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)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (http://www2.niddk.nih.gov)

Title:  Consortium of Food Allergy Research (CoFAR) and CoFAR Statistical and Clinical Coordinating Center (CoFAR SACCC) (U19 and U01)

Announcement Type
This Funding Opportunity Announcement (FOA) is a reissue of RFA-AI-04-034.

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

Request For Applications (RFA) Number:  RFA-AI-09-039  

Catalog of Federal Domestic Assistance Number(s)
93.855,  93.847

Key Dates
Release Date: July 7, 2009
Letters of Intent Receipt Date:  October 9, 2009
Application Receipt Date:  November 10, 2009
Peer Review Date:  March, 2010
Council Review Date:  May 2010
Earliest Anticipated Start Date:  July 2010
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/qa/revniaid.htm
Expiration Date:  November 11, 2009

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

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(s) 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, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

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

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose 

This FOA issued by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), invites applications for the continuation and expansion of the Consortium of Food Allergy Research (CoFAR). The Consortium will consist of a collaborative clinical research program to develop new approaches to treat and prevent IgE-mediated food allergy, including food allergy-associated anaphylaxis and food allergy-associated eosinophilic gastrointestinal disease (EGID). Within the context of these disorders, the goals of the program are to: (1) develop immune intervention strategies for prevention and treatment, (2) identify the mechanisms underlying the natural histories of these disorders, and (3) define the genetic components of these disorders. The consortium may consist of both collaborative multi-project as well as individual research projects. In addition this FOA will provide support for a Statistical and Clinical Coordinating Center (SACCC) to support the clinical research.

Background

Food allergy is an immunologic disease responsible for substantial morbidity and mortality. Food allergy occurs in almost 4% of children and adults, and has a higher prevalence in children under age 4, and appears to be increasing in prevalence. Severe food allergic reactions may cause anaphylaxis and death. In the United States, there are approximately 14,000-30,000 annual anaphylactic episodes due to food allergic reactions. Eight foods (milk, egg, peanuts, tree nuts, fish, shellfish, soy and wheat) cause 90% of all allergic reactions to foods, and peanuts and tree nuts are the most common food allergens causing severe allergic reactions. Food allergic disorders encompass IgE-mediated hypersensitivity and other immune mechanisms including IgG-mediated and T cell-mediated hypersensitivity. The most common forms of food allergy, and food allergy-associated anaphylaxis, are mediated by IgE antibodies. IgE antibody-mediated events contribute to the gastrointestinal (GI), cutaneous, respiratory, cardiovascular and systemic symptoms associated with severe food allergy. Although the number of deaths from food allergy is low, the risk of severe reactions is substantial. Even with vigorous attempts to avoid allergenic foods, food allergic individuals have an average of at least one accidental exposure resulting in an allergic reaction every four years. There is no treatment for food allergy other than allergen avoidance and treatment of life-threatening reactions. Moreover, there are no biomarkers predicting the likelihood of a severe allergic reaction and the severity of a prior reaction to a food is a poor predictor of severity of subsequent reactions.

IgE-mediated food allergy is an apparent failure of the development of oral tolerance. However, the observation that exposure of young children to skin preparations containing peanut oil increases sensitization to peanuts is consistent with an alternative possibility, that the development of food allergy is associated with skin and other non-oral routes of exposure to food. Current research cannot yet determine the overall importance of either pathway.

Two major clinical conditions associated with IgE-mediated food allergy are food allergy-associated anaphylaxis and eosinophilic gastrointestinal diseases (EGID); EGID includes eosinophilic esophagitis (EE), the most common form of EGID, and eosinophilic accumulation in gastrointestinal organs other than the esophagus. Food allergy and food allergy-associated anaphylaxis are part of the same disease process, but, as stated above, a diagnosis of food allergy gives little predictive value of the risk of severe reactions and anaphylaxis. The relationship of IgE-mediated food allergy to EGID is not fully understood, although about half of patients with EGID have IgE antibodies to food allergens, and some of these patients have a beneficial clinical response to removal of food allergens from their diet.

Fuller understanding of the food allergy, food allergy-associated anaphylaxis, and food allergy-associated EGID may be obtained by several different types of studies, including observational (including natural history) studies, genetic studies, and therapeutic interventions to prevent and treat the diseases.

