NIGMS CENTERS OF EXCELLENCE IN COMPLEX BIOMEDICAL SYSTEMS RESEARCH

RELEASE DATE:  April 29, 2003

RFA: GM-03-009

National Institute of General Medical Sciences (NIGMS) 
 (http://www.nigms.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):
93.309, 93.821, 93.859, 93.862

Letter of Intent Receipt Date: September 3, 2003

Application Receipt Dates: October 14, 2003

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   Where to Send Inquiries
o   Letter of Intent
o   Submitting an Application
o   Peer Review Process
o   Review Criteria
o   Receipt and Review Schedule
o   Award Criteria
o   Required Federal Citations

PURPOSE OF THIS RFA

This document re-announces the National Institute of General Medical Sciences 
(NIGMS) RFA for the establishment of new academic Centers of Excellence in 
Complex Biomedical Systems Research (CE/CBSR) that was published in the NIH 
Guide on January 26, 2001.  The goal of the CE/CBSR program is to promote 
institutional development of pioneering research and training programs 
focused on quantitative, systems level analysis of biological phenomena of 
biomedical importance within the NIGMS mission.  NIGMS supports fundamental 
inquiries focused on cell biology and biophysics, genetics and developmental 
biology, human physiology in the areas of trauma, burn, inflammation, and 
multiorgan failure, and pharmacology and anesthesiology.  NIGMS does not 
support research focused on diseases that are the domain of other Institutes 
and Centers within the NIH.  The CE/CBSR program also is responsive to the 
Biomedical Information Science and Technology Initiative (BISTI) and its call 
for National Programs of Excellence in Biomedical Computing (NPEBC).

Non-exclusive examples of appropriate research foci of CE/CBSR Centers are 
the organization and dynamic behaviors of subcellular, cellular, and 
developing systems, the relationship of genetic and environmental variation 
to the expression of phenotype, and the understanding of organ system 
responses to injury and stress.  Approaches might include computationally-
based modeling; e.g., of processes such as the cell cycle, pattern formation 
during embryogenesis, the flux of substrates and intermediates in metabolism, 
system wide responses to pharmaceuticals, and cellular stress responses. 
Statistical and other mathematical tools may be used to analyze the genetic 
architecture of complex traits, and network analysis may be applied to 
understanding the integrated systemic host responses to trauma, burn, or 
other injury. 

The P50 Center Grant mechanism will support the development of multi-
investigator teams capable of engaging biomedical complexity with a scope of 
activities not possible with other funding mechanisms.  Activities will 
encompass research and training, as well as workshops, symposia, and other 
forms of outreach.  Centers will support research activities that may include 
the development of new instrumentation and methods, bioinformatics 
infrastructure, and new theoretical frameworks.  Training activities may 
include programs in computational and information sciences.  Partnering with 
undergraduate institutions, especially those with substantial numbers of 
underrepresented minority students, is encouraged.

RESEARCH OBJECTIVES

Background

The biomedical sciences have undergone a fundamental shift in both the 
conceptual and technical approaches that can be brought to bear on certain 
problems of profound importance.  These problems center on the understanding 
of the behavior of biological systems whose function is the product of 
spatial and temporal ordering of myriad interacting components.  Examples of 
first attempts to understand these phenomena can be found at all levels of 
biological organization, including the modeling of the genetic circuitry of 
bacteriophage lambda regulation, the modeling of the yeast cell division 
cycle, and the quantitation of cellular processes such as metabolic flux and 
response to stress.  At higher levels of organization, modeling approaches 
are being used to understand the orderly development of biological pattern in 
model organisms such as Drosophila.  At the clinical level, new approaches 
are being explored to understand the integrated activity of tissues and 
organs.  Part of the impetus for systems-scale approaches rests on recent 
advances in acquiring data of the necessary quality and quantity to permit 
computer based modeling.  Among the most striking recent examples is the 
availability of complete DNA sequences for a number of organisms, including 
humans.  This advance has made it feasible to generate a truly comprehensive 
"parts list" for any organism and to track changes over time.  Potentially, 
the enumeration of all the informational units of the genomes (protein coding 
regions, regulatory elements), their processed forms, and their positional 
significance, should be possible and, for some microorganisms, close at hand. 

