PAR-99-158: NIDCR CLINICAL TRIAL PILOT GRANT

Department of Health
and Human Services (HHS)

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NIDCR CLINICAL TRIAL PILOT GRANT Release Date: August 23, 1999 PA NUMBER: PAR-99-158 National Institute of Dental and Craniofacial Research PURPOSE The National Institute of Dental and Craniofacial Research (NIDCR) is committed to identifying effective preventive, diagnostic and treatment approaches to craniofacial, oral and dental diseases and disorders that will improve health by supporting well-executed clinical trials. Clinical trials in one of the following five scientific areas are encouraged and sought: Inherited Craniofacial Diseases and Injury, Infectious Diseases, Neoplastic Diseases of the Head and Neck, Chronic Disabling Diseases including pain conditions, temporomandibular joint diseases, autoimmune diseases, and bone diseases, and Biomimetics, Tissue Engineering and Biomaterials. The Institute is also interested in supporting clinical trials aimed at evaluating interventions that can have their effect on other systemic conditions (e.g., preterm low birthweight babies, cardiovascular disease, diabetes) through prevention, diagnosis or treatment of craniofacial, oral or dental conditions (e.g., oral infections) and promotion of craniofacial, oral and dental health. The National Cancer Institute (NCI) also has an active interest in clinical trials related to head and neck cancer and may also fund pilot grants in this area. Before proceeding to a full-scale randomized clinical trial, pilot clinical studies are often required. The objective of the NIDCR Clinical Trial Pilot Grant is to support pilot studies to obtain preliminary data necessary to address preliminary design and methodological issues for clinical trials. These pilot grants may support studies to: refine the intervention strategy (e.g., dosage, duration, delivery system, etc), develop and test surrogate endpoints of disease or health, develop diagnostic criteria and/or survey instruments, establish measures of safety or efficacy, and/or develop organizational structures including a field-tested manual of operations. It is expected that results of pilot studies will optimize design of the eventual full-scale trial. These grants are not intended to support small, under- powered clinical trials. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This PA, NIDCR Clinical Trial Pilot Grant, addresses the priority areas of craniofacial, oral and dental health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non- profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. All multi-center applications must include a coordinating center. MECHANISM OF SUPPORT The mechanism of support for the NIDCR Pilot Clinical Trial Grant is the research project grant (R01). Grants for single center trials may not exceed $500,000 per year in total costs (direct costs plus facilities and administrative) for 3 years. For multi-center trials each enrollment center and the coordinating center may apply separately or the coordinating center may apply on behalf of itself and each enrollment center. In either case, the total costs for each enrollment center may not exceed $250,000 and that for the coordinating center may not exceed $350,000 per year for 3 years. The award may not be renewed. Given the nature of this Program Announcement, the modular grant application policy will not apply. RESEARCH OBJECTIVES Dental and craniofacial diseases and disorders are among the most common health problems affecting the people of the United States and around the world. The burden imposed by a variety of dental and craniofacial diseases and disorders range from birth defects such as cleft lip and palate, which occurs in every 1 in 525 to 714 live births, to injuries to the head and face, resulting in nearly 20 million emergency room visits per year, to devastating head and neck cancers, accounting for 8000 deaths and over 30,000 new cases per year. The treatment of over 1.2 million cancer patients each year can lead to painful mouth ulcers, mucositis, rampant dental caries, fungal infections, impaired taste and loss of function of the salivary glands. Oral infections still remain common in our populations. Dental caries is experienced by 45% of school children and 94% of adults have experienced this infection at some point in life. Periodontal infections occur in 90% of individuals older than 13 years and may be associated with other systemic diseases or conditions such as diabetes, cardiovascular disease, respiratory infections, and pre-term/low birth weight babies. Orofacial pain is likely to have been experienced by over 20% of adults in the past six months, is a major component of temporomandibular joint diseases (TMD) for at least 6% of adults, and is a major component of Bell"s palsy, trigeminal neuralgia and fibromyalgia. Salivary gland dysfunction in the form of Sjogren"s syndrome affects between 1 and 4 million Americans while over 30,000 individuals who have cystic fibrosis are also at higher risk for concomitant salivary gland dysfunction. Further, over 500 prescription drugs have xerostomic (dry mouth) side effects, increasing the risk for both bacterial and fungal oral infections as well as other oral conditions. Oral candidiasis is commonly found in HIV-infected patients. The objective of the NIDCR Clinical Trial Pilot Grant is to address preliminary design and methodological issues for specific clinical trials used to evaluate interventions for the treatment or prevention of craniofacial, oral and dental conditions and promotion of craniofacial, oral and dental health. To meet this objective the proposed pilot study must successfully incorporate creative and realistic solutions to difficult problems in clinical research for the particular intervention being evaluated. By providing resources to collect essential data required for the design of a subsequent full-scale clinical trial it is anticipated that applicants will be in a better position to address in a definitive way the core design issues that are typically involved in clinical trials research. The NIDCR Clinical Trial Pilot Grant may include: studies to refine the intervention strategy (e.g., dosage, duration, delivery system, etc.), development and testing of surrogate endpoints of disease or health, diagnostic criteria and/or survey instruments, studies to define and refine the target population, and/or collection of preliminary data for establishing measures of efficacy and safety. In preparing for the definitive clinical trial, a pilot study will address questions that are formulated to optimize the design of the eventual trial. It is outside of the scope of the pilot grant to collect data that addresses the clinical question with lower than acceptable power or to conduct a fully developed but small-scale clinical trial. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 20, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 28, 1994. INCLUSION OF CHILDREN IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subject research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving children as subjects should read the "NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS," which were published in the NIH Guide for Grants and Contracts, Volume 27, No. 8, March 6, 1998. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted at the standard application deadlines as indicated in the application kit. Applications kits are available at most institutional offices of sponsored research and maybe obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435- 0714, email: grantsinfo@nih.gov. The title and number of the program announcement must be typed in Section 2 on the face page of the application. As with most applications to NIH, the research plan is limited to 25 pages. All information for review of the NIDCR Clinical Trial Planning Grant application must be included in the body of the application, appendices will not be considered during the review for this mechanism. The completed original application and three legible copies must be sent or delivered to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892 BETHESDA, MD 20817 (for express/courier service) In order to facilitate the review of applications assigned to the NIDCR, the applicant must, at the same time, mail or deliver two copies of the application to: Dr. H. George Hausch Division of Extramural Research National Institute of Dental and Craniofacial Research 45 Center Drive, Room 4AN-38D MSC 6402 Bethesda, MD 20892-6402 REVIEW CONSIDERATIONS Applications will be reviewed evaluated for scientific and technical merit by an appropriate peer review group convened by the NIDCR in accordance with the review criteria stated below. As part of the initial merit review all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Advisory Dental and Craniofacial Research Council. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. Significance. If the aims of the pilot study are achieved, could it help in the eventual design of a well-designed full clinical trial? Will such a trial address an important clinical or health problem, including issues relating to reducing health disparities? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of results from a full trial on the concepts or methods that drive this field? In addition, the following must be addressed: - The state of equipoise in the health care and patient communities with respect to the treatment or prevention of the disease under investigation. - The scientific basis for the proposed intervention including discussion of current practice and alternative interventions. - Impact of the proposed intervention on health care, health and quality of life. Approach. Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? The following should be addressed: - Study Design and Procedures including: sequence of clinical studies, including the proposed pilot study, that will produce a definitive clinical trial, translation of the clinical question into statistical hypotheses, selection of outcome measure(s), inclusion and exclusion criteria, availability, recruitment and retention of patients, plans to include children, both genders and minorities and their subgroups as appropriate for the scientific goals of the research, secondary questions (including capacity for post hoc analyses), detailed protocol with standardized procedures that will be used for this pilot study, ethical and safety issues and quality control procedures, and necessity for randomization and masking. - Data Analysis including: specific methods to be used for data analysis, the sample size for the pilot study may not be adequate to detect any but the largest treatment differences however the data from this study should provide a basis for providing sample size estimates for future trials, and population and demographics of the clinical condition. - For multi-center trials (in addition to the items above): standardization and quality control of protocols over time and across centers, data capture and distribution procedures, and trial administration and governance. Innovation. Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? Investigator. Is the principal investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? The following should be addressed: - Training and expertise in the clinical problem and the proposed intervention. - Training and expertise in clinical trials. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? The initial review group will also examine the provisions for the protection of human subjects, the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other recommended applications. Quality of the proposed project as determined by peer review, availability of funds, and program priority will be considered in making funding decisions. INQUIRIES Inquiries are encouraged early in the development of the application. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Maryann Redford Division of Extramural Research National Institute of Dental and Craniofacial Research 45 Center Drive, Room 4AN-24B, MSC 6402 Bethesda, MD 20892-6402 Telephone: (301) 594-5588 FAX: (301) 480-8318 Email: Maryann.Redford@nih.gov Direct inquiries regarding fiscal matters to: Mr. Martin R. Rubinstein Division of Extramural Research National Institute of Dental and Craniofacial Research 45 Center Drive, Room 4AN-44A, MSC 6402 Bethesda, MD 20892-6402 Telephone: (301) 594-4800 Email: Martin.Rubinstein@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.121. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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