Date: January 27, 2015
Place: Conference Room 6
National Institutes of Health
The 208th meeting of the National Advisory Dental and Craniofacial Research Council (NADCRC) was convened on January 27, 2015, 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 12:02 p.m.; it was followed by the closed session for Council business and consideration of grant applications from 1:05 p.m. until adjournment at 1:48 p.m. Dr. Martha Somerman presided as Chair.
Dr. Hector G. Balcazar (via telephone)
Dr. Teresa Ann Dolan
Dr. Jane B. Lian (via telephone)
Dr. Mary L. Marazita
Dr. Anne C. R. Tanner
Dr. Jane A. Weintraub
Dr. Benjamin Alexander White, Jr.
Dr. J. Leslie Winston
Ad Hoc Participants
Dr. Yang Chai
Dr. Richard Peters Darveau
Ms. Tracy Smith Hart
Members of the Public
Dr. Shenda Baker, President and COO, Synedgen Inc., Claremont, CA
Dr. Christopher H. Fox, Executive Director, International Association for Dental Research (IADR)/American Association for Dental Research (AADR), Alexandria, VA
Mr. Timothy Leeth, Senior Director for Federal Relations, Policy Center - Advocacy and Government Relations, American Dental Education Association (ADEA), Washington, D.C.
Dr. Evelyn Lucas-Perry, Director of Public Policy Research, Policy Center- Educational Research and Analysis, ADEA, Washington, D.C.
Dr. Daniel Meyer, Senior Vice President of Professional Affairs and Chief Science Officer, American Dental Association, Chicago, IL
Dr. Carolyn Primus, Principal, Primus Consulting, Bradenton, FL
Federal Employees Present
National Institute of Dental and Craniofacial Research
Dr. Martha J. Somerman, Director
Dr. Alicia Dombroski, Executive Secretary, and Director, Division ofExtramural Activities (DEA)
Dr. Lillian Shum, Director, Division of Extramural Research (DER)
Dr. Robert Angerer, Scientific Director, Division of Intramural Research (DIR)
Dr. Janice Lee, Deputy Clinical Director, DIR
Dr. John W. Kusiak, Office of the Director (OD), Senior Advisor to the Director
Dr. Sayo Adunola, OD, Office of Science Policy and Analysis (OSPA)
Dr. Jane C. Atkinson, DER, Center for Clinical Research (CCR)
Dr. Karina Boehm, OD, Office of Communications and Health Education (OCHE)
Dr. Dave Clark, DER, Behavioral and Social Sciences Research Branch (BSSRB)
Mr. George Coy, Office of Administrative Management (OAM), Chief, Financial Management Branch (FMB)
Dr. Kevin Crist, DBA, Grants Management Branch (GMB)
Ms. Mary A. Cutting, DER, CCR
Mr. Bret Dean, OAM, FMB
Dr. Donald DeNucci, DER, CCR
Dr. James L. Drummond, DER, Integrative Biology and Infectious Diseases Branch (IBIDB)
Dr. Bruce Dye, OD, OSPA
Dr. Dena Fischer, DER, CCR
Dr. Leslie Frieden, DEA, Research Training and Career Development Branch (RTCDB)
Mr. Joel Guzman, DER
Dr. Emily Harris, DER, Translational Genomics Research Branch (TGRB)
Ms. April Harrison, DEA, GMB
Ms. Jeannine Helm, DER, Translational Genomics Research Branch (TGRB)
Dr. Victor Henriquez, DEA, Scientific Review Branch (SRB)
Dr. Jonathan Horsford, OSPA
Ms. Candice Isaac, NIH Intern, DEA, SRB
Dr. Tamara James, OD, OSPA
Dr. WendyKnosp, OD, OSPA
Dr. Raj Krishnaraju, DBA, SRB
Ms. Susan Lowenthal, DEA, GMB
Dr. Nadya Lumelsky, DER, IBIDB
Dr. R. Dwayne Lunsford, DER, IBIDB
Dr. Yu-Ling Minteer, OD, OSPA and OCHE
Dr. Marilyn Moore-Hoon, DEA, SRB
Mrs. Debbie Pettitt, DBA, GMB
Mr. John Prue, OD, Office oflnformation Technology (OIT)
Dr. Melissa Riddle, DER, BSSRB
Ms. Delores Robinson, DBA
Mr. Mark Schaaf, OIT
Dr. Steven Scholnick, DER, TGRB
Dr. Marushka Silveria, OD, OSPA
Ms. Megan Skidmore, NIH Intern, OAM, FMB
Ms. Kathleen Stephan, OD, Associate Director for Management, OAM
Other NIH Employees
Dr. Matthew Portnoy, NIH SBIR/STTR Program Manager, Office of Extramural Research, NIH
Mr. Nyron Rouse, Office of the Director, NIH Training Center
Dr. Gary Schumacher, ADA Paffenbarger Research Center, National Institute of Standards and Technology, Department of Commerce, Gaithersburg, MD
I. WELCOME AND INTRODUCTIONS
Dr. Martha Somerman, Director, NIDCR, called the 208th meeting of the Council to order. She welcomed Council members, guests, and other attendees who were participating via the NIH videocast. She invited guests atthe meeting to introduce themselves.
Dr. Somerman introduced Ms. Kathleen Stephan, NIDCR' s new Associate Director for Management. She noted that Mr. George Coy, who has been serving as Acting Associate Director for Management, will resume his role as Chief, Financial Management Branch (FMB), Office of Administrative Management. Ms. Carol Loose, who has been Acting Branch Chief, FMB, will resume her previous duties in FMB. Dr. Somerman noted that Ms. Stephan has extensive administrative experience at the NIH and comes most recently from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. She held previous positions at the National Cancer Institute and the National Center for Complementary and Alternative Medicine, which recently was renamed the National Center for Complementary and Integrative Health.
