Expired PAR-08-196: NIDCR Clinical Trial Implementation Cooperative Agreement (U01)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Part I Overview Information

Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Dental and Craniofacial Research (NIDCR), (http://www.nidcr.nih.gov)

Title: NIDCR Clinical Trial Implementation Cooperative Agreement (U01)

Announcement Type
New

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

September 16, 2011 - This PAR has been reissued as PAR-11-339.
February 23, 2011 The Expiration Date for this announcement has been changed to May 8, 2011 per NOT-OD-11-048, which redefines the U01 activity code and announces the transition of U01 applications to electronic submission through Grants.gov using the SF424 (R&R) forms for due dates on or after May 25, 2011.
November 24, 2009 - This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the 06/2009 version of the PHS 398 application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the 11/2007 version of the PHS 398 application forms and instructions.

Looking ahead: As part of the Department of Health and Human Services' implementation of e-Government the NIH will gradually transition each research grant mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. For more information and an initial timeline, seehttp://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-035.html. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html).

Program Announcement (PA) Number: PAR-08-196

Catalog of Federal Domestic Assistance Number(s)
93.121

Key Dates
Release Date: July 9, 2008
Letters of Intent Receipt Date(s): Six weeks before submission
Application Submission Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details
AIDS Application Submission Dates(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#review
Council Review Date(s): Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#review
Earliest Anticipated Start Date: Standard dates apply; please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#review
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: Changed to May 8, 2011 (Per NOT-OD-11-048) ; Original Date September 8, 2011

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. This FOA issued by the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, will support investigator-initiated Phase I, II, III, or IV clinical trial cooperative agreement applications only from NIDCR Clinical Trial Planning (R34) grant awardees (see PAR-08-195 for information about NIDCR Clinical Trial Planning Grants) unless an exception is granted. Each clinical trial implementation application will use the PHS 398 grant application with special instructions and will include a final draft of the clinical trial protocol, the Clinical Investigators Brochure or equivalent, and a Manual of Procedures resulting from the R34 grant. These documents must meet all National Institutes of Health (NIH), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) requirements. All awards will be made as cooperative agreements.
Mechanism of Support. This FOA will utilize the NIH single project (U01) cooperative agreement award grant mechanism.
Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary between applications, 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 relevance of the proposed trial to the NIDCR mission and strategic plan, trial complexity, anticipated duration, and associated operational trial proposed costs.
Budget and Project Period. It is anticipated that most trials will be completed in less than 5 years. The maximum amount of time requested for clinical trial implementation cooperative agreements may not exceed five years Although the NIDCR financial plans provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible 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.
Number of PDs/PIs. More than one PD/PI, or multiple PDs/PIs, may be designated on the application.
Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct..
Resubmissions. Resubmission applications will be accepted. Such application must include an Introduction addressing the previous peer review critique (Summary Statement).
Renewals. Applicants may submit a renewal application
See Section IV.1 for application materials.
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936

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. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and 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 and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

The NIDCR is committed to identifying effective preventive, diagnostic and treatment approaches for oral and craniofacial diseases and disorders. Improving associated health through the generation of robust data from well-designed and executed clinical trials is a high priority for the NIDCR.

As announced in NOT-DE-08-002, the NIDCR will support investigator-initiated clinical trials through a two part grant process: (1) a clinical trial planning grant (R34) followed by (2) a clinical trial implementation cooperative agreement (U01). This FOA, NIDCR CLINICAL TRIAL IMPLEMENTATION COOPERATIVE AGREEMENT (U01) addresses the clinical trial implementation; a companion FOA, PAR-08-195 NIDCR CLINICAL TRIAL PLANNING GRANT (R34), addresses design and planning of the trial.

Overview of the NIDCR policy for investigator-initiated clinical trials

The first step (Part 1) of the NIDCR clinical trials grant process is the Clinical Trial Planning Grant (R34). The NIDCR will support clinical trial planning grants (R34) for complete planning, design and documentation of investigator-initiated Phase I, II, III, or IV clinical trials. A clinical trial is defined by NIH as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether biomedical or behavioral interventions are safe, feasible, acceptable, efficacious, and effective. The R34 grant will provide up to one year of support for clinical trial planning. Pre-approval from the NIDCR is required for submission of an R34 application. R34 applications will be peer reviewed by NIDCR study sections. R34 awardees who complete their planning activities and have compelling justification to proceed to a clinical trial will submit a cooperative agreement application (U01) for clinical trial implementation (details are presented in this FOA). If the investigators conclude that a clinical trial is not warranted, the reasons for not proceeding with the U01 implementation application must be documented in a report to the NIDCR that summarizes the R34 award activity.

