NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR CANCER
 
RELEASE DATE:  January 16, 2004
 
RFA Number:  RFA-CA-05-001  
 
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):  93.395 
 
LETTER OF INTENT RECEIPT DATE:  April 19, 2004
APPLICATION RECEIPT DATE:  May 19, 2004  
 
This RFA is a reissue of RFA-CA-99-010, which was published in the NIH 
Guide on April 14, 1999.

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism 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 Developmental Therapeutics Program, Division of Cancer Treatment 
and Diagnosis, National Cancer Institute (NCI) invites applications to 
continue the National Cooperative Drug Discovery Group (NCDDG) Program 
for the discovery of new and more effective anticancer treatments.  
This program will further the NIH Roadmap Initiatives 
(http://nihroadmap.nih.gov) and the NCI goal of eliminating the 
suffering and death due to cancer by the year 2015.  For this Request 
for Applications (RFA), the term NCDDG will apply, whether the products 
are from natural sources or of synthetic or biological origin. 
Applications are sought from both new and re-competing NCDDGs (also 
called Groups).  

This RFA will support broad, innovative, interdisciplinary, multi-
project approaches to the discovery of new, rationally based or 
natural-source derived anticancer treatments or strategies.  The 
initiative provides a framework for interactions that will reduce the 
time from concept to product.  A multi-institutional, public-private 
partnership approach involving academic, nonprofit, and/or 
commercial/industrial institutions with Government staff participation 
is envisioned because the creative talents in the required scientific 
disciplines are rarely available in a single institution.  Although not 
required, the active participation of industry is encouraged because it 
will allow this segment of the scientific community to contribute its 
considerable intellectual and material resources.  Further, the 
interaction of academic and non-profit research institutions with 
industry and Government will facilitate subsequent development and 
marketing of new therapies, although these latter activities are not 
within the scope of this RFA.  Biological or molecular targets for drug 
discovery and the sources and types of natural products to be 
investigated will be selected by the applying Group.  

Subsequent studies required for development of new treatments (e.g., 
formulation development, large-scale production for clinical trials, or 
toxicology in support of Investigational New Drug Applications, etc.) 
as well as the clinical trial itself, are beyond the scope of this RFA.  
However, a timely evaluation of products is encouraged.  The 
development of analogs of established or well-studied anticancer agents 
is not responsive to this RFA. 

RESEARCH OBJECTIVES

Background

Important discoveries in molecular biology, cell biology, chemistry and 
related fields, together with major technological advances, permit the 
design of highly selective and specific approaches to discovery of new 
cancer therapies.  Harnessing these exciting advances for development of 
more effective cancer therapy requires the organization of outstanding 
scientists from diverse scientific disciplines within the biological, 
chemical, and pharmacological sciences into highly synergistic research 
teams without regard to institutional affiliation.  To realize this 
objective as well as to make use of facilitating resources of NCI's 
Developmental Therapeutics Program within these teams, the NCI acted on 
the advice of the former Division of Cancer Treatment's Board of 
Scientific Counselors and established the NCDDG program in 1982.  Since 
then the NCDDG program has been recompeted several times.  For 
additional information on history and past accomplishments of NCDDGs, 
visit the web site: http://dtp.nci.nih.gov/ (under Grants and 
Contracts).

NCDDGs are peer-reviewed, multi-component, interdisciplinary projects 
focused on discovery of new approaches for treatment of cancer.  An NIH 
intramural laboratory or a foreign institution may participate as a 
Laboratory Program or a Scientific Core in an NCDDG submitted by a 
domestic institution.  NCDDGs are funded as cooperative agreements, a 
mechanism in which the NCI, through its extramural staff, is an active 
partner in the Group.  NCI staff, represented by a Project Coordinator 
appointed after award, provides advice and guidance in the area of drug 
discovery and development and facilitates access to NCI resources 
including repositories, chemical searches, and screens.  Resources for 
development include, but are not limited to, scale-up synthesis, 
formulation, pharmacology, toxicology, and Investigational New Drug 
Applications (INDAs) to the Food and Drug Administration (FDA).  
Information can be found at the DTP web site: http://dtp.nci.nih.gov/.  
Clinical trials support may be made available through the Cancer Therapy 
Evaluation Program (CTEP): http://ctep.info.nih.gov/.  Additional pre-
clinical developmental support may be obtained though the Rapid Access 
to Intervention Development (RAID) or Drug Discovery Group (DDG) 
mechanisms (http://dtp.nci.nih.gov/).

Objectives and Scope

The purpose of this RFA is to encourage the discovery of novel 
treatments or strategies to eliminate suffering and death due to cancer.  
Groups should use innovative approaches to drug discovery based on 
recent advances in tumor biology and the molecular understanding of 
cancer.  Projects directed at molecular targets and regulatory pathways 
specifically altered in tumor cells are encouraged, whereas approaches 
based solely on inhibition of cellular proliferation without regard to 
exploitation of alterations in cancer cells are discouraged. Specific 
approaches may encompass a wide range of topics such as gene therapies, 
monoclonal antibodies, and vaccines; biological response modifiers; 
design of agents to interfere with transcription factors, signal 
transduction, cell adhesion factors, angiogenesis, hormone or other 
receptors; and other novel targets involved in the initiation and/or 
maintenance of the transformed state and for which a strong rationale 
can be provided.  Development and use of new chemical libraries, 
structural biology, proteomics or computer modeling of receptor targets 
should be considered.  Non-mammalian models may be used if appropriate 
to the goals of the project.  Applications related to treatment of 
childhood cancers as well as AIDS-related malignancies are encouraged.  
It should be emphasized that approaches to realization of the goals of 
this RFA are broad and limited only by the creativity and scientific 
abilities of the applicants.  For more information on the research 
priorities of NCI in cancer prevention and treatment, visit 
http://cancer.gov/pdf/nci_2005_plan.

