CLINICAL TRIALS IN ORGAN TRANSPLANTATION (CTOT)

RELEASE DATE:  December 9, 2003

RFA Number:  RFA-AI-04-003 (Reissued as RFA-AI-08-015)

Department of Health and Human Services (DHHS) 

PARTICIPATING ORGANIZATION: 
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Allergy and Infectious Diseases (NIAID) 
 (http://www.niaid.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
 (http://www.niddk.nih.gov)
National Heart, Lung and Blood Institute (NHLBI) 
 (http://www.nhlbi.nih.gov)  

CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:
No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research 
No. 93.849, Kidney Diseases, Urology and Hematology Research
No. 93.837, Heart and Vascular Diseases Research
No. 93.838, Lung Diseases Research
No. 93.839, Blood Diseases and Resources Research

LETTER OF INTENT RECEIPT DATE:  February 16, 2004
APPLICATION RECEIPT DATE:  March 15, 2004

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) 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

PURPOSE OF THIS RFA 

The Division of Allergy, Immunology, and Transplantation (DAIT) of the 
National Institute of Allergy and Infectious Diseases (NIAID), National 
Institutes of Health (NIH) invites applications from consortia of 2 or more 
institutions to participate in a clinical studies program of immune-mediated 
pathologic processes in organ transplantation. The purpose of this program is 
to support a cooperative, multi-site consortium for interventional or 
observational clinical studies, accompanied by mechanistic studies, to enhance 
our understanding of and ultimately reduce the immune-mediated morbidity and 
mortality of organ transplantation. These studies will be carried out in 
pediatric and adult candidates for and recipients of organ transplants as 
multi-center clinical trials that will (1) evaluate new therapeutic regimens 
to overcome immunologic barriers to graft acceptance and/or long-term graft 
and patient survival, (2) evaluate approaches to the treatment or prevention 
of immune-mediated complications of transplantation; (3) investigate the 
underlying mechanisms of action of the pathologic processes, agents or 
regimens under study; (4) develop diagnostic tests for and/or surrogate 
biomarkers that will facilitate routine surveillance, early diagnosis and 
ongoing monitoring of those processes that contribute to post-transplant 
morbidity and mortality.  Studies of hematopoietic stem cell transplantation 
(HSCT) are excluded, unless HSCT is a component of a study of organ 
transplantation. Studies of islet transplantation for treatment of type I 
diabetes are also excluded.

RESEARCH OBJECTIVES

Organ or tissue replacement is the treatment for end-stage organ failure when 
other therapies have failed or are not available, and when the person affected 
by organ failure is deemed likely to benefit from organ transplantation. The 
benefits of organ transplantation, as evidenced by prolonged survival and/or 
improved quality of life, have been clearly demonstrated for children and 
adults suffering from a wide range of congenital and acquired diseases. 
However, normal life expectancy and health-related quality of life are rarely, 
if ever, restored by organ transplantation. Although 1-year survival after 
organ transplantation has improved markedly over the last 15 years, there has 
been little success in reversing the decline in long-term graft and patient 
survival that is seen in recipients of any organ transplant, in whom the 
prevalence of morbidities such as systemic hypertension, diabetes mellitus, 
renal insufficiency, and malignancy remain high as compared with the general 
population.  The barriers to short and long-term success of transplant 
procedures are predominantly the result of incompatibility between donor and 
recipient, acute and chronic rejection, and complications of long-term 
pharmacologic immune suppression.

Responsive applications to this RFA will propose multi-center clinical trials 
and/or observational studies, with associated mechanistic studies, that will 
improve our understanding of and/or evaluate interventions to reduce the 
immune-mediated morbidity and mortality of organ transplantation.  Examples of 
conditions to be studied include, but are not limited to: 

1. Pre-existing immunologic barriers (such as anti-HLA antibodies or ABO 
incompatibility) to successful transplantation.

