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
Institute on Alcohol Abuse and Alcoholism (NIAAA) (http://www.niaaa.nih.gov)
Title: The Role
of Mitochondria in Alcohol-Induced Tissue Injury (R01)
Announcement Type
New
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.
Request for Applications (RFA) Number: RFA-AA-08-002
Catalog of Federal
Domestic Assistance Number(s)
93.273
Key Dates
Release/Posted Date: May 25, 2007
Opening Date: September 30, 2007 (Earliest
date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): October 1, 2007
NOTE: On time submission requires that
applications be successfully submitted to Grants.gov no later than 5:00 p.m.
local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): October 30, 2007
Peer Review Date(s): February/March,
2008
Council Review Date(s): May 2008
Earliest Anticipated Start
Date(s): July 2008
Additional Information To Be
Available Date (Activation Date): Not Applicable
Expiration Date: October 31, 2007
Due Dates for E.O. 12372
Not Applicable
Additional
Overview Content
Executive Summary
This Funding Opportunity Announcement (FOA) issued by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, solicits Research Project Grant (R01) applications that propose to study biological processes involving the mitochondria in alcohol-induced tissue injury.
Table of Contents
Part I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity
Description
1. Research Objectives
Section II. Award Information
1. Mechanism of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria
Section
IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and
Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically
to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
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 Contacts
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
Background:
Excessive acute or chronic ingestion of alcohol often leads to various medical disorders, resulting in enormous economic and public health burdens on our society. These medical disorders include addiction and alcohol-induced tissue injuries such as alcoholic hepatitis and liver cirrhosis, pancreatitis, cardiomyopathy, immune system defects, fetal abnormalities, and brain damage. Alcohol’s effects on these organs often impact the structure and function of mitochondria, which play a central role in cellular energy metabolism, production of reactive oxygen species (ROS), and programmed cell death. Altered mitochondrial function, apoptosis, or excessive oxidative stress may contribute to the pathogenesis of many human diseases, including neurodegenerative diseases, metabolic diseases, and aging-associated dysfunction. It has been known that alcohol can significantly affect the morphology and ATP-production ability of mitochondria. However, little is known about the mechanisms of these effects and contribution of alcohol-induced mitochondrial dysfunction in causing tissue damage. Taking advantage of recent technological advances such as mitochondrial genomics, proteomics, and imaging, studies on mitochondria may shed light on various mechanisms and provide new avenues for the diagnosis and treatment of alcohol-induced tissue injury.
The mitochondrion is a compartmentalized organelle central to energy production in the cell. It consists of two membranes of phospholipid bilayer, dividing mitochondrion into two compartments, the inter-membrane space and matrix. The outer membrane is widely permeable to ions and small molecules (< 5 KD) because of large pores made of the trans-membrane mitochondrial protein, porin (also known as Voltage-Dependent Anion Channel, VDAC), although the open/closed state of mitochondrial porin may be regulated. The inner mitochondrial membrane is much less permeable and, therefore, serves as an electrical insulator and chemical barrier to separate the matrix from the cytosolic environment, and maintains a proton gradient necessary for proper mitochondrial energy production. Mitochondria contain a range of enzymes involved in the metabolism of carbohydrates, lipids, amino acids, and urea, and in the biosynthesis of heme. ATP is generated by oxidative phosphorylation driven by the proton electrochemical gradient generated through the electron transport chain in the inner mitochondrial membrane, while most of the citric acid cycle and fatty acid oxidation take place in the mitochondrial matrix. The number of mitochondria in each cell or tissue varies widely, depending on cellular energy demands. Each mitochondrion contains multiple copies of a small circular genome that encodes only 37 genes in mammals. Thirteen of these 37 genes encode mitochondrial proteins essential for the respiratory chain. The remainder encode ribosomal and transfer RNAs, which are important for mitochondrial protein synthesis. Individual mitochondrial genomes appear to replicate at random throughout cell cycle. Mitochondria are not generated de novo. Rather, their biogenesis can happen at any point in the cell cycle through fission of mature mitochondria. The mitochondrial fusion and fission can generate a more integrated or more distributed mitochondrial network.
