INTEGRATIVE CANCER BIOLOGY PROGRAMS
 
RELEASE DATE:  December 1, 2003
 
RFA Number:  RFA-CA-04-013 

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

  March 6, 2009 - This RFA has been reissued as (RFA-CA-09-011).

Department of Health and Human Services (DHHS)

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

COMPONENT OF PARTICIPATING ORGANIZATION:  
National Cancer Institute (NCI)  
 (http://www.nci.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.396
 
LETTER OF INTENT RECEIPT DATE:  February 13, 2004 
APPLICATION RECEIPT DATE:  April 13, 2004 

THIS RFA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE OF THIS RFA 

The goal of this initiative is to promote the analysis of cancer as a 
complex biological system, by supporting the development of reliably 
predictive in silico or computational models of cancer initiation and 
progression that can ultimately lead to the development of improved 
cancer interventions.  The overall thrust of this program will be the 
integration of experimental and computational approaches towards the 
understanding of cancer biology.  This initiative will encourage the 
emergence of integrative cancer biology as a distinct field.

NCI recognizes that biomedical research is entering an era in which 
computational approaches will be increasingly used to deepen our 
understanding of biological behavior.  Building upon mechanistic 
descriptions of individual biological constituents, there will be an 
increasing emphasis on concepts and methods that target systems and 
their integrated behavior and increasing dependence of cancer 
biologists on expertise from computational sciences as well as other 
fields of science that consider complex systems.  This initiative is 
intended to facilitate the establishment of research programs in 
integrative cancer biology, which bring together cancer biologists and 
scientists from fields such as mathematics, physics, information 
technology, imaging sciences, and computer science to work on a common 
cancer biology problem. An ideal program in integrative cancer biology 
will be organized around an important problem in cancer that balances 
and seamlessly integrates experimental biology with computation and 
modeling. Standard and high-throughput experimental methods will 
generate large volumes of data, which will be used, in part, as input 
for computational/modeling approaches to the biological problem.  

These Integrative Cancer Biology Programs (ICBPs) will fund teams 
capable of addressing questions of cancer complexity with a wide scope 
of research activities.  In order to further develop the field, the 
Programs will participate in active knowledge dissemination and have a 
role in educating future investigators in necessary approaches and 
skills.  To accomplish this the individual Programs will also be 
responsible for establishing training and outreach programs.  The 
Programs will operate independently but will be linked through a 
central focus on cancer, a common bioinformatics infrastructure, and a 
planned NCI-sponsored coordination committee consisting of the 
principal investigators (PIs) of the Programs, key program personnel 
and NCI staff.

NCI interests related to this initiative include analysis of genome-
scale data sets, understanding signal-transduction networks that 
maintain and promote the malignant process, and the performance of 
computationally-based modeling of critical cancer-related cell 
processes such as proliferation, migration, apoptosis, transcription 
and differentiation.  The NCI is also interested in understanding the 
cellular and molecular interactions within the cancer microenvironment 
that facilitate tumor development and progression.

Applications responsive to this initiative must concentrate on human 
cancer or on well-credentialed vertebrate models of human cancer.  
Since it is well recognized that cancer involves fundamental cellular 
processes that are often effectively studied in such model systems as 
yeast, worms, and flies, programs may incorporate these systems in 
comparative studies centered on human or higher-order vertebrate 
systems.  While under appropriate circumstances NCI supports studies 
exclusively on lower model systems, such studies are generally referred 
to the National Institute of General Medical Sciences (NIGMS) for 
consideration.  Groups interested in exploring complexity in such model 
organisms should refer to a series of NIGMS initiatives, including 
NIGMS Programs of Excellence in Complex Biomedical Systems Research 
(RFA GM-03-009).  The NCI, through the NIH Biomedical Information 
Science and Technology Initiative or BISTI, also supports smaller 
specific applications primarily focused on bio-computing and 
bioinformatics.  If the potential applicant has questions regarding the 
appropriateness of his/her proposed research project, he/she should 
contact program staff or address the issue in the letter of intent.  
Individual investigators will find an up-to-date list of relevant 
program announcements at http://www.bisti.nih.gov.
 
