RELEASE DATE:  December 11, 2003

RFA Number:  RFA-AI-04-002 (This RFA has been reissued, see RFA-AI-05-022)

Department of Health and Human Services (DHHS)  

National Institutes of Health (NIH) 

National Institute of Allergy and Infectious Diseases (NIAID) 

No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research



o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations


The purpose of this RFA is to solicit applications from single institutions or 
consortia of institutions to establish cooperative interdisciplinary research 
programs for large-scale, broad-scope genomic studies in clinical 
transplantation, including solid organ, tissue, and cell transplantation.  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) delineate immune responses relating to the onset 
and severity of acute and chronic graft rejection; (3) predict responses to 
immunosuppressive therapeutics to allow tailoring of therapy; and (4) 
elucidate the genetic basis of variability in graft survival between 
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 the development of more 
effective treatment and prevention strategies to improve long-term graft 
survival and provide a better quality-of-life for transplant recipients. 


Transplantation is the preferred therapy for the majority of end-stage organ 
diseases, and, in 2002, almost 25,000 organ transplants were performed in the 
United States.  One-year graft and patient survival rates have improved 
dramatically during the past 15 years, and approach 90% for many organs.  A 
major factor contributing to this short-term improvement is the development of 
more efficacious immunosuppressive agents that prevent or treat acute 
rejection.  However, long-term graft survival has not improved appreciably 
since the early 1980s, due, in large part, to a poor understanding of the 
mechanisms of chronic graft failure.  

Improving transplantation outcomes requires a greater understanding of the 
genetic basis of the immune response to organ and tissue allografts.  Decades 
of research focused on the extraordinary genetic polymorphism of the major 
histocompatibility complex (MHC) and its role in graft survival have 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 (TNF-alpha, TGF-beta, 
IFN-gamma, lymphotoxin, IL-1, IL-4, IL-6 and IL-10), adhesion molecules (ICAM-
1, L-selectin, and E-selectin), and co-stimulatory/regulatory molecules (B7 
and CTLA-4).  Similarly, the efficacy and toxicity of immunosuppressive agents 
such as steroids and Tacrolimus in some transplant patients have correlated 
with polymorphisms in the multidrug resistance gene (MDR1).  Genetic 
variations between genders and races may also influence transplantation 
outcomes.  A recent review of transplants performed worldwide indicated 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, the three-year 
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, which 
lead to higher production of inflammatory cytokines and increased expression 
of costimulatory molecules compared to Caucasians.  Overall, studies 
delineating the contributions of gene polymorphisms or gene expression 
variation in transplantation outcomes have been relatively few and limited in 
scope.  Large-scale, broad-scope studies of gene polymorphisms and expression 
in donor organs and recipients will help elucidate the genetic basis of immune 
response differences and risk factors, such as gender and race, that result in 
acute and chronic graft rejection.  In addition, these studies should lead to 
the development of safer and more efficacious immunosuppressive therapies.  

During the past decade, genomic research has benefited from significant 
technological advances in measuring and identifying gene expression, and in 
determining genotypes, single nucleotide polymorphisms (SNPs), microsatellite 
polymorphisms, and SNP haplotypes.  In addition, the initial sequencing of the 
human genome has created new opportunities and challenges to apply these 
technologies to decipher the biological significance of genes, gene 
expression, and polymorphisms as they relate to human diseases, including the 
clinical outcomes of organ and cell transplantation.  Furthermore, knowledge 
gained through the International HapMap Project 
(, which is charting genetic variations within 
the human genome that contribute to many diseases, will inform efforts in 
transplantation genomics.  Recently, researchers have also made tremendous 
advances in SNP and microsatellite polymorphism discovery within immune 
response genes, underscoring the timeliness of undertaking larger, targeted 
efforts in transplantation genomics.  

