and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of
Health (NIH) (http://www.nih.gov)
Components of Participating Organizations
National Heart, Lung, and
Blood Institute (NHLBI) (http://www.nhlbi.nih.gov)
Title: New Approaches to Non-Viral Systems for Gene Transfer
Applications for Heart, Lung, and Blood Diseases (R21/R33)
Announcement Type
New
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: PAR-06-243
Note: This is published in Grants.gov as Opportunity Number PA-06-243.
Catalog of Federal Domestic Assistance Number(s)
93.837, 93.838, 93.839
Key Dates
Release/Posted Date: March
24, 2006
Opening Date: August 12, 2006 (Earliest date an application may be
submitted to Grants.gov).
Letters of Intent
Receipt Date(s): Not Applicable
Application Submission Date(s): September 12, 2006; September 12, 2007; September 12,
2008
Peer
Review Date(s): October/November
2006; October/November 2007; October/November 2008
Council Review
Date(s): February 2007;
February 2008; February 2009
Earliest
Anticipated Start Date(s): April 1, 2007;
April 1, 2008; April 1, 2009
Additional
Information To Be Available Date: Not
Applicable
Expiration
Date: September 13, 2008
Due Dates for E.O. 12372
Not Applicable
Additional Overview
Content
Executive Summary
This Funding Opportunity Announcement (FOA) issued by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), invites applications from organizations/institutions that propose the development of new and efficient non-viral vectors that can overcome the limitations of viral vectors for gene therapy clinical trials in heart, lung, and blood diseases.
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
Purpose
The purpose of this
Funding Opportunity Announcement (FOA) issued by the National Heart, Lung, and
Blood Institute (NHLBI), National Institutes of Health (NIH), is to foster
applications from organizations/institutions that propose the development of
new and efficient non-viral vectors that can overcome the limitations of viral
vectors and be used for gene therapy clinical trials in heart, lung, and blood
diseases.
Background
Gene therapy has tremendous potential to provide highly specific, safe, and effective treatments for many different diseases, ranging from single gene effects to complex conditions that are primarily due to environmental causes. However, its potential can be realized only with safe and effective delivery systems. A key factor in the success of gene therapy is the development of delivery systems that are capable of efficient and safe gene transfer in a variety of tissues. Despite some of the initial success in the clinic, viral gene delivery systems have limitations of immune response, toxicity, and chromosomal integrations.
Non-viral gene delivery systems offer an alternative strategy and have the potential to provide nucleic-acid based therapeutics that closely resemble traditional pharmaceuticals and ameliorate some of the more common limitations with viral vectors. Two promising classes of non-viral vectors are the nanoparticles, that are condensed from DNA and can be internalized by cells, and matrices or micro/nanoparticles that can entrap DNA for sustained release. This delivery method is receiving increasing attention because of ease of synthesis, low immunogenicity, and unrestricted plasmid size. Non-viral vectors have the potential to be administered repeatedly with minimal host immune response. In addition, they face less of a challenge than viral vectors with regard to pharmaceutical issues such as scale-up, storage stability, and quality control. Non-viral vectors also have an advantage over viral vectors because of their versatility. Rigidity, hydrophobicity, charge density, biodegradability, and molecular weight of non-viral vectors are all parameters that can be adjusted to achieve an optimal composite with DNA. Versatility is particularly important in view of the broad range of gene therapy applications and their unique demands. Direct naked DNA administration, or its administration mediated by electroporation, ultrasound, high pressure bombardment, cationic lipid, and polymer represents the different modalities of non-viral gene transfer.
Several barriers must be overcome for an exogenous gene to reach the nucleus of the cell from the extracellular space. For intracellular delivery, the DNA must be condensed to a size that permits internalization by the cells. Non-viral vectors such as cationic polymers can serve as the condensing agent. While considerable progress has been made in the design of polymers to deliver nucleic acids, there remain significant challenges to improving non-viral gene expression to the therapeutic level. Further mechanistic insights from in vitro intracellular trafficking and in vivo transport studies will be needed to guide the design of the next generation of polymeric gene carriers. Cell types with different metabolic characteristics may require DNA-nanoparticles of different properties for optimal transfection. Different vectors may be required for different routes of administration. For instance, nanoparticles optimized for oral ingestion may not be suitable for intramuscular injection, where ready dissociation of DNA from the nanoparticles is crucial for high grade expression. Although many challenging tasks remain, it is likely that as our understanding of gene delivery improves, new and efficient non-viral vectors will be developed.
Research Scope
The primary intent of this FOA is to stimulate the development of new and efficient non-viral vectors that may allow scientists to use them in gene therapy clinical trials. High-risk applications are encouraged, and the innovative nature of the application is emphasized in the review criteria.
Applications submitted in response to this FOA should focus on topics related to the development of new non-viral vectors. This program will speed the design for new and improved non-viral vectors that can overcome or improve some of the current drawbacks of the non-viral family of vectors. It will investigate the cellular barriers that prevent efficient delivery of DNA, factors that control stability, pharmacokinetics, and bio-distribution of non-viral vectors. Tissue-specific and site-specific integrating or self replicating vectors will be explored, including vectors with long-term transgene expression with eukaryotic transposable elements and RNA interference delivery methods. This program will encompass a range of novel delivery methods, including the application of electric fields to facilitate cell permeabilization (electroporation), lipid-associated DNA constructs (lipofection), high-velocity gold particles coated with DNA that directly penetrates cell membranes (gene gun), ultrasonic waves that enhance gene expression levels (ultrasound), and explore the use of silica nanoparticles as DNA carriers. Modified nanoparticles combined with optical tracking offers an especially promising direction for targeted therapy with enhanced efficacy.
