Date: September 24, 2007
Place: Building 31, Conference Room 6
National Institutes of Health
Bethesda, Maryland
U.S. DEPARTMENT OF HEALTH
AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
The 186th meeting of the National Advisory Dental and Craniofacial Research Council (NADCRC) was convened on September 24, 2007, at 8:30 a.m., in Building 31, Conference Room 6, National Institutes of Health (NIH), Bethesda, Maryland. The meeting was open to the public from 8:30 a.m. to 12:00 p.m. followed by the closed session for Council business and consideration of grant applications from 1:00 p.m. until adjournment at 2:30 p.m. Dr. Lawrence A. Tabak presided as Chair.
Members Present:
Dr. Gilda Barabino
Dr. Matthew J. Doyle
Dr. Marianne Bronner-Fraser
Dr. Eli Capilouto
Dr. Elias Boneta
Dr. Cecile Feldman
Ms. Katherine Hammitt
Dr. Josephine Lai
Dr. Jon D. Levine
Dr. Anne S. Lindblad
Dr. Harold Morris
Dr. Malcolm Snead
Dr. Philip Stashenko
Dr. George Taylor
Members of the Public Present:
Dr. Kenneth Anusavice, University of Florida
Dr. Eugene Anderson, American Dental Education Association
Mr. Jack Bresch, American Dental Education Association, Washington, DC
Dr. Aida A. Chohayeb, Women Network Collective Research, Washington, DC
Dr. Perry Kirkham, Purdue University
Ms. Gina Luke, American Association for Dental Research
Dr. Daniel Melamud, NYU School of Dentistry
Ms. Myla Moss, American Association for Dental Research
Dr. Bruce Pihlstrom
Mr. Daryl Pritchard, American Association for Dental Research, Alexandria, VA
Mr. Louis Terracio, New York University
Federal Employees Present:
National Institute of Dental and Craniofacial Research:
Dr. Lawrence A. Tabak, Director, NIDCR
Dr. Isabel Garcia, Deputy Director, NIDCR
Dr. Robert C. Angerer, Scientific Director, Division of Intramural Research (DIR)
Dr. Norman S. Braveman, Executive Secretary, NADCRC and NIDCR Board of Scientific Counselors, and Assistant to the Director, OD
Mr. Peter Anas, NIDCR
Dr. Jane Atkinson, NIDCR, CCR
Dr. Albert Avila, NIDCR
Dr. Henning Birkdal-Hansen, Associate Director for Program Development, NIDCR
Mr. Hong Cao, NIDCR
Dr. Maria Teresa Canto, NIDCR
Dr. Lois Cohen, NIDCR
Mr. Kevin Crist, NIDCR, GMB
Ms. Mary Daley, Chief Grants Management Officer, GMB, DEA
Dr. Alicia Dombroski, Deputy Director, Division of Extramural Activities
Dr. Kathy Hayes, NIDCR
Ms. Joann Hertges, NIDCR
Dr. Lynn King, NIDCR
Dr. Eleni Kousvelari, Acting Director, CBI
Dr. Raj Krishnaraju, NIDCR
Dr. John W. Kusiak, Director, Molecular and Cellular Neuroscience Program, CIBID
Dr. Yujing Liu, Scientific Review Administrator, SRB, DEA
Dr. Nadya Lumelsky, Program Director, Tissue Engineering and Regenerative Dental Medicine Program, CBI
Dr. R. D. Lunsford, NIDCR
Ms. Amy McGuire, NIDCR
Dr. Pamela McInnes, Director, CIBID
Dr. Mostafa Nokta, Program Director, AIDS and Immunosuppression Program, CIBID
Dr. Ruth Nowjack-Raymer, Program Director, Health Disparities Research Program, CCR
Dr. Melissa Riddle, NIDCR
Dr. Yasaman Shirazi, Program Director, Epithelial Cell Regulation and Transformation Program, CIBID
Dr. Lillian Shum, Program Director, Mineralized Tissue and Salivary Gland Physiology Program, CIBID
Ms. Rebecca Wagonner-Miller, NIDCR
Ms. Traci Walker, Committee Management Assistant, OD
Dr. Peter Zelarowski, NIDCR
Other Federal Employees:
Ms. Linda Berman, SSS
Ms. Mary Fran Deutsch, OPERA
Ms. Linda Naini, SSS
Mr. Craig Vandewalle, USAF
OPEN SESSION
I. WELCOME AND INTRODUCTIONS
Dr. Lawrence A. Tabak, Director, NIDCR, called the meeting to order and welcomed everyone. He invited the Council members, NIDCR staff and meeting guests to introduce themselves.
