and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of
Health (NIH), (http://www.nih.gov)
International
Rett Syndrome Association (IRSA), (http://rettsyndrome.org)
Rett Syndrome
Research Foundation (RSRF), (http://www.rsrf.org)
Components of Participating
Organizations
National Institute of
Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov)
National
Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)
National
Institute of Child Health & Human Development (NICHD), (http://www.nichd.nih.gov)
Title: Basic and Clinical Research on Rett Syndrome and MECP2
(R21)
Announcement Type
This is a reissue of PAS-05-024,
which was previously released March 25, 2005.
Update: The following update relating to this announcement has been issued:
NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted 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/Apply for Grants (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.
Two steps are required for on time submission:
1) The application must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the submission/receipt date (see Key Dates below).
2) Applicants must complete a verification step in the eRA Commons within two business days of notification from NIH. Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.
Program Announcement (PA) Number: PAS-06-274
Catalog of Federal Domestic Assistance Number(s)
93.853, 93.242, 93.865
Key Dates
Release/Posted
Date: March 24, 2006
Opening
Date: May 2, 2006 (Earliest date an
application may be submitted to Grants.gov)
Letter of
Intent Receipt Date(s): Not applicable
Application Submission Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer
Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest
Anticipated Start Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Additional Information To Be Available Date (URL Activation Date): Not
Applicable
Expiration
Date: November 2, 2007 (now January 8, 2008 per NOT-OD-07-093)
Due Dates for E.O. 12372
Not Applicable
Additional Overview
Content
Executive Summary
The National Institute of Neurological Disorders
and Stroke (NINDS), the National Institute of Child Health and Human
Development (NICHD), the National Institute of Mental Health (NIMH), the
International Rett Syndrome Association (IRSA) and the Rett Syndrome Research
Foundation (RSRF) invite research grant applications aimed at understanding
and/or treating Rett Syndrome (RTT). The recent demonstration that mutations in
the MECP2 gene cause most cases of RTT has created new opportunities for both
basic and clinical research. Included within the scope of this funding
opportunity announcement (FOA) with set-aside funds are developmental, neuroanatomical,
molecular genetic, and pathophysiological research, therapy development
projects and clinical studies. Studies of the role of MeCP2 in basic biological
processes or in the etiology of other neurological or neurobehavioral disorders
are also appropriate.
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. Electronic
Transmission of an Application to the NIH
C.
Application Processing
4. Intergovernmental
Review
5. Funding
Restrictions
6. Other Submission
Requirements
Section
V. Application Review Information
1. Criteria
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
3. Reporting
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
Part II
- Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH) have entered into a public-private partnership with the International Rett Syndrome Association (IRSA) and the Rett Syndrome Research Foundation (RSRF) to jointly sponsor this funding opportunity announcement (FOA) with set-aside funds aimed at understanding and/or treating Rett Syndrome (RTT). This FOA invites investigator-initiated grant applications to conduct research relevant to the basic understanding, cure, prevention and improved treatments for RTT and its complications.
RTT is a severely debilitating neurodevelopmental disorder historically believed to affect about 1 in 10,000 females. Evidence from recent genetic testing suggests that the prevalence may be much higher. Girls with RTT appear to develop normally until about 6 to 18 months of age at which time they enter a period of regression. These children lose speech, purposeful hand and motor skills and cognitive abilities that they had acquired, while also developing seizures, repetitive hand movements and other motor disturbances, autonomic dysfunctions such as breathing irregularities, social withdrawal (including autism) and growth and mental retardation. There is no cure for RTT, and current treatment for the disorder is symptomatic (e.g., controlling seizures). Until recently, little progress had been made in understanding the cause of RTT or in developing approaches for its treatment. However, the demonstration that mutations in the MECP2 gene are responsible for the majority of cases of RTT suggests new avenues for research and therapy development. The goal of this FOA is to accelerate RTT research by capitalizing on these opportunities.
RTT is unlike any other pediatric neurological disorder in that it cannot be classified simply as a degenerative condition, storage disease, or developmental malformation. Although MECP2 mutations are now known to cause RTT, the function of this gene during development is not clearly understood. The MeCP2 protein was originally identified by its ability to bind specifically to CpG-methylated DNA, and it has been shown to repress transcription in a methylation-dependent fashion. However, its precise mechanism of action has not been determined and MeCP2 target genes remain undefined. There is currently no clear pathophysiological or neurodevelopmental model to explain how MECP2 mutations cause the symptoms associated with this devastating disease. Understanding the connection between loss of MeCP2 function and RTT will be critical for developing rational therapeutic interventions.
