Part I Overview Information
Department of Health and Human Services
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)
National Institute on Aging (NIA), (http://www.nia.nih.gov)
National Institute of Alcohol Abuse and Alcoholism (NIAAA), (http://www.niaaa.nih.gov/
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov/)
Title: Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (Phased Innovation Award [R21/R33])
This is a reissue and modification of , which was previously released April 21, 2003 and now is divided into separate Funding Opportunity Announcements (FOAs) for R21/R33, R21, and R33 funding mechanisms.
Update: The following update relating to this announcement has been issued:
NOTICE: Applications submitted in response to this FOA for Federal assistance must be subm itted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/ApplyforGrants (hereafter called Grants.gov/Apply).
A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.
Program Announcement (PA) Number: PA-06-463
Catalog of Federal Domestic Assistance Number(s)
This Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), National Institute of Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH), invites Phased Innovation (R21/R33) grant applications from organizations/institutions that propose the development of novel radioligands for positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging in human brain, and that incorporate pilot or clinical feasibility evaluation in pre-clinical studies, model development, or clinical studies.
- R21 phase: Direct costs are limited to a maximum of $150,000 per year.
- R33 phase: Direct costs are limited to less than $500,000 per year.
- The combined R21/R33 award is limited to five years in duration and neither the R21 phase nor the R33 phase can be longer than three years.
Table of Contents
Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
1. Research Objectives
The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), National Institute of Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) is to facilitate the development of agonist and antagonist PET and SPECT probes for molecular targets that are implicated in the pathophysiology of brain and behavioral disorders (e.g., receptors, intracellular messengers, disease-related proteins). The use of radiotracers for imaging molecular events in preclinical and clinical studies is essential for understanding the circuitry that underlies normal brain function and the pathophysiology of brain disorders. The long-term goal of this FOA is to facilitate the broad application of neuroimaging probes in pathophysiological studies, drug discovery/development research, and in biomarker development//qualification studies as quantifiable indicators of disease progression and treatment efficacy.
Tremendous opportunities exist for the application of PET and SPECT imaging in studies of the pathophysiology and treatment of brain disorders, but relatively few radioligands are currently available for functional imaging of target molecules implicated in normal brain function, aging, and in brain and behavioral disorders. Increasing the availability of PET and SPECT radiotracers will aid in: a) understanding the abnormal biological processes which underlie mood disorders and other brain disorders; b) determining the interaction of a drug or drug candidate with a specified target; c) guiding initial dosing of new therapeutic agents; and d) as central biomarkers of the illness, with the potential to predict symptom onset, monitor the progression of the disease, and assess the efficacy of therapeutic compounds. The NIMH Strategic Plan for Mood Disorders Research is available at http://www.nimh.nih.gov/strategic/stplan_mooddisorders.cfm.
This FOA is intended to stimulate the development of radioligands for molecular targets (e.g., receptors, cell adhesion molecules, intracellular messengers, and disease related proteins) that are of broad interest to the scientific community. The widespread availability and use of these radioligands are expected to: 1) accelerate research on identifying and characterizing the neural circuits and pathways implicated in the pathophysiology of brain disorders (especially mental and behavioral disorders, substance abuse, neurodegenerative disorders, and pediatric brain disorders) and brain changes with age, and 2) facilitate the identification of new therapeutic targets and the development of new compounds as potential therapeutic agents. Research partnerships among investigators in both academia and pharmaceutical and biotechnology industries are encouraged to more rapidly develop PET and SPECT radiotracers and apply neuroimaging in drug discovery, biomarker development//qualification, and pathophysiological studies.
Molecular targets for which radioligands (agonist and antagonist ) are needed
include, but are not limited to, the following. Please contact program staff
listed in Section VII.1., “Scientific/Research
to determine program priorities and molecular targets of interest to specific NIH Institutes or refer to the Internet addresses listed above for each of the participating NIH Institutes.
The following objectives would make appropriate topics for proposed R21/R33 projects. This list is not meant to be all-inclusive.
See Section VIII, Other
Information - Required Federal Citations, for policies related to
Section II. Award Information
1. Mechanism of Support
This funding opportunity will use the NIH Exploratory/Developmental Grant and Exploratory/Developmental Grant Phase II Phased Innovation Grant (R21/R33) award mechanisms. Applicants using only the R21 mechanism or only the R33 mechanism will not be considered. Applicants are encouraged to contact NIH program staff with any questions about the appropriate mechanism. See Section VII.1., “Scientific/Research Contacts.”
As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.
This funding opportunity uses just-in-time concepts. For both the R21 and the R33 phases, applicants must complete and submit detailed budget requests using the SF424 Research and Related (R&R) Budget component provided in the SF424 (R&R) Application Package and the SF424 (R&R) Application Guide (see specifically Section 4.7, “R&R Budget Component,” of the Application Guide). Modular budgets are not permitted for this funding opportunity.
Exploratory/developmental grant support is for new projects only; competing renewal (formerly “competing continuation”) applications will not be accepted. Up to two resubmissions (formerly “revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted. See NOT-OD-03-041, May 7, 2003.
2. Funds Available
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
For the R21 phase of the application, direct costs are limited to a maximum of $150,000 per year. For the R33 phase of the application, direct costs must be limited to less than $500,000 per year. The combined R21/R33 award is limited to five years in duration and neither the R21 nor the R33 phase can be longer than three years.
Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.
The award of R33 funds will be based on program priorities, on the availability of funds, and on successful completion of negotiated scientific milestones as determined by NIH staff in the context of peer review recommendations.
1. Eligible Applicants
1.A. Eligible Institutions
You may submit an application(s) if your organization has any of the following characteristics:
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
The development and strengthening of partnerships between scientists from academia and the pharmaceutical industry is a highly desirable outcome of this FOA and is strongly encouraged. Pharmaceutical scientists are encouraged to actively participate as Project Director/Principal Investigator (PD/PI) or key personnel/collaborator in the R21 and/or the R33 phase of the project.
Scientists from NIH Intramural laboratories may participate as key personnel/collaborators in the project. However, intramural scientists may not serve as principle investigators while being paid with intramural funds. As key personnel/collaborators, it may become necessary to convert the grant application to a cooperative agreement grant mechanism with corresponding Terms and Conditions related to such a cooperative agreement. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from this FOA. A formal letter from the intramural scientist must be included as part of the grant application with a copy of this letter sent to the Scientific Director. The letter should be limited to a description of the intramural scientist's collaborative work under the grant. The grant applicant is responsible for writing the section of the grant that describes the proposed collaboration within the grant, which the NIH investigator should see and approve. For applications that include NIH intramural components, the intramural resource level will not be included in the total cost of the overall application. The involvement of Intramural scientists needs to be consistent with NIH Policy (http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm).
2. Cost Sharing or Matching
This program encourages, but does not require, cost sharing with biotechnology, pharmaceutical, or disease foundations, as defined in the current NIH Grants Policy Statement.
3. Other-Special Eligibility Criteria
Applicant organizations may submit more than one application, provided each application is scientifically distinct.
To download an SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/
and follow the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.
Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Started
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.
Several of the steps of the registration process could
take four weeks or more. Therefore, applicants should immediately check with
their business official to determine whether their institution is already
registered in both Grants.gov and the Commons.
The NIH will accept electronic applications only from organizations that have
completed all necessary registrations.
1. Request Application Information
Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.
Note: Only the forms package directly
attached to a specific FOA can be used. You will not be able to use any other
SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although
some of the "Attachment" files may be useable for more than one
For further assistance contact GrantsInfo, Telephone 301-435-0714, Email: GrantsInfo@nih.gov.
Telecommunications for the hearing impaired: TTY 301-451-0088.
2. Content and Form of Application Submission
Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).
The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH.
There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”
The SF424 (R&R) application is comprised of data arranged in separate
components. Some components are required, others are optional. The forms package
associated with this FOA in Grants.gov/APPLY
will include all applicable components, required and optional. A completed
application in response to this FOA will include the following components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form
Several special provisions apply to applications submitted by foreign organizations:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
3. Submission Dates and Times
See Section IV.3.A for details.
3. A. Submission, Review and Anticipated Start Dates
Opening Date: September 1, 2006 (Earliest date an application may be
submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable
Application Submission/Receipt Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm for details.
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward for details.
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward for details
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward for details
3.A.1. Letter of Intent
A letter of intent is not required for this funding opportunity.
3.B. Submitting an Application Electronically
to the NIH
To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.
3.C. Application Processing
Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.
Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.
Upon receipt, applications will
be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete
applications will not be reviewed.
There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.
The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an “Introduction” addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).
4. Intergovernmental Review
This initiative is not subject to intergovernmental review.
5. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.
The incurrence of pre-award costs
in anticipation of a competing or non-competing award imposes no obligation
on NIH either to make the award or to increase the amount of the approved
budget if an award is made for less than the amount anticipated and is inadequate
to cover the pre-award costs incurred. NIH expects the grantee to be fully
aware that pre-award costs result in borrowing against future support and
that such borrowing must not impair the grantee's ability to accomplish the
project objectives in the approved time frame or in any way adversely affect
the conduct of the project. See the NIH
Grants Policy Statement.
6. Other Submission Requirements
The NIH requires the PD/PI to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”
Renewal (formerly “competing continuation” or “Type 2”) applications are not permitted.
Specific Instructions for Preparing a Combined R21/R33 Phased Innovation Award Application
Appendix material should be limited. The following materials may be included in the Appendix:
The milestones proposed in the application should be well described, quantifiable, and scientifically justified to allow program staff to assess progress in the R21 phase. The milestones will be considered in evaluating the approach proposed by the investigator. A discussion of the milestones relative to the progress of the R21 phase and the implications of successful completion of the milestones for the R33 phase should be included. Applications lacking this information, as determined by the NIH staff, will be returned to the applicant without review. The clarity and completeness of the R21/R33 application with regard to specific goals and feasibility milestones are critical.
Prior to funding an application, the Program Officer will contact the applicant to discuss the proposed milestones and any changes suggested by the review panel as indicated in the Summary Statement. The Program Officer and the applicant will negotiate and agree on a final set of milestones. These will be the basis for judging the success of the R21 work. For funded applications, the Project Director/Principal Investigator (PD/PI) will submit a progress report to the Program Officer upon completion of the R21 milestones. Receipt of this progress report will trigger an administrative program review that will determine whether or not the R33 should be awarded. The release of R33 funds will be based on successful completion of negotiated scientific milestones, on program priorities, and on the availability of funds.
The R21 and R33 cannot be funded in the same fiscal year.
1. In the “Research & Related Other Project Information” Component (item 6 – Project Summary/Abstract”):
As part of the Summary/Abstract attachment, identify concisely the fundamental research and/or technology or tool to be developed, its innovative nature, its relationship to presently available capabilities, and its expected impact on biomedical research.
2. In the “Research & Related Budget” Component – Section K (“Budget Justification”):
For the R21 phase of the application, direct costs are limited to a maximum of $150,000 per year. For the R33 phase of the application, direct costs are limited to less than $500,000 per year. R21 budgets can only exceed this cap to accommodate Facilities and Administrative (F&A) costs of subcontracts to the project. The combined R21/R33 application is limited to five years in duration and neither the R21 nor the R33 phase can be longer than three years.
The application should provide a detailed budget for each Budget Period of the R21 phase and the R33 phase. All budgets should include a written justification Section K, “Budget Justification.” In Section K of each Budget Period, the application should indicate whether it is the R21 or the R33 phase. The modular budget format is not permitted for this funding opportunity.
An annual meeting of all investigators funded through this program will be held to share progress and research insights that may further progress in the program. For this purpose, applicants should request travel funds for the PD/PI and one additional senior investigator to attend a two-day meeting each year, the location of which will be announced. Applicants should also include a statement in their applications indicating their willingness to participate in such meetings and to cooperate with other researchers.
3. In the”PHS398 Research Plan Component” – Research Plan Attachments:
Item 1: Introduction to Application (Resubmission or Revision only). Use only if you are submitting an SF424 (R&R) Resubmission or Revision (Cover Page Item 8).
All Resubmission (previously known as “revision” or “amendment”) or Revision (previously known as “competing supplements”) applications must include an “Introduction.“
The Introduction should not exceed three pages for a resubmission application. The Introduction is excluded from the 25 page limit of the Research Plan.
Item 2: Specific Aims.
A specific section labeled “Milestones” should appear at the beginning of the Specific Aims attachment. The advantage of the combined R21/R33 mechanism is that it offers a seamless transition between the exploratory phase and the development phase of a project. Milestones should be well described, quantifiable, and scientifically justified. Applicants should write the milestones assuming that scientifically literate program officers who may not be active researchers in the specific specialty being evaluated will use them to evaluate the progress that has been achieved. Milestones should not be simply a restatement of the specific aims or a timeline. Applications lacking this information will be returned to the applicant without review.
Include headers titled “R21 Phase Specific Aims” and “R33 Phase Specific Aims.” Under each header, state the specific objectives of the research and development effort, including the technical questions you will try to answer to determine the feasibility of the proposed approach. Since the goal of the R21 phase of this FOA is the development of novel radioligands for PET and SPECT imaging in preclinical and clinical studies or innovative technologies for radioligand development, hypothesis testing, per se, may not be the driving force in developing such a proposal, and therefore, may not be applicable. For the R21 portion of the grant application, preliminary data are not required, although they should be included when available.
Item 3: Background and Significance
Elaborate on the innovative nature of the proposed research. Clarify how the fundamental tools or technologies to be developed will result in a significant improvement over existing approaches. Explain the potential of the proposed technology for having an impact on a compelling area of biomedical research. Clearly identify how the project, if successful, will result in new capabilities for biomedical research, the immediacy of the opportunity, and how any proposed technologies or tools differ from existing technologies or tools.
Item 4: Preliminary Studies
While preliminary data are not required for submission of the R21 phase, this section should provide current thinking or evidence in the field that substantiates the feasibility of the R21 phase. If the applicant does have preliminary data, it should be presented in this section.
Item 5: Research Design and Methods
Follow the instructions in the SF424 Application Guide. Include headers titled “R21 Phase Research Design and Methods” and “R33 Phase Research Design and Methods,” and address the research design and methods for the R21 and R33 phases in the appropriate sub-section.
Plan for Sharing Research Data
It is the NIH policy that the research resources developed through this FOA become readily available to the research community for further research, development, and application, in the expectation that this will lead to knowledge of benefit to the public.
Applications must include a plan to share data that may be gathered in the course of the project with the scientific community. It is expected that the PD/PI’s data sharing plan will include the following elements: (1) mechanisms by which all protocols, procedures, methodologies, toxicology information, unlabeled PET or SPECT precursors, IND filing info are widely distributed to qualified investigators in the scientific community; (2) a protocol and criteria for wide dissemination of these data, information, and materials and (3) a timetable for distribution.
Applicants are invited to utilize NIH supported repositories such as the NIMH Chemical Synthesis and Drug Supply Program (http://nimh-repository.rti.org/) or the NIDA Drug Supply Program to make unlabeled PET and SPECT ligands widely available to the scientific community.
Applicants are invited to utilize NIH supported databases such as the NIMH/Society for Non-Invasive Imaging in Drug Development (SNIDD) Tracer Database (http://kidb.bioc.cwru.edu/snidd/) or the NIH Roadmap Molecular Imaging and Contrast Agent Database (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=micad.TOC&depth=2) to enable centralized access to and dissemination of imaging radiotracer information (e.g., protocols, methodologies, toxicology, safety, dosimetry, IND-filing) prior to or at the time of publication.
Reviewers will assess the adequacy of the proposed plan as detailed in the review criteria section. The sharing plan as approved, after negotiation with the applicant when necessary, will be a condition of the award.
A separate section labeled "Milestones" should be included at the end of the Research Plan of the R21 phase of the application. The Milestones will be used as criteria to make objective evaluations of progress at the end of the R21 phase. In addition to well-defined, quantifiable Milestones, the suitability of the proposed Milestones for assessing the success of the R21 phase and the implications of successful completion of these Milestones for the proposed R33 study should also be discussed. Examples of quantifiable Milestones could include: identification and synthesis of a lead compound with characteristics suitable for PET or SPECT imaging; radiolabeling of lead compound(s) for in vivo imaging; in vivo imaging in rodents and/or primates to assess biodistribution and physicochemical properties of the radioligand; use of animal models to assess pharmacokinetic properties of the radioligand (binding potential, sensitivity to displacement by agonists or antagonists at the target site); determination of preclinical toxicology and pathology for the submission of an exploratory IND (Investigational New Drug) or IND application to the Food and Drug Administration (FDA); or IRB approval for clinical studies.
The reasonableness of the data sharing plan or the
rationale for not sharing research data will be assessed by the reviewers.
However, reviewers will not factor the proposed data sharing plan into the
determination of scientific merit or the priority score. For more information
on data sharing, see http://grants.nih.gov/grants/policy/data_sharing/.
Sharing Research Resources
NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this
funding opportunity must include a plan to share protocols, procedures,
unlabeled PET and SPECT ligands, analytical tools, IND filing information,
and other materials that may be developed in the course of the project with
the scientific community.
The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., “Reporting.”
1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.
Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.
As part of the initial merit review, all applications will:
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:
The goals of NIH-supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria 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 an 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. However, to meet the goals of this FOA, “Innovation” will be given additional weight in the review process.
Significance: Does this study address an important scientific health problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?
Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?
Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the PD/PI and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?
Environment: Does the scientific environment in which the work will be done
contribute to the probability of success? Do the proposed studies benefit
from unique features of the scientific environment, or subject populations,
or employ useful collaborative arrangements? Is there evidence of institutional
2.A. Additional Review Criteria:
Are the milestones quantitative? Are the proposed milestones appropriate for judging the success of the R21 work? Are the proposed milestones appropriate in determining whether the R33 phase should be awarded? Do the milestones establish feasibility for all aspects of the proposed R33 work?
For the R21/R33 Phased Innovation Award application, the initial review group will evaluate the specific goals for each phase and the feasibility milestones that would justify expansion to the R33 phase. A single priority score will be assigned to each scored application. As with any grant application, the initial review group has the option of recommending support for a shorter duration than that requested by the applicant and basing the final merit rating on the recommended portion of the application. For the R21/R33 application, this may result in a recommendation that only the R21 phase be supported, based on concerns related to the application's specific goals and the feasibility milestones justifying expansion to the R33 phase. Deletion of the R33 phase by the review panel or presentation of inadequate milestones in the application may affect the merit rating of the application.
In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:
Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See item 6 of the Research Plan component of the SF424 (R&R).
Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders,
all racial and ethnic groups (and subgroups), and children as appropriate
for the scientific goals of the research will be assessed. Plans for the recruitment
and retention of subjects will also be evaluated. See item 7 of the
Research Plan component of the SF424 (R&R).
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF424 (R&R) will be assessed.
Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.
2.B. Additional Review Considerations
Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the number of person months listed for the effort of the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?
2.C. Sharing Research Data
Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).
2.D. Sharing Research Resources
NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.
Program staff will be responsible
for the administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., “Reporting."
1. Award Notices
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.
Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., “Funding Restrictions.”
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.
When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
We encourage your inquiries concerning this funding
opportunity and welcome the opportunity to answer questions from potential
applicants. Inquiries may fall into three areas: scientific/research, peer
review, and financial or grants management issues:
1. Scientific/Research Contacts:
Linda Brady, Ph.D.
Director, Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 7204
Bethesda, MD 20892-9641
Telephone: (301) 443-3563
FAX: (301) 402-4740
Susan Molchan, M.D.
Program Director, AD Neuroimaging Initiative
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging, NIH
Gateway Bldg., Suite 350
7201 Wisconsin Ave.
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Antonio Noronha, Ph.D.
Division of Neuroscience and Behavior
National Institute of Alcohol Abuse and Alcoholism, NIH
5635 Fishers Lane, Room 2061, MSC 1705
Bethesda, MD 20892-1705
Telephone: (301) 443-1705
FAX: (301) 594-0673
Steven Grant, Ph.D.
Division of Clinical Neuroscience and Behavioral Research
National Institute on Drug Abuse, NIH
6001 Executive Boulevard, Room 3170
Bethesda, MD 20892-9551
Telephone: (301) 443-4877
FAX: (301) 443-6814
2. Peer Review Contacts:
3. Financial or Grants Management Contacts:
Grants Management Branch
Division of Extramural Activities
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 6118
Bethesda, MD 20892-9605
Telephone: (301) 443-3858
FAX: (301) 443-6885
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their institutions on issues related to institutional policies and local IRB rules, as well as local, state and federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of scientific merit or the priority score.
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 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 funding opportunity 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.
Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004, receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.
Inclusion of Women And Minorities in Clinical Research:
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 clinical research projects unless a clear and compelling justification is 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 clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R); and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: (a) all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.
Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.
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 (http://grants.nih.gov/grants/funding/children/children.htm).
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 applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.
NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.
NIH is requesting that authors submit manuscripts resulting from (1) currently funded NIH research projects or (2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.
For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://PublicAccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual.
Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information," the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR Website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.
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 FOA is related to one or more of the priority areas. 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 at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
The PHS strongly encourages all grant recipients
to provide a smoke-free workplace and discourage the 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
Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40-hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.
Office of Extramural
National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
Department of Health
and Human Services (HHS)
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