Part I Overview Information

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Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), ( http://www.nih.gov/)

Components of Participating Organizations
National Cancer Institute (NCI), (http://www.cancer.gov)

Title: Correlative Studies with Specimens from Multi-Site Trials (R21)

Announcement Type
This Funding Opportunity Announcement (FOA) is a reissue of PA-05-062, which was previously released March 3, 2005.

Update: The following update relating to this announcement has been issued:

• April 4, 2008 - This PA has been reissued as (PA-08-133).
• October 2, 2007 - Expiration Date adjusted to accommodate recent changes to standing submission deadlines, per NOT-OD-07-093.

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Two steps are required for on time submission:

1) The application must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the submission/receipt date (see Key Dates below).

2) Applicants must complete a verification step in the eRA Commons within 2 business days of notification from NIH. Note: Since e-mail can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.

Program Announcement (PA) Number: PA-06-296

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394, 93.395

Key Dates
Release/Posted Date: March 29, 2006
Opening Date: May 2, 2006 (earliest date an application may be submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not applicable.
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Receipt Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Earliest Anticipated Start Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Additional Information To Be Available Date (URL Activation Date): Not applicable.
Expiration Date: March 2, 2008 (Expired April 4, 2008 per PA-08-133)

Due Dates for E.O. 12372
Not Applicable.

Additional Overview Content

Executive Summary

This funding opportunity is intended to support correlative studies by using tumor specimens collected during multi-institutional clinical trials. The Cancer Therapy Evaluation Program (CTEP), the Cancer Diagnosis Program (CDP), and the Cancer Biomarkers Research Group (CBRG) from the NCI will cooperatively sponsor this funding opportunity with the following objectives to: (1) provide investigators with support for correlative studies using trial-related tumor specimens to compare genetic variations and molecular changes from the cell nucleus, the cytosol, and the cell surface and extracellular matrix to tumorigenesis and progression, drug resistance, therapeutic effectiveness of interventions, and patients' clinical outcomes; (2) decipher mechanisms and to evaluate new cancer interventions by utilizing these tumor tissue resources and accumulated clinical trial results for better cancer risk assessment, early detection, and prediction of response to various cancer therapies and prevention strategies; and (3) promote translational research and foster collaborations between basic researchers and clinical investigators from academia, private industry, and non-profit organizations to ensure that new findings will be rapidly translated into clinical practice.

• Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications; therefore, the anticipated number of awards is not known.
• This FOA utilizes the NIH Exploratory/Developmental Grant (R21) mechanism and runs in parallel with an FOA of identical scientific scope, PA-05-062, that solicits applications under the NIH Research Project Grant (R01) mechanism.
• 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 applications received.
• The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Direct costs are limited to $275,000 over an R21 2-year period, with no more than $200,000 in direct costs allowed in any single year.
• Eligible organizations include: for-profit organizations; non-profit organizations; public or private institutions, such as universities, colleges, hospitals and laboratories; units of State governments; units of State Tribal governments; units of local governments; units of local Tribal governments; eligible institutions of the Federal government; domestic institutions; foreign institutions; and faith-based or community-based organizations.
• Eligible Project Directors/Principal Investigators (PDs/PIs) include any individuals from the applicant institutions who have the skills, knowledge, and resources necessary to carry out the proposed research. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Applicants may submit more than one application, provided each application is scientifically distinct.
• See Section IV.1 for application materials. The SF424 (R&R) Application Guide for this FOA is located at these Web sites:

• http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General_Ver2.doc (MS Word);
• http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General_Ver2.pdf (PDF).
• For general information on SF424 (R&R) Application and Electronic Submission, see these the following Web sites:
• SF424 (R&R) Application and Electronic Submission Information at http://grants.nih.gov/grants/funding/424/index.htm;
• General information on Electronic Submission of Grant Applications at http://era.nih.gov/ElectronicReceipt/.

• Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

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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. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose and background

The Cancer Therapy Evaluation Program (CTEP) and the Cancer Diagnosis Program (CDP), Division of Cancer Treatment and Diagnosis (DCTD) National Cancer Institution (NCI), support a program of integrated national networks of clinical investigators and institutions (NCI Clinical Trials Cooperative Groups) for the conduct of large scale, multi-institutional clinical trials. The Community Oncology and Prevention Trials Research Group, Division of Cancer Prevention (DCP), NCI, supports programs to improve clinical oncology in community settings and conducts prevention and control trials. The Early Detection Research Network (EDRN) of the Division of Cancer Prevention, NCI, has created a research platform for collaborating with the clinical trials community and appointed liaisons for the various NCI Cooperative Groups. The EDRN is available for assistance in validation studies and researchers may form collaborations through its Associate Member Program.