The challenges are substantial.  A significant fraction of newly identified 
coding regions have no known relatives in existing indices of function, and 
the identification of regulatory elements presents a significant informatics 
challenge.  Much progress is being made in adapting existing methods (such as 
gene inactivation) to high-throughput functional analysis, and developing 
newer computational approaches grounded in evolutionary theory.  A higher 
order problem presents itself in understanding how the genome-encoded 
components and the "stuff" of the living state (metabolites, ions, water) are 
constituted in networks of interacting molecules with particular 
distributions in time and space.  Advances in imaging techniques and analytic 
methods promise to yield copious quantitative and spatial data on specific 
molecules in biological systems.  Knowledge of the network and changes in its 
components over time, and the local rules by which the individual components 
distribute material and information will substantially advance our knowledge.

At the organismal level, phenotype must take into account the relationships 
and interactions of biological and environmental variables. Basic biological 
systems, including gene sequences, structures, and pathways that direct 
metabolism and development vary within individuals, among individuals, among 
populations, and among species.  Advances in complex systems level 
understanding must ultimately include models that account for this variation.   

Medical, biotechnological, and other uses of biological information 
increasingly depends on our ability to understand the principles and dynamics 
that explain the behavior of the system as a whole.  Whether the goal is to 
understand the consequences of disease or injury, or to identify particular 
molecular targets for drug interventions, or to modify the metabolism of 
microorganisms to produce medicines, the challenge is "predictability."  
Predicting how the system of interest will respond to an intervention is a 
computational problem.  For biological systems this challenge is daunting.  

The effort to get a quantitative "handle" on biological systems and their 
integrated behavior requires diverse expertise. In particular, contributions 
from the computational disciplines of engineering, physics, and computer 
science are needed.  The development of new theoretical frameworks will in 
large part be a mathematical endeavor.  As modeling and simulation studies 
advance in sophistication, there will be a demand for better quality and 
increased quantities of data, and therefore the development of new 
instrumentation and methods.  The organization and representation of these 
new data streams, and their integration with preexisting knowledge, will 
challenge current capabilities in bioinformatics.

The organization of projects incorporating multidisciplinary approaches and 
the recruitment and training of skilled personnel are not simple 
undertakings, and these CE/CBSR Centers grants are designed to support these 
activities.  In addition to research contributions, successful Centers will 
provide their home institutions with the means to implement organizational 
and professional changes that will make interdisciplinary research in complex 
biological systems and bioinformatics attractive career options for both 
established and entry level investigators.  The institutions will receive the 
resources to recruit new investigators who have the skills needed to develop 
new methods and tools, and to develop appropriate training programs in 
computational and information sciences.  In addition, the Centers will 
disseminate expertise and knowledge through workshops and symposia, and, 
because the Centers will be pioneering a new era in biological sciences, they 
will provide outreach activities to undergraduate institutions, including 
minority-serving institutions.  

NIGMS currently supports the analysis of complex biological systems through 
investigator-initiated research project grants, using the R01, P01, R21, and 
other appropriate grant mechanisms.  However, the resources needed to conduct 
the multi-faceted, multi-disciplinary projects that may be required to 
achieve significant advances in these complex areas may be beyond the scope 
of the typical R01 or P01 grant.  Therefore, this RFA presents an opportunity 
for applicants to assemble large teams of investigators from diverse 
disciplines that may not be possible with other funding mechanisms.

High priority will be given to projects that integrate multi-investigator, 
multi-disciplinary approaches with a high degree of interplay between 
computational and experimental approaches.  Innovation is critical.  A 
variety of organizational models are possible, and it is not the purpose of 
this announcement to prescribe any particular one.

Current initiatives related to CE/CBSR can be found in prior NIGMS program 
announcements: http://www.nigms.nih.gov/funding/complex_systems.html.

Some groups interested in the scope of this RFA might find the P01 mechanism 
more suited to the scale of their efforts; they should consult the prior 
announcement at the URL: http://grants.nih.gov/grants/guide/pa-files/
PA-98-077.html.

Scope of Research

The NIGMS intends to support Centers of Excellence in Complex Biomedical 
Systems for research areas that 1) are central to its mission, and 2) focus 
on developing new computational approaches to biomedical complexity.    
Research areas that historically have been computationally based (e.g., 
molecular structure and modeling) are excluded as a focus of this Center 
program.  Research projects focusing on disease processes and their specific 
organ systems are not eligible.  NIGMS mission areas for which Centers of 
Excellence in Complex Biomedical Systems Research would be particularly 
appropriate include, but are not limited to, the following: 

o  Pattern formation and developmental processes in model systems (e.g., 
Drosophila, C. elegans, etc.)
o  Metabolic networks and the control of the flux of substrates, 
intermediates, and products in cell physiology
o  Signaling networks and the regulatory dynamics of cellular processes such 
as cell cycle and apoptosis, and response to environmental stress
o  Supramolecular machines, such as the replisome, spliceosome, and molecular 
motor assemblies in cell division and motility
o  Organ system networks involved in multi-organ failure in shock, trauma, 
and burn injury
o  Genetic architecture of biological complexity related to inherited 
variation and environmental fluctuations.  

