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 Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov)

Title: NIAID Clinical Trial Implementation Cooperative Agreement (U01)

Announcement Type
This Funding Opportunity Announcement (FOA) is a reissue with modifications of PAR-05-113.

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

• June 16, 2011 - This PAR has been reissued as PAR-11-234.
• February 23, 2011 The Expiration Date for this announcement has been changed to May 14, 2011 to accommodate the existing May 13, 2011 submission date and 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.
• January 6, 2011 - See Notice NOT-AI-11-025 The purpose of this Notice is to announce a substantive change to requirements articulated and to provide a clarification.
• May 5, 2010 - See Notice NOT-AI-10-024 New NIAID Policy: Investigator-Initiated Clinical Trials.

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-10-186

Catalog of Federal Domestic Assistance Number(s)
93.855; 93.856

Key Dates
Release Date: May 5, 2010
Application Due Date(s) for AIDS & Non-AIDS: July 22, 2010, September 13, 2010, January 13, 2011, May 13, 2011, September 13, 2011, January 13, 2012, May 14, 2012, September 13, 2012, January 14, 2013
Peer Review Date(s): September, 2010, December, 2010, April, 2011, August, 2011, December, 2011, April, 2012, August, 2012, December 2012, April, 2013
Council Review Date(s): January 2011, May, 2011, October 2011, January 2012, May, 2012, October, 2012, January 2013, May 2013
Earliest Anticipated Start Date(s): November, 2010, March, 2011, July, 2011, November, 2011, March 2012, July, 2012, November 2012, March, 2013, July 2013
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/qa/revniaid.htm
Expiration Date: Changed to May 14, 2011 (Per NOT-OD-11-048) ; Original Date January 15, 2013

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

• Purpose. The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) is to invite applications that propose implementation of investigator-initiated high-risk clinical trials. The trials must be hypothesis-driven, related to the research mission of the NIAID and considered a high priority by the Institute. Investigators are encouraged to visit the NIAID website for additional information about the research mission and high-priority research areas of the NIAID http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/.) Only one clinical trial may be proposed in each NIAID Clinical Trial Implementation (U01) Cooperative Agreement application.
• Mechanism of Support. This FOA will utilize the NIH Cooperative Agreement (U01) mechanism, and will run in parallel with two related FOAs, PAR-10-184 and PAR-10-185, that invite applications that propose planning of investigator-initiated clinical trials and implementation of non-high-risk investigator-initiated clinical trials, respectively. Pre-approval by the NIAID is required for submission of an application under all three FOAs.
• Funds Available and Anticipated Number of Awards. The total amount awarded and the number of awards will depend upon the numbers, quality, duration, and costs of the applications received.
• Budget and Project Period. 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.
• Application Research Strategy Length: The U01 Research Strategy section may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. See http://grants1.nih.gov/grants/funding/funding_program.htm
• 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. Applicants may submit a resubmission application, but such an application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016). Resubmissions from PAR-05-113 (http://grants.nih.gov/grants/guide/pa-files/PAR-05-113.htm) are allowed.
• Renewals. Renewal applications may not be submitted under this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
• Application Materials. All applications, including resubmission, revision, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions. 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

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
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. Dispute Resolution Process
3. Reporting

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for implementation of investigator-initiated, high-risk 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 new biomedical or behavioral interventions are safe, efficacious, and effective .

The proposed trial must be hypothesis-driven, related to the research mission of the NIAID and address a research area considered a high priority by the Institute.

This FOA will utilize the NIH Cooperative Agreement (U01) award mechanism, and will run in parallel with two related FOAs, PAR-10-184 and PAR-10-185, that invite applications for NIAID Clinical Trial Planning (R34) Grants, which support planning activities for investigator-initiated clinical trials, and NIAID Clinical Trial Implementation (R01) Grants, which support implementation of investigator-initiated, non-high-risk clinical trials, respectively.

