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

Title:  Genomics of Transplantation Cooperative Research Program (U01, U19)

Announcement Type
This is a reissue of RFA-AI-05-022.  

Request For Applications (RFA) Number:  RFA-AI-10-019

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

Key Dates
Release Date:  July 23, 2010
Letters of Intent Receipt Date: October 19, 2010
Application Receipt Date: November 19, 2010
Peer Review Date: March, 2011
Council Review Date: May, 2011
Earliest Anticipated Start Date: July, 2011
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/qa/revniaid.htm 
Expiration Date:  November 20, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute of Allergy and Infectious Diseases (NIAID) invites new or renewal applications from single institutions or consortia of institutions to participate in a cooperative interdisciplinary research program for large-scale, broad-scope genomic studies in clinical transplantation of solid organ, tissue, and cells. The goals of this program are to identify and characterize gene polymorphisms and gene expression patterns that: (1) correlate with and/or predict transplantation outcomes; (2) define immune responses relating to the onset and severity of acute and chronic graft rejection; (3) predict responses to immunosuppression to allow tailoring of therapy; and (4) elucidate the genetic basis of variability in graft survival between populations or individuals. The long-term goal of the program is to understand the genetic basis of immune-mediated graft rejection and differences in transplant outcomes to provide a rational basis for developing more effective treatments to improve long-term graft survival and provide a better quality-of-life for transplant patients.
• Mechanism of Support. This Funding Opportunity Announcement (FOA) will utilize the single project (U01), and multi-project (U19) Cooperative Agreement award mechanism.
• Funds Available and Anticipated Number of Awards. The NIAID anticipates that approximately $4 million total costs will be available in FY 2011 to fund two to four new or renewal U01 and/or U19 awards.
• Budget and Project Period. The total project period for an application submitted in response to this FOA may not exceed five years. Budgets for direct costs of up to $350,000 and $1,100,000 per year for U01 and U19 applications, respectively, may be requested. With appropriate justification, additional  funds of up to  a maximum of $700,000 in direct costs may be requested in any year in which observational clinical study enrollment and/or clinical samples/outcome data collections are proposed. It is anticipated that direct costs for the enrollment and /or samples/outcomes data collections will vary significantly among proposals and under most circumstances will be substantially less than $700,000.
• Application Research Strategy Length: In the U19 application, the Research Strategy sections of the Program Overview and each individual Research Project may not exceed 12 pages, and the Research Strategy section for the individual Cores, may not exceed 6 pages, including tables, graphs, figures, diagrams, and charts.  In the U01 application, the Research Strategy section may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts.  See Table of Page Limits
• 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 and individuals with disabilities are encouraged to apply for NIH support.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications. Applicants  may not submit more than two applications. An individual PD/PI may only submit one application as PD/PI or as part of a multiple PD/PI team. However, a PD/PI may serve as a collaborator on another U01/U19 application provided there is no scientific overlap with the application submitted as the PD/PI or as part of a multiple PD/PI team.
• Resubmissions.  Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications are permitted in response to this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
• Application Materials. 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(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
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

The National Institute of Allergy and Infectious Diseases (NIAID) invites new or renewal applications from institutions or consortia of institutions to participate in a cooperative interdisciplinary research program for large-scale, broad-scope genomic studies in clinical transplantation of solid organ, tissues, and cells.  The goals of this program are to identify and characterize gene polymorphisms and gene expression patterns that: (1) correlate with and/or predict transplantation outcomes; (2) define immune responses relating to onset and severity of acute and chronic graft rejection; (3) predict responses to immunosuppressive intervention to allow tailoring of therapy; and (4) elucidate the genetic basis of variation in graft survival between individuals and/or populations.  The long-term goal of the program is to understand the genetic basis of immune-mediated graft rejection and differences in transplant outcomes, and thereby provide a rational basis for development of more effective treatments, prevention strategies to improve long-term graft survival, and provide a better quality-of-life for transplant recipients.

Background

Transplantation is the preferred therapy for the majority of end-stage organ diseases.  Over the last ten years, 20,000-25,000 organ transplants were performed each year in the United States.  Over the past 15 years, one-year graft and patient survival rates have improved significantly due, in part, to development of more efficacious immunosuppression to prevent or treat acute rejection. However, long-term graft survival has not improved appreciably due to the inadequacy and toxic effects of immunosuppression regimens and a poor understanding of mechanisms of chronic graft failure.  Further research on the genetic basis of the immune response to organ and tissue allografts is required to advance our understanding of the underlying mechanisms of graft rejection and transplant associated morbidities.  Early genetic studies focused mainly on genetic polymorphism of the major histocompatibility complex (MHC) and its role in graft survival, and provided valuable insights into the relative risk for graft failure of MHC gene disparities between donors and recipients.  In recent years, investigators have also demonstrated intriguing associations between transplant outcomes and polymorphisms in a variety of genes encoding cytokines, chemokines and their receptors, and adhesion, co-stimulatory, and regulatory molecules.  Similarly, the efficacy and toxicity of immunosuppressive agents have correlated with polymorphisms in drug metabolizing enzymes.  Genetic variations between gender and race may also influence transplantation outcomes.  Some studies suggest that recipients of solid organs from female donors have poorer outcomes than recipients of organs from male donors.  Similarly, while one-year graft survival is equivalent for African-Americans and Caucasians, long-term graft survival rate is significantly lower for African-Americans.  In the few studies addressing this health disparity, adverse transplantation outcomes among African-Americans were correlated with certain gene polymorphisms that lead to higher production of inflammatory cytokines and altered metabolism/lower absorption of immunosuppressive therapeutics compared to Caucasians. Overcoming barriers to long-term graft and patient survival will require further genomic research to elucidate the genetic basis of immune response differences and risk factors that result in acute or chronic graft rejection. Ultimately, these studies will also lead to the development of safer and more efficacious immunosuppressive therapies. 

