NINDS Advisory Council Meeting Minutes, September 12-13, 2013

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 12-13, 2013

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 188th meeting on September 12-13, 2013, in Building 45, Conference Room E1/E2, on the National Institutes of Health (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:


September 12, 2013: 8:00 a.m. to 3:45 p.m. for the review and discussion of program development, needs, and policy; and


September 12, 2013: 3:45 p.m. to 4:50 p.m. for the consideration of individual grant applications
September 12, 2013: 4:50 p.m. to 5:45 p.m. for the review of the Board of Scientific Counselors' Reports
September 13, 2013: 8:00 a.m. to 11:00 a.m. for the consideration of individual grant applications.

Council members present were:
Dr. Ben Barres
Dr. E. Antonio Chiocca
Dr. Robert Darnell
Dr. Byron Ford
Dr. David Ginty
Dr. David Goldstein
Mr. Paul Gross
Dr. Sharon Hesterlee
Dr. Eve Marder
Dr. Kevin McNaught
Ms. Ilene Penn Miller
Dr. Jonathan Mink
Dr. Robert Pacifici
Ms. Amy Comstock Rick
Dr. Ralph Sacco
Dr. Amita Sehgal

Council Roster (Attachment 1)

Council members absent:
Dr. David Holtzman
Dr. David Julius

Ex Officio Members present:
Captain Michael Colston, Department of Defense
Dr. Robert Ruff, Department of Veterans Affairs

Members of the public present for portions of the open meeting included:
Dr. Stefano Bertuzzi, American Society for Cell Biology
Mr. Phil Cronin, Francis, Edward, and Cronin, Inc.
Ms. Susan Dickinson, Association for Frontotemporal Degeneration
Ms. Beatriz Duque Long, Epilepsy Foundation of America
Ms. Taryn Gnip, NOVA Research Company
Ms. Barbara Hunt, CADASIL Association
Dr. Tom Jacobs, University of Texas
Dr. Dawn Mancuso, Hydrocephalus Association
Ms. Anne McGuinness, CADASIL Association
Dr. Thomas Montine, University of Washington
Dr. Michael Nunn, The Salk Institute
Ms. Michelle Rodrigues, SRI International
Dr. Nadine Tatton, Association for Frontotemporal Degeneration
Ms. Ashly Westrick, Hydrocephalus Association
Dr. Shimere Williams, Lewis and Burke Associates
Mr. Kevin Wilson, American Society for Cell Biology

Federal attendees are listed at the end of these minutes.

I.  Call to Order and Opening Remarks 

Dr. Story Landis, Director, NINDS, welcomed Council members, visitors, and staff to the 188th meeting of the National Advisory Neurological Disorders and Stroke Council meeting.

Dr. Landis introduced four new Council members:  David Julius, Ph.D., professor and chair of Physiology and Morris Herzstein Endowed Chair in Molecular Biology and Medicine at the University of California, San Francisco; Ilene Penn Miller, J.D., LLM, vice president of Hope for Hypothalamic Hamartomas; Jonathan W. Mink, M.D., Ph.D., chief of Child Neurology, vice chair of Neurology and professor in the Neurology, Neurobiology & Anatomy, Brain & Cognitive Sciences, and Pediatrics Departments at the University of Rochester Medical Center in New York; and Ralph Lewis Sacco, M.D., Olemberg Family Chair in Neurological Disorders, professor and chair of Neurology, and executive director of the Evelyn McKnight Brain Institute at the University of Miami Miller School of Medicine, and chief of Neurology Service at Jackson Memorial Hospital in Miami.

Due to conflicts, Dr. David Julius and Dr. David M. Holtzman were unable to attend this Council meeting.

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

Dr. Robert Finkelstein, Director, Division of Extramural Research (DER), NINDS, introduced Ms. Kelly Baker, who works with Ms. Ruth Linn, Committee Management Officer.

Approval of Council Minutes -- Dr. Finkelstein requested, and the Council voted for, approval of the May 23-24, 2013, Council meeting minutes.

The following future Council meeting dates were confirmed:

January 30-31, 2014
May 29-30, 2014
September 11-12, 2014
February 12-13, 2015     
May 28-29, 2015
September 10-11, 2015

(Thursday and Friday)
(Thursday and Friday)
(Thursday and Friday)
(Thursday and Friday)
(Thursday and Friday)
(Thursday and Friday)

Expedited Review Process – Each Council round, a subset of Council members approve applications in advance of the meeting with scores within the payline for which there are no unresolved issues.  Dr. Finkelstein thanked Byron Ford, David Goldstein, and Amy Comstock Rick for handling this responsibility for fiscal year (FY) 2014.  For the current Council round, 162 applications were eligible to be expedited, including 8 K applications and 1 cooperative agreement.  One hundred twenty six of these awards have already been made, and the others will be issued after Council. 

DER Announcements – Dr. Finkelstein introduced new staff:  Dr. Janet He, Program Director, Systems and Cognitive Neuroscience Cluster; Dr. Jim Koenig, Program Director, Neural Environment Cluster; Dr. Karen David, Program Analyst, Systems and Cognitive Neuroscience Cluster; and Dr. Letitia Weigand, Program Analyst, Office of Training, Career Development, and Workforce Diversity.