NCDDGs focused on the discovery and evaluation of new entities from 
natural sources should emphasize the novelty of the natural product 
sources and use molecular target-based screening assays.  Biosynthetic 
approaches are considered within the scope of the RFA. The development 
or use of pre-clinical models based on their ability to discriminate for 
antitumor activity and to test the rationale for natural product 
selection and isolation is encouraged.

Programs for collection and screening of natural product extracts or 
existing combinatorial libraries without strong rationales for material 
selection or testing models, and projects designed to produce analogs of 
extensively studied natural products or their derivatives are not 
responsive to this RFA. To be considered responsive to this RFA, natural 
product discovery Groups must include lead optimization strategies, such 
as modern combinatorial chemistry technology.  If appropriate, Group 
projects could include analysis of new and relevant procedures to 
evaluate in vivo efficacy that will facilitate decisions regarding 
potential clinical utility. Approaches could include development of 
molecular end points or non-invasive agent imaging for tumor and organ 
distribution analysis.  Development and use of assays that can be 
applied to clinical evaluation following completion of NCDDG-supported 
research are especially encouraged. Funds for projects or cores which 
depend on the successful completion of other activities, such as the 
availability of certain reagents or scale-up synthesis, may be included, 
but use of such phase-in funds will be restricted and released only on 
specific written approval by the NCI.

Definitions:

AWARDEE.  The institution to which the NCDDG U19 is awarded.

BIOLOGICAL RESPONSE MODIFIER.  Agent that alters the relationship 
between the tumor and its host by altering the host's response to the 
tumor cells.

CORE, ADMINISTRATIVE.  An administrative unit located at the Principal
Investigator's institution that coordinates all Group activities. It is 
separately budgeted from the PI's Laboratory Program (if any) and 
budgets for activities pertinent to the Group as a whole, such as travel 
for intra-Group meetings.

CORE, SCIENTIFIC.  A separately budgeted scientific service component 
which provides essential facilities or services to two or more of the 
proposed Laboratory Programs.  Core components typically use established 
procedures or protocols rather than generating new research. An NIH 
intramural laboratory or foreign institution may participate as a 
Scientific Core.

CORE LEADER.  The director of a scientific core component who is 
responsible for the conduct of that core.

DRUG.  In the context of this RFA, a term used broadly to encompass 
synthetic agents, natural products and biological products, as well as 
novel therapeutic strategies and inventions designed to treat and cure 
cancer.  Strategies also encompass creative methods to maximize 
antitumor selectivity.

GROUP.  See NCDDG below.

LABORATORY PROGRAM.  A research component headed by a Program Leader 
within an NCDDG with a separate, detailed research plan and budget.  An 
NIH intramural laboratory or foreign institution may participate as a 
Laboratory Program.

NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG).  A unit consisting of 
a Principal Investigator, Program Leaders, Core Leaders (if any), their 
respective programs (at least three laboratory programs), and an NCI 
Coordinator (from the NCI extramural staff, appointed after award) that 
functions as a unit with a common goal: the conceptualization, 
invention, and evaluation of new entities and strategies or rational 
selection, isolation, and evaluation of new entities from natural 
sources for treatment and cure of cancer.  In this RFA, the terms NCDDG 
and Group are used synonymously.

NATURAL PRODUCT.  In the context of the NCDDG program, a term used 
broadly for any naturally occurring chemical or biological entity of 
non-human origin selected and evaluated pre-clinically against cancer.

NCI COORDINATOR.  A scientist from the NCI extramural program staff who 
is appointed by the NCI Program Official just before award, who 
participates as a member of the Group, interacts scientifically with the 
Group and facilitates the role of NCI as partner in the Group. The 
Program Official also may serve as the NCI Coordinator for a Group.

NCI PROGRAM OFFICIAL.  The senior staff member of the Grants and 
Contracts Operations Branch, Developmental Therapeutics Program, 
Division of Cancer Treatment and Diagnosis who provides leadership and 
guidance for the overall NCDDG Program within the NCI, maintains overall 
scientific balance for the NCDDG Program, and ensures that the NCDDG 
Program is consistent with the NCI mission for treatment research.

PRINCIPAL INVESTIGATOR.  The scientist who is designated by the 
applicant institution to direct the NCDDG. The PI will assume 
responsibility and accountability to the applicant institution and to 
the NCI for the performance and proper conduct of the NCDDG in 
accordance with the terms and conditions specified in this RFA.  An NIH 
intramural scientist or a scientist from a foreign institution may not 
serve as a Principal Investigator.

PROGRAM LEADER.  A senior scientist with proven independent research 
capabilities who serves as director of one of the scientific Laboratory 
Programs of the Group and is responsible for the scientific conduct of 
that program. The Principal Investigator of the Group may be a Program 
Leader. An NIH intramural scientist or a scientist from a foreign 
institution may serve as a Program Leader.
 
MECHANISM OF SUPPORT
 
This RFA will use the NIH cooperative agreement (U19) award mechanism.  
As an applicant you will be primarily 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 earliest anticipated award date is May 2005.  
Applications that are not funded in the competition described in this 
RFA may be resubmitted as NEW investigator-initiated applications using 
the standard receipt dates for NEW applications described in the 
instructions to the PHS 398 application.

