NINDS Advisory Council Meeting Minutes, May 25-26, 2000

The National Advisory Neurological Disorders and Stroke (NANDS) Council was convened for its 148th meeting on May 25, 2000, in Building 31, Conference Room 10, National Institutes of Health, Bethesda, Maryland. Dr. Gerald Fischbach, Director of the National Institute of Neurological Disorders and Stroke (NINDS), served as Chairperson.

In accordance with Public Law 92-463, the meeting was:

Open: May 25, 2000 -- 8:40 a.m. to 4:55 p.m.

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

Closed: May 25, 2000 -- 4:55 p.m. to 5:15 p.m.

May 26, 2000 - 8:45 a.m. to 11:30 a.m.

for discussion and consideration of individual grant applications.

Council members present were:

Mr. Robert V. Abendroth Ms. Kathleen Hunter
Ms. Jeanne Carpenter Mr. Morton Kondracke (absent 5/26)
Ms. Alicia Conill Dr. John Mazziotta
Dr. Martha Denckla Dr. George Ojemann
Dr. Darryl DeVivo Dr. Jerome Posner
Dr. Uta Francke Dr. Joshua Sanes (absent 5/26)
Dr. John Griffin Dr. Richard Tsien (absent 5/26)
Dr. Julian Hoff

Council members absent were:

Dr. Peter MacLeish

Council Roster (Attachment 1)

Ex Officio Members present:

Dr. John Booss, Department of Veterans Affairs
Dr. Andrew Dutka, Department of Defense

Members of the public present for portions of the open meeting included:

Ms. Lisa Cash, Spinal Cord Connections
Mr. Ron Bartek, Friedreich's Ataxia Research Alliance
Mr. Larson Hafner - The Blue Sheet
Ms. Melinda Kelly - Paralyzed Veterans Association
Dr. Lawrence Abbott - Brandeis University
Ms. Dianne Flescher - Epilepsy Foundation
Dr. Sharon Moss - American Speech and Hearing Association

NINDS employees present for portions of the meeting included:

Dr. Audrey S. Penn Dr. Constance Atwell Dr. Gerald Fischbach Ms. Brenda Kibler Dr. Cheryl Kitt Dr. F. J. Brinley Dr. Al Kerza Dr. Giovanna Spinella Dr. William Heetderks Dr. Paul Nichols Ms. Margaret Jacobs Ms. Marian Emr Dr.KatherineWoodbury-Harris Dr. Philip Sheridan Mr. Jim Stoneman Dr. Robert Baughman Dr. Eugene Oliver Mr. Phillip Wiethorn Dr. Charlotte McCutchen Ms. Shirley Broderick Dr. Alan Willard Dr. Arlene Chiu Mr. Gahan Briethaupt Dr. Mary Ellen Cheung Dr. Yuan Liu Dr. Joana Rosario Ms. Mary Miers Ms. Nancy Hart Dr. Thomas Miller Dr. Lewis Rowland Ms. Joellen Harper Dr. Toby Behar Ms. Verly Taylor Dr. Emmeline Edwards Ms. Quandra Scudder Ms. Cikena Reid

Dr. John Marler Dr. Paul Sheehy Dr. Lillian Pubols Mr. Levon Parker Ms. Nena Wells Dr. Gabrielle Leblanc Dr. Thomas Jacobs Ms. Maureen Hambrecht Ms. Ruth Linn Mr. Andy Baldus Dr. Robert Zalutsky Mr. Kevin Kirby Dr. Alfred Gordon Dr. Paul Scott Dr. Deborah Hirtz Dr. Story Landis Ms. Marcia Vital Ms. Mary Graham Ms. Carol Rowan Ms. Sandra Talley Mr. George Bramhall Ms. Shannon Garnett Ms. Natalie Frazin Dr. David Eckstein Ms. Pam Jones Mr. Paul Girolami Ms. Stephanie Clipper Dr. Diane Murphy Dr. Henry Khachaturian Ms. Debbie Jarman Ms. Marvene Horwitz Mr. Ken Bond Mr. Paul Myers Ms. Dianna Jessee Ms. Mary Tomanek

Other Federal employees present for portions of the meeting included:

Dr. Brent Stanfield, NIMH
Dr. Dennis Glanzman, NIMH
Mr. Timothy Hays, NIMH
Dr. David Simpson, CSR
Mr. Greg Downing, OD
Ms. Janice Solomon, FIC
Dr. David Shore, NIMH
Dr. Herman Teitelbaum, CSR