In May 2003, NIAID convened a multidisciplinary Expert Panel on the genomics 
of transplantation to discuss the state-of-the-science in complex-trait 
disease genomics, identify areas of research emphasis, and identify gaps in 
knowledge and scientific opportunities to fill these gaps. This RFA is based, 
in part, on the Panel’s recommendations and will initiate a cooperative 
research program, which may be expanded in future years, to apply genomics 
research to critical scientific questions in organ, tissue, and/or cell 
transplantation. Understanding the mechanisms of graft rejection and responses 
to therapy should allow prediction of outcomes and thus have a major impact on 
the development of new immunosuppressive therapeutics and tailoring of 
existing therapeutic strategies.  In addition, these studies should facilitate 
identification of genetic markers to be used as diagnostic and prognostic 


This RFA will initiate the establishment of a cooperative research program in 
transplantation genomics, supporting collaborative multidisciplinary teams 
with expertise in various disciplines, including transplantation medicine, 
genetics, immunology, molecular biology, pharmacogenomics, biostatistics, and 
bioinformatics.  This RFA calls for the use of recipient and donor samples, as 
well as clinical data, for 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 in response to immunosuppressive 
therapeutics; and/or (3) the identification of SNPs, SNP haplotypes, or 
microsatellite polymorphisms that correlate with and/or predict differences in 
transplant outcomes in individuals due to race or gender.  The primary 
research focus must be transplantation genomics.  However, a minor proteomics 
component, if an integral part of the proposed genomics studies, may be 
included.  Development or optimization of bioinformatics and statistical tools 
will be necessary to: (1) facilitate sharing of data among investigators; (2) 
analyze multi-dimensional genomic data with clinical data; and (3) evaluate 
multigenic and varied therapeutic effects, particularly given the challenges 
due to the limited numbers and heterogeneous character of the patients and 
patient groups.  Clinical trials of interventional agents or strategies, or 
interventional or observational clinical studies associated with the proposed 
genomic studies must have independent financial support and will not be 
supported under this RFA.  Proposed mechanistic studies associated with 
clinical trials supported by industry are particularly encouraged, but 
clinical trials supported by any source, public or private, are eligible.

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

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

This RFA will not support:

o  Clinical trials, interventional or observational clinical studies. However, 
applicants may request support for clinical procedures to obtain patient 
samples provided that these procedures are justified and not included in 
associated clinical trial;
o  Studies investigating the effects of HLA disparities between recipients and 
donors; or
o  Hematopoietic stem cell transplantation (HSCT) studies, including HSCT 
engraftment, unless HSCT is a component of organ or non-hematopoietic tissue 
transplantation, or the focus of the genomics studies is graft-versus-host 
disease.  In addition, genomic studies of anti-tumor responses in HSCT are not 
within the scope of this RFA.


This RFA will use the NIH cooperative agreement (U01) and/or the NIH multi-
project cooperative agreement (U19), "assistance" mechanisms, rather than 
"acquisition" mechanisms. The applicant will be solely responsible for 
planning, directing, and executing the proposed project. This RFA is a one-
time solicitation. Future unsolicited, competing-continuation applications 
based on this project will compete with all investigator-initiated 
applications and will be reviewed according to the customary peer review 
procedures. The anticipated award date is September 1, 2004. Applications that 
are not funded in the competition described in this RFA may be resubmitted as 
NEW investigator-initiated applications using the standard receipt dates for 
NEW applications described in the instructions to the PHS 398 application.

The NIH U01 and U19 are cooperative agreements award mechanism in which the 
Principal Investigator 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 "Cooperative Agreement Terms and Conditions of 

Essential elements of the multi-project cooperative agreement mechanism (U19) 
include: 1) a minimum of two interrelated individual research projects 
organized around a central theme; 2) collaborative efforts and interaction 
among independent projects and their investigators to achieve a common goal; 
3) a single principal investigator who will be scientifically and 
administratively responsible for the group effort; 4) a single applicant 
institution that will be legally and financially responsible for the use and 
disposition of funds awarded; and 5) where necessary, support for “core” 
resources or facilities, each of which shall be utilized by at least two 
research projects in order to facilitate the research effort.

The total project period for applications submitted in response to this RFA 
may not exceed five years.