2. Chronic, progressive allograft destruction (e.g., allograft nephropathy, 
obliterative bronchiolitis) after organ transplantation.

3. Immunomodulatory interventions targeting innate immunity and/or 
autoimmunity in transplant donors or recipients. 

4. New, less toxic immunosuppressive agents or regimens, or innovative 
approaches to develop donor-specific tolerance.

5. Prevention or treatment of post-transplant lymphoproliferative disorder and 
malignancy.

6. Susceptibility to and prevention of the adverse consequences (e.g., 
nephropathy, systemic hypertension, diabetes mellitus, malignancy) of current 
post-transplant immunosuppressive regimens.

Proposals must include a plan for associated mechanistic studies. These 
mechanistic studies will be weighed equally with the clinical studies in the 
review of applications. Collaboration with other NIAID initiatives in the 
performance of mechanistic studies is encouraged, and will be facilitated by 
NIAID program staff. Mechanistic studies may include, but are not limited to:

1. The underlying mechanisms of action of the therapeutic approaches under 
investigation.

2. Development, evaluation, and validation of diagnostic tests for and/or 
surrogate markers of the relevant immunologic processes that will facilitate 
routine surveillance, early diagnosis and ongoing monitoring of those 
processes that contribute to post transplant morbidity and mortality. The use 
of non-invasive or minimally invasive approaches is strongly encouraged. 

3.  Development of assays to define and monitor immunoreactivity in order to 
guide real-time dose adjustments of the immunosuppressive regimen.

4. Identify genetic determinants of outcome or response to therapy in tissue 
and organ transplant recipients.

Studies may use samples from sources other than the subjects participating in 
the consortium’s clinical studies.  Applicants must identify the source of 
patient materials required for the mechanistic studies and provide 
documentation of the availability of the appropriate number and type of 
patient materials and the willingness of the source to make such samples 
available to the investigators.  As in the case of the proposed clinical 
protocol, award of the Cooperative Agreement does not imply that any proposed 
mechanistic studies will be implemented. Actual studies to be performed will 
be selected or designed by the Mechanistic Studies Subcommittee and approved 
by the Steering Committee.

When research involves human specimens, an NIH brochure is available to assist 
investigators in understanding how human subjects regulations (45CFR46) apply 
to their research: “Research on Human Specimens: Are You Conducting Research 
Using Human Subjects?” http://www.cdp.ims.nci.nih.gov/policy.html.

Creative approaches to overcoming the statistical or epidemiologic challenges 
of a small and heterogeneous patient group are encouraged. For each study 
performed within the cooperative group, all participating clinical sites will 
utilize uniform study designs and standardized data collection procedures. 
Proposals for animal studies of any sort, including xenotransplantation 
studies, will not be accepted. Interventions may target recipients and/or 
donors. 

MECHANISM OF SUPPORT

This RFA will use the NIH cooperative agreement (U01). 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 
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 is a cooperative agreement 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 
Award." The total project period for applications submitted in response to 
this RFA may not exceed five years. At this time, the NIAID has not determined 
whether and how this solicitation will be continued beyond the present RFA.

This RFA uses just-in-time concepts. It also uses the modular budgeting 
format. (see http://grants.nih.gov/grants/funding/modular/modular.htm). 
Specifically, if the investigator is submitting an application with direct 
costs in each year of $250,000 or less, use the modular format. This program 
does not require cost sharing as defined in the current NIH Grants Policy 
Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm

FUNDS AVAILABLE

The participating IC(s) intends to commit approximately $7.8 million in FY 
2004 to fund 3 to 5 new grants in response to this RFA. An applicant may 
request a project period of up to 5 years and a budget for direct costs of up 
to $2 million per year. 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 RFA are 
contingent upon the availability of funds and the receipt of a sufficient 
number of meritorious applications. 