Dr. Somerman announced that Dr. John Kusiak has been appointed Senior Advisor to the Director, NIDCR, and will become Acting Deputy Director, NIDCR. She noted that Dr. Kusiak, who was Acting Chief, Integrative Biology and Infectious Diseases Branch (IBIDB), Division of Extramural Research (DER), will continue to represent the NIDCR in trans-NIH activities.
Dr. Somerman encouraged the Council members to peruse the 2014 New Investigator Profiles, which was provided to them. Commenting on her written Director's Report to Council: January 2015, she mentioned that NIDCR's meeting with representatives of the American Dental Association (ADA) on December 17 also included Ms. Mary Dietrich, ADA's Director of Congressional Affairs [see pp. 2-3 in the report.]
NIDCR staff introduced additional personnel who have recently joined the NIDCR. Mr. John Prue, Chief, Office of lnformation Technology (OIT), introduced Mr. Mark Schaaf, who recently joined the OIT staff. On behalf of Dr. Margo Adesanya, Acting Director, Office of Science Policy and Analysis (OSPA), Dr. Jonathan Horsford, Health Science Policy Analyst, OSPA, introduced the following three new staff members: Dr. Bruce Dye, the new director of NIDCR's Dental Public Health Residency Program, who will also direct and conduct dental epidemiology and public health research; Dr. Wendy Knosp, a health science policy analyst who will focus on legislative issues; and Dr. Yi-Ling Minteer, a program support assistant who will serve in both OSAP and the NIDCR Office of Communications and Health Education (OCHE).
Dr. Dye introduced two new residents in the Dental Public Health Residency Program: Dr. Sayo Adunola, a behavioral scientist with a D.D.S./Ph.D. from the University of Maryland, who is using NHANES data to study unmet dental needs; and Dr. Marushka Silveria, who has a Ph.D. in epidemiology and an M.P.H. from the University of Massachusetts at Amherst and is studying factors that affect choices in oral behaviors among Latino and Hispanic populations.
Dr. Yasaman Shirazi, Division of Exramural Activities (DEA), introduced Ms. Candice Isaac, an intern in the NIH Pathways Internship Program, who will assist the SRB in support of NIDCR's peer review function. Mr. Coy introduced Ms. Megan Skidmore, an NIH intern who is on rotation with the NIDCR.
Dr. Robert Angerer, Scientific Director, introduced Dr. Janice Lee, who is currently Deputy Clinical Director, Division of lntramural Research (DIR), and will become NIDCR's new Clinical Director, DIR, as soon as an effective date is announced. He noted that Dr. Lee served in the DIR in 2000-2002 and was appointed Deputy Clinical Director in 2013. Prior to this appointment, she was a professor in the department of oral and maxillofacial surgery at the University of California at San Francisco. Dr. Angerer remarked that Dr. Lee is an international expert in clinical craniofacial reconstruction and has made significant contributions to the NIDCR, which include development of the DIR draft strategic plan.
Dr. Angerer thanked Dr. James Melvin for his skillful leadership as DIR's Clinical Director since 2009. He noted that Dr. Melvin led the revitalization of the clinical program and will resume his full-time research in DIR's Secretory Mechanisms and Dysfunction Section.
Dr. Somerman welcomed three ad hoc participants whose appointments as Council members are pending. Introduced at the Council's September 2014 meeting, these are: Dr. Yang Chai, Ostrow School of Dentistry, University of Southern California, Los Angeles; Dr. Richard Peters Darveau, School of Dentistry, University of Washington, Seattle; and Ms. Tracy Smith Hart, Osteogenesis Imperfecta Foundation, Gaithersburg, Maryland.
II. FUTURE MEETING DATES
September 18, 2015
January 22, 2016
September 20, 2016
III. APPROVAL OF MINUTES FROM PREVIOUS MEETING
Dr. Alicia Dombroski, Executive Secretary, NADCRC, also welcomed the Council members, guests, and virtual participants. She invited the Council to consider and approve the minutes of the September 17, 2014, Council meeting. The Council unanimously approved the minutes.
IV. REVIEW OF COUNCIL OPERATING PROCEDURES
Dr. Dombroski noted that the NADCRC reviews its operating procedures at the January Council meeting. She informed the Council that the NIDCR is not recommending any changes to the current procedures. She invited the Council to recommend changes, and none was offered. The Council unanimously approved the operating procedures.
V. REPORT OF THE DIRECTOR, NIDCR
Dr. Somerman reported on the NIDCR budget for Fiscal Year (FY) 2014 and FY 2015 and several NIH initiatives. She invited Council's questions on the written Director's Report to Council: January 2015, which was provided to the Council members and is available on the NIDCR website.
FY 2014 Budget: "That Was the Year That Was"
Dr. Somerman reported that the NIDCR's FY 2014 budget totaled approximately $397.8 million, rising slightly from the significant cut in FY 2013. The NIDCR allocated the budget as follows: extramural research (77 percent, or approximately $308.6 million), intramural research (16 percent, or approximately $64.7 million), and research management and support (6 percent, or approximately $24.4 million, ofwhich about 32 percent goes to NIH central assessments).
Elaborating on the extramural research budget, Dr. Sotnerman reported that the NIDCR supported a total of 627 research grants (which accounted for 79 percent of the extramural budget). The grants included 534 research project grants (RPGs), of which 167 were new, competing RPGs (awarded from approximately 780 RPG applications submitted). Also included were Small Business Innovation Research and Small Technology Transfer Research (SBIR/STTR) awards (which accounted for 3.2 percent of the extramural budget), research centers (4 percent), career development (2 percent), and other research (1 percent). The NIDCR also supported 266 research training awards (4 percent) and 21 research contracts (7 percent). The extramural support funded many activities across a wide portfolio of program areas.
