GOAL THREE: Identify innovative clinical research avenues to improve oral, dental and craniofacial health.

The nation's progress against oral diseases will be accelerated by rigorous clinical studies whose outcomes have the potential to fundamentally change dental practice and improve oral, dental and craniofacial health. Research designs and analytical methods that enhance the efficiency and lower the cost of clinical studies are needed—in particular, the use of biomarkers as surrogate endpoints, the availability of more accurate and sensitive validation reference standards, and the development of more accurate measures of disease susceptibility. The NIDCR recognizes the need for partnering with the extramural research community, professional and scientific organizations, industry, and other public and private institutions that can facilitate the development of new approaches and technologies to enhance the conduct of oral disease clinical trials.

One particularly important venue for cross-disciplinary collaboration is the Clinical and Translational Science Award (CTSA) program¹⁸. This NIH-funded national clinical research consortium is transforming how clinical and translational research is conducted across the country. The NIDCR strongly encourages its investigators to interface with the CTSAs to take full advantage of this important resource. At the end of Fiscal Year 2008, 23 schools of dentistry were actively participating in this program that also offers multi-disciplinary training to junior clinical researchers.

Objective III-1: Conduct well-designed, definitive clinical research studies that improve oral, dental and craniofacial health and support more effective care delivery and health policies.

The NIDCR is committed to identifying effective preventive, diagnostic and treatment approaches for craniofacial, oral and dental diseases. The Institute's highest priority in this area will be to fund clinical trials that can provide scientific evidence to change clinical practice or health policy, thus improving patient outcomes. The Institute will support all stages of innovative treatment approaches to facilitate the translation of science into clinical practice, including the evaluation of existing diagnostic, prevention and treatment modalities. Areas of interest for NIDCR-supported clinical investigations include:

• early detection and identification of risk factors for dental caries, periodontal disease, oral cancer, orofacial clefts, Sjögren's Syndrome, HIV/AIDS-associated oral diseases and chronic orofacial pain;
• interventions based on relationships between oral infectious diseases and other conditions such as diabetes and pulmonary disease;
• novel treatment strategies for chronic oral health disorders and diseases including orofacial pain associated with temporomandibular muscle and joint disorders as well as oral cancer;
• prevention and treatment of oral diseases in underserved populations;
• new approaches for preventing and treating mucosal infections;
• investigations of mechanisms leading to salivary dysfunction associated with Sjögren's syndrome;
• evaluation and treatment of skeletal diseases and craniofacial disorders and malformations.

The NIDCR's intramural research program provides a valuable opportunity to conduct translational and clinical research relevant to the mission of the Institute. In particular, this program takes advantage of the combined expertise and resources, including the NIH Clinical Center, available to the thousands of researchers from various Institutes and Centers working on the NIH campus in Bethesda, Maryland. NIDCR intramural scientists, as appropriate, translate basic research findings into phase I clinical trials of novel treatments to evaluate their safety in people.

Over the next five years, intramural scientists will conduct clinical studies including a targeted oral cancer therapy; the use of adult stem cells to heal wounds with new bone; and development of a unique compound that can selectively delete specific cells from the nervous system that produce intractable chronic pain.

Objective III-2: Support practice-based research and create a national-level dental practice collaborative for community-based research and oral health surveillance.

The capacity of the oral health research community to conduct clinical research and to use science-based findings depends on a critical mass of investigators skilled in the design and conduct of clinical trials and community-based research. The NIDCR will support oral health scientists and practitioners with specific expertise in areas such as prevention and health promotion, diagnostic technology, drug development and testing, and community-based investigations, as well as in translational research.

In 2005, the NIDCR awarded three seven-year grants to establish practice-based research networks (PBRNs) that are conducting well-designed clinical studies that address everyday issues in the delivery of oral health care. The impetus behind the networks is the need for science-based data to guide dental treatment decisions. Each regional network conducts short-term clinical studies that compare the benefits of different dental procedures, dental materials, and prevention strategies under a range of patient and clinical conditions. Other network projects, such as surveys and de-identified reviews, as allowed by the Health Insurance Portability and Accountability Act, estimate disease prevalence, treatment trends and the prevalence of less common oral conditions among individuals accessing dental care.