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I. Call to Order and Opening Remarks

Dr. Gerald Fischbach, Director, NINDS, welcomed the Council members, guests and staff to the 148^th Council meeting. He encouraged all to attend a Council dinner that evening to thank Dr. George Ojemann, Dr. Darryl DeVivo, Dr. Andrew Dutka, and Ms. Alicia Conill for their service on the Council. Dr. Fischbach also introduced Dr. Anand Kumar, Associate Professor, Division of Geriatrics/Psychiatry, University of California at Los Angeles, and Chair of the Center for Scientific Review (CSR) Brain Disorders and Clinical Neurosciences 1 Initial Review Group, as a special visitor.

II. Report of the Associate Director for Extramural Research

Dr. Constance Atwell, Associate Director for Extramural Research, NINDS, reported on the following topics:

Council Procedures

Government in the Sunshine Act and Federal Advisory Committee Act:

Conflict of Interest

Consideration of Minutes of Previous Meeting

The minutes of the Council meeting of February 10 - 11, 2000, were considered and accepted as written.

Consideration of Dates for Future Council Meetings

September 14-15, 2000 (Thursday and Friday)
February 15-16, 2001 (Thursday and Friday)
May 24-25, 2001 (Thursday and Friday)
September 13-14, 2001 (Thursday and Friday)
February 14-15, 2002 (Thursday and Friday)
May 30-31, 2002 (Thursday and Friday)
September 12-13, 2002 (Thursday and Friday)

Program Announcements/Request for Applications

Dr. Atwell reminded Council of the many Program Announcements (PAs) and Requests for Applications (RFAs) published in the NIH Guide for Grants and Contracts since the last meeting. Copies had been e-mailed to Council members since their last meeting.

Reports Book

Dr. Atwell called Council's attention to the Report Book which included a list of all funding actions since the previous Council meeting. A new addition to this book, as requested by Council, is a listing showing the payment status of all High Program Priority applications.

Unsolicited Exploratory Grant Mechanism (R21)

Dr. Atwell requested feedback from Council members on the introduction of an unsolicited exploratory grant mechanism at NINDS. This mechanism, the R21, which has been used previously in RFAs issued by NINDS, supports the collection of preliminary data for high risk/high impact research. New investigators can apply through this mechanism to establish a track record and senior investigators can use this mechanism to explore new technologies or areas of research outside of their fields. The R21 grant will have a two-year duration and provide grantees up to $125,000 direct costs each year.

In the discussion that followed, Council members suggested that these applications be reviewed by the NINDS Scientific Review Branch (SRB) to expedite funding for research that may have a high impact. Dr. Atwell and Dr. Pubols acknowledged this point, but indicated that the CSR would review these applications for the first few rounds, until NINDS could assess the volume of applications and the impact of moving the review to the SRB. [NINDS has subsequently decided to review the R21 applications in SRB.]

Other Items

Dr. Atwell noted that the expedited review process, which is working very well, has allowed NINDS to pay 78 grants for this Council round before the actual Council meeting.

Dr. Atwell introduced the following new staff: Dr. Henry Khachaturian, Training, Career Development and Referral Officer; Dr. Dennis Landis, who has a special appointment to improve clinical training and career development programs at NINDS; Ms. Cikena Reid, Committee Management Assistant; Dr. Belinda Morin, Program Analyst in the Systems and Cognitive Neuroscience cluster; and Dr. David Eckstein, Program Analyst in the Neural Environment cluster.

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III. Report of the Director, NINDS

Dr. Fischbach announced the appointment of Dr. Guy McKhann as Associate Director for Clinical Research beginning July 1, 2000. He noted Dr. McKhann's distinguished career in neurology and his long association with NIH in various advisory capacities. Dr. McKhann will assist in implementing some aspects of the strategic plan, particularly in the areas of clinical trials and disease and patient oriented research in the Intramural Division.

Genomics and gene therapy were mentioned as issues currently commanding attention at NIH. Dr. Fischbach stated that both the 15 member Government-supported consortium and Celera Genomics would announce completion of the first draft of the human genome by early summer. There are several open questions surrounding this project related to how much cooperation/collaboration will exist between government investigators and Celera in managing this data and making it available to the public. Dr. Fischbach expressed hope that the leadership in both groups would continue to work together on this project.