This RFA uses just-in-time concepts.  It uses the non-modular budgeting 
formats. Applicants should follow the instructions for non-modular 
budget research grant applications.  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.  

The NIH U19 is a cooperative agreement award mechanism.  In the 
cooperative agreement mechanism, the Principal Investigator retains the 
primary responsibility and dominant role for planning, directing, and 
executing the proposed project, with NIH staff being substantially 
involved as a partner with the Principal Investigator, as described 
under the section "Cooperative Agreement Terms and Conditions of 
Award.”  Plans for future competitions of this RFA are currently 
indefinite.

FUNDS AVAILABLE 
 
NCI intends to commit approximately $12 million in FY 2005 to fund 10 
to12 new and/or competitive continuation grants in response to this 
RFA.  An applicant may request a project period of up to 5 years and a 
budget for total costs of up to $1.2 million per year. Because the 
nature and scope of the proposed research will vary from application to 
application, it is anticipated that the size and duration of each award 
will also vary. Although the financial plans of the 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.  Foreign 
collaborators are allowed as Leaders of Programs or Cores.
 
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 

A.  The Group's objectives and goals should be relevant to and 
compatible with the NCI's mission in cancer treatment as stated in this 
RFA.  Applicants should describe their plans to accommodate the stated 
NCDDG requirements, criteria, and NCI involvement.

B.  All proposed Groups must consist of at least three 
interdisciplinary Laboratory Programs with each complementing the 
others’ expertise.  While no maximum number of programs is stipulated, 
when a consortium exceeds five programs the overall Group may become 
difficult to manage.  Groups may also have Scientific and/or 
Administrative Cores that provide essential services to two or more 
Laboratory Programs, but a Core cannot serve as one of the three 
required Laboratory Programs.

C.  The Principal Investigator and each Program Leader must provide a 
signed statement of acceptance of the participation of NCI staff during 
performance of the award as outlined under "NCI Staff Responsibilities" 
below.

D.  A plan should be described for decision-making regarding 
identification and evaluation of promising agents for development.  A 
plan should be provided for developmental activities not supported by 
this RFA but required for introduction of an agent into clinical trial.

E.  For projects involving natural products, a plan for lead 
optimization should be included.

F.  Participation by pharmaceutical companies and biotechnology firms 
is strongly encouraged.  Industrial partners should include key 
personnel who have authority within the company to allocate resources 
to ensure successful completion of the proposed discovery and 
development efforts.

G.  INTELLECTUAL PROPERTY AND PATENT COVERAGE:  Since the discovery of 
new and improved anticancer treatments is the objective of this effort 
and active involvement by industrial laboratories is facilitated by the 
existence of adequate patent coverage, it is essential that successful 
applicants (those likely to receive awards) provide plans to assure 
such coverage.  The situation could be complicated since multiple 
institutions are likely to be involved.  Following peer review of the 
application, each successful applicant Group must therefore provide a 
detailed description of the approach to be used for obtaining patent 
coverage and for licensing where appropriate, in particular where the 
invention may involve investigators from more than one country and 
institution.  Procedures must be described for resolution of legal 
problems should they arise. Your attention is drawn to the NIH 
Extramural Technology Transfer Policies and Documents at 
http://ott.od.nih.gov/NewPages/602-rev2.htm.  

A formal statement of Patent Agreement among all Group members and 
their institutions as well as a detailed description of procedures to 
be followed for resolution of legal problems which may develop, signed 
and dated by the organizational official authorized to enter into 
patent arrangements for each Group member and member institution, must 
be developed.  The signed agreement must be submitted after review and 
prior to award to the assigned NCI Coordinator. 

For applications involving natural products, a formal statement of 
agreement must be provided and signed by authorized representatives of 
all institutions in the Group, assuring that an equitable sharing of 
royalties or profits arising from the discovery, if any, will be 
returned to indigenous peoples, research collaborators, research 
institutions or Governmental entities as appropriate, in the country of 
origin of the natural product sample from which the lead or drug was 
derived.  The signed document must be submitted prior to award to the 
assigned NCI Coordinator. 

A plan must be developed for disposition of natural product samples, 
compound libraries, etc., that are generated over the course of the 
award in conformance with TERMS AND CONDITIONS OF AWARD, Item 1., 
listed below.  The signed document must be submitted prior to award to 
the assigned NCI Coordinator. 

The three documents listed above will be considered confidential and 
should not be included with the application.  These documents must be 
provided after the peer review of applications but before award to the 
assigned NCI Coordinator.  However, awards will not be made until these 
documents are received and approved by NCI.

H.  Funds from this RFA can be used for sample acquisition only from 
locations, domestic or foreign, where the Investigators have secured 
signed documents of Memorandum of Understandings and have obtained 
collection permits.

I.  An NIH intramural scientist (IMS) may not serve as the Principal 
Investigator of an NCDDG but may participate in a Group as a Program 
Leader, Scientific Core Leader, collaborator, or consultant. However, 
an IMS may not receive salary, equipment, supplies, or other 
remuneration from this RFA.  The IMS must obtain approval of his/her 
NIH Institute Scientific Director to allocate resources to the project.  
This letter must specify that no more than $500,000 direct costs of 
intramural resources will be allocated to the project and provide 
assurance that the conduct of the project will comply with the DHHS 
regulations for research involving human subjects (if applicable) and 
with the PHS policy of vertebrate animal research. The participation of 
an intramural scientist is independent of and unrelated to the role of 
the NCI Program Official and Coordinator as described below in TERMS 
AND CONDITIONS OF AWARD. For NCDDG applications that include NIH 
intramural components, the intramural resource level will be accounted 
for in the total cost of the overall application.

