NINDS Advisory Council Meeting Minutes, September 20-21, 2012

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

Summary of Meeting[1]
September 20-21, 2012

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 185th meeting on September 20-21, 2012, in Building 31, Conference Room 6, on the NIH campus, 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:

Council members present were:

Council Roster (Attachment 1)

Council members absent were:
Ms. Amy Comstock Rick

Ex Officio Members absent:
Dr. Robert Ruff, Department of Veterans Affairs

Members of the public present for portions of the open meeting included:
Dr. Ray Dorsey, Johns Hopkins University
Mr. Ronald Bartek, Friedreich's Ataxia Research Alliance
Dr. Dawn Mancuso, Hydrocephalus Association
Dr. John Kehne, Translational Neuropharmacology Consulting, LLC
Dr. Andrea Baruchin, Foundation for the NIH
Ms. Elizabeth Kwasnik, Parkinson’s Action Network
Dr. Shimere Williams, UC
Rachael Crockett, Foundation for Physical Therapy
Ms. Nancy Moy, SRI International
Claudia Davis, American Heart Association
Theresa Spahr, Booz Allen Hamilton
Tracy Casteuble, Epilepsy Foundation

I.  Call to Order and Opening Remarks 

Dr. Landis, Director, NINDS, welcomed Council members, visitors, and staff to the 185th meeting of the National Advisory Neurological Disorders and Stroke Council meeting. 

Dr. Landis introduced four new Council members:  Dr. E. Antonio Chiocca, who recently joined Brigham and Women's and Faulkner Hospitals in Boston as the chair of Neurosurgery, and as co-director for the Institute for Neurosciences and a surgical director in the neuro-oncology program at the Dana-Farber Cancer Institute; Dr. David Goldstein, the director of the Center for Human Genome Variation and a Professor in the Department of Molecular Genetics of Microbiology at Duke University Medical Center in Durham, NC; Dr. Byron Ford, Professor in the Department of Neurobiology and the Director of the Neuroprotection, Neurorepair and Stroke Program at the Morehouse School of Medicine in Atlanta, Georgia; and  Amy Comstock Rick, J.D., Chief Executive Officer of the Parkinson’s Action Network (PAN), a Washington D.C.-based national nonprofit focused on educating the public and government leaders on better policies for research and an improved quality of life for people living with Parkinson’s disease.  Unfortunately, due to a conflict, Ms. Rick was unable to attend this Council meeting.

Dr. Robert Ruff, the VA ex officio member also had a conflict and could not attend this meeting.  The Department of Defense is in the processing of identifying a replacement ex officio member for Dr. Geoff Ling who retired from the Army this summer.  Dr. Landis welcomed Dr. Rebecca Frederick, a AAAS Science and Technology Policy Fellow in the NINDS Office of Science Policy and Planning.

II.  Report of the Associate Director for Extramural Research, NINDS

Approval of Council Minutes -- Dr. Finkelstein requested, and the Council voted approval, for the May 24-25, 2012, Council meeting minutes.

The following future Council meeting dates were confirmed:

Expedited Review Process -- A subset of Council members approve applications with scores within the payline for which there are no unresolved issues prior to the meeting.  Dr. Finkelstein thanked Drs. David Ginty, David Holtzman, and Kevin McNaught for handling this responsibility for this fiscal year.  For this Council round, 170 applications were eligible to be expedited including 7 career or K applications.  One hundred fifty one of these have already been issued and most of the others will be issued shortly after Council.   

DER Announcements -- Dr. Finkelstein announced that Dr. Dan Tagle, a Program Director who was with the Neurogenetics Cluster took a new position with the National Center for Advancing Translational Sciences (NCATS) in late August as Associate Director of Special Initiatives.  Dan had been a vital member of the NINDS extramural community for 11 years.  Prior to joining NINDS, Dan had been on the intramural side with NHGRI.  Next, he announced that Dr. Naomi Kleitman, Program Director, Repair and Plasticity Cluster, NINDS, will be leaving NINDS in November for a new position with The Craig H Neilsen Foundation.

Dr. Walter Koroshetz, Deputy Director, NINDS, introduced Ms. Kate Saylor, Special Assistant to the Deputy Director.  Kate came to NINDS through the Presidential Management Fellow Program.