RESEARCH OBJECTIVES
 
Background

The biomedical sciences have undergone a dramatic shift in both the 
conceptual and technical approaches that can be brought to bear on 
fundamental biological problems.  These problems center on the 
understanding of the behavior of biological systems whose function is 
governed by the spatial and temporal ordering of multiple interacting 
components.  This initiative is designed to foster the emergence of the 
new field of systems biology focused on the understanding of cancer as 
a complex disease. It will enable the formation of teams of researchers 
from a spectrum of fields, including biology, imaging, engineering, 
technology, bioinformatics, and computational modeling, who can focus 
on understanding and modeling some aspect of the complexity of cancer.

Cancer is a complex system on at least two levels.  First, malignant 
transformation leads to profound changes in the genetic and metabolic 
networks that control the functioning of the cell. We will never fully 
understand the development and progression of cancer without 
understanding the networks that support functioning in the normal human 
cell and the changes brought about by transformation.  Second, it is 
now clear that the biology of a tumor depends not only on the 
characteristics of the malignant cell, but also on the tissue 
microenvironment, and other characteristics of the host in which the 
tumor exists.  There are critical reciprocal influences among malignant 
cells, stromal cells, intercellular matrix components, and a host of 
soluble mediators, some produced locally and some systemically.  There 
is also a complex interplay between the developing tumor and the immune 
system.  All of these components are critical in the development of 
cancer; understanding them is critical to successful management of the 
disease.

Complete understanding of living processes will certainly come first in 
systems much simpler than human cancer.  Examples of first attempts to 
understand and model mathematically complex phenomena include the 
circuitry of bacteriophage lambda regulation, the yeast cell division 
cycle, and the quantitation of cellular processes such as metabolic 
flux and response to stress.  However, the need to have an impact on 
human disease dictates that some effort be made as soon as possible to 
analyze and model immediately relevant systems such as cancer.  Cancer 
is particularly suited to such analyses, given its complexity and the 
wealth of information about the underlying genetics, cell biology and 
cellular interactions. Cancer is largely a disease of genes, in which 
cumulative mutations in a spectrum of proto-oncogenes and tumor 
suppressor genes lead to the initiation and progression of cancer. The 
products of these mutant genes often include those associated with 
signal transduction pathways, with regulation of cell cycle and of 
apoptosis, each of which represents a complex cellular process. The 
cancer-associated mutations lead to perturbations in these processes, 
and thus could serve as models in the analysis of intracellular 
networks and in the development of in silico models.

Part of the impetus for systems-scale approaches rests on recent 
advances in acquiring data of the necessary quality and quantity to 
permit systems-wide analysis, including 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.  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.  The NCI 
has generated a large amount of data on gene expression in normal and 
cancer cells through such programs as Cancer Genome Anatomy Project 
(CGAP) and the Mammalian Gene Collection (MGC).  These programs and 
other efforts have supplied considerable data on the “parts list” for 
human cancer cells.   Thus, among the diseases, cancer is ideally 
suited for analysis by a systems, or integrative, biological approach.

A comprehensive understanding of these genome-scale datasets depends on 
our ability to apply computational or mathematical modeling to them.  
The development of testable models is necessary as a framework for 
further experimentation, data analysis and validation.  In turn, new 
data will help to refine model development.   Multi-component, 
interactive processes at the sub-cellular, cellular, tissue, and organ 
levels should be amenable to modeling and simulation in ways previously 
limited by the lack of adequate data.  Because this field is largely 
undeveloped, there is an opportunity to facilitate its development.  
Although these programs will be aimed at addressing and solving long 
term questions in cancer biology, they are expected to be focused on 
solving smaller and more specific problems in a 5-year to 10-year time 
frame.

Addressing this opportunity requires a concerted effort at integrating 
the various disciplines into a collaborative systems biology program 
consisting of a cohesive group of dedicated researchers working on a 
common problem in cancer biology.  Traditional molecular and genetic 
approaches, generally reductionist in nature, will continue to be 
needed and will be critical aspects of the ICBPs.  However, they will 
need to be augmented with concepts and methods that will enable global 
data integration and systems analyses.  This will require the 
involvement of scientists with new areas of expertise, particularly 
from the computational disciplines of mathematics, engineering, 
physics, and computer science.  The need for quantitative data will 
drive the development of new instrumentation and methods, along with 
efforts in data validation and integration.  The organization and 
representation of these data streams and their relation to preexisting 
knowledge will require bioinformatics advances, and the development of 
computer-based cancer biology hypotheses generated by testable models 
and intra- and inter-cellular simulations will require mathematical 
expertise, as will the development of new theoretical frameworks.  It 
is expected that models and databases will be shared through an effort 
coordinated by the NCI.