Following the completion of Part 1, the clinical trial planning process, investigators may apply for Part 2, the Clinical Trial Implementation Cooperative Agreement (U01). The NIDCR will accept, peer review, and consider funding applications for implementation of investigator-initiated clinical trials only from R34 awardees except on rare occasions. Each clinical trial implementation application will use the PHS 398 grant application and include the clinical protocol, Clinical Investigator's Brochure where appropriate or other equivalent document(s) that contains relevant non-clinical and preclinical data on study products, a Manual of Procedures, and meet all applicable NIDCR, NIH, Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) policy requirements. FDA Good Clinical Practice guidelines can be found at http://www.fda.gov/oc/gcp/default.htm. Consolidated guidance for clinical trials is presented at http://www.fda.gov/cder/guidance/959fnl.pdf. Planning grant awardees must prepare their protocols, Clinical Investigators' Brochures, and Manuals of Procedures to meet this guidance (see http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/ for the NIDCRs Clinical Protocol and Manual of Procedures templates). Information about Institutional Review Board and Independent Ethics Committee (IRB/IEC) registration and assurances is found at http://www.hhs.gov/ohrp/.

A clinical trial implementation cooperative agreement application should describe all necessary components to successfully conduct a clinical trial. This would include a description of the administrative structure, the identification and qualifications of the study chair, the data coordinating center, appropriate clinical site(s) and specialized core facilities (if applicable). The materials developed in the R34 phase will allow the applicant to initiate study staff training followed by study subject recruitment soon after an expedited peer review and final NIDCR approval of the clinical study application. In order not to delay the initiation of the study, the peer review and award of grant will be completed within four months of the receipt of the application when possible.

The NIDCR issued an NIH Guide notice concerning the conduct of clinical trials (NOT-DE-08-001 published on March 27, 2008). Standard NIDCR Terms and Conditions of Award for clinical studies and trials were updated. Awardees are required to comply with these Clinical Terms of Award. The details can be found at the following locations: NIDCR Clinical Terms of Award and Guidance for Complying with the NIDCR Clinical Terms of Award

Resources that may be available to support clinical trials during clinical trial implementation can be obtained from the NIDCR program staff. NIDCR clinical research policy and guidance information as well as NIDCR templates are available at the following website: http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/

Examples of studies that might be supported by this FOA include but are not limited to:

Clinical trials involving chemotherapeutic, pharmacologic, or other interventions to prevent and/or treat periodontal diseases (particularly aggressive periodontitis) and various types of dental caries (e.g., ECC, root caries, and caries related to head and neck radiation);
Clinical trials focusing on the prevention or treatment of oral manifestations or complications of infections caused by herpes viruses, human papilloma virus, Human Immunodeficiency Virus (HIV), or other human viruses;
Clinical trials testing new therapeutics or management strategies for oral candidiasis and other fungal infections;
Clinical trials to prevent or manage salivary dysfunction and xerostomia; and
Clinical trials testing methods to increase preventive health behaviors or change oral health outcomes through behavioral modification.

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 NIDCR Clinical Trial Implementation Cooperative Agreement (U01) 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 non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

The NIDCR has not determined if this FOA will be reissued. Plans beyond the current funding opportunity are indefinite.

2. Funds Available

Although the financial plans of the NIDCR provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Expected direct cost amounts for individual awards as well as project duration will vary depending on the scope and size of the clinical trial proposed. Most clinical trials should be able to be completed in less than five years. Applicants for clinical trial implementation cooperative agreements may request up to a maximum of five years of support for trial implementation. Only under compelling and unusual circumstances will competing renewal applications be accepted for an additional period of support.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education
Hispanic-serving Institutions
Historically Black Colleges and Universities (HBCUs)
Tribally Controlled Colleges and Universities (TCCUs)
Alaska Native and Native Hawaiian Serving Institutions
Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Small Businesses
For-Profit Organizations (Other than Small Businesses)
State Governments
Indian/Native American Tribal Governments (Federally Recognized)
Indian/Native American Tribal Governments (Other than Federally Recognized)
Indian/Native American Tribally Designated Organizations
County Governments
City or Township Governments
Special District Governments
Independent School Districts
Public Housing Authorities/Indian Housing Authorities
U.S. Territory or Possession
Regional Organizations
Eligible agencies of the federal government
Non-domestic (non-U.S.) Entities (Foreign Organizations)
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 is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, 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 grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. 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 PDs/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.

