (including subject enrollment, timeline and data collection) – should be used at the planning stages and throughout the trial's execution.  Response action plans also should be in place to determine how problems in trial execution will be remedied.

  • Reconsider the planning grant.  NINDS currently offers planning grants that provide seed money for setting up a trial.  However, the benefit of these grants is unclear.  They are nearly as difficult to write and review as a full trial proposal, and they do not always lead to trials.  The planning grant should be eliminated, and the planning process should be built into each trial.  [Later, Dr. Ment noted that the Clinical Trials Subcommittee and the Clinical Trials Group have likewise proposed eliminating the planning grant.]

  • Assist investigators with contractual and regulatory requirements, and incorporate completion of these requirements into trial planning.  To improve the efficiency of the contractual process between NINDS and the investigator's home institution, NINDS should create a standard work-scope and contract for all sites involved in a multi-center study.  NINDS also could reduce the regulatory burden imposed on multi-center clinical studies by facilitating the use of centralized institutional review boards (IRBs), rather than the customary use of multiple, local IRBs.  NIH should sponsor a meeting to explore other ways to assist investigators with the regulatory process.

  • Assume more leadership in enabling researchers to share ideas, data and scarce resources.  NINDS should take advantage of research (projects and /or resources) supported by other funding entities that might be useful to further research relevant to the NINDS mission. The Institute should take an active role in identifying such funding entities including other Institutes and Centers, Foundations, industry and its own intramural labs, and establishing collaborations with them.  The Clinical and Translational Science Award (CTSA) network provides a framework for collaborative clinical research, and NINDS should continue to explore how to leverage this network for collaborative studies in neuroscience.  NINDS should minimize the impact of scarce resources by supporting the development of core facilities and databases to be shared broadly throughout the clinical neuroscience community.

  • Enhance the infrastructure for clinical research by:

Leading in the development of standardized outcome measures, which would allow comparison of results across different clinical studies and different disease entities.

Fostering the construction and management of clinical research databases.  In addition to lacking standardized outcome measures for generating data, clinical researchers lack standardized ways to name, collect, organize and mine their data.  NINDS could confront this problem by developing an intramural program with expertise in database construction and management.

Enhancing efforts to train clinical researchers.  There is a dearth of researchers capable of leading a clinical trial at a single site, let alone a multi-center trial.  To confront this issue, NINDS offers institutional and individual grants that support training in clinical research (T32 and K23 awards).  NINDS should expand these programs and devise new ones.

Strengthening the NINDS Clinical Trials Group.  The Clinical Trials Group, a part of the Division of Extramural Research, works with the Clinical Trials Subcommittee to handle concept clearance and final approval of trials costing >$1 million.  Group members are talented and committed, but many would benefit from additional hands-on experience in clinical research.  Meanwhile, the Group should help cultivate the skills of clinical researchers in the NINDS intramural program.  With their research experience supplemented by training in regulatory and administrative processes, these individuals would be poised to provide expert advice to other clinical researchers.

Translational Science Module – Summary presented by Dr. Federoff

Task and Procedures

This group was charged with evaluating NINDS support of translational research, developing recommendations for improvement, and developing criteria for selecting diseases and strategies for future translational investment.  As defined by the group, translational research begins with an understanding of disease mechanism(s) and ends with an Investigational New Drug approval (IND) or Investigational New Device Exemption (IDE) from the FDA.  Possible products of translational research include methods for disease screening, diagnosis, and prevention; treatments such as drugs, biologics, surgeries and behavioral interventions; and tools to predict treatment response.  Because the research is product-driven rather than hypothesis-driven, it involves unique challenges, and stakeholders, with industry, foundations, and the financial sector figuring prominently.  It may require large investments at high risk.

The module identified major topics in translational research – from progress in specific diseases to common challenges across diseases – and broke into subgroups to address each one.  These topics were then reviewed by the entire group and distilled into several cross-cutting recommendations.  In addition to these recommendations, Dr. Federoff noted the importance of creating a smooth transition from basic to translational research and from translational to clinical.

Key Findings and Recommendations

  • Establish an Office for Translational Research (OTR) with broad responsibility for program leadership and coordination.  Most academic researchers are unaware of or unable to access the technological and regulatory resources needed in translational research.  Thus, one priority of the OTR should be to develop outreach and education activities aimed at the academic community.  Another priority should be to establish partnerships with academia, the private sector, clinical research groups, the patient community and FDA.  Dr. Landis noted that the Office of Technology Development was recently renamed the Office of Translational Research to reflect growing opportunities in translational research, and to recognize that over time, the activities of the Office have shifted in that direction.  A search is underway to identify a Director for this office.