Observational/natural history studies may utilize specimens and clinical data to identify immunologic (or other) changes over time that correlate with the clinical course. The current CoFAR observational study is designed to utilize this approach. Two examples of questions being addressed in the CoFAR study are: (1) Among young children who are allergic to egg, which immunologic parameters predict resolution of egg allergy vs. persistence of egg allergy? (2) Among young children with egg allergy, which immunologic parameters predict the development of new allergy to peanuts vs. non-development of peanut allergy?

Atopic diseases, including food allergy, have a genetic component. The genes responsible for IgE-mediated food allergy remain largely unknown, although there is clear evidence for familial aggregation of sensitization to food allergens. Recent advances, including the completion of the Human Genome Project and the International HapMap project, have increased the opportunity to define the genetics of human food allergy.

Although there have been only limited studies of the genetics of food allergy, some specific genes have been implicated as associated with food allergy, including SPINK5 and filaggrin. The genetic basis of food allergy-associated anaphylaxis is unknown, but anaphylaxis may be associated with some genes distinct from those responsible for food allergy. The genetic basis of EGID is unknown, but some genes distinct from those responsible for food allergy, including genes associated with eotaxin-3 and other genes associated with eosinophil biology, may be important.

Experimental management of food allergy has focused on immune-based approaches to prevent or treat this disease. In the last several years, a large NIAID-sponsored primary prevention trial of peanut allergy has been initiated in England (http://clinicaltrials.gov/ct2/show/NCT00329784?term=Lack%2C+gideon&rank=1). In addition to prevention trials, several approaches have been used to treat existing food allergy. Administration of a monoclonal anti-IgE to peanut-allergic individuals led to an increase in the number of peanuts that were tolerated without allergic reactions, but a substantial number of subjects in this study appeared to be unresponsive. There is both a scientific and a clinical need to determine whether existing experimental therapeutic approaches induce desensitization or tolerance. Moreover, there is also a need to define the underlying immunological processes that lead to both outcomes.

There is little information about human clinical trials to prevent or treat IgE-mediated food allergy-associated anaphylaxis. Several recent clinical trials of EGID have demonstrated some beneficial effects of food allergen elimination diets, elemental diets, corticosteroids, and other approaches. These trials have not yet clarified the relationships between IgE-mediated food allergy and EGID.

The research approaches proposed in this FOA, including clinical trials, observational/natural history studies and genetic studies on IgE-mediated food allergy, food allergy-associated anaphylaxis, and food allergy-associated EGID, are among the recommendations of the 2006 NIH Expert Panel on Food Allergy Research, finalized in 2007. This full report can be found at: http://www3.niaid.nih.gov/topics/foodAllergy/research/ReportFoodAllergy.htm.

RESEARCH OBJECTIVES and SCOPE

The objectives of the CoFAR research program are to: explore the pathophysiology of human IgE-mediated food allergy and the related conditions, IgE-mediated food allergy-associated anaphylaxis and IgE-mediated food allergy-associated EGID, and to develop and evaluate clinical approaches to prevent and treat these diseases. Under the CoFAR program, applicants are encouraged to develop close interactions among basic scientists and clinical investigators and accelerate the translation of basic research advances into clinical application.

This FOA solicits for two separate components of the CoFAR program:

1.    The CoFAR research component will support clinical studies (observational/natural history studies and genetic studies), and clinical trials. CoFAR research applications may be submitted under the U01 mechanism (single project) or the U19 mechanism (multi-project).

2.    The CoFAR SACCC component will provide coordination, assistance, centralized data management, and statistical/analytical support for all human studies undertaken by CoFAR; and statistical/analytical support of preclinical studies (if proposed). The CoFAR SACCC must be submitted under the U01 mechanism.

A. General Overview of Requirements for CoFAR U01 or U19 Research Applications.

Applicants may submit either a U01 (single project) or a U19 (multi-project) research program application. The U01 application must contain only one project, while the U19 application must contain at least two research projects organized around a central hypothesis and should synergize to accomplish a common goal (if additional research projects are proposed in a U19 application, they must also relate to the central hypothesis), and may contain an Administrative or Clinical Core and/or Scientific Core(s).