Gene therapy was mentioned as the second major issue, spotlighted by the recent incident at the University of Pennsylvania. This situation, in addition to provoking a call for new regulations, has raised questions regarding the definition of informed consent and whether NIH should "police" grantees or act in the usual advisory capacity.

Dr. Fischbach informed the Council of an Institute Directors budget retreat scheduled for June. The agenda for this meeting would probably focus on NIH-wide initiatives such as building and renovation and the need for collaboration among Institutes. An example of this collaboration is the National Neuroscience Research Center which will bring together all intramural neuroscience at NIH to facilitate the translation of basic research into clinically useful therapies. There is $47 million in the budget for this building this year and $26 million next year. It is anticipated that $290 million will be needed in total for the project.

Dr. Fischbach described the current status of budget negotiations for FY 2001. NIH is on course to double its budget by FY 2003. The President's budget recommends about a 5 percent increase, while the Senate has recommended a 15.2 percent increase. Since the former number would require significant programmatic adjustments, it is hoped that the final increase will be more in line with the Senate's recommendation.

Dr. Fischbach underscored NINDS support for new investigators. Although the R29 funding mechanism, which was directed toward new investigators, was eliminated, NIH and NINDS continue to have a commitment to supporting new investigators, as is evidenced by the high percentage of new awards that are granted to new principal investigators.

Dr. Atwell provided an addendum to the discussion with a presentation on cost trends for single investigator awards. She indicated that the average direct cost for these awards has increased by about 10 percent per year since 1997. Contributing to this trend may have been grantees' inclination to ask for more (given recent NIH budget increases); a decrease in the budget reductions by NINDS staff from 10 percent to 5 percent; and the elimination of the R29. In spite of the general concern that NIH's modular grant policy would result in higher grant costs, data on modular grants awarded in FY 2000 do not support this contention.

Dr. Fischbach briefly described recent planning efforts within the Institute that have resulted in the activation of two new clusters - the Neurogenetics cluster and the Clinical Trials group. Neurogenetics would join the current Program Clusters: Neurodegeneration; Neurodevelopment (inactive); Repair and Plasticity; Synapses and Circuits; Cognitive Neuroscience and Neural Environment. Clinical Trials would be included in the group of programs that extend across clusters: Special Programs; Training and Career Development; and Technology Development. NINDS will work annually with a subset of the original Program Planning Panel to assess implementation of the NINDS Strategic Plan and every two to three years assemble the whole group to develop a new plan.

NINDS has also begun disease specific planning, beginning with the Parkinson's Disease Research Plan submitted to Congress in March. The Neurodegeneration cluster has developed a tracking system to organize data on conferences, workshops, publications, new initiatives, and new grants as they occur. This data will be made available to the public on the web. Future planning efforts will include epilepsy, stroke, and brain tumor. The first planning meeting on brain tumor research will be held in July in conjunction with the National Cancer Institute. All of these planning groups will have an external chairperson and produce a report on the work of the group within five to six months of the initial meeting.

Dr. Fischbach reviewed some of the new program initiatives that NINDS will support this fiscal year. He remarked that the Steering Committee endorsed a new initiative on cognitive deficits following brain trauma as a much needed effort, given that brain trauma is the leading cause of death in people under the age of 45 in this country. This initiative was developed by Dr. Mary Ellen Cheung. A second initiative led by Dr. Robert Baughman seeks to establish microarray centers as one of the contributions that NINDS will make toward bringing array technology to the research community. There are directives in place within this initiative to encourage the development of public databases and collaborative interactions and to establish training in microarray technology. These grants will also use the cooperative agreement mechanism, which will require substantial involvement by NINDS staff in research activities. Within the Intramural Division, NINDS has also begun the establishment of an array center on campus. Dr. Fischbach mentioned a third initiative on HIV and the peripheral nervous system, which is directed toward research on peripheral neuropathy.

Dr. Fischbach commended the staff for the large number of NINDS-sponsored workshops within the past couple of months. He described a workshop on high throughput screening sponsored by the Technology cluster, the result of which will be a contract to fund the creation of high throughput assays. A major discussion in the workshop related to the limited access that exists for chemical libraries and whether NINDS will become involved in the creation and distribution of chemical libraries. Significant collaboration with industry will be required in this effort. Dr. Fischbach also mentioned a workshop on spinal cord injury, one of six focussed workshops which will be held over the next year. This workshop brought together several immunologists and neurobiologists to discuss inflammatory processes in response to injury.

