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National Advisory Neurological Disorders and Stroke Council
Summary of Meeting
January 31-February 1, 2013
The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 186th meeting on January 31-February 1, 2013, 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)
Ex Officio Members absent:
Dr. Robert Ruff, Department of Veterans Affairs
Captain Michael Colston, Department of Defense
Members of the public present for portions of the open meeting included:
Mr. Ronald Bartek, Friedreich's Ataxia Research Alliance
Dr. Dawn Mancuso, Hydrocephalus Association
Ms. Ashly Westrick, Hydrocephalus Association
Dr. Andrea Baruchin, Foundation for the NIH
Dr. Shimere Williams, Lewis and Burke Associates
Dr. Naomi Kleitman, Craig H. Neilson Foundation
Ms. Michelle Rodrigues, SRI International
Tracy Casteuble, Epilepsy Foundation
Claudia Louis, American Heart Association
Dr. Rebecca Oberman, Mucolipidosis Type IV (ML4) Foundation
Dr. Chris Carter, Society for Research on Women’s Health
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 186th meeting of the National Advisory Neurological Disorders and Stroke Council meeting.
Dr. Landis introduced new Council member Amy Comstock Rick who was unable to attend the September 2012 meeting. Ms. Rick is Chief Executive Officer of the Parkinson’s Action Network, a 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.
Dr. Robert Ruff, ex officio member from the Department of Veterans Affairs, could not attend this meeting. The Department of Defense recently identified Captain Michael Colston as a new ex officio member on Council. Captain Colston is Director, Mental Health Program, Clinical and Program Policy, Office of the Assistant Secretary of Defense (Health Affairs). Due to the late notice of his appointment, Captain Colston was unable to attend this meeting.
Next, Dr. Landis introduced new staff within the NINDS Office of the Director: Dr. Linda Porter was appointed as the Pain Health Science Policy Advisor and serves as the Designated Federal Official for the Interagency Pain Research Coordinating Committee; Dr. Cheryse Sankar, is a Health Program Specialist working with Dr. Porter; and Dr. Chris Thomas and Ms. Kathryn DeMott are science writers in the NINDS Office of Communication and Public Liaison.
II. Report of the Associate Director for Extramural Research, NINDS
Approval of Council Minutes -- Dr. Finkelstein requested, and the Council voted approval, for the September 20-21, 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, 135 applications were eligible to be expedited including 5 career or K applications and 10 SBIR/STTR applications. Fifty two of these have already been issued and most of the others will be issued shortly after Council. Due to the uncertainty of the NINDS budget, a limited number of awards were issued prior to the Council meeting.
DER Announcements -- Dr. Finkelstein introduced Dr. Pamela Wernett, a program analyst in the Neurodegeneration Cluster. Dr. Finkelstein announced that Dr. Tom Jacobs, a Program Director from the Neural Environment Cluster took a new position in early January as Associate Vice Chancellor for Federal Relations, University of Texas System, in Washington, D.C. Tom had 19+ years of experience with the Stroke, BBB, Neuroimaging and Brain Tumor Programs at NINDS. Finally, Dr. Finkelstein announced that Dr. Merrill Mitler, Program Director from the Systems and Cognitive Neuroscience cluster, NINDS, had left NINDS to begin a detail in the Office of Extramural Research. Merrill had been responsible for the sleep portfolio and other areas.
OTR Announcements -- Dr. Rajesh Ranganathan, Director, Office of Translational Research (OTR), introduced four new members of the office: Dr. John Kehne, Acting Head of the Anticonvulsant Screening Program (ASP) and will also contribute to the oversight and management of the Cooperative Translational Program (U01/U44); Dr. Margaret Ochocinska, Health Program Specialist, supporting both the CounterACT and Anti-Convulsant Screening Program teams; Dr. Rebecca (Becky) Roof, Health Program Specialist, supporting the SBIR/STTR program; and Dr. Amir Tamiz, Program Manager for the Blueprint Neurotherapeutics Program.
Council Operating Procedures -- Once a year, Council is required to endorse the Council Operating Procedures, which includes the Council Delegated Authorities. Council moved to approve the Operating Procedures.