Dr. Tabak welcomed new Council member Ms. Katherine Hammitt, noting that she has been a strong patient advocate for the Sjogren’s syndrome Foundation and has played a key role in the Friends of the NIDCR. He also introduced two new scientific review administrators in the Scientific Review Branch, Dr. Mario Rinaudo and Dr. Rebecca Wagenaar Miller. Dr. McInnes, Director, Center for Integrative Biology and Infectious Diseases, introduced Dr. Melissa Riddle, the newly appointed Chief of the Behavioral and Social Sciences Branch in the NIDCR intramural program. Prior to employment at NIDCR, Dr. Riddle was responsible for an extramural program at the National Institute of Drug Abuse in behavioral interventions to reduce substance abuse leading to HIV infection. She is also active in evaluating programs for the Interdisciplinary Research Working Group of the NIH Roadmap.
II. APPROVAL OF MINUTES
Dr. Norman Braveman, executive secretary of the Council, invited approval of the minutes of the May 18, 2007 Council meeting. On motion duly made and seconded, the minutes were unanimously approved.
III. REPORT OF THE DIRECTOR, NIDCR
Dr. Lawrence Tabak
Dr. Tabak reported that he had testified before the Senate Appropriations Subcommittee for Labor, HHS and Education on the NIH fiscal year 2008 proposed budget, an experience that was a rewarding discussion with the Subcommittee that offered an opportunity to highlight recent advances at NIH. The President’s FY 2008 budget calls for $389.7 million for NIDCR, with $51 million for the Office of the Director.
There were a number of speaking opportunities for the Director since the last Council meeting, including a recent interview at Montclair State University for a television program, Tomorrow’s Medicine Today. NIH Director Dr. Elias Zerhouni participated in the interview, as did Dr. David Zuchanski, a noted cancer researcher at Johns Hopkins University. The interview will be edited for a program on the Public Broadcasting System.
Dr. Tabak noted that the Deputy Director, Dr. Isabel Garcia, has been active in community outreach, including delivering the keynote address at the first meeting of the Consortium on Informatics, convened at the Tufts School of Dental Medicine. The objective of the Consortium is to develop a standardized electronic health record to enable data sharing among research institutions. In addition, Dr. Garcia was awarded the Juan Carlos Findlay Award at the USPHS Officers Association’s Scientific and Training Symposium in June, presented to her for outstanding achievement and leadership in improving access to health care. The award was named for Dr. Findlay who isolated the mosquito vector for yellow fever in 1881.
There have been a number of research-related update programs. In September, the NIH hosted the Third Annual Directors’ Pioneer Awards Program, at which Dr. David Relman spoke. He is an imminent infectious disease researcher and a leader in the area of the Human Microbiome Project and the chairman of the NIDCR Board of Scientific Counselors.
Dr. Tabak announced that NIDCR has instituted improvements in the RO3 grants program, increasing the budget cap from $100,000 to $150,000 over two years, and decreasing the PI time effort requirement from 25% to 20%. This should provide a greater incentive for researchers to consider the RO3 program.
There have been some significant successes by NIDCR trainees and career development awardees, including first R01 awards to Dr. Jessica Lee (UNC) and Dr. Janet Quinn (ADA Paffenberger Research Center), and second R01 awards to Dr. Kristin Artinger (University of Colorado Health Science Center) and Dr. Janina Lewis (Virginia Commonwealth University). There have also been a number of recent publications from K awardees.
Finally, Dr. Tabak announced that Dr. Bruce Pihlstrom had retired from federal service since the last Council meeting. He had served as Acting Director for the Center for Clinical Research. He made a special contribution by supporting dentistry and other health care professions within the Clinical and Translational Science Awards Program.