In the past decade, genomic research has been revolutionized by technological advances in genome sequencing and gene expression profiling that have improved accuracy, speed and cost effectiveness. Researchers have also made tremendous advances in single nucleotide polymorphism (SNP) discovery within the immune response genes that are associated with immune responses to infection or susceptibility to autoimmune diseases.  These advances underscore the timeliness of targeted studies in transplantation genomics. 

In 2004, the NIAID established the Genomics of Transplantation Cooperative Research Program (GTCRP) through a targeted solicitation (RFA-AI-04-002) for broad scope studies of gene polymorphisms and expression in transplant donors and recipients in order to capitalize on recent advances in the field of genomics.  The original program was expanded in 2006 through another solicitation (RFA–AI-05-022). The goal of the GTCRP is to apply genomics research to critical scientific questions in organ, tissue, and cell transplantation.  Studies funded under this Program have resulted in identification of novel genomic and proteogenomic biomarkers that predict early and late stage chronic allograft rejection.  In addition, investigators have uncovered novel putative genetic polymorphisms associated with pharmacokinetics and metabolism of immunosuppressive medications.  The current FOA will renew the GTCRP. A better understanding of the genetic basis of graft rejection and response to therapy should allow prediction of outcomes and thus have a major impact on the development of new therapeutics and patient-specific tailoring of existing immunosuppressive therapeutic regimens to improve efficacy and reduce drug toxicity.  In addition, these studies should lead to identification of genetic markers for use as diagnostic and prognostic tools.

Research Objectives

The Genomics of Transplantation Cooperative Research Program will support collaborative multidisciplinary teams with expertise in transplantation medicine, genetics, immunology, molecular biology, pharmacogenomics, biostatistics, and bioinformatics.  Under this FOA, applicants will propose research using  recipient and donor samples, coupled with clinical data, for hypothesis-driven or discovery-based and hypothesis-generating, large-scale, broad-scope, prospective and/or retrospective genomic studies in clinical transplantation.  The research focus may address: (1) the identification of unique immune response genes or gene expression patterns during acute and chronic graft rejection; (2) the identification of genetic variation that influences or determines the response to immunosuppressive therapeutics; and/or (3) the identification of SNPs, haplotypes, or microsatellite polymorphisms that correlate with and/or predict differences in transplant outcomes in individuals due to race, gender, or ethnicity.  The primary research focus must be transplantation genomics.  However, a minor proteomics, or epigenomics component, if an integral part of the proposed genomics studies, may be included as an aim or sub-aim of a U01 application or as a project or aim/sub-aim in a U19 application.  Application of rigorous statistical tools is expected to: (1) analyze multi-dimensional genomic data with clinical data; and (2) evaluate multigenic and varied therapeutic effects resulting from the limited numbers and the heterogeneous character of patients and patient groups. Applicants must provide: (1) plans for management of data at their own sites and, where applicable, establishment or refinement of a database; (2) statistical methods of data analysis and power calculations; and (3) interim and long-term objectives and milestones.

Applicants may propose to obtain clinical samples and data in several ways. Clinical samples and data may be derived from ongoing or completed clinical trials or observational studies in which samples are or were obtained for the expressed purpose of future genetic research or informed consent is obtained for these genomics studies. Alternatively, the applicant may propose to establish an observational clinical study to obtain clinical data and research samples. If establishment of an observational study is proposed, a part-time study coordinator must be included in the application.  Support for clinical procedures to obtain samples that are not part of an associated clinical trial or study (e.g., additional biopsies) must be clearly described and justified.  Regardless of the method used to obtain clinical specimens, studies serving as the source of specimens and/or data for GTCRP must be conducted in compliance with Good Clinical Practice (GCP) and the federal regulations governing human subjects research. Clinical trials or studies supported by any source, public or private, are eligible.

Examples of relevant research may include, but are not limited to the following areas:

• Determination of gene expression profiles of donor organs and recipients prior to transplantation, before clinical signs of rejection, and during acute and chronic rejection.
• Identification of unique SNPs, haplotypes, and microsatellite polymorphisms in both donors and recipients, and correlation of these genetic variations with responses to immunosuppressive therapy.
• Determination of gene polymorphisms and/or expression patterns associated with race, ethnicity, age, and/or gender in graft rejection and responses to immunosuppression.
• Identification of DNA sequence-mediated regulation of gene expression associated with graft survival or rejection.
• Development of noninvasive diagnostic/prognostic tests based on gene expression that will predict or confirm acute and/or chronic rejection.

This FOA will not support:

• Studies using animal models.
• Clinical trials or interventional clinical studies. However,  this FOA will support obtaining clinical samples and data, and clinical procedures to obtain samples provided these procedures are justified and not included in associated clinical trials.
• Studies investigating the effects of HLA disparities between recipients and donors.
• Hematopoietic stem cell transplantation (HSCT) studies, including HSCT engraftment, unless HSCT is a component of organ or non-hematopoietic tissue transplantation.  In addition, genomic studies of anti-tumor responses in HSCT are not within the scope of this FOA.