Dr. Somerman reported that investigator-initiated RPGs (ROls) continued to be the "bread and butter" of NIDCR's extramural program, accounting for the majority of funds expended. She noted that cooperative agreements continued to be an important area of support and that the NIDCR continued to indease its use of the R56 (High-Priority Short-Term Project Grant) bridging grant. In addition, she noted that, in accordance with a congressional mandate to expand SBIR/STTR programs, the NIDCR will increase the percentage allocated to these two programs to 3.65 percent in FY 2017. In FY 2014, the NIDCR funded 30 SBIR/STTR awards, for a total cost of $9.7 million ($1.2 million for STIR, and $8.5 million for SBIR). [See section VIII below for the NADCRC's special session on SBIR/STTR programs.]
Dr. Somennan reported that the NIH success rates for RPGs declined markedly between FY 2001 and FY 2014 and that the NIH is undertaking a major effort to increase these rates despite the flat NIH budgets. In FY 2014, the success rates for RPGs at the NIH and the NIDCR increased slightly, to 18.1 percent for the NIH and 21.4 percent for the NIDCR.
Dr. Somennan noted that the NIDCR funded three specific initiatives in FY 2014. These were for functional characterization of oral cancer initiating cells (11 awards), innovative approaches and technologies for examining the uncultivable bacteria of the oral microbiota (2 awards), and FaceBase 2: craniofacial development and dysmorphology—data management and integration hub (11 awards).
FY 2015 Budget and Initiatives
Dr. Somennan reported that NIDCR's FY 2015 operating budget totals approximately $397.7 million. This amount, which is less than the FY 2014 budget, may be further reduced by the impact of transfers to the Secretary, U.S. Department of Health and Human Services (HHS). Dr. Somennan noted that the NIH budget authorization was included in the $1.2 trillion "Cromnibus" spending bill for FY 2015, which was signed by President Obama on December 17, 2014, and authorized spending for all Federal agencies except the Department of Homeland Security. The NIH appropriation is for $30.1 billion, which is $150 million more than in FY 2014.
Dr. Somennan highlighted several items of interest to the NIH and NIDCR in the spending bill. These include specific funding increases for brain and pediatric research; collaboration with the National Academy of Sciences to examine the public's understanding of scientific research; and language relevant to junior investigators (e.g., programs to increase their success rates, approaches to reduce the age when they obtain their first R01, and continued support for innovator/pioneer awards).
Dr. Somennan noted that Congress's draft legislation on the 21st Century Cures initiative is expected soon. She highlighted changes within key congressional appropriations and authorizing committees for the NIH, as a result of the mid-term elections, and noted that the NIH has benefited from bipartisan support in these committees. She added that the 114thCongress includes three dentists: Representative Mike Simpson (R-ID), Representative Paul Gosar (R-AZ), and just-elected Representative Brian Babin (R-TX).
Dr. Somennan noted that NIDCR's purchasing power has declined continually since FY 2003 and is much less in FY 2015 than it was in FY 2003. Although the NIDCR appropriations rose slightly in FY 2014 after the cut in FY 2013, it remains flat in FY 2015, whereas NIDCR's purchasing power continues to fall, due to the effect of inflation.
Dr. Somennan noted that the quality of research supported through NIDCR extramural and intramural programs remains high and that the Institute will continue to expand initiatives as a way to attract scientists into dental, oral, and craniofacial research. The NIDCR initiatives for FY 2015 include Requests for Applications (RFAs) in the following areas: planning grants for dental, oral, and craniofacial tissue regeneration consortium resource centers; next-generation rapid testing and point-of-care diagnosis for oral pathogens; approaches to eliminate HIV and opportunistic infections from oral reservoirs; targeting co-dependent molecular pathways in oral cancer; and a multidisciplinary and collaborative research consortium to reduce oral health disparities in children. The Council will be reviewing applications submitted for these initiatives during FY 2015.
In addition, the NIDCR has released the following five FY 2015 Program Announcements (PAs): NIDCR Behavioral or Social Intervention Clinical Trial Planning Grant; NIDCR Clinical Trial or Biomarker Clinical Validation Study Planning Grant; NIDCR Clinical Trial or Biomarker Clinical Validation Study Cooperative Agreement; Biology of the Temporomandibular Joint in Health and Disease; and Building Genetics and Genomic Knowledge about Dental, Oral, and Craniofacial Diseases and Disorders. The due dates for submitting applications in response to these PAs are open.
Dr. Somerman listed additional opportunities which the NIDCR is developing as future Funding Opportunity Announcements (FOAs) open to all researchers. These include the effects of e-cigarette aerosol mixtures on oral and periodontal epithelia; immune system plasticity in pathogenesis and treatment of complex dental, oral, and craniofacial diseases; novel or enhanced dental restorative materials for class V lesions; oral mucosal immunization approaches for HIV prevention; pharmacogenomics of oral pain management; and NIDCR institutional research training programs.
Dr. Somerman commented on three NIH-wide activities. She reported that the NIH has funded 11 centers under the Big Data to Knowledge (BD2K) trans-NIH initiative led by Dr. Philip Bourne, Associate Director of Data Science, NIH. She emphasized that the dental research community needs to be involved in this initiative, and she noted that no proposals have been submitted by dental researchers. She encouraged the Council members to consider the initiative and to help advertise it to their colleagues and within their communities.
Dr. Somerman reported that the National Children's Study Working Group of the Advisory Council to the Director (ACD), NIH, has submitted its report, which recommends that the current study, as outlined, is not feasible and that alternative approaches are needed. Dr. Somerman said that the NIH is closing down the program, but interest in children's health remains high.
