The 173 rd meeting of the National Advisory Dental and Craniofacial Research Council (NADCRC) was convened on October 2, 2003, at 2:30 p.m., in Building 31, Conference Room 2C19, National Institutes of Health (NIH), Bethesda, Maryland. The meeting was open to the public from 2:30 p.m. until adjournment at 4:10 p.m. Dr. Lawrence A. Tabak presided as Chair.
This meeting was originally scheduled for September 18, 2003, but had to be postponed when the Federal Government was shut down due to impending hurricane weather. The Council subsequently participated in a mail ballot to complete the grant review process and allow for funding decisions before the September 30, 2003, deadline. The open session was rescheduled for October 2 and was conducted as a telephone conference to accommodate the schedules and participation of Council members. The open meeting allowed for NIDCR reporting to the public and for Council's review of concept clearances.
Members Present:
Dr. Louise T. Chow
Dr. Nereyda P. Clark
Dr. Samuel F. Dworkin
Dr. Linda G. Griffith
Dr. Mark C. Herzberg
Dr. Howard K. Kuramitsu
Dr. Harold Morris
Dr. Linda C. Niessen
Dr. Michael J. Reed
Members of the Public Present:
- Dr. Robert J. Collins, Deputy Executive Director, American Association for Dental Research, Alexandria, VA
- Dr. Christopher Fox, Executive Director, International Association for Dental Research, Alexandria, VA
- Mr. Jonathan McLeod, Manager of Legislative and Regulatory Policy, American Dental Association, Washington, DC
- Dr. George W. Taylor, University of Michigan School of Medicine, Ann Arbor, MI
Federal Employees Present:
National Institute of Dental and Craniofacial Research:
- Dr. Lawrence A. Tabak, Director, NIDCR
- Dr. Dushanka V. Kleinman, Deputy Director, NIDCR
- Ms. Carolyn Baum, Committee Management Specialist and Council Secretary, Office of the Director (OD)
- Dr. Patricia S. Bryant, Health Scientist Administrator and Program Director, Behavioral and Social Sciences Research Program, Division of Population and Health Promotion Sciences (DPHPS)
- Dr. María Teresa Canto, Health Scientist Administrator and Program Director, Population Studies Program, DPHPS
- Ms. Mary Daley, Chief Grants Management Officer, Grants Management Branch (GMB), Division of Extramural Activities (DEA)
- Mr. William Foley, Grants Management Specialist, DEA
- Ms. Christen Geiler, Computer Specialist, Office of Information Technology (OIT), OD
- Dr. H. George Hausch, Acting Director, DEA
- Dr. Jeffrey Hyman, Epidemiologist, Health Policy, Analysis and Development Branch (HPAD), DPHPS
- Dr. John W. Kusiak, Health Scientist Administrator and Program Director, Molecular and Cellular Neurobiology Program, Division of Basic and Translational Sciences (DBTS)
- Dr. James A. Lipton, Special Assistant, Research Infrastructure and Curriculum Development Program, OD
- Dr. Dennis F. Mangan, Chief, Infectious Diseases and Immunity Branch, DBTS
- Dr. J. Ricardo Martinez, Executive Secretary, NADCRC, and Associate Director for Program Development, OD
- Ms. Ellie Murcia, Program Analyst, OD
- Ms. Yewande Morgan, Dental Public Health Resident, HPAD, DPHPS
- Dr. Mostafa Nokta, Health Scientist Administrator and Program Director, AIDS and Oral Manifestations of Immunosuppression Program, DBTS
- Dr. Ruth Nowjack-Raymer, Health Scientist Administrator and Program Director, Health Disparities Research Program, DPHPS
- Dr. Bruce L. Pihlstrom, Acting Director, DPHPS
- Ms. Diana Rutberg, Grants Management Specialist, GMB, DEA
- Dr. Ann L. Sandberg, Acting Director, DBTS
- Dr. Jaya Satish, Health Scientist Administrator, Cellular and Molecular Biology, Physiology, and Biotechnology Branch, DBTS
- Dr. Robert H. Selwitz, Chief, HPAD, and Director, Residency Program in Dental Public Health at NIDCR, DPHPS
- Dr. Yasaman Shirazi, Health Scientist Administrator and Program Director, Epithelial Cell Regulation and Transformation Program, DBTS
- Ms. Traci Walker, Committee Management Assistant, OD
OPEN PORTION OF THE MEETING
I. CALL TO ORDER
Dr. Lawrence A. Tabak, Director, NIDCR, called the meeting to order. He invited all the participants, on the conference call and in the conference room, to introduce themselves. He welcomed three new Council members: Dr. Linda G. Griffith, Dr. Mark C. Herzberg, and Dr. Michael J. Reed. Dr. Tabak also welcomed Dr. George W. Taylor, whose approval as a Council member is pending. Three additional individuals have been proposed as Council members: Dr. Eli Capilouto, Dr. Matthew Doyle, and Dr. Josephine Lai.