NIGMS strongly encourages investigators who propose to develop applications 
to discuss their ideas with NIGMS program staff prior to submission to ensure 
that applications will be responsive to the NIGMS mission and intent for this 
program.

Center Developmental Activities

Centers will likely support the development of new mathematical tools, 
theory, and technologies that foster computational solutions.  Examples are 
network theoretical structures for understanding genetic and physiological 
regulatory circuitry, systems of equations allowing the description of 
signaling dynamics, analytical tools to discover the relationship of 
genotypic variation to phenotype, and computer models of morphological 
changes during development.

The substantial bioinformatics challenge of engaging large data streams and 
developing models has been highlighted in the BISTI report 
(http://www.nih.gov/about/director/060399.htm): "To make optimal use of 
information technology, biomedical researchers need, first of all, the 
expertise to marry information technology to biology in a productive way.  
New hardware and software will be needed, together with deepened support and 
collaboration from experts in allied fields.  Inevitably, those needs will 
grow as biology moves increasingly from a bench-based to a computer-based 
science, as models replace some experiments and complement others, as lone 
researchers are supplemented by interdisciplinary teams.  The overarching 
need is for an intellectual fusion of biomedicine and information 
technology."  To this end, Centers may include bioinformatics tool 
development that could include DNA sequence feature search programs, 
specialized databases, development of data sharing and representation 
formats, and data mining algorithms, etc..  The plan may also include the 
design of new instrumentation that may be required, for example, to obtain 
time series measurements of multiple parameters of cell and tissue function, 
including spatial information by imaging technologies.  

Centers will be expected to provide national leadership in complex systems 
research.  To do so, they will be expected to support training and outreach 
activities that will insure the flow of information and expertise both into 
and out of the Center.  One reason for the current lack of adequately 
qualified personnel is that there are too few appropriate environments 
available to support training.  The establishment of Centers under this 
program is intended to help to alleviate this shortage by serving as an 
academic focus for systems approaches.  To maximize their impact, Centers 
should integrate the training of young investigators and broaden the training 
of established investigators.  Graduate students and postdoctoral fellows 
should participate in the research.  Additional training activities that 
leverage strengths of the institution and the research program of the Center 
are encouraged.  Such training could be at the undergraduate, graduate, or 
professional levels.  The NIGMS strongly urges the inclusion of partnering 
programs that will help minority-serving institutions to develop capabilities 
in these new arenas.  

Workshops, visiting investigatorships, and courses that may develop from 
Center activities will serve the wider community of investigators and their 
institutions by disseminating scientific knowledge and organizational 
information.

Center Directors may be asked to join a committee to provide feedback on the 
success of the CE/CBSR program.  

MECHANISM OF SUPPORT

This RFA will use the NIH P50 Specialized Center Grant mechanism.  As an 
applicant you 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 July 1, 2004.  Applications submitted in response to the previous RFA 
announcements of this program, and unfunded, may be revised and resubmitted 
for this RFA.  

This RFA uses just-in-time concepts and the non-modular budgeting formats.  
This program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

FUNDS AVAILABLE

The NIGMS intends to commit approximately $6 million in FY04 to fund 2-3 new 
P50 Center 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 $2M 
per year, exclusive of facilities and administrative costs for collaborating 
institutions.  Funds for initial large equipment may be requested in excess 
of this $2M limit if prior approval is obtained from staff responsible for 
scientific/research issues, listed below, prior to application submission.  
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 NIGMS provide 
support for this program, awards pursuant to the RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 
applications.  In any event, the total length of support for any P50 Center 
under this program will be limited to a maximum of ten years.  

ELIGIBLE INSTITUTIONS

You may submit an application if your institution is a domestic organization 
and has any of the following characteristics:
o   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

Foreign institutions are not eligible to apply.

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 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. 