Applications not meeting these requirements will be considered non-responsive to this FOA and will not be reviewed.

Applicants are encouraged to contact NIAID Program staff, listed below under Section VII.1 Agency Contacts, well in advance of the application submission date to discuss the proposed research program.  This will allow staff to provide appropriate guidance as needed with regard to this initiative.  Discussion with Program staff does not guarantee funding of an application.

Additional Information for Multi-Project (U19) Applications

The description of the U19 should include a clear and concise plan that depicts the interrelationships among the research groups, the relevant experience/expertise and the contribution of each individual; an organizational chart of the U19 cooperative group showing the name, organization, and scientific discipline of the PD/PI (or multiple PDs/PIs) and of all key scientific and technical personnel. If the application is from a consortium of institutions, the applicant should provide a plan to assure the maintenance of close cooperation and effective communication among members of the U19 cooperative group.  An Administrative Core is required, however, Scientific Cores are not required, but may be proposed if essential to the execution of the research projects. 

Research Project: Applications for the U19 multi-project award mechanism must contain at least two individual research projects organized around a common theme or hypothesis, with demonstrated synergy among the research projects, administrative core and scientific cores (if proposed).

Administrative Core (Required): Each application should provide for an Administrative Core headed by the contact PD/PI of the application who is responsible for the overall management, communication, coordination and supervision of the Program. The description of the Administrative Core should include plans for oversight of the program; overall plans for the structure and roles of administrative staff; plans for collaborations and communications among the program PD/PIs, Project Leaders and Core Leaders; how fiscal and other resources will be prioritized, allocated and managed; and how research-related travel, publications, communication expenses and training will be budgeted.

Scientific Cores (Optional): If proposed, a scientific core must support at least two projects within the U19 application. A scientific core will be headed by a Scientific Core Leader and 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.

GTCRP Steering Committee

The GTCRP Steering Committee serves as the governing body of the GTCRP and is responsible for identifying scientific opportunities, emerging needs, and impediments; preparing group progress reports, when requested by the NIAID Project Scientist; and overseeing group collaborations whenever applicable.  The voting membership of the Steering Committee is comprised of one U01/U19 PD/PI from each U01 and U19 award, one additional U19 project leader from each U19 award, to be selected by the U19 PD(s)/PI(s), and the PD/PI of the NIAID Statistical and Clinical Coordinating Center for Organ Transplant Clinical Trials (SACCC). The NIAID Project Scientist serves as a non-voting member of the Steering Committee.  The Steering Committee will meet face-to-face within the first two months following award and at least once annually, thereafter.  Unless agreed to by the NIAID Project Scientist, annual meetings will be held in Bethesda, MD. Budget requests should include travel funds to attend Steering Committee meetings for the PD(s)/PI(s) and for one project leader for U19 projects. For more information about the Steering Committee composition and responsibilities, please see Section VI.2.A.3 “Collaborative Responsibilities”.

Collaboration with the NIAID Statistical and Clinical Coordinating Center for Organ Transplantation (SACCC)

NIAID recently awarded the Coordinating Center for Organ Transplant Clinical Trials under RFA-AI-09-015 to RhoFED.   The SACCC supports NIAID’s clinical studies in organ transplantation conducted by the following 18 NIAID-sponsored clinical networks:  the Clinical Trials in Organ Transplantation (CTOT) Consortium, the Clinical Trials in Organ Transplantation in Children (CTOT-C) Consortium and the Genomics of Transplantation Cooperative Research Program (GTCRP). The SACCC does not support the current GTCRP, and the SACCC support for the GTCRP activities will not begin until after awards are made under this renewal FOA. The SACCC will serve as a resource to GTCRP awardees and awardees will be required to collaborate with the SACCC based on the individual U01 or U19 research needs, e.g. collection and analysis of clinical outcome data, data validation, or tracking of adverse events.  The GTCRP Steering Committee will review the needs of GTCRP research projects and provide recommendations to the NIAID Project Scientist and the individual GTCRP PI regarding the optimum extent of collaborations with the SACCC. All sites participating in the GTCRP will be required to submit clinical and genomic data to a central study database maintained by the SACCC. The SACCC will have the capability to provide statistical expertise, data management, specimen tracking, and clinical site monitoring, and will work with NIAID staff to ensure that studies are conducted in compliance with Good Clinical Practice (GCP) and the federal regulations governing human subject’s research. The SACCC PI will be a voting member of the GTCRP Steering Committee. See Section VI. Award Administration Information, 2.A.3. Collaborative Responsibilities, Collaboration with the NIAID Statistical and Clinical Coordinating Center for Organ Transplantation (SACCC) for more information about services the SACCC may provide, where appropriate.

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 U01 (single project) and U19 (multi-project) cooperative agreement  award mechanisms.  The Project Director/Principal Investigator (PD/PI) 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 funding opportunity will use 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

• The NIAID anticipates that approximately $4.0 million in total costs will be available in FY 2011 to fund two to four new and/or renewal applications in response to this FOA.  Future year amounts will depend on annual appropriations.
• Budgets for direct costs of up to $350,000 and $1.1 million per year for U01 and U19 applications, respectively, may be requested. With appropriate justification, additional  funds of up to a maximum of $700,000 in direct costs may be requested in any year in which observational clinical study enrollment and/or clinical samples/outcome data collections are proposed. It is anticipated that direct costs for the enrollment and /or samples/outcomes data collections will vary significantly between proposals and under most circumstances will be substantially less than the maximum amount.
• Although the financial plan of the NIAID provides support for this program, awards pursuant to this FOA are contingent upon the availability of funds and receipt of a sufficient number of meritorious applications.
• At this time, it is not known if this FOA will be reissued.