Dr. Tabak noted that the following three Council members would be retiring from the Council: Drs. Samuel F. Dworkin and Joan Y. Reede and Ms. Kim S. Uhrich.
II. APPROVAL OF MINUTES
The minutes of the Council's meeting on June 16, 2003, were considered and unanimously approved.
III. FUTURE COUNCIL MEETING DATES
The following dates for future Council meetings were confirmed:
January 20, 2004
May 25, 2004
September 28, 2004
January 28, 2005
June 10, 2005
September 23, 2005
IV. REPORT OF THE DIRECTOR
Dr. Tabak presented an overview of NIDCR activities and events since the last Council meeting, highlighting items from the written Director's Report (see Attachment III).
Activities of the NIDCR Director. Dr. Tabak reported that, because of the hurricane weather in the Washington, DC, area, he was not able to fly to Sydney, Australia, to attend the FDI World Dental Congress, but was able to give his presentation on “Saliva as the Diagnostic Fluid of Choice” by teleconference.
Budget Update. Dr. Tabak noted that the President's Budget for FY 2004 requests $382.4 million for NIDCR (including AIDS), which is an increase of approximately 2.9 percent over the FY 2003 appropriation of $371.6 million. Final congressional action is pending. Since October 1 (the beginning of FY 2004), NIH has been operating on a continuing resolution. Dr. Tabak referred the Council members to the NIDCR Congressional Justification narrative for the FY 2004 budget, which is presented on the NIDCR Web site.
DHHS/NIH/NIDCR Activities. Dr. Tabak commented on many activities that have taken place since the previous Council meeting. He noted that the publication A National Call to Action to Promote Oral Health has been issued and is available online at: http://www.nidcr.nih.gov/DataStatistics/SurgeonGeneral/NationalCalltoAction/default.htm. This document is the result of a public–private partnership led by the Office of the Surgeon General, U.S. Department of Health and Human Services (DHHS).
Dr. Tabak also noted that the National Research Council and Institute of Medicine (IOM) issued the report of its study on NIH organization changes. Published on July 29, 2003, the report is entitled Enhancing the Vitality of the National Institutes of Health: Organizational Change to Meet New Challenges and is available online from the National Academies Press at http://www.nap.edu/books/0309089670/html/ . On the day of the Council meeting, October 2, Dr. Elias Zerhouni, Director, NIH, Dr. Harold Varmus, former Director, NIH, and Dr. Harold Shapiro, chair of the IOM panel that conducted the study, testified before a joint committee of Congress on the need for reauthorization of NIH.
Dr. Tabak reported several personnel changes at NIH, as follows. On August 27, Dr. Jeremy Berg was appointed Director, National Institute of General Medical Sciences. On September 1, Dr. Story Landis became Director, National Institute of Neurological Disorders and Stroke. On August 30, Dr. Claude Lenfant, Director, National Heart, Lung, and Blood Institute (NHLBI), retired from Federal Service; Dr. Barbara Alving, Deputy Director, NHLBI, is Acting Director. Dr. Kenneth Olden, Director, National Toxicology Program and National Institute of Environmental Health Sciences, has announced his intention to step down from both posts, but will remain in these positions until a replacement is found. At the end of September, Dr. Ellie Ehrenfeld, Director, NIH Center for Scientific Review (CSR), stepped down for this position, but will continue as Chief, Picornavirus Replication Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases; Dr. Brent Stanfield, Deputy Director, CSR, is Acting Director.