Dr. Somerman said that a response from the external review of the NIH Intramural Research Program, which includes reflections on its next 10 years, will be presented to the ACD at its next meeting, in June 2015. She noted that comments received during this review include encouraging the NIH to increase trans-NIH collaboration among institutes and centers (ICs), to foster collaboration between intramural and extramural programs, and to sustain support for the NIH Clinical Center.
Dr. Christopher H. Fox, Executive Director, International Association for Dental Research/American Association for Dental Research, noted that the Cromnibus bill calls for a 5-year strategic plan for the NIH. He asked how the NIDCR and Council will ensure that NIDCR's successes are conveyed in the plan. Dr. Horsford replied that the NIDCR has not yet received any information concerning how the NIH will respond to the legislation, but the NIDCR will ensure that it is "at the table" and represented in the planning effort and eventual plan.
VI. BIENNIAL REPORT TO COUNCIL ON TRACKING AND INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH
Dr. Jane Atkinson, Director, Center for Clinical Research, NIDCR, presented the 2015 Biennial Advisory Council Report Certifying Compliance with the NIH Policy on Inclusion Guidelines, dated January 27, 2015. Like all ICs, the NIDCR is required to report on the tracking and inclusion of women and minorities in clinical research every 2 years to its advisory council. The NIH Revitalization Act of 1993 requires that the NIH ensure that women and minorities and their subpopulations be included in all clinical research; that women and minorities and their subpopulations be included in Phase III clinical trials in numbers adequate to allow for valid analyses of differences in intervention effects; that cost is not an acceptable reason for excluding these groups; and that the NIH initiate programs and support for outreach efforts to recruit and retain women and minorities and their subpopulations as participants in clinical studies.
Dr. Atkinson summarized FY 2013 and FY 2014 data on applications reviewed and enrollment of women and minorities. She noted that more than 95 percent of extramural grant applications that involved human subjects met the target enrollment inclusion requirements when submitted to the Initial Review Group for peer review. She also noted that, in comparison with data from FY 2011 and FY 2012, the number of subjects enrolled was similar, whereas the number of clinical protocols had decreased somewhat.
Dr. Atkinson reported that the FY 2013 and FY 2014 data on enrolled subjects by sex/gender and ethnicity show that most (58.6 percent in FY 2013, and 51.6 percent in FY 2014) were female; that enrolled subjects who were Hispanic or Latino comprised 11.8 percent in FY 2013 and 13.9 percent in FY 2014; and that 9.1 percent of enrolled subjects in FY 2014 were of unknown gender. She noted that data from the protocols indicated that sex/gender reporting was not available for some studies utilizing specimens from bio-repositories. Three studies accounted for 92 percent and 95 percent of the enrolled subjects with unidentified sex/gender reported in FY 2013 and FY 2014, respectively. The data on race for the 2 years show that most enrolled subjects were white (52.9 percent and 65.1 percent, respectively), followed by black or African American (18.3 percent and 10.1 percent, respectively), and Asian (10.9 percent and 6.0 percent, respectively). Participants who chose not to report their race are included in the Unknown category (comprising 12.6 percent and 12.0 percent, respectively). The remaining categories are American Indian/Alaska Native, Hawaiian/Pacific Islander, and those reporting more than one race-each of which comprised approximately 3 percent or less of enrolled subjects. Dr. Atkinson noted that, in FY 2011 and FY 2012, the percentage enrollmentin each category was similar to that for the NIH [comparison with NIH data for FY 2013 and FY 2014 NIH was not available at the present time].
With regard to enrollment in Phase III trials, Dr. Atkinson reported that more than 4,000 subjects were enrolled in three Phase III trials in FY 2013 and that approximately 6,000 subjects were enrolled in four Phase III trials in FY 2014. Most of the subjects (more than 60 percent) enrolled in Phase III trials were female. Dr. Atkinson noted that participation of some minority populations was higher in Phase III trials than in all aggregated studies because the Phase III trials targeted populations with health disparities. For example, the percentage of participants who were American Indian/Alaska Native was 61.3 percent and 48.4 percent in FY 2013 and FY 2014, respectively, compared with those who were Hispanic (36.5 percent and 38.7 percent, respectively) and those who were Black or African American (0.8 percent and 10.1 percent, respectively).
Dr. Atkinson also reported data on the enrollment of women and minorities in clinical research conducted in the NIDCR Intramural Program. She noted that slightly fewer than 5,000 subjects were enrolled in 18 intramural research protocols in FY 2013 and that approximately 3,600 subjects were enrolled in 19 intramural research protocols in FY 2014. Female participation was high (67 percent and 74 percent, respectively), while Hispanic participation (6 percent) was lower than that in extramural studies. The percentage of Black/African American participants was 12 percent and 13 percent, respectively, and that of Asian participants was 7 percent and 8 percent, respectively.
Dr. Atkinson reported that in October 2014, the NIH launched a new system (the Inclusion Management System) to track NIH compliance on inclusion of women and minorities in clinical research. She noted that in the new system, principal investigators (rather than the NIH) enter inclusion data. Also, the system allows for program monitoring of enrollment, using embedded tools displaying actual versus planned enrollment for each racial and ethnic category, and for end-of-year reports on inclusion that separate the data on studies of existing data sets from those enrolling new subjects. Dr. Atkinson said that the NIDCR is on track with the entire NIH in implementing the system. In addition, the NIDCR is working with investigators who are contributing samples to tissue data banks to assure their reporting of inclusion data.
In response to a question from the Council about the recent decline in number of clinical protocols, Dr. Atkinson noted that this is a trend to monitor. Asked about the possibility of disaggregating the racial categories of Hispanic subjects, she noted that participants are asked to self-identify and that many Hispanics self-identify as white. She anticipated that the new system may make it possible to tease out such overlaps.
The Council voted unanimouslyto accept the biennial report.