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.

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
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

Foreign institutions/organizations are not eligible to apply as the primary applicant but may enter into a consortium that has a domestic institution as the primary applicant (U01 or U19).

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI 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 program support.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://grants.nih.gov/grants/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.

Multiple PDs/PIs may be designated on the primary U01 or U19 application.  However, only one Project Leader (PL) or Core Leader (CL) may be designated for each project or core, respectively, for multi-project U19 applications.

A PD/PI, or PD/PI on a multi-PI application, U19 Project Leader or U19 Core Leader may serve as a collaborator for another application provided there is no scientific overlap with the application submitted by the PD/PI, multi-PD/PI, U19 Project Leader  or U19 Core Leader.  However, an investigator may be a PD/PI, multi-PD/PI, U19 Project Leader, or U19 Core Leader on only one application.

The PD/PI is expected to commit substantial time and effort to ensure success of the program. A minimum effort of 1.8 calendar months for a U01 or U19 PD/PI or multiple PD/PI; and a minimum effort of 1.2 calendar months for a U19 Project Leader is expected.

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 not submit more than two applications.An investigator may only submit one application as PD/PI, multiple PD/PI, U19 Project Leader, or U19 Core Leader, but may serve as a collaborator on another U01/U19 application provided there is no scientific overlap with the application submitted as the PD/PI, multiple PD/PI, U19 Project Leader, or U19 Core Leader.

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 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: [email protected].

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 and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

The exceptions from the PHS 398 instructions and detailed information on the application structure and components are provided in Section IV.6 “Other Submission Requirements”.  All applicants must follow the specific instructions in that section.

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.

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, 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

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 19, 2010
Application Receipt Date: November 19, 2010
Peer Review Date: March, 2011
Council Review Date: May, 2011
Earliest Anticipated Start Date: July, 2011

3.A.1. Letter of Intent

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

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

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

The letter of intent is to be sent by the date listed 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
For Express Couriers: 20817-1824
Telephone:  (301) 435-9369 
FAX:      (301) 480-2408
Email:   [email protected]

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
For Express Couriers: 20817-1824
Phone:  (301) 435-9369 
Fax:      (301) 480-2408
Email:   [email protected]

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/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements

Each U01 or U19 application must address the following three additional issues within their application: 

A. Studies with Human Samples

Applicants may propose to obtain clinical samples and data  in several ways as described under the Research Objectives.  Instructions in the PHS398 “Part II Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan” should be closely followed.  

If establishment of an observational study is proposed, a part-time study coordinator must be included in the application.  In addition, applicants proposing their own observational clinical study must include a Clinical Protocol Synopsis.  The Clinical Protocol Synopsis should be included at the end of the Human Subjects section, 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 used for obtaining informed consent and, if applicable, assent;
• approaches 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;
• 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;
• deposition of information into a database, and follow-up with participants;
• current and future plans for stored or shared samples (and the prior informed consents permitting this) or use of any established sample sets; and
• documentation of the ability to acquire human samples and clinical data for the proposed studies.

Complete Clinical Protocol: In addition, if proposed clinical samples and data are obtained from an independently-funded clinical trial or study, the complete clinical protocol and informed consent form(s) for the associated clinical trial or study must be included with the application.  This information should be included immediately after the Research Plan section of the application, prior to the checklist. There are no specific page limits for this section, but applicants are encouraged to be brief. 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).  The PD/PI of the clinical study or trial as well as his or her academic institution and the financial and regulatory sponsors (i.e., the IND holder) must provide written confirmation of their commitment to provide the specimens and/or data specified in the application.

Applicants may find the following information useful in the preparation of the application: The NIH brochure entitled "Research on Human Specimens: Are You Conducting Research Using Human Subjects?" and  OHRP guidance on Repositories, Tissue Storage Activities and Data Banks http://www.hhs.gov/ohrp/humansubjects/guidance/reposit.htm.  

Note: If an application includes a foreign component, the applicant must address provisions for meeting the country-specific requirements for sharing of clinical specimens and data, and other related logistic issues. This information will be requested by NIAID after application submission using the Just-in-Time procedure.  Applicants do not need to submit this information within their application at the time of submission.   

B. Data Management and Statistical Considerations

Applicants must include plans for management of data at their own sites and, where applicable, establishment or refinement of their database; in addition, applicants must provide a statistical plan including methods of data analysis and power calculations. Include a justification for the required sample size. A restatement of the sample size calculations from an associated clinical trial is insufficient.  Applications must describe the statistical procedures that will be used to analyze the data.  If appropriate to your application, discuss whether it is necessary to perform the genomic studies on all subjects enrolled in the parent trial or whether a sample would be sufficient.  A statistician must be part of the research team and active in preparation of the proposal.  Following award, all statistical plans and data management plans will be reviewed by the NIAID Statistical and Clinical Coordinating Center for Organ Transplantation (SACCC), which may make recommendations for alterations of the plans.  The data management and analysis plan should be included within the page limits of the Research Strategy section.