ELIGIBLE INSTITUTIONS

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

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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

SPECIAL REQUIREMENTS

Applicants are encouraged to contact NIAID program staff well in advance of 
the application submission date, to discuss the proposed research program.  
These contacts help to ensure that applicants have a clear understanding of 
the goals, policies and priorities of this RFA.  They also will allow staff to 
assess responsiveness to this RFA and provide appropriate guidance as needed, 
with regard to this initiative as well as other NIAID initiatives in 
transplantation research.  Applicants must demonstrate the scientific 
expertise required to design, conduct, and analyze all mechanistic studies. 
Alternatively, the applicant may propose that some mechanistic studies be 
performed in collaboration with other existing NIAID-funded research groups or 
core facilities.

Successful applicant consortia will be merged to create a single consortium of 
institutions and investigators that will develop a scientific agenda and 
collaborative program of clinical and mechanistic studies. The study 
organization will include the following: a Steering Committee; a Mechanistic 
Studies Subcommittee; other subcommittees created as deemed necessary by the 
Steering Committee; an independent Data and Safety Monitoring Board (DSMB) 
appointed by NIAID; and a separately-funded data coordination and management 
center (DCMC) that will be directed by NIAID.  

The Steering Committee will be the main governing body of the CTOT group. The 
Steering Committee will develop a scientific agenda for the group, and 
prioritize study protocols in accordance with this agenda. All major 
scientific decisions will be determined by a majority vote of the Steering 
Committee.  The Steering Committee will have primary responsibility for the 
general organization of the studies and for finalizing and approving common 
clinical protocols. The Steering Committee will be responsible for the conduct 
and monitoring of studies and reporting study results.  

For each study, one PI will take the lead responsibility for drafting the 
protocol, although the Steering Committee and the NIAID Scientific Coordinator 
will provide input. A Mechanistic Studies Subcommittee (see “Collaborative 
Responsibilities”, below) will review and approve or modify the proposed 
mechanistic studies. 

Each investigational or therapeutic protocol will be implemented in as many 
participating sites as are needed and appropriate for the individual study, 
with a minimum of 2 sites participating in each study. As specific protocols 
are developed, support will depend on the availability of funds. For clinical 
sites, funds will be provided on a per patient basis.  All participating 
clinical sites must be willing to accept this funding arrangement. “Start up” 
costs for clinical research resources that must be in place prior to 
enrollment of subjects may be exempt from this requirement, subject to 
approval by the Steering Committee and the NIAID Program Director.
 
Clinical protocols must be approved by local institutional review boards and 
the NIAID Transplant DSMB before initiation.  The exact number of protocols 
supported in the five-year program will depend on the nature and extent of the 
investigations approved by the Steering Committee.  A database will be 
developed to support epidemiological studies and other clinical studies. 
Investigators in the CTOT group will be encouraged to develop collaborations 
with other laboratory and basic research investigators, as well as with 
industry. Any collaboration with industry will be developed with the 
assistance of the DAIT Office of Clinical Activities (OCA) and conducted under 
a DAIT Clinical Trials Agreement. Any specific collaboration involving the 
resources or protocols of the CTOT group will require approval by the Steering 
Committee.

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

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.

The administrative and funding instrument used for this program is cooperative 
agreement (U01), 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.

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. 
Recipient institutions must agree as a term of award to accept per-patient 
funding for clinical activities. “Start up” costs for clinical research 
resources that must be in place prior to enrollment of subjects may be exempt 
from this requirement, subject to approval by the Steering Committee and the 
NIAID Program Director.

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: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. 
The full policy, including terms and conditions of award, is 
available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

This award provides support for one or more NIH-defined Phase III clinical 
trials. The NIH Policy for research supported as an NIH Phase III Clinical 
Trial has been updated in Section III.B. of the “NIH Guidelines on the 
Inclusion of Women and Minorities as Subjects in Clinical Research”, updated 
August 1, 2000 (URL listed below under REQUIRED FEDERAL CITATIONS). A 
description of plans to conduct analyses, as appropriate, by sex/gender and/or 
racial/ethnic groups must be included in clinical trial protocols and the 
results of the subset analyses must be reported to NIH in Progress Reports, 
Competitive Renewal Applications, and in the required Final Progress Report, 
as stated in Section III.B. of the Guidelines.