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator as well as the 
institutional official at the time of award.  Failure to abide by any of 
the Terms and Conditions of Award pertaining to awardee responsibilities 
stipulated in this Section may result in a reduction of funding, 
withholding of support, suspension or termination of the award.
 
These special Terms and Conditions of Award are in addition to and not 
in lieu of otherwise applicable OMB administrative guidelines, DHHS 
Grant Administration Regulations at 45 CFR parts 74 and 92, and other 
DHHS, PHS, and NIH Grant Administration policy statements.
 
The administrative and funding instrument used for this program is a 
cooperative agreement (U19), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during 
performance of the activity.  To qualify as an NCDDG, the overall 
program must include a minimum of three laboratory programs.  Under the 
cooperative agreement, the NIH purpose is to support and/or stimulate 
the recipient's activity by involvement in and otherwise working jointly 
with the award recipient in a partner role, but it is not to assume 
direction, prime responsibility, or a dominant role in the activity.  
Consistent with this concept, the dominant role and prime responsibility 
for the activity resides with the awardee for the project as a whole, 
although specific tasks and activities in carrying out the studies will 
be shared between the awardee and the NCI Coordinator.
 
1.  Awardee Rights and Responsibilities
 
a. The Principal Investigator will have primary authority and 
responsibility to define objectives and approaches and to plan 
and conduct the proposed research.  She/he will assume 
responsibility and accountability to the applicant organization and to 
the NCI for performance and proper conduct of the research supported in 
the NCDDG, including the NIH intramural component, if applicable, in 
accordance with the TERMS AND CONDITIONS OF AWARD.
 
b. The Principal Investigator, Program Leaders, and NCI Coordinator will 
meet periodically to review progress, plan and design research 
activities, and establish priorities.  The frequency of meetings, not 
fewer than two per year, will be determined by the Principal 
Investigator who will be responsible for scheduling the time and place 
(generally at one of the performance sites) and for preparing concise 
proceedings or minutes (two or three pages) which will be delivered to 
the members of the Group within 60 days of the meeting.  NCI Coordinator 
or Program Official may not chair Group meetings.
 
c. The Government, via the NCI Coordinator, will have access to data 
generated under this cooperative agreement and may periodically review 
the data consistent with current DHHS, PHS, and NIH policies.  However, 
the awardee will retain primary custody of and have primary rights to 
data, and timely publication of major findings by the Group members is 
encouraged.  Publication or oral presentation of work done under this 
agreement will require appropriate acknowledgment of NCI support, 
including the assigned cooperative agreement award number.  
Dissemination of information on synthetic or natural substances supplied 
to the Group by NCI (e.g., for comparative testing purposes, as 
reference material, etc.) will require clearance by NCI to assure 
conformity with existing confidentiality agreements with suppliers.
 
d. Ownership of natural product samples and combinatorial libraries 
acquired during the course of the research rests with the Group.  The 
Group must follow its policy, approved by NCI, for final disposition of 
the samples and ownership rights in the event that the samples are 
transferred to other parties who use them to make discoveries.
   
e. In order that samples be fully evaluated for anticancer potential 
after the Group has concluded its evaluation, but before the samples are 
transferred to other parties for evaluation in other therapeutic areas, 
it is requested that the Group provide lists of completed samples to the 
NCI Coordinator, who may facilitate additional biological evaluation in 
NCI's contract-based screening facilities or at an additional testing 
resource of mutual agreement to NCI and the Group.
 
f. The NCI recognizes that most countries retain interest in samples 
collected within their domains.  All applicants who propose foreign 
collections of natural products must provide a formal statement of 
agreement to NCI prior to award, signed by authorized representatives of 
all Group member institutions, for equitable return of a portion of any 
profits or royalties derived from NCDDG discoveries to indigenous 
peoples, research collaborators, cooperating institutions or 
Governmental entities in the countries of origin, as appropriate to 
their contributions.
 
g. Foreign trips for collection purposes must be itemized separately.  
These funds will be restricted by NCI and require prior approval for 
release.  Written approval for release of funds will be granted only 
after appropriate clearance documentation from the source country is 
provided.
 
2.  NCI Staff Responsibilities
 
NCI will participate as a member of the Group and will be represented by 
an NCI Coordinator, who will have substantial scientific programmatic 
involvement during the conduct of this activity that is above and beyond 
the normal stewardship for grant awards.  In all cases, the role of NCI 
will be to assist and facilitate and not to direct activities.
 
The NCI Coordinator, as well as any other Group member, may assist in 
research planning; may suggest studies within the scope of the Group's 
objectives and research activities; may present to the Group 
experimental findings from published sources or from contract projects 
in support of these suggestions; may participate in the design of 
experiments agreed to by the Group; and may participate in the analysis 
of results.  However, the NCI Coordinator will not conduct laboratory 
studies.
 
Upon recommendation of the NCI Coordinator, NCI may utilize its drug 
development resources (http://www.dtp.nci.nih.gov/) in support of Group 
research activities when such resources may be required on an occasional 
basis.  The following is a list of resources that may be supplied if 
they become desirable during performance, are not anticipated as a 
continuing need, and are readily available:
 
a. Reference compounds for standardization of test systems, as 
analytical standards, and for related purposes.
 
b. Needed resources such as test materials and information that may not 
otherwise be available to the Group.
 
c. Data from testing conducted in resource contract laboratories.
 
d. Laboratory testing capacity, whenever appropriate and possible, in 
the current contract- based preclinical therapy-related laboratory 
testing program.  The Group is expected to provide sufficient test 
material for such testing.
 
e. Searches of computer files for information about materials, chemical 
structures and biological activities, if requests for such searches are 
sufficiently focused to avoid excessive costs.  Information given to a 
Group will be restricted by any standard confidentiality agreements 
between the Government and suppliers of test materials to the 
Government.
 
f. Experimental animals and cultured cells, if available, to Groups 
whose main research activities do not require these materials on a 
regular basis.  Groups whose experimental approach involves studies that 
require animals on a regular basis must budget for these costs in their 
application.
 