III. Report of the Director, NINDS
Dr. Landis provided Council members with an update on the NIH budget for FY13, which began on October 1, 2012. On September 13, 2012, the U.S. 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. In accordance with the Budget Control Act of 2011 (P.L. 112-25), a series of automatic across-the-board spending cuts (sequestration) to defense and nondefense programs were scheduled to go into effect on January 3, 2013, following the failure of the Joint Select Committee on Deficit Reduction to propose, and Congress to enact a plan, to reduce the deficit by $1.2 trillion. On January 2, 2013, The American Taxpayer Relief Act of 2012 (P.L 112-240) was enacted, delaying a possible sequester resolution until March 1, 2013. If no resolution has been reached by this time, a new sequester will be ordered by President Obama on March 1, 2013. NIH continues to operate cautiously, pursuant to the law, until final FY13 funding is determined. As in other years when operating under a Continuing Resolution, NIH will fund non-competing grants at 90% of the approved level.
NINDS paid almost all grants from October 2012 Council from its FY12 budget allocation and is currently expediting grants to the 12th percentile. Dr. Landis indicated that the Institute hopes to be able to award grants to the 15th percentile; however, the ability to do so is contingent upon the outcome of ongoing federal budget negotiations. Moreover, Dr. Landis reported that because competing continuation, A0 (first submission) R01 applications within 10 percentile points of the payline have an excellent track record for obtaining funding upon subsequent submission, NINDS will continue to support these projects through one-year bridge awards. In addition, the Institute will resume considering High Program Priority (HPP) grants for funding beginning with the May 2013 council round. The HPP process is the mechanism used by NINDS to fund certain applications with scores above the automatic payline because they are particularly important to the NINDS mission.
Report on the NIH Advisory Committee to the Director (ACD) Biomedical Workforce Working Group
Dr. Landis reported on the NIH’s plans to implement recommendations from the NIH ACD Working Group on the Future of the Biomedical Workforce (BMWWG). This working group was asked to develop a model for a sustainable and diverse U.S. biomedical research workforce by training the optimal number of people for the appropriate types of positions that will advance science and promote health. The overall purpose of the ACD’s recommendations is to ensure future U.S. competitiveness and innovation in biomedical research by creating pathways that:
Within this framework, the BMWWG recommended a number of actions to support a sustainable biomedical research infrastructure with regard to the training of graduate students, postdoctoral researchers, and physician scientists. In response, the NIH formed an implementation committee to develop a plan to move forward with the recommendations of the working group.
The BMWWG noted that graduate students and postdoctoral fellows in the U.S. are supported on a combination of NIH training grants, fellowships, and research project grants, many of which are not designed to provide formal training. To ensure that all graduate students and postdoctoral fellows supported by the NIH receive excellent training, the BMWWG recommended that NIH increase the proportion of these trainees supported by training grants and fellowships compared to those supported by research project grants, without increasing the overall number of positions. In addition, the BMWWG noted that as many NIH trainees work in the biotech and pharmaceutical industries in research and non-research positions, and recommended instituting training programs for non-traditional careers. In response to these recommendations, NIH is creating a new grant program seeking innovative approaches to complement traditional research training in biomedical sciences at institutions that receive NIH funds. It will encourage institutions to leverage funds with existing institutional offices and programs, local resources outside the institution, or that partner with industry or other entities.
Additional measures to improve graduate student and postdoctoral training include:
In addition, a trans-NIH committee will be formed to consider the scope of the various options to support the salaries of NIH funded grantees and determine what type of data needs to be gathered to inform the deliberations.
Report on the NIH ACD Working Group on Diversity in the Biomedical Research Workforce
Dr. Landis reported on the NIH’s plans to implement recommendations from the NIH ACD Working Group on Diversity in the Biomedical Research Workforce (WGDBRW). NIH Director, Dr. Francis Collins, charged the ACD with forming the WGDBRW to examine the findings and implications of the Ginther, et al. study, which demonstrated a discrepancy in success rates for research grant (R01) applications between White applicants and Black applicants, even after controlling for numerous observable variables. In addition, the working group was charged with providing concrete recommendations toward improving the recruitment and retention of underrepresented minorities (URM), people with disabilities, and people from disadvantaged backgrounds across the lifespan of a biomedical research career from graduate study to acquisition of tenure in an academic position or the equivalent in a non-academic setting.