SPECIAL REQUIREMENTS

Centers will receive an administrative site visit during the third year of 
the first grant cycle.  The fifth year of funding will depend on the outcome 
of that administrative review, and the Principal Investigator (PI) will 
receive advice about NIGMS interest in accepting a competing renewal 
application to extend the initial award.

The Principal Investigator of Center Grant must commit a minimum effort of 
30%. 

The Center will be expected to have a Board of Advisors, drawn from experts 
outside the project.  These advisors will meet annually to review and provide 
guidance on Center activities.  While a description of the Board's activities 
should be included in the application, potential members of the Board should 
not be named, contacted, or selected until an award has been made.  This 
stipulation will allow a wider pool of potential reviewers of the 
application.  Costs for activities of the Board of Advisors should be 
included in the budget.

The NIH is interested in ensuring that the information about new methods, 
technologies, computer software, and high-throughput functional data that are 
developed through this program become readily available to the research 
community for further research and development.  Such sharing will eventually 
lead to information and products that improve the health of the public.  For 
this reason, applicants should develop and propose specific plans for sharing 
of data, materials, and software generated through the grant, taking into 
consideration the Guidance issued by NIH http://ott.od.nih.gov/ and 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.  To the 
extent that established public databases have the capability for collecting 
and disseminating the data that would be collected under the grant, it is 
NIGMS's strong preference that a plan for the rapid deposition of data into 
such public databases be described in the application.

The scientific review group will comment on the proposed plan for sharing and 
data release.  The adequacy of the plan will also be considered by NIH staff 
as one of the criteria for award.  The proposed sharing plan, after 
negotiation with the applicant when necessary, will be made a condition of 
the award.  Evaluation of renewal applications will include assessment of the 
effectiveness of data, materials, and software release.

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 your questions about scientific/research issues to: 

James J. Anderson, Ph.D.
Center for Bioinformatics and Computational Biology
National Institute of General Medical Sciences, NIH
45 Center Drive, Room 2AS-25A, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-0943
FAX: (301) 480-2228
Email: andersoj@nigms.nih.gov

o   Direct your questions about peer review issues to:

Helen R. Sunshine, Ph.D.
Office of Scientific Review  
National Institute of General Medical Sciences, NIH 
45 Center Drive, Room 3AN.12F, MSC 6200 
Bethesda, MD 20892-6200  
Telephone: (301) 594-2881 
FAX: (301) 480-8506
Email: sunshinh@nigms.nih.gov

o   Direct your questions about financial or grants management matters to:

Joseph Ellis  
Grants Administration Branch  
National Institute of General Medical Sciences, NIH  
45 Center Drive, Room 2AN-32C, MSC 6200 
Bethesda, MD 20892-6200  
Telephone: (301) 594-5135 
FAX: (301) 480-1969 
E-mail: ellisj@nigms.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 the 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 NIGMS 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:

James J. Anderson, Ph.D.
Center for Bioinformatics and Computational Biology
National Institute of General Medical Sciences
45 Center Drive, Room 2AS-25A, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-0943
FAX: (301) 480-2228
Email: andersoj@nigms.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. 
For further assistance contact Grants Info, Telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.  

SUPPLEMENTAL INSTRUCTIONS:  The applicant should identify clearly in the 
abstract and more fully in the research plan the new approaches and 
collaborations, and the specific biological questions that are to be explored 
as a result of the establishment of the Center.  The synergies to be achieved 
through the establishment of multi-disciplinary teams and novel 
collaborations should be fully described. 

The P50 grant application should specify the administrative and 
organizational structure(s) that will be used to support the research.  It is 
anticipated that the Center projects will be multi-disciplinary and will draw 
on a variety of resources.  Thus, a well thought out and carefully described 
organization will be required.  The PI is responsible for ensuring that 
scientific goals are met, and for developing and managing a decision-making 
structure and process that will allow resources to be allocated (and 
reallocated, if necessary) to meet those goals. Projects of the complexity, 
both scientific and managerial, that NIGMS anticipates will characterize 
these Centers will require a substantial amount of the PI's effort to achieve 
success.  Therefore, the PI will be required to devote at least 30% effort to 
the leadership and implementation of the Center.  If core facilities or 
shared resources are required, these should be described, as should their 
management and service to the research projects.  The applicant should 
explain how different components of the organization, including key 
personnel, will interact, why they are essential to accomplishing the 
research, and how the combined resources create capabilities that are more 
than the sum of the parts.  "Centers-without-walls" are welcome under this 
solicitation.  If any of the components are physically separated from each 
other (i.e., located in different departments or institutions), the applicant 
should address how interactions will be facilitated.  NIGMS is not specifying 
a specific organizational structure (e.g., specific numbers of projects and 
cores) in this RFA, preferring that applicants develop the structure that 
would best promote the research.  However, applicants should note that the 
effectiveness of the proposed structure will be a criterion of the evaluation 
prior to an award and will be monitored after an award is made. 