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.

Each PI will be a voting member of the Steering Committee and will be required 
to participate in all Steering Committee activities and to follow the policies 
and procedures that are developed by the Steering Committee.  The PIs will be 
required to provide primary study data to NIAID for management, quality 
control, and analysis.  The awardees will retain custody of and have primary 
rights to all data developed under these awards, subject to Government rights 
of access consistent with HHS, PHS, and NIH policies. The PIs’ 
responsibilities regarding Steering Committee membership, protocol development 
and conduct, and data coordination and management are described under 
Collaborative Responsibilities.

3. NIAID Staff Responsibilities

An NIAID Program Director will be responsible for the normal program 
stewardship, including monitoring program progress, approving changes and 
concurring in proceeding into study implementation stage.  The Government, via 
the NIAID Program Director, 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.

Program Review
The NIAID Program Director, together with the DCMC and the Steering Committee, 
will review the progress of each participating institution through 
consideration of the annual reports, site visits, patient logs, etc.  This 
review may include, but is not limited to, compliance with the study protocol, 
meeting patient enrollment targets, adherence to uniform data collection 
procedures, and the timeliness and quality of data reporting.

The NIAID reserves the right to terminate or curtail any 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.

Organizational Changes
Certain organizational changes require the prior written approval of the NIAID 
Program Director.  These changes include the addition or replacement of a 
physician, scientific investigator, affiliate, component, or research base 
that is associated with this study.  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.

The NIAID Program Director may also serve as the NIAID Scientific Coordinator.

NIAID Scientific Coordinator 
 
NIAID staff assistance will be provided by the Clinical Transplantation 
Section Chief, DAIT, who will serve as or designate the NIAID Scientific 
Coordinator. 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.  

The NIAID Scientific Coordinator will serve as a voting member of the Steering 
Committee and will participate in all Committee activities.  The NIAID 
Scientific Coordinator will also serve on the Mechanistic Studies 
Subcommittee.

Protocol Development
As a member of the Steering Committee, the NIAID Scientific Coordinator will 
serve as a resource with respect to the design of the protocol and will, along 
with the DCMC, assist the Steering Committee in protocol development.

Publication and Presentation of Study Findings
The NIAID Scientific Coordinator may contribute, through review, comment, 
analysis, and/or co-authorship, to reporting results of the study to the 
investigator community and other interested scientific and lay organizations.  
Co-authorship by the NIAID Scientific Coordinator will be subject to approval 
in accordance with NIH policies regarding staff authorship of publications 
resulting from extramural awards.

Regulatory Affairs
The Chief of Regulatory Affairs/OCA/DAIT will be responsible for providing 
guidance and assistance in the development, assembly, and submission of all 
required regulatory documents, e.g. those regarding the use investigational 
drugs, to the Food and Drug Administration.  

4. Collaborative Responsibilities

Steering Committee.  A Steering Committee will be established to serve as the 
main governing body of the cooperative research program.  At a minimum, the 
Steering Committee will be composed of the following individuals: the NIAID 
Scientific Coordinator; the Principal Investigators; one additional Senior 
Investigator from each successful applicant consortium; the PI of the DCMC; 
and the Chair of the Mechanistic Studies Subcommittee (see below).  A Senior 
Investigator is the person responsible for on-site scientific direction and 
implementation of the consensus protocols at his/her participating 
institution.  Senior Investigators must be physicians with substantial 
experience in organ transplantation and in the design, implementation, and 
evaluation of clinical trials.  Each PI may designate one Senior Investigator 
to serve on the Steering Committee. The designated Senior Investigator may not 
be from the same institution as the PI, and will serve on the Steering 
Committee for 12 months. At the last steering committee of each 12-month 
period, the PIs will indicate the designated Senior Investigators who will 
serve during the next 12-month period.  Additional members, voting or non-
voting, may be added to the steering committee by majority vote of the 
Steering Committee; non-voting members may be added at the discretion of the 
NIAID Program Director. All major scientific decisions will be determined by 
the Steering Committee, with each Principal Investigator, Senior Investigator, 
Chair of the Mechanistic Studies Subcommittee, and the NIAID Scientific 
Coordinator having one vote.  The NIAID and the DCMC are limited to one vote 
each on the Steering Committee. The first two meetings of the Steering 
Committee will be convened by the NIAID Scientific Coordinator. At the second 
meeting, the group will elect a Chairperson from among the Steering Committee 
members; the NIAID Scientific Coordinator and the PI of the DCMC are not 
eligible to be the Steering Committee Chair.  