VII. CONCEPT CLEARANCE
Dr. Dombroski noted that the purpose, scope, and objective of concepts developed by NIDCR staff for funding are presented at the Council's open, public meetings for discussion and Council's review and approval. Staff presented one concept, as follows.
Dr. Lillian Shum, Director, DER, presented the concept of a new NIDCR Award for Sustaining Outstanding Achievement in Research (SOAR), which would utilize the R35 grant mechanism. The R35 is a pilot NIH-wide mechanism which ICs can utilize and tailor to meet specific needs. For the NIDCR, the overall goal for SOAR is to provide sustained and flexible support to NIDCR-funded investigators who have outstanding records of research productivity and are entering their mid-career stage, to enable them to conduct exceptionally innovative research that has unusual potential to improve improving dental, oral, and craniofacial health.
Dr. Shum noted that the SOAR concept is responsive to a recent posting (July 14, 2014) by Dr. Sally Rockey and Dr. Francis Collins, entitled "Formula for Innovation: People + Ideas + Time." The authors encourage development of new ways of investing biomedical research dollars to provide sustained support for investigators and to allow them the "freedom to innovate and explore new lines of inquiry."
Dr. Shum noted that the National Cancer Institute (NCI) is the first IC to issue an FOA using the R35 mechanism. The basic requirements of the mechanism are as follows: Only applications from a single program director or principal investigator are allowed (i.e., applications from multiple directors or investigators will not be accepted). The level of effort proposed must be a minimum of 50 percent of the investigator's time. A direct cost of up to $750,000 per year is allowed, and up to 8 years of support could be provided. In their applications, in lieu of "specific aims," applicants are asked to describe an overall vision for their research program, as well as research challenges and directions, with emphasis on innovation for advancing their research field.
Dr. Shum presented the options that the NIDCR is considering for its SOAR award. She noted that eligibility would be limited to investigators who have completed one R01/U01 project period and have had 5-9 years of continuous NIDCR R01/U01 support. Letters of support would be required from the applicant's institution. Reviewers would evaluate the investigator's prior accomplishments and his or her plans to build on these accomplishments to formulate a highly innovative research program. Reviewers also would assess whether the investigator's track record of scientific innovation and productivity could continue at a soaring trajectory toward ground-breaking research. In addition, they would review the investigator's track record of mentorship and service to the research community.
Dr. Shum noted that awardees would be expected to consolidate their NIDCR R01 support. They could apply for additional NIDCR support only during the extension segment of the award (i.e., years 6-8), but could apply for additional support from other ICs at any time. The initial period of the award would be for 5 years, which could be extended for up to 3 years depending on progress reviews. Progress would be assessed annually based on standard reporting requirements. Awardees would be invited to an annual meeting to present their accomplishments, focusing on innovation. And, investigators would have the freedom, within the broadly defined scope of the research, to move in unanticipated directions while emphasizing research of high risk or unusual potential.
Following Dr. Shum's presentation, two discussants for the Council, Dr. Mary L. Marazita and Dr. Yang Chai, commented on the proposed concept. Dr. Marazita noted that the NIDCR R35 award is an exciting new program that would fill an important gap in research training and career development. She commended the NIDCR on the proposed goals and structure. In response to her suggestion that the process for "bundling" NIDCR' s research support should be flexible so as to allow for different funding cycles of awards, Dr. Shum noted that the aim would be to merge an investigator's NIDCR ROls into the R35.
Dr. Chai thanked the NIDCR for the opportunity to comment on the proposed concept. He noted that requiring a 50 percent level of effort will help to ensure the quality of research conducted, and he suggested that applicants be required to have had successful re-competitions of their ROl as a demonstration of their commitment to the research area.
The Council applauded the concept as an exciting opportunity for investigators. In response to questions, Dr. Shum reiterated that the NIDCR is defining mid-career investigators eligible for this award as those who have had 5-9 years of continuous NIDCR support. She suggested that within NIDCR's current portfolio, perhaps a couple of hundred of investigators would be eligible to apply for the R35. She noted that the number of investigators receiving an R35 award is not likely to be large because it is a pilot mechanism, the success of which has not been measured, and that the NIDCR will want to balance its investment in this and other mechanisms. Dr. Shum said that the NIDCR anticipates issuing the FOA as a one-time opportunity and that it could possibly become a continuing program. She noted also that the NIDCR could request funding support for the pilot effort from the NIH Office of the Director. The Council commented that an applicant's demonstration of mentorship will be important.
The Council unanimously approved the concept.
VIII. SPECIAL SESSION ON THE SMALL BUSINESS INNOVATION AND TECHNOLOGY TRANSFER RESEARCH GRANT PROGRAMS
Dr. R. Dwayne Lunsford, Coordinator, Small Business Programs, and Director, Microbiology Program, Integrative Biology and Infectious Diseases Branch (IBIDB), DER, introduced the session and speakers. The first two speakers presented an overview of the NIH and NIDCR SBIR and STIR programs. The second two speakers, who have received SBIR awards, provided a grantee's perspective.
Overview of the HHS/NIH Small Business Programs
Dr. Matthew Portnoy, SBIR/STTR Program Manager, Office of Extramural Research, NIH, summarized the history, budget, criteria, and current status of the SBIR and STIR programs. The NIH is the largest HHS participant in the two congressionally mandated programs and is the second largest participant, after the U.S. Department of Defense (DoD), among all Federal agencies.
Dr. Portnoy noted that the Congress mandated the SBIR and STIR programs 10 years apart (1982 and 1992, respectively) and reauthorized them in FY 2011 with a combined authorization of set-aside funds through FY 2017. The SBIR program enables for-profit small business concerns to engage in Federal research and development (R&D) with potential for commercialization. The STIR program facilitates cooperative R&D between small business concerns and not-for-profit U.S. research institutions with potential for commercialization. The overall aims are complementary, but different: the SBIR program supports technological innovation and privatesector commercialization of Federal R&D, while the STIR program specifically supports technology transfer between small businesses and research institutions.