Applicants for U19 grants must follow special application guidelines in the 
AWARDS; this brochure is available via the WWW at:  


The NIAID, intends to commit approximately $2,000,000 in FY 2004 to fund 1 to 
3 new cooperative agreements in response to this RFA. An applicant may request 
a project period of up to five years.  Because the nature and scope of the 
proposed research will vary from application to application, it is anticipated 
that the size and duration of each award will also vary.  Although the 
financial plans of the NIAID provide support for this program, awards pursuant 
to this RFA are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.  

At this time, the NIAID has not determined whether or how this solicitation 
will be continued beyond the present RFA.


The applicant may submit (an) application(s) if the institution has any of the 
following characteristics: 

o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign institutions/organizations


Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to develop 
an application for support. Individuals from underrepresented racial and 
ethnic groups as well as individuals with disabilities are always encouraged 
to apply for NIH programs.


Applicants are encouraged to contact NIAID Program staff well in advance of 
the application submission date to discuss the proposed research program. This 
contact allows staff to assess responsiveness to this RFA and provide 
appropriate guidance as needed.

1.  Description of Research Projects

Applications must propose clear research plan(s) and project goal(s) to be 
completed during the award period.  The applicant must clearly state the 
interim objectives 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.  The application 
must also demonstrate the scientific and technical expertise required to 
design, conduct and analyze mechanistic studies responsive to this RFA.

2.  Development of a Productive Collaborative Program

Each U01 or U19 application must demonstrate the organization’s ability to 
participate effectively in the NIAID Genomics of Transplantation Cooperative 
Research Program.  The application must include a written commitment to: 
participate in the NIAID Genomics of Transplantation Cooperative Research 
Program; 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 “Cooperative Agreement 
Terms and Conditions of Award: NIH Staff Responsibilities.”

For a U19 multi-project cooperative agreement, the application must provide: a 
clear and concise plan, in narrative and diagrammatic form, that depicts the 
interrelationships among the research groups, their relevant 
experience/expertise, and the contribution of each to fulfillment of the 
objectives of this RFA; an organizational chart of the U19 cooperative group 
showing the name, organization, and scientific discipline of the PI and of all 
key scientific and technical personnel. If the application is from a 
consortium of institutions, the applicant must provide a plan to assure the 
maintenance of close cooperation and effective communication among members of 
the U19 cooperative group. 

For U01 and U19 cooperative agreements, the application must provide a clear 
and concise research plan demonstrating a multi-disciplinary approach 
including, but not necessarily limited to, expertise in transplantation 
research, genomics, and biostatistics/bioinformatics.

3.  Studies with Human Samples

Although clinical trials will not be supported under this RFA, human samples 
and clinical data will be utilized in the research supported by this program.  
Research samples may be derived from ongoing clinical trials or completed 
clinical trials in which samples were maintained for the expressed purpose of 
future genetic research.  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.  Applications should 
address plans for human subjects, including definition(s) of the 
population(s), plans for recruitment and retention; informed consent forms 
(including describing descriptions of plans for subject confidentiality, 
deposition of information into a database, and follow-up with participants); 
plans for stored or shared samples (and the prior informed consents permitting 
this); or use of any established sample sets. It is highly recommended that 
proposed consent forms for the genomics studies have clear language that (1) 
distinguishes mechanistic studies from the clinical trials with which they may 
be linked; (2) clarifies and ensures that subjects can refuse to participate 
in the mechanistic genomics study and still participate in the clinical trial; 
and (3) stipulates that there will be no charges to the subjects for the 
additional studies.  Any incentives provided to subjects to participate in the 
mechanistic studies (if in addition to those under the clinical trial or 
study) should be clearly described and justified.

Applications must include documentation of the ability to acquire human 
samples and clinical data for the proposed studies.  The NIH brochure entitled 
"Research on Human Specimens: Are You Conducting Research Using Human 
Subjects?" may also be of use to applicants 
(  OHRP guidance on Repositories, 
Tissue Storage Activities and Data Banks should also be considered

IRB approval of the consent form(s) is not required at the time of submission 
of the application. However, at a minimum, a draft of the consent form to be 
used for the genomics studies must be included, as well as the consent form 
for the associated clinical trial, if different.