Objectives and Scope

The NCI will support Integrative Cancer Biology Programs in research 
areas that have the potential to enhance understanding of human cancer.  
NCI mission areas for which these Programs would be particularly 
appropriate include, but are not limited to, the following: 

o Gene expression, including epigenetic, transcriptional and 
translational control systems
o Metabolic networks and the control of the flux of substrates, 
intermediates, and products in cell physiology and cancer-related 
pathology
o Signaling networks and the regulatory dynamics of cellular processes 
such as cell cycle and apoptosis, and response to environmental stress, 
as they relate to cancer
o Supramolecular machines, such as the replisome, spliceosome, 
molecular motor assemblies in cell division and motility, and those 
related to DNA repair, as they are altered in cancer
o Cell-cell and cell-matrix interactions that are critical to the 
functioning of the tumor microenvironment
o Temporal processes such as cancer initiation and progression
o Host systems such as tumor immunology

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

This RFA presents an opportunity for applicants to assemble teams of 
investigators from diverse disciplines that is not possible with other 
funding mechanisms.  Projects must integrate multi-investigator, multi-
disciplinary approaches with a high degree of interplay between cancer 
biological experimental approaches and computational and theoretical 
approaches.  It is expected that individual programs will generate in 
silico models that will be testable and available to the larger cancer 
research community.  Critical aspects that must be addressed in any 
application include cancer biology, mathematical/computational 
modeling, bioinformatics, and educational/outreach programs.  
Organizing projects that incorporate these approaches, and training and 
recruiting personnel, are complicated processes; these large Program 
grants (P50) are designed to facilitate these activities.  A variety of 
approaches and organizational program structures are possible, and it 
is not the purpose of this announcement to prescribe any particular 
one.  The program may be described as a single undertaking or broken 
out as specific interrelated projects with associated cores.  It is 
expected that a program would contain both fully developed projects 
along with specific pilot projects that are still in the developmental 
phase.

The training of professionals who are well-versed in bioinformatics and 
mathematical modeling and who have a deep understanding of the biology 
of cancer is critical for current and future progress of the field.  
Educational programs, both internal to the individual programs and 
external for the greater scientific community, that address the 
component disciplines of the integrative cancer biology approach need 
to be developed within the framework of a cancer biology research 
effort.  It is expected that training and education activities will be 
established within the Programs and should include areas appropriate to 
the scope of research, including training in traditional cancer biology 
and in computational and information sciences.  A full menu of 
educational efforts may be included, ranging from formal undergraduate, 
graduate, and post-graduate programs to courses and seminars for 
students and working researchers, visiting-scientist programs, one-to 
two-week intensive training programs, and other innovative programs to 
help spread the knowledge and resources generated.  These educational 
programs will be directed towards and help integrate the various 
scientific disciplines of the individual program efforts.  The Programs 
will be expected to help “seed” the greater scientific community by 
disseminating expertise and knowledge.  To inform the biomedical 
research community at large, plans for workshops and symposia may be 
included.  Because the Programs will be pioneering a new era in 
biological sciences, they are expected to provide outreach activities 
to traditional and non-traditional research institutions through 
supplement and partnership programs.  Since each Program will have 
unique strengths and resources, the proportion of research and training 
should be determined individually by each applicant.
 
Recognizing the difficulty of assembling such trans-disciplinary teams, 
planning grants (P20) will also be awarded to provide the time and 
resources needed to establish appropriate collaborations across the 
broad spectrum of scientific disciplines that need to be represented 
within the Program.  The Exploratory Grant (P20) mechanism should be 
used when the applicant wishes to request a period of planning and 
preliminary investigation.  The planning grant application must 
explicitly demonstrate how these specific grant activities will lead to 
collaborative efforts, and describe in substantial detail a vision of 
the research to be conducted by the Program.  These preliminary efforts 
will be focused on the assemblage of teams and small pilot projects.  
It is expected that successful completion of a planning ICBP grant will 
enable the awarded group to fully develop an integrative cancer biology 
program using institutional and outside support.  Upon future 
assessment of the overall program by NCI, these P20s may also compete 
for full Program status in any potential future issuance of the RFA or 
similar programs in either public or private settings.  Awarding of a 
P20 does not imply a commitment from the NCI to future funding of a 
full Program.