If multiple PD/PIs submit an application to conduct a clinical trial, an appropriate clinical trial governance structure must be defined including identification of the overall study chair.

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

Only NIDCR clinical trial planning (R34) grantees are permitted to submit applications for clinical trial implementation awards in response to this FOA unless an exception is granted by the NIDCR.

Resubmission applications will be accepted. These applications must include an Introduction addressing the previous peer review critique (Summary Statement). Applicants may submit a renewal application.

Only a single NIH project (U01) cooperative agreement application may be submitted for a single clinical trial from individuals who have received a R34 NIDCR Clinical Trial Planning Grant. .

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

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

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

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:

Request budgets in U.S. dollars.
Contain detailed budgets. See NOT-OD-06-096.

In addition, for applications from foreign organizations:

Charge back of customs and import fees is not allowed.
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% Facilities and administrative (F&A) 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.

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed 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 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, and should include 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.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review and Anticipated Start Dates
Application Receipt Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the Principal Investigator
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

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 at the beginning of this document.

The letter of intent should be sent to:

Jane C. Atkinson, D.D.S.
Program Director, Clinical Trials Program
National Institute of Dental and Craniofacial Research
6701 Democracy Blvd., Room 634, MSC 4878
Bethesda, Maryland 20892-4878
Phone: (301) 435-7908
FAX: (301) 480-8322
email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant application forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix materials must be sent to:

Lynn Mertens King, Ph.D.
Chief, Scientific Review Branch
Division of Extramural Activities
National Institute of Dental and Craniofacial Diseases
1DEM, Room 662, MSC 4878
6701 Democracy Boulevard
Bethesda, MD 20892-4878
Telephone: (301) 594-5006
E-mail: [email protected]

3.C. Application Processing

Applications must be submitted on or before the application receipt/submission dates described above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm.

Upon receipt applications will be evaluated for completeness by CSR. Incomplete applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity 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. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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 or renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 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 NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements and Information

Applicants must use the currently approved version of the PHS 398 available at http://grants.nih.gov/grants/funding/phs398/phs398.html. Because the clinical trial protocol, Clinical Investigator's Brochure or equivalent, and the Manual of Procedures (MOP) or equivalent will provide details on study design and conduct, the PHS 398 application should be brief. In addition, the application must contain the following supplemental information:

A cover letter indicating the NIDCR has agreed to accept the application.
Appendices must include:

A final draft of the clinical protocol
A detailed final protocol to be submitted for IRB review;
Manual of Procedures (MOP);
Clinical Investigator's Brochure when appropriate or other equivalent document(s) that contain relevant non-clinical and preclinical data on study products;
Consent forms and, if applicable, assent forms;
Plan for the acquisition and administration of study agent(s);
Complete set of suitable documents for submission to the appropriate regulatory authorities;
Training plans for study staff;
Site quality management plan;
Product development plan if study product will be under Investigational New Drug Application (IND) or Investigational Device Exemption (IDE); and
Any other materials essential for the implementation of the clinical trial.

Awardees under this FOA must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Research Strategy Page Limitations

Item 3 of the Research Plan is limited to 12 pages. The study protocol, MOP or equivalent, and Clinical Investigators Brochure or equivalent, as well as any of the other items noted above, are to be submitted as appendices.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year

Applicants requesting $500,000 or more in direct costs for any year (excluding consortium F&A costs) must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as plans are being developed for the study;

2) Obtain agreement from the IC staff that the IC will accept the application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all new, renewal, revision, or resubmission applications. See NOT-OD-02-004, October 16, 2001.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CDs only. Include five identical CDs in the same package with the application. (See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.)

Do not use the Appendix to circumvent the page limitations. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance, research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Specific Instructions for Foreign Applications

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.

Section V. Application Review Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria described below will be considered in the review process:

2. Review and Selection Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIDCR and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned an impact/priority score.
Receive a written critique.
Receive a second level of review by the National Advisory Dental and Craniofacial Research Council

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:

Scientific merit of the proposed project as determined by scientific peer review.
Availability of funds.
Relevance of the proposed project to program priorities.