Applications submitted for the CoFAR U01 and U19 Research Program:

Research topics supported under the CoFAR U01 and U19 research projects include human IgE-mediated food allergy and/or food allergy-associated anaphylaxis and/or food allergy-associated EGID. Although studies on EGID must include a focus on IgE-mediated food allergy-associated disease, these studies may also compare subjects with known food allergy to those without known food allergy.

Research topics focused on non-IgE-mediated diseases such as celiac disease will be considered nonresponsive and will not be reviewed.

All research must involve human subjects, either as part of a clinical trial or observational/natural history study or genetic study, or for collection of samples for genetic studies. Genetic studies may use samples from either new cohorts or from pre-existing cohorts. The CoFAR U01 or U19 application may be conducted using any of the following research approaches:

Additional information concerning approaches to be used for research applications submitted for the CoFAR U19:

A U19 application must contain a minimum of two projects. Specific requirements for this FOA are that the projects in the U19 application must include, at a minimum, one clinical trial, and either an observational/natural history study or a genetic study. A second requirement for this FOA is that at least one of the projects in the U19 must focus specifically on research on IgE-mediated food allergy (i.e., not food allergy-associated anaphylaxis or food allergy-associated EGID).

Applications for the CoFAR U19 program may propose Cores (Administrative or Scientific) in support of the required two minimum research projects.  

An Administrative Core would provide administrative support for the overall U19 research program. Applications for this type of Core should provide a plan discussing the structure and roles of administrative staff, including the training and experience of proposed staff and the functions they will perform; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; and how research-related activities will be budgeted. Funding for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, communication expenses, etc., should be requested here. 

A Science Core, for example a Clinical Core must support at least two of the proposed research projects. The application must indicate the specific projects to be served by the Scientific Core.  This section of the application should present a clear picture of the facilities, techniques, and skills that the core will provide and describe the role of the Scientific Core Leader and each of the key participants.  The apportionment of dollars, or percentage of dollars, that will be required to support each component research project which will utilize each scientific core should also be presented.

B.  General Overview of Requirements for CoFAR Statistical and Clinical Coordinating Center (SACCC) Applications.

The SACCC will provide coordination, assistance, and support for all human studies conducted by CoFAR investigators. The SACCC will provide only statistical/analytical support for preclinical studies. SACCC responsibilities for human studies include statistical design, data collection and analysis, centralized data management, safety oversight, clinical site monitoring, and logistical support for the Consortium Steering Committee and the NIAID Allergy and Asthma Data and Safety Monitoring Board (DSMB). Specifically, the SACCC will provide assistance in the following areas:

CONSORTIUM STEERING COMMITTEE

The Consortium Steering Committee, composed of PDs/PIs from the CoFAR U01s and U19s, the PLs of the research projects within the U19 application, the PD/PI of the SACCC, and the NIH Project Scientist, will serve as the overall governing body for the Consortium with respect to review, implementation, modification, completion or termination of research directions and with respect to development of clinical studies (consisting of observational/natural history studies and/or genetic studies), clinical trials and mechanistic studies. All protocols for clinical studies, clinical trials and mechanistic studies will be implemented only after review by the Steering Committee. The Consortium Steering Committee will meet twice yearly to review Consortium progress, develop, review and approve protocols, and develop policies and procedures affecting the Consortium activities.

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 will use the U19 and U01 Cooperative agreement award mechanisms for the CoFAR research program and the U01 Cooperative agreement award mechanism for the CoFAR SACCC.

The Principal Investigator (PD/PI) for either the U19 or U01 Cooperative agreement retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with the participation of the Steering Committee, and with NIH staff being substantially involved as a partner with the Principal Investigator(s), as described under the Section VI.2. Administrative and National Policy Requirements, 2.A “Cooperative Agreement Terms and Conditions of Award.”

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 funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator (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".  Plans to continue this initiative beyond the current funding opportunity are indefinite.

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 IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, NIAID and NIDDK have not determined whether or how this solicitation will be continued beyond the present FOA.

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 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.  Individual applicants may not submit more than one application in response to this FOA.

Resubmissions.  Resubmission applications are not permitted in response to this FOA. 