C. Milestones and Timelines

In a chart or table, applicants should clearly state the interim and long-term objectives and milestones to be achieved during the project, identify impediments or critical decision points that could require a revision in the work plan, and provide a detailed timeline for the attainment of each goal and milestone. This information should be labeled accordingly and located in the Approach section within the page limits of the Research Strategy section of the application.

Supplemental Instruction for the Preparation of Multi-Project (U19) 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 project 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 below are divided as follows:

A. General Instructions – addresses 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 – describes 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 – Describes 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 Form PHS 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.

When multiple PDs/PIs are proposed, use the Face Page-Continued page to provide items 3a-3h for all PDs/PIs.  The Contact PI should be listed on block 3 of Form Page 1-Face Page, with additional PDs/PIs listed on the Face Page-Continued.

2. Form Page 2

Using Page 2 of Form 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 PD(s)/PI(s) of the multi-project application, followed by the Project and Core Leaders of the component research projects and cores, and 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 project by project and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to 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 PHS Form 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. Detailed budgets are required within the descriptions of each project and core (see below).  If the FOA allows for budget requests beyond 5 years, use a second Form Page 5 to reflect the additional budget years requested. 

6. Biographical Sketch Format Page

Biographical sketches of all Senior/key Personnel and Other Significant Contributors for all components should be placed at the end of the application with the PI(s)/PD(s) 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)

Specific Aims (Limited to 1 page.)

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.

Research Objectives and Strategic Plan (Limited to 12 pages.)

This narrative section summarizes the overall research plan for the multi-project application and is limited to 12 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.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5.  Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information.  Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy.  Preliminary Studies for new projects and progress reports for renewal projects as part of a renewal or revision application must be included as part of the approach section.

If the application is a renewal, provide a Progress Report as part of the Approach section  within the Program Overview (Research Objectives and Strategic Plan) of the application that highlights past performance and the major accomplishments from the funding period since the last competitive review as described in the PHS 398 Instructions.  Summarize the importance of the findings, and emphasize the progress made toward achievement of the specific aims of the program. In addition to discussing results from individual research projects and cores, describe the synergy and collaborations that occurred within the Program. 

9.  Leadership Plan for Multiple PDs/PIs (required if applicable)

Applications designating multiple PDs/PIs for the overall Program must include a new section, entitled “Multiple PD/PI Leadership Plan”, as part of the Program Overview.  This Plan must describe: a rationale for choosing a multiple PD/PI approach; the governance and organizational structure of the leadership team and the research projects and cores; communication plans, processes for making decisions on scientific direction, and procedures for resolving conflicts; the administrative, technical, and scientific roles and responsibilities 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 also be delineated.  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. “Appendix Materials” below, for instructions on submitting appendix materials.

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

B. Specific Instructions for Individual Research Projects

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each research project.

For each individual Research Project, include:

Cover page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Research Plan

Resources

1. Cover Page

The Face Page of the 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: (mmddyy - e.g., 07/01/2007)

To: (mmddyy - 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: (e.g., $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 PHS Form 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 Project Leader, followed by other key project 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. Individual Research Project Research Plan

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the individual research project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual research project's relationship to the multi-project program goals and how it relates to other individual research projects or cores.

Research Strategy (Limited to 12 pages.)

Use this section to describe how the proposed individual research project 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 individual research project's relevance to the primary theme of the application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5.3.  Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information.  Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. 

If the individual research project is a renewal, provide a Progress Report within the Approach section.

If the individual research project is new, provide Preliminary Studies within the Approach section.

6. Resources

Provide information on resources available for the project.  Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.)  For Early Stage Investigators, describe institutional investment in the success of the investigator.  If there are multiple performance sites, describe the resources available at each site.  Describe any special facilities used for working with biohazards or other potentially dangerous substances.

7. 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).

C. Specific Instructions for Core(s)

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each proposed core.

For each individual Core, include:

Cover page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Research Plan

Resources Format Page

1. Cover Page.  The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application.  Instead, use the 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 (which are a subset of the information provided on a Face Page - see PHS 398):

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., 5/14/06, or Pending), and Federalwide Assurance (FWA) number

Vertebrate Animals (Yes or No)

If Yes,

IACUC Approval Date (e.g., 4/15/07, or Pending), and Animal welfare assurance number

Proposed Period of Support

From: (mmddyy, e.g., 07/01/2007)

To: (mmddyy, e.g., 06/30/2012)

Costs Requested for Initial Budget Period

Direct Costs (e.g. $50,000)

Total Costs (e.g. $70,000)

Costs Requested for the Entire Budget Period

Direct Costs (e.g. $212,323)

Total Costs (e.g. $297,252)

Applicant Organization (ABC University; 111 Main Street; Anywhere, Else 99999)

The following are specific instructions for sections of the PHS 398 application form that are to be completed differently than usual.  For all other items in the core application, follow the usual PHS 398 instructions.

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 core activities and services will be conducted.

Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

3. Form Page 3.  Prepare a Table of Contents for the core using page 3 of Form 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. Core Research Plan

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed core. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the core’s relationship to the multi-project program goals and how it relates to the individual research projects or other cores in the application.

Research Strategy (Limited to 6 pages.)

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 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.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5.3.  Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information.  Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. 

If the core is a renewal, provide a Progress Report within the Approach section.

If the core is new, provide Preliminary Studies within the Approach section.