Generally, the full Program (P50) awards are reserved for those teams 
of investigators who can demonstrate an existing infrastructure 
supporting well-developed projects and integration of both scientific 
direction and management.  If these components are not in place or need 
further development then applicants should apply for the planning grant 
(P20).  Applicants should contact program staff if there is a question 
as to which mechanism is most appropriate.  Both the P20 and P50 
awardees will be considered full members of the ICBP and be expected to 
participate in Coordinating Committee and associated activities, and to 
comply with data deposition Guidelines, as established by the 
Coordinating Committee and the NCI.

MECHANISMS OF SUPPORT
 
This RFA will use NIH Specialized Center Grant P50 and Exploratory 
Grant P20 award mechanisms.  As an applicant, you will be solely 
responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  The anticipated award 
date is September 30, 2004. 

This RFA uses just-in-time concepts.  It also uses the non-modular 
budgeting format. (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).   Follow the 
instructions for non-modular budget research grants applications. 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 
 
NCI intends to commit approximately $10 million in FY 2004 to fund 2-3 
P50 Programs and 2-3 P20 Planning Grants in response to this RFA.  An 
applicant for a P50 Program may request a project period of up to 5 
years and a budget for total costs not to exceed $15 million for the 
duration of the award, or an average of $3 million/year.  However, 
overall annual budgeting of the P50s will be flexible according to the 
needs and maturity of individual programs. Therefore, newly established 
programs may require less funding the first year, but greater funding 
in subsequent years, whereas more developed efforts may require larger 
“up-front” allocations for salaries, equipment, technology, etc.  An 
applicant for a P20 planning grant may request a project period of up 
to three years and a budget for total costs of up to $500,000/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 NCI 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
 
You may submit (an) application(s) if your 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 institutions/organizations
o 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 
 
It is anticipated that awardees will be generating and analyzing large 
datasets dealing with cellular properties.  To facilitate an interface 
with existing NCI datasets and interchange of data within the research 
and clinical communities, potential applicants will be invited to 
attend a pre-submission workshop to discuss the problems and potential 
of standard data formats and discuss possible guidelines for data 
sharing.  This workshop will be co-sponsored by the NCI Center for 
Bioinformatics (NCICB).  Participation in a pre-application ICBP 
bioinformatics meeting will be open to all parties interested in 
applying to the RFA.  An announcement of the date and location of this 
workshop has been published concurrently with this RFA.  The meeting is 
tentatively scheduled for the end of January in the Washington, D.C., 
area.  Please consult NOT-CA-04-005
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-04-005.html) 
for details on the pre-application meeting.  Information will also be 
available on the Division of Cancer Biology website 
(http://dcb.nci.nih.gov/).  The workshop will be an opportunity to 
clarify questions about the overall program and to discuss specific 
concerns about data standards, infrastructure, and approaches to 
sharing of data and models as related to the ICBP and the community.  
The pre-submission workshop proceedings will be posted on a public NCI 
web site.  Attendance at the pre-meeting is neither required nor is it 
necessary for a successful application.  It is intended to be an 
opportunity for clarification and discussion on the larger question of 
data integration.

To enhance interactions among the funded Programs, PIs, Co-PIs, key 
personnel from both P50 and P20 grants, and NCI scientific staff will 
constitute a “Coordinating Committee” that will meet twice a year to 
discuss current accomplishments, barriers encountered, and to identify 
areas of opportunity and unrepresented areas of expertise and 
individuals whose contributions should be brought to bear on addressing 
cancer complexity.  The NCI would anticipate supporting these new 
opportunities through supplemental funds to the awards.  PI’s and co-
PI’s will be required to attend these Coordinating meetings and 
applicants will be expected to include funds for these semi-annual 
meetings in their travel budget.  These meetings also will serve as a 
venue in which the bioinformatics platform and tools will be evaluated 
and discussed and suggestions for enhancements made to NCICB.