Dr. Portnoy reported that in FY 2014, the SBIR and STIR programs received 2.8 percent and 0.4 percent, respectively, of the NIH extramural budget—for a total of approximately $758 million ($663 million and $95 million, respectively). He noted that the NIH accounts for about 98 percent of all HHS dollars for the programs and that 24 of 28 NIH components participate. Total support by the ICs ranges from less than $1 million, from the National Library of Medicine, to about $110 million, from NCI. In FY 2013, total support across all Federal agencies was approximately $2.3 billion.
Dr. Portnoy described the SBIR/STIR program as a three-phased program of discovery, development, and commercialization, beginning with a feasibility study (Phase I) and moving on to full research/R&D activity (Phase II) with competing renewal/R&D (Phase IIB), and ending with commercialization (Phase III). He outlined the budgets and timelines for each phase, noting that they are greater in Phase II/IIB than in Phase I, and he said that the NIH is generally not involved in Phase III, which is a time for partnering and fulfilling an exit strategy.
Dr. Portnoy summarized the eligibility criteria for applicants. · He noted that SBIR and STIR awards are always made to a small business, which is defined as a for-profit U.S. business with 500 or fewer employees, and that NIH SBIR/STIR participants tend to be small startups with only 10-20 employees. Three tiers of ownership of the small business are possible, but majority ownership must be held by U.S. citizens or residents, are quirement that is determined at the time of award. With few exceptions, all work must be done within the United States. And, for STIR awardees, the formal cooperative R&D effort must include a minimum of 40 percent performed by the small business and a minimum of 30 percent performed by the U.S. research institution.
Dr. Portnoy highlighted several critical differences in the programs with regard to partnering and work requirements and a principal investigator's employment status. He commented that the most common query from potential applicants is whether to apply for an SBIR or an STIR award. He encouraged potential applicants to contact the NIH's SBIR/STIR program officers in the ICs to address any concerns. Dr. Portnoy noted that, in FY 2014, the NIH launched an informative, interactive NIH SBIR/STTR website (http://sbir.nih.gov) which includes a section entitled "New to SBIR/STTR," which provides up-to-date information for new applicants.
Dr. Portnoy reported that the success rate for Phase I and Phase II SBIR and STIR awards was higher in FY 2014 than in FY 2013. For these years, the success rates for SBIR awards were 18.1 percent and 40.5 percent, respectively, while those for STIR awards were 20.3 percent and 42.5 percent, respectively. He noted also that the success rate for fast-track SBIR awards increased from 15.7 percent to 21.6 percent, whereas the success rate for fast-track STTR awards fell from 26.8 percent to 8.3 percent.
Elaborating on the provisions of the FY 2011 reauthorization of the SBIR and STTR programs, Dr. Portnoy noted the following changes: (i) The minimum percentage of set-aside monies, as required by law, increases to 2.9 percent and 0.4 percent, respectively, in FY 2015, and rises to 3.0 percent and 0.45 percent, respectively in FY 2016. In FY 2017, the SBIR set-aside rises to 3.2 percent, while the STIR set-aside remains at 0.45 percent. (ii) New SBIR/STIR standard due dates for applications become effective on September 5, 2015. For cycle I, the due date is now September 5; for cycle II, the due date is January 5; and for cycle III, the due date is April 5. There is no August 15,2015, due date (see notice NOT-OD-15-038 at http://grants.nih.gov). (iii) Small business concerps that are majority-owned by multiple venture capital operating companies (VCOCs), hedge funds, and/or private equity firms are now eligible to apply (see NOT-OD-13- 071). (iv) NIH SBIR/STIR applicants may now "switch" programs at Phase II or Phase IIB to any active NIH SBIR/STIR solicitations, thus giving awardees flexibility to apply for different phases and/or programs. (v) Small businesses that are seeking an SBIR award and are ready for the Phase II stage of development can bypass applying for a Phase I grant by utilizing a separate FOA (see PAR-14-088 and PAR-14-265). This pilot program is authorized through FY 2017 for only the NIH, DoD, and Department of Education.
Dr. Portnoy noted that the NIH issues many FOAs for SBIR and STIR programs. He said that most applications are received in response to "parent" HHS-wide solicitations (i.e., PA-14-071, SBIR; and PA-14-072, STIR). In addition, the NIH supports an SBIR Contract Solicitation and other opportunities announced in the NIH Guidefor Grants and Contracts. Dr. Portnoy mentioned that approximately 95 percent of SBIR/STIR awards are grants, and 5 percent are contracts. He noted that the NIH also offers gap funding between the SBIR/STIR phases, as well as two technical assistance programs—a Niche Assessment Program (NAP) for Phase I awardees, and a Commercialization Assistance Program (CAP) for Phase II awardees. [For further details and information, see http://sbir.nih.gov.]
Dr. Somerman thanked Dr. Portnoy for his thorough presentation. The Council suggested that the tracking of awardees could help explain why some Phase I recipients do not go on to apply for Phase II awards. The Council commended the NIH's inclusion of success stories on the SBIR/STIR website and noted that the site does not include an example from dental research. Dr. Portnoy commented that the site's success stories are submitted by companies.
Overview of the NIDCR Small Business Program
Dr. Lunsford presented a first-time "snapshot" of the NIDCR' s small business program, using FY 2014 data. He noted that retail sales in the dental product market totaled approximately $2.2 billion in the first half of FY 2013, according to data from the Dental Trade Alliance, and that the largest sales by far came from dental restoratives and infection control products. He noted that the total sales amount placed dental products in the middle of retail sales for the top 10 pharmaceutical drugs in FY 2013.