  • Seek guidance from external advisors on general and program-specific issues.  NINDS should establish a panel of advisors to the new OTR Director, consisting of senior individuals in academia, biotechnology and pharmaceutical companies, and the venture capital community.  Drawing from these same communities, the Institute also should establish steering committees for the Cooperative Program in Translational Research and the Anticonvulsant Screening Program.

  • Pursue outreach activities that will help drive translational research and advance therapies to commercialization.  NINDS should develop a drug discovery short course for investigators.  The Institute should increase working liaisons with key partner groups, such as foundations, industry, academia, FDA, and financial institutions.

  • Establish a systematic and transparent process for identifying diseases that are ripe for translational research.  Criteria should include the potential to reduce disease burden, understanding of the disease mechanism and possible molecular targets (for a drug, biomarker, etc.), availability of research tools and resources, and the path to clinical trials and commercial development.  NINDS should engage the research and patient communities in assessing disease readiness and implementing translational strategies.

  • Focus and galvanize the research community around major challenges in translational research.  Such challenges include development of: methods to deliver drugs across the blood-brain barrier, animal models of disease that are more predictive of human responses to therapy, and biomarkers for early detection of disease and early testing of potential therapies.  There is a need for an integrated approach to biomarker development, from discovery to FDA approval and clinical use.

  • Utilize the Small Business grant programs (SBIR and STTR) more effectively.  These programs are intended to speed the development of commercial products from federally funded research, but commercialization remains complex and slow.  NINDS should consider commissioning a panel of scientists with strong business backgrounds to evaluate and restructure the Small Business programs.  NINDS should take a more proactive role in directing Small Business funds toward critical areas, such as those discussed immediately above.

  • Provide investigators with resources that minimize the costs and risks of translational research.  NINDS should fund a medicinal chemistry resource to optimize promising compounds into new drugs.  NINDS should also enhance access to informatics tools and in vitro ADME (absorption, distribution, metabolism, excretion) services used to predict how a compound might behave as a drug.

Basic Science Module – Summary presented by Dr. Westbrook

Task and Procedures

This group was tasked with reviewing NINDS' investment in basic neuroscience research.  Areas of special focus included:  the balance among basic, clinical and translation research; the balance among different areas within basic research; funding mechanisms; training; and shared resources.  Subgroups were formed to review these topics and to develop recommendations.  At the outset, basic research was defined as research on the functions of the normal nervous system, as well as disease mechanism research and other "disease-related" basic research. 

Key Findings and Recommendations

  • Continue to devote a majority of the budget to basic neuroscience research.  Despite the conception that basic research has little value in curing disease, roughly 50 percent of the basic research funded by NINDS is disease mechanism or disease-related research.  In addition, non-disease related or purely basic research has contributed to major scientific breakthroughs. NIH must continue to support these efforts to advance our basic understanding of nervous system function in health and in disease, partly because industry will not.  NINDS also must enhance its efforts to educate the public about the value of basic neuroscience research.

  • Continue to support the full range of sub-disciplines within neuroscience.  The module analyzed NINDS and NIH support across sub-disciplines of neuroscience and found no area to be over-represented. The group also piloted a prototype topic mapping tool (www.nihmaps.org) .  Using this tool, individual grants can be visualized as points on a map and "geographically" positioned according to topic area.  The approach can reveal connections between different areas of research, and has value in demonstrating the fact that basic mechanisms (and breakthroughs) cross disease boundaries.

  • Allocate at least 70 percent of the extramural grants budget toward investigator-initiated research projects (R01s).  The number of R01 grants and the funds awarded per grant decreased from 2003 to 2008, while the number and funding for some types of cooperative (U) grants and for Program Project (P01) grants increased during the same period.  Success rates and renewal rates for P01s were also considerably higher than for R01s.  Yet, analysis of productivity, publication output, and impact of NINDS-funded research, reveals no evidence that P01s enabled greater success or progress than R01s.  The apparent diversion of funds from the R01 to the P01 is likely having a negative effect on innovative, high-impact research.  R01 funding should be restored to 70 percent (2004 level) of the total NINDS grants budget.