Based on the available data, the WGDBRW formulated a number of recommendations related to increasing the number of URM in the workforce pipeline, mentoring URM scientists, and strengthening the infrastructure of under-resourced institutions with a documented track record of producing and supporting URM scientists, and the potential role of bias. In response, the NIH formed an implementation committee to develop strategies for moving forward with the recommendations of the Working Group. With the goals of increasing the diversity of the NIH-funded workforce and ensuring that all applicants are treated fairly in the peer review system, four interrelated approaches with be implemented:
Report on the NIH ACD Working Group on Data and Informatics
Dr. Landis reported on the NIH’s plan to implement recommendations from the ACD Data and Informatics Working Group (DIWG). Dr. Frances Collins charged the DIWG with providing expert advice on the management, integration, and analysis of large biomedical datasets, with particular focus to the following areas:
In response to this charge, the DIWG made a number of recommendations, including:
Two initiatives are planned to overcome the roadblocks identified by the DIWG. The Big Data to Knowledge (BD2K) initiative will enable the biomedical research enterprise to maximize the value of biomedical data by developing new policies to encourage data and software sharing, by facilitating broad use of biomedical big data, by developing and disseminating analysis methods and software, by enhancing training for biomedical big data, and by establishing centers of excellence for biomedical big data. InfrastructurePlus will create an adaptive environment at NIH to sustain world class biomedical research. These initiatives will be supported by the common fund and will be governed by the trans-NIH Advisory Data Council, composed of the administrative data council and the scientific data council.
IV. Update on Stroke Planning Process
Dr. Paul Scott reviewed the NINDS’s recent activities leading to the development of nine research priorities in stroke. 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 modified Delphi process using impact, feasibility, and need for NINDS investment as the key prioritization criteria. The nine research priorities identified are as follows:
In response to these priorities and recommendations, NINDS intends to: establish a clinical trials network for all Phase II and Phase III stroke clinical trials, further develop recommendations related to Vascular Cognitive Dementias at the National Alzheimer’s Project Act Workshop on AD-Related Dementias, and organize a trans-NIH workshop to define how best to advance basic vascular biology.
V. Concept Clearance for FY 2013 Proposed Initiatives
Dr. Scott Janis, Program Director in the NINDS Office of Clinical Research, requested concept clearance for a NINDS Stroke Clinical Trials Network. As relayed by Dr. Scott, the Stroke Planning Committee recommended the Institute create a clinical trials network for stroke, the goal of which is to bring together leaders in the stroke community who will use a streamlined approach to develop, promote, and conduct a balanced portfolio of high-quality, multi-site Phase II and Phase III clinical trials and biomarker validation studies that are focused in key interventions across stroke prevention, treatment, and recovery. The network will serve as a coordinated infrastructure that will more rapidly and efficiently translate scientific opportunities in stroke. Dr. Finkelstein requested and was granted, a motion to move forward with the development of this concept.
Dr. Mona Hicks, Program Director in the NINDS Repair and Plasticity Cluster, requested concept clearance for two initiatives that will be supported using gift funds provided by the National Football League to the Foundation for the National Institutes of Health (FNIH) for the study of sports-related conditions. The first initiative will provide an opportunity for a multicenter team to: 1) more fully characterize the neuropathology associated with chronic traumatic encephalopathy (CTE) and delayed effects of traumatic brain injury (TBI) through systematic, rigorous, and collaborative studies of post-mortem biospecimens; 2) validate the neuropathological criteria for a postmortem diagnosis of CTE and delayed posttraumatic neurodegenerative diseases through independent and blinded analyses; and 3) identify neuroimaging signatures of the neuropathology as a foundation for the development of diagnostic tools in the future. The goal of the second concept is to enhance research on sports-related traumatic brain injury (TBI) and spinal cord injury (SCI) by providing a mechanism for investigators to obtain preliminary data for a larger research proposal in the future. The effects of single and repetitive neurotrauma are both of interest, as well as, research studies on risk factors, the development of biomarker and diagnostic tools, and preclinical interventions to prevent or attenuate injury or promote neural plasticity. Dr. Finkelstein requested and was granted, a motion to move forward with the development of both of these concepts.
VI. Update on NINDS Funding for Research Resources
Dr. Ned Talley, Program Director in the NINDS Channels, Synapses, and Circuits cluster, provided Council with an update on NINDS’s support for research resources, and in particular, for resource core activities. Institutional Center Core Grants (P30s) are multi-component awards, designed to support shared resources and facilities for categorical research. NINDS’s support for these grants has increased from $5.1M (8 centers) to $20.9M (33 centers) over nine years, and the question of how the Institute might support this type of activity most efficiently and with the broadest impact was raised before Council. Dr. Talley reported that in addition to maintaining support for the P30 program, NINDS was planning to implement a High Impact Neuroscience Research Resource Grant (R24) program to support single component resource projects that will serve broad communities of neuroscience researchers, or offer unique services that otherwise would be unavailable.