Background

In FY2009 NIAID funded $1.36 billion in clinical research. A subset of this funding was devoted to clinical trials, which is one research strategy NIAID uses to improve the understanding of the clinical mechanisms of infectious, immunologic, and allergic diseases and to improve prevention, diagnosis, and treatment. For additional information about the mission, strategic plan, and research interests of the NIAID, applicants are encouraged to consult the NIAID web site http://www3.niaid.nih.gov/about/whoWeAre/planningPriorities/ .

Clinical Trial Infrastructure

Historically, NIAID has supported a wide variety of clinical research activities through a clinical trial infrastructure funded through cooperative agreements, solicited under NIAID Requests for Applications (RFAs), and contracts, solicited under NIAID Requests for Proposals (RFPs). This infrastructure focuses on high-priority disease research areas. Examples include the HIV/AIDS Clinical Trial Networks supported by the Division of AIDS (http://www3.niaid.nih.gov/about/organization/daids/Networks/daidsnetworks.htm), the Division of Microbiology and Infectious Diseases Clinical Trials Programs and Networks (http://www3.niaid.nih.gov/about/organization/dmid/programs.htm), and the Immune Tolerance Network supported by the Division of Allergy, Immunology and Transplantation (http://www.immunetolerance.org/). NIAID’s clinical research infrastructure includes coordinating centers, statistical units, data centers, central laboratories, clinical centers, and other specialized resources.

Investigator-Initiated Clinical Trials

Although the clinical research infrastructure is crucial to furthering the Institute’s research, NIAID recognizes that additional models of clinical research may be important to advancing its research mission; therefore, NIAID has established the investigator-initiated clinical trial program for clinical trials that cannot or will not be conducted through existing NIAID-supported clinical trial infrastructure. This program consists of support for the NIAID Clinical Trial Planning (R34) Grant, the NIAID Clinical Trial Implementation (R01) Grant and the NIAID Clinical Trial Implementation (U01) Cooperative Agreement.

The NIAID Clinical Trial Implementation (R01) Grant (PAR-10-184) is designed to support non-high-risk clinical trials, while the NIAID Clinical Trial Implementation (U01) Cooperative Agreement (PAR-10-186) is designed to support high-risk clinical trials, as defined by NIAID below and in the associated policy statement (see NOT-AI-10-024). The NIAID Clinical Trial Planning Grant (R34) is available to support planning activities associated with either high- or non-high-risk clinical trials. However, the NIAID Clinical Trial Planning (R34) Grant (PAR-10-185) is not a prerequisite for either NIAID implementation award. If a clinical trial is ready for implementation, and readiness is adequately supported by documentation, submission of an R01or U01 application may occur if prior approval has been provided by NIAID.

For additional information about NIAID’s investigator-initiated clinical trial program, see http://funding.niaid.nih.gov/ncn/clinical/iict.htm .

Scope

The NIAID Clinical Trial Implementation (U01) Grant supports implementation of trials that address high priority research related to the mission and goals of NIAID and that are considered high-risk by the NIAID.

A high-risk clinical trial is defined by the NIAID as having one or more of the following attributes:

• provision of a non-routine intervention, that is, an intervention or non-routine use of an intervention that would not otherwise be provided for the condition under study in the local facility where the study is being conducted;
• administration of an unlicensed product; or
• administration of a licensed product for an unapproved indication.

A non-high-risk trial would not have any of the attributes listed above; for example, it would involve provision of a routine intervention and administration of a licensed product for an approved indication. For the purposes of this FOA, examples of routine interventions might include, but would not be limited to: liver biopsy only to measure a research outcome and provision of anti-inflammatory agents and/or immunosuppressants to suppress and prevent transplant rejection, etc.

Implementation support is defined as support for activities related to the conduct of the clinical trial, including, but not limited to:

• training of study personnel;
• enrollment and recruitment of study subjects;
• data collection, management and quality control;
• laboratory work and data analyses;
• study management and oversight;
• establishment of committees to manage the complexity of the trial
• preparation of the final study report; and
• other related post-enrollment activities.

Each NIAID Clinical Trial Implementation (U01) award will support the implementation of a single clinical trial. Applications that include more than one clinical trial will not be reviewed.