It is estimated that mammalian mitochondria contain approximately 1500 proteins. With only 13 proteins encoded by the mitochondrial genome, more than 99% of the mitochondrial proteins are encoded by the nuclear genome and transported to the mitochondria by highly regulated mechanisms. For this reason, the majority of known mitochondrial diseases is attributable to mutations in nuclear genes and not inherited maternally. In the past, most research efforts have been focused on the core functions of mitochondria, such as oxidative phosphorylation and apoptosis. Despite the significance of mitochondria for the cell and human health, a very limited number of mitochondrial proteins have been identified and characterized. Recently, tremendous advances have been made through proteomics, bioinformatics, and other approaches to expand the inventory of known mitochondrial proteins to 1080 in human. The application of proteomics has been a valuable approach to the study of alcohol-induced protein changes in mitochondria. In an animal model of chronic ethanol exposure, quantitative changes in 43 mitochondrial proteins were demonstrated. Despite intensive studies on a limited number of mitochondrial proteins, very little is known about the majority of mitochondrial proteins in terms of their function, regulation, and relevance to human disease.
It has been well-documented that both acute and chronic alcohol intake can affect the structure and function of mitochondria in a variety of tissues in humans or in animal models. The effects of alcohol on mitochondria were first observed as morphological changes, viz., mitochondrial enlargements and shape distortions, as well as disruption of cristae. The effects of alcohol on mitochondrial function that accompany structural alterations have only been partially recognized. Ethanol exposure reduces the synthesis of ATP by inhibiting the electron transport chain and oxidative phosphorylation, increases the reduction level of NADH, and reduces fatty acid oxidation. Ethanol also increases the levels of malonyl-CoA by activating acetyl-CoA carboxylase, thus inhibiting fatty acid transport into the mitochondrion and increasing fatty acid synthesis. In addition, ethanol exposure alters mitochondrial protein synthesis and damages mitochondrial DNA. Mitochondria are the major source for the production of reactive oxygen species (ROS) through cellular respiration, and alcohol metabolism further increases ROS production by increasing the ratio of NADH/NAD+. ROS is also produced by cytochrome P450 2E1 (CYP2E1) which metabolizes alcohol at high concentrations. Although most CYP2E1 is localized outside the mitochondria, some CYP2E1 is expressed in the mitochondrial inner membrane. Chronic alcohol exposure induces both microsomal and mitochondrial CYP2E1, and results in a greater increase of the enzyme in mitochondria (69%) than in microsomes (43%). In addition to the production of ROS, oxidation of alcohol through alcohol dehydrogenase (ADH) or CYP2E1 generates acetaldehyde. Acetaldehyde is a highly reactive and toxic metabolite that is oxidized predominantly through the low-Km mitochondrial aldehyde dehydrogenase (ALDH). A restriction in its oxidation may contribute to mitochondrial damage. Furthermore, alcohol reduces intracellular antioxidant defense mechanisms, thus contributing to ROS accumulation. These processes may also affect cell fate through oxidative stress-related signaling pathways. Oxidative damage to the mitochondria can alter membrane permeability, membrane potential, and calcium homeostasis, and causes inappropriate activation of the mitochondrial permeability transition. This damage, in turn, causes mitochondrial swelling and cristae fracture, leading to cytochrome c release and further ROS production, and eventually apoptosis through activation of the caspase signaling cascade. Accumulation of ROS such as superoxide, hydrogen peroxide, and hydroxyl radicals, along with a compromised antioxidant capacity, can also affect other cellular functions by damaging organelles other than mitochondria in the cells of various tissues. In addition, a variety of cellular stress signaling pathways that integrate mitochondrial function with other parts of the cell can affect the sensitivity of mitochondria to ROS and other damaging agents and help determine cell fate.