Dr. Tabak noted that he, Dr. Landis and Dr. Patricia Brady, Director, National Institute of Nursing Research, will cochair the NIH Pain Consortium.
Additional details on DHHS/NIH/NIDCR activities are provided in the written Director's Report.
Scientific Advances. Dr. Tabak referred the Council to the many scientific advances described in the written Director's Report.
Personnel Changes at NIDCR. Dr. Tabak reported that NIH operations are shifting toward a trans-NIH orientation. The NIH Roadmap for Medical Research is part of this reorientation of the NIH “way of doing business.” Dr. Tabak is serving on a number of NIH committees to facilitate this reorientation and chairs several committees, including a new steering committee that is serving as a governance committee for NIH.
To assist Dr. Tabak in this expanded role, Ms. Wendy A. Liffers will become Associate Director for Policy Integration, Office of the Director, effective October 18. Ms. Liffers is Director, Office of Science Policy and Analysis (OSPA), NIDCR. In the new position, Ms. Liffers will function as a senior advisor and counselor to Dr. Tabak on trans-NIH activities and policy issues. Dr. Isabel Garcia will serve as Acting Director, OSPA, overseeing implementation of the NIDCR Strategic Plan, and will continue as Co-Director, Residency Program in Dental Public Health at NIDCR.
Dr. Tabak encouraged the Council members to visit the NIH Web site (http://www.nih.gov), which includes information about the broad endeavor to foster a corporate approach at NIH. He noted that this major change at NIH will involve all institutes and centers (ICs) and the extramural community. Dr. Zerhouni presented the NIH Roadmap for Medical Research at a press conference on September 30.
V. CONCEPT CLEARANCES
For the benefit of new Council members, Dr. Tabak reviewed the concept clearance process. NIDCR staff presented nine concepts for Council's review and approval. Four concepts were developed by staff in the Division of Population and Health Promotion Sciences (DPHPS), and five were developed by staff in the Division of Basic and Translational Sciences (DBTS).
Division of Population and Health Promotion Sciences
Dr. Ricardo Martinez, Executive Secretary, NADCRC, introduced Dr. Bruce L. Pihlstrom, Acting Director, DPHPS, who presented a brief update of NIDCR's clinical research program. Dr. Pihlstrom noted that NIDCR has developed this program over the past year as part of its implementation of the NIDCR Strategic Plan. In June 2002, the Council approved two concepts, for a clinical trials program and for infectious disease clinical trials. The former was initiated in December 2002, and a program announcement requesting applications for the latter will be issued in late fall 2003.
Dr. Pihlstrom commented that clinical research involves other activities as well as clinical trials. The four concepts to be presented by staff emphasized observational, epidemiological, behavioral, social science, and health disparities research. Dr. Pihlstrom noted that NIDCR anticipates requesting applications in the four concept areas in late fall 2003. The four concepts are summarized as follows.
Exploratory Grants in Epidemiological, Behavioral/Social Sciences and Oral Health Disparities Research
Dr. María Teresa Canto, Health Scientist Administrator and Program Director, Population Studies Program, DPHPS, described a proposed Program Announcement (PA) to stimulate developmental and exploratory research and to strengthen the NIDCR clinical research program by testing methods and collecting preliminary data. Grants would be awarded using the NIH Exploratory/ Developmental Research Grant Award (R21) mechanism for new projects in the early and conceptual stages of research. Examples of the research that would be supported include epidemiological research (e.g., studies of diagnostic criteria and genetic/environmental determinants); behavioral research (e.g., studies of methods for assessing and influencing oral health literacy or attitudes and behaviors affecting oral health); and health disparities research (e.g., studies to develop, modify, and validate methods for assessing and influencing health in minority and special needs populations).
In discussion, the Council encouraged NIDCR to cite cognitive neuroscience research whenever advocating epidemiological and social science research. The Council suggested accordingly that the title of the concept be changed to add the words “Cognitive Neuroscience” after “Behavioral/Social Sciences.” Dr. Canto indicated that NIDCR would incorporate the change as allowed within the space allotted for a PA title.