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, and weighted 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 meritorious impact/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.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance: Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Does the applicant address the following?

A clear statement of the question(s) that the trial will address and its importance;
Information adequate to determine the significance and timeliness of, as well as the need to perform, the trial;
Preliminary data or the literature supporting the need for a clinical trial to test the proposed hypothesis or intervention;
The biological mechanisms and clinical data that support conducting the trial;
The potential of the outcome to change clinical practice, community behaviors or health care policy;
The generalizability of potential findings if this is a Phase III trial;
Reasons for selection of the intervention, study agent(s), and mode of delivery, including specific details such as dose or a particular procedure;
Other interventions including both clinical and economic advantages and disadvantages of each; and
The ethical issues surrounding the trial and the disease/condition under study.

Investigator(s): Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the application include a clear statement of the leadership and organization of the study including:

Identification of a principal investigator, and, for multicenter trials, a core of potential center investigators and staffing for a data coordinating center;
Appropriateness and qualifications of the principal investigator and make-up and responsibilities of the administrative and scientific committees such as the steering committee, executive committee, and publication committee;
Qualifications of the trial statistician and data center to implement and monitor the study, and analyze and report study results if the NIDCR contract data coordinating center will not be used;
Professional training and experience of the clinical trial organizers in such areas as the clinical problem under study, administration of complex projects and study design;
Inclusion of statisticians, data managers and study coordinators;
Plans to add or drop enrollment centers; and
For multi-center trials, the organizational structure of the trial, especially the proposed structure of the study in terms of relationships among the administrative center, data coordinating center, participating enrollment centers, and the laboratory/ testing center.

Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Is the experimental design adequate and does it address the following?

Translation of the clinical question into a statistical hypothesis;
Primary and secondary outcome variable(s) and data to be collected, including relevance to the clinical and statistical hypothesis being tested;
Criteria for evaluating outcome variables;
Clinical significance of the outcome variable(s);
Appropriateness of a composite outcome if multiple outcome variables are combined;
Sample size and duration of the trial;
Randomization if needed, masking (if appropriate), controls, and inclusion/exclusion criteria;
Ancillary therapies;
Plans to standardize and monitor adherence to the clinical protocol;
Interim data monitoring;
Use of common data elements;
Plans to obtain any study agent;

Methods for standardization of procedures for data management to assess the effect of the intervention and quality control; and

Appropriateness of the general statistical approach and specific analytic techniques and plans for handling dropouts, missed visits, and losses to follow-up.
For clinical trial applications with multiple PD/PIs, is the defined governance structure appropriate and is an overall study chair identified?

The criteria listed above apply to all clinical trials. For multi-center trials, there are additional criteria that must be addressed. Does the application address the following?

Completeness and sufficient detail of the Manual of Procedures (MOP) to assure consistency in protocol implementation across subjects and the clinical site(s);
Standardization/quality control of, and adherence to, the clinical protocol and data collection or distribution guidelines, and the use of a data coordinating center;
Procedures for technical monitoring of the study center(s) for adherence to protocol and for data and safety monitoring, whether data and safety monitoring will be on a current basis, and the impact of these procedures on data quality;
Adequacy of plans for maximizing standardization of definitions, procedures, measurements, training and calibration of examiners across enrollment site(s) or clinic(s);
Plans for coordinating randomization procedures and assignments, data transmittal, patient assignment, and for transmitting policy and procedural advice to the investigators at the participating centers;
Likelihood that the MOP will provide reassurance that scientific integrity and patient safety will be closely monitored and increase the likelihood that the results of the study will be scientifically credible; and
Reasonableness of the specific time line for implementing and completing the trial. Does the time line allow adequate time for start-up and development, for establishing and implementing a data and safety monitoring plan, for developing and testing forms, and for setting up databases?.

Environment: Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Are there adequate plans for the development of an effective organizational structure for carrying out the proposed study?

Is there an appropriate scientific environment for conducting the proposed study?
Are adequate facilities in place to conduct clinical trials?
Is the study population required for the proposed study available?

In addition to the above review criteria, the following criteria will be addressed and considered in the determination of scientific merit.

Clinical Trial Documentation (Study protocol, Clinical Investigator's Brochure or equivalent, and MOP or equivalent):

Are the materials complete, appropriate, and adequate to allow training of study staff and recruitment of study subjects if a cooperative agreement award is made?
Are all the clinical trial documents compliant with GCP?