An emerging area of research is the regulation of mitochondrial function and cellular energetics by peroxisome proliferator-activated receptors (PPAR), especially the role of the PPARg coactivator-1 (PGC-1) family of transcriptional coactivators, particularly PGC-1a. PPAR receptors appear to have a considerable role in the regulation of lipid metabolism, glucose homeostasis, and cellular differentiation. PGC-1 coactivators interact with both nuclear receptor and non-nuclear receptor transcription factors to regulate mitochondrial biogenesis and increase mitochondrial energy production. Recently, PGC-1a has been shown to control the production of ROS, thereby maintaining proper mitochondrial function. PGC-1 is highly responsive to a variety of environmental cues and regulates metabolic pathways and biological processes in a tissue-specific manner. Little is known about the actions of alcohol consumption on PPAR and its coactivators, and the subsequent contributions towards producing alcohol-induced tissue injury.
The integrity of the mitochondrial genome and fidelity of its replication, transcription, and translation are critical for the function of the mitochondria. Mutations in the mitochondrial genome can cause ATP insufficiency, overproduction of reactive oxygen species, and increased sensitivity to apoptosis, leading to a variety of human disorders. Despite its importance for the function of mitochondria and the cell as a whole, the mitochondrial genome is relatively prone to damage. Whereas nuclear genome is protected by its associated histone proteins and a sophisticated DNA repair system, only one repair mechanism has been shown to exist in mitochondria. The lack of protective histone and reduced fidelity of DNA replication and DNA repair make mitochondrial genome more sensitive to the attacks of free radicals produced in mitochondria, or other DNA damaging agents notably acetaldehyde. As a result, the mutation rate of the mitochondria genome in mammals is 10 to 20 times greater than that of the nuclear genome. The nucleotide substitution rate for mitochondrial genome during evolution is 10 times greater than that of nuclear genome. Ethanol can cause overproduction of ROS. If acetaldehyde, the first metabolite of ethanol, is not further metabolized to acetate in mitochondria, it can form DNA adducts and cause sequence alteration of the DNA. In this way, chronic consumption of alcohol could cause mutations in mitochondria DNA. Accumulation in mitochondria of such mutations could lead to the impairment of mitochondrial function and contribute to alcohol-induced disorders. Furthermore, variations in mitochondrial genes among different people could also contribute to their susceptibility or resistance to alcohol-induced tissue injury. Examination of mitochondrial DNA for mutations or variations in human or animal models after chronic exposure of ethanol should yield some insightful answers to this hypothesis.
The effects of alcohol on mitochondria involve alterations in many structural and functional components. In addition to mitochondrial oxidative damage and the potential damage to DNA, protein synthesis, and protein transport of mitochondria, it is also important to understand how alcohol affects mitochondrial dynamics, including fusion and fission processes and transport of mitochondria through the cell, mitochondrial protein function, mitochondrial metabolism, and signaling pathways that determine its function. The ultimate goal of this FOA is to decipher the molecular events and interconnecting metabolic and signaling networks affecting mitochondria that result in alcohol-induced tissue injury. A better understanding of the role of mitochondria in alcohol-induced tissue injury may provide new avenues for diagnostic and therapeutic interventions.
Research Objectives:
NIAAA is interested in understanding the role of mitochondria in alcohol-induced tissue injury. The major focus of this FOA is three-fold: (1) The effects of alcohol on mitochondrial structure and function; (2) The contribution of genetic variations of mitochondrial DNA and nuclear-encoded mitochondrial proteins to the susceptibility or resistance of individuals to alcohol-induced tissue injury; (3) The development of mitochondria-related biomarkers or therapeutic targets for alcohol-induced tissue injuries. Studies using human samples, animal models, tissue culture cells, or in vitro biochemical systems are all considered to be appropriate in response to this FOA.
Examples of appropriate studies include but are not limited to:
References:
Cahill, A., Stabley, G.J., Wang, X., and Hoek, J.B. (1999). Chronic ethanol consumption causes alterations in the structural integrity of mitochondrial DNA in aged rats. Hepatology 30, 881-888.
Calvo, S., Jain, M., Xie, X., Sheth, S.A., Chang, B., Goldberger, O.A., Spinazzola, A., Zeviani, M., Carr, S.A., and Mootha, V.K. (2006). Systematic identification of human mitochondrial disease genes through integrative genomics. Nat Genet 38, 576-582.
Chan, D.C. (2006). Mitochondria: Dynamic Organelles in Disease, aging, and Development. Cell 125, 1241-1252.