6. Resources

Provide information on resources available for the core.  Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.)  For Early Stage Investigators, describe institutional investment in the success of the investigator.  If there are multiple performance sites, describe the resources available at each site.  Describe any special facilities used for working with biohazards or other potentially dangerous substances.

7. 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).

See Section IV.2, “Content and Form of Application Submission” and additional text above for page limitations associated with multi-project applications.

PHS398 Research Plan Sections

All application instructions outlined in the PHS398 Application Instructions are to be followed, with the following additional requirements:

• Specific Aims is limited to 1 page.
• Research Strategy for U19 applications in the Program Overview (Research Objectives and Strategic Plan) and Research Projects is limited to 12 pages and for the Cores is limited to 6 pages, including tables, graphs, figures, diagrams, and charts.
• Research Strategy for U01 applications, 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). 

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.

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 should 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/.

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 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:

• 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/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 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 the aims are achieved, could the results be applied to diagnosis, treatment, or prevention of immune–mediated graft rejection and contribute to long-term graft survival?

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? Is the level of effort of the PD/PI or U19 Project Leader sufficient to ensure success of the program?  Is there adequate scientific and technical expertise related to design, conduct, analysis, and interpretation of Genomic/Proteomic outcomes from  transplantation studies? If proposed, is the study coordinator sufficiently experienced in the execution of clinical studies of this nature and size proposed?

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?  Are the source and procedures for the collection of clinical samples or proposed biospecimens clearly described and are all the logistics and feasibility issues addressed and adequately justified??   Are there sufficient preliminary data to support the proposed research projects? Are the objectives and milestones clearly laid out for the project and are detailed timelines provided for the attainment of each goal? Are the data collection, management, and storage databases/resources adequate for the proposed studies?

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?

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?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/priority score.

Review Criteria for a (U19) Multi-Project Application

Overall Impact of the Multi-Project Application: Is the program as a whole scientifically compelling? Are there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the program?  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?  Does the PI/PD(s) have the leadership and scientific ability to develop an integrated and focused research program?  Will the PI/PD(s) and other Project/Core Leaders devote adequate time and effort to the program?  For renewal applications, what are the accomplishments and progress achieved during the prior funding period? Is there adequate evidence of sufficient institutional support for the PD/PI(s) in terms of laboratory space, equipment and other resources?  For applications designated multiple PDs/PIs, is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PDs/PIs?  Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate?  

Administrative Core: 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 program appropriate?  Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?  Is the experience, level of commitment, and availability of the administrative Core Leader and administrative staff adequate to manage the program? Are plans for communication among the member of the U19 adequate to facilitate collaborative activities?

Scientific Cores (if applicable):  Is provision of resources and core services for the individual 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?

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.  Vertebrate animal research is not applicable to this FOA.

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.  Resubmission applications not allowed in response  to this FOA.

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

Revision Applications.  Revision applications are not allowed in response to this FOA.

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.  Foreign organizations not allowed as primary applicant in response to this FOA.

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

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of the proposed project to program priorities
• Compliance with resource sharing policies

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.

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/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 to NIH Policy, NIAID has terms and conditions of awards involving human subjects research (http://funding.niaid.nih.gov/ncn/clinical/clinterm.htm).  Additional guidance is provided for the use of clinical samples, including Repositories, Tissue Storage, and Data Banks, by the Office for Protection from Research Risks (OPRR) (http://www.hhs.gov/ohrp/humansubjects/guidance/reposit.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 Principal Investigators (PD/PI) will have the primary responsibility for defining the research objectives,  approaches, and details of the projects within the guidelines of the FOA; setting project goals, milestones, and timelines to achieve the proposed goals and objectives; overseeing/performing the scientific activities; ensuring successful completion of milestones within the timeframe and budget proposed; cooperating with NIAID programmatic, technical, and administrative staff; and administratively managing the U19 or U01.

Each U01 and U19 will have one and two votes on the GTCRP Steering Committee, respectively.  Each PD/PI will attend Steering Committee meetings and serve as a voting member of the Steering Committee.  However, for grants with multi PDs/PIs, only one PD/PI will be a voting member per award, and for the initial year, the voting member will be the Contact PD/PI, but may rotate to another PD/PI in subsequent years to be determined by the multiple PDs/PIs of the award.  In addition, each U19 PD/PI will appoint one Project Leader from their U19 to be a voting member of the Steering Committee. The Project Leader voting membership may rotate among Project Leaders at the U19 PD/PI’s discretion.  The PDs/PIs will participate in all Steering Committee activities, attend Steering Committee meetings, and will follow the policies and procedures developed by the Steering Committee.  Other members of the U awards may serve as non-voting members as determined by the Steering Committee.  The PD/PI for the SACCC will serve as a voting member of the Steering Committee.

The PD/PIs of the U awards may be required by NIAID to collaborate with the NIAID Statistical and Clinical Coordinating Center (SACCC) based on the individual projects needs and Steering Committee recommendations.   Prior to award each PD/PI must provide official documentation of the organization’s ability to participate effectively in the GTCRP and the commitment of the PD/PIs to serve on the Steering Committee; adhere to the decisions reached by the Steering Committee; and accept the participation and assistance of NIH staff in accordance with the guidelines outlined under the “Cooperative Agreement Terms and Conditions of Award: NIH Staff Responsibilities”.