The Council unanimously approved the concept.
Epidemiological, Behavioral, and Health Disparities Research
Dr. Patricia S. Bryant, Health Scientist Administrator and Program Director, Behavioral and Social Sciences Research Program, DPHPS, described a proposed PA to stimulate studies on behavioral and environmental determinants of oral health in individuals and communities and to develop strategies to improve oral health across all segments of the population. Examples of the research to be supported include epidemiological research (e.g., longitudinal studies of incidence and risk factors for oral infectious diseases or understudied conditions such as salivary dysfunction and oral facial pain); behavioral research (e.g., studies in population groups to evaluate and test methods to improve oral health literacy and to identify behavioral and environmental determinants of compliance with oral health regimens); and health disparities research (e.g., studies to enhance patient–provider communication and to improve oral health outcomes in disadvantaged or underserved populations). Dr. Bryant noted that the findings from this research would be used to enhance NIDCR-supported clinical research.
In discussion, the Council commented on the importance of oral health literacy, the need for broad educational efforts beginning in preschool, and the need for device development and physical therapy programs related to oral health for individuals with physical disabilities. Dr. Dushanka V. Kleinman, Deputy Director, NIDCR, noted that NIH and NIDCR have published an oral health curriculum supplement for elementary school teachers entitled “Open Wide and Trek Inside.” This publication is part of the NIH Curriculum Supplement Series for grades 1-2.
The Council unanimously approved the concept.
Research on Special Needs Populations and the Elderly
Dr. Ruth Nowjack-Raymer, Health Scientist Administrator and Program Director, Health
Disparities Research Program, DPHPS, presented a proposed PA to encourage research on understudied special needs populations and to support oral health projects nested within ongoing funded research in special needs or elderly populations. She noted that the NIDCR Strategic Plan emphasizes the need for a full range of research for all vulnerable populations, including those with special needs, such as individuals who have physical disabilities, mental retardation, or HIV/AIDS and elderly persons with disabilities. Examples of the research to be supported in special needs and elderly populations include epidemiological research (e.g., studies to document the prevalence, incidence, and determinants of oral, craniofacial, and dental diseases) and behavioral and other types of clinical research (e.g., studies of the impact of oral disease on oral health quality of life and general health outcomes, efficacy of care, and approaches to prevent or control detrimental oral effects of medications, treatments, or feeding practices).
The Council unanimously approved the concept.
Practice-Based Research Network (PBRN)
Dr. Jeffrey Hyman, Epidemiologist, Health Policy, Analysis and Development Branch, DPHPS, described a proposed Request for Applications (RFA) to establish PBRNs that would support a variety of clinical studies that have clear and clinically relevant outcome measures. Applicants may propose to develop a network, operate a network, and/or conduct clinical studies in a network. Dr. Hyman noted that PRBNs are a popular approach for conducting clinical studies. Using this cost-effective approach, researchers can conduct clinical trials and studies directly in the practice community and can focus more closely on effectiveness than on efficacy. Dr. Hyman noted that PBRNs are ideally suited to clinical research conducted in dental practices and will enable NIDCR to support a large number of clinical studies at reasonable cost. Researchers will be able to draw on the experience and insight of practitioners when framing research questions, and the results are likely to be more acceptable to practitioners and to be translated into practice. Dr. Hyman noted commented that NIDCR expects universities and coordinating centers to respond to the RFA and anticipates funding each PBRN for 5 to 8 years.
The Council applauded this concept. Members asked for clarification of some details. The Council emphasized the need for longer-term funding of networks, beyond the typical 3 to 5 years for NIH awards and, preferably, approaching 10 years. Members encouraged NIDCR to ask applicants to describe the research content or issues to be addressed by the PBRN and to include a curriculum component in the RFA to allow for training of practitioners in dental schools or continuing education programs. The Council also encouraged NIDCR to note in the RFA the importance of collaboration with other scientists and of maintaining a high level of science and peer review.
The Council unanimously approved the concept.
Division of Basic and Translational Sciences
Dr. Ann L. Sandberg, Acting Director, DBTS, introduced the presenters for the five concepts developed by DBTS.