VII. Report of the Data Sharing Working Group
Drs. Barbara Vickery, Mary Kay Floeter, and Mr. Paul Gross presented the work and the recommendations of the NINDS Data Sharing Working Group (DSWG). The NINDS has invested significantly in collecting clinical research data and has an interest in making maximum use of these data. Sharing data from completed clinical trials and epidemiological studies, either for re-use or for aggregating with datasets from other studies, is a potential way to make greater use of clinical data to address new research questions beyond those posed by the original research team. In 2012, the DSWG was convened and charged by the Institute with providing a vision for how NINDS could proactively address: 1) the concerns of patients and investigators who have contributed the datasets, 2) the needs of investigators wishing to use the datasets, and 3) the anticipated advances in information/privacy technology and electronic medical records. Following two conference calls, an in-person meeting, and discussions with other NIH ICs and stakeholders, the DSWG provided the Institute with a number of recommendations covering: data standards, tools to promote sharing and collaboration, and incentives for maximizing the scientific value and use of large datasets.
VIII. Report from the Office of Translational Research
Dr. Rajesh Ranganathan, Director of the NINDS Office of Translational Research (OTR), continued a discussion initiated at the September 2012 NANDS Council meeting aimed at better defining the role of NINDS in Translational Research. To inform this discussion, Dr. Ranganathan highlighted four programs run by the Office, including the Cooperative Program in Translational Research, the Spinal Muscular Atrophy (SMA) Project, the Blueprint Neurotherapeutics Network, and the NINDS Small Business Programs. Guiding these programs is the principle that informs all the programs within OTR: the need for NINDS to adapt and collaborate to get therapeutics to humans.
The NINDS Exploratory Program (PAR-13-023; tR21) and the NINDS Cooperative Program (PAR-13-022; U01/U44) in Translational Research were launched in 2002 with the goal of stimulating preclinical development of therapeutics in non-profit and small business sectors. These are investigator-initiated programs that feature special review, are milestone-driven, and facilitate various aspects of the translation of drugs, biologics, and devices. Activities supported by the tR21 program include the development of screening assays and models, investigation of structure-activity relationships (SAR), development of pre-clinical efficacy data for identified candidate therapeutics, and the development of animal models for testing therapeutic target engagement. Activities supported by the U01 Program include preclinical efficacy testing, predictive ADME (absorption, distribution, metabolism, and excretion), toxicology testing, biodistribution studies, optimization of candidate therapeutics, manufacturing of candidate therapeutics for IND and Phase 0 studies, IND/IDE submission, and Phase 0, proof-of-concept studies. Dr. Ranganathan described the current portfolio, highlighted a number of projects that have obtained an IND through this program, and discussed various ways that NINDS can employ the use of milestones to more effectively manage the program.
Dr. Robert Pacifici highlighted the recent history of the SMA Project to Council. The SMA Project is a program that was initiated by NINDS in 2005 to enter the translational research space on a disease with an unmet medical need that was ripe for drug discovery. The program was organized around a network of contract research organizations (CROs) with an initial budget of $20M. SMA results from the loss of function of a single gene, Survival Motor Neuron 1 (SMN1), which encodes the SMN protein. Increasing production of SMN protein from a "back-up" copy of the gene, the SMN2 gene, offered an attractive treatment strategy, as compounds that could increase SMN protein production from the SMN2 gene had already been identified. Indoprofen was chosen as the starting point for a medicinal chemistry program after a systematic review of FDA approved drugs that had demonstrated that this compound could significantly increase SMN expression in a human reporter gene assay and in fibroblast cells derived from SMA patients. In addition, the increase in expression observed with indoprofen treatment translated into improved in utero survival in a very severe mouse model of SMA. Over a 5-year-period, the SMA Project synthesized and screened more than 1,400 analogs of indoprofen. Of the compounds screened in tier 1 assays, over 150 were selected for further characterization and advanced to the next tier of the testing funnel. Among the indoprofen series of compounds, one analog in particular, ALB-111, emerged as a potential drug candidate for SMA. Although significant increases in SMN protein levels were observed in a moderate SMA mouse model treated with ALB-111 for 15 days, when tested in a more severe mouse model of SMA, the benefits were more limited. Subsequent analysis suggests that the main hurdle with ALB-111 is its limited solubility. Since the close-out of the SMA project in June 2012, NINDS is actively engaging drug development partners to out-license ALB-111 as a late-stage lead development candidate.