Focusing on the SBIR and STIR programs, Dr. Lunsford reported that the NIDCR funds investigator-initiated applications received in response to two solicitations, SBIR PA-14-071 and STIR PA-14-072, which are broadly written to cover all dental-related research. The NIDCR also supports the following two targeted FOAs: (i) Imaging Diagnostics of Dental Diseases and Conditions (STIR PA-12-193 for R41/R42 awards, and SBIR PA-12-195 for R43/R44 awards), which expires 4/6/15; and (ii) Early Stage Development of Technologies in Biomedical Computing, Bioinformatics, and Big Data Science (SBIR PA-14-154 for R43/R44 awards), which expires 5/18/17. A third FOA, Next-Gen Rapid Testing and Point-of-Care Diagnosis for Oral Pathogens (STIR RFA-DE-15-001 for R41/R42 awards), expired 11/21/14.
In FY 2014, the NIDCR allocated 2.8 percent of its extramural budget (or approximately $8.5 million) to the SBIR program and 0.4 percent (or approximately $1.2 million) to the STIR program, and approximately $45,500 was transferred as an NIH administrative assessment. The largest number of grants funded clinical research and materials development, and other research areas were cancer, salivary glands and immunology, tissue engineering, behavioral and social sciences, AIDS/immunosuppression, and mineralized tissue. Dr. Lunsford noted that the current portfolio does not include research in microbiology, as applications in this area are handled by the NIDCR's extramural Microbiology Program.
Dr. Lunsford noted that the SBIR/STIR program also supports a diverse portfolio of companies. In recent years, these companies have contributed, for example, to refinement of the 3D tooth atlas and use of whole plasma and derivitized tubing in dentistry.
Development of a Novel Polysaccharide Drug for Oral Care: A Small Business Perspective
Dr. Shenda Baker, President and COO, Synedgen, Inc., Claremont, CA, and former NIDCR SBIR awardee, described the oral care product development program at Synedgen, Inc., recent research at the company, and challenges in drug development. She highlighted the value of the SBIR program, its impact on her work, and lessons learned.
Dr. Baker noted that interest in developing a novel polysaccharide drug for oral care arises from the need to prevent and control infection. Summarizing the infection process, she noted that access to cell surfaces and their toll-like receptors, or innate immune sentinels, is regulated by polysaccharides and glycocalyx—and that when immune responses become exacerbated, which occurs when surfaces are breached and threats are unchecked, inflammatory diseases (e.g., periodontal disease, mucositis) and diseases rooted in systemic inflammation (e.g., diabetes, cystic fibrosis, colon cancer) take hold. Dr. Baker said that Synedgen is developing targeted polysaccharides to modify the glycobiology of cell surfaces so as to solve real-time problems in mucosal, pulmonary, and dermal damage and inflammation and infection. The researchers are mimicking the role of defensins and protective surface-active polysaccharides at mucosal and dermal interfaces in the oral cavity, gastrointestinal (GI) tract, airways, and dermis.
Dr. Baker described Synedgen as a forward-thinking, medical technology company dedicated to developing life-saving products and therapies that encourage wound healing, reduce complications of tissue damage and inflammation, prevent infection by drug-resistant bacteria, and remove the biofilms in which they thrive. She noted that initial synthesis and testing of concept polysaccharides took place at Harvey Mudd College, using private corporate funding, and that subsequent research, conducted at Synedgen, was funded initially by a grant from the U.S. Department of Army, which supported exploratory research on infection and wound healing in oral, GI, and ophthalmic areas. Dr. Baker noted that angel investors have been and continue to be critical in supporting items (e.g., infrastructure, attorneys, marketing, patents, travel) that are not covered by government grants.
Dr. Baker emphasized that the NIH SBIR program is key to "driving" a particular product and that without NIDCR's SBIR funds, Synedgen would not have been able to move forward in the areas of periodontal disease or mucositis. Having a Phase I SBIR award enabled the researchers to establish preliminary proof-of-concept, with in vitro data, for antimicrobial and regenerative treatment of periodontal disease. They quantified the residence time of a polysaccharide on a cell surface and found that the higher the dose and duration, the greater the effect. Using in vitro assays, they showed that the polymer polyacrylamide gel (PAAG) reduces biofilm adhesion and plaque accumulation, adheres to the epithelial surface despite rinsing, limits binding of methicillin-resistant Staphylococcus aureus (MRSA) to epithelia, encourages wound healing, and moderates damageand pathogen-associated molecular patterns.
With the Phase II SBIR award, Synedgen researchers focused on treating mucositis, a common debilitating side effect of chemotherapy, radiotherapy, and a compromised immune system. Dr. Baker noted that they were able to establish efficacy, in animals, of Synedgen's Regenasyn™, a topical treatment to prevent infection and improve healing in cases of radiation therapy of the head and neck. They also scaled up manufacturing of the product and conducted preclinical topical and systemic toxicology tests. Dr. Baker noted that the need for such a product (market opportunity and size) is high, that the potential market share is large, and that there is a dearth of effective options currently.
Dr. Baker highlighted the value and importance of SBIR's CAP and NAP. She noted that the most valuable components that CAP provides are a template for fundraising "roadshows," a business development consultant, presentations on key aspects of fundraising, and most importantly, face-to-face meetings with pharmaceutical representatives and other small businesses. She said that SBIR awardees also need tools for identifying and accessing "the right" individuals in strategic partner organizations who can obtain and provide funding. Dr. Baker noted that the NAP was more immediately helpful than the CAP, for it enabled Synedgen to conduct a market assessment, which is both important and expensive.