A timeline for the project should be presented.  This timeline should outline 
how the project's goals can be met within the time frame of a CE/CBSR grant.  
The timeline also will assist the investigators, NIGMS, and its advisors in 
evaluating progress toward the project's goals.  For those projects for which 
the investigator deems it appropriate to do so, NIGMS encourages applicants 
to present explicit, quantitative milestones.

If the Center is to be organized into projects, then the page limits 
specified in the PHS 398 form for sections a-d of the Research Plan will 
apply for each project.  If, however, the Center is to integrate its 
activities in such a way that describing individual projects would not be 
helpful, then the limit for the narrative section (a-d) is 40 pages.  Please 
note that there is no requirement to submit this maximum number of pages; 
instead, concise, articulate applications are desired.

NIGMS encourages applicants to devise a strategy for the Center's training 
and outreach components that best take advantage of the research program, the 
investigators' talents, and other institutional resources, to offer unique 
and substantial training opportunities for students and other investigators.  
The CE/CBSR will therefore augment programs previously developed by NIGMS 
(see http://grants.nih.gov/grants/guide/pa-files/PAR-99-146.html, 
http://grants.nih.gov/grants/guide/pa-files/PA-98-082.html) for expanding the 
cadre of investigators working in computational biology. 

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 applications 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 copies of the application, 
including all appendices, must be sent to: 

Helen R. Sunshine, Ph.D.
Office of Scientific Review  
National Institute of General Medical Sciences
45 Center Drive, Room 3AN-12F, MSC 6200 
Bethesda, MD 20892-6200

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.  
Unfunded applications submitted for a previous version of this RFA may be 
submitted as revised applications that will include an Introduction 
describing the changes and improvements made, with text clearly marked to 
indicate the changes.  

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by CSR and for 
responsiveness by the NIGMS.  Incomplete 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 NIGMS in accordance with the review procedures stated below.  
As part of the initial merit review, all applications will:

o   Receive a written critique
o   Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score.
o   Receive a second level review by the NIGMS National Advisory 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 your 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 your 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.  If the P50 Center Grant application 
includes distinct subprojects, the scientific merit of each will be assessed, 
based on its merit as an independent effort and its potential 
importance/contribution to the success of the overall effort (the projects 
will not receive separate scores, however). 

SIGNIFICANCE:  Does the 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 principal 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 the other researchers?  

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 
including any needed expansion of facilities, improvement of infrastructure, 
and relief from other academic duties where necessary?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, the 
application will also be reviewed with respect to the following:

o   Quality and appropriateness of the management plan, including the
effectiveness of the management structure and the PI's ability to lead and 
coordinate the activities.  Do the individual components exhibit a high 
degree of interrelatedness and synergy? Are the proposed core facilities (if 
any) essential to the success of the center?
o   Adequacy of plans for a Board of Advisors to provide scientific and
managerial oversight.  
o   Quality of the proposed training plan and outreach activities and their
likely effectiveness in meeting community needs, including provisions for 
engaging under-represented minorities. Will this center serve as a model for 
cross-disciplinary interactions?

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

DATA SHARING:  The adequacy of the proposed plan to share data.

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:  September 3, 2003
Application Receipt Date:  October 14, 2003
Peer Review Date:  February – March 2004
Council Review:  May, 2004
Earliest Anticipated Start Date:  July 1, 2004

AWARD CRITERIA 

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

o  Scientific merit (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

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (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).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
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 PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement 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://grants.nih.gov/grants/stem_cells.htm 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 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 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.

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 
RFA is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance Nos. 93.309, 93.821, 93.859, and 93.862 at 
http://www.cfda.gov/ and is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.  
Awards are made under the authorization of Sections 301 and 405 of the Public 
Health Service Act as amended (42 USC 241 and 284) and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to 
the terms and conditions, cost principles, and other considerations described 
in the NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at http://grants.nih.gov/grants/policy/policy.htm.

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

Return to Volume Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files.