Renewals.  Renewal applications are permitted in response to this FOA

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

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

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

SPECIAL INSTRUCTIONS

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 such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

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

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date:  October 9, 2009
Application Receipt Date:  November 10, 2009
Peer Review Date:  March 2010
Council Review Date:  May 2010
Earliest Anticipated Start Date:  July 2010

3.A.1. Letter of Intent

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

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 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Phone:  301-435-9369
Fax:  301-480-2310
Email: pmehrotra@niaid.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the 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 material 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 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Phone:  301-435-9369
Fax:  301-480-2310
Email: 
pmehrotra@niaid.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute.  Incomplete and/or non-responsive 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 review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

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. The Grants Policy Statement can be found at NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

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

6. Other Submission Requirements

Supplemental Instructions for the Preparation of Multi-Project Applications

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application (U19).  Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme.  Applicants preparing single project applications (U01) should follow the PHS Form 398.

The supplemental instructions for multi-project applications are divided as follows:

A. General Instructions – address collaborative efforts among research projects, the administrative and organizational structure as well as the overall facilities and environment, and the overall budget.
        
B. Specific Instructions for Individual Projects – describe modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

C. Specific Instructions for Core Units – Cores must provide services or resources to support at least two research projects. Instructions describe modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

A. General Instructions

All applications must be submitted on PHS Form 398. The multi-project grant application should be assembled and paginated as one complete document.

1.  Form Page 1 - Face Page.  Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

2.  Form Page 2.  Using Form Page 2 of the PHS 398, provide a succinct but accurate description (abstract) of the OVERALL multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Principal Investigator of the multi-project application, followed by the Project Leaders of the component research projects and cores, other key personnel, and then other significant contributors.

3.  Form Page 3 - Table of Contents.  Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed by project and core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g. Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

4.  Composite Budget. Do not use Form Page 4 of the PHS 398. Instead, using the suggested format presented below, prepare a composite budget for all proposed years of support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component

Year 1

Year 2

Year 3

Year 4

Year 5

All Years

Project 1. Invest.

125,000

130,000

135,200

140,608

146,232

677,040

Project 2. Study

125,000

130,000

135,200

140,608

146,232

677,040

Project 3. Develop.

100,000

104,000

108,160

112,486

116,985

541,631

Core A. Admin. Core.

50,000

52,000

54,080

56,243

58,493

270,816

Core B. DNA

25,000

50,000

52,000

54,080

56,243

237,323

             

Totals

425,000

466,000

484,640

504,025

524,185

2,403,850

5.  Form Page 5. Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry.

6.  Biographical Sketch Format Page. Biographical sketches of all professional personnel for all components should be placed at the end of the application with the Principal Investigator first, followed by those of other key personnel in alphabetical order.

7.  Resources Format Page. Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

8.  Program Overview (Research Objectives and Strategic Plan).  This narrative section summarizes the overall research plan for the multi-project application and is limited to 25 pages. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program – by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique.

If the application is a renewal, this section should also highlight past performance and the major accomplishments from the prior funding period.  In addition to discussing results from individual projects, describe the synergy and collaborations that occurred.  For individual research projects that will be continued, additional details should be provided in the Progress Report section of the Research Plan within the application for the Research Project.

9. Leadership Plan for Multiple PD/PIs (If proposed in the application)

For applications designating multiple PD/PIs, a 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, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PD/PIs, including responsibilities for human or live vertebrate animal subject studies as appropriate.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PD/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.

10. Checklist. One Checklist, placed at the end of the application, is to be submitted for the entire application.

11. Appendix Materials.  Refer to Section IV.6. Other Submission Requirements and Information, for instructions on submitting appendix materials.

For each project or core in the multi-project application, 3 publications plus other approved material are allowed.  

12. Resource Sharing Plan. One Resource Sharing Plan, placed at the end of the application, is to be submitted for the entire application.

B. Specific Instructions for Individual Research Projects

1.  Cover Page. The Face Page of the PHS 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research project. This Cover Page will demarcate each individual research project and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

Project Number and Title: (e.g., 1. Preclinical Evaluation of HIV Microbicides)

Name of Project Leader: (e.g., Jones, Roberta A.)