Dr. Fischbach discussed a breakthrough in the use of MRI as a surrogate marker in clinical trials.

He noted that there are few markers that the FDA will accept as surrogates in clinical trials and that the development of better surrogate markers could lead to a drastic reduction in the costs of clinical trials. At a recent workshop, attended by staff from the FDA, there was general consensus that there is a high correlation between disease progression in multiple sclerosis and the appearance of new lesions. The result of the workshop may be serious consideration by the FDA of MRI as a surrogate marker, at least in Phase I and Phase II clinical trials, and even more significant, a change in the strategy of treating some neurological disease.

Dr. Fischbach concluded by calling attention to a recent article in Nature, which described recent experiments involving a drosophila model of Parkinson's disease. Dr. Mel Feany at Harvard Medical School introduced normal and mutant forms of alpha-synuclein genes in flies. The flies exhibited a loss of dopamine containing neurons and developed Lewy bodies, both characteristic of Parkinson's disease. The flies also developed a movement disorder, also an expected outcome of Parkinson's disease. Dr. Fischbach remarked how this study demonstrated the homology of functions across billions of years of evolution and how investigators can study human diseases in organisms which can be manipulated genetically.

Dr. Atwell requested that Council members join her in thanking Dr. Phil Sheridan for his many years of service to NINDS. Dr. Sheridan will leave NINDS this month for a new position at the FDA.

In response to Council's previously expressed concern regarding the quality of the review for neuroscience applications, Dr. Atwell called attention to the lists of CSR Working Groups that had been made available to Council members in their meeting documents. These advisory groups, of which there is one for each CSR review group, will assess the effectiveness of the review process through participation in the June review sessions.

Copies of the slides used in Dr. Fischbach's presentation are attached as Appendix 1.

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IV. NINDS Strategic Plan on Health Disparities

Dr. Fischbach introduced Dr. Joana Rosario, Program Director, Office of Special Programs in Neuroscience, NINDS, to provide an overview of the NINDS Five-Year Strategic Plan on Minority Health Disparities. This report will be incorporated in a Congressionally mandated NIH Plan on Health Disparities. Dr. Fischbach welcomed input from Council.

Dr. Rosario stated that, consistent with NIH's goal of addressing six health gaps by the year 2010, NINDS has developed a strategic plan which will address the differences in the incidence, prevalence, mortality and burden of disease and other adverse health conditions that exist among specific racial/ethnic minority population groups in the United States. Current NINDS initiatives include: Specialized Neuroscience Research Programs (SNRPs) at minority institutions, (which will increase from five to eight this FY); the SNRP on HIV and the Central Nervous System, the applications for which are currently in review; and the Stroke and Cardiovascular Prevention Intervention Research Program, which will be reviewed with Council in September.

In developing the Plan, the staff formulated the following objectives: the identification of neurological conditions known or strongly suspected to reflect disparities; the recognition of gaps in knowledge that contribute to disparities; and the definition of areas of research focus for NINDS to pursue alone or in collaboration with other Institutes or Centers. Through consultation with NINDS Program Directors and the extramural scientific community, the staff identified eight areas of focus where NINDS could potentially have the greatest impact on minority health. In addition to these areas of research, the staff recommended an expansion of efforts to enhance training and career development opportunities, professional networking opportunities between research intensive institutions and those serving minority populations, education and outreach activities in minority communities, and minority participation in neurological research.

Through implementation of the plan, NINDS hopes to learn more about the magnitude of disparity for different disorders, the history of neurological complications in minorities, and the interaction between genetic disposition and the environment in the development of neurological disorders in minorities. This process should also lead to the development of models for monitoring trends in stroke, better diagnostic tools, and models for the prevention of disparities. Additionally, the staff hopes to have a positive impact on the recruitment and retention of minorities in research, the enhancement of research capacity at minority institutions, and expansion in outreach and educational activities in minority communities. The Plan has been made available to the public and specifically to organizations and individuals with an interest in health disparities for review and comment. Dr. Rosario thanked the staff of NINDS and the many members of the extramural research community who contributed to the formulation of the Plan.