AIDS-Related Oral Malignancies and Tumors
Dr. Mostafa Nokta, Health Scientist Administrator and Program Director, AIDS and Oral Manifestations of Immunosuppression Program, DBTS, described a proposed RFA to improve understanding of the biological basis of the development of AIDS-related oral cancers and tumors and to identify targets for treatment, early diagnosis, and monitoring of disease progression. He noted that the hallmark of HIV infection is a gradual depletion of CD 4+ cells which eventually leads to a state of immunosuppression that predisposes patients to oral cancers, warts, and preneoplastic oral lesions, many of which are aggressive and hard to treat. The incidence of some tumors and malignancies has changed since the introduction of highly active antiretroviral therapy (HAART) in the late 1990s. For example, the incidence of Kaposi's sarcoma has decreased significantly, while the incidence of others (e.g., plasmablastic lymphoma and oral warts) has increased. The reasons for these differences are not known. The proposed PA would support research to determine the genetic susceptibility of hosts to oral tumors and malignancies, pathogenic mechanisms of viral infections (e.g., Epstein-Barr virus, Kaposi's sarcoma virus, human papillomavirus) that promote malignancies, the genomics and proteomics of tumors, and novel molecular targets for therapy, diagnosis, and monitoring. NIDCR anticipates that the initiative would stimulate new research to define the genetic, physiological, immunological, and biochemical basis for development of AIDS-related oral malignancies.
In discussion, the Council supported this effort as a fine, comprehensive program that fits well with the NIH Roadmap initiatives.
The Council unanimously approved the concept.
Development of In Vitro Models of Oral Mucosa Relevant to AIDS and Mucosal Infections
Dr. Nokta described a proposed RFA to encourage research leading to the development and validation of physiologically relevant in vitro models of the oral mucosa for study of HIV infection and oral complications associated with AIDS under highly controlled conditions. He noted that this research is difficult to do in patients because of the inability to control for xerostomia and to use infectious agents. The in vitro models will provide a basis for exploring diagnostic, therapeutic, and prevention strategies for HIV infections, concurrent viral infections, and AIDS-associated complications. Dr. Nokta noted that recent advances in tissue engineering and molecular and cell biology have led to methodologies for constructing tissues using carefully designed scaffolds on which cells proliferate and differentiate. These bioengineered tissues can be manipulated to express phenotypic surface markers and to produce immune modulatory cytokines, such as the interleukins and tumor necrosis factor. The challenge is to develop a system that comprises mucosal epithelial cells and other cellular elements, including those of the immune system (e.g., lymphocytes, macrophages, dendritic cells), as well as appropriate extracellular matrix proteins. NIDCR anticipates that investigators responding to this RFA will capitalize on new findings in scaffold development, cell biology of the oral mucosa, genomics and proteomics, bioimaging, and real-time analysis of gene expression.
In discussion, the Council agreed that this initiative to develop organotypic models was timely and important and could advance research on HIV/AIDS and other diseases such as oral cancer and fungal infections. Members suggested that the RFA specify the use of human tissues and the source of these tissues (i.e., from healthy donor volunteers).
The Council unanimously approved the concept.
Multidisciplinary Approach for Research on Oral Complications of HIV Infection
Dr. Nokta presented a proposed RFA to encourage multidisciplinary, highly integrated research on the oral complications of HIV infection and their prevention. He noted that this field of research is sufficiently mature to benefit from integrated multidisciplinary studies on a common theme. A comprehensive approach to address the oral complications of HIV infection is timely and would expedite research in areas such as the association of complications with chronic viral infections of the oral cavity, HIV-related salivary gland disorders, and oral mucosal immunity to microbial pathogens. NIDCR expects that the research would increase knowledge of the basic mechanisms involved in the pathogenesis of oral disorders associated with AIDS and will include identification of novel targets and strategies for preventing and managing these pathological conditions. The initiative would have potential to attract distinguished investigators from a variety of disciplines and to create environments that nurture young investigators in research on the oral manifestations of AIDS.
In discussion, the Council noted that this initiative would be a welcome opportunity to broaden the field of research to the full range of disciplines. The Council suggested that multidisciplinary studies should include epidemiology, behavioral, and public health research, pain research, and research on maintenance of oral functions (e.g., eating, swallowing).