The Committee will meet in person or by teleconference at least four times 
during the first 12 months of the study and at least twice annually 
thereafter.  This Committee will have primary responsibility for developing 
the common clinical protocols, approving the design and implementation of all 
mechanistic studies (via the mechanistic studies subcommittee), facilitating 
the conduct and monitoring of all clinical trials and mechanistic studies, 
analyzing and interpreting study data, and reporting study results. Studies 
will not be approved if the NIAID or the Steering Committee determines that it 
will not be feasible to accrue patients within the specified time frame.   In 
addition, the steering committee will develop mechanisms for monitoring 
accrual performance and criteria for continued participation by each 
participating institution in the consortium. The Steering Committee will 
review the budget and expenditures at least once each year at a face-to-face 
meeting. Clinical trials and mechanistic studies will proceed into the 
implementation stage only with the concurrence of both the Steering Committee 
and the NIAID Program Director.  Each Steering Committee member will be 
expected to participate in all Steering Committee activities, e.g., meetings, 
conference calls, special subcommittee activities, etc. as may be necessary.  
The Steering Committee shall appoint a Mechanistic Studies Subcommittee, as 
described below.  Other Subcommittees may be appointed, as required, by the 
Steering Committee.

The steering committee or a designated sub-committee will prepare an annual 
report containing the following information: Progress in ongoing and newly-
initiated clinical trials and mechanistic studies; subject accrual and 
protocol compliance at all participating clinical sites; manuscripts 
published, in press, and in preparation; presentations at regional, national, 
and international meetings; and budget review. The first such report will be 
presented at a joint meeting of the steering committee and mechanistic studies 
subcommittee not later than 13 months after the initial notice of award, and 
yearly thereafter.  The NIAID Scientific Coordinator will not participate 
substantively in the development or submission of the annual report, and will 
serve as the primary NIAID staff member responsible for review of the report 
by the sponsoring agency.

Mechanistic Studies Subcommittee.  The Steering Committee shall appoint a 
Mechanistic Studies Subcommittee to review and approve or modify proposed 
mechanistic studies. Each PI shall select two representatives from his/her 
consortium as voting members of the Mechanistic Studies Subcommittee.  In 
addition, the NIAID Scientific Coordinator shall serve as a voting member.  
The Mechanistic Studies Subcommittee may ask the Steering Committee to appoint 
additional Mechanistic Studies Subcommittee members if additional expertise in 
a specific area is needed.  The Mechanistic Studies Subcommittee shall elect a 
Chair from among its non-Federal members. The Chair shall serve as a voting 
member of the Steering Committee.  The Subcommittee will meet at least twice 
yearly and its members will be expected to participate in all meetings, 
conference calls, and other Subcommittee activities.

Data and Safety Monitoring Board (DSMB).  An independent DSMB, appointed by 
the NIAID, will review progress at least annually and report their findings to 
the NIAID Program Director.  Clinical protocols and mechanistic studies will 
be subject to review by the DSMB, in an advisory capacity, prior to 
implementation. The DSMB review will focus on the safety, ethics, and 
scientific and statistical integrity of the studies.