4.  Establishment of Database

Applications must include proposed plans for data management including: data 
access by investigators participating in the project; data analysis; 
statistical/bioinformatics support; and where applicable, establishment of a 
database(s).  Timely release of data to the NIH-supported and/or public 
databases is expected in accordance with the guidelines set by the Steering 
Committee and the NIH data sharing policy available at:

5.  Statistical Considerations

Methods of data analysis and power calculations must be included.  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.  It is strongly recommended that a 
statistician be part of the research team and active in preparation of the 
proposal.  Documentation of the appropriate statistical expertise should also 
be included in the application where applicable.

6.  Studies with Associated Clinical Trials

The complete clinical protocol and informed consent form(s) for the associated 
clinical trial must be included with the application as an appendix.  While 
drafts of the consent forms at participating sites are not required, it would 
be useful to include them if they are available.  NIH will treat as 
confidential any scientific, pre-clinical, clinical, or formulation data and 
information that the sponsor deems to be proprietary and confidential.

In order to ensure coordination between the genomic studies and the associated 
clinical trial, the principal investigator and his or her academic 
institution, the sponsor(s) of the clinical trial (including drug companies, 
if applicable), and the IND sponsor, if not one of the above, must provide 
written agreements for the conduct of the proposed studies as presented in the 

7.  Steering Committee

The NIAID will establish a Steering Committee within 60 days of award to serve 
as the governing body of the Cooperative Research Program.  At a minimum, the 
Steering Committee will be composed of the U01/U19 Principal Investigators, a 
subproject investigator of U19 awards, and the NIAID Scientific Coordinator.  
Each member of the Steering Committee will have one vote.  The NIAID may 
identify and appoint an outside scientific advisory panel, of which up to two 
members will serve on the Steering Committee as non-voting members.  A 
Chairperson will be selected by the Steering Committee from among the non-
federal Committee members. Subcommittees of the Steering Committee may be 
established as necessary. The Steering Committee will meet two times annually 
in Bethesda, MD.  Proposed budgets should include funds to cover travel costs 
for these meetings.  Each Steering Committee member will be expected to 
participate in all meetings and activities, e.g., conference calls and special 
subcommittees as required.

8.  Memorandum of Understanding

Prior to award, the applicant must provide to the funding institute a 
memorandum of understanding signed by the applicant, an appropriate 
representative of the applicant institution, the principal investigator of the 
associated clinical trial, and an appropriate representative of the financial 
sponsor of the associated clinical trial, and IND holder if different.  This 
memorandum will indicate agreement and will outline the specifics of the 
agreement for the following areas: 1) data from the genomic studies (including 
ownership, analysis, access, and release), 2) access to the data from the 
associated clinical trial (how/when) that are needed to analyze the genomic 
studies, including procedures for prevention of unblinding of the parent 
trial, 3) documentation of quality assurance procedures for both the parent 
trial and the genomic studies, and documentation of Data Safety Monitoring 
procedures for the parent trial, especially for efficacy trials, 4) ownership 
of intellectual property developed during the genomic studies, and 5) 
publication of the results of the genomic studies.


The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator as well as the 
institutional official at the time of award.

These 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 part 74 and 92, and other HHS, PHS, and NIH Grant Administration 
policy statements.

Cooperative agreements are subject to the administrative requirements outlined 
in OMB circulars A-102 and A-110. All pertinent HHS, PHS, and NIH grant 
regulations, policies and procedures, with particular emphasis on PHS 
regulations at 42 CFR Part 52 and HHS regulations at 45 CFR Part 74, are 
applicable. These special terms and conditions pertaining to the scope and 
nature of the interaction between the NIAID and the investigators will be 
incorporated in the Notice of Grant Award. However, these terms will be in 
addition to, not in lieu of, the customary programmatic and financial 
negotiations that occur in the administration of cooperative agreements.

The administrative and funding instrument used for this program is the 
cooperative agreement (U01) or multiproject cooperative agreement (U19), an 
"assistance", rather than an "acquisition", mechanism, in which substantial 
NIH scientific and/or programmatic involvement with the awardee is anticipated 
during the performance of the activity. Under the cooperative agreement, the 
NIH purpose is to support and/or stimulate the recipient's activity by 
involvement in and otherwise working jointly with the award recipient in a 
partner role, but it is not to assume direction, prime responsibility, or a 
dominant role in the activity. Consistent with this concept, the dominant role 
and prime responsibility for the activity resides with the awardees for the 
project as a whole, although specific tasks and activities in carrying out the 
research will be shared among the awardees and the NIAID Scientific 
Coordinator through the Steering Committee.