IV. DISCUSSION OF THE REORGANIZATION OF THE EXTRAMURAL RESEARCH PROGRAMS
Dr. Lawrence Tabak
Dr. Tabak explained a recent reorganization of NIDCR. Prior to the reorganization there had been a Center for Integrative Biology and Infectious Diseases, under which were there branches -- Integrative Biology and Infectious Diseases, Translational Genomics Research and Behavioral and Social Sciences Research. Those three branches have been placed under a new Division of Extramural Research and the Center has been subsumed in the new Division.
V. UPDATE ON THE NIH PEER REVIEW ASSESSMENT
Dr. Lawrence Tabak
Dr. Tabak announced that NIH has, in partnership with the scientific community, begun an assessment of the peer review process. Science has become more complex, interdisciplinary research has become more important and prevalent, and the assessment will deal with how the peer review system has responded to those changes.
Two NIH groups are supporting the study -- an external work group of the Advisory Committee to the NIH Director (Dr. Tabak and Dr. Keith Yamamoto, co-chairs), and an internal working group on peer review with Dr. Tabak and Dr. Jeremy Berg, NIGMS serving as co-chairs. The working groups are currently involved in several initiatives looking at the mechanisms of peer review, a “diagnostic” phase of the assessment. Hundreds of inquiries have been sent to various members of the research community asking for opinions about peer review processes, core values, criteria, and scoring. Dr. Tabak emphasized that additional comments are welcome, whether or not an individual received an inquiry, and all comments will be considered even though the official comment period has ended. Dr. Tabak added that a series of “town meetings” were being held in several cities that would include members of the research community as well as representatives of associations and patient advocacy groups.
The review is on a fast track at the direction of the NIH Director, who is anticipating a report by December 2007. After looking at how other non-HHS agencies handle peer review, the work groups will develop a number of pilot programs for the spring of 2008. All of this data will provide the resources for the development of a revised peer review policy.
To provide a glimpse of some of the ideas being considered by the work groups, Dr. Tabak presented several “emerging ideas.” For example, one is the focus of the review: should it be on the project or the person; should it be retrospective or prospective; and should there be different kinds of applications for different kinds of projects? In the area of review mechanics, should there be a two-stage review (along the lines of an editorial review), electronic review, a way for applicants and reviewers to interact, different application requirements for new concepts versus extensions of established lines of research, a method for presenting interdisciplinary research applications, a process to deal with multiple applications by the same PI, and a way to provide feedback to applicants?
Concerning reviewers, should reviewers have access to data about similar projects, should there be incentives and/or penalties to encourage effective reviews, and should the scoring process be improved to give the applicant frank information about the quality of the application, so that a poor or inadequate applications would not receive an inflated, though unfundable, score that might encourage the applicant to spend more time on the resubmission process?
During discussion, Dr. Tabak explained that a contractor had been hired to develop a plan to classify and tabulate the responses. The contractor is charged with defining the majority opinions on the various questions, but also to identify individual responses that that appear to have value but do not fit into the basic majority categories. Dr. Tabak noted that it is conceivable that the majority opinion may deem the present peer review system acceptable. Even so, sufficient points will be identified to provide fodder for future enhancements to the process.
There were a number of suggestions from the Council. There was a comment that the focus of the process should be on improving reviewers. Some reviewers fall short of expectations as do some Scientific Review Administrators and there may be a morale issue to be addressed. In the past participation in a study section was a more collegial and rewarding experience than it is now; some see peer review as a chore and some incentives should be considered to counter that perception. One positive development would be to reduce the number of reviews and especially re-reviews, and it would be helpful to streamline the process, something that electronic submission may make more practicable. If the time frame of the review cycle were reduced, it would accommodate more rapid resubmission. It was also noted that an increase in the availability of grant money would help, although Dr. Tabak noted that this was not in the purview of the work groups. Finally, there was a comment that standardization of the application might help reviewers move through the process more efficiently.