The PD/PI will be responsible for the timely submission for publication of manuscripts (co)authored by members of the grant and supported in part or in total under this agreement.  All publications resulting from work done in this consortium will be submitted to the Program Officer at least one week prior to journal submission and within two weeks of acceptance for publication so that an up-to-date summary of the cooperative program accomplishments can be maintained and NIAID press releases can be prepared, if applicable.  Publications or oral presentations of work performed under this agreement are the responsibility of the PD/PI and appropriate Project Leaders and require acknowledgement of NIAID support.  Timely publication of major findings is encouraged.

Awardees are expected to make new information and materials, including research samples, tools, methods, and data obtained under GTCRP grants known and available to the research community and other members of this Program in a timely manner through publications, web announcements, reports to NIAID, and/or other mechanisms, subject to the rights described below. In addition, the awardees are required to submit data obtained under this FOA support to NIAID/NIH -supported and/or public databases in accordance with policies agreed upon and established by the Steering Committee, the NIH data sharing policy available at http://grants.nih.gov/grants/policy/data_sharing/ , and submission of genome-wide association studies (GWAS) data as detailed below under Section VIII, Required Federal Citations.  Awardees may also be required to submit data to the NCBI database, dbGAP http://www.ncbi.nlm.nih.gov/gap.

Certain organizational changes require the prior written approval of the NIAID Program Director. These changes include the addition or replacement of an investigator, component, or research base that is associated with the studies. A change in the PI, or in any key personnel identified on the Notice of Award, must have the prior written approval of the NIAID Grants Management Specialist in consultation with the NIAID Program Director.

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

2. A.2. NIH Responsibilities

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

A program official from the NIAID Division of Allergy, Immunology and Transplantation (DAIT), will serve as NIAID's Project Scientist for this Program.  The NIAID Project Scientist will serve as facilitator of GTCRP activities and scientific endeavors and provide advice, technical assistance, and guidance on technical and management issues, such as subcommittee requirements.  The NIAID Project Scientist will serve as a liaison/facilitator in identifying potential resources, and identifying potential collaborations to further the goals of the GTCRP. The NIAID Project Scientist will also serve as resource of scientific and policy information related to the goals of the awardee’s research.  However, the role of the NIAID Project Scientist will be to facilitate and not to direct the GTCRP activities.

The NIAID Project Scientist will serve as a non-voting member of the Steering Committee and will ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.  It is anticipated that decisions in most Steering Committee activities will be reached by consensus and the NIAID Project Scientist will be given the opportunity to offer input into the process, but the manner of reaching this consensus and the primary decision making responsibility will rest with the Steering Committee

The NIAID Project Scientist will evaluate scientific overlap among successful applicants and the progress of individual projects.  Under special circumstances (e.g., duplicative or overlapping specific aims between two awardees) the NIAID Project Scientist may request modification of the peer-reviewed aims and/or may direct the Steering Committee to establish guidelines and review procedures for modification of the peer-reviewed aims.   

In addition, the NIAID Program Officer will be responsible for normal scientific and programmatic stewardship of the award and will be named in the Notice of  Award.  The assigned NIAID Program Officer may also serve as an NIAID Project Scientist.  This stewardship role will include monitoring program progress and approving changes.  The Government, via the NIAID Program Officer, 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.

Release of each annual funding increment by NIAID will be based on an NIAID review of progress towards achieving the previously agreed upon research goals, interim objectives, and milestones.  It is recognized that project goals may require revision and re-negotiation during the course of the project period.  The NIAID reserves the right to terminate or curtail a study (or any individual awards) in the event of a substantial shortfall in study milestones or other major breach of the approved project.

2.A.3. Collaborative Responsibilities

The Steering Committee

The GTCRP Steering Committee will serve as the governing board of this program.  Each U01 and U19 will have one and two votes, respectively.  At minimum voting membership of the Steering Committee will include each U01/U19 Principal Investigator, one additional individual Project Leader from each U19 award, to be named by the U19 PD/PI and which may be rotated to other U19 Project Leaders, at the discretion of the U19 PD/PI.  A single PD/PI from each multi-PD/PI grant award will serve as a voting member of the Steering Committee.  The SACCC PI will serve as a voting member of the Steering Committee. Selected scientists other than the awardees may serve as voting members when additional expertise is required for committee breadth and balance, to be determined by majority vote of the Steering Committee.  A Chairperson will be selected by the GTCRP Steering Committee voting members from among the voting Committee members.  Note that for purpose of this FOA, U19 Core Leaders are not considered Project Leaders. The GTCRP Steering Committee can appoint additional non-voting members by majority vote.  In addition, the NIAID Project Scientist may appoint two external scientists as Advisory Working Group (acting in a scientific advisory capacity to NIAID) to the Steering Committee as non-voting members. The NIAID Project Scientist will also serve as a non-voting member.

The SACCC will schedule the meetings of the GTCRP Steering Committee.  The NIAID Project Scientist will actively participate with the Chair in developing the meeting agenda.  The GTCRP Steering Committee will meet within two months of award and at least annually thereafter, usually in the Bethesda, MD area.  Additional meetings may be held via teleconferences.  Proposed budgets should include travel costs for the PI to attend these meetings.  Each Steering Committee member will be expected to participate in all meetings and activities, e.g. conference calls and special subcommittee as required. Awardee members of the GTCRP Steering Committee will be required to accept and implement common guidelines, policies, and procedures approved by the Steering Committee.  A letter from each PI stating compliance to all policies and guidelines established by the Steering Committee will be required prior to award. 