These "Terms and Conditions of Award" require that the NCI Coordinator 
approve the following: changes in the Principal Investigator or Program 
Leaders; reports intended for inclusion in Investigational New Drug 
Applications (INDAs) and Clinical Brochures; redistribution, outside the 
NCDDG, of biological and chemical materials received from the 
Government; and dissemination of research findings resulting from the 
use of such materials.
 
3.  Collaborative Responsibilities
 
The following Collaborative Responsibilities are based on the premise 
that the NCDDG is a unit consisting of a Principal Investigator, Program 
Leaders, Core Leaders, and their respective programs, and an NCI 
Coordinator which functions as a unit as specified in this RFA.  Foreign 
institutions and NIH intramural laboratories may be participants as 
Programs or Scientific Cores but not as the awardee institution, and 
their scientists may not serve as the Principal Investigator.
 
a. The principal end product of NCDDG activities will be the discovery 
of new entities and strategies for development to clinical trial.  
Subsequent developmental work through private resources is encouraged.  
Alternatively, the Group may recommend that development be sponsored by 
NCI.  In the latter case, it will be necessary for the Principal 
Investigator and NCI Coordinator to cooperate in the analysis, 
summarization, preparation, and presentation of data to the appropriate 
NCI staff.
 
b. NCI will retain the option to cross-file or independently file an 
application for investigational clinical trial (e.g., an Investigational 
New Drug Application [INDA] to the United States Food and Drug 
Administration) of any invention resulting from these NCI supported 
cooperative agreements.  Reports of data generated by the Group or any 
of its members required for inclusion in INDAs and Clinical Brochures 
and for cross-filing purposes shall be submitted promptly by the 
Principal Investigator to the NCI Coordinator upon request.  Such 
reports shall include background information, methods, results, and 
conclusions.  They will be subject to approval and revision by NCI and 
may be augmented with test results from other Government-sponsored 
projects prior to submission to the appropriate regulatory agency.
 
4.  Arbitration
 
Any disagreement that may arise on scientific/programmatic matters 
(within the scope of the award, including the NIH intramural component) 
between the awardee and the NCI may be brought to arbitration.  An 
arbitration panel will be composed of three members: one Group designee, 
one NCI designee, and a third designee with expertise in the relevant 
area chosen by the other two.  This special arbitration procedure in no 
way affects the awardee's right to appeal an adverse action that is 
otherwise appealable in accordance with PHS regulations at 42 CFR Part 
50, Subpart D, and DHHS regulations at 45 CFR Part 16.
 
WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues: 

o Direct your questions about scientific/research issues to

Mary K. Wolpert, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 8153, MSC 7456
Bethesda, MD  20892-7456
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-8783
FAX: (301) 402-5200
Email: wolpertm@exchange.nih.gov

For specific information related to chemistry or structural biology 
contact:

Dr. Ronald Dubois 
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 8153, MSC 7456
Bethesda, MD  20892-7456
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-8783
FAX: (301) 402-5200
Email: duboisro@mail.nih.gov 

For specific information related to natural products research, contact: 

Dr. Yali Hallock 
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 8153, MSC 7456
Bethesda, MD  20892-7456
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-8783
FAX: (301) 402-5200
Email: hallocky@mail.nih.gov

o Direct your questions about peer review issues to:

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

Ms. Jill Rogers
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda, MD  20892-7150
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-8796
FAX:  (301) 496-8601
Email:    jr261m@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 to by the date listed at the 
beginning of this document.  The letter of intent should be sent to:

Mary K. Wolpert, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPS Room 8153, MSC 7456
Bethesda, MD  20892-7456
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-8783
FAX: (301) 402-5200
Email: wolpertm@exchange.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 Grants Info, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov. 

SUPPLEMENTARY INSTRUCTIONS:  The submission of a single application for 
a proposed NCDDG is required (that is, all parts of the application 
must be packaged together and submitted by the applying organization).

Because of the interdisciplinary and usually multi-institutional nature 
of an NCDDG, the special requirements of the RFA, and the special 
provisions which must be followed when NIH intramural laboratories are 
participants, the following guidance is provided to help the applicant 
include all necessary information and still provide a document that can 
be readily reviewed.  Applications that are incomplete will be returned 
without review.  Information about the NCDDG program can be found at 
http://dtp.nci.nih.gov.

FORMAT OF APPLICATION

General instructions for the preparation of applications are contained 
in the Grant Application Form PHS 398 (revised 5/2001) and can be found 
at http://grants.nih.gov/grants/funding/phs398/phs398.html.  These 
instructions are designed primarily for traditional research project 
(R01) applications.  NCDDG applications require additional information 
as outlined below.  Page limitations are presented in the PHS 398 
instructions and these should be followed for each individual 
Laboratory Program and Core unless otherwise noted.  Please note that 
an NCDDG is headed by a Principal Investigator and includes research 
components called Laboratory Programs headed by Program Leaders and may 
include Cores headed by Core Leaders.  Programs are equivalent to R01 
projects as far as the PHS 398 Instructions are concerned and the 
instructions are the same except as noted below.