Dey, A. and Cederbaum, A.I. (2006). Alcohol and oxidative liver injury. Hepatology 43, S63-S74.
Kayser, E.B., Hoppel, C.L., Morgan, P.G., Sedensky, M.M. (2003). A mutation in mitochondrial complex I increases ethanol sensitivity in Caenorhabditis elegans. Alcohol Clin Exp Res 27, 584-592.
Kelly, D.P., and Scarpulla, R.C. (2004). Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18, 357-368.
Lane, N. (2006). Power House of Disease. Nature 440, 600-602.
Mootha, V.K., Bunkenborg, J., Olsen, J.V., Hjerrild, M., Wisniewski, J.R., Stahl, E., Bolouri, M.S., Ray, H.N., Sihag, S., Kamal, M., Patterson, N., Lander, E.S., and Mann, M. (2003). Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell 115, 629-640.
Quintanilla, M.E., Tampier, L., Sapag, A., Israel, Y. (2005). Polymorphisms in the mitochondrial aldehyde dehydrogenase gene (Aldh2) determine peak blood acetaldehyde levels and voluntary ethanol consumption in rats. Pharmacogenet Genomics 15, 427-431.
Quintanilla, M.E., Tampier, L., Valle-Prieto, A., Sapag, A., Israel, Y. (2005). Complex I regulates mutant mitochondrial aldehyde dehydrogenase activity and voluntary ethanol consumption in rats. FASEB J 19, 36-42.
Sawyer, D.E. and Houten, B.V. (1999). Repair of DNA damage in mitochondria. Mutation Research 434, 161-176.
Schapira, A.H.V. (2006). Mitochondrial diseases. Lancet 368, 70-82.
Suh, S.K., Hood, B.L., Kim, B.J., Conrads, T.P., Veenstra, T.D., Song, B.J. (2004). Identification of oxidized mitochondrial proteins in alcohol-exposed human hepatoma cells and mouse liver. Proteomics 4, 3401-3412.
Venkatraman, A., Landar, A., Davis, A.J., Chamlee, L., Sanderson, T., Kim, H., Page, G., Pompilius, M., Ballinger, S., Darley-Usmar, V., Bailey, S.M. (2004). Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatotoxicity. J Biol Chem 279, 22092-22101.
Venkatraman, A., Landar, A., Davis, A.J., Ulasova, E., Page, G., Murphy, M.P., Darley-Usmar, V., Bailey, S.M. (2004). Oxidative modification of hepatic mitochondria protein thiols: effect of chronic alcohol consumption. Am J Physiol Gastrointest Liver Physiol 286, G521-527.
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 Announcement (FOA) will use the NIH Research Project Grant (R01) award mechanism.
The applicant will be solely responsible for planning, directing, and executing the proposed project.
This FOA uses Just-in-Time information concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are a U.S. organization and 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).
U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.
Competing renewal (formerly competing continuation ) and resubmission applications will not be accepted under this FOA. At this time, it is not known if this FOA will be reissued.
2.
Funds Available
Because the nature and scope
of the proposed research will vary from application to application, it is
anticipated that the size and duration of each award will also vary. Although
the financial plans of the Institutes and Centers (ICs) provide support for
this program, awards pursuant to this funding opportunity are contingent upon
the availability of funds and the submission of a sufficient number of
meritorious applications.
The participating organization(s) National Institute on Alcohol Abuse and Alcoholism intends to commit approximately $2 million dollars in fiscal year 2008 to fund 6-8 applications.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
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 institution/organization has any of the following
characteristics:
1.B. Eligible Individuals
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her organization 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.
More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).
The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.
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
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/applicants/apply_for_grants.jsp and follow the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.
Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Registered
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.
Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.
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 organization/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 the 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
301-710-0267, Email: GrantsInfo@nih.gov.
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 for this FOA through Grants.gov/Apply.
The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in 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 or Research & Related Budget,
as appropriate (See Section IV.6., Special Instructions, regarding appropriate
required budget component.)