Plans for Patient Recruitment/Retention: Does the application document the following:

Availability of the requisite eligible subject pool in proposed clinical center(s);
The status of evidence showing whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected (see Inclusion of Women and Minorities in Clinical Research below);
Plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals;
Retention plans and practices; and
Criteria for withdrawal.

Safety Monitoring: Is the safety monitoring plan adequate and does it address the following?

Risks involved;
Ethical aspects of risks;
Risk-benefit balance;
Informed consent procedures;
Safety Monitoring Plan;
Data Safety and Monitoring Board (required for a Phase III trials and others if necessary; and
Provisions for early termination.

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

Resubmission Applications (formerly revised/amended applications): When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Protections for Human Subjects: For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children: When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

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.

Additional Review Considerations

As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications from Foreign Organizations. Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The impact/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. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or impact/priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

Data Sharing Plan. [http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm]
Sharing Model Organisms. [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
Genome Wide Association Studies (GWAS). [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

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 (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the Notice of Award will be mailed to the business official.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The terms and conditions of award are representative of the specific terms and conditions that will be negotiated with an applicant prior to award. The terms and conditions will be modified as appropriate to each clinical trial consistent with necessary roles and responsibilities. At a minimum, all awardees must abide by the conditions set forth in the NIDCR Clinical Terms of Award.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Project Director/Principal Investigator (PD/PI) Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIDCR staff in those aspects of scientific and technical management of the study as stated in these terms and conditions;
Meeting NIDCR policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIDCR policy was published in the NIH Guide on March 27, 2008, and is available at: http://grants1.nih.gov/grants/guide/notice-files/NOT-DE-08-001.html. The full policy, including terms and conditions of award, is available at the following NIDCR Website locations: http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/NIDCRClinicalTermsofAward.htm and http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/Guidance.htm. Upon implementation of the protocol, each field center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, data collection, and quality control;
Retaining custody of and having primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies;
Managing involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NIDCR;
Making all study materials and procedure manuals available in the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDCR/NIH; and
Obtaining prior written approval of the NIDCR Grants Management Specialist, in consultation with the NIDCR Program Officer, for changes in any of the key personnel identified in the Notice of Grant Award.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIDCR staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies;
Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration;
Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from the NIDCR grantees and contractors, advising in management and technical performance, or participating in the preparation of publications; and
Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

An NIDCR Medical Officer will monitor the clinical trials and serve as the Medical Monitor. Should a pharmaceutical or biotechnology company sponsoring a clinical trial choose to name its own Medical Monitor, then the NIDCR Medical Officer will work with the company-assigned Medical Monitor.

The NIDCR reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which the NIDCR does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject ethical issues that may dictate a premature termination.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

As appropriate to the funded clinical trial, the following collaborative responsibilities will be incorporated in the grant award:

A Steering Committee (SC), composed of the principal investigator, as well as the principal investigators of the field center(s), the Data Coordinating Center and the specialized core facilities (if any), and one NIDCR representative (the Project Scientist). The NIDCR Project Scientist will have voting membership on the SC and, as appropriate, its subcommittees. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. Awardees will be required to accept and implement the common protocol and procedures approved by the SC. As the components of the SC may be geographically dispersed, the SC should meet with monthly conference calls, supplemented as deemed necessary by face-to-face meetings.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Jane C. Atkinson, D.D.S.
Program Director, Clinical Trials Program
National Institute of Dental and Craniofacial Research
1DEM, Room 634
6701 Democracy Blvd., MSC 4878
Bethesda, MD 20892-4878
Telephone: (301) 435-7908
Fax: (301) 480-8322
E-mail: [email protected]

2. Peer Review Contacts:

Lynn Mertens King, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
1DEM, Room 662, MSC 4878
6701 Democracy Blvd.
Bethesda, MD 20892-4878
Telephone: (301) 594-5006
E-mail: [email protected]

3. Financial or Grants Management Contacts:

Mary Daley
Chief, Grants Management Branch
National Institute of Dental and Craniofacial Research
1DEM, Room 658
6701 Democracy Blvd, MSC 4878
Bethesda, MD 20892-4878
Telephone: (301) 594-4808
Fax: (301) 480-3562
E-mail: [email protected]

Section VIII. Other Information

Required Federal Citations

Vertebrate Animals:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the impact/priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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.

Inclusion of Women, Minorities, and Children:
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 new PHS Form 398; 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-09-116.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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html), investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigators NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.