Development of Disease Biomarkers (R01)

Development of Disease Biomarkers (R01) is sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This opportunity supports mission-aligned projects and measurable outcomes.

Expired PA-07-052: Development of Disease Biomarkers (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Part I Overview Information of Health and Human Services Institutes of Health (NIH ) ( http://www.

nih. gov ) Components of Participating Organizations Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( http://www. niddk.

nih. gov ) Institute of Biomedical Imaging and Bioengineering (NIBIB) ( http://www. nibib.

nih. gov ) National Institute on Alcohol Abuse and Alcoholism ( http://www. niaaa.

nih. gov ) Supplements (ODS) ( http://ods. od.

nih. gov ) Title: Development of Disease Biomarkers is a reissue of PA-06-147 , which was previously Update: The following update relating to this announcement has been issued: June 4, 2009 - This PA has been reissued as (PA-09-204). May 28, 2009 - See Notice NOT-DK-09-013 Extension of Expiration Date for NIDDK Program Announcements.

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) BE SUBMITTED IN PAPER FORMAT. in conjunction with the application guidelines included with this announcement for Grants (hereafter called Grants. gov/Apply).

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 . Announcement (PA) Number: PA-07-052 Domestic Assistance Number(s) 93.

848, 93. 849, 93. 286, 93.

273, 93. 891, 93. 271, 93.

272 Release/Posted Date: November 21, 2006 Opening Date: January 5, 2007 (Earliest date an application may be submitted to Grants. gov) Letters of Intent Receipt Date(s): N ot 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): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm Peer Review Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Council Review Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Additional Information To Be Available Date (URL Activation Date): Not Applicable Expiration Date: (New Expiration Date September 8, 2009 per NOT-DK-09-013 ) Original Date: March 6 , 2009 Purpose .

This Funding Opportunity Announcement (FOA) will provide resources to validate candidate biomarkers for well-defined human diseases of liver, kidney, urological tract, digestive and hematologic systems, and endocrine and metabolic disorders, diabetes and its complications, and obesity, for which there are no or very few biomarkers, or for which standard biomarkers are currently prohibitively invasive or expensive.

A biomarker is an indicator of a disease process, and could replace hard clinical end points as a measure of the effect of new therapies. Responsive studies will validate candidate biomarkers in well-defined patient populations, provide new technologies to monitor biomarkers or establish reliable assays for validated markers. Mechanism of Support.

This FOA will utilize the NIH Research Project Grant (R01) award mechanism and runs in parallel with an FOA of identical scientific scope, PA-06-146 , that solicits applications under the Developmental/Exploratory Research Funds Available and Anticipated Number of Awards.

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. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the Eligible Institutions/Organizations.

Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity; Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations.

Project Directors/Principal Investigators (PDs/PIs) . Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.

of Applications. Applicants may submit more than one application, provided each application is scientifically distinct. and Resubmissions.

Applications can be renewed by competing for additional project periods. Applicants may submit a resubmission application, but such application must include an Introduction (3 pages maximum) addressing the previous peer review critique (Summary Statement). of PDs/PIs.

More than one PD/PI, or multiple PDs/PIs, may be designated on the Application Materials. See Section IV. 1 for application materials.

general information on SF424 (R&R) Application and Electronic Submission, see these Web sites: (R&R) Application and Electronic Submission Information: http://grants. nih. gov/grants/funding/424/index.

htm information on Electronic Submission of Grant Applications: http://era. nih. gov/ElectronicReceipt/ Impaired.

Telecommunications for the hearing impaired is available at: TTY 301-451-5936. Part I Overview Information Part II Full Text of Announcement Section I. Funding Opportunity Section II.

Award Information Section III. Eligibility Information 2. Cost Sharing or Matching 3.

Other-Special Eligibility Criteria Section IV. Application and Submission 1. Request Application Information 2.

Content and Form of Application Submission 3. Submission Dates and Times A. Submission, Review, and B.

Submitting an Application Electronically to the NIH C. Application Processing 4. Intergovernmental Review 6.

Other Submission Requirements Section V. Application Review Information 2. Review and Selection Process A.

Additional Review Criteria B. Additional Review Considerations D. Sharing Research Resources 3.

Anticipated Announcement and Award Dates Section VI. Award Administration 2. Administrative and National Policy Requirements 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 II - Full Text of Announcement Section I.

Funding Opportunity Description The goal of this Funding Opportunity Announcement (FOA) is to validate biomarkers for well-defined human diseases of liver, kidney, urological tract, digestive and hematologic systems, and endocrine and metabolic disorders, diabetes and its complications, and obesity, for which there are no or very few biomarkers, or for which standard biomarkers are currently prohibitively invasive or expensive.

New biomarkers will stimulate bench to bedside translation by providing measures of the biological effects of potential new treatments. The ideal biomarker can be measured in a minimally invasive way, can be measured repeatedly over time, identifies early stages of disease, is indicative of disease prognosis, and correlates well with progression and response to therapy.