The success of the PBRNs, or any practice-based collaborative program, depends on a focus on real-world clinical issues and the capacity to generate information that will be of practical value to practitioners and patients alike. It is critical that these studies center on topics and procedures that dentists and dental hygienists themselves identify as relevant and helpful to their clinical decision making. Over the next five years, the NIDCR will support a second generation of practice-based research efforts that will build and expand on the work undertaken thus far.

Objective III-3: Provide resources to promote product and clinical development toward the ultimate commercialization of oral health therapies.

Looking forward, it is important that the NIDCR adopts the most innovative technologies to advance the development of novel oral health products and therapies. The Institute welcomes additional interchange, relationships and partnerships with industry in both the oral health and broader biomedical research and technology sectors.

To accelerate technology development, the Institute also will fund interdisciplinary research approaches with an emphasis on basic and translational studies. Biomimetics, nanotechnology and nanoscience, diagnostic technologies, stem cell research and materials science (including biocompatibility), and the use of technologies to deliver evidence-based behavioral interventions all fall within the sphere of this research area. In order for these discoveries to improve health and quality of life, they need to be incorporated into everyday practice. For that reason, the Institute will emphasize technology transfer as an important research component and will support small business innovation grants to help speed the translation of scientific findings into practice.

The NIDCR is a leader in the development of saliva-based diagnostic tests for a variety of diseases and conditions, including oral cancer. Miniaturization of detection devices will ultimately allow for the placement of a sentinel device directly in the mouth, potentially yielding real-time surveillance of hundreds of biomarkers that could alert people to consult their health professionals at the earliest sign of disease. Adequate technologies to develop salivary diagnostics on a large scale do not yet exist, but are essential for creating a battery of tests and diagnostic panels for predicting or detecting the onset and progression of diseases. The Institute will support research to develop such technologies as the first step in building the scientific infrastructure required to expand oral fluid-based diagnostics. Already, NIDCR-funded scientists have begun to evaluate which of the gene products in saliva correlate with various disease processes such as oral cancer¹⁹.

Objective III-4: Ensure breadth and depth of the clinical research pipeline, fostering collaboration between oral health care practitioners, clinical scientists and basic researchers.

The capacity of the oral health research community to conduct clinical research, and to use the findings from that research, needs to be augmented through enhanced training and the creation of an able cadre of scientists skilled at conducting clinical trials and community-based research.

The NIDCR will create a new career development pathway that will enable the Institute and schools of dentistry to work together to provide training and mentorship for clinician scientists.

The NIDCR provides several opportunities for combined D.D.S./Ph.D. training. These include:

• an institutional T32 grant program to provide support for an integrated dental and graduate research training program leading to both the D.D.S./D.M.D. and Ph.D. degrees;
• individual predoctoral dental scientist fellowships that broaden the reach of the T32 program by providing individual fellowships to dental scientists at any school of dentistry in the U.S.; and
• the Dental Scientist Training Program (DSTP), modeled after the highly successful Medical Scientist Training Program²⁰ supported by the National Institute of General Medical Sciences.

A recently conducted NIDCR research training program analysis highlighted the troubling pipeline trend that few NIDCR dental school trainees go on to independent research careers: The evidence suggests that dentists are not as successful as those without dental degrees in obtaining independent research funding.

The Institute believes that providing the support for dentist-scientists to obtain high-quality postdoctoral training with protected research time will help them to be more competitive for subsequent, independent awards. Currently, many dentist-scientists do not have a dedicated period of postdoctoral research training, as do their non-dentist Ph.D. counterparts, because most dentists, including dual-degree dentists, combine clinical residency and postdoctoral research experiences. To address this issue, the NIDCR will create a new career development pathway that will enable the Institute and schools of dentistry to work together to provide training and mentorship for clinician scientists. The NIDCR will also introduce a modified K99/R00 award mechanism (see Objective II-2) to enable dentists to pursue a rigorous mentored postdoctoral research experience in a first phase, followed by independent tenure-track support in a second phase.

The NIDCR also encourages the oral health research community to develop and maintain clinical research partnerships with other components of academic health centers, the practicing community, and other sites that support multidisciplinary research teams. In particular, the Institute strongly encourages partnerships that make use of the resources of the NIDCR intramural program and the CTSA consortium (see Goal III).