Recent research has led to a number of new discoveries based on the MECP2 gene and its role in RTT. For example, MeCP2 has been identified as an activity-dependent transcriptional regulator of genes such as BDNF which is known to have a role in brain development and function. A new isoform of the MeCP2 protein has been discovered and is much more prevalent in the human brain than the originally described form. Importantly, introduction of the MeCP2 protein into post-mitotic nerve cells of adult MECP2 deficient mice rescues the RTT-like symptoms in these mice. These latter findings suggest that gene-based therapies to replace or correct the defective MECP2 gene or the design of specific inhibitors for downstream targets may be able to prevent RTT symptoms in children afflicted by this disease.
MECP2 mutations have recently been implicated in several disorders in addition to RTT. These include X-linked recessive mental retardation, autism, Angelman syndrome, and neonatal onset encephalopathy. The MECP2 gene may account for a significant fraction of cases of mental retardation in the general population, as well as for other broadly expressed phenotypes. Progress in RTT research will therefore be important for understanding and treating a variety of other brain disorders.
Applications submitted in response to this FOA should focus on a topic related to understanding and/or treating RTT. Studies of the involvement of MECP2 in other neurological or neurobehavioral disorders, which may shed light on RTT, are also appropriate if translational impact on RTT is anticipated. Possible areas of investigation include, but are not limited to:
See Section VIII, Other Information - Required Federal
Citations, for policies related to this announcement.
Section
II. Award Information
1. Mechanism of Support
This funding opportunity will
use the National Institutes of Health (NIH) Exploratory/Developmental Research
Grant (R21) award
mechanism. The applicant will be solely responsible for planning, directing,
and executing the proposed project.
This funding opportunity uses just-in-time concepts. It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular Budget Component, of the Application Guide).
An R21 is not renewable.
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
The participating organizations intend to commit a total of $2,600,000 to this FOA and two parallel announcements of identical scientific scope that use the R01 and R03 mechanisms, in addition to funds available for applications sent in response to this FOA that score within the paylines of the participating NIH institutes. Payment of applications depends on the overall scientific merit of the applications and the availability of funds.
The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Direct costs are limited to $275,000 over the two years of the R21 award, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this Program Announcement funding opportunity.
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 IC(s) provide support for this
program, awards pursuant to this funding opportunity are contingent upon the availability
of funds and the receipt of a sufficient number of meritorious applications.
Facilities and
administrative (F&A) costs requested by consortium participants are not
included in the direct cost limitation, see NOT-OD-05-004.
Section
III. Eligibility Information
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 their 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.
2. Cost Sharing or Matching
This program does not require
cost sharing as defined in the current NIH
Grants Policy Statement.
3.
Other-Special Eligibility Criteria
Applicants
may submit more than one application, provided each application is
scientifically distinct.
Section IV. Application and Submission Information
Registration and Instructions for Submission via Grants.gov
To download a 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:
PD/PIs should work with their institutions/organizations to make sure they are registered in the NIH 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
2) Organizational/Institutional Registration in the eRA Commons
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 FOA.
For further
assistance contact GrantsInfo, Telephone 301-435-0714, Email: [email protected].
Telecommunications
for the hearing impaired: TTY 301-451-5936.
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 Tips and Tools for Navigating Electronic Submission on the front page of 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:
Required
Components:
SF424
(R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research
& Related Other Project Information
Research
& Related Senior/Key Person
PHS398
Cover Page Supplement
PHS398
Research Plan
PHS398
Checklist
PHS398 Modular Budget
Optional Components:
PHS398
Cover Letter File
R&R
Subaward Budget Attachment(s) Form
Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)
Foreign
Organizations
Several
special provisions apply to applications submitted by foreign organizations:
Proposed
research should provide a unique research opportunity not available in the United States.
3. Submission Dates and Times
See Section IV.3.A for details.
3.A.
Submission, Review and Anticipated Start Dates
Opening Date: May 2, 2006 (Earliest
date an application may be submitted to Grants.gov)
Letter of Intent Receipt Date(s): Not applicable
Application
Submission Date(s): Standard dates apply. See http://grants.nih.gov/grants/funding/submissionschedule.htm for
details.
Peer Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward for
details.
Council Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward for
details.
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward for
details.
3.A.1.
Letter of Intent
A letter of intent is not required for the funding
opportunity.
3.B. Electronic
Transmission of an Application 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.