In the discussion that ensued, questions were raised regarding regional/geographic variations in the incidence of diseases among minorities and whether genetic factors will be examined. Dr. Rosario reassured Council that these factors would be considered. Council members also emphasized the need for more education and outreach to minority populations on diet and other factors which may contribute to diseases. Council also proposed collaboration with agencies such as the Veteran's Administration, which has sponsored gender and ethnic disparity research in stroke, HIV, and pain. In the area of pain research, Dr. Fischbach made note of recent findings on the scarcity of pharmacies in minority communities that carry prescription pain medications as evidence of how the health care delivery system is failing minorities. These new NINDS initiatives will cost approximately $6 million in the first year of implementation.

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V. NINDS Conference/Workshop Reports

Epilepsy Conference

After an introduction by Dr. Fischbach, Ms. Margaret Jacobs, Program Director, NINDS Channels, Synapses and Circuits Cluster, summarized the proceedings from "Curing Epilepsy: Focus on the Future"--the epilepsy conference held on the NIH campus March 30 - 31, 2000. The conference brought together over 500 participants from NIH, industry, advocacy groups and the research community to discuss a cure for epilepsy. The meeting included presentations from persons living with epilepsy, a videocast from Hillary Rodham Clinton, and interactions with participants throughout the country via a web cast. Over 100 people attended the meeting to introduce a new NINDS RFA directed toward junior investigators involved in translational epilepsy research.

The conference focused on three major topics: interrupting and monitoring epileptogenesis; genetic strategies; and developing new therapies. Participants responded enthusiastically to the charge to refocus their dialogue from the usual discussion of treating seizures to an exploration of the underlying mechanisms that cause epilepsy and methods of preventing seizures. The sessions included discussion of methods of interrupting and monitoring epileptogenesis and the impact of advances in genetic studies on the search for a cure. In the sessions on therapies, the discussion focused on tailored therapies, novel delivery systems, and several non-pharmacological methods of intervention. Some of the recommendations for future goals included: to develop an understanding of the basic mechanisms of epileptogenesis; to develop new genetic strategies; and to develop new therapies.

Ms. Jeanne Carpenter, NANDS Council member, continued the conference summary by reiterating the significant shift within the American Epilepsy Society (AES) from an emphasis on treating epilepsy to seeking a cure. She thanked everyone for their involvement and noted the benefit of the internet in broadening the reach of the conference and providing access, for those unable to attend, to the many prominent investigators on the panels. The AES has tried to move forward on the energy generated by the conference by publishing a summary document which is currently in use in lobbying efforts on the Hill and in educational efforts.

Computational and Theoretical Neuroscience Workshops

Dr. Fischbach introduced Dr. Yuan Liu, Program Director, NINDS Channels, Synapses and Circuits Cluster, to discuss recent work in informatics and computational neuroscience. Dr. Liu reviewed the recommendations from the Council Committee on Informatics presented at the last Council meeting. She announced that NINDS had recently sponsored two workshops: Neuroimaging Informatics on April 24, 2000, and Computational and Theoretical Neuroscience on April 28, 2000. The Neuroinformatics workshop produced four major recommendations: (1) endorsement of an NIH-wide Neuroinformatics Technology Initiative (NIFTI) led by NINDS and NIMH; (2) strong support for solving the problem of data interoperability; (3) an emphasis on enhancements for informatics tools; and (4) the establishment of an advisory board. Dr. Liu thanked Dr. Richard Tsien, NANDS Council member, for co-chairing the second workshop and introduced him to provide a summary of the proceedings.

Dr. Tsien recognized Dr. Dennis Glanzman from NIMH, Dr. Eve Marder, workshop co-chair, and Dr. Ruzena Bajcsy of the National Science Foundation, for their involvement in the workshop. Workshop planners aimed to demonstrate the significance of computational and theoretical neuroscience, identify promising areas of research, and develop ways to promote future work in these areas. Dr. Tsien offered that recent rapid advances in neuroscience have created a tremendous number of isolated sets of information in need of synthesis. In order to develop a cure for a disease, it is necessary to understand the disease as a whole, to integrate quantitative information from the cellular to the circuit to the systems level. This approach should result in more translational research and enhanced strategies to generically address various disease mechanisms. The goal of neuroinformatics, therefore, is to place all of the components in context, to support understanding of a disease, to link animal models and disease and to inspire novel research and fresh hypotheses. Dr. Tsien emphasized that progress in computational and theoretical neuroscience is contingent on NIH encouraging innovative research and countering the view in the research community that applications with a more conservative approach are received more favorably in NIH study sections.