1. Monitoring Clinical Studies

When clinical studies or trials are a component of the research proposed, 
NIAID policy requires that studies be monitored commensurate with the degree 
of potential risk to study subjects and the complexity of the study. AN 
UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is 
available at:
The full policy, including terms and conditions of award, is 
available at:

2. Awardee Rights and Responsibilities

Awardees will have primary responsibility for defining the research 
objectives, approaches and details of the projects within the guidelines of 
the RFA and for performing the scientific activity. Specifically, awardees 
have primary responsibility as described below.

The Principal Investigators will: determine and coordinate the project 
activities scientifically and administratively; set project goals and 
timelines to achieve the proposed goals; accept and implement common 
guidelines approved by the Steering Committee; submit data to NIH-supported 
and/or public databases in accordance with policies agreed upon and 
established by the Steering Committee and the NIH data sharing policy 
available at:; attend 
Steering Committee meetings and serve as a voting member of the Steering 
Committee; and participate in the cooperative nature of the group.  It is 
recognized that goals may require revision and re-negotiation during the 
course of the project period.  Release of each funding increment by NIAID will 
be based on an NIAID review of progress towards achieving the previously 
agreed upon research goals.  Awardees will retain custody of and have primary 
rights to the data developed under these awards, subject to Government rights 
of access consistent with current HHS, PHS, and NIH policies.

NIAID intends to support the peer-reviewed studies proposed in the awarded 
grant applications.  However, under special circumstances (e.g. duplicative or 
overlapping specific aims between two awardees), the Steering Committee will 
establish guidelines and review procedures, and will evaluate and determine 
opportunities for collaboration, redirection or modification of the peer-
reviewed or new projects when applicable and necessary. This policy is in 
keeping with the terms and conditions of the cooperative agreement mechanism.

The awardee will implement the approved memorandum of understanding that will 
indicate agreement and will outline the specifics of the agreement for the 
following areas: 1) data from the genomic studies (including ownership, 
analysis, access, and release), 2) access to the data from the associated 
clinical trial (how/when) that are needed to analyze the genomic studies, 
including procedures for prevention of unblinding of the parent trial, 3) 
documentation of quality assurance procedures for both the parent trial and 
the genomic studies, and documentation of Data Safety Monitoring procedures 
for the parent trial, especially for efficacy trials, 4) ownership of 
intellectual property developed during the genomic studies, and 5) publication 
of the results of the genomic studies.

3. Studies with Human Samples

Although clinical trials will not be supported under this RFA, human samples 
and clinical data will be utilized in the research supported by this program.  
The NIAID Program Director will facilitate compliance with NIH policies for 
monitoring activities commensurate with the degree of potential risk to human 
subjects.  The NIAID policy including terms and conditions of award is 
available at:  The NIH brochure 
entitled "Research on Human Specimens: Are You Conducting Research Using Human 
Subjects?" may also be of use to applicants 
OHRP guidance on Repositories, Tissue Storage Activities and Data Banks should 
also be considered

4. NIAID Staff Responsibilities

NIAID staff assistance will be provided by a Program Director from the 
Transplantation Basic Sciences Section, Transplantation Immunobiology Branch, 
Division of Allergy, Immunology and Transplantation (DAIT), who will serve as 
NIAID's Scientific Coordinator and will be a voting member of the Steering 
Committee. The NIAID Scientific Coordinator will have substantial 
scientific/programmatic involvement during the conduct of this activity 
through technical assistance, advice and coordination above and beyond normal 
program stewardship for grants, as described below.  