Data Coordination and Management.  Data Coordination and Management will be 
carried out by a separately funded Data Coordination and Management Center 
(DCMC). Each participating institution will be responsible for providing 
primary study data to NIAID via the DCMC for management, quality control, and 
analysis, using procedures and standards determined by the Steering Committee 
and the DCMC.  The NIAID will provide, via its program staff and the DCMC, the 
following: technical assistance and data management services to the 
participating institutions with respect to quality control, uniformity of data 
collection, management of the collective database, and data analysis; 
centralized data collection and management; and quality assurance.  Specific 
analyses to be performed will be directed by the Steering Committee. In the 
event of a specific safety concern, the DSMB may also request specific 
analyses from the DCMC.  The results of those analyses will be delivered to 
the Steering Committee, which is responsible for determining how the results 
are interpreted, whether the results should influence ongoing data collection, 
and how the findings should be disseminated. All participating sites will have 
access to all data originating from their sites.  The awardees will retain 
custody of and have primary rights to all data developed under these awards, 
subject to Government rights of access consistent with HHS, PHS, and NIH 
policies.  Although the participating institutions will be closely involved 
with these centralized data collection and management services, the 
participating institutions will be responsible for on-site data collection and 
transmittal. 

Publication and Presentation of Study Findings.  Timely publication of major 
findings is encouraged.  Publications and oral presentations of work performed 
under this agreement will require appropriate acknowledgment of the 
participating institutions and NIAID support.  Analyses to be performed using 
the collective data from all participating institutions will be determined and 
directed by the Steering Committee.  Participating institutions wishing to 
perform analyses of local data will inform the Steering Committee of any such 
analyses prior to initiation in order to avoid duplication.  Review and 
approval by the Steering Committee will be required for all analyses prior to 
publication or presentation according to criteria that will be developed by 
the Steering Committee. The Steering Committee may establish a Publications 
Subcommittee to carry out this function.

Monitoring Study Progress.  The Steering Committee will establish mechanisms 
for assessing the performance of the participating institutions, including 
institutions participating in consortia arrangements, with particular 
attention to accrual of adequate numbers of eligible patients, timely 
submission and quality of required data and conscientious observance of 
protocol requirements.

5. 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 or by the individual awardee in the event 
of an individual disagreement, a second member selected by the NIAID, and the 
third member with expertise in the relevant area and selected by the two prior 
members will be formed to review any scientific or programmatic issue that is 
significantly restricting progress. While the decisions of the Arbitration 
Panel are binding, these special arbitration procedures will in no way affect 
the awardee's right to appeal an adverse action in accordance with PHS 
regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 CFR Part 
16.

WHERE TO SEND INQUIRIES

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 
issues:

o Direct questions about scientific/research issues to:

Nancy D. Bridges, M.D.
Chief, Clinical Transplantation Section
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Tel (301) 496-5598
Email: nbridges@niaid.nih.gov

Judith Massicot-Fisher, Ph.D.
National Heart, Lung, and Blood Institute
Telephone: (301) 435-0510
FAX: (301) 480-1454
Email: massicoj@nhlbi.nih.gov

Catherine M. Meyers, M.D.
Director, Inflammatory Renal Diseases Program
Division of Kidney, Urologic & Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Tel (301) 451-4901
Email: Cm420i@nih.gov

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
e-mail: es170m@nih.gov

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
Email:  ad22x@nih.gov

LETTER OF INTENT

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

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

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
e-mail: es170m@nih.gov

SUBMITTING AN APPLICATION 

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 http://www.dunandbradstreet.com/. 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 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.
 
SUPPLEMENTARY INSTRUCTIONS:

See also the SPECIAL REQUIREMENTS section above.