Human Subjects: (Yes or No)
If Yes, exemption number:
(or)
IRB Approval Date: (e.g., 12/13/2006,or "Pending")
(and)
Federalwide Assurance  (FWA) number:

Vertebrate Animals: (Yes or No)
If Yes, IACUC Approval Date: (e.g., 11/17/2006, or Pending)
(and)
Animal welfare assurance number:

Proposed Period of Support:
From: (mmddyyyy - e.g., 07/01/2007)
To: (mmddyyyy - e.g., 06/30/2112)

Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)
Direct Costs: (e.g., $ 150,000)
Total Costs: (e.g., $162,000)

Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)
Direct Costs: $700,000

Applicant Organization:
(full address)

2.  Form Page 2. Provide a Description (abstract) of the research proposed in the project according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the research project will contribute towards attainment of the multi-project program objectives.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Principal Investigator of the multi-project application, followed by the Project Leaders of the component research projects and cores, other key personnel, and then other significant contributors.

3.  Form Page 3. Prepare a Table of contents for the research project using Form Page 3 of the PHS 398.

4. Budget Pages (PHS 398 Form Pages 4 and 5).  Prepare a detailed budget and justification for the research project using Form Pages 4 and 5 of the PHS 398.

5. Biographical Sketches. Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

6. Resources Format Page.  Provide information on resources available for the project

7.  Research Plan (Items 2-5 cannot exceed 25 pages)

Item 2 -- Specific aims: List in priority order, the broad, long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the project's relationship to the multi-project program goals and how it relates to other projects or cores. This section is typically one page.

Item 3 -- Background and Significance: Use this section to describe how the proposed research will contribute to meeting the program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

8. Clinical Trial Synopsis or Clinical Study Synopsis.  These sections do not count toward the page limits of the PHS398.  The Clinical Trial Synopsis may not exceed 10 pages. The Clinical Study Synopsis may not exceed five pages. Details regarding the content of each synopsis are presented in Section IV. 6. Other Submission Requirements and Information.

9. Appendix. Do not create an appendix for an individual project.

C.  Specific Instructions for Cores (if proposed)  

1. Cover Page. The Face Page of the PHS 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual core. This Cover Page will demarcate each core and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page:

Core Letter and Core Title
(e.g., A. Monoclonal Antibody Production Core)

Name of Core Leader
(e.g., Smith, Robert A.)

Human Subjects (Yes or No)
If Yes, Exemption Number
(or)
IRB Approval Date (e.g., 5/14/2006, or Pending)
(and)
Federal Wide Assurance (FWA) number

Vertebrate Animals (Yes or No)
If Yes, IACUC Approval Date (e.g., 4/15/2007, or Pending)
(and) Animal welfare assurance number

Proposed Period of Support
From: (mmddyyyy, e.g., 07/01/2007)
To: (mmddyyyy, e.g., 06/30/2012)

Costs Requested for Initial Budget Period
(e.g., Direct Costs: $50,000)
(e.g., Total Costs: $70,000)

Costs Requested for the Entire Budget Period
(e.g., Direct Costs: $212,323)
(e.g., Total Costs: $297,252)

Applicant Organization
(full address)

2. Form Page 2. Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the multi-project program objectives.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Principal Investigator of the multi-project application, followed by the Project Leaders of the component research projects and cores, other key personnel, and then other significant contributors.

3. Form Page 3. Prepare a Table of Contents for the core using Form Page 3 of the PHS 398.

4. Budget Pages (PHS 398 Form Pages 4 and 5).  Prepare a detailed budget and justification for the core using Form Pages 4 and 5 of the PHS 398.

5. Biographical Sketches. Do not repeat the biographical sketches of participating investigators since this information will be located at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

6. Resources Format Page.  Provide information on resources available for the core.

7. Core Research Plan (Items 2-5 cannot exceed five pages for Administrative Core and cannot exceed ten pages for Scientific Cores such as a clinical trial)

Item 2 - Specific Aims: List in priority order, the broad, long-range objectives of the proposed core. In addition, state the core's relationship to the multi-project program goals and how it relates to the research projects or other cores in the application.

Item 3 - Background and Significance: Use this section to describe how the proposed core activities will contribute to meeting the program’s goals and objectives and explain the rationale for the selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the multi-project application.