After the awarding of grants, specific program guidelines for the 
bioinformatic data will be established by the ICBP Coordinating 
Committee.  The coordinating committee will develop standards and 
guidelines for the exchange and dissemination of information and data 
for the benefit of the ICBP and the greater community.  It will be 
required that the data exchange and dissemination guidelines be 
compatible with the overall NCI bioinformatics system that supports 
other NCI sponsored initiatives.  As previously stated, awardees will 
be required to share data and models generated through this grant with 
each other and through an established centralized NCI or public 
resource, in a timely fashion and as stipulated in the guidelines that 
are ultimately adopted by the Coordinating Committee and the NCI.  
These guidelines will also be publicly available on the NCI website.

In addition, awardees will be strongly encouraged to leverage or 
interact, whenever possible, with appropriate existing programs both 
within NIH as well as other public (e.g., NSF) and private efforts.  
This would include non-traditional biomedical researchers and programs.

Programs 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 will receive advice about NCI interest in accepting a 
competing renewal application to extend the initial award.

The Principal Investigator of a Program must commit a minimum effort of 
30 percent.

Programs 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.

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:

Dan Gallahan, Ph.D., Chief
Structural Biology and Molecular Applications Branch
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5000
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
TEL: (301) 435-5226
FAX: (301) 480-2854
Email: dg13w@nih.gov

o Direct your questions about peer review issues to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Telephone: (301) 496-3428
FAX: (301) 402-0275 
Email:  ncirefof@dea.nci.nih.gov

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

Bill Wells
Grants Administration Branch 
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda, MD  20892-7150
Telephone:  (301) 496-8796
FAX:  (301) 496-8601
Email: wellsw@mail.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 NCI 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:

Dan Gallahan, Ph.D., Chief
Structural Biology and Molecular Applications Branch
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5000
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
TEL: (301) 435-5226
FAX: (301) 480-2854
Email: dg13w@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:

The applicant should identify clearly in the abstract and more fully in 
the research plan the specific questions in current cancer biology that 
are to be explored and the new approaches and collaborations that will 
result from the establishment of the Program.  The synergies to be 
achieved through the establishment of multi-disciplinary teams and 
novel collaborations should be fully described.  It is anticipated that 
the proposed projects will be multi-disciplinary and will draw on a 
variety of resources.  Thus, a well thought out and carefully described 
organization is required.  The PI is responsible for ensuring that 
scientific goals are met, and for developing and managing a decision-
making and administrative structure and process that will allow 
resources to be allocated (and reallocated, if necessary) to meet those 
goals.  This will be particularly important for multi-institutional 
programs.  A management plan should be included outlining the 
organization and administration of the proposed ICBP.

P50 Application

The P50 grant application should specify the administrative and 
organizational structure(s) that will be used to support the research.  
Projects with the complexity, both scientific and managerial, that NCI 
anticipates will characterize these Programs will require a substantial 
amount of the PI's effort to achieve success.  Therefore, the PI will 
be required to devote at least 30 percent effort to the leadership and 
implementation of the Program.  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" or multi-institutional programs 
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.  NCI 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. 

All P50 applications must describe their plans for training and 
education.  The range of activities that may be included is described 
under “Objectives and Scope” section of the RFA.  Applicants are 
encouraged to contact program staff if they have specific questions.

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

The Program may be presented with distinct but interrelated projects or 
as a comprehensive narrative of the objectives, scope, and specific 
aims.  A well justified measure of budgetary flexibility is encouraged.  
For example, if individual projects are described, some may explicitly 
be pilot projects, and it is not necessary that any of the projects 
continue for the full term of the award.  If such flexibility will be 
used, the process by which resources will be redirected should be 
described fully.  Regardless of the structure of the application, the 
research plans (sections a-d of the PHS 398 form) for all projects, 
core(s) and training /outreach activities should not exceed 100 pages.  
Please note that there is no requirement to submit this maximum number 
of pages; instead, concise, articulate applications are desired.