In closing, Dr. Tabak noted that significant input had been received from individuals involved in the Roadmap tests, and that the work group leaders would meet with individuals involved in the last peer review assessment
VI. RESEARCH, CONDITION AND DISEASE CATEGORIZATION (RCDC) UPDATE
Dr. Timothy Hays, Office of the Director, NIH
Dr. Timothy Hays explained that NIH has reported research expenditures to Congress annually. The various reports covers 360 research categories, most of which are posted on the NIH Office of Budget web site (http://www.nih.gov/news/fundingresearchareas.htm). The process of selecting those categories and tracking them over time is about to be changed. The incentive for the change was partly the result of two National Academy reports, which prompted NIH to initiate a pilot program in 2004. That pilot, the Research, Condition, and Disease Categorization (RCDC) project, was initially successful and resulted in a congressional mandate to establish it as a continuing program.
The RCDC system categorizes all research grants, intramural research, and research and development (R&D) contracts for all institutes and centers in one database. The 360 categories are being standardized to apply to all NIH institutes and centers (previously each center developed its own definition wording, which introduced inconsistencies in the way data was coded). It tracks all funding and lists each project on the basis of the 360 categories. It is designed to be rapidly updated and allows the creation and inclusion of new categories as they emerge.
Research projects will be described in the system (title, abstract, specific aims) in detail and a number of standard key descriptors will be included in each project file, including total funding. An extensive dictionary of words and phrases (over 300,000) will allow the employment of a text mining strategy against the research descriptions for categorization purposes. If a project falls within a category, the total funding for the project will be recorded in that category. Projects can fall into multiple categories which is the same as the current NIH reporting strategy and will continue to be explained to anyone who will use the NIH reporting system where RCDC categorization data will be displayed.
The system will become operational in late 2008 and the results will be released in February 2009. Since it will rely on specific definitions for each category which may vary from earlier definitions, there will be significant differences from the current system for some categories (differences in both funding amounts and in project listings). There will be a year when use of the new and old methodologies will be used (Fiscal Year 2007) to display how the category numbers differ solely due to a change in methodology.
During the discussion, Dr. Hays explained that the new NIH reauthorization requires NIH to begin associating patents and publications to research projects. OPASI would like to use these measures in addition to other metrics for future evaluation and analysis. There was a comment that the outcome measurement should include a qualitative element, as well as the quantitative data mentioned (papers and patents). This would allow a “story line” to be developed over time to show project accomplishments, which could be incorporated in a revised project description.
Asked whether the RCDC system would reveal gaps in research, Dr. Hays explained that there was consideration of using the NIH and other databases from other agencies and organization to ascertain whether there are actual gaps and in what way the gaps that do exist should be addressed.
Asked about the long-term expectations for the RCDC, Dr. Hays noted that the focus is on getting the system up and running, but that there is clearly a potential for long-term research planning. Dr. Tabak cautioned that the 2008 data should be considered a baseline and that future applications beyond those currently envisioned (basically a reporting tool) would have to develop later. He added that the reporting process had been in operation for years, but its consistency had been less than optimal because of the lack of standardized definitions. This new RCDC approach will provide a consistent view of all NIH research.
VII. CONCEPT CLEARANCES
Dr. Braveman announced that the Council would consider five concept clearances for new areas of research.
A. Harnessing Inflammation for Reconstruction of Oral and Craniofacial Tissues
Dr. Nadya Lumelsky
Dr. Nadya Lumelsky explained that this research initiative was a joint effort of two NIDCR programs at the Center for Integrative Biology and Infectious Diseases. The objective of this initiative is to develop new approaches and paradigms for controlling tissue inflammatory microenvironment as a means to overcome acute and/or chronic inflammation and to facilitate reconstruction of oral and craniofacial tissues damaged by disease or injury. Inflammation is a process that protects tissue from bacterial infection and other insults, but if the inflammation is not resolved it can progress to chronic inflammation, which can destroy tissue. It is important, therefore, to understand how tissues resolve or fail to resolve inflammation. It is known that resolution of inflammation is not a simple process of suppressing the inflammation -- there are spatial and temporal aspects to the process. It is apparent that traditional treatment and modes of delivering therapeutics are not sufficiently effective. Biotechnology and nanotechnology may provide answers.
Dr. Malcolm Snead, noting that inflammation is an aspect of most injury and disease, agreed that it was appropriate to seek ways to thwart the inflammatory process in a proactive way. This research is timely and appropriate. Dr. Gilda Barabino agreed that advances in tissue engineering also support the timeliness of research that might identify ways to manipulate and deliver molecules in the framework of the inflammatory process. Dr. Phillip Stashenko observed that the research described deals mainly with infectious disease, so that infectious disease clinicians should be included in the research design.