The P01 grant should be eliminated to help restore R01 funding.  Council members raised concern that P01s may be necessary to bring basic scientists into collaborative, disease-focused projects, and to educate them about clinical areas where their research can be applied.  Other members countered that there are other means to support collaboration and knowledge sharing between basic and clinical scientists, including multi-investigator R01 grants.

The Small Grant program (R03) should be used to support small, exploratory or pilot projects that may lack the preliminary findings usually required to secure an R01.  The description of the R03 in the NINDS funding guidelines should be revised to reflect this purpose.

The Exploratory/Developmental Grant program (R21) should be eliminated.  The R21 has a reputation for being a safe haven for new investigators, but in fact, has become a trap.  Since 1998, there has been an increase in applications for R21s, but not a corresponding increase in awards.  With the proposed change in the focus of the R03, the R21 also becomes redundant.

There has been an increase in U01 awards that requires further investigation and justification.  There has been a substantial proliferation of U01 projects supported by NINDS, from 3.7 percent of the grants budget in 2003 to 9.5 percent in 2008.  While U01s are valuable for funding milestone-driven research, there is concern that they are diverting funds away from R01 investigator-initiated grants.

  • Support resources that are needed to advance the field, and periodically assess the impact of this support.  NINDS should set aside a fraction of its budget for resource support.  This budget should be reviewed and a poll of neuroscientists should be taken to assess need every 2-3 years.  Resources should not be funded if they are readily available from or could be made more efficiently by the private sector, although seed money may be appropriate to help investigators take advantage of such resources.  To defray costs, NINDS should take advantage of the opportunity to partner with other ICs, the Common Fund, nonprofit groups and industry.  Oversight and assessment of NINDS-funded resources should include:  pre-defined outcome measures, regular usage surveys for facility- and collection-type resources, yearly performance checks, a sunset after 5 years for tool-building projects or use of the SBIR mechanism as an alternative, and an advisory board that meets regularly.  NINDS should enhance its outreach about available resources by sending a yearly email update to grantees and by offering grants that support travel to labs with responsibility for shared facilities or with specialized knowledge.

  • Continue programs to train investigators, with more emphasis on late-stage predoctoral training. 

NINDS should continue to invest in institutional (T32) training grants, as these support academic programs capable of reaching many individuals.

Future investment in T32 grants should be weighted toward late-stage predoctoral students (in the 2nd year of their Ph.D. programs and later), as opposed to early-stage predoctoral students or postdoctoral fellows.  Broad-based training for early predoctoral students is adequately served by the Jointly Sponsored Institutional Predoctoral Training Program in the Neurosciences, in which NINDS participates.  Meanwhile, focused training for postdocs is adequately served by individual (F32) training grants.  Late-stage predoctoral students who have committed to an area of investigation tend to fall through the cracks.

More effort should be made to train Ph.D. scientists in disease, rather than train M.D. scientists in basic research.  Rather than expanding programs to recruit clinicians into research (K08 and K23), T32 predoctoral grants could be oriented toward disease-related research.  This recommendation provoked mixed reactions from Council.

The NIH Pathway to Independence (K99/R00) program, which supports the transition from a postdoc to a faculty position, has shown early signs of success.  If outcomes continue to be positive, the program should be expanded.

Training grant applications place heavy burdens on applicants and reviewers.  These burdens may improve with ongoing changes in NIH-wide peer review, but should be monitored.

Each training program should be evaluated by a set of outcome measures tailored to its unique goals.

Overview and Discussion

Dr. Landis asked the Module co-chairs to indicate which of their recommendations deserve the highest priority.  The chairs of the clinical and translational panels were not able to attend this portion of the meeting, so their priority statements were made by other panel members.

  • Diseases – Establish a new relational database and a new priority-setting process to determine investment across the spectrum of neurological diseases.
  • Clinical – Dedicate more funds to clinical research, work more effectively with investigators to conceptualize and implement clinical trials, and enhance the infrastructure for supporting clinical trials.
  • Translational – Create an Office of Translational Research and appoint someone to lead it who has unique expertise in product-driven research and a unique rapport with extramural researchers, industry, foundations, and the financial sector.
  • Basic – Save the R01, and evaluate whether other funding mechanisms provide as much of a return on the dollars invested

V.  Council Subcommittee Reports 

Training, Career Development and Special Programs Subcommittee--Dr. Westbrook, Chair

R25 Supplements

The subcommittee discussed supplements to the Research Education Programs for Residents and Fellows in Neurology and Neurosurgery (R25).  This initiative funds the development of institutional programs to train medical residents and fellows for careers in research.  Participating residents and fellows may apply for supplements that provide salary support, and these applications will be reviewed internally by NINDS.