Dr. Rajesh Ranganathan, Director, Office of Translational Research (OTR) introduced two new members of OTR:  Ms. Karen French, Program Analyst,  Blueprint Neurotherapeutics Program and Ms. Wendy Vasquez,  Program Coordinator, Anticonvulsant Screening Program & Counter Agents against Chemical Threats Program. 

Loan Repayment Program--Dr. Finkelstein reported that NINDS had 107 eligible applications for the two Loan Repayment Programs (LRP) in which it participates.  NINDS was able to pay 62 applications -- 38 for the Clinical Research LRP and 24 for the Pediatric Research LRP.  These are success rates of 56% (38/68) for the clinical LRP and 62% (24/39) for the Pediatric Research LRP.  Of the 62 awardees, there were 43 M.D.s, 7 M.D./Ph.D.s, 11 Ph.D.s, and one PharmD.  Areas of Specialty included 28 in Neurology, 16 in Pediatrics/Pediatric Neurology, five in Neuropsychology/Neuropsychiatry, four in Neurosurgery, four in Rehabilitation Medicine/Physical Therapy, and five in “other.”

III.  Report of the Director, NINDS

NIH Budget
Dr. Landis provided a brief update on the NIH budget for FY13, which begins on October 1, 2012.  On September 13, 2012, the US House of Representatives passed H.J. Res. 117, a continuing Resolution to fund the federal government until March 27, 2013.  The temporary funding measure continues funding at the current rate of operations for federal agencies, programs, and services as a whole; however the NIH budget allocation is 0.6% greater than in 2012.  On January 1, 2013, sequestration will begin unless an alternative agreement for controlling the federal deficit is reached prior to this time.  The White House Office of Management and Budget has released a report on the impacts of the sequestration indicating that NIH’s budget would be reduced by 8.2% or $2.5 billion.  NIH does not yet have guidance for implementation of the sequestration.

Celebration of Science
NIH joined Faster Cures and the Milken Institute’s Center for Acceleration Medical Solutions for a Celebration of Science from September 7-9, 2012.  More than 1,000 leaders in medical research, bioscience, patient advocacy, industry, philanthropy and public participated in this event to reaffirm the importance of bioscience and, in doing that, to change the world for future generations.  Dr. Landis noted that on September 8, 2012, a series of talks were held at NIH that are archived on the NIH website: http://www.nih.gov/about/director/09272012_celebrationofscience.htm.

New Directors appointed
Dr. Landis announced that Dr. Gary Gibbons had been selected to head the National Heart, Lung, and Blood Institute.  Prior to his appointment, Dr. Gibbons was the Director of the Cardiovascular Research Institute and Chairperson of the Department of Physiology at Morehouse School of Medicine.  Dr. Gibbons is a member of the Institute of Medicine, and his research interests are in vascular biology, genomic medicine and the pathogenesis of vascular diseases.

In addition, Dr. Chris Austin was selected to lead the recently formed National Center for Advancing Translational Sciences (NCATS).  Dr. Austin trained as a neurologist and developmental neurobiologist at Harvard Medical School.  Prior to his selection for this role, Dr. Austin was the acting Director of the Division of Preclinical Innovation at NCATS.  Since coming to NIH from Merck in 2002, Dr. Austin directed the knockout mouse project, the Molecular Libraries Program, the National Chemical Genomics Center, and the Therapeutics for Rare and Neglected Diseases (TRND) Program.

Current NCATS Activities
Dr. Landis reported on two programs that were recently launched by NCATS. “Organ on a chip” is a collaboration between the NIH, the Defense Advanced Research Projects Agency (DARPA) and the U.S. Food and Drug Administration, to develop 3-D human tissue chips that accurately model the structure and function of human organs, such as the lung, liver, and heart. Once developed, researchers can use these models to predict whether a candidate drug, vaccine or biologic agent is safe or toxic in humans in a faster and more cost-effective way than current methods.  On July 24, 2012, 17 awards were issued by NIH, 3 of which have a neuroscience focus: models for predictive neural toxicity and teratogenicity (Principal Investigator: James A. Thomson, V.M.D., Ph.D.), Neurovascular unit on a chip (Contact Principal Investigator: John P. Wikswo, Ph.D.), and a 3-D model of human brain development (Principal Investigator: Thomas Hartung, M.D., Ph.D.).  NIH has committed $75 million over five years to this program. 

On May 3, 2012, the NIH launched the Discovering New Therapeutic Uses for Existing Molecules program, a collaborative pilot program designed to spur the drug development process by finding new uses for compounds that already have cleared several key steps in the development process, providing scientists with a strong head-start in this complex and time-consuming process. Through this collaboration, eight pharmaceutical companies have agreed to make 58 of their high-quality compounds available for research. By making these resources broadly available, NIH and its partners aim to stimulate the development of therapies for diseases that still lack treatments.  The available compounds have undergone significant research and development by industry, including safety testing in humans and therefore provide a strong foundation for moving forward.  NCATS is anticipating contributing $20M in FY13 towards advancing this program.  Participation in this program is a two phase process: applicants will submit a short X02 pre-application, and successfully reviewed pre-applications will be invited to follow up with a complete UH2/UH3 application.  Of the 158 pre-applications, 14 are NINDS specific.

NINDS News
Dr. Landis provided council with a number of NINDS-related updates:

• On September 5, 2012, the National Football League (NFL) announced a $30 million donation to the Foundation for the National Institutes of Health.  The unrestricted gift is the NFL's single-largest donation to any organization in the league's 92-year history.  Specific plans for the research remain to be developed, but potential areas under discussion include accelerating the pace of discovery to support the most innovative and promising science of the brain, including: chronic traumatic encephalopathy (CTE); concussion management and treatment; and the understanding of the potential relationship between traumatic brain injury and late-life neurodegenerative disorders, especially Alzheimer's disease (AD).  Dr. Koroshetz will be leading the development of programs to be funded by these monies.
• On September 12, 2012, the NINDS hosted the 6th annual Nonprofit Forum to talk with advocacy organizations about current events at NINDS, ways to partner with the Institute, identification of research gaps, and ways that voluntary groups can work with NINDS to fill those gaps. 
• Dr. Landis reported on the NINDS efforts to improve the quality of NINDS-supported preclinical and clinical research through rigorous study design and transparent reporting.    She noted that Dr. Shai Silberberg would provide a summary of the workshops and NINDS activities in this area. 
• NINDS will take the lead to organize a planning meeting for AD-related dementias in 2013 in response to the National Alzheimer’s Project Act.  Dr. Landis noted that the National Institute on Aging organized the National Plan to address AD as part of a Council working group, and indicated that NINDS may do the same.
• Dr. Landis showed Council members a graphical representation of competing R01 applications reviewed and funded in FY11 as a function of the score.  She noted that a number of other Institutes display similar information on their websites (NIGMS, NIAMS, and NCI) and requested Council feedback on whether such information would be useful.  A number of Council members indicated their support for making this type of information public to investigators, as it may be helpful to dispel rumors.

IV. Translational Research at NINDS

Dr. Rajesh Ranganathan, Director of the NINDS Office of Translational Research (OTR), provided Council members with an overview of the office, and an update of the NINDS Anticonvulsant Program (ASP) and the NIH CounterACT (Countermeasures Against Chemical Threats) programs (update provided by Dr. David Jett) with the goal of better defining the role of NINDS in Translational Research.  To set the stage for discussion, Dr. Ranganathan provided an overview of the changing landscape of neuroscience drug discovery.  He noted that in recent years, although a small percentage of FDA drug approvals are for neurological indications, Pharma and Venture Capital funding for Research and Development for new neurotherapeutics continues to decline despite biotech VC funding remaining stable.  Moreover, in recent years, biotech IPOs have been limited to companies with Phase II or Phase III data in hand, while 10 years ago, companies could launch a successful IPO with preclinical data, suggesting an increasingly risk-averse environment for R&D funding.  To combat these challenges, industry is pursuing new partnering models to eliminate silos and to move therapy development forward.

The mission of the NINDS OTR is to facilitate the preclinical discovery and development of new therapeutic interventions for neurological disorders.  Dr. Ranganathan briefly described a number of OTR programs designed to advance this mission, and noted their diversity with respect to the types of funding mechanisms used to support them and to their program design.  In greater detail, Dr. Ranganathan described the ASP which was established in 1975 to provide services and expertise to investigators developing anticonvulsants.  Through a contract to the University of Utah, researchers from academia and industry can submit compounds for screening in a series of rodent seizure models.  Since its inception, the ASP has worked on 547 projects, screened over 30,000 compounds, and had a role in 10 marketed drugs since 1990.  Investment in ASP is $4.6M in FY12, of which $2.9M comes from the NINDS budget while the remaining $1.7M comes from the CounterACT program, whose budget is provided through a supplement to the NIH appropriation.  In 2011, the ASP working group, a working group of the NINDS council considered ASP’s value to epilepsy research and drug development within the current scientific and pharmaceutical landscape and made recommendations for the program moving forward.  Recommendations include revising the mission of the ASP to focus on:  disease modification, pharmacoresistant epilepsies, true comorbidities of epilepsy, and more targeted and optimized interventions. 

Dr. David Jett provided Council members with an overview of the NIH CounterACT program, which is a trans-NIH translational research effort to develop the best therapeutics possible for preventing death and injury after chemical emergency events such as terrorist attacks or large scale industrial accidents.  CounterACT is one component of the NIH biodefense program overseen by NIAID that also includes programs focused on biological threats and radiation/nuclear threats.  NINDS manages the chemical component of the biodefense program as so many of the agents of study target the nervous system.  The budget for CounterACT in FY12 is $48M.  The research agenda for CounterACT was established by the 2007 NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Chemical Threats.  Several NIH ICs participate in CounterACT, which supports small R21 grants, SBIR grants, larger milestone-driven cooperative agreements, and contract facilities.  Funded projects are focused on four broad chemical classes and span all phases of therapy development.  Dr. Jett described the RAMPART study, a successful CounterACT partnership between the NIH, DoD, Pfizer, and the University of Michigan testing whether intramuscular midazolam is as effective as IV lorazepam at stopping convulsions prior to arrival at the ED.

Dr. Ranganathan concluded the session by setting the stage for future Council discussions of OTR.  He identified a number of guiding principles for moving the office forward and for thinking about NINDS’s role in therapy development: the need to get therapeutics to humans, the need for partnerships (e.g., between OTR and the Office of Clinical Research, between OTR and biotech, etc.), and the need to adapt to the ever-changing landscape of therapy development.

V.  SPOTRIAS Evaluation Report

SPOTRIAS Evaluation Report
Dr. Ray Dorsey, Associate Professor of Neurology, Johns Hopkins University, reported on a recent evaluation of the NINDS SPOTRIAS program.   The Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network was established in 2001 as a national network of centers aimed to promote new therapeutic approaches for acute stroke.  SPOTRIAS Network seeks to improve stroke outcomes through a comprehensive approach, including: fostering collaboration between emergency medicine and neurology, recruiting and training the next generation of researchers, promoting rapid diagnosis, advancing effective treatment all aimed at reducing disability and mortality in stroke.  Dr. Dorsey reported on the evaluation methodologies and findings for each of the main goals of the SPOTRIAS program, and reported that overall, SPOTRIAS’s greatest successes were in collaborating and training.  In addition, Dr. Dorsey reported on a number of suggestions from SPOTRIAS investigators to improve the program: centralize some functions (e.g., data management) and redefine others (biospecimen repositories), expand number of SPOTRIAS centers, consider inclusion of phase III studies, and improve prioritization of studies going forward.  

Report of the Stroke Research Priorities Meeting—Stroke Planning Phase 2
Council members Drs. Barbara Vickrey and Thomas Brott reported on the second phase of stroke planning by the Stroke Research Priorities Group.  This two phase planning process began in fall 2011, with a review of the work of the Stroke Progress Review Group and culminated with a meeting in August 2012 to identify priority areas in stroke research.  Potential opportunities were identified by the community through an RFI and the final research priorities identified by three workgroups (focused on treatment, prevention, and recovery) through a Delphi process using impact, feasibility and need for NINDS investment as the key prioritization criteria.  The nine research priorities identified are as follows:

• Expand and Improve Existing Stroke Trial Networks to Accelerate Translation
• Preclinical and Clinical Studies to Improve Early Reperfusion Therapy and Establish the Limitations of Late Reperfusion Therapy
• Preclinical and Clinical Studies to Achieve Robust Brain Protection
• Prevention of Vascular Cognitive Impairment
• Imaging Biomarkers in Stroke Prevention: From Bench to Bedside
• Expediting High-Priority Comparative Effectiveness Trials in Stroke Prevention 
• Accelerating the Translation of Stroke Research in Preclinical Animal Models into Clinical Studies of Highly-promising Treatments
• Translational Research Using Neural Interface Devices for Stroke and Other Neurologic Disorders
• Program for Translational Research Targeting Early Recovery After Stroke in Humans

Council voted to accept the draft report.

VI.  Update on the NINDS Workshop on Optimizing the Predictive Value of Preclinical Research

Dr. Shai Silberberg, Program Director, Channels, Systems and Circuits Cluster, reported on a workshop held by NINDS to discuss strategies to optimize the predictive value of preclinical research.  It is becoming increasingly appreciated by the scientific community that many studies cannot be reproduced due to lack of methodological rigor and associated bias.  NINDS has taken a number of actions to improve the review of manuscripts and grants to begin to address some of these issues.  In August 2011, NINDS released a Notice in the NIH Guide (NOT-NS-11-023) encouraging the scientific community to adequately describe in their applications the design, execution and interpretation of the proposed studies as well as in the supporting data.  Concurrently, a list of “points to consider” was generated to help investigators address issues of rigor and bias in the development of their grant applications.  NINDS reviewers have been instructed to pay closer attention to these parameters in their reviews.  In June 2012, the NINDS convened the major stakeholders (e.g., journal editors, funders, reviewers, and investigators) to begin to discuss these issues in the review of manuscripts.  The main recommendations stemming from the workshop have been recently published (Nature 490, 187-191) and include:

• All relevant stakeholders share the responsibility of bringing about meaningful improvement in the quality of reporting.
• Grant applications and scientific publications which include in vivo animal experiments should, at a minimum, report on:
  • Randomization
  • Blinding
  • Sample size estimation
  • Handling of all data
• Clear guidance (e.g., checklist) should be provided to submitters and reviewers
• Increased focus on education and training

VII.  Concept Clearance for FY 2014 Proposed Initiative

Dr. Mona Hicks, Program Director, Repair and Plasticity Cluster, NINDS, requested concept clearance for NINDS to join in a partnership with the Department of Defense, the European Union, and Canada as part of an international initiative for Traumatic Brain Injury, the goal of which is to create a database with detailed high-quality information from 10,000 children and adults with TBI.  It is extremely difficult to get a signal in a clinical trial for TBI due to the extreme heterogeneity of TBI and its pathophysiology.  Each organization proposes to work through their mechanisms to populate the database in a standardized fashion, but will collectively share their data across sites.  NINDS proposes to support a hypothesis driven, high-impact study that will also collect data on 4000 people with TBI for inclusion in this large dataset.  Council voted to approve concept clearance for this initiative.

VIII.  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.

Research Training and Career Development Programs
The Council reviewed a total of 76 research career development and institutional training grant applications; of this total, 69 applications had primary assignment to NINDS, and 42 of them (60.9 percent) were scored in the amount of $5.6 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 $2.0 million (15 grants).

Research Project and Center Awards
The Council reviewed a total of 1,773 research project and center applications; of this total, 1,516 applications had primary assignment to NINDS, and 854 of them (56.3 percent) were scored/percentiled in the amount of $261.6 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 $66.3 million (262 grants).

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, three Javits awards were recommended.

Small Business Innovation Research and Small Technology Transfer Award Programs
The Council reviewed a total of 150 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 130 applications had primary assignment to NINDS and 78 of them (60.0 percent) were scored in the amount of $19.6 million first-year direct costs.  It is anticipated that, of the SBIR and STTR applications competing at this Council, NINDS will be able to pay first-year direct costs of approximately $1.0 million (6 grants

IX.  Adjournment

The meeting was adjourned at 10:40 a.m. on Friday, September 21.

Other Federal employees present for portions of the meeting included:

Dr. Amy Adams, NIDCR
Dr. Nina Silverberg, NIA
Dr. Ann Knebel, NINR
Dr. Lisa Gilotty, NIMH
Dr. Wei-Qin Zhan, CSR
Dr. Gene Carlsea, CSR
Dr. Alexander Yakovlev, CSR
Dr. Laurent Taupenot, CSR
Dr. Vilen Movsesyan, CSR
Dr. Carol Hamelink, CSR
Dr. Nicholas Gaiano, CSR
Dr. Rene Etcheberrigaray, CSR
Dr. Keith Crutcher, CSR
Dr. Peter Guthrie
Dr. Yuan Luo, CSR
Dr. Suzan Nadi, CSR
Dr. Samuel Edwards, CSR
Dr. Biao Tian, CSR

¹For 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.