PAR-01-119: PILOT STUDIES FOR CLINICAL TRIALS IN NEUROLOGICAL DISORDERS

Department of Health
and Human Services (HHS)

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This Program Announcement expires on July 31, 2004, unless reissued. PILOT STUDIES FOR CLINICAL TRIALS IN NEUROLOGICAL DISORDERS Release Date: July 25, 2001 (see replacement PAR-03-174) PA NUMBER: PAR-01-119 National Institute of Neurological Disorders and Stroke THIS PAR USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. MODULAR INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO $250,000 PER YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN SECTION C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT http://grants.nih.gov/grants/funding/phs398/phs398.html. PURPOSE The NINDS is committed to identifying effective treatments for neurological disorders by supporting well-executed clinical trials. Before proceeding to a full-scale clinical trial, pilot clinical studies are often required. The NINDS announces its interest 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 PILOT STUDIES FOR CLINICAL TRIALS IN NEUROLOGICAL DISORDERS grant (for brevity referred to as NINDS Pilot Studies grant) is to obtain preliminary data and conduct studies to support the rationale for a subsequent full-scale clinical trial of an intervention to treat or prevent neurological disease. RESEARCH OBJECTIVES The research project should directly address how the pilot study will advance the design of a subsequent full-scale clinical trial. The application should also address the intrinsic scientific merit of the study conducted under the NINDS Pilot Studies Grant, whether or not a full-scale trial is performed. Examples of relevant research include, but are not limited to, the following: 1. Studies to refine the intervention strategy (dosage, duration, delivery system). 2. Studies to define and refine the target population. 3. 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 rather than address the clinical question with lower power. The objective of the NINDS Pilot Studies Grant is to increase the quality of clinical research to evaluate interventions for the treatment or prevention of neurological disease. 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. MECHANISM OF SUPPORT This PAR will use the National Institutes of Health (NIH) R01 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 PA may not exceed 3 years. 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. INQUIRIES Inquiries concerning this PAR are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: John R. Marler, M.D. Associate Director for Clinical Trials National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 2216 Bethesda, MD 20892-9520 Telephone: (301) 496-9135 Fax: (301) 480-1080 Email: jm137f@nih.gov Barbara Radziszewska, Ph.D., M.P.H. Clinical Research Project Manager National Institute of Neurological Disorders and Stroke 6001 Executive Blvd., Room 2216 Bethesda, MD 20892-9520 Telephone: (301) 496-2076 Fax: (301) 480-1080 Email: br94h@nih.gov Direct inquiries regarding review issues to: Lillian Pubols, Ph.D. Chief, Scientific Review Branch NSC/NINDS/NIH 6001 Executive Boulevard Bethesda, MD 20892-9529 Telephone: (301) 496-5324 Fax: (301) 402-0182 E-mail: lp28e@nih.gov Katherine Woodbury Harris, Ph.D. SRA, Scientific Review Branch NSC/NINDS/NIH 6001 Executive Boulevard Bethesda, MD 20892-9529 Telephone: (301) 496-5980 Fax: (301) 402-0182 E-mail: kw47o@nih.gov Direct inquiries regarding fiscal matters to: Gladys Melendez-Bohler Senior Grants Management Specialist NIH/NINDS/GMB/Suite 3290 6001 Executive Blvd. Rockville, MD 20892 Telephone: (301) 496-9231 Fax: (301) 402-0219 Email: bohlerg@ninds.nih.gov APPLICATION PROCEDURES The PHS 398 research grant application instructions and forms (rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in applying for these grants and will be accepted at the standard application deadlines (http://grants.nih.gov/grants/dates.htm) as indicated in the application kit. This version of the PHS 398 is available in an interactive, searchable PDF format. Although applicants are encouraged to begin using the 5/2001 revision of the PHS 398 as soon as possible, the NIH will continue to accept applications prepared using the 4/1998 revision until January 9, 2002. Beginning January 10, 2002, however, the NIH will return applications that are not submitted on the 5/2001 version. For further assistance contact GrantsInfo, Telephone 301/710-0267, Email: GrantsInfo@nih.gov. Applicants planning to submit an investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended/revised version of the preceding grant application types requesting $500,000 or more in direct costs for any year are advised that he or she must contact the Institute or Center (IC) program staff before submitting the application, i.e., as plans for the study are being developed. Furthermore, the application must obtain agreement from the IC staff that the IC will accept the application for consideration for award. Finally, the applicant must identify, in a cover letter sent with the application, the staff member and Institute or Center who agreed to accept assignment of the application. This policy requires an applicant to obtain agreement for acceptance of the original application as well as any subsequent revisions. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 at http://grants.nih.gov/grants/guide/notice-files/not98-030.html. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS 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. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in applying for these grants, with modular budget instructions provided in Section C of the application instructions. Applicants are permitted, however, to use the 4/1998 revision of the PHS 398 for scheduled application receipt dates until January 9, 2002. If you are preparing an application using the 4/1998 version, please refer to the step-by-step instructions for Modular Grants available at http://grants.nih.gov/grants/funding/modular/modular.htm. Additional information about Modular Grants is also available on this site. The title and number of the program announcement 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 mail or courier service) In order to facilitate the review of applications assigned to the NINDS, the applicant should, at the same time, mail or deliver two copies of the application to: Dr. Lillian Pubols Chief, Scientific Review Branch NINDS, NIH 6001 Executive Boulevard Bethesda, MD 20892-9529 Rockville, MD 20852 (Courier service only) EMAIL: lp28e@nih.gov Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC Program Director or Principal Investigator should be included with the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NINDS. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the PAR will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NINDS 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 the applications under review, will be discussed, assigned a priority score, and receive a second level review by the NINDS National Advisory 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. (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? In evaluating significance, the reviewers should also consider the state of equipoise in the medical and patient communities and the potential impact of the proposed intervention on health care and quality of life. (2) 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? In addition to the standard evaluation criteria described above, applications will also be reviewed with respect to the following: The adequacy of plans for sequence of clinical studies, including the proposed pilot study, that will produce a definitive clinical trial; The scientific soundness of the proposed methodology, such as translation of the clinical question into statistical hypotheses, selection of outcome measure(s), inclusion and exclusion criteria, plans for randomization and masking, secondary questions (including capacity for post hoc analyses); The completeness and quality of the protocol and standardized procedures that will be used for this pilot study; The ethical aspects of the study and the appropriateness of subject safety protections; And the adequacy of quality control procedures. Reviewers will also evaluate plans for data management and analyses. However, sophisticated data management procedures are not required for a pilot study, although this study may be used to test these procedures. Likewise, description of specific methods to be used for data analyses is not required; it is assumed that in most cases, pilot studies will provide mostly descriptive statistics. Reviewers will evaluate plans for demographic subgroup analyses, if applicable. In evaluating plans for the sample size for the pilot, the reviewers should take into account that pilot studies need not be oriented toward detecting treatment differences; however, the data from this study should provide a basis for reliable sample size estimates for future trials. (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)? The reviewers should consider training and expertise in the clinical problem and the proposed intervention, and training and expertise in clinical trials. (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, all applications will also 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 will also 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 or the environment, to the extent they may be adversely affected by the project proposed in the application. AWARD CRITERIA Applications will compete for available funds with all other recommended applications. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, program priority, and program balance. 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" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. DATA AND SAFETY MONITORING PLAN For phase I and II clinical trials, investigators must submit a general description of the data and safety monitoring plan as part of the research application. For further information, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. This policy announcement is found in the NIH Guide for Grants and Contracts Announcement dated June 5, 2000, at the following website: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. 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 a 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. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at: http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm Applicants may wish to place data collected under this RFA (PA) in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. 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 PA, PILOT STUDIES FOR CLINICAL TRIALS IN NEUROLOGICAL DISORDERS , is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/. AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 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, 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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