Over the past 5 years, there have been more than 1,500 NCI-sponsored clinical trials, including cancer treatment and prevention trials. More than 200,000 cancer patients have participated in these trials. Among these trials, there have been 660 clinical trials conducted by Cooperative Groups and 410 trials that were conducted in cancer/clinical centers. Many of these trials have accumulated large numbers of tumor specimens together with accompanying well-annotated information about patients' demographics, pretrial/baseline histories, diagnoses, treatments, follow-up data from cancer interventions, and prognoses. These tumor specimens contain: many valuable genetic, diagnostic, and prognostic biomarkers; molecules and proteins relating to cell cycle and/or intracellular signal transduction pathways; and informative molecular profiles relevant to specific cancer intervention and cancer progression. Utilizing these extremely valuable resources is a tremendous opportunity to identify new mechanisms and develop more effective cancer interventions at a molecular level. Furthermore, using these specimens which are linked to annotated clinical data in correlative studies will extend NCI's previous scientific efforts and also complement NCI's current and future endeavors in identifying new targets for cancer intervention in a cost-effective manner.

With advances in the understanding of molecular cancer genetics and basic cancer biology as well as the development of powerful new technologies including microarrays, proteomics, and bioinformatics, both basic and clinical investigators are now in better positions to conduct correlative studies with the well-annotated tumor specimens. This funding opportunity further encourages researchers to take advantage of newly developed technologies and existing tumor specimens and promotes collaborations and interactions between basic researchers and clinical investigators. Now, it is feasible to compare a spectrum of molecular and genetic changes from cell nucleus, cytosol, cell surface, and extracellular matrix to tumorigenesis, tumor progression, drug resistance, and therapeutic effectiveness of various cancer interventions. In addition, investigators can link: (1) newly identified biomarkers to specific cancers for early detection and diagnosis; (2) activation/deactivation of signal transduction pathways to specific cancer prevention, treatment, drug resistance, and clinical outcome; and (3) tumor cellular and molecular changes to various clinical trials' success and failure. Furthermore, the tumor specimens will enable researchers to conduct correlative studies not only vertically within an individual trial but also horizontally among multiple trials. All of these advances will help investigators to improve future clinical trials and to develop better cancer interventions.

NCI encourages correlative laboratory studies linked to large scale multi-institutional clinical trials to improve therapeutic and preventive approaches. Currently, many laboratory investigators may not have access to patient specimens or outcome data for large-scale analysis. The Clinical Trials Cooperative Groups have established tumor and specimen banks for specific diseases, and reference laboratories necessary for the diagnosis and monitoring of patients. These clinical trials organizations maintain statistical databases and are capable of comparing and correlating laboratory data to clinical outcome.

The objectives of this funding opportunity are to foster collaborations and interactions between basic researchers, scientists working in private industry, and clinical investigators to perform clinical translational research on promising predictive and prognostic markers. These studies should focus on clinical correlative or mechanistic studies that will be useful for cancer risk assessment, early detection, and prognosis, and the predicting responses to therapy and to prevention interventions. These studies should focus on correlations between biologic features of tissue specimens (collected from the NCI Cooperative Groups or other large multi-institutional clinical trials) and patient outcomes.

This funding opportunity will utilize the exploratory/developmental grant (R21) mechanism to support pilot exploratory studies.

The correlative studies should be based on strong and testable hypotheses. A clear rationale should be given for the experimental design and technical methodologies selected. The hypotheses tested must relate to potential clinical applications such as patient monitoring for preventive or therapeutic interventions, development of new therapeutic strategies, and/or testing new biomarkers for the identification of patient subsets for specific prevention or treatment approaches. The laboratory assays must use specimens from patients receiving defined treatments in large clinical trials such as phase III clinical trials. Applications must include a statistical section describing the study design and plans for analysis of data designed to test the hypotheses. All investigators are encouraged to work with multi-institutional organizations or form a consortium in order to access sufficient numbers of patient specimens and clinical information to test the proposed hypotheses.

Some examples of laboratory-therapy correlates may include but are not limited to: (1) phenotypic or genotypic alterations which appear to correlate with the development of therapy resistance; (2) loss or inactivation of tumor suppressor genes related to prognosis; (3) analysis of basal membrane factors or genes related to tumor invasion and metastases; (4) studies of chromosomal rearrangements or deletions that may be used for risk assessment, early detection, or prognosis; (5) correlation of tumor growth factors or oncogenes with response to therapies during cancer progression; (6) alterations in cell cycle control; (6) characterization of immune response with association to new immunotherapies for prevention or treatment; (7) evaluation of serum or tumor biomarkers for risk assessment, early detection, or prognosis; (8) analyses of expression of cellular receptors for growth factors or differentiating agents; (9) defining and targeting specific signal transduction pathways and populations of cells for therapy; (10) analysis of in vitro response of tumor cells to growth factors/differentiating agents; and (11) evaluation of accessible sites for precancerous changes occurring in less accessible sites, for example the oral cavity as a surrogate site for the lung in smokers. Surrogate sites may be anatomically associated, such as oral cavity to lung cancer, or may be functionally related, such as scalp hair follicles to prostate cancer, both of which have androgen receptors.