The Council unanimously approved the concept.
Regenerative Dental Medicine
Dr. Sandberg presented a proposed RFA to encourage use of human stem cells (embryonic and post-natal) and bioengineering approaches for the repair and regeneration of orofacial tissues and organs. She noted that scientists have recently identified post-natal stem cells from a number of orofacial structures (e.g., dental pulp) and that use of human embryonic stem cells in research is now scientifically possible. Consequently, researchers have an opportunity to use these stem cells in combination with new biomaterials to regenerate complex structures. The RFA would encourage studies to (i) understand the unique properties of embryonic and post-natal stem cells in orofacial tissues; (ii) develop methods to induce appropriate stem cell expansion and differentiation and assemble a functional tissue prototype in vitro; and (iii) design and develop new bioinspired materials for cell transplantation. NIDCR expects that the initiative would encourage researchers from different disciplines (e.g., cell and molecular biology, genetics, physics, engineering, computer, clinical sciences) to collaborate and collectively explore new avenues for regenerative dental medicine.
In discussion, the Council noted that this initiative complements the previous concept of multidisciplinary research on oral complications of HIV infection.
The Council unanimously approved the concept.
Mechanisms of Orofacial Pain: Anatomy, Genomics, and Proteomics
Dr. John W. Kusiak, Health Scientist Administrator and Program Director, Molecular and Cellular Neurobiology Program, Division of Basic and Translational Sciences (DBTS), described a proposed RFA to stimulate research on the molecular mechanisms underlying chronic orofacial pain by using interdisciplinary approaches to identify proteins and protein networks critical to processing nociceptive information. He noted that the impetus for the initiative lies in the completion of the sequencing of the human genome and the rapid development of genomic, proteomic, and imaging approaches that now enable researchers to study, more globally, the molecular mechanisms leading to orofacial pain and strategies for treating orofacial pain. Untreated acute pain leads to chronic pain, debilitation, and reduced quality of life, and the costs of not being able to treat chronic pain effectively are substantial. The RFA would encourage researchers to use genomic, proteomic, imaging, and computational technologies to discover the molecular mechanisms involved in acute orofacial pain, transition from unrelieved acute pain to chronic pain (i.e., neuroplasticity), neuronal hyperexcitability manifested as hyperalgesia and allodynia, and chronic, orofacial pain disorders of inflammatory and neuropathic origin. NIDCR anticipates that the research would lead to identification of new therapeutic targets and novel approaches for managing orofacial pain.
In discussion, the Council noted that the initiative was exciting. The Council encouraged NIDCR to revisit the concept and, with reference to the NIH Roadmap, consider broadening the research that would be supported to include behavioral and emotional correlates of acute and chronic phases of pain and the transition from acute to chronic pain. The Council discussed the need for objective, measurable markers of nociception that could be correlated with individuals' perceptions of acute and chronic pain.
The Council unanimously approved the concept.
CLOSED PORTION OF THE MEETING
As stated at the beginning of these minutes, the Council held a mail ballot prior to the October 2 meeting for consideration of grant applications. This process 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).
For the mail ballot, there was a discussion of procedures and policies regarding voting and confidentiality of application materials, committee discussions, and recommendations. Members absented themselves from voting on applications from their own institutions, or other applications in which there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to this effect.
VI. REVIEW OF APPLICATIONS
Grant Review
For the mail ballot, the Council considered 358 applications requesting $73,405,751 in total costs. The Council recommended 266 applications for a total cost of $56,043,622 (see Attachment II).
ADJOURNMENT
The meeting was adjourned at 4:10 p.m. on October 2, 2003.
CERTIFICATION
I hereby certify that the foregoing minutes are accurate and complete.
_____________________________
Dr. Lawrence A. Tabak
Chairperson
National Advisory Dental and Craniofacial Research Council
_____________________________
Dr. J. Ricardo Martinez
Executive Secretary
National Advisory Dental and Craniofacial Research Council
ATTACHMENTS
I. Roster of Council Members
II. Table of Council Actions
III. Director's Report to the NADCRC, September 2003
NOTE: A complete set of open-portion handouts is available from the Executive Secretary.