Description, Performance Sites, and Key Personnel (PHS 398 Form Page 2 
and Continuation Pages:  This section should concisely state the 
overall goals of the NCDDG and clearly state the contribution of each 
component to the overall goals.  Key personnel for the entire Group 
including consultants and consortium collaborators should be listed 
alphabetically.  Use the terms "Program Leader" and "Core Leader" as 
appropriate to identify personnel performing these roles.

Research Grant Table of Contents (PHS 398 Form Page 3 and Continuation 
Pages:  The application is reviewed as a whole as well as Program by 
Program; therefore, prepare a detailed Table of Contents that enables 
reviewers to find specific information readily.  Identify Laboratory 
Programs by number, title, and responsible investigator.  Identify 
Cores by letter, title and responsible investigator.  A sample table of 
contents is included at the end of these special instructions to show 
the order and format in which the application should be organized.

Agreement to Accept NCI Participation (PHS 398 Continuation Pages):  
The agreement to accept NCI participation in the NCDDG as described in 
the RFA text, and signed by all parties, must be inserted in the 
application after the Table of Contents.

Budget Instructions for Initial Budget Period: Follow the Detailed (not 
modular) Budget Instructions for Initial Budget Period (PHS 398 Form 
Page 4.  Items in this section of the PHS 398 Instructions must be 
followed carefully in preparing the total NCDDG budget.  Budgetary 
information is also required for each grant component as part of the 
write up for that component (Laboratory Program or Core).  Specify and 
justify personnel effort even if no salary support is requested.

Present a detailed composite budget for all requested support for the 
first year, using page 4 of the PHS 398 application form. If 
collaborative efforts or "purchased services" involving other 
institutions or organizations are anticipated, itemize all costs 
associated with such third party participation, including any 
applicable Facilities and Administrative (F&A) costs on a separate 
budget page and enter the total under the "Consortium/Contracted Costs" 
direct costs budget category.  For details on consortium budgets, see 
the NIH Grants Policy Statement (03/01) at  
http://grants.nih.gov/grants/policy/nihgps_2001/index.htm. Under 
NIHGPS (03/01) in the left hand corner of the screen, scroll down to 
Part II: Other Terms then click Consortiums.

Travel costs for Group meetings should be included in the budget for 
the Administrative Core.  All other scientific travel should be 
included in the budget for each individual Program or Scientific Core.

Budget Instructions for Entire Proposed Period of Support (PHS 398 Form 
Page 5 and Continuation Pages:  Present a composite summary budget for 
all years of requested support for the overall Group by category, i.e., 
personnel, equipment supplies, etc.  All increases for future years, 
whether standard cost of living or projected special requirements, 
should be stated explicitly and clearly justified.  Often the various 
research tasks necessary to reach the Group's goals may need to be 
phased in, at least in part, in sequential fashion.  In such cases, the 
budgets for the individual Laboratory Programs should, logically, 
reflect an appropriate change in relative emphasis among tasks until an 
operational steady state situation is attained.  Detailed justification 
for phase-in budgets must be provided.  Costs for Group meetings and 
intra-Group communications should be budgeted in the Administrative 
Core taking care not to duplicate these costs in the budgets for 
individual Programs.  Budgetary provision should be made for items such 
as scale-up synthesis; actual use of funds for these purposes will be 
restricted by the NCI to the purposes stated and funds will be released 
if and as needed only on specific recommendation of the NCI Program 
Official.
                   
Foreign trips for collection purposes must be itemized separately.  
These funds will be restricted by NCI and require prior approval.  
Approval for release of funds will be granted only after appropriate 
clearance documentation from the source country is provided.  
 
Biographical Sketches (PHS 398 Format page "BIOGRAPHICAL SKETCH" and 
Continuation Page; PHS 398 Instructions):  Biographical sketches as 
described in this section of the instruction sheet must not exceed four 
pages.  Therefore, cite only the most relevant publications.  Place the 
biographical sketches in alphabetical order by last name immediately 
after the budget sections.  Do not repeat biographical sketches in each 
Program component.  Biosketches are required for all professional 
personnel participating in individual Laboratory Programs and cores and 
for all consultants.  Include all biosketches in the application and 
not in an appendix.

Overall NCDDG Description (PHS 398 Continuation Pages):  The overall 
NCDDG description should explicitly provide the required information in 
the order noted below.  This description should not exceed 25 pages, 
excluding publications. 

o Goals:  Present the general problem area to be studied, the overall 
long-term objectives of the research described in this application and 
the hypotheses to be tested.  Discuss the relationship of your goals to 
the discovery of new treatments for cancer.

o Interrelationships:  The NCDDG is a confederation of interrelated and 
interdependent Laboratory Programs.  It is important to address the 
integration of the components, demonstrating how each individual 
program and core benefits from and contributes to the overall Group as 
well as how the Group intends to interact with the NCI.  A diagram 
illustrating the effective interactions between components may be 
helpful to reviewers.  Details should be provided about Group meetings 
which are expected to be held at least twice per year and how frequent 
communication between Group meetings will be maintained.  The agreement 
to accept NCI participation should be discussed in this section.

o Research Plan:  This section delineates the research addressed by the 
Group as a whole and explains the strategic approach to the problem, 
briefly mentioning each component (Laboratory Program or Scientific 
Core) as it relates to the overall NCDDG.  Descriptions of prior 
collaborative efforts among investigators in the Group, as well as the 
sequence of events leading to the current application may also be 
included in this section.  It is important to discuss the advantages 
expected from a group effort, and how they will further the goals of 
the research.