The workshop concluded with an examination of strategies to overcome obstacles to the advancement of theoretical neuroscience. The research community must encourage more collaboration between those in theoretical work and those in experimental work. Sufficient mathematics must be incorporated in training programs to encourage investigators to use more computational and theoretical approaches. The skilled evaluation of research applications employing these approaches is hampered by the limited number of neuroscientists with expertise in these areas. Dr. Tsien suggested that interdisciplinary training is the best approach to address these issues, encouraging young investigators to learn theoretical methods early in their training and more experienced investigators to augment their skills through workshops or courses. Dr. Tsien then introduced Dr. Laurence Abbott, Professor, Department of Biology, Brandeis University, and a leading expert in the field of computational neuroscience, to discuss his research.

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VI. Moving from Representation to Computation: The Role of Theory

Dr. Abbott noted that we know a great deal about how information is represented in various regions of the brain through selective neural responses and sensory maps. Much less is known about how neural circuits use this information to perform behaviorally relevant computations. A notable exception involves the coordinate transformations needed in reaching to visual targets. A combination of experimental and theoretical work has quite convincingly revealed how the neural circuits of the posterior parietal cortex performed these transformations. This has led to, among other things, models of neglect in patients with parietal lesions. The computational mechanism uncovered in parietal cortex appears to generalize to other regions and tasks. For example, analogous processes have been observed in the ventral visual stream in association with attentional effects. These may play an important role in object recognition. Thus, we may have uncovered a fairly general principle of neural computation. The interplay between experimental and theoretical approaches that characterized this analysis is likely to play an increasingly important role as we expand our knowledge of the brain from representation to computation.

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VII. Informed Consent

Following a brief discussion of issues raised in Dr. Abbott's' presentation, Dr. Fischbach introduced from the Office of the Director, NIH, Dr. Ruth Fischbach, Senior Advisor for Biomedical Ethics, Office of Extramural Research, and Dr. Jeffrey Cohen, Associate Director, Office for Protection from Research Risks (OPRR), Office of Extramural Research. Dr. Uta Francke, NANDS Council member, would join them for a discussion of informed consent.

Dr. Ruth Fischbach began by stating that the informed consent discussion would address the following questions: (1) How do we define a human participant? (2) From who do we need informed consent? (3) How do we define risk? and (4) How do we protect the rights and welfare of those who volunteer to participate in studies?

As a springboard for discussion, Dr. Fischbach drew attention to the case of Mr. Richard Curtin, the father of a participant in an NIH-sponsored study at Virginia Commonwealth University (VCU), whose protest regarding invasion of privacy led to an internal investigation that eventually shut down several research projects. Upon reading a questionnaire sent to his daughter, who was a potential participant in a VCU-based study involving twins, Mr. Curtin protested that the principal investigator did not have permission to pose questions concerning the health of other family members besides the participating daughter, as these members had not given consent to participate in the study. When Mr. Curtin received what he deemed an inadequate and unresponsive reply, he reiterated his concerns to his Congressman, NIH, and other government agencies, ultimately resulting in a shutdown of 1,500 research projects at VCU.

Dr. Cohen indicated that the case set no precedent, but was decided using guidelines from 45 CFR 46, Federal Policy for the Protection of Human Research Subjects. Under these guidelines, OPRR determined that the secondary subjects in the VCU study fit the definition of human subjects and their participation in the study should have been reviewed for possible exemption for informed consent, a determination of whether a full or expedited IRB review of the matter was necessary, and the necessity of informed consent. Given that the potential exposure of this confidential data placed Mr. Curtin's security clearance at risk, in accordance with existing guidelines, his written consent to participate in the study should have been obtained.

Dr. Uta Francke continued the presentation, describing her exploration of the Curtin situation as President of the American Society of Human Genetics. Dr. Francke stated that many investigators are uninformed as to the timing of the applicability of human subject regulations. Twin studies generally solicit data on a broad range of topics which can be segmented for use in a variety of research projects. The requirements on consent from secondary human subjects are not always practical, and in many cases, these rules may slow the research process and possibly lead IRBs to restrict the scope of subject questionnaires to avoid violating federal regulations. Dr. Francke suggested that more training be made available to IRBs and investigators. She cautioned that in the wake of the incident, IRBs may be reluctant to grant waivers for written consent even when appropriate.