Research
& Related Budget (required for foreign applications)
Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form
Foreign
Organizations (Non-domestic (non-U.S.) Entity)
NIH policies concerning grants to
foreign (non-U.S.) organizations can be found in the NIH Grants Policy
Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.
Applications from foreign organizations must:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
SPECIAL INSTRUCTIONS
Applications with Multiple PDs/PIs
When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.
Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.
All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.
Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.
If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.
Applications Involving a Single Institution
When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.
Applications Involving Multiple Institutions
When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.
When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.
3.
Submission Dates and Times
See Section IV.3.A. for details.
3.A.
Submission, Review, and Anticipated Start Dates
Opening
Date: September 30, 2007(Earliest date an application may be submitted to
Grants.gov)
Letters of Intent Receipt
Date(s): October 1, 2007
Application
Submission/Receipt Date(s): October 30, 2007
Peer
Review Date(s): February/March, 2008
Council
Review Date(s): May 2008
Earliest
Anticipated Start Date(s): July 2008
3.A.1. Letter of Intent
Prospective applicants are asked to submit a letter of intent that includes the following information:
Although
a letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows IC
staff to estimate the potential review workload and plan the review.
The letter of
intent is to be sent by the date listed in Section
IV.3.A.
The letter of
intent should be sent to:
Abraham Bautista, Ph.D.
Chief, Extramural Project Review Branch
Office of Extramural
Activities
National Institute on
Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
Telephone: 301-443-9737
Fax: 301-443-6077
Email: bautista@mail.nih.gov
3.B. Submitting an Application Electronically to the
NIH
To submit an application in response to this
FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp
and follow steps 1-4. Note: Applications must only be submitted electronically.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.
3.C.
Application Processing
Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application
submission/receipt date(s). (See Section IV.3.A. for
all dates.) If an application is
not submitted by the receipt date(s) and time, the application may be delayed
in the review process or not reviewed.
Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.
Upon receipt, applications will be evaluated for
completeness by the CSR and responsiveness by the National
Institute on Alcohol Abuse and Alcoholism. Incomplete and non-responsive
applications will not be reviewed. If the application is not responsive to the
RFA, NIH staff may contact the applicant to determine whether to return the
application to the applicant or submit it for review in competition with
unsolicited applications at the next appropriate NIH review cycle.
There will
be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives
the Grants.gov acknowledgments. The AOR and the PI receive Commons
acknowledgments. Information related to the assignment of an application to a
Scientific Review Group is also in the Commons.
Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.
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.
Although the financial plans of the National Institute on Alcohol Abuse and Alcoholism provide support for this program, awards pursuant to this FOA are contingent upon the availability of funds.
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 or competing renewal (formerly
competing continuation ) 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 or competing renewal 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
PD/PI Credential (e.g., Agency Login)
The NIH requires the PD/PI(s) 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.
Organizational DUNS
The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
PHS398 Research Plan Component Sections
Items 2-5 of the PHS398 Research Plan component are limited to 25 pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component 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.
All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:
Special Instructions for Modular Grant applications
R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs (excluding consortium F&A costs) must be submitted in a modular budget format. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm. When submitting a modular budget, the applicant organization will include only the PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further instructions regarding the use of the PHS398 Modular Budget component.
Foreign organizations may not submit modular budgets. See NOT-OD-06-096.
Appendix Materials
NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.
Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).
Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.
Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better 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.
Foreign Applications (Non-domestic (non-U.S.) Entity)
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 Web site, 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 expects that grant 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 sharing
research resources plan 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). 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
Applications
that are complete and responsive to the FOA will be evaluated for scientific
and technical merit by an appropriate peer review group convened by National
Institute on Alcohol Abuse and Alcoholism in accordance with the review
criteria stated below.
As part of the initial merit review, all applications will:
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:
The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.
Note that an
application does not need to be strong in all categories to be judged likely to
have major scientific impact and thus deserve a high priority score. 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? For applications
designating multiple PDs/PIs, is the leadership approach, including the
designated roles and responsibilities, governance, and organizational structure,
consistent with and justified by the aims of the project and the expertise of
each of the PDs/PIs?
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 PD/PI(s) and other key personnel 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 PD/PI(s) and investigative team bring complementary and
integrated expertise to the project (if applicable)?