Research plans should be in the form of detailed concept proposals, organized 
as specific aims, background and significance, preliminary studies, and 
research design and methods (sections A-D). Proposals must be presented in 
sufficient detail to allow reviewers to judge significance, approach, 
innovation, and environment. The ability of the applicant consortium to 
perform the clinical and mechanistic studies should be clear. Methods of data 
analysis and sample size justification for the proposed clinical study, as 
well as scientific rationale for the mechanistic proposed mechanistic studies 
must be included. However, submission of a detailed, final clinical protocol 
is neither required nor encouraged, as the choice of studies to be performed 
and final protocol development will be accomplished subsequent to award, under 
the guidance of the Steering Committee.  The research plan for both required 
proposals (see below) should not exceed 40 pages. 

The application must include two (2) concept proposals for clinical studies 
that meet the objectives and scope of this RFA. One proposal must be organ 
specific, while the other must be designed to address a transplant-related 
immunologic problem that may be studied in a diverse group of organ recipients 
(e.g., renal transplant recipients and heart transplant recipients, or liver 
transplant recipients and lung transplant recipients, or any other combination 
of recipients of different organs).  Each of the 2 proposals may propose a 
clinical intervention, or one of the two protocols may be observational in 
design. Each clinical proposal must be accompanied by mechanistic studies 
designed to expand our understanding of the basic mechanisms of alloimmunity, 
innate immunity in the transplant setting, and/or graft dysfunction. 
Descriptions of proposed mechanistic studies are to include: identification of 
and rationale for the immune, genetic, and/or surrogate markers selected, 
including data from animal and/or human studies; a description of the source, 
quantity, and number of patient samples required; methodologies proposed to 
collect and analyze samples; and a discussion of how the results of the 
proposed mechanistic studies will improve the capacity to utilize immune, 
genetic and/or surrogate markers to predict patient outcome.  

The applicant should state clearly how anticipated study results can be 
expected to contribute to improvements in patient/graft survival.

Additional requirements are as follows:

1. The applicant institution and each institution participating in the 
consortium must document their experience and capacity to recruit and retain 
study participants, and provide a description of the population currently 
available for each proposal. Furthermore, the applicant and participating 
institutions must explicitly state that the approved trials within the CTOT 
group will have priority over any subsequent non-CTOT group study in organ 
transplantation.  Exemptions from this agreement will require approval by the 
NIAID and the Steering Committee.

2. The application must identify the single applicant organization that will 
be legally and financially responsible and accountable for the use and 
disposition of funds awarded on the basis of this RFA to other institutions 
participating in the consortium, and show availability of personnel and 
facilities capable of performing and supporting the administrative functions 
necessary. 

3. The application must name a single PI who will have scientific 
responsibility for the application as a whole, including all consortium-
related research activities.  The PI must be a physician with substantial 
experience in organ transplantation and in the design, implementation, and 
evaluation of clinical trials.  The applicant consortium must contain two or 
more participating institutions. Consortium member institutions may be 
clinical participants, in which case they must have a UNOS-certified program 
in organ transplantation, or they may be mechanistic study participants, in 
which case they must have demonstrated expertise in the research techniques 
necessary for the proposed study. Applications must name a single Senior 
Investigator for each participating institution in the consortium who will be 
responsible for on-site clinical and scientific implementation, direction and 
management of the clinical protocols, and the coordination of requirements for 
mechanistic studies of underlying mechanisms and immune/surrogate markers. A 
letter from each Senior Investigator, indicating a commitment to participate 
and the qualifying characteristics of his/her institution, must be included 
with the application.

4. The applicant must provide a clear and concise plan, in narrative and 
diagrammatic form, that depicts the interrelationships among the members of 
the consortium, their relevant experience/expertise, and the contribution of 
each to fulfillment of the objectives of this RFA, as well as an 
organizational chart of the consortium showing the name, organization, and 
scientific discipline of the PI and of all key scientific, technical and 
administrative personnel. 

5. The application must provide a plan to ensure the maintenance of close 
cooperation and effective communication among members of the consortium; 
letters of commitment to this plan from all participating institutions; and 
evidence of the capability of the applicant organization and each institution 
in an applicant consortium to participate and interact effectively in 
cooperative, multi-center clinical trials.