Applicants must propose a time-sensitive, milestone-driven clinical trial and describe the clinical trial stages, criteria for completion of the stages and contingency plans for each stage. Any anticipated impediments that could require a revision in the timeline must be identified and accompanied by a discussion of alternative approaches. The trial must be hypothesis- driven, include a randomized design, and have clear primary and secondary endpoints. A description of the study population, why it is an appropriate group to study the research question(s) posed, subject eligibility, inclusion and exclusion criteria, and a feasible recruitment and enrollment plan must also be included. Statistical methods appropriate for the study design, and adequate plans for data monitoring and safety are required. An overview of the state of the science, current status and relevance of the trial, and discussion of the clinical protocol must be presented in the application.

All clinical trial planning activities must be completed by the time of application submission and investigators must be ready to implement the proposed trial at the time of award.

NIAID reserves the right to specify: 1) whether an IND/IDE application should be submitted to an appropriate regulatory agency; and 2) the entity (NIAID, primary awardee, etc.) who will hold the IND/IDE.

Investigators are referred to NIAID’s Clinical Research Toolkit website (http://www3.niaid.nih.gov/LabsAndResources/resources/toolkit/default.htm) for protocol templates and guidance, clinical research resources, and links to program divisions. Investigators are strongly encouraged to contact NIAID s program divisions (Section VII.1. Scientific/Research Contacts) for information regarding division-specific clinical research policies and procedures.

Milestones

Delineation of milestones is a key characteristic of the NIAID Clinical Trial Implementation (U01) Cooperative Agreement. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.

Applications must include a series of milestones for completion of the clinical trial and provide contingency plans should there be delays in attaining them. The milestones will undergo peer review and will be incorporated into the terms of award.

NIAID U01 clinical trial implementation cooperative agreements will NOT support clinical trial planning tasks such as:

• Development of study design
• Identification of collaborators and enrollment sites
• Development of the clinical protocol and informed consent
• Development of the statistical analysis plan
• Development of the data management plan
• Development of the Investigator’s brochure or equivalent

Investigators seeking support for the planning and design of clinical trials should refer to the NIAID Clinical Trial Planning (R34) Grant FOA (PAR-10-185).

NIAID U01 clinical trial implementation cooperative agreements will NOT support non-high-risk clinical trials. Investigators seeking support for non-high-risk clinical trials should refer to the NIAID Clinical Trial Implementation (R01) Grant FOA (PAR-10-184).

NIAID U01 clinical trial implementation cooperative agreements will NOT provide support for clinical trials that fall outside the mission and high-priority research areas of the NIAID.

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

Section II. Award Information

1. Mechanism of Support

This funding opportunity announcement (FOA) will use the NIH 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".

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 NIAID 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 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
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • 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 programs.

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.

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

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

Resubmissions. Applicants may submit a resubmission application, but such applications must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications are permitted only a single amendment (A1). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016). Original new and competing renewal applications that were submitted prior to January 25, 2009 are permitted two amendments (A1 and A2). For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.

Applicants who submitted a new application in response to PAR-05-113 may submit a resubmission application in response to this FOA.

Renewals. Renewal applications may not be submitted.

Pre-approval. Pre-approval from NIAID is required for submission of the NIAID Clinical Trial Implementation (U01) Cooperative Agreement application, including new and resubmission applications. NIAID staff will consider whether the proposed clinical trial meets the goals and mission of the Institute and whether it is appropriate to conduct it as an investigator-initiated clinical trial, but will not evaluate the technical and scientific merit of the proposed trial. Technical and scientific merit will be determined during peer review. Applicants whose projects do not meet NIAID s programmatic needs or are not appropriate as investigator-initiated clinical trials, will not be granted permission to submit an application. If the NIAID ascertains that substantial staff involvement may not be necessary, submission of the application may be considered under the Clinical Trial Implementation (R01) Grant FOA (PAR-10-184), but will not be considered under this FOA. NIAID reserves the right to determine that support for clinical trials may be directed through other available mechanisms supported by NIAID.