o Lead Optimization: Discuss how the Group plans to optimize lead 
structures discovered in Group research.

o Development Plan:  As required in the RFA, discuss how the Group 
intends to pursue leads discovered in the research towards advanced 
pre-clinical and clinical development.

o Preliminary Studies (for new applications):  This section should 
focus on research already underway and current accomplishments of the 
investigators.  More detailed preliminary results are to be included 
separately under each individual Laboratory Program or Core.  Items to 
be included are a summary of major accomplishments attributed to the 
participating investigators that relate to the overall theme of the 
Group and a list of all publications and manuscripts accepted for 
publication already produced by the interactions of the participating 
investigators.

o Progress Report (for competing renewal applications):  This section 
should describe the achievements of the Group since the last 
competitive review with emphasis on the discovery of new anticancer 
treatments and new leads.  Separate progress reports are included in 
the individual Laboratory Programs, so this section should focus on the 
overall Group rather than reiterating information provided in each 
component.  Include the following:

Summarize the major accomplishments that can be attributed to the 
Group.  Identify which components were involved in these 
accomplishments.  

Discuss the role of the NCI in your accomplishments. 

Discuss any changes in the composition of the Group and the reasons for 
the changes.

Provide a list of all publications and completed manuscripts that have 
resulted from the award.  Indicate those which involved participation 
of more than one Group component.

o Institutional Environment and Resources:  Discuss the overall 
resources that are available to the Group, particularly those which 
relate to the overall Group and provide special opportunities.  These 
could include resources of industrial collaborators, consultants, etc.  
The resources and environments specific to the laboratory components 
and cores are to be detailed in their individual parts of the 
application.

o Organization and Administrative Structure:  Describe in detail and by 
diagram the chain of authority for decision making and administration, 
beginning at the level of the Principal Investigator. Include all 
investigators responsible for individual Laboratory Programs and cores 
and detail how the tasks are planned, coordinated, and evaluated.  If 
internal or external advisory groups are to be used, list the 
membership (actual but not proposed members) and describe the role of 
each.  List in a separate table all consultants, both paid and unpaid.

o Literature Cited:  While this section is not included in the page 
limitation, it is important to be concise and to select only those 
literature references pertinent to the overall description. List 
complete literature citations as directed in the PHS 398 Instructions.  

o Appendix: Again, this section is not included in the page 
limitations. Organize appendix materials in the following sequence:  
Appendix material for the overall NCDDG, followed by appendix material 
for numbered Laboratory Programs, if needed, followed by appendix 
material for lettered Cores, if needed.  Limit the appendix to those 
few most essential publications necessary to document your application
o Laboratory Programs:   Describe each Laboratory Program (term used to 
describe an individual research project in a Group) in sufficient 
detail to enable reviewers to judge the scientific merit from the 
written application.  Use the outline below. In each Laboratory 
Program, sections A-D of the Research Plan should not exceed 25 pages.

Cover Page (Use a PHS 398 Continuation Page and NOT form page 1, FACE 
PAGE from PHS 398). Clearly denote the Laboratory Program number, the 
title of the Laboratory Program, the name of the Program Leader, and 
the Program Leader's Institution.

Key Personnel (PHS 398 Form page 2). The title of Principal 
Investigator is reserved for the director of the overall Group.  The 
directors of the individual Laboratory Programs should be referred to 
as "Program Leaders".

Omit Table of Contents (already included in OVERALL section). 

Budget. Use detailed budget formats even if no more than $250,000 
direct costs per year are requested for an individual program. Use PHS 
398 Form Pages 4 and 5 and PHS 398 Instructions, Pages 10-14.  A 
detailed budget is required for the first year and the budget summary 
for each additional year.  The budget justifications are to be 
explicit, including those for changes for future years.

Omit Biographical Sketches as these are included elsewhere in the 
application.

Resources and Environment:  List only those specific to the Laboratory 
Program. Clearly explain the position of Program Leaders from 
pharmaceutical companies.  The Program Leader should be responsible for 
allocation of resources required for the research. No page limitation.

Research Plan:  

Laboratory Program aspects - Include Sections A, B, C and D. Limited to 
25 pages.

Relation of Laboratory Program to overall NCDDG:  (This item is not 
included in PHS 398 Instructions.)  Describe in this section the 
relevance of the Laboratory Program to the primary theme of the Group 
and the collaborations with other investigators within the Group. 
Limited to one page.

Human Subjects:  If any organizational component within an NCDDG uses 
human subjects, this information must be noted on the face page for the 
overall application.

If human subjects are involved in the application, be sure to address 
all aspects including Gender and Minority Inclusion for Research 
Involving Human Subjects and Inclusion of Children as Participants in 
Research Involving Human Subjects. HS 398 Instructions, Pages 17-2.  
There are no page limitations here but be succinct and address the four 
points for each laboratory program that uses human subjects.  

Vertebrate Animals: If any organization within a NCDDG uses vertebrate 
animals, this information must be noted on the face page for the 
overall application.  Again, there are no page limitations but be 
succinct, and address the five points for each laboratory program that 
uses vertebrate animals.

Consultants/Collaborators:  (PHS 398 Continuation Pages).  List only 
those consultants or collaborators who are specific to this Laboratory 
Program. No page limitation.

Literature Cited:  (PHS 398 Continuation Pages; PHS 398 Instructions, 
Page 28).  List complete literature citations at the end of each 
Laboratory Program.  Each citation must include the names of all 
authors, full title, name of book or journal, volume, pages and year of 
publication. No page limitation but select only pertinent references.