Researchers who have previously not collaborated with the NCI Cooperative Groups or Division of Cancer Prevention Programs are encouraged to contact them and discuss potential collaborations to obtain access to NCI-supported specimen banks and outcome data for laboratory analysis under this funding opportunity. NCI staff (please see Agency Contacts) will be able to provide assistance in identifying NCI Cooperative Groups that would be interested in collaborating with basic science investigators on laboratory and clinical studies of new markers. The NCI Tissue Expediter is available to assist investigators in determining the appropriate tissue resource for their research project. Additional information is available at this Web site: http://resresources.nci.nih.gov/database.cfm?id=601.

Information on how to access NCI-supported specimen banks including contacts for the NCI Cooperative Group banks is available on NCI’s Specimen Resource Locator Web site. The NCI Cooperative Groups have mechanisms in place to review proposals for access to NCI Cooperative Group tissue banks from prevention and treatment trials. A letter from the appropriate NCI Cooperative Group Chairperson confirming approval to provide specimens in the event of NCI funding of the FOA grant application should be included in the grant application. For Intergroup tissue banks, a letter from the Intergroup tissue bank chairperson should also be included.

See Section VIII, Other Information - Required Federal Citations for policies related to this announcement.

Section II. Award Information

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1. Mechanism of Support

This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses just-in-time concepts. It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular Budget Component, of the Application Guide).

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation ) applications will not be accepted. Up to two resubmissions (formerly revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted. See NOT-OD-03-041, which was published in the NIH Guide on May 7, 2003.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NIH 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 total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $275,000 over an R21 2-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined 2-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this Program Announcement funding opportunity.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, which was published in the NIH Guide.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

• For-profit organizations
• Non-profit organizations;
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Units of State governments
• Units of State Tribal governments
• Units of local governments
• Units of local Tribal governments
• Eligible agencies of the Federal government
• Foreign Institutions
• Domestic Institutions
• Faith-based or community-based organizations

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her 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.

2. Cost Sharing or Matching

Not applicable. 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

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Registration and Instructions for Submission via Grants.gov

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To download a SF424 (R&R) Application Package and SF424 (R&R) SBIR/STTR Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/GetStarted); and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm).

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started.

• Your 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.
• If 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.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional 1 to 2 business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  E-mail [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  E-mail [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with Grants.gov.
• The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.
• This registration/affiliation must be done by the Signing Official (SO) or their designee who is already registered in the Commons.
• Both the PD/PI and SO need separate accounts in the NIH eRA Commons since both are required to verify the application.

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 4 weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo; Telephone: 301-710-0267, E-mail: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R &R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

The SF424 (R &R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget

Optional Components:
PHS398 Cover Letter File
R&R Subaward Budget Attachment(s) Form

Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)

Foreign Organizations:
Several special provisions apply to applications submitted by foreign organizations:

• Charge back of customs and import fees is not allowed.
• 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 percent 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 a unique research opportunity not available in the United States.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date: May 2, 2006 (earliest date an application may be submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not applicable.
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Receipt Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Earliest Anticipated Start Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A.) for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Upon receipt, applications will be transferred from Grants.gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the SO for the organization must verify the submission via Commons within 2 business days of notification of the NIH validation.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

Renewal (formerly competing continuation or Type 2 ) applications are not permitted.

All application instructions outlined in the SF424 (R&R) application are to be followed, with the following requirements for R21 applications:

• R21 applications will use the modular budget format and "Just-in-Time" concepts, with direct costs requested in $25,000 modules, up to the total direct costs limitation of $275,000 over an R21 2-year period. No more than $200,000 in direct costs will be allowed in any single year;
• Although preliminary data are not required for an R21 application, they may be included;
• Items 2-5 of the Research Plan of the R21 application may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts;
• Introduction (required for a resubmission application) is limited to one page; and
• Preliminary data are not required but may be included if available.

Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

• R21 appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism. The following materials may be included in the appendix:
  • Up to five publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication.
    • Publications in press: Include only a publication list with a link to the public available on-line journal article or the PubMed Central (PMC) submission identification number. Do not include the entire article.
    • Manuscripts accepted for publication but not yet published: The entire article may be submitted electronically as a PDF attachment.
    • Manuscripts published but an online journal link is not available: The entire article may be submitted electronically as a PDF attachment.
  • Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.
  • Graphic images of gels, micrographs, etc., provided that the image (may be reduced in size) is also included within the 15-page limit of Items 2-5 of the Research Plan. No images may be included in the Appendix that are not also represented within the Research Plan.
  • Do not use the Appendix to circumvent the page limitations of the Research Plan. An application that does not observe these limitations may be delayed in the review process.

Plan for Sharing Research Data

Not applicable.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., Reporting.

Section V. Application Review Information

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