The Blueprint Therapeutics Network (BPN) was created to combine the strengths of NIH investigator-initiated ideas with industry expertise. Using a number of key features of both the Cooperative Program and the SMA Project, the BPN functions as a virtual pharma company to develop investigator-submitted drug discovery projects. To date, 11 projects have entered the network covering a range of neurological conditions including mild cognitive impairment, narcolepsy, depression, macular degeneration, Parkinson’s disease, and Alzheimer’s disease. As projects progress through the research pipeline, milestones are employed to winnow non-viable drug candidates, conserving resources for projects with the greatest chance for translational success.
Lastly, Dr. Ranganathan described the Small Business program, a congressionally mandated set-aside (2.95% of the extramural budget) program focused on Research and Development for potential commercialization. The scope of the NINDS small business program is broad, and includes neurotherapeutics, diagnostics, and tools for neuroscience research. The SBIR/STTR Reauthorization Act of 2011 resulted in a number of changes to the program across the Federal Government, including modifications to award size, award caps, and program set-asides, creating additional challenges for management of the NINDS program.
IX. Biennial Report: Inclusion of Women and Minorities as Subjects in Clinical Research
Dr. Martin Mendoza, Health Program Specialist, NINDS Office of Clinical Research, provided Council with an update on the inclusion of women and minorities in NINDS-funded clinical research. The NIH Revitalization Act of 1993 (PL 103-43) requires that women and minorities be included in all NIH-funded clinical research in appropriate numbers based on scientific question being studied. Under this Act, each Institute is required to prepare a biennial report describing the manner in which the Institute has complied with its tracking obligations. Each year, PIs submit their targeted and actual enrollment numbers in competing applications and in annual progress reports. NINDS reports inclusion enrollment for extramural projects via the NIH population tracking application linked to the NIH IMPAC II database. For the two-year 2011-2012 reporting period, total participant enrollment in NINDS-funded clinical research increased from 205,501 in 2011 to 223,485 in 2012. The proportion of women, non-whites, and Hispanics remained stable during this two-year time period. In recent years, NINDS has participated in a number of inclusion-directed efforts to improve the enrollment of women and minorities in its research programs.
X. Council Consideration of Pending Applications
This portion of the meeting, involving specific grant review, was closed to the public. The Council gave special attention to applications from foreign institutions and other applications which needed specific discussion. Prior to the discussion of the grants, Dr. Finkelstein reminded Council regarding conflict of interest and confidentiality as follows:
Conflict of Interest
The regulations concerning conflict of interest were reviewed. Council members were reminded that materials furnished for review purposes and discussion during the closed portions of the meeting are considered privileged information. All Council members present signed a statement certifying that they had not been involved in any conflict of interest situations during the review of grant applications.
During the closed session, any information that is discussed and the outcome of any recommendation are considered privileged information. They may not be discussed outside of the closed session. If an applicant requests support for his or her application from a Council member, the Council member must respond that he/she is not permitted to discuss the application. Any inquiry should be referred to Dr. Robert Finkelstein, the Council Executive Secretary, who will then refer the questions to the appropriate staff member for response.
Research Training and Career Development Programs
The Council reviewed a total of 333 research career development and institutional training grant applications; of this total, 306 applications had primary assignment to NINDS, and 191 of them (62.4 percent) were scored in the amount of $13.2 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 $7.2 million (75 grants).
Research Project and Center Awards
The Council reviewed a total of 1,840 research project and center applications; of this total, 1,547 applications had primary assignment to NINDS, and 859 of them (55.5 percent) were scored/percentiled in the amount of $248.8 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 $64.5 million (224 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, five Javits awards were recommended.
Small Business Innovation Research and Small Technology Transfer Award Programs
The Council reviewed a total of 192 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 190 applications had primary assignment to NINDS and 110 of them (57.9 percent) were scored in the amount of $31.4 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 (12 grants).
The meeting was adjourned at 10:40 a.m. on Friday, February 1.
NINDS employees present for portions of the meeting included:
Other Federal employees present for portions of the meeting included:
Dr. Merrill Mitler, OD
Dr. Dianne Rausch, NIMH
Dr. Wei-Qin Zhan, CSR
Dr. Rene Etcheberrigaray, CSR
Dr. Paek Lee, CSR
Dr. Seetha Bhagavan, CSR
Dr. Laurent Taupenot, CSR
Dr. Yuan Luo, CSR
Last Modified March 26, 2013