Temporary Suspension of K24 Applications

The Midcareer Investigator Award in Patient-Oriented Research (K24) provides support for clinicians to engage in patient-oriented research and to act as mentors for beginning clinical investigators.  Following a review of past applications and the original program announcement language, the subcommittee found that the program lacks a clear definition of mentoring.  The program will be temporarily suspended pending further evaluation. Statement added 5-12-2010: As of August 2009, NINDS resumed accepting K24 applications. Please see NOT-NS-09-016 for details of NINDS priorities for the K24 program, and the NINDS training website for additional details.

Training Ph.D.’s for Disease-Related Research

The subcommittee discussed ways to improve the recruitment and training of Ph.D.’s in disease-related research.  One possibility might be a program modeled after HHMI's Med Into Grad Initiative or the HHMI-NIBIB Interfaces Initiative.

Clinical Trials Subcommittee--Dr. Laura Ment, Chair

Women and Minorities in Clinical Research

The subcommittee reviewed the participation of women and minorities in NINDS-funded clinical trials.  By congressional mandate, NIH-funded clinical research must include women and minorities in appropriate numbers based on the scientific question under study.  From 2005 to 2008, there were more females than males enrolled in NINDS-funded clinical studies.  During the same period, enrollment of Hispanic, African American, American Indian/Alaska Native and Asian individuals increased, and the number of participants of unknown or unreported race decreased.  The subcommittee discussed ways to continue this positive trend, including sending clinical trials coordinators into communities with large minority populations, and translating public outreach materials into Spanish.

Clinical Trial Implementation

Working with the Clinical Trials Group, the subcommittee has proposed a new procedure for concept clearance and implementation of Phase III clinical trials.  Under this procedure, implementation would occur in three phases over a 5-7 year period:  Concept clearance (year 1), planning/start-up/feasibility (years 2-3), and completion (years 4-7).  Funding would be committed at each phase of the trial.  A major change from current procedure is the elimination of the planning grant, which provides seed funds for writing trial protocols, organizing trial sites and other aspects of the trial.  Under the new procedure, these activities would be built into trial implementation.

Basic and Preclinical Programs Subcommittee--Dr. Povlishock, Chair

The subcommittee reviewed NIH's center programs in neurological disease research, including the Udall Centers of Excellence in Parkinson's Disease (NINDS), the Wellstone Muscular Dystrophy Cooperative Research Centers (NINDS), and the Alzheimer's Disease Research Centers (NIA).  Discussion focused on how to maintain program balance, encourage collaboration, and foster innovation.  A consensus emerged that in the interests of increasing program balance and reducing administrative burden on NINDS staff, it is probably more effective to support these centers through a grant (P50) steered by a coordinating committee, rather than through a cooperative agreement (U54).  It was agreed that the coordinating committee should play a role in fostering collaboration within each program, and that yearly or twice-yearly meetings would enhance collaboration and innovation by center investigators.  To support these meetings and other collaborative efforts, NINDS could provide modest seed funds ($100,000/1 year), and should encourage participation by advocacy groups.

VI.  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. 

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, 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 Training and Career Development Programs

The Council reviewed a total of 141 research career development and institutional training grant applications; of this total, 95 applications had primary assignment to NINDS, and 77 of them (81.1 percent) were recommended for support in the amount of $14.2 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 $5.0 million.

Research Project and Center Awards

The Council reviewed a total of 1,868 research project and center applications; of this total, 1,124 applications had primary assignment to NINDS, and 646 of them (57.5 percent) were recommended for support in the amount of $206.0 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 $57.5 million.

Senator Jacob Javits Neuroscience Investigator Awards

The Senator Jacob Javits Neuroscience Investigator Awards are made to distinguished investigators who have a record of scientific excellence and productivity, who are actively pursuing an area of research of strategic importance, and who can be expected to continue to be highly productive for a seven-year period.  Candidates are nominated and selected at each Council meeting.  At this meeting, no Javits awardees were recommended.

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, 107 applications had primary assignment to NINDS and 57 of them (53.3 percent) were recommended for support in the amount of $13.8 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 $3.2 million.

VII.  Adjournment

The meeting was adjourned at 9:55 a.m. on Friday, February 6.

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 Strok

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.

(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