During performance of the award, the NIAID Scientific Coordinator, with 
assistance from other scientific program staff who are designated based on the 
research topic and their relevant expertise, may provide appropriate 
assistance, advice, and guidance by: participating in the design of the 
activities; advising in the selection of sources or resources; coordinating or 
participating in the collection and/or analysis of data; advising in 
management and technical performance; or participating in the preparation of 
publications.  However, the role of NIAID will be to facilitate and not to 
direct the activities. It is anticipated that decisions in all activities will 
be reached by consensus and the NIAID staff will be given the opportunity to 
offer input into this process. The manner of reaching this consensus and the 
final decision-making authority will rest with the Principal Investigator and 
the Steering Committee.

In addition, the NIAID Program Director will be responsible for normal 
programmatic monitoring and stewardship for the award.  Other appropriate 
NIAID program staff assistance will be coordinated by the Program Director.  
The NIAID Program Director will approve changes in proposed research 
objectives and redirection of research projects.  The NIAID reserves the right 
to terminate or curtail a study (or any individual award) in the event of (a) 
substantial shortfall in participant recruitment, follow-up, data reporting, 
quality control, or other major breach of the protocol; (b) substantive 
changes in the consensus protocol to which the NIAID does not agree; (c) 
reaching a major study endpoint substantially before schedule with persuasive 
statistical significance; or (d) human subject ethical issues that may dictate 
a premature termination.

An NIAID Program Director will be assigned to perform normal program 
stewardship responsibilities for this award.  The Program Director may serve 
as the Scientific Coordinator.

5.  Organizational Changes
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.

6. Collaborative Responsibilities

The Steering Committee

A Steering Committee will serve as the governing board of the cooperative 
group of researchers.  At a minimum, voting membership of the Steering 
Committee will include the NIAID Scientific Coordinator, each U01/U19 
Principal Investigator, one sub-project investigator from each U19 award, and 
selected scientists other than the awardees when additional expertise is 
required for committee breadth and balance. The Steering Committee will 
appoint additional members by majority vote.  In addition, the NIAID may 
appoint up to two members of an NIAID scientific advisory panel to the 
Steering Committee as non-voting members. Federal votes cannot exceed 25%.  
Awardee members of the Steering Committee will be required to accept and 
implement common guidelines and procedures approved by the Steering Committee.

The NIAID Scientific Coordinator will schedule the meetings of the Steering 
Committee and actively assist the Chair in developing the meeting agendas.  
The Committee will meet at least twice the first year and annually thereafter.  
At least one of the meetings in the first year and the annual meetings will be 
in Bethesda, MD.  Subcommittees may be established by the Steering Committee 
as necessary.  The NIAID Scientific Coordinator will ensure coordination of 
the Steering Committee’s activities and implementation of the group’s 

The Steering Committee or a designated subcommittee will prepare an annual 
report containing the following information: 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; data submitted to databases; and future plans.  The 
first such report will be submitted to the NIAID Scientific Coordinator not 
later than 13 months after the initial notice of award, and yearly thereafter.

The Steering Committee will:

o  Serve as the main governing board;
o  Evaluate progress of the transplantation genomics projects and provide 
guidance to investigators regarding study implementation and conduct;
o  Establish protocols and subcommittees for evaluation, review, 
recommendation and modification of peer-reviewed, new, or ongoing genomic 
studies from consortium members and/or new collaborators;
o  Establish standards for data collection, analysis, and data management;
o  Establish centralized data and statistical analysis cores as needed;
o  Review and provide recommendations for human subjects protection issues;
o  Consider the representative views of other researchers in the program;
o  Advise NIH on scientific opportunities, emerging needs, and impediments;
o  Ensure the timely release of data to the NIH supported and/or public 
o  Prepare Annual Reports; and
o  Develop guidelines for publication of collaborative project results

Cooperation with Other NIH-Sponsored Programs

In order to most efficiently utilize research resources and rapidly exchange 
scientific information to promote transplantation genomics objectives, it is 
anticipated that cooperation or opportunities to collaborate with other NIAID 
funded programs, such as the Cooperative Clinical Trial in Pediatric 
Transplantation, will be initiated in future years and will be coordinated and 
facilitated by the NIAID Program Director.