Section IV. Application and Submission Information

1. Address to Request Application Information

The current 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: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Prepare all applications using the PHS 398 application forms in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

Applications must be prepared using the 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, the 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. Receipt, Review and Anticipated Start Dates
Application Due Date(s) for AIDS & Non-AIDS: July 22, 2010, September 13, 2010, January 13, 2011, May 13, 2011, September 13, 2011, January 13, 2012, May 14, 2012, September 13, 2012, January 14, 2013
Peer Review Date(s): September, 2010, December, 2010, April, 2011, August, 2011, December, 2011, April, 2012, August, 2012, December 2012, April, 2013
Council Review Date(s): January 2011, May, 2011, October 2011, January 2012, May, 2012, October, 2012, January 2013, May 2013
Earliest Anticipated Start Date(s): November, 2010, March, 2011, July, 2011, November, 2011, March 2012, July, 2012, November 2012, March, 2013, July 2013

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

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:

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
For Express Couriers: 20817-1824
Telephone: (301) 435-9369, (301) 496-2550
Fax: (301) 480-2408
Email: pm158b@nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt/ date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review.

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 applications 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 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 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

Requirement of Pre-approval for Application Submission

Pre-approval of programmatic appropriateness from the NIAID is required for submission of an application in response to this FOA. Applicants must contact the applicable NIAID program division (see Section VII. 1. Scientific/Research Contacts) at least 10 weeks before the application due date. An approval letter to submit the application must be obtained from the appropriate NIAID Division Director and included with the application.

Special Requirements for the Research Plan of the Application

Specific Aims

The goals of the trial and the expected outcome(s) should be concisely stated in the Specific Aims section, which is limited to 1 page. The specific objectives of the trial must be clearly and concisely presented, including a specification of the primary and major secondary endpoints to be measured. There should be a clear explanation of the importance of various endpoints.

Research Strategy

The following three sections comprise the Research Strategy: Significance, Innovation, and Approach. In addition, the Research Strategy may not exceed 12 pages and must include:

• a discussion of the significance of the problem being studied, the need for the trial, and the potential impact of the results of the trial, as well as how the trial will test the hypothesis(es) proposed;
• a concise description of the overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the trial;
• a description of and rationale for the proposed study design;
• a description of the intervention to be tested and the protocol to be followed in each arm of the trial, including a discussion of potential biases or challenges in the protocol and how they will be addressed;
• statistical methods that are appropriate for the study design, including sample size and power calculations and the underlying assumptions (and data) used to link these calculations to the endpoints and to the hypothesis(es) being tested;
• a discussion of studies that led to the proposed clinical trial and information or data from preliminary studies which address the need for and the feasibility of the trial; and
• a description of the study organization and administration, including, but not limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any sub-contractors or service providers for personnel or facilities.

Requirements for the Human Subjects Section

Instructions in the PHS398 Part II Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan should be closely followed.

Clinical Protocol Synopsis

The clinical protocol synopsis should be included at the end of the Human Subjects section. Applications that lack the Clinical Protocol Synopsis will not be peer reviewed. The clinical protocol synopsis may not exceed 3 pages and must include the following information:

• a description of the study population, including subject eligibility and inclusion/exclusion criteria;
• sampling, recruitment and enrollment plans, including a discussion of the availability of subjects for the proposed study and the ability of enrollment center(s) to recruit and retain the proposed number of subjects;
• the process to be used for obtaining informed consent and, if applicable, assent;
• approaches to be used for retention, cooperation and follow-up of subjects and to address any anticipated changes in the composition of the study population over the course of the trial;
• methods of assignment of subjects to study groups and of randomization;
• if appropriate to the study, a description and justification for the selection of the dose, frequency and administration of the intervention(s);
• a description of each enrollment site and how data from the site(s) will be obtained, managed, and protected;
• descriptions of all clinical, laboratory, physiological, and/or behavioral tests to enable the research questions to be answered; and
• a description of the data management and quality control plan, including methods for monitoring the quality and consistency of the intervention(s) and data collection; policies and methods for ensuring blinding of study results; and data confidentiality and subject privacy.