On motion duly made and seconded, the concept clearance related to inflammation and reconstruction was unanimously approved.
B. FaceBase Project: Functional Genomics of Development and Disease
Dr. Lillian Shum
Dr. Lillian Shum discussed the FaceBase Project, an initiative that includes elements of data collection, integration and analysis at the systems level, as well as eventual clinical applications. The research will rely on building the FaceBase resource, a database that houses data including the genomics of craniofacial birth defects to facilitate the design of strategies for the restoration of craniofacial structures affected by these defects, disease or injury. The FaceBase Project should encourage multidisciplinary participation in craniofacial research.
FaceBase offers three opportunities. First, we will build a database for collected data, supported by a bioinformatics hub that will facilitate management of research data for the craniofacial research community. Second, we will have research consortia including a number of collaborative projects, each of which will target a specific aspect of craniofacial development and diseases. Third, FaceBase will facilitate technology development as a resource to encourage innovative approaches to craniofacial research (e.g., high resolution imaging of developmental processes in vivo). The ultimate goal is to understand the complex regulatory network governing normal craniofacial morphogenesis and the variations that lead to diseases and disorders.
Dr. Marianne Bronner-Fraser endorsed the research project, noting that it could bring together disparate investigators working on a whole range of related projects from genetics to developmental biology to imaging. It could encourage an integrative approach to the research. Dr. Jon Levine agreed that the concept addresses a major health problem that calls for effective research, and that research could be improved by bringing the players together in a more integrative approach. Dr. Snead asked how such a disparate group of researchers, from very different research organizations, looking at very different areas than craniofacial, could be brought together by the project. Dr. Shum indicated that initially it would focus on research of the craniofacial complex, but future collaboration with other institutes, such as NICHD, which is building a birth defects database, is warranted. Dr. Tabak added that there is an important resource in the Blueprint for Neuroscience Research Project, to which this effort could in time be linked. He agreed that the initial focus would be limited to the craniofacial research community.
On motion duly made and seconded, the concept clearance related to the FaceBase Project was unanimously approved.
C. HIV/AIDS
Dr. Mostafa Nokta
Dr. Mostafa Nokta requested concept clearance approval for an interdisciplinary study of oral complications related to HIV/AIDS infection in specific vulnerable populations, including IV drug abusers, minorities and children. African Americans comprise about 17% of the US population, but almost half of HIV-infected individuals belong to that minority. Oral lesions often aid in early diagnosis of HIV infection and disease progression. Children are also significantly affected. In addition to the infectious complications of the oral cavity, HIV infected children develop dental caries at a higher rate than the general population, and exhibit delayed dental eruption and retention of primary teeth.
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Therefore, it would be a significant contribution to the knowledge base to define the burden of disease, deterrence of the origins of HIV-related oral disease, and the improvement in access to proper dental health care for the vulnerable populations. The research would address those issues, as well as look at salivary gland disorders and oral mucosal response to the microbial pathogens associated with HIV infection.
Dr. George Taylor agreed that the research was timely and important, not only for the prevention of the conditions mentioned and the expansion of the epidemiology knowledge base, but for the overall improvement in health care and quality of life in these vulnerable, minority populations. Dr. Stashenko agreed that the concept’s unique characteristic is that it addresses a specific population that is particularly vulnerable to HIV infection.
On motion duly made and seconded, the concept clearance related to the study of HIV/AIDS in relation to oral health was unanimously approved.
D. Clinical Trials Management Support Contract
Dr. Pamela McInnes
Dr. McInnes requested Council concurrence with the establishment of a clinical research management and data coordinating support contract to provide support for NIDCR’s entire research program, intramural and extramural research that includes Phase I to Phase IV clinical studies. Current management is decentralized and not as well coordinated as it should be -- reporting, pharmacovigilance, quality monitoring, data safety monitoring, etc. It is time to bring these functions under a more coordinated and streamlined organizational structure. That would include collaboration on study design and development of proposals, help in preparing study documents, study-specific training, clinical trials operations, data management, statistical analysis support, monitoring for safety and quality, regulatory support (e.g., working with FDA on INDs), logistical support for a range of study requirements, and assistance in achieving publication of papers related to studies.