Especially of interest would be studies designed to test the validity of candidate biomarkers or new technologies to monitor candidate biomarkers in patient tissue samples or small groups of well-characterized patients. For biomarkers already validated in human subjects, the larger effort might be to establish a reliable assay prior to pursuing larger patient studies.

Priority will be given to those projects with high promise for improving clinical care in the relatively near future. Studies of potential biomarkers conducted in animal models of disease, and extended prospective clinical trials for marker validation against hard clinical endpoints, are outside the scope of this initiative.

defined as a physical, functional, or biochemical indicator of a physiological or disease process that has diagnostic and/or prognostic utility. Our ability to study and treat disease is hampered by a lack of unique, reliable, quantifiable, easily measured biomarkers that correlate well with disease progression.

These diseases include diabetes, endocrine and metabolic disease, kidney, urological, hematological, obesity, liver and digestive diseases. For researchers interested in liver disease, this announcement addresses several areas considered high priority as delineated in the recently published Trans-NIH Action Plan for Liver Disease Research ( http://liverplan. niddk.

nih. gov ). For many diseases, there is no good way to detect disease in the early stages, and consequently the clinical presentation is at a stage at which reversal or optimal control is very difficult.

For other diseases, there are no methods for monitoring disease progression or the efficacy of potential therapeutic interventions short of frank, clinically observable signs or symptoms. This can make clinical trials for new therapies impractical or very expensive, since large numbers of patients must be followed for the long periods of time needed to achieve hard clinical endpoints such as diabetes, organ failure, or death.

Furthermore, incentives are low and hurdles are high to develop new drugs and therapies for diseases that lack widely accepted and clearly defined clinical endpoints, such as diabetic neuropathy. Clinical trials are especially difficult to design for chronic diseases.

(either a measurement from a readily obtained biologic sample or made directly in patients) would reduce the need to achieve hard clinical endpoints in clinical trials, and would therefore help to lower the associated costs by reducing the number of patients needed and the time during which they are monitored.

Such biomarkers must be quantifiable and correlate well with clinical and biochemical measures of disease progression, and should be relatively inexpensive and noninvasive so that they can be measured serially over time. that could be validated under this FOA have been identified in a number of ways.

NIH and the pharmaceutical industry are both highly invested in identifying potential biomarkers of disease through discovery-oriented searches, using technologies such as genomics, proteomics, and other high-throughput approaches. A variety of recent NIH initiatives have sought to recruit projects both to refine the existing technologies for biomarker discovery, and to apply them to diseases of interest.

Biological samples from well-characterized patients studied in clinical trials have been made available in some cases for these discovery efforts. (For information regarding ancillary studies to NIDDK clinical trials, please see http://www. niddk.

nih. gov/fund/ancillary-studies/descriptions-ancillary-studies. htm .)

In addition, mechanistic studies often give rise to the identification of molecules found in blood, breath or urine, tissue attributes, physiological changes, etc., that could be developed into quantitative biomarkers. Although more discovery research is required, this is not within the scope of the current initiative. Th is FOA encourages the development of candidates towards validation as acceptable biomarkers.

Before a biomarker can be considered as a good surrogate that would be clinically useful or appropriate for monitoring the efficacy of a therapy, a tremendous amount of effort must go toward development and validation of these biomarkers. This initiative includes well-characterized patients or in biological samples from well-characterized patients, to show that a biomarker or a set of biomarkers is unique for a disease of interest.

in human subjects to determine whether a biomarker correlates well with pathogenesis, disease processes, progression or regression of disease, response to therapy, accepted clinical endpoints, or improve the biomarker assay system to be robust, repeatable, quantitative and translatable to many laboratories, or to fall within costs that are appropriate for clinical use.

sampling or biomarker monitoring strategies that are non-invasive and/or acceptable to patients and clinical staff. include but are not limited to: invasive to non-invasive markers of liver, biliary, pancreas and kidney fibrosis. sensory and autonomic diabetic neuropathy prior to loss of function.

cell injury, repair, regeneration and markers that predict drug induced hepatotoxicity or can distinguish progressive liver injury from transient adaptive aminotransaminase elevations due to and total body iron and copper accumulation.

disease activity for inflammatory diseases, such as IBD, hepatitis (autoimmune hepatitis, fatty liver disease, HIV-coinfected hepatitis), cholangitis (PSC, PBC), esophagitis, vasculitis, inflammation in kidney, pancreas, adipose tissue in obesity or diabetes, and chronic wounds secondary to diabetic neuropathy. pancreatic beta cell function, mass and markers of insulin resistance.

markers of angiogenesis (fat, muscle, pancreas, nervous tissue). assessable, quantitative markers of liver, pancreas and kidney function, dysfunction, and disease. transplant rejection, immunosuppression, and tolerance.

detection of hepatocellular dysplasia or early hepatocellular or detection of esophageal intestinal metaplasia or early Barrett's esophagus. See Section VIII, Other Information - Required Federal Citations , for policies related to this This FOA will use the NIH Research Project Grant ( R01) award mechanism. applicant will be solely responsible for planning, directing, and executing the 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 ). 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. 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. 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 , III.