Data and Safety Monitoring (DSM) Plan

A Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical research must be included for all clinical trials (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html). All applications or study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing and reporting reportable events (adverse events and unanticipated problems), to the applicable regulatory agencies (e.g., Institutional Review Board (IRB), the NIAID/NIH, the Office of Biotechnology Activities (as appropriate), the Office of Human Research Protections, the Food and Drug Administration, and the Data and Safety Monitoring Board (if one is used). The DSM Plan must address the following areas:

• who will manage and conduct the monitoring
• what will be monitored
• proposed monitoring time points
• where the monitoring will occur
• how the reportable events will be managed and reported
• how sites/centers, and participating facilities (labs, pharmacies) will be monitored

Milestone Plan and Complete Clinical Protocol

A Milestone Plan and Complete Clinical Protocol must be included after the Research Plan and will not count toward the page limit for the Research Plan. Applications that lack the Milestone Plan and/or the Complete Clinical Protocol will not be reviewed.

Milestone Plan

Applicants are required to provide detailed project performance and timeline objectives in a section entitled Milestone Plan . This section may not exceed 3 pages and must include:

• a timeline for the following general milestones, as applicable:
• completion of regulatory approvals
• enrollment of the first subject
• enrollment of 25%, 50%, 75% and 100% of the projected recruitment time period for all study subjects, including women, minorities and children (as appropriate)
• completion of data collection time period
• completion of primary endpoint and secondary endpoint data analyses time period
• completion of final study report
• detailed protocol-specific performance milestones and timeline; these milestones will be negotiated at the time of the award, if appropriate.

Complete Clinical Protocol

The Complete Clinical Protocol must be included immediately after the Milestone Plan. Investigators are referred to the Trans-NIAID Clinical Research Toolkit website for clinical protocol guidance and templates (http://www3.niaid.nih.gov/LabsAndResources/resources/toolkit/protocol). Investigators are urged to be succinct.

Just-in-Time Information

This FOA uses NIH just-in-time procedures (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm) for some documentation related to readiness to begin clinical trial implementation. If the application is under consideration for funding, the requirement for certification of IRB approval of the proposed use of human subjects, evidence of compliance with the Education in the Protection of Human Research Participants policy, and information on Current Other Support may be deferred until after completion of the peer review and just prior to funding.

Additional information that may be required as part of just-in-time procedures includes:

• training materials and plans for study staff
• Complete Manual of Operations
• evidence that the following requests for approvals have been submitted:
• IRB or Ethical Committee approval of the final protocol and the informed consent form (and assent form if applicable)
• other necessary approvals (e.g., Institutional biosafety committee) of the final protocol, as applicable

For additional information about the NIH "just-in-time" concept see Section II. 1. Mechanism of Support, Section VI.1. Award Notices.

PHS398 Research Plan Sections

All application instructions outlined in the PHS 398 Application Instructions are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:

• Introduction (required for a resubmission application) is limited to 1 page.
• Specific Aims is limited to 1 page.
• Research Strategy, including tables, graphs, figures, diagrams, and charts, is limited to 12 pages. See Table of Page Limits.

Budget

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

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

Because all applications must include detailed scientific and operational plans, funding needs for the entire trial and data analysis period must also be included. Investigators must submit a complete, justified, individual budget for each year of support requested. All costs requested and all changes in budgets after the first year should be clearly identified and justified. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating site or core, if multiple sites or cores are proposed. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail along with supporting letters signed by individuals who have the authority to make fiduciary commitments on behalf of the institution. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget or as Estimated Project Funding.

Further information concerning budget preparation may be obtained from the Office of Grants Management contact listed in Section VII. 3. Financial/Grants Management Contact(s).

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 10 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, revision, or resubmission applications. See NOT-OD-02-004.

Letters of Support:

In the Letters of Support section of the Research Plan, provide all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, cores, laboratories, pharmacies and other collaborators. If co-funding or in-kind support is planned from non-NIH sources, letter(s) outlining details of the commitment (e.g. type, amount and source of support), signed by a business official on organization letterhead, must included in Letters of Support section.

Appendix Materials

All paper PHS 398 applications submitted 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.

The following additional documents must be included in the Appendix material:

• the informed consent form(s) and, if applicable, assent form(s)
• the statistical analysis plan
• identification and qualifications of clinical trial site(s), pharmacies and laboratories
• copies of data collection forms, questionnaires or other relevant materials
• the Investigator s Brochure or equivalent for the study products(s)
• the Table of Contents of the Manual of Procedures
• a comprehensive Laboratory Plan
• documentation of availability of study agents and support for acquisition and administration of study agent(s)
• the Data Management Plan
• the Site Quality Management Plan
• copies of data collection forms, questionnaires or other relevant materials

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: Regardless of the amount requested, investigators 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 for this FOA. See NOT-OD-06-096.

Section V. Application Review Information

1. Criteria

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

2. Review and Selection Process

Review Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID 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 Allergy and Infectious Diseases Council.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact 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 scored review criteria, and additional review criteria (as applicable for the project proposed).

Scored 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? If proposed, do the mechanistic studies contribute to the understanding of the disease or treatment? Are the study objectives(s) and hypothesis(es) adequately defined?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, 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? Do the PD/PIs and key personnel have the necessary expertise in statistics, data management and study coordination to implement the proposed clinical trial and meet milestones and timelines? Are committee structures appropriate to the complexity of the trial? For multicenter trials, does the application identify a core of potential center investigators and staffing for a coordinating center? Is the organizational structure of the multicenter trial appropriate?

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? Does the application adequately address the following: the intervention, study agent(s), and mode of delivery; availability of the eligible study population; informed consent or assent form, as applicable; statistical hypothesis and analysis; endpoint(s) and data to be collected; sample size, power calculation, and duration of the trial; randomization, masking, and inclusion/exclusion criteria; ancillary therapies; plans to standardize and monitor adherence to the clinical protocol; and methods for standardization of procedures for data, site, and quality management? Does the application provide adequate milestones? Is the plan for acquisition and handling of study agent(s) appropriate? Does the application adequately address differences in the intervention effect due to sex/gender and race/ethnicity? Does the application clearly describe plans for recruitment outreach, enrollment, and retention? Is the plan for regulatory approval likely to be successful? Does the application adequately address potential ethical issues? Does the application adequately address the clinical trial documentation (e.g., the investigator's brochure or equivalent)? Does the application adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP) compliance? For multi-center trials, does the application adequately address the standardization/quality control of, and adherence to, the clinical protocol and data collection and/or distribution guidelines, and the use of a data coordinating center?

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? Does the application adequately address plans to add or drop enrollment centers; the availability of the requisite eligible volunteer pool; the availability of children, women and minority individuals as trial participants and specific recruitment and retention plans for their inclusion; plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

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. For additional information, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

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.

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. Renewals are not allowed in this FOA.

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.

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/priority score.

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.

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).

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 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.

Selection Process

Applications submitted in response to this FOA 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.

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 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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice of Award. 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).

In addition, awards made under this FOA will be subject to the NIAID Clinical Terms of Award. The NIAID Clinical Terms of Award apply to all NIAID awards that entail research involving human subjects (see http://www.niaid.nih.gov/ncn/clinical/clinterm.htm). Implementation of the NIAID Clinical Terms of Award ensures that the conduct of the clinical trial meets widely-accepted standards, including guidance and regulations (e.g., International Conference on Harmonisation E6: Good Clinical Practices, http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm). Guidance for complying with the NIAID Clinical Terms of Award is provided for investigators on the NIAID website at: http://www.niaid.nih.gov/ncn/clinical/clintermguidance.htm.

Further, the terms and conditions for an award for a clinical trial will incorporate all general and protocol-specific milestones agreed upon between NIAID and the awardee before the award is made. This will include, but will not be limited to, any modifications to the milestones proposed in the application as a result of peer review or recommendations by NIAID program or grants management staff. The terms and conditions of award will also include any requirements regarding minimum effort of specific key personnel, and any other identified requirements for completion of the approved research.

As with any award, continuation of funding is contingent upon satisfactory progress. Continuation of funding will be dependent upon the awardee’s ability to demonstrate adequate progress toward milestone attainment. Actual enrollment will be compared to the benchmarks and criteria identified in the application and negotiated prior to award. Studies in which recruitment milestones are not met as per criteria established pre-award or for which regulatory approval has not been met within one year, and are deemed unlikely to improve sufficiently to bring the study to completion within an acceptable budget or timeframe, may be closed for lack of progress following review and consideration by NIAID staff.

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.

These terms and conditions of award are representative of the specific terms and conditions that will be negotiated with an applicant prior to 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 their 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 NIAID staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.
• Meeting NIAID policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. AN UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf
• Upon implementation of the protocol, ensuring that 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, volunteer management, data collection, and quality control.
• Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIAID support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIAID.
• Putting all study materials and procedure manuals into 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 NIAID/NIH.
• Obtaining prior written approval of the NIAID Grants Management Specialist in consultation with the NIAID Program Officer for any change 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 NIAID 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. NIAID 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 NIAID grantees and contractors, advising in management and technical performance, or participating in the preparation of publications.
• Provide medical monitoring by an NIAID Medical Officer who 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 NIAID Medical Officer will work with the company-assigned Medical Monitor.
• Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team, which may include attendance at the safety monitoring (or DSMB) and related committee meetings.
• Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, volunteer logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.
• Monitor progress of study milestones; as with any award, continuation, even during the period recommended for support, is contingent upon satisfactory progress. Progress will be monitored by an internal panel with outside consultants as needed and determined by the NIAID. The schedule for these interim reviews will be based upon the duration of the clinical trial period. Continuation of funding will be dependent upon the awardee’s ability to show adequate progress towards milestone accomplishment.
• At each scheduled interim review, compare actual enrollment to the benchmarks and criteria identified in the application and negotiated prior to award; awardees who do not accomplish the negotiated milestones shall submit a milestone report which will include a discussion of why the milestones were not met in the agreed upon timeframe, and propose a corrective recruitment action plan. The corrective recruitment action plan shall include: amended milestones, plans to achieve the amended milestones and any additional items required by NIAID staff. The plan shall be provided to NIAID staff no later than 2 months following the missed milestone.

Studies in which recruitment milestones are not met as per criteria established pre-award, or for which regulatory approval has not been met within one year, and are deemed unlikely to improve sufficiently to bring the study to completion within an acceptable budget or time frame, may be closed for lack of progress following review and consideration by NIAID staff.

If a study is finally determined to lack feasibility and will no longer accrue subjects, awardees are required to submit a close-out plan to NIAID staff in 2 months timeframe of a decision either by NIAID staff or the grantee that an awarded study is no longer feasible. The plan must be approved and signed by the Institutional Official and the PI/PD(s) listed on the award prior to submission.

NIAID 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 NIAID 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 various field centers, the Data Coordinating Center and of the specialized core facilities (if any), and one NIAID representative (the Project Scientist ) . The NIAID 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. Dispute Resolution 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 dispute resolution. A Dispute Resolution 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 dispute resolution 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 Contact(s):

Matthew J. Fenton, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Room 6503, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-8973
Fax: (301) 480-5824
Email: fentonm@niaid.nih.gov

Mr. Martin Gutierrez
Division of Acquired Immunodeficiency Syndrome
National Institute of Allergy and Infectious Diseases
Room 4258, MSC-7620
6700-B Rockledge Drive
Bethesda, MD 20892-7620
Telephone: (301) 451-2703
Fax: (301) 402-1506
Email: mgutierrez@niaid.nih.gov

Ms. Elizabeth Holloman
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 4504, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: (301) 402-8339
Fax: (301) 480-0728
Email: hollomone@niaid.nih.gov

2. Peer Review Contact(s):

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
For Express Couriers: 20817-1824
Telephone: (301) 435-9369, (301) 496-2550
Fax: (301) 480-2408
Email: pm158b@nih.gov

3. Financial/Grants Management Contact(s):

Ms. Laura Eisenman
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2120, MSC-7614
6700-B Rockledge Drive
Bethesda, Maryland 20892-7614
Telephone: (301) 402-5541
Fax: (301) 493-0597
Email: le55d@nih.gov

Section VIII. Other Information

Required Federal Citations

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

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.

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. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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 And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-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 investigator’s 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 (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) 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. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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

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