Environment: Do(es) the
scientific environment(s) 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 the Human Subjects Sections
of the PHS398 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 the Human Subjects Sections of the PHS398 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 adequacy of the plans for their care and use
will be assessed. See the Other Research Plan Sections of the PHS398 Research
Plan component of the SF424 (R&R).
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. The priority score should not be affected by the
evaluation of the budget.
Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.
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.
2.D. Sharing Research
Resources
NIH policy expects that
grant 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 sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible. Program staff will be
responsible for the administrative review of the plan for sharing research
resources.
The
adequacy of the resources sharing plan and any related data sharing plans will
be considered by Program staff of the funding organization when making
recommendations about funding applications. The effectiveness of the resource
sharing will be evaluated as part of the administrative review of each Non-Competing Grant
Progress Report (PHS 2590), See Section VI.3.,
Reporting.
Model Organism Sharing Plan: Reviewers are
asked to assess the sharing plan in an administrative note. The sharing plan
itself should be discussed after the application is scored. Whether a sharing
plan is reasonable can be determined by the reviewers on a case-by-case basis,
taking into consideration the organism, the timeline, the applicant's decision
to distribute the resource or deposit it in a repository, and other relevant
considerations.
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
When multiple
years are involved, awardees will be required to submit the Non-Competing Grant
Progress Report (PHS 2590) annually and financial statements as required in
the NIH
Grants Policy Statement.
We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research, peer review, and financial or grants
management issues:
1.
Scientific/Research Contact(s):
Q. Max Guo, PhD
Program Director
Division of Metabolism
and Health Effects
National Institute on
Alcohol Abuse and Alcoholism
5635 Fishers Lane,
Room 2021
Bethesda, MD 20892-9304
Tel.: 301-443-0639
Fax: 301-594-0673
Email: qmguo@mail.nih.gov
Jos M. Vel zquez,
Ph.D.
Program Director
Division of Metabolism
and Health Effects
National Institute on
Alcohol Abuse and Alcoholism
5635 Fishers Lane,
Room 2023
Bethesda, MD 20892-9304
Tel. 301-402-9408
Fax: 301-594-0673
Email: jvelazqu@mail.nih.gov
Roger G. Sorensen,
Ph.D., M.P.A.
Program Director
Division of
Neuroscience and Behavior
National Institute on
Alcohol Abuse and Alcoholism
5635 Fishers Lane,
Room 2053
Bethesda, MD 20892-9304
Tel.: (301) 443-2678
Fax: (301) 443-1650
Email: rsorense@mail.nih.gov
2. Peer Review Contact(s):
Abraham Bautista,
Ph.D.
Chief, Extramural
Project Review Branch,
Office of Extramural
Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
Tel.: (301) 443-9737
Fax: (301) 443-6077
Email: bautista@mail.nih.gov
3. Financial/Grants Management Contact(s):
Judy Fox, Chief
Grants Management
Branch
National Institute on
Alcohol Abuse and Alcoholism
5635 Fishers Lane,
Room 3023
Bethesda, MD 20892-9304
Tel.: (301) 443-4704
Fax: (301) 443-3891
Email: jfox@mail.nih.gov
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 (45 CFR 46) 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 the 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. 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 (HHS) 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 HHS Office for Civil
Rights (OCR).
Decisions about
applicability and implementation of the Privacy Rule reside with the researcher
and his/her institution. The OCR website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and
proposals for NIH funding must be self-contained within specified page
limitations. For publications listed in the appendix and/or Progress report, Internet
addresses (URLs) or PubMed Central (PMC) submission identification numbers must
be used for publicly accessible on-line journal articles. Publicly
accessible on-line journal articles or PMC articles/manuscripts accepted for
publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the
full reference in either the Bibliography & References Cited section, the
Progress Report Publication List section, or the Biographical Sketch section of
the NIH grant application. A URL or PMC submission identification number
citation may be repeated in each of these sections as appropriate. There is no
limit to the number of URLs or PMC submission identification numbers that can
be cited.
Healthy
People 2010:
The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.
Authority and
Regulations:
This program is described in
the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections 301
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 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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