7. Arbitration

Any disagreement that may arise on scientific or programmatic matters (within 
the scope of the award), between award recipients and the NIAID may be brought 
to arbitration. An arbitration panel will be composed of three members - one 
selected by the Steering Committee (with the NIAID representation not voting) 
or by the individual awardee in the event of an individual disagreement, a 
second member selected by NIAID, and the third member selected by the two 
prior selected members. This special arbitration procedure in no way affects 
the awardee's right to appeal an adverse action that is otherwise appealable 
in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS 
regulation at 45 CFR Part 16.


We encourage inquiries concerning this RFA 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 

o Direct questions about scientific/research issues to:

Crystal Y. Koh, Ph.D.
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Room Number 3026, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-5598
FAX: (301) 480-0693

o Direct questions about peer review issues to:

Edward W. Schroder, Ph.D.
Chief, Microbiology and Immunology Review Branch
Scientific Review Program, DEA, NIAID, NIH, DHHS
6700-B Rockledge Drive MSC 7616
Bethesda, MD 20892-7616
Zip code for express couriers: 20817 
Phone:  301-435-8537
FAX: 301-402-2638

o Direct questions about financial or grants management matters to:

Ann Devine
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room number 2118, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone:  (301) 402-5601
FAX:  (301) 480-3780


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

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

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 NIAID staff to estimate the potential review workload and plan 
the review.

The letter of intent is to be sent by the date listed at the beginning of this 
document. The letter of intent should be sent to:

Edward W. Schroder, Ph.D.
Chief, Microbiology and Immunology Review Branch
Scientific Review Program, DEA, NIAID, NIH, DHHS
6700-B Rockledge Drive MSC 7616
Bethesda, MD 20892-7616
Zip code for express couriers: 20817 
Phone:  301-435-8537
FAX: 301-402-2638


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  Applications must have a DUN and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form.  The PHS 
398 document is available at in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 


It is highly recommended that the appropriate NIAID program contact be 
consulted before submitting the letter of intent and during the early stages 
of preparation of the application. (See program contact under INQUIRIES).

Applicants for U19 cooperative agreements must follow special application 
guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR 
MULTI-PROJECT AWARDS; this brochure is available from NIAID listed under 
INQUIRIES via the WWW at:

This brochure presents specific instructions for sections of the PHS 398 (rev. 
5/01) application form that should be completed differently than usual. For 
all other items in the application, follow the usual instructions in the PHS 

See the SPECIAL REQUIREMENTS section above for additional application 
requirements and instructions.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application. Type the RFA number on the label. Failure to use this label could 
result in delayed processing of the application such that it may not reach the 
review committee in time for review. In addition, the RFA title and number 
must be typed on line 2 of the face page of the application form and the YES 
box must be marked. The RFA label is also available at:

SENDING AN APPLICATION TO THE NIH: 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
Bethesda, MD 20817 (for express/courier service)

At the time of submission, two additional exact copies of the grant 
application and all five sets of any appendix material must be sent to:

Edward W. Schroder, Ph.D.
Chief, Microbiology and Immunology Review Branch
Scientific Review Program, DEA, NIAID, NIH, DHHS
6700-B Rockledge Drive MSC 7616
Bethesda, MD 20892-7616
Zip code for express couriers: 20817 

Applications that are not received as a single package on or before March 15, 
2004 or that do not conform to the instructions contained in PHS 398 (rev. 
5/01) Application Kit (as modified in, and superseded by, the NIAID BROCHURE 
judged non-responsive and will be returned to the applicant.

APPLICATION PROCESSING: Applications must be received by the application 
receipt date listed in the heading of this RFA. If an application is received 
after that date, it will be returned to the applicant without review.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA 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 an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA 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.

Concurrent submission of an R01 and a Component Project of a Multi-project 
Application: Current NIH policy permits a component research project of a 
multi-project grant application to be concurrently submitted as a traditional 
individual research project (R01) application. If, following review, both the 
multi-project application and the R01 application are found to be in the 
fundable range, the investigator must relinquish the R01 and will not have the 
option to withdraw from the multi-project grant. This is an NIH policy 
intended to preserve the scientific integrity of a multi-project grant, which 
may be seriously compromised if a strong component project(s) is removed from 
the program. Investigators wishing to participate in a multi-project grant 
must be aware of this policy before making a commitment to the Principal 
Investigator and awarding institution.


Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIAID.

Incomplete and/or non-responsive applications will be returned to the 
applicant without further consideration. Applications requesting support for 
clinical trials of interventional agents or strategies, as well as for 
interventional or observational clinical studies will be non-responsive and 
returned without review.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NIAID in accordance with the review criteria stated below. As part of the 
initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Allergy and 
Infectious Diseases Council


The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. In the 
written comments, reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals:

o Significance
o Approach
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application’s overall score, weighting them as appropriate 
for each application. The application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score. For example, an investigator may propose to 
carry out important work that by its nature is not innovative but is essential 
to move a field forward.

SIGNIFICANCE: Does this study address an important problem? If the aims of the 
application are achieved, how will scientific knowledge be advanced? What will 
be the effect of these studies on the concepts or methods that drive this 

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

INNOVATION: Does the project employ novel concepts, approaches or methods? Are 
the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

INVESTIGATOR: Is the investigator appropriately trained and well-suited to 
carry out this work? Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?

The general review criteria for U19 multi-project cooperative agreement 
applications are presented in the NIAID brochure entitled "INSTRUCTIONS FOR 

ADDITIONAL REVIEW CRITERIA: In addition, the following review criteria will be 
considered in the determination of scientific merit and priority score:

1.  Scientific merit of hypothesis-driven or discovery-based genomic studies 
that correlate with clinical outcomes.

2.  Adequacy of multidisciplinary approach to conduct synergistic, basic 
and/or applied research to achieve the goals of Genomics of Transplantation 
Cooperative Research Program.

3.  Technical and administrative feasibility of plans to conduct studies with 
human samples.

4.  Database and statistical considerations: adequacy of proposed methods of 
data analysis and power calculations, and proposed plans and personnel for 
data management including data access by investigators participating in the 
project, statistical/bioinformatics support, and where applicable, 
establishment of a database(s).

subjects and protections from research risk relating to their participation in 
the proposed research will be assessed. (See criteria included in the section 
on Federal Citations, below)

plans to include subjects from both genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the 
research. Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 

to be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.


SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct 
costs in any year of the proposed research are expected to include a data 
sharing plan in their application. The reasonableness of the data sharing plan 
or the rationale for not sharing research data will be assessed by the 
reviewers. However, reviewers will not factor the proposed data-sharing plan 
into the determination of scientific merit or priority score. (See 
instructions and URL to policy in the Federal Citations, below.)

BUDGET: The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.


Letter of Intent Receipt Date:     February 16, 2004
Application Receipt Date:          March 15, 2004
Scientific Peer Review Date:       June, 2004
Advisory Council Review:           August, 2004
Earliest Anticipated Start Date:   September, 2004


Award criteria that will be used to make award decisions include:

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Programmatic priorities


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.

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). The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the participants. 
(NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and 
Contracts, June 12, 1998:  

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $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. Investigators should seek 
guidance from their institutions, on issues related to institutional policies, 
local IRB rules, as well as local, state and Federal laws and regulations, 
including the Privacy Rule. Reviewers will consider the data sharing plan but 
will not factor the plan into the determination of the scientific merit or the 
priority score.

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 AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
a complete copy of the updated Guidelines are available at
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 

The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

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 that is available at

requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  
This policy announcement is in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at

Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public 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

Applicants may wish to place data collected under this RFA 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.

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). Those who must comply with the Privacy Rule (classified 
under the Rule as “covered entities”) must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
( 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

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to 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 RFA is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at 


This program is described in the Catalogue of Federal Domestic Assistance at in the following citations: No. 93.855, Immunology, 
Allergy, and Transplantation Research and No. 93.856, Microbiology and 
Infectious Diseases Research. Awards are made under authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and administered under NIH grants policies and Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92. This program is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.

The NIH Grants Policy Statement is available at This document includes general 
information about the grant application and review process; information on the 
terms and conditions that apply to NIH Grants and cooperative agreements; and 
a listing of pertinent offices and officials at the NIH.  All awards are 
subject to the terms and conditions, cost principles, and other considerations 
described in the NIH Grants Policy Statement. 

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

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
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