OTR Announcements – Dr. Rajesh Ranganathan, Director, Office of Translational Research (OTR), introduced three new members of the Office:  Shalini Sharma, a chemist supporting the Anticonvulsant Screening Program; Dr. Hao Wang, Program Director, who will oversee OTR’s cooperative agreement (U01) and translational R21 grant portfolios; and Dr. Pat Walicke, Medical Officer.  Next, he announced the retirement of Ms. Liz Geiger, a program support assistant who is retiring after 38 years of government service.

OCR Announcements – Dr. Petra Kaufmann, Director, Office of Clinical Research (OCR), introduced Joanna Vivalda, a clinical trials specialist.

III.  Report of the Director, NINDS

Advances in the Past Year – Dr. Landis reported a number of major NINDS research advances that occurred during the past year.  NeuroNEXT (Network for Excellence in Neuroscience Clinical Trials) is currently running with three Phase II trials: Spinal Muscular Atrophy (SMA) Biomarkers in the Immediate Postnatal Period of Development; A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Activity of Ibudilast (MN-166) in Subjects with Progressive Multiple Sclerosis; and A Phase II Trial of Rituximab in Myasthenia Gravis.  The Network was created to conduct studies of treatments for neurological diseases through partnerships with academia, private foundations, and industry.  NeuroNEXT is designed to expand the capability of NINDS to respond quickly to new opportunities to test promising new treatments for neurological disorders, and to increase the efficiency of clinical trials before embarking on larger studies.  A program modeled after NeuroNEXT is being established in the next year to perform phase II and III trials in stroke prevention, treatment, and rehabilitation.

Dr. Landis reported on the completion of two NINDS-supported clinical trials, ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) and IMS3 (Interventional Management of Stroke Trial 3), whose results should influence clinical practice.  Another trial, LS1 Study of Creatine for Treatment of Early-stage Parkinson’s Disease, was closed due to futility; longer patient follow-up was not likely to demonstrate a statistically significant difference between creatine and placebo.  This study was able to recruit and follow over 1,500 patients over a course of five years without any significant loss of the patient population.

Council member Dr. David Goldstein and his research team discovered de novo mutations that cause epileptic encephalopathies identified in six genes via exome sequencing, suggesting specific biological pathways.

The Porter Neuroscience Center is a 600,000-square-foot biomedical research building devoted to brain sciences.  Phase I of the construction, which represents approximately 45 percent of the facility, was completed in 2004 and is now fully occupied by a variety of scientists from different Institutes, working in collaboration in an array of research laboratories, animal care facilities, imaging suites, offices, and associated support facilities.  Phase 2, which was made possible by special American Recovery and Reinvestment Act (ARRA) funds, is opening in October 2013 with a symposium and dedication.  Eighty-five investigators from ten Institutes will occupy the completed space.

The Human Connectome Project (HCP) is an approximately $40 million NIH Blueprint effort to map the neural pathways that underlie human brain function.  The NIH Blueprint for Neuroscience Research is a cooperative effort among the 15 NIH Institutes, Centers, and Offices that support neuroscience research.  One piece of the project, run by Harvard/Massachusetts General Hospital and the University of California, Los Angeles, is focused on the development of advanced technology for diffusion magnetic resonance imaging (MRI) for the collection of in vivo structural connectivity data.  The other focus of the project is to create an imaging database of human connectomes from 1,200 normal young adults.  Washington University in St. Louis and the University of Minnesota are studying twins and their non-twin siblings to characterize the variability of adult human brain circuitry, and its relation to behavior and genetics.

NIH Budget – Dr. Landis reported on the status of the NIH and NINDS budgets for FY2013 and FY2014.  From 1995 to 2003, the NINDS extramural grants budget steadily increased, but has since remained flat and decreased, for the first time, in 2013.  In FY13, the NINDS budget was 5.7% less than FY12 due to a 5% budget cut resulting from the sequester, passed as part of the Budget Control Act of 2011 (P.L. 112-25) and a 0.7% budget cut resulting from transfers to the Department of Health and Human Services.  The NIH Budget as a whole was reduced by about $1.7B and that of the NINDS by about $92M.  To implement these cuts, individual Institutes and Centers were encouraged by the NIH Office of the Director to develop their own plans to balance cuts across Extramural, and Intramural.  In response to these cuts, NINDS cut 3.5% from RPG non-competing grants, the Division of Intramural Research, and Research Management and Support (RMS).  Despite these cuts, NINDS will maintain commitments to training and career awards and will pay grants to the 14th percentile, due to increased efficiencies in clinical trials, program closures, and grant turnover.  Dr. Landis noted that some of the consequences of sequestration include cuts to ongoing projects, fewer new projects funded, and the potential for young investigators to be discouraged from careers in research.

The FY2014 budget has not yet been set.  Congress may pass a Continuing Resolution (CR) to fund the government until December; however, if a CR for FY2014 is not passed by October 1, 2013, the government will shut down.  If there is a CR, the NIH budget will be cut an additional 2 percent from FY2013.  As in years past, noncompeting Type 5 grants will be awarded at 90 percent of the awarded level until a budget is issued.  The FY2015 budget is in preparation, despite there currently being no FY2014 budget.

NINDS Planning Efforts 
Alzheimer’s disease-related dementias:  NINDS has collaborated with the National Institute on Aging (NIA) to develop plans for Alzheimer’s disease-related dementias (ADRD).  The NINDS Council will provide input on the Alzheimer’s disease-related dementias report, which then will go to the National Alzheimer's Project Act (NAPA) Advisory Council on Alzheimer's Research, Care and Services for feedback and approval of recommendations.  Recommendations from the ADRD meeting will be discussed later in the day.

Parkinson’s disease: Under the Morris K. Udall Parkinson’s Disease Research Act of 1997, NIH is required to conduct a planning effort for Parkinson’s disease (PD) every two years.  NINDS has run two very large planning efforts since the legislation was enacted (in 2002 and 2006), and in the intervening years has run smaller, more focused efforts (e.g. on biomarkers for PD).  In January 2014, NINDS will host a third large-scale planning effort to look at PD in a more holistic fashion as the field has evolved significantly since 2006.  Recommendations emerging from this effort will be presented at the February 2014 NANDS Council meeting.

Muscular Dystrophy: A muscular dystrophy planning effort is about to begin that will be coordinated by NINDS, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung, and Blood Institute (NHLBI). Recommendations emerging from this planning effort will be presented to the Muscular Dystrophy Coordinating Committee in FY14.

The BRAIN Initiative – President Obama announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative on April 2.  The goals of the initiative are to: accelerate development and application of innovative technologies to construct a dynamic picture of brain function that integrates neuronal and circuit activity over time and space; build on the growing scientific foundation—neuroscience, genetics, physics, engineering, informatics, nanoscience, chemistry, mathematics, etc.—to catalyze an interdisciplinary effort of unprecedented scope; and provide tools to enhance many areas of research and methods for deeper understanding of all brain disorders.  Three government agencies—NIH, the Defense Advanced Research Projects Agency (DARPA), and the National Science Foundation—committed over $100 million in funding in FY2014 to support this effort.  A number of private organizations also have launched major initiatives in brain sciences.  The Simmons Foundation will soon launch a global brain initiative.  The pharmaceutical industry, device companies, and information technology (IT) companies (e.g., Google) have expressed interest in participating in the BRAIN initiative.

NIH Director Dr. Francis Collins has established the BRAIN Working Group of the Advisory Committee to the Director (ACD), comprising 15 leading neuroscientists, to lead the initiative at NIH.  Members were selected for their visionary leadership and expertise and were charged with articulating scientific goals and developing a plan, including timetables, milestones, and costs.  The BRAIN Working Group will seek broad input by holding open meetings and workshops.  The Working Group has held four two-day conferences since announcement of the initiative: May 29-30 in San Francisco, CA on Molecular Approaches; June 26-27 in New York, NY on Large-scale Recording Technologies and Structural Neurobiology; July 29-30 in Boston, MA on Computation, Theory, and Big Data; and August 29-30 in Minneapolis, MN on Human Neuroscience.

An interim report on high-priority areas for FY2014 funding will be delivered on September 16 during an ACD conference call.  A final report will be presented to the ACD in June 2014.  If the ACD endorses the interim report and Dr. Collins accepts it, the NIH Blueprint for Neuroscience Research then will be charged with developing an implementation plan for FY2014 initiatives.  NIH set aside $40 million for BRAIN in FY2014 allocated from a number of different sources:  NIH Blueprint - $10 million; Office of the Director - $10 million; NINDS - $7.5 million; National Institute of Mental Health - $7.5 million; National Institute on Drug Abuse - $4 million; and National Institute of Biomedical Imaging and Bioengineering - $1 million.  BRAIN efforts will be coordinated between current federal and private foundation partners.  Additional partners, including other foundations and device, pharmaceutical, and IT companies will be engaged.

IV.  NINDS Strategies to Enhance Diversity of Neuroscience Researchers

Dr. Michelle Jones-London, Program Director, Office of Training, Career Development, and Workforce Diversity, NINDS, reported on strategies to enhance the diversity of neuroscience researchers.

NINDS Diversity Scientific Training and Career Opportunities – NINDS diversity scientific training and career opportunities span the career stages from high school to the postdoctoral phase and new faculty.  NINDS provides individual awards including the NIH F31: Predoctoral Fellowship to Promote Diversity, NINDS K22: Postdoc to Faculty Transition Award, and the NINDS K01: Career Development Award for New Tenure Track Faculty. In addition, the Institute supports institutional awards, including:  T32: Institutional Research Training Grant NIH Blueprint R25 which pairs diverse undergraduate students with neuroscience-focused T32 programs and the NINDS R25: Neuroscience Development for Advancing the Careers of a Diverse Research Workforce which supports educational programs designed to attract, train, and further the careers of diverse graduate, postdoctoral, and junior faculty.

NINDS Research Supplements to Promote Diversity in Health-related Research – NINDS provides Research Supplements to Promote Diversity in Health-related Research the goal of which is to increase opportunities for diverse individuals to work in NIH-funded laboratories.  These are “bridge funds” that are awarded for two to three years and provide protected time for a trainee to develop his/her own research skills, preliminary data and publications, and other elements necessary  to develop an application for an individual NIH application.  An applicant’s transition and mentoring plan is included in the specific terms and conditions of the award.

NINDS has been consistently committed to providing funding for this program over the past five years.  In FY2012, NINDS received 55 applications for diversity supplements and awarded 38 (69%) of these applications.  This award rate is in line with the average diversity supplement award rate (68%) for all NIH Institutes and Centers (ICs).  The majority of NINDS diversity supplement supportees are predoctoral students followed by postdocs.  The two ethnic groups that receive the highest numbers of supplements are Blacks and Hispanics.

Dr. Jones-London addressed several questions that arose at the May 2013 Council meeting regarding the return on investment of this program.   Between 2006 and 2011, 255 diversity supplement applications were received, of which 71 percent (181) were awarded funding.  Awardees represented 89 different universities or institutions.  Fifty-eight percent of the awardees were female; 42 percent of awardees were male.  At the time the supplement was awarded, 9 percent of awardees were undergraduate students and 9 percent were at the postbaccalaureate level.  For FY2002-2012, 53 percent of undergraduate awardees entered or completed an advanced degree program: 16 in PhD programs; 1 in an MD/PhD program; and 15 in medical schools/residencies. For the same fiscal years, 50 percent of postbaccalaureate awardees entered or completed advanced degree programs: 12 in PhD programs; 3 in MD/PhD programs; and 6 in medical schools/residencies.

There were 81 graduate student awardees in FY2006-2011. Currently, 60 of those awardees remain in academia; 9, in industry; 11, in medicine; 17, in postdoc positions, and 36, in graduate schools.  From this group, there have been 46 applications for F31 awards and 24 awardees (52% success rate).  Sixty-three percent of the awardees who have remained in academia have published research papers in the past two years.  From FY2006 to FY2011, 49 awardees were at the postdoc level. Thirty-eight of those individuals remain in academia. There have been 42 NIH grant applications submitted from this group (23 F32s, 13 K awards, 6 R awards); 15 of these applicants have received funding.  Seventy-nine percent of the individuals who have remained in academia have published research papers in the past two years.

From these findings, Dr. Jones-London concluded that a majority of diversity supplement recipients from all career stages (91%) in this cohort remain in some area of the biomedical enterprise.  In addition, the program appears to act as a feeder to individual training awards, with a trend of higher success rates for diversity supplement F and K awardees.  

K22 and K01 Diversity Career Development Awards – NINDS recently released two new diversity career development awards: the K22 and K01.  The goal of these awards is to retain those individuals already trained in neuroscience and provide the resources and tools needed for the transition to independence.  The K22 award is for advanced postdoctoral fellows with two to five years of postdoctoral experience, and includes two phases.  Phase I is a two- to three-year mentored phase providing salary up to $50,000 and research costs up to $25,000.  Phase II provides two to three years of support (salary up to $85,000 and research costs up to $100,000) and is contingent on obtaining a tenure-track or equivalent position.  The K01 award is for junior faculty with three or less years of experience in the first faculty tenure-track position or equivalent.  This award provides three years of total support with salary up to $85,000 and research costs up to $100,000.

Neuroscience Scholars Program – NINDS has supported the R25 Neuroscience Scholars Program (NSP) at the Society for Neuroscience (SfN) for over 30 years.  This program is a three-year fellowship to enhance career development and professional networking opportunities for underrepresented and diverse undergraduate students, graduate students, and postdoctoral fellows in neuroscience.  Each year of the fellowship, scholars are provided with a stipend for career enrichment activities and access to career-enhancing networking and mentoring opportunities.  Of the scholars who received support in 2002-2008, 88 percent now work in academic institutions and 6 percent, in government or industry.  Sixty percent submitted at least three peer-reviewed journal articles during a five-year period after the fellowship.  Eighty-three percent of past scholars have submitted at least one grant application, and 84 percent have received at least one competitive neuroscience grant.

V.  Report from the Alzheimer’s Disease-Related Dementias Conference

Dr. Thomas Montine, Alvord Professor and Chair, Director of Neuropathology, University of Washington, presented the report and recommendations from the NINDS-led Alzheimer’s Disease-related Dementias conference in 2013.

Background – The National Alzheimer’s Project Act (P.L. 111-375) was signed into law by President Obama on January 4, 2011.  The Act calls for a national plan to address Alzheimer’s disease, with the goal of preventing and effectively treating the disease, including Alzheimer’s disease-related dementias (ADRD), by 2025.  NIA led the Alzheimer’s Disease Research Summit 2012: Path to Treatment and Prevention, and NINDS led the Alzheimer’s Disease-Related Dementias: Research Challenges and Opportunities in May 2013.

The Alzheimer’s Disease-related Dementias Steering Committee was formed in September 2012 with preconference work spanning from October 2012 to April 2013.  The conference was held May 1-2, 2013, and was followed by postconference work through July 2013.  The draft report was first circulated in August 2013 and is being presented to the Council today. If approved, it will be presented to the NAPA Council in October 2013.

Conference – The ADRD Steering Committee convened groups of international experts from academia, industry, and NIH to address five topics: Multiple Etiology Dementias and Health Disparities (both overarching for the National Plan), and Lewy Body Diseases, Vascular Brain Injury in the Context of ADRD, and Frontotemporal Dementias & Other Tauopathies (all ADRD-specific).  The charge of each topic-specific committee was to develop up to eight prioritized research recommendations with approximate timelines for completion or full implementation.  Early on, the Steering Committee recognized that there would be overlap in recommendations in each of the five topic areas.  The preconference work concluded with posting and distributing the prioritized research recommendations prior to the conference.

Dr. Montine shared the thoughts of ADRD Steering Committee member Dr. David Holtzman, who was unable to attend today’s Council meeting.  Dr. Holtzman broadly agrees with the ADRD research recommendations but takes specific exception to the relative priority of some of the recommendations.  The Steering Committee sought consensus among almost 80 scientists with representation from different research areas.

The ADRD Conference was sponsored by NINDS with strong participation by NIA, the Alliance for Aging Research, the Alzheimer’s Association, the Association for Frontotemporal Degeneration, and USAgainst Alzheimer’s.  Each topic area committee was charged with presenting a summary of its research recommendations and rationale for prioritized recommendations and timelines.  The goal of the conference was to provoke discussion among group experts and solicit feedback and opinions from the audience.  There were 567 conference registrants: 322 attended in-person and over 200 participated online.  It was a lively two-day public discussion culminating in an “open mike” session and review of all suggested recommendation revisions.  

The topic-specific committees revised research recommendations, prioritization, and timelines based on discussion and feedback from the conference.   A “sign-off” conference call was conducted with the topic chairs in July.  The Steering Committee then drafted the report, circulated it to the topic chairs for feedback, made revisions, and recirculated the report.  Last week, a conference call was held with ADRD Steering Committee members and NINDS leadership to discuss the report.

Recommendations – Research recommendations were prioritized based on advancing scientific discovery needed to achieve the NAPA goal of prevention or effective intervention for ADRD by 2025.  Each topic committee reached consensus on priority after long deliberation.  The timelines for the research recommendations are independent of priority; the timelines are estimates of the interval from the present time to anticipated completion or full implementation of the recommendations.

High-priority/short-term recommendations by topic area include:

  • Multiple Etiology Dementias
    Differential Diagnosis: Develop clinical algorithms for detection of prototypical neurodegenerative dementias.
    Epidemiology: Conduct population-based studies of prevalence and incidence in diverse ethnic groups and age ranges.
  • Lewy Body Dementias
    Establish longitudinal cohorts with common measures.
  • FTD and Other Tauopathies
    Clinical Science: Expand efforts to genotype patients with FTD to identify new genetic risks.
  • Vascular Brain Injury in the Context of ADRD
    Clinical-based Studies: Develop noninvasive markers key to vascular processes related to cognitive impairment.

High-priority/longer-term recommendations by topic area include:

  • Health Disparities
    Recruitment: Initiate and leverage ongoing longitudinal community-based cohort studies of incident dementia in diverse populations using a variety of tools.
    Treatment and Prevention: Enhance the design of all trials of vascular health interventions to improve their application to diverse populations.
  • FTD and Other Tauopathies
    Basic Science: Clarify the mechanisms of tauopathogenesis.
  • Vascular Brain Injury in the Context of ADRD
    Basic Science: Develop next-generation experimental models.
    Clinical-based Studies: In human studies, validate noninvasive markers of vascular injury in the context of cognitive impairment.

Dr. Montine also reviewed the short- and longer-term intermediate and additional priorities identified by the ADRD Steering Committee.  Although the ordering of priorities and timelines differ, several recommendations apply across ADRD (and AD):

  • Fundamental research to fill critical knowledge gaps
  • Training and education to ensure durable progress
  • Improved diagnostics
  • Optimized repositories
  • All recommendations within the Health Disparities topic
  • Culmination of research in effective interventions.

Dr. Montine concluded his presentation by summarizing the accomplishments of the ADRD Steering Committee.

Approval of Alzheimer’s Disease-related Dementias Report – Dr. Finkelstein requested, and the Council voted approval for, with 2 abstentions, the ADRD report with a one-page summary of the Council’s comments.

VI.  Promoting Rigor and Reproducibility – An Update

Dr. Shai Silberberg, Program Director, Channels, Synapses, and Circuits Cluster, NINDS, provided an update on the efforts of NINDS and NIH to promote rigor and reproducibility in research findings.

Background – A number of publications in recent years have suggested that the inability to reproduce key research findings is due to a lack of transparency in reporting, chance observations, and associated bias.

Actions Taken by NINDS – In response to these findings, NINDS has been working to improve the quality of NINDS-supported preclinical and clinical research through a number of actions.  A notice  was published in the NIH Guide (NOT-NS-11-023), Improving the Quality of NINDS-supported Preclinical and Clinical Research through Rigorous Study Design and Transparent Reporting, that encouraged investigators to adequately describe in their applications the design, execution, and analysis of the research they are proposing to conduct and of the data they are using in support of their applications.  In addition, the NINDS made changes to its in-house review of applications.  Applications selected for a full discussion by NSD-K are now evaluated with added focus on the scientific rationale/premise of the study.  A modified critique template for the Translational U01 review is intended to evaluate whether the data used in support of the application are from rigorously designed experiments and whether the proposed experiments are designed using rigorous methodological approaches to minimize potential bias.  

On June 20-21, 2012, NINDS held a workshop, Optimizing the Predictive Value of Preclinical Research, which brought together editors from high-profile scientific journals, representatives from funding organizations, and prominent reviewers and investigators.  Major recommendations resulting from workshop discussions 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, and handling of all data.
  • Clear guidance (e.g., checklist) should be provided to submitters and reviewers.
  • Education and training are needed.

A report from this workshop, A Call for Transparent Reporting to Optimize the Predictive Value of Preclinical Research, was published in Nature(490; 187–191).

Response to Recommendations – In response to the workshop report recommendations, Nature Publishing Group released new publication guidelines stating that they will more systematically ensure that key methodological details are reported, give more space to the methods sections, examine statistics more closely, and encourage authors to be transparent (e.g., by including their raw data).  Science Translational Medicine soon followed suit by releasing revised standards for the reporting of experimental design and statistics in their research articles (Sci Transl Med; 5(190); 1-2).  

NIH Initiative to Enhance Reproducibility and Transparency of Research Findings – Dr. Francis Collins, Director, NIH created an ad hoc committee to evaluate what could be done across NIH to increase the reproducibility and transparency of research findings.  This committee made a number of recommendations which were presented to Dr. Collins and subsequently to the Institute and Center Directors.  Following feedback from the Directors, final recommendations were developed.
Three underlying issues were identified as contributors to the lack of reproducibility of research findings: poor training, poor evaluation, and perverse reward incentives.  To guide the recommendations of the Committee, five principles were identified:

  1. Raise community awareness
  2. Enhance formal training
  3. Improve the evaluation of applications
  4. Protect the integrity of science by adopting more systematic review processes
  5. Increase stability for investigators

The following recommendations and action items emerged from the Committee:

Recommendation 1: Encourage ICs to discuss the issue with Advisory Councils and Boards of Scientific Counselors and/or hold workshops to signal attention to the issue of reproducibility to stakeholder communities.  
Recommendation 2: Integrate modules and/or courses on experimental design into existing required training courses and award terms and conditions.  The Office of Intramural Research was charged with piloting a module on research integrity that could be added to the ethics training course required for NIH intramural fellows.  Following this pilot, the Office of Extramural Research will make the module available to the Extramural community and encourage its adoption by Institutional training programs.
Recommendation 3: Consider options for an evaluation process of the “scientific premise” of a grant application.  Select ICs will perform pilot evaluations of this recommendation.  
Recommendation 4: Collaborate further with scientific journals and the scientific community on efforts to improve rigor.  As part of this effort, the NIH will evaluate the PubMed Commons pilot, which allows scientists to post comments on original research articles.
Recommendation 5:  Adapt the NIH biosketch to allow investigators to place their work into a functional context.  Select ICs, primarily the National Cancer Institute (NCI), will perform pilot evaluations of changes to the biosketch to include elements that aid in framing the Principal Investigator’s (PIs) work and describing the applicant’s contribution to the publications cited.  NCI also recently adopted an Outstanding Investigator Award to address perverse incentives by providing substantial longer-term support to experienced investigators.  Additional suggestions were to consider the use of guidelines and/or checklists to systematically evaluate grant applications and consider the advisability and approach to supporting replication/reproducibility studies or centers.  Ongoing pilot efforts by the NINDS and the NIA to replicate preclinical findings will be evaluated.  

The NINDS pilot study, Independent Replication of Promising Animal Model Results, was designed to evaluate the need, feasibility, costs, and roadblocks to independent replication.  Three recently funded translational U01s of drugs that exhibited robust effects in rodents were selected for replication in the pilot.  A number of challenges emerged during this pilot, including the long duration for completion of the studies (29-38 months), partial completion of the proposed experiments, and questionable quality of some replication experiments.  In addition, the pilot revealed that a majority of behavioral outcome studies did not replicate.

VII. Concept Clearance for FY2014 Proposed Initiatives

Dr. Beth-Anne Sieber, Program Director, Neurodegeneration Cluster, NINDS, requested concept clearance for NINDS to solicit exploratory grant (P20) applications intended to support planning for and initiation of collaborative activities to advance Parkinson’s disease research.  The goal of the proposed program is to formalize collaborative structures and establish a foundation of research discovery that would lead to a subsequent application for an NINDS Morris K. Udall Center of Excellence (P50).  Use of the P20 mechanism to encourage the establishment of new teams to pursue innovative PD research originated from NINDS discussions on ways to strengthen the Udall Centers program.  NINDS recently used a similar strategy to promote collaboration and Center development in epilepsy research.  The Council voted to approve concept clearance for this initiative.

Dr. Mona Hicks, Program Director, Repair & Plasticity Cluster, NINDS, requested concept clearance for NINDS to support multidisciplinary investigators to detect, define, and clinically characterize the progression of repetitive traumatic brain injury (TBI)-related neurodegeneration in at-risk middle-aged former athletes or others with a history of repetitive head impacts.  The concept for this prospective observational study came from a workshop convened by NINDS and through discussions with the Foundation for NIH (FNIH) Sports Health Research Program.  The study will be funded by the FNIH.  This request for applications will provide a foundation for future studies aimed at developing tools to detect chronic traumatic encephalopathy and types of repetitive TBI-related neurodegeneration in younger individuals.  The Council voted to approve concept clearance for this initiative.

Dr. Avindra Nath, Intramural Clinical Director, NINDS, requested concept clearance for creation of a K22 Career Transition Award for NINDS intramural clinical fellows.  The intramural NINDS program has 15-20 clinical fellows in various stages of training, with about 3-5 new fellows each year.  Since the clinical fellows have NIH appointments, they are not eligible to apply for K08 or K23 Career Development Awards.  The proposed K22 award would have two phases.  Awardees would spend the first two years in the intramural program as fellows.  The second, three-year phase would require a tenure-track position at an extramural institution with 75 percent protected time for neurologists and 50 percent for neurosurgeons.  Applications would be reviewed by the NINDS study section (NST-1) that reviews similar career awards.  The Council voted to approve concept clearance for this initiative.

VIII.  Presentations by the Division of Intramural Research, NINDS

Impact of Sequester on NINDS Intramural Budget – Dr. Alan Koretsky, Scientific Director, NINDS, presented an overview of the Intramural Research Program (IRP) and the impact of sequestration.  The NINDS IRP is 63 years old and has focused on basic neuroscience and patient-based research and intervention from its start.  It houses neuroscience, neurology, and neurosurgery under one administrative structure.  Dr. Koretsky noted the quality of the intramural program’s review, the large number and high quality of PIs, and the large number and quality of facilities.  Currently, the NINDS IRP supports 49 PIs: 36 tenured PIs; 11 on tenure track; and 2 investigators with independent resources.  There are about 50 staff scientists and clinicians and about 250 fellows.  Active training is provided at all career stages.  The IRP is conducting approximately 130 clinical protocols and 90 animal protocols.  About 300 papers are published per year with 10 percent in the highest-impact journals. The IRP has 16 active CRADAs with industry and approximately 70 patents in process.

Prior to FY2013, NINDS experienced four years of a flat budget, but with rising costs.  NINDS noticed the limiting trend of the budget early and took aggressive approaches to find efficiencies.  Prior to sequestration, no cuts were made to PIs in the IRP.  The sequester means a 3.5 percent cut in the total FY2013 budget, and due to fixed costs, this results in about an 8 percent cut to the science.  In FY2012, the budget of NINDS was about $157 million.  Central NIH costs and salaries that cannot be cut account for $93 million of the budget, which leaves the remaining $64 million to absorb the $5 million sequester cut.  Flexibilities allow these cuts to occur over FY2013 and FY2014.  The total FY2013 NINDS budget is $152 million: $53 million to central costs; $23 million to administrative costs; and $76 million for science and support.  In FY2013, tenured PIs took a 4.4 percent across-the-board cut, and administration took a 4.4 percent cut on operating costs.  In FY2014, administration will try to take a 4.4 percent cut to its total budget, NINDS will try to find efficiencies in science (e.g., possibly close the DNA facility), and there may be across-the-board or targeted cuts to PIs.

Scientific Presentation: Development of Large Scale Optical and Electron Microscopy to Study the Neural Basis of Behavior – Dr. Kevin Briggman, Investigator, Circuit Dynamics and Connectivity Unit, NINDS, presented an overview of the research conducted in his laboratory to develop large-scale optical and electron microscopy-based methods to functionally and structurally map neuronal circuits in the central nervous systems of mice and fish.  The long term goal of the lab is to build computational models of visual-guided behaviors in vertebrate brains. The data needed to develop accurate models critically depends on the ability to record whole-brain functional and anatomical data. Dr. Briggman described initial efforts to develop such technology to non-invasively record from larval zebrafish, a model organism for the study of the neural basis of behavior and disease. The lab has constructed a light-sheet microscope to record from nearly all neurons in the zebrafish brain approximately once per second while the fish is in a virtual reality environment and is able to react to visual stimuli. In parallel, a novel ultramicrotome was developed to automate the collection of 3D electron microscopy data. This microtome is being used within a scanning electron microscope to section a complete zebrafish brain at nanometer resolution. These two technologies will be combined to integrate the study of the function and structure in a vertebrate brain, addressing such questions as how fish initially recognize and subsequently hunt prey-like stimuli and the degree to which structure predicts function in the central nervous system.

IX.  Review of the Division of Intramural Research Board of Scientific Counselors’ Reports         

In the closed session, Dr. Koretsky presented the findings and recommendations of the Board of Scientific Counselors based on their review of specific Division of Intramural Research laboratories/units during 2012.  The Council discussed the reports of the Board and accepted them.

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 requiring specific discussion.  Prior to discussion of the grants, Dr. Finkelstein reminded Council members regarding conflict of interest and confidentiality.

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, Council Executive Secretary, who will then refer the question to the appropriate staff member for response. 

Research Training and Career Development Programs – The Council reviewed a total of 310 research career development and institutional training grant applications; of this total, 303 applications had primary assignment to NINDS, and 176 of them (56.7 percent) were scored in the amount of $7.3 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 $4.7 million (71 grants).