P20 Application

The Exploratory Grant (P20) mechanism should be used when the applicant 
wishes to request a period of planning and preliminary investigation.  
The planning grant application must explicitly demonstrate how these 
specific grant activities will lead to collaborative efforts, and 
describe in substantial detail a vision of the research to be conducted 
by the Program.  These preliminary efforts will be focused on the 
assemblage of teams and small pilot projects.  Because of the 
complexity of the project and the development, the PI will be required 
to devote at least 30 percent effort to the leadership and 
implementation of the Program.

Cost that would be allowable for the Planning grant (P20) include, but 
are not limited to, administrative cost for the planning effort, cost 
for meetings and retreats, cost for the development of specialized 
resources, cost of pilot projects and cost for the recruitment of 
critical personnel.

The planning activities to be carried out, and the justification for 
their necessity, should be described.  This should include the research 
plan for collection of preliminary data, and the scientific planning 
that will ensue to develop the Program.  The application should also 
describe the activities proposed to strengthen the interdisciplinary 
team of researchers, to create a management structure for the team, and 
to develop the courses, curriculum, and other options that will be 
included in the training plan.  The Program may be presented as 
distinct but interrelated projects or as a comprehensive narrative of 
the objectives and scope.  In either case, the page limitation for the 
research plans (sections a-d of the PHS 398 form) for all planning and 
pilot project activities should not exceed 50 pages.  Please note that 
there is no requirement to submit this maximum number of pages; 
instead, concise, articulate applications are desired.

INTELLECTUAL PROPERTY MANAGEMENT PLAN 

Certain research plans will require collaboration and coordination 
between investigators at different institutions, some of whom may not 
be NIH funding recipients and who may have pre-existing intellectual 
property obligations to third parties.  The technology transfer/IP 
management/licensing officer or equivalent of the principal 
investigator’s institution is to submit an intellectual property (IP) 
management plan.  Intellectual property management plans are a just-in-
time requirement; it is not necessary to include the plan in the grant 
application but plans must be in placed before the end of the first 
budget period.

The applicant institution should provide a written assurance that it 
will protect the intellectual property rights of the ICBP investigators 
and their collaborators and under no circumstances engage in 
formal/legal agreements with commercial sources (e.g., pharmaceutical 
companies) that would compromise the ability of ICBP investigators to 
have unhampered access to institutional resources in ICBP related 
research or participate fully in collaborations with any other 
researchers.  The statement of commitment should also include a written 
assurance that in its interactions with commercial entities under 
sponsored research agreements, the ICBP will comply with the 
requirements of the Bayh-Dole Act and NIH funding agreements while 
upholding basic principles of academic freedom.  Sponsored research 
agreements with commercial entities should be entered into by the ICBP 
only upon due consideration of the points outlined in "Developing 
Sponsored Research Agreements: Considerations for Recipients of NIH 
Research Grants and Contracts (Federal Register, Vol. 59, No. 215, 
Tuesday, November 8, 1994, pp. 55674-55679)," a copy of which can be 
viewed at: http://ott.od.nih.gov/spons_research.html.  The statement 
of commitment should also include a written assurance that the ICBP 
will manage its interactions with third parties so that they do not 
restrict the program’s ability to receive and disseminate biomedical 
research materials from and to the scientific community.  Likewise, 
letters should be supplied by any relevant third parties confirming 
their adherence to these policies.

Questions regarding intellectual property management plans should be 
directed to
   
   Technology Transfer Branch
   National Cancer Institute, NIH, DHHS
   (301) 496-0477

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/labels.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 and 
all copies of the appendix material must be sent to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Rockville, MD  20852 (for express/courier service)

Appendices should be comprised of single-sided, unbound materials, with 
separators between documents.

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER 
INSTITUTE WILL NO LONGER BE ACCEPTED.  This policy does not apply to 
courier deliveries (i.e., FEDEX, UPS, DHL, etc.) 
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html)  
This policy is similar to and consistent with the policy for 
applications addressed to Centers for Scientific Review as published in 
the NIH Guide Notice 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

APPLICATION PROCESSING: Applications must be received on or before 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 NCI.  Incomplete and/or nonresponsive 
applications will not be reviewed. 

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 Division of Extramural Activities of the 
NCI in accordance with the review criteria stated below.  As part of 
the initial merit review, all applications will:

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 written critique
o Receive a second level review by the National Cancer Advisory Board.
 