8. Appendix. Do not create an appendix for a core.

For all other items in the individual core application, follow the usual PHS 398 instructions

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

In addition to the standard PHS398 application information, all CoFAR U19 or U01 research applications must also include a Clinical Trial Synopsis, a Clinical Study Synopsis, or both (where applicable) consisting of the following information: 

Clinical Trial Synopsis:  All clinical trial projects must provide a single clinical trial synopsis addressing the following aspects of the proposed clinical trial.  Up to ten pages will be allowed and will not count against the 25-page limit in PHS398 (Sections 2-5).  This section should be placed after Section 5 of the Research Plan in the PHS398. If multiple synopses are included (i.e., one for each Clinical Trial and one for each Clinical Study), they should follow each other at the end of Section 5.  

Clinical Study Synopsis:  All clinical study projects (observational/natural history or genetic study) must provide a clinical study synopsis addressing the following aspects of the proposed clinical study.  Up to five pages will be allowed and will not count against the 25-page limit.  This section should follow Section 5 of the Research Plan in the PHS398.  If multiple synopses are included, they should follow each other at the end of Section 5. 

Research Plan Page Limitations

See Section IV.6, “Content and Form of Application Submission for research plan page limitations.

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 of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

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

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

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

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

Section V. Application Review Information


1. Criteria

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

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by 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:

The following will be considered in making funding decisions:

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.

Review Criteria for the CoFAR Research Projects (U01), individual research projects within the multi-project (U19) applications and CoFAR SACCC (U01) applications.

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

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

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

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

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

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  Is the quality of the mechanistic studies associated with each clinical trial and each observation/naturalistic history study adequate and feasible?  Do the mechanistic studies integrate well with the clinical trials and clinical studies?

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? 

Additional Review Criteria for U19 (multi-project) applications:

Review Criteria for an Administrative Core (if proposed)

Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program?  Is the management plan for fiscal accountability and communication within the Project appropriate?  Are the plans for coordination, communications, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate? Are the experience, level of commitment, and availability of the Administrative Core Leader and administrative staff adequate to manage the program?

Review Criteria for Scientific Core(s) (if proposed)

Is provision of resources and core services to two or more of the Research Projects critical and justified?  Is the relationship of a scientific core to the central focus of the overall program strong?  Is the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate?  Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate?

Review Criteria for Evaluating the Overall U19 Application

Is the program as a whole scientifically compelling? Are there coordination and synergy of the individual research projects (and cores, if proposed) towards the achievement of the central hypothesis?  Are the overall program goals significant and focused on studies that meet the objectives of the FOA?  Will the integration of the individual projects into a single program be more beneficial than pursuing each project independently?  Is the significance and/or the innovation of the individual project enhanced by the integration into a single program? Will the PD/PI and PL (and CL, if applicable) devote adequate time and effort to the program, and are there sufficient plans for communication among the individual projects?  For renewal applications, what are the accomplishments and progress achieved during the prior funding period? For applications designating multiple PDs/PIs, is the Leadership Plan, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

Additional Review Criteria for the CoFAR SACCC (U01)

Does the applicant have both the expertise/capabilities and demonstrated experience to support the clinical research activities of CoFAR? Does the applicant have expertise and experience with statistical support, design and analyses of both clinical and mechanistic data, and preparation of reports and analyses to be used for publications and presentations?  Does the applicant have experience with clinical trial design, implementation and management, as well as expertise and experience in terms of safety oversight and reporting, including development of data and safety monitoring plans?  Is the applicant familiar with all aspects of protocol development?  Does the applicant have experience with regulatory activities, including preparation, submission and distribution of regulatory submissions, and assistance in preparation of IND application to the FDA?  Does the applicant have demonstrable knowledge and experience in data management and reporting, including establishing and maintaining a secure computer-based system? Does the applicant provide adequate plans for  receipt, distribution and quality control of study products and the provision of logistical support for meetings and teleconferences? For applications designating multiple PDs/PIs, is the Leadership Plan, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

Additional Review Criteria for all applications.  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.

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

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.

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.

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

Select Agent 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).

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.htm).

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

The 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. Principal Investigator Rights and Responsibilities

The PI(s) of CoFAR and of the CoFAR SACCC will have the primary responsibility for defining the research objectives, approaches and details of the projects within the guidelines of the FOA and for performing the scientific activity.

PIs will be responsible for establishing and following the policies of the Steering Committee and for the development and review of progress. PIs are expected to participate in Steering Committee meetings.

PIs agree to participate in the cooperative research program, including serving on the Steering Committee, adhering to Steering Committee policies and decisions, and accepting the participation and assistance of NIH staff in accordance with the guidelines described in Section VI.2.A.3.  “Cooperative Agreement Terms and Conditions of Award: NIH Responsibilities.”

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: The Project Scientist may provide appropriate guidance and support in the design of research activities, may serve as a resource for protocol design and development, may provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, may advise in the selection of sources or resources (e.g., determining where a particular reagent can be found), may advise in management and technical performance, or participating in the preparation of publications. The NIAID Project Scientist will be a voting member of the Steering Committee and participate in all Steering Committee activities, including conference calls, subcommittees and special committees. However, the role of the NIAID Project Scientist will be to facilitate and not direct activities. It is anticipated that decisions in all activities will be reached by consensus and that the NIAID Project Scientist will participate in this process.

Collaborations with industry will require the assistance of the NIAID Division of Allergy, Immunology and Transplantation (DAIT) Clinical Research Program, and be conducted under a NIAID Clinical Trials Agreement.

The NIAID reserves the right to terminate or curtail a study or any individual award.

The DAIT, NIAID Office of Regulatory Affairs or designee will be responsible for providing guidance and assistance in the development, assembly and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, devices or products, to the Food and Drug Administration or other Health Authorities. NIAID will act as the IND sponsor for single center or multi-center studies carried out by CoFAR, or will be responsible for delegating the sponsor responsibility to another qualified party (i.e. a pharmaceutical industry sponsor) subject to the Principal Investigator’s approval.

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

All protocols developed in CoFAR will be reviewed by NIAID program staff and the NIAID Allergy and Asthma Data Safety Monitoring Board (DSMB).

Additionally, an NIAID program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This stewardship includes monitoring program progress, approving changes and concurring in proceeding into study implementation stage. Release of each yearly funding increment for CoFAR U19s and U01s will be based on a review of progress, and for the CoFAR SACCC, evaluation will be based on achieving effective support of clinical trials and clinical studies and the DSMB. The Government, via the NIAID Program Official, will 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.

2.A.3. Collaborative Responsibilities

A Consortium Steering Committee will serve as the governing board for CoFAR. All participants in CoFAR are bound by the policies and procedures developed by the Steering Committee; adoption of such policies and procedures requires a majority vote.  Awardees under this FOA will be required to accept and implement policies approved by the Consortium Steering Committee.

Membership in the Consortium Steering Committee will include the PI(s) of each CoFAR U19 award, each CoFAR U01 award, the PI of the CoFAR SACCC, and the NIH Project Scientist.  Neither the PI of the CoFAR SACCC or the NIH Project Scientist may shall serve as the Chair of the Consortium Steering Committee.  The Steering Committee meetings will be organized by the Chair of the Steering Committee.  Each member of the Steering Committee will have one vote.

Steering Committee responsibilities will include: development of a scientific agenda for CoFAR; approval of study protocols prior to their implementation (study protocols implemented CoFAR may differ from the clinical studies proposed by the awardees in response to this RFA); and development of policies and procedures governing the activities of CoFAR, including but not limited to ongoing evaluation of site performance, presentation and publication of study findings, evaluation of new proposed studies, addition of new clinical sites, and management of conflicts of interest. The Steering Committee will meet twice per year in Bethesda, MD.

2.A.4. Arbitration Process

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

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

Section VII. Agency Contacts


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

1. Scientific/Research Contacts:

Marshall Plaut, M.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Room 3069, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: 301-435-4425
FAX:  301-402-0175
Email: mplaut@niaid.nih.gov

2. Peer Review Contacts:

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 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Phone:  301-435-9369
Fax:  301-480-2310
Email: 
pmehrotra@niaid.nih.gov

3. Financial or Grants Management Contacts:

Devon Bumbray-Quarles
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2253, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Telephone:  301-402-6213
FAX:  301-493-0597
Email: DBumbray@niaid.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 (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

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

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

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

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

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 new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

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

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

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

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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


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