Do NOT include a checklist for each Laboratory Program.  There should 
be only one checklist at the very end of the entire application, and 
that should come from the organization submitting the overall NCDDG.

Cores:  (PHS 398 Continuation Pages).  The Cores within a Group may 
include laboratory facilities, equipment, and services which will be 
shared by two or more Laboratory Programs.  A core may also include 
support of administration, such as the costs of business management, 
consultants, and secretarial services associated with the Group where 
these items are not included in the institution's indirect cost rate.  

Using a Form PHS 398 Continuation Page, denote "Core Component" 
(followed by a letter if there is more than one core), the title of the 
core, and the name and institution of the Core Leader. 

The Administrative Core at the Principal Investigator's institution 
must be designated as "Core A", followed by Scientific Cores, if any.  
An Administrative Core may be omitted in special circumstances, such as 
an application from a single institution.

For each Scientific Core component, follow the specific instructions 
and page limitations for the Laboratory Program, above, except that in 
place of the item "Research Plan", describe the role of the core 
component as a resource to the NCDDG as a whole.  Clearly present the 
facilities, resources, services, and professional skills that the core 
component provides.

Checklist for overall application (Use PHS 398, CHECKLIST FORM PAGE: 
Self-explanatory.

Additional documentation of a legal and proprietary nature, described 
in the RFA under SPECIAL REQUIREMENTS, will need to be sent to the NCI 
Coordinator assigned to the application before an award can be made. 
This information will be considered confidential and will not be 
provided to reviewers as part of the application material.  This 
documentation must be signed by authorized representatives of all Group 
participants.  The three documents include a Patent Agreement (required 
by all Groups), a formal statement providing assurance that an 
equitable portion of profits will be returned to indigenous people from 
the country of origin (required by Groups discovering drugs from 
natural products obtained from foreign sources), and a plan for 
ownership and use of natural product extracts or chemical libraries 
after the Group has decided that they are no further value to the Group 
Programs (required by Groups generating these products). Although this 
documentation is to be sent when requested by NCI staff after the peer 
review of applications but before award, applicant organizations would 
be well advised to have this information ready to be supplied. 
Incumbent applicants can state on an appropriate continuation page that 
there are no changes from previously submitted information, if this is 
the case.

SAMPLE TABLE OF CONTENTS:  IN ORDER TO AID THE REVIEW OF APPLICATIONS, 
PLEASE ORGANIZE YOUR MATERIALS IN THE ORDER SHOWN IN THIS SAMPLE TABLE.

SECTION I

Face Page
Table of Contents
Agreement to Accept NCI Participation
Detailed Group budget for First 12-Month Period
Budget Estimate for Each Year of Funding
Biographical Sketches (alphabetical order by last name)

SECTION II

Overall NCDDG Description:
Goals
Interrelationships
Research Plan
Development Plan
Preliminary Studies/Progress Report
Institutional Environment and Resources
Organization and Administrative Structure
Literature Cited with complete titles and authors
   
Laboratory Program 1 (Title):
Cover Page
Description of Research Plan/ List of Key Personnel
Detailed budget for First 12-Month Period
Budget Estimate for Each Year of NCDDG
Resources and Environment
Research Plan
(Human Subjects)
(Vertebrate animals)
Consultants/Collaborators
Literature Cited with complete titles and authors

Laboratory Program 2 (Title):
Cover Page
Description of Research Plan/ List of Key Personnel, etc.

Core Component A (Title) (Administrative Core, if present):
Cover Page
Description of Core/List of Key Personnel
Detailed budget for First 12-Month Period
Budget Estimate for Each Year of NCDDG
Resources and Environment
Role and Justification for the Core Component
   
Core Component B (Title) (Scientific Core, if Present):
Cover Page
Description of Core/List of Key Personnel
Detailed budget for First 12-Month Period
Budget Estimate for Each Year of NCDDG
Resources and Environment
Role and Justification for the Core Component
(Human Subjects)
(Vertebrate animals)
Literature Cited with complete titles and authors

Check List

Appendix (if appendix is needed, put documents in following sequence):
Overall Group Description
Numbered Laboratory Programs
Lettered Cores

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 us 
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)
Telephone:  (301) 435-0715

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)
Telephone:  (301) 496-3428

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 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 CSR and 
responsiveness by 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 applicants 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 NCI National Cancer Advisory 
Board (NCAB).

REVIEW CRITERIA

Review Criteria for NCDDG as a Whole

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 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 the following 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application.

o Significance 
o Approach
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be 
judged likely to have major scientific impact and thus deserve a high 
priority score.  For example, an investigator may propose to carry out 
important work that by its nature is not innovative but is essential to 
move a field forward.

All applications will be judged on the basis of the scientific merit of 
the proposed project and documented ability of the investigators to 
meet the RESEARCH OBJECTIVES of the RFA.  Although the technical merit 
of the proposed studies is important, the likelihood of identifying a 
clinical trial candidate and the plan for pre-clinical development 
activities beyond the scope of the RFA will be part of the evaluation.

Within this framework the specific goal of this RFA is the discovery 
and pre-clinical analysis of new agents to treat cancer.  The reviewers 
will address the following criteria in assigning priority scores, 
weighting them as appropriate for each application.  Individual 
Programs and Cores within the NCDDG, as well as the NCDDG as a whole, 
will be evaluated.  Note that each Program within the NCDDG does not 
need to be strong in all categories as long as it contributes a 
necessary function to the goals of the Group.

Each application will be evaