RFA-HD-00-024: PILOT CLINICAL TRIAL GRANTS FOR PHARMACOLOGICAL INTERVENTIONS IN PEDIATRIC TBI

Department of Health
and Human Services (HHS)

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PILOT CLINICAL TRIAL GRANTS FOR PHARMACOLOGICAL INTERVENTIONS IN PEDIATRIC TBI Release Date: Spetember 5, 2000 RFA: HD-00-024 National Institute of Child Health and Human Development (http://www.nichd.nih.gov) National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov) Letter of Intent Receipt Date: October 2, 2000 Application Receipt Date: November 17, 2000 THIS RFA USES THE MODULAR GRANT AND JUST-IN-TIME CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE The National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS) are committed to evaluate the efficacy of specific pharmacological interventions to improve outcomes in pediatric patients following Traumatic Brain Injury (TBI), by supporting well-executed clinical trials. Before proceeding to a large clinical trial, pilot clinical studies are often required. The NICHD and NINDS are interested in supporting pilot studies required to obtain necessary information to clearly establish the clinical basis for proceeding to a full- scale trial. The purpose of a Pilot Clinical Trial Grant for Pharmacological Interventions in Pediatric TBI is to obtain preliminary data and conduct studies to support the rationale for a subsequent full-scale clinical trial of pharmacological intervention. HEALTHY PEOPLE 2010 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS- led national activity for setting priority areas. This RFA is related to one or more priority areas. Potential applicants may obtain "Healthy People 2010" at: http://www.health.gov/healthypeople. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, 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. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) Individual Exploratory/ Developmental Research Grant (R21) award mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this RFA may not exceed two years. This RFA is a one-time solicitation. The anticipated award date is July 1, 2001. Specific application instructions have been modified to reflect MODULAR GRANT and JUST-IN-TIME streamlining efforts being examined by the NIH. Complete and detailed instructions and information on Modular Grant applications can be found at http://grants.nih.gov/grants/funding/modular/modular.htm. FUNDS AVAILABLE The NICHD and NINDS each intend to commit approximately $750,000 in total costs [direct plus Facilities and Administrative (F&A) costs] in FY 2001 to fund up to seven new grants in response to this RFA. An applicant may request a project period of up to two years and a budget for direct costs of up to $150,000 per year. Although this program is provided for in the financial plans of NICHD and NINDS, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. RESEARCH OBJECTIVES Background Over the past decade, many neuroprotective agents have been developed to improve the outcome in patients with acute cerebral disorders such as stroke, subarachnoid hemorrhage, and head injury. A number of different classes of drugs (e.g., calcium channel blockers, glutamate antagonists, cholinesterase inhibitors) have been tested in head-injured adults across the stages of recovery. Although there are data regarding the mechanism of action of such drugs in adults, little information exists on the safety or efficacy of pharmaceuticals in children. Adjunctive pharmacological treatment has also been suggested to facilitate behavioral management during the rehabilitation process and to improve functional outcome. While small case studies in adults suggest that some of these agents may be useful for improving attention and memory and, possibly, for enhancing plasticity, there is a dearth of information on appropriate dosages and effects of these agents in pediatric TBI patients. Research Scope The objective of the NICHD/NINDS Pilot Clinical Trial Grant is to promote clinical trials research to evaluate efficacy of pharmacological interventions for the physiological and behavioral sequelae of TBI in pediatric patients. To meet this objective, the proposed pilot study must successfully incorporate creative and realistic solutions to difficult problems in clinical neurological research for the particular intervention being evaluated. Research topics responsive to this RFA include, but are not limited to, the following: o Collection of preliminary data for establishing measures of efficacy and safety in children, o Neuropsychological studies that target higher cognitive functions as possible outcome measures, o New statistical methods that approach such issues as change over time, assessment based on specific recovery curves of individual children, or psychosocial parameters before and after injury, o Studies to refine intervention strategies (dosage, duration, delivery system) for children across age ranges, o Development of new pharmacotherapies for children that consider age as a factor, o Development of paradigms to focus on age-specific biology, including toxicological risks within age groups, o Evaluation of interactions of pharmacological agents and behavioral treatments, o Studies to define and refine target population among developmental stages in children, o Studies of the safety of drugs being tested/used in adult TBI, o Approaches to long-term assessment of behavioral change among various ages of older children injured within the first four years of postnatal life. The application should directly address how the Pilot Grant will advance the design of a subsequent full-scale clinical trial. The application also should address the intrinsic scientific value of the study to be conducted under the Pilot Grant, whether or not a full-scale trial is performed. In preparing for the definitive clinical trial, a pilot study should address questions that are formulated to optimize the design of the eventual trial rather than address the clinical question with lower power. 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 sub-populations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided indicating 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 UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The revisions relate to NIH defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS 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 subjects 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 human subjects should read the NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects, published in the NIH Guide for Grants and Contracts, March 6, 1998, and available on the Internet at: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. Investigators may also obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. URLs IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NICHD staff to estimate the potential review workload and plan the review. The letter of intent is to be sent to Dr. Beth Ansel at the address listed under INQUIRIES, below, by October 2, 2000. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research, on the Internet at http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892- 7910, telephone 301-710-0267, E-mail: grantsinfo@nih.gov. Application Instructions The modular grant concept establishes specific modules in which direct costs may be requested as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in- time concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers, and NIH staff. The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants, with the modifications noted below. For responses to this RFA, Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $150,000 per year. The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions described below: o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in $25,000 increments up to a maximum of $150,000) and Total Costs [Modular Total Direct plus Facilities and Administrative (F&A) costs] for the initial budget period. Items 8a and 8b should be completed indicating the Direct and Total Costs for the entire proposed period of support. o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD: Do not complete Form Page 4 of the PHS 398. It is not required and will not be accepted with the application. o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT: Do not complete the categorical budget table on Form Page 5 of the PHS 398. It is not required and will not be accepted with the application. o NARRATIVE BUDGET JUSTIFICATION: Prepare a Modular Grant Budget Narrative page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for sample pages.) At the top of the page, enter the total direct costs requested for each year. This is not a Form Page. o Under Personnel, list ALL project personnel, including their names, percent of effort, and roles on the project. No individual salary information should be provided. However, the applicant should use the NIH appropriation language salary cap and the NIH policy for graduate student compensation in developing the budget request. For Consortium/Contractual costs, provide an estimate of total costs (direct plus F & A) for each year, each rounded to the nearest $1,000. List the individuals/organizations with whom consortium or contractual arrangements have been made, the percent effort of key personnel, and the role on the project. Indicate whether the collaborating institution is foreign or domestic. The total cost for a consortium/contractual arrangement is included in the overall requested modular direct cost amount. Include the Letter of Intent to establish a consortium. Provide an additional narrative budget justification for any variation in the number of modules requested. o BIOGRAPHICAL SKETCH: The Biographical Sketch provides information used by reviewers in the assessment of each individual"s qualifications for a specific role in the proposed project, as well as to evaluate the overall qualifications of the research team. A biographical sketch is required for all key personnel, following the instructions below. No more than three pages may be used for each person. A sample biographical sketch may be viewed at: http://grants.nih.gov/grants/funding/modular/modular.htm. - Complete the educational block at the top of the form page, - List position(s) and any honors, - Provide information, including overall goals and responsibilities, on research projects ongoing or completed during the last three years, - List selected peer-reviewed publications, with full citations. o CHECKLIST: This page should be completed and submitted with the application. If the F&A rate agreement has been established, indicate the type of agreement and the date. All appropriate exclusions must be applied in the calculation of the F&A costs for the initial budget period and all future budget years. o The applicant should provide the name and telephone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. Submission Instructions The RFA label available in the PHS 398 (rev. 4/98) application form must be stapled to the bottom of the face page of the application and must display the RFA number HD-00-024. A sample RFA label is available at http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this is in the pdf format. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application should also be sent to: L. R. Stanford, Ph.D. Director, Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03F, MSC 7510 Bethesda, MD 20892-7510 Bethesda, MD 20854 (for express/courier service) Applications must be received by November 17, 2000. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR and for responsiveness by NICHD and NINDS. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be reviewed for scientific and technical merit by a review group convened by the Division of Scientific Review, NICHD. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit will be discussed, assigned a priority score, and receive a second level review by the National Advisory Council of NICHD and/or NINDS. 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. (1) Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual frameworks, 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? (3) 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? (4) Investigator: Is the 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)? (5) 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? In addition to the above criteria, in accordance with NIH policy, applications also will be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects also will be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans, animals, and the environment, to the extent they may be adversely affected by the project proposed in the application. Schedule Application Receipt Date: November 17, 2000 Letter of Intent Receipt Date: October 2, 2000 Peer Review Date: February/March 2001 Council Review: June 2001 Earliest Anticipated Start Date: July 1, 2001 AWARD CRITERIA Funding decisions will be based on scientific and technical merit as determined by peer review, program balance and need, and the availability of funds. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Beth M. Ansel, Ph.D., CCC-SLP Director, Clinical Practices Research Program National Center for Medical Rehabilitation Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 2A03, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 402-2242 FAX: (301) 402-0832 E-mail: Beth_Ansel@nih.gov Mary Ellen Cheung, Ph.D. National Institute of Neurological Disorders and Stroke Neuroscience Center 6001 Executive Boulevard, Room 2209, MSC 9525 Bethesda, MD 20892-9525 Rockville, MD 20852 (courier service) Telephone: (301) 496-1447 FAX: (301) 480-1080 E-mail: mm108w@nih.gov Direct inquiries regarding fiscal matters to: Ms. Mary Ellen Colvin Grants Management Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17H, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-1304 FAX: (301) 402-0915 E-mail: ColvinM@mail.nih.gov Ms. Rita Rollins-Hickey Grants Management Branch National Institute of Neurological Disorders and Stroke Neuroscience Center 6001 Executive Boulevard, Room 3254, MSC 9525 Bethesda, MD 20892-9525 Telephone: (301) 496-7488 E-mail: rr46W@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.929 and 93.853. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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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