Eligibility Information application(s) if your institution/organization has any of the following Public/State Controlled Institution of Higher Private Institution of Higher Education Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education) Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education) For-Profit Organization (Other than Small Business) U.S. Territory or Possession Indian/Native American Tribal Government (Federally Indian/Native American Tribal Government (Other than Indian/Native American Tribally Designated Non-domestic (non-U.S.) Entity Hispanic-serving Institution Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations 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 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 . This program does not require cost sharing as defined in the current NIH more than one application, provided each application is scientifically distinct . Section IV.

Application and Submission Information (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: ( http://www. grants.

gov/applicants/get_registered. jsp ) eRA Commons ( http://era. nih.

gov/ElectronicReceipt/preparing. htm ) with their institutions/organizations to make sure they are registered in the 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 organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants. gov registration process. your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time.

A valid TIN or EIN is necessary for CCR registration. CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days. questions regarding Grants.

gov registration to: Business Hours: M-F 7:00 a. m. - 9:00 p.

m. Eastern Time 2) Organizational/Institutional Registration in the eRA Commons find out if an organization is already Commons-registered, see the " List of Grantee Organizations Registered in NIH eRA Commons. questions regarding the Commons registration to: Phone: 301-402-7469 or 866-504-9552 (Toll Free) Business hours M-F 7:00 a.

m. 8:00 p. m.

Eastern Time Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) The individual(s) designated as PDs/PIs on the application must also be registered in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application. hold a PD/PI account in the Commons.

Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account. When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization.

PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons. This registration/affiliation must be done by the AOR/SO or their designee who is already registered in the Commons. AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

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. 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 1. Request Application Information download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.

gov/Apply . 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: [email protected] . Telecommunications for the hearing impaired: TTY Content and Form of Application Submission 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 .

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 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 Project/Performance Site Locations Research & Related Other Project Information Research & Related Senior/Key Person PHS398 Cover Page Supplement PHS398 Modular Budget or Research & Related Budget , as appropriate (See Section IV.

6 . , Special Instructions , regarding appropriate required budget component.) & Related Budget (required for foreign applications) Research & Related Subaward Budget Attachment(s) Foreign Organizations ( Non-domestic 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 .

from foreign organizations must: Request budgets in U.S. dollars. detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component). See NOT-OD-06-096 .

Charge back of customs and import fees is not Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8. 5 x 11 within each PDF. Funds for up to 8% administrative costs (excluding equipment) may be requested.

See NOT-OD-01-028 , March 29, 2001. Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards. Organizations must comply with Federal/NIH biosafety and biosecurity regulations.

See Section VI. 2. , Administrative and National Policy Requirements.

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.

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 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 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) or Section I of the Research Plan in the PHS 398), 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 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 Involving a Single Institution within a single institution, follow the instructions contained in the SF424 Involving Multiple Institutions 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 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. Submission Dates and Times See Section IV.

3. A. for details.

Submission, Review, and Anticipated Start Dates 2007 (Earliest date an application may be submitted to Grants. gov) Letters of Intent Receipt Date(s): Not Applicable Application Submission/Receipt Date(s): Standard dates apply, please see http://grants. nih.

gov/grants/funding/submissionschedule. htm Date(s): Standard dates apply, please see http://grants1. nih.

gov/grants/funding/submissionschedule. htm#reviewandaward Date(s): Standard dates apply, please see http://grants1. nih.

gov/grants/funding/submissionschedule. htm#reviewandaward Anticipated Start Date(s): Standard dates apply, please see http://grants1. nih.

gov/grants/funding/submissionschedule. htm#reviewandaward letter of intent is not required for the funding opportunity. 3.

B. Submitting an Application Electronically to the NIH To submit an application in response to this FOA, applicants should access this FOA via http://www. grants.

gov/applicants/apply_for_grants. jsp and follow steps 1-4. Note: Applications must only be submitted electronically .

PAPER APPLICATIONS WILL NOT BE ACCEPTED. 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 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.

everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days. to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window.

This option should be used if the AOR/SO determines that warnings should be addressed or if information was lost or compromised during transmission. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors), it will automatically move forward after two business days if no action is taken.

Please remember that some warnings may not be applicable or may need to be addressed after application submission. the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.

gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.

gov system issue. the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants. gov system failure, a changed/corrected application still can be submitted, but it will be subject to late policy guidelines and may not be accepted.

The reason for this delay should be explained in the cover letter attachment. the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

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 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 (3 pages maximum) addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R). 4.

Intergovernmental Review subject to intergovernmental NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants 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