NIAID intends to support the peer-reviewed studies proposed in the awarded grant applications.  However, prior to implementation all studies will be evaluated by the Steering Committee for scientific overlap within the consortium, opportunities to optimize use of resources and harmonize technologies, and potential collaboration opportunities among the group. The Steering Committee will establish guidelines and review procedures for modification or redirection of the peer-reviewed projects based on the evaluation.  In addition, the NIAID Project Scientist will evaluate scientific overlap among successful applicants and under special circumstances (e.g., duplicative or overlapping specific aims between two awardees) may request modification of the peer-reviewed aims and/or may direct the Steering Committee to establish guidelines and review procedures for modification of the peer-reviewed aims.  These policies are in keeping with the terms and conditions of the cooperative agreement mechanism.

The Steering Committee will establish subcommittees to address the following: conflict of interest, publication policies, and data support and management.  Additional subcommittees will be established as needed. The GTCRP Steering Committee or a designated subcommittee will prepare a group progress report, when requested by the NIAID Project Scientist and generally at the completion of the second year of funding and either annually or biannually after the first report.  This progress report will, at minimum, contain the following information:  project overviews; group progress of ongoing and newly-initiated projects; manuscripts published, in press, and in preparation; presentations at regional, national, and international meetings; other activities of the group; and future plans.  The first such report will be submitted to the NIAID Project Scientist no later than four months after the NIAID Project Scientist requests a report, or a time agreed upon by the NIAID Program Official and the Steering Committee Chair. 

The Steering Committee will:

• Evaluate all peer-reviewed projects, prior to their implementation, for overlap and optimal collaboration.
• Establish goals for the GTCRP and Steering Committee guidelines and policies within three months of the initial Steering Committee meeting.
• Evaluate progress of the GTCRP projects and provide guidance to investigators regarding study implementation and conduct.
• Establish protocols and subcommittees for evaluation, recommendation, and modification of ongoing studies from cooperative group members.
• Establish standards for data collection, analysis, and data management, where applicable.
• Advise NIAID on scientific opportunities, emerging needs, and impediments.
• Prepare cumulative group progress reports.
• Establish collaborations, when appropriate, with NIAID clinical trials programs and establish guidelines for their conduct.
• Review the needs of the GTCRP research projects and the services available through the NIAID-sponsored SACCC.
• Provide recommendation for collaboration between the GTCRP and SACCC for individual and collaborative projects.
• Develop guidelines for publication of collaborative project results.

Collaboration with the NIAID Statistical and Clinical Coordinating Center for Organ Transplantation (SACCC)

The role of the NIAID SACCC is described in the Research Objectives.  Because of the complexity of the data involved in the GTCRP studies, each PI will work with the SACCC to develop a data management and analysis plan following award. The final data and analysis plans will be subject to NIAID review and approval.

Examples of the resources provided by the SACCC include the following, where appropriate:

• Provision of clinical study design and statistical expertise, including the performance of data analyses as specified by study protocols or as requested by the steering committee, the Data and  Safety Monitoring Board, or the NIAID Project Scientist;
• Development of a Statistical Analysis Plan for each consortium study. Plans for the analysis of high throughput data requiring complex analyses (e.g., microarray data and genomic data) will be the primary responsibility of the clinical study PIs. However, the data center will have the capability to provide assistance in development of statistical analysis plans and data management, including assistance with development of data dictionaries and definitions, and data reconciliation, and provision of clinical data sets for analysis;
• Establishment of reliable and efficient electronic systems, compliant with pertinent regulations of the FDA or other Health Authorities, for electronic data capture and management of data generated by clinical and  genomic studies;
• Development and implementation of policies and procedures for quality control of study data;
• Development of policies and procedures for quality assurance of clinical site performance, collection and tracking of regulatory/clinical documents, and performance of clinical site monitoring;
• Training of clinical sites for specific protocols and in standards of GCP;
• Preparation and distribution of protocol documents, manuals of procedures, and other materials necessary for implementation of studies;
• Preparation of reports as directed by the Steering Committee or NIAID Project Scientist, and participation in the preparation of scientific manuscripts;
• Tracking of fluid and tissue specimens for laboratory studies; and
• Support of regulatory activities including adverse event reporting and tracking, document preparation and delivery for regulatory requirements of domestic or foreign Health Authorities. These functions may be performed by the applicant organization or by subcontract to the applicant organization.

Cooperation with Other NIH-Sponsored Programs

In order to most efficiently utilize research resources and rapidly exchange scientific information to promote the GTCRP objectives, it is anticipated that cooperation or opportunities to collaborate with other NIAID funded programs, such as the Clinical Trials in Organ Transplantation (CTOT), the Clinical Trials in Organ Transplantation in Children (CTOTC), the Immune Tolerance Network (ITN), the HLA Genomics and Immune-Mediated Diseases, and  the Statistical and Clinical Coordinating Center (SACCC) will be initiated post award and will be coordinated and facilitated by the NIAID Program Official.

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 does not alter 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:

Nasrin Nabavi, Ph.D.
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Room number 6223, MSC 6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-5598
FAX: (301) 480-0693
Email: [email protected]

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
For Express Couriers: 20817-1824
Telephone:  (301) 435-9369 
FAX:      (301) 480-2408
Email:   [email protected]

3. Financial or Grants Management Contacts:

Maggie C. Wells
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2250, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 594-9847
FAX:    (301) 493-0597   
Email: [email protected]

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.

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/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-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 (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.