6. The application must include a written commitment from the PI, and from the 
Senior Investigators of participating sites, to accept the participation and 
assistance of NIAID staff in accordance with the guidelines outlined under 
"Cooperative Agreement Terms and Conditions of Award: NIAID Staff 
Responsibilities."  The application must also include a written commitment to 
the cooperative organization and willingness to adhere to the decisions 
reached by that Committee, including following the consensus protocols and 
mechanistic studies. 

7. All costs required for the proposed protocols and mechanistic studies must 
be included in the application and must be fully justified.  These include the 
additional costs of clinical research associated with the proposed protocols, 
costs for patient recruitment and follow-up, mechanistic studies, data 
collection, and participation in on-site quality assurance audits.  Requested 
budgets should also include: (1) travel to the Bethesda, MD area for four 1-
day Steering Committee meetings during the first 12 months, and twice annually 
thereafter, for the Principal Investigator and one Senior Investigator for 
each participating consortium, and (2) travel to the Bethesda, MD area for 
meetings of the Mechanistic Studies Subcommittee for the two representatives 
from each consortium, to coincide with steering committee meetings.

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: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

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 must be received on or before March 15, 2004. Applications that 
are not received as a single package on the receipt date will be 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.
PEER REVIEW PROCESS

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 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

REVIEW CRITERIA

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. 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.  

o Significance
o Approach
o Innovation
o Investigator
o Environment
   
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 
field?

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?

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

Mechanistic studies will be weighed equally with the clinical studies in the 
review of applications.

For the Principal Investigator:

1. Evidence of commitment and contributions to the field of organ 
transplantation, and of ability to provide the leadership necessary to achieve 
multi-site adherence in a clinical research protocol.

For Participating Clinical Sites:

1. Demonstrated knowledge of clinical organ transplantation, and a documented 
commitment to the study of clinical aspects organ transplantation by the 
investigators and their institutions.

2. Evidence of successful experience in recruitment and retention of research 
subjects in multicenter clinical studies, and particularly studies of clinical 
organ transplantation.

3. Documentation of center transplant volume adequate to contribute (among all 
organ recipient groups) at least 10 adult or 5 pediatric subjects per year to 
the proposed studies. 

4. Evidence of prior experience in working collaboratively in carrying out a 
clinical study protocol. 

For Sites Performing Mechanistic Studies:

1. Evidence of expertise in and prior experience with conduct of mechanistic 
studies pertaining to the immunologic areas under study using specimens of 
human origin.

2.  A documented commitment to the study of the basic immunologic aspects of 
organ transplantation by the investigators and their institutions.

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
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)

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 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, 
below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are 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. 

ADDITIONAL CONSIDERATIONS

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.

RECEIPT AND REVIEW SCHEDULE

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

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.

REQUIRED FEDERAL CITATIONS

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).  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 and Safety Monitoring, NIH Guide for Grants and 
Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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.  
http://grants.nih.gov/grants/policy/data_sharing 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.

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 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 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are 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 RESEARCH INVOLVING HUMAN SUBJECTS: 
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 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTSNIH policy 
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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see 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.  
Applications that do not provide this information will be returned without 
review.

PUBLIC 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 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 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA 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.

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). 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 
(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. 
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 PA 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 Catalogue of Federal Domestic Assistance at 
http://www.cfda.gov/ in the following citations: No. 93.855, Immunology, 
Allergy, and Transplantation Research; No. 93.856, Microbiology and Infectious 
Diseases Research; No. 93.849, Kidney Diseases, Urology and Hematology 
Research; No. 93.837, Heart and Vascular Diseases Research; No. 93.838, Lung 
Diseases Research;  and No. 93.839, Blood Diseases and Resources 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 
http://grants.nih.gov/grants/policy/policy.htm. 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.


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