Research Project and Center Awards – The Council reviewed a total of 2,417 research project and center applications; of this total, 1,920 applications had primary assignment to NINDS, and 969 of them (40 percent) were scored/percentiled in the amount of $336.6 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 $109.5 million (299 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 Business Technology Transfer Award Programs – The Council reviewed a total of 136 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 134 applications had primary assignment to NINDS and 77 of them (57.1 percent) were scored in the amount of $18 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 million (10 grants).

IX.  Adjournment

The meeting was adjourned at 11:00 a.m. on Friday, September 13.

NINDS employees present for portions of the meeting included:

NINDS employees present for portions of the meeting included:

Dr. Alan Willard
Ms. Ruth Linn
Dr. Scott Janis
Dr. Deborah Hirtz
Ms. Nena Wells
Dr. Story Landis
Dr. Yuan Liu
Dr. Ernie Lyons
Dr. Robert Finkelstein
Dr. John Porter
Dr. David Owens
Dr. Jane Fountain
Dr. Beth-Anne Sieber
Dr. May Wong
Dr. Stephen Korn
Dr. Tracy Chen
Ms. Shannon Garnett
Mr. Ken Frushour
Dr. Heather Rieff
Dr. Linda McGavern
Dr. Claudia Moy
Dr. Paul Scott
Dr. Robert Zalutsky
Dr. Laura Mamounas
Dr. Courtney Ferrell Aklin
Dr. Amelie Gubitz
Ms. Louise Ritz
Dr. Crina Frincu
Dr. Birgit Neuhuber
Dr. Alfred Gordon
Dr. David Yeung
Dr. Chuck Cywin
Dr. Rajesh Ranganathan
Dr. Martin Mendoza
Dr. Ipolia Ramadan
Dr. Timothy LaVaute
Dr. Ursula Utz
Dr. Elizabeth Webber
Dr. Audrey Penn
Dr. JoAnn McConnell
Dr. Yolanda Vallejo
Dr. Margaret Ochocinska
Dr. Amir Tamiz
Dr. Katie Pahigiannis
Ms. Adrienne Ivory
Dr. Patrick Hussmann
Dr. Vicky Whittemore
Ms. Joanne Odenkirchen
Ms. Barbara McMakin
Dr. Karen David
Dr. Debra Bergstrom
Dr. Cheryse Sankar
Dr. Andrew Skinner
Ms. Marilyn Johnson
Ms. Lisa Joliet
Dr. Andrey Kuzmichev
Dr. Letitia Weigand
Ms. Amanda Sibley
Dr. Daofen Chen
Dr. Randall Stewart
Dr. Shanta Rajaram
Dr. Shai Silberberg
Dr. Ramona Hicks
Dr. Debra Babcock
Ms. Pamela Mayer
Dr. Walter Koroshetz
Ms. Tijuanna Decoster
Dr. Cara Long
Dr. Anna Taylor
Ms. Kelly Baker
Dr. Rebecca Farkas
Ms. Quynh Ly
Dr. Jim Gnadt
Dr. Salina Waddy
Dr. Christine Torborg
Dr. Roderick Corriveau
Dr. Michelle Jones-London
Dr. Katrina Gwinn
Dr. Ran Zhang
Dr. Yejun He
Dr. Coryse St. Hillaire-Clarke
Dr. Francesca Bosetti
Dr. Kip Ludwig
Dr. Jill Morris
Ms. Jamie Roberts
Ms. Christina Vert
Dr. Natalia Strunnikova
Dr. Petra Kaufmann
Dr. William Benzing
Dr. Margaret Sutherland
Ms. Marian Emr
Dr. David Jett
Dr. Ned Talley
Mr. Taek Oh
Mr. Philip Wiethorn
Ms. Nancy Hart
Dr. D. Elizabeth McNeil
Dr. Pamela Wernett
Dr. Wendy Galpern
Mr. Paul Girolami
Ms. Karin French
Dr. John Kehne
Ms. Margo Warren
Dr. Raul Saavedra
Dr. Robert Riddle
Ms. Maureen Hambrecht
Ms. Christine Lam
Dr. Brandy Fureman
Ms. Shalini Sharma
Ms. Liz Geiger
Dr. Hao Wang
Dr. Pat Walicke
Dr. Jim Koenig
Ms. Stacey Chambers
Dr. Rebecca Roof
Ms. Stephanie Fertig

Other Federal employees present for portions of the meeting included:

Ms. Tara Schwetz, OD
Dr. David Shurtleff, NCCAM
Dr. Creighton Phelps, NIA
Mr. Dever Powell, OD
Dr. Amy Adams, NIDCR
Dr. Wei-Qin Zhan, CSR
Dr. Laurent Taupenot, CSR
Dr. Sharon Low, CSR
Dr. Suzan Nadi, CSR
Dr. Cristina Backman, CSR
Dr. Peter Guthrie, CSR
Dr. Heidi Friedman, CSR
Dr. Geoffrey Schofield, CSR
Dr. Rene Etcheberrigaray, CSR
Dr. Carole Jelsema, CSR

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

Robert Finkelstein, Ph.D.
Executive Secretary
National Advisory Neurological Disorders and Stroke Council

Director, Division of Extramural Research
National Institute of Neurological Disorders and Stroke

Story C. Landis, Ph.D.
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.

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.