REVIEW CRITERIA

The goals of NCI-supported research are to advance our understanding of 
cancer biology, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate 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 attack a 
highly significant research problem for which some of the details of 
approach have not been established through preliminary data.

Review Criteria for P50 Applications:

SIGNIFICANCE: 
o Does this Program address an important problem in cancer biology?
o If the aims of the application are achieved, how will scientific 
knowledge in cancer biology be advanced?
o What will be the effect of these studies on the concepts and methods 
that drive the field of cancer biology and those that drive the 
emerging field of integrative biology?

APPROACH: 
o Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of 
the project, within the limits inherent in an emerging, complex 
approach to biological research? 
o Does the applicant acknowledge potential problem areas and consider 
alternative tactics?
o Is the management plan appropriate for a large-scale, highly 
integrated Program of this type?  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 Program?
o Is the training and outreach plan appropriate, i.e., is it likely to 
meet the needs of the Program and the scientific community in cancer 
and integrative biology?  Does it integrate well with and leverage 
existing educational and training resources at the institution(s)?  
Will this Program serve as a model for cross-disciplinary activities?
o Is there evidence of strong interaction and feed-back among the 
biology and computational components of the Program?
o Are there appropriate plans to maximize Program flexibility by 
incorporating pilot projects and redirecting resources to maximize 
progress?  Are the plans for oversight of such changes adequate?
o Is there an adequate plan to organize external scientific and 
managerial oversight of the Program, including the selection of pilot 
studies for funding? 

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

INVESTIGATOR: 
o Is the Principal Investigator appropriately trained and well suited 
to lead and coordinate a Program of this size and complexity?
o Does the overall research team have sufficient expertise in all of 
the critical aspects of this undertaking, i.e., cancer biology, 
mathematical modeling, bioinformatics, and training/outreach?

ENVIRONMENT: 
o 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? 
o Is there strong evidence of institutional support?  Is the Program 
that is being developed recognized as a major element within the 
organizational structure of the institution?

Review Criteria for P20 Applications:

SIGNIFICANCE:
o Does this Program plan to address an important problem in cancer 
biology? 

APPROACH:
o Is the scientific research plan of high quality?  Are the exploratory 
research components well justified and do they contribute to the goals 
of the planning effort?  Is it likely that the proposed planning grant 
will culminate in the ability to develop a competitive P50 grant 
application, or to obtain support through other means?
o Is there an appropriate plan for acquisition, organization, and 
deployment of equipment and human resources needed to attain the goals 
of the exploratory research?  Is there an adequate level of effort from 
key personnel?
o Is the plan to develop an effective training/outreach component 
appropriate?
o Is the plan to solicit and fund pilot studies adequate?

INNOVATION:
o Would the proposed Program be innovative in organization, scientific 
approach, or resources that could be mobilized, relative to more 
established efforts in integrative cancer biology?

INVESTIGATOR:
o Is the Principal Investigator appropriately trained and well suited 
to lead and coordinate a planning effort of this kind?
o Is there an adequate pool of expertise at the applicant 
institution(s) in all of the critical aspects of integrative cancer 
biology, or are there plans to supplement available expertise through 
collaboration and/or recruitment?

ENVIRONMENT:
o Does the applicant institution(s) provide an environment conducive to 
the development of a high-quality research effort in integrative cancer 
biology?
o Is the institution(s) committed to the Program in terms of space, 
administrative authority, and other necessary resources, e.g., donated 
faculty time, use of equipment, etc?  Will the Program that is being 
developed be recognized as a major element within the organizational 
structure of the institution? 

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:

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 REVIEW CONSIDERATIONS 

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of 
the proposed research must 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 
url in 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 13, 2004 
Application Receipt Date:  April 13, 2004 
Peer Review Date:  June 2004
Council Review:    September 14, 2004
Earliest Anticipated Start Date:  September 30, 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

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 "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.  
A continuing education program in the protection of human participants 
in research is available online at: http://cme.nci.nih.gov/

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.

In addition to the mandated efforts for ICBP data sharing, applicants 
may wish to place data collected under this RFA in some other 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 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 (also cite 
other relevant policies)

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


H H S Department of Health
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