Upon receipt, applications will
be transferred from Grants.gov to the NIH Electronic Research Administration
process for validation. Both the PD/PI and the SO for the organization must
verify the submission via Commons within 2 business days of notification of the NIH validation.
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 Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.
Renewal (formerly competing continuation or Type 2 ) applications are not permitted.
All application instructions outlined in the SF424 (R&R) application are to be followed, with the following requirements for R21 applications:
Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
Letter of Authorization:
Because applications will be co-funded by the NIH, IRSA and RSRF, all applicants are requested to submit a brief letter to the NIH indicating that the application and the Summary Statements for such applications and the Progress Reports of funded grants can be shared with IRSA and RSRF. Letters of authorization should be prepared by the PD/PI and co-signed by the official signing for the applicant organization. This letter should be submitted as part of the PHS398 Cover Letter File Component of the SF424 (R&R) application.
This FOA will not accept R21 applications that include clinical trials or other clinical studies of potential therapies (see: http://www.ninds.nih.gov/funding/r21guidelines.htm). Applications that involve human subjects may be submitted to NINDS if the proposal does not include any clinical intervention AND the proposed research includes safety monitoring of study participants that can be performed appropriately within the budgetary and time constraints of the R21 mechanism. Any R21 proposal that does not meet the above criteria or does not provide adequate plans for the protection of the safety, privacy and confidentiality of study participants will not receive an award.
Specific
Instructions for Modular Grant applications.
Applications
requesting direct costs in each year of $250,000 or less (excluding consortium
F&A costs), must be submitted in a modular budget format using the Modular
Budget Component provided in the SF424 (R&R) Application Package and
Instructions Guide (see specifically Section 5.4). The modular budget format
simplifies the preparation of the budget in these applications by limiting the
level of budgetary detail. Applicants request direct costs in $25,000 modules.
Plan for Sharing
Research Data
The precise content
of the data-sharing plan will vary, depending on the data being collected and
how the investigator is planning to share the data. Applicants who are planning
to share data may wish to describe briefly the expected schedule for data
sharing, the format of the final dataset, the documentation to be provided,
whether or not any analytic tools also will be provided, whether or not a
data-sharing agreement will be required and, if so, a brief description of such
an agreement (including the criteria for deciding who can receive the data and
whether or not any conditions will be placed on their use), and the mode of
data sharing (e.g., under their own auspices by mailing a disk or posting data
on their institutional or personal website, through a data archive or enclave).
Investigators choosing to share under their own auspices may wish to enter into
a data-sharing agreement. References to data sharing may also be appropriate in
other sections of the application.
All applicants must
include a plan for sharing research data in their application. The data sharing
policy is available at http://grants.nih.gov/grants/policy/data_sharing.
All investigators responding to this funding opportunity should include a
description of how final research data will be shared, or explain why data
sharing is not possible.
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.
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 should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.
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, http://grants.nih.gov/grants/funding/2590/2590.htm).
See Section VI.3. Reporting.
The sharing of biomaterials, data, and software in a timely manner has been an essential element in the rapid progress that has been made in the genetic and molecular analysis of human diseases. All applicants who respond to this FOA must propose plans for sharing data and biomaterials generated through the grant. Applicants should explain how funds for the storage and distribution of data and biomaterials will be obtained, and may request such funds in the budget of the application. It is expected that the information to be shared will include clinical, diagnostic, and pedigree structure information. Biomaterials to be shared should include patient DNAs and cell lines, mouse or other animal models (see below: Requirements for a sharing plan for Model organisms ) and other resources and reagents generated through the grant. When possible, data and biomaterials should be placed in databases or repositories that will permit their efficient distribution to investigators throughout the scientific community (for example, the NIMH Human Genetics Initiative for autism data and biomaterials; see http://nimhgenetics.org). Rapid sharing of data and biomaterials is strongly encouraged by the NIH and by IRSA and RSRF.
The investigator's data and resource sharing plan should when applicable specify the following elements: (1) the creation of comprehensive and verified databases that contain all clinical, diagnostic, and genetic information collected and produced in the project; (2) if possible, the establishment of high-quality cell lines, from which DNA will be extracted and stored, for all subjects studied from whom blood or other biological samples have been obtained; (3) mechanisms by which all databases and any biomaterials (DNA samples, cell lines, mouse or other animal models, reagents) are widely distributed to qualified investigators in the scientific community; (4) a protocol for wide dissemination of these data and biomaterials; and (5) a timetable for distribution.