Dr. Baker reported that Synedgen has two oral care products on the market (an oral rinse and a pre-market artificial saliva); is working with partners to develop, in the near- to mid-term, oral care products for cystic fibrosis sinusitis, oral mucositis, and gingivitis and periodontal disease; and, for the long term, hopes to develop a product for sinusitis. She highlighted three success "drivers" in the product development pipeline-competitive advantage, probability of success, and ease of the regulatory process. Dr. Baker also noted the following three challenges in developing oral care products: (i) development of animal models (e.g., periodontal disease, mucositis) that are reflexive of human tissue and flora; (ii) assurance of funding for the "valley of death" phase (i.e., when scaling up manufacturing, conducting toxicology tests, planning clinical trials, and preparing for regulatory oversight); and (iii) appreciating the competition between developing over-the-counter commodities and pursuing investigational new drug (IND) approval with the U.S. Food and Drug Administration (FDA), which influences R&D of oral care products.
In closing, Dr. Baker said that invention is only a small part of the overall drug development process and that the SBIR program is invaluable for helping small businesses establish proof-ofconcept and scale up. She suggested that the SBIR program could further help awardees by targeting several key value-inflection points—statistical demonstration and validation (in Phase I), and the major hurdle of IND approval (in Phase II).
My SBIR Journey with Quick-Set
Dr. Carolyn Primus, Principal, Primus Consulting, Bradenton, Florida, described her journey with the SBIR program to develop and commercialize the dental material Quick-Set. She noted that an NIDCR SBIR grant enabled her to start a company, Avalon Biomed Inc.™; to employ graduate students and part-time help who helped to establish manufacturing procedures, set up an international quality system, and research and validate several products; and to sell produces in the United States and internationally. She thanked the NIDCR for making the SBIR program accessible to dental researchers, and she noted that other researchers have contributed and provided input to her research.
Dr. Primus outlined the following requirements which Quick-Set meets: It has all the qualities of the current "gold standard" material, Mineral Trioxide Aggregate (MTA). It has a faster setting time than MTA (15 minutes, compared with 3 hours) and is acid-resistant. And, as a bioactive subgingival dental cement, Quick-Set is suitable for use in surgical or non-surgical endodontic procedures, promotes regeneration of periodontal ligament and cementum, and enhances the biological seal of the root canal system, thereby reducing re-infection and promoting tooth retention.
Dr. Primus described the development of her interest in dental materials. She noted that in her early professional career, she conducted research in the laboratories of several major companies and, subsequently, became director of R&D and quality assurance at Dentsply Ceramco, where she applied ceramic engineering skills and led the development of 100 new products. Then, for 10 years with Dentsply Tulsa, she focused on endodontic materials and procedures, handled the manufacturing of Gray ProRoot® MTA, and invented related products. Since 2008, she has headed Avalon Biomed Inc.™ and has been on the faculty of Lake Erie College of Medicine (LECOM) School of Dental Medicine, in Bradenton, Florida.
Dr. Primus noted that, in 2008, she initiated research on Quick-Set. After learning about the SBIR program from NIDCR's webinars on SBIR grants and from research colleagues, she established Primus Consulting in 2009 and applied for an SBIR grant, for which she received funding in June 2010. The Phase I SBIR award enabled the testing of prototype materials, with researchers at Georgia Regents University (GRU) College of Dental Medicine; optimization ofthe Quick-Set formula and properties; formation of an S corporation, Primus Technologies; and organization of a strategy for commercialization, which included formation of Avalon-Biomed Inc.™. Dr. Primus noted that a subsequent Phase II SBIR grant, awarded in September 2012, supported biocompatibility studies (at GRU) and animal testing (at Baylor University College of Dentistry) of Quick-Set, further optimization and manufacturing, and equipment purchases and setup. She noted that the research pointed to a problem with staining and the need for a colorstable, Quick-Set2, formula. The SBIR grant enabled development of a non-straining Quick-Set2, and follow-on funding allowed for validation of the changes in the formula.
Dr. Primus noted that the Avalon-Biomed Inc.™ team was accepted into the SBIR CAP in September 2014. The team is having ongoing conversations with its assigned mentor (Larta Institut ), has completed the training, and will be presenting its fundraising "roadshow" at the NIDCR in March 2015. Dr. Primus said that the company is about ready to take Quick-Set to market and is receiving positive reviews on two other, foundational endodontic cement products (Grey MTA Plus® and NeoMTA™ Plus®) that are already on the market. She noted that achieving sufficient sales to break even is a major challenge and that, in 2016, the company will continue to sell the two products and hopes to introduce Quick-Set. For the future, the company aims to develop more MTA-related products.
Dr. Primus emphasized that for SBIR awardees, the pathway to business development and profitability is non-linear, even with the best of ideas. And, in addition to pursuing their research goals, awardees need to acquire business skills in handling financial data, obtaining capital, creating a brand, developing a marketing plan, and sales. Small businesses also need legal advice on, for example, which business model to adopt and how to assure their intellectual property rights. Networking to identify partners and to find thought leaders and, eventually, "angel" investors is critical. Dr. Primus depicted the pathway to building a successful business and commercializing a product as incredibly complicated, having many twists and turns, and fraught with "cold sweats and nightmares."
IX. ADJOURNMENT OF OPEN SESSION
Dr. Somerman adjourned the open session of the Council meeting at 12:02 p.m.
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
The Council considered 395 applications requesting $155,526,554 in total costs. The Council recommended 276 applications for a total cost of $83,483,456 (see Attachment II).
The meeting was adjourned at 1:48 p.m. on January 27, 2015.
I hereby certify that the foregoing minutes are accurate and complete.
Dr. Martha J. Somerman
National Advisory Dental and
Craniofacial Research Council
Dr. Alicia Dombroski
National Advisory Dental and
Craniofacial Research Council
I. Roster of Council Members
II. Table of Council Actions