In the discussion that followed, Council members agreed that ensuring confidentiality of collected data is the most difficult aspect of compliance with the regulations. Certificates of confidentiality do not protect data, except from court subpoenas. All the traditional methods of protecting data, locked cabinets and passwords, are not 100 percent effective. Even encoding records provides only a limited safeguard, if coding information is available to link data to individuals. It was suggested that given the difficulty of preventing leaks of information, legislation should be introduced to prohibit discrimination based on genetic information, a major concern to subjects in genetic research.

In cases where research data is located in more than one country, it was noted that the regulatory burden is doubled as investigators must comply with the requirements in both locales. There was concurrence on the need for agencies such as the Fogarty International Center and the World Health Organization to address streamlining and standardization in this process.

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VIII. Council Committee Reports

Informatics and Computational Neuroscience

Dr. John Mazziotta, NANDS Council member, reported that this Committee had decided to artificially break up informatics and computational neuroscience to best address issues in both areas. However, the two areas are linked, with informatics focused on data storage and organization, and computational neuroscience on operations to massage this data. Dr. Mazziotta made note of two NINDS-sponsored workshops, one on informatics and one on computational neuroscience. The latter has been summarized in a report. In the future, the Committee will examine areas of study such as astro-physics, meteorology, and electrical engineering, which may offer existing tools and systems that could be adopted by the neuroscience community. The Committee will also assess training programs for new and experienced investigators and how grant applications involving informatics and computational neuroscience fare in review groups.

Training and Career Development

Dr. Julian Hoff, NANDS Council member, indicated that the Committee has discussed strategies to stimulate more research at all levels of training from the student level to the early faculty level. Specifically, the Committee has examined approaches to improve and increase flexibility in the career development award series. This process, which

will culminate in a report in early September, will look at the duration of these awards, the funding level, salary caps, and the impact of medical training debt on research careers.

Dr. Henry Khachaturian, NINDS Training and Career Development Officer, described some of the actions taken by NINDS since the last Council meeting. The Individual Predoctoral Fellowships (F31) has been introduced. An option for a third year has been added to the two year F32 grants, while the K08 awards have been extended to a maximum of five years from the original three.

Dr. Story Landis, Director, Division of Intramural Research, NINDS, requested approval from Council for a new Career Transition Award (K22). This initiative has the dual goal of increasing the quality of postdoctoral fellows in the intramural program and providing more training opportunities for clinical fellows, as well as, facilitating their transition to extramural research careers. Awardees can request a maximum of five years, with this time split roughly equally between work as a senior postdoctoral fellow in the NINDS intramural program and as a principal investigator in a tenure track position at an extramural research institution.

In response to questions regarding the cost of the program, Dr. Landis indicated that each fellow would cost $150,000 for each portion of the grant, intramural and extramural, plus additional overhead expenses for extramural. These grant monies from extramural would enhance the ability of these candidates to obtain tenure track positions at research institutions.

The Council returned to the question of how critical debt relief is to attracting more physicians to research careers. Dr. Fischbach noted that this is an issue of concern to all Institutes at NIH and probably requires legislative action. With Council support, Dr. Fischbach volunteered to lead the effort toward the establishment of a program of debt relief. The U.S. Armed Services programs which provide medical training in exchange for future service was offered by Council as a possible model.

Dr. Fischbach thanked the Committees for their work since the last Council meeting. He announced the formation of the Health Disparities Committee with a general solicitation for volunteers.

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IX. Clinical Trials at NINDS

Dr. Fischbach reviewed with Council some of the latest changes in the cluster organization at the Institute. He announced the activation of two new clusters, Clinical Trials and Neurogenetics. Dr. Fischbach then introduced Dr. John Marler, Associate Director for Clinical Trials, to brief the Council on the work of this cluster.

Dr. Marler noted how rapid breakthroughs in basic neuroscience research have produced tremendous opportunities in clinical trials. As a reflection of NINDS' current involvement in clinical trials, existing projects managed by the Extramural Program absorb about 5 percent of NINDS' total budget, making NINDS sixth among NIH Institutes in terms of total expenditures on clinical trials.

The management of clinical trials includes unique responsibilities. Because these grants usually exceed $500,000 per year and will be funded through cooperative agreements, NINDS staff members will have more involvement in planning and implementing these projects. Program Directors must devote significant time to working with monitoring committees for these projects and pay particular attention to appropriate compliance with human protection guidelines. Program Directors assume these duties in addition to managing a portfolio of disorder-related grants. Dr. Marler reviewed data on staffing at other NIH Institutes relative to clinical trial workload, which seemed to indicate that NINDS should consider devoting more staff resources to this cluster to effectively manage the anticipated growth in grants.

In the discussion that followed, Dr. Marler acknowledged that having limited staff resources devoted to clinical trials has not yet had a negative impact on NINDS-sponsored clinical trials, but these results stemmed from the vigilance of the staff in addressing issues before they evolved into larger problems. In response to concerns raised over the lack of applications for NINDS clinical trial planning grants, Dr. Marler indicated that many investigators skip planning grants and write applications for clinical trials to save time in the review process, based on confidence that the proposed project is significant enough to receive approval.

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X. Translational Research Conference

Dr. Fischbach introduced Mr. Robert Abendroth, NANDS Council Member, to discuss his experience with a recent workshop on translational research. Mr. Abendroth described as noteworthy the range of participants in this conference, the focus on bench to bedside and the similarities in the approach of this group, and the NINDS strategic plan. Bringing together scientists, representatives of advocacy groups/foundations, bioengineering and other companies, the workshop concentrated on new strategies for motivating basic scientists to apply their research to disease and creating an environment that will lead to successful collaborations among all concerned with curing disorders. Some of the possible methods discussed were (1) creating partnerships between academia and biotechnology companies, (2) more funding of research by nonprofit organizations, and (3) the establishment of an umbrella organization to, among other functions, coordinate joint funding of technologies that are key to research but that are not commercially viable. It was acknowledged at the meeting that many obstacles will hinder the implementation of these strategies, but joint efforts will enhance the probability of success.

Dr. Fischbach requested that the Council vote to support NINDS' participation in a Brain Tumor Progress Review Group that will meet in July. The motion carried.

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XI. Council Review 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 applications for which there were concerns about human subjects, including appropriate representation of women and minority subjects, or laboratory animals.

Research Training and Career Development Programs

The Council reviewed a total of 53 research career development grant applications; of this total, 33 applications had primary assignment to NINDS, and 24 of them (72.7 percent) were recommended for support in the amount of $2.5 million first-year direct costs. It is anticipated that, of the research career development grants competing at this Council, NINDS will be able to pay first-year direct costs of approximately $2.0 million.

Research Grant Awards

The Council reviewed a total of 1,161 research grant applications; of this total, 688 applications had primary assignment to NINDS, and 475 of them (69.0 percent) were recommended for support in the amount of $122.0 million first-year direct costs. It is anticipated that, of the research grants competing at this Council, NINDS will be able to pay first-year direct costs of approximately $60.7 million.

Senator Jacob Javits Neuroscience Investigator Awards

The Senator Jacob Javits Neuroscience Investigator Awards are made to distinguished investigators who have a record of scientific excellence and productivity, who are actively pursuing an area of research of strategic importance, and who can be expected to continue to be highly productive for a seven-year period. Candidates are nominated and selected at each Council meeting. At this meeting, the Council recommended three investigators as Javits awardees.

Small Business Innovation Research and Small Technology Transfer Award Programs

The Council reviewed a total of 162 Small Business Innovation Research (SBIR) and Small Technology Transfer Award (STTR) grant applications; of this total, 107 applications had primary assignment to NINDS and 73 of them (68.2 percent) were recommended for support in the amount of $9.9 million first-year direct costs. It is anticipated that, of the SBIR and STTR applications competing at this Council, NINDS will be able to pay first-year direct costs of approximately $3.0 million.

Academic Research Enhancement Award Program

The Council reviewed a total of 19 Academic Research Enhancement Awards (AREA) applications; of this total, 13 applications had primary assignment to NINDS, and 10 of them (76.9 percent) were recommended for support in the amount of $1.0 million direct costs. It is anticipated that NINDS will be able to pay first-year direct costs of approximately $0.6 million.

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XII. Adjournment

The meeting was adjourned at 11:30 a.m. on Friday, May 26, 2000.

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

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.