Dr. Matthew Doyle observed that the project would be a cost-effective, core capability with standard operating procedures and consistent accountability. Given the highly complex research structure, regulatory mandates, the need for pharmacovigilance and budget efficiency, the proposal is timely and well-designed. He suggested that governance and organizational structure be carefully considered, and a written strategic plan should be developed. There should be a single responsible person in NIDCR to guide the program to fruition and there should be a formal advisory committee or board established to support the individual responsible. Consideration should be given to obtaining outside help (e.g., from an academic institution) in developing the organization. Finally, if an outside contract is selected, there should be well-defined roles for NIDCR intramural/extramural staff and the PIs and specific procedures defined to interface with the organization. Dr. Doyle endorsed the project.
Dr. Elias-Boneta also supported the proposal, recalling a number of under-powered studies and studies of weak design that he had seen in the past few years. Secondly, since studies involve human subjects, there could be a training component that specifically deals with cultural sensitivity. Communications with the local communities should be part of that training. He noted that the last review of the guidelines for detection criteria was in 1991, it would be appropriate to consider an update to that and to epidemiological guidelines. Dr. Elias-Boneta affirmed his support of the proposal.
There was an extended discussion about the specific responsibilities and authority that the organization would have. Dr. McInnes explained that the organization would not displace any functions that currently exist in any study which are necessary for the study to be properly carried out. However, if a study lacked any aspect of organization, management, structure, quality and safety assurance, the support available from the organization would not be optional. Dr. Tabak explained that it would be a resource for PIs in developing effective study protocols and structures, and a staff extender for NIDCR that would ensure that all studies had the proper support to effectively accomplish all required aspects of a high quality study in a consistent manner.
On motion duly made and seconded, the concept clearance related to the clinical trials management support contract was unanimously approved.
E. Developing Complex Models of Oral Behavior
Dr. Melissa Riddle
Dr. Melissa Riddle requested Council consideration of the proposal to develop complex models of oral behavior. The goal is to discover new ways to conceptualize and model behavioral and social contributors to oral health, and then to develop a foundation for successful oral health interventions. During the past decades the field of behavioral and socials science has developed a more and more sophisticated foundation for such a study. These tools are available to apply to the problems related to maintaining oral health, which has at the same time revealed a much more complex nature. Since traditional research has been mainly linear, relying on cause and effect analysis, Dr. Riddle stated that a more sophisticated, longitudinal research approach is now appropriate, relying on the complex modeling systems that are now available. Those systems allow the researcher to analyze daily life functions and interactions with family, society, and the individual’s health care provider network.
Dr. Anne Lindblad agreed that the timing was right for selecting appropriate complex modeling systems to conduct longitudinal studies to show that personal behavior choices do affect oral health. Dr. Eli Capilouto agreed, noting that the current atmosphere that includes an Internet that encourages personal experience sharing should be helpful in accumulating data for the complex modeling systems. He added that a real challenge will be translating the research results into a practical approach to customizing health care.
On motion duly made and seconded, the concept clearance related to the development of complex models of oral behavior was unanimously approved.
VIII. ADJOURNMENT OF THE OPEN SESSION
Dr. Braveman adjourned the open session at 12:00 p.m., to reconvene in closed session at 1:00 p.m.
CLOSED SESSION
This portion of the meeting was closed to the public in accordance with the determination that it was concerned with matters exempt from mandatory disclosure under Sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).
X. REVIEW OF APPLICATIONS
Grant Review
ADJOURNMENT
The meeting was adjourned at 2:30 p.m.
CERTIFICATION
I hereby certify that the foregoing minutes are accurate and complete.
________________________ _________________________
Dr. Lawrence A. Tabak Dr. Norman S. Braveman
Chairperson Executive Secretary
National Advisory Dental and National Advisory Dental and
Craniofacial Research Council Craniofacial Research Council
ATTACHMENTS
I. Roster of Council Members
II. Table of Council Actions
III. Director’s Report to the NADCRC, September 2006
NOTE: A complete set of open-portion handouts is available
from the Executive Secretary.