Some examples of research topics for this FOA include, but are not limited to, the following:
However, applications that propose Phase III clinical trials will not be considered responsive to this FOA and will not be accepted for review.
See Section
VIII, Other Information - Required Federal Citations for policies related
to this announcement.
N/A
Section
II. Award Information
1. Mechanism of Support
This funding opportunity will use the combined Exploratory/Developmental Grants and Exploratory/Developmental Grants Phase II (R21/R33) grant mechanisms. Applications using only the R21 mechanism or the R33 mechanism will not be considered. Applicants are encouraged to contact NHLBI 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 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 NHLBI 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.
For the R21 phase of the application, direct costs are limited to a maximum of $250,000 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.
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 as the Project Director/Principal Investigator (PD/PI) 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 programs.
2. Cost Sharing or Matching
This
program does not require cost sharing as defined the current NIH
Grants Policy Statement.
3. Other-Special Eligibility Criteria
Not Applicable
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
Grants.gov Customer Support
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email [email protected]
2) Organizational/Institutional Registration in the eRA Commons
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
Email [email protected]
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.
Applicants 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 301-710-0267, 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 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
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
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/R33 uses ONLY the detailed Research & Related Budget. (Do not use the PHS 398 Modular 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: August 12, 2006 (Earliest date an application may be submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not Applicable
Application Submission Date(s): September 12, 2006; September 12, 2007; September 12, 2008
Peer Review Date(s): October/November 2006; October/November 2007; October/November 2008
Council Review Date(s): February 2007; February 2008; February 2009
Earliest Anticipated Start Date(s): April 1, 2007; April 1, 2008; April 1, 2009
3.A.1.
Letter of Intent
A letter of intent is not required for this 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.
Specific Instructions for Preparing a Combined R21/R33 Phased Innovation Award Application
The R21/R33 Phased Innovation Award application must be submitted as a single application with one PHS398 Cover Page Supplement component and one Research & Related Budget component. Although it is submitted as a single application, it should be clearly organized into two phases with each of the PHS398 Research Plan Attachments, Items 2-5 (Specific Aims, Background and Significance, Preliminary Studies, Research Design and Methods), beginning with discussion of the R21 phase followed by discussion of the R33 phase. The milestones can be no more than one page at the beginning of the Specific Aims attachment (Item 2). The total length of the Research Plan attachments section, Items 2-5, cannot exceed 25 pages plus one page for milestones, or 26 pages total.
Appendix materials 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 a 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 $250,000 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 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 attachment in 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.
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 26 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 a scientifically literate non-expert 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. State concisely and realistically what the proposed research is intended to accomplish in terms of its potential for technological innovation.
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 (R&R) 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.
Applicants should also address plans to make the products, tools, or technologies forthcoming from this research available to the relevant biomedical research user community.
Plan
for Sharing Research Data
All
applicants must describe their plans for disseminating information about, and
providing access to the technology developed under this grant support.
For example, the technology might be made available as a fee-for-service,
through sale of instruments and/or reagents, through collaboration, through
publication and posting of results, plans and methods, or by other means.
Applicants should include a brief one paragraph description of how final research data will be shared, or explain why data-sharing is not possible. The specific nature of the data to be collected will determine whether or not the final dataset may be shared. If the final data are not amenable to sharing, for example, if they are proprietary, this must be explained in the application.
Applicants are encouraged to discuss their data-sharing plan with the Institute/Center staff likely to accept assignment of their application.
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. 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. For
more information on data sharing, see http://grants.nih.gov/grants/policy/data_sharing/ and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.
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.
The
adequacy of the resources sharing plan and any related data sharing plans will
be considered by NHLBI program staff 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.
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
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 NIH R21 exploratory/developmental grant is a mechanism for supporting novel scientific ideas or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research. An exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
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? To what degree does the proposed
research support the needs of the targeted gene therapy research community?
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? What is the time frame for developing the proposed approaches, tools or
technologies? Is this time frame suitable for meeting the gene therapy research
community’s needs?
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 support?
2.A.
Additional Review Criteria:
In
addition to the above criteria, the following items will 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 and appropriateness of the proposed
budget and the requested period of support in relation to the proposed research.
The priority score should not be affected by the evaluation of the budget.
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. NHLBI
program staff will be responsible for monitoring the data sharing policy. For
more information on data sharing, see http://grants.nih.gov/grants/policy/data_sharing/ and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.
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.
NHLBI
program staff will be responsible for the administrative review of the plan for
sharing research resources.
The
adequacy of the resources sharing plan and any related data sharing plans will
be considered by NHLBI program staff 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 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.
3. Reporting
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:
Heart
Sonia I. Skarlatos, Ph.D.
Acting Director, Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 8128
Bethesda, MD 20892-7956
Telephone: (301) 435-0466
Fax: (301) 480-7971
Email: [email protected]
Blood
Pankaj
Qasba, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 10161
Bethesda, MD 20892-7950
Telephone: (301) 435-0055
Fax: (301) 480-0867
Email: [email protected]
Lung
Susan
Banks-Schlegel, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 10220
Bethesda, MD 20892-7952
Telephone: (301)
435-0202
Fax: (301) 480-0202
Email: [email protected]
2. Peer Review Contacts:
Not
Applicable.
3. Financial or Grants Management
Contacts:
Mary Baylor
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 7146
Bethesda, MD 20892-7926
Telephone: (301) 435-0152
Fax: (301) 480-3310
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).
Beginning October 1, 2004, all investigators submitting an NIH application or
contract proposal 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) application; 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. 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 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 Part 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 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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