The Initial Review Group will evaluate the proposed sharing plan and comment on its adequacy in an administrative note in the Summary Statement. Reviewers will not factor the proposed data-sharing plan into the determination of scientific merit or priority score. The adequacy of the plan will be considered by NIH staff in determining whether the grant shall be awarded. The sharing plan as approved, after negotiation with the applicant when necessary, will be a condition of the award.
Section V. Application Review Information
1. Criteria
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:
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. For example, an investigator may
propose to carry out important work that by its nature is not innovative but is
essential to move a field forward.
Significance: Does this study address an
important 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 principal investigator 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 support?
2.A. Additional Review
Criteria:
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 percent effort listed for 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 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.
The presence of a data sharing plan will be part of the terms and conditions of
the award. The funding organization will be responsible for monitoring the data
sharing policy.
Program staff will be responsible for the administrative review of the plan for sharing research data.
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 (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.
The reviewers will be asked to assess the adequacy of the investigator's data and resource sharing plan with respect to the following elements when appropriate: (1) the creation of comprehensive and verified databases that contain all clinical, diagnostic, and genetic information collected and produced in the project; (2) if possible, the establishment of high-quality cell lines, from which DNA will be extracted and stored, for all subjects studied from whom blood or other biological samples have been obtained; (3) mechanisms by which all databases and any biomaterials (DNA samples, cell lines, mouse or other animal models, reagents) are widely distributed to qualified investigators in the scientific community (please see: http://grants2.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html for requirements for Model Organism sharing plans); (4) a protocol for wide dissemination of these data and biomaterials; and (5) a timetable for distribution. The Initial Review Group will evaluate the proposed sharing plan and comment on its adequacy in an administrative note in the Summary Statement. Reviewers will not factor the proposed data-sharing plan into the determination of scientific merit or priority score.
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.
3. Anticipated Announcement and Award Dates
Not applicable
Section VI. Award Administration Information
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 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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).
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 Also Section
IV.5. Funding Restrictions.
2. Administrative and
National Policy Requirements
The terms and conditions
of the award may include specific requirements for data and/or resource sharing
including depositing cell lines, DNA samples, biomaterials or other mouse and
animal models into National repositories.
All
NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as
part of the Notice of Award. For these terms of award, see the NIH Grants Policy Statement Part
II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm)
and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and
Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
3. Reporting
Awardees will be required to submit the PHS
Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm)
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:
Laura A. Mamounas,
Ph.D.
Neurogenetics
and Development Program
National
Institute of Neurological Disorders & Stroke
6001
Executive Blvd., Room 2132, MSC 9525
Bethesda, MD 20892-9525
Telephone:
(301) 496-5745
Fax:
(301) 402-1501
Email: [email protected]
Mary Lou
Oster-Granite, Ph.D.
Mental
Retardation and Developmental Disabilities Branch
Center
for Research for Mothers and Children
National Institute of Child Health & Human Development
6100
Executive Boulevard, Rm 4B09D, MSC 7510
Bethesda, MD 20892-7510
Telephone:
(301) 435-6866
Fax:
(301) 496-3791
Email: [email protected]
Steven O.
Moldin, Ph.D.
Division
of Neuroscience & Basic Behavioral Science
National
Institute of Mental Health
6001
Executive Blvd., Room 7191, MSC 9643
Bethesda, MD 20892-9643
Telephone:
(301) 443-2037
Fax:
(301) 443-9890
Email: [email protected]
2. Peer Review Contacts:
Not applicable
3. Financial or Grants Management Contacts:
Ms. Kathleen Howe
Grants
Management Branch
National
Institute of Neurological Disorders and Stroke
6001
Executive Boulevard, Room 3266
Bethesda, MD 20892
Telephone:
(301) 496-9231
Fax:
(301) 402-0219
Email: [email protected]
Mr. J.
Chris Robey
Grants
Management Branch
Center
for Developmental Biology and Perinatal Medicine
Room
8A17K, MSC 7510
6100
Executive Blvd.
National Institute of Child Health and Human Development
Bethesda, MD 20892-7510
Telephone:
(301) 435-6996
Fax: (301)
402-0915
Email: [email protected]
Ms. Carol
J. Robinson
Grants
Management Branch
National
Institute of Mental Health
6001
Executive Boulevard, Room 6118, MSC 9605
Bethesda, MD 20892-9605
Telephone:
(301) 443-3858
FAX:
(301) 443-6885
Email: [email protected]
Section VIII. Other Information
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 (http://publicaccess.nih.gov/publicaccess_manual.htm).
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. 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. 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 PA 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 NIH Grants Policy Statement can
be found at http://grants.nih.gov/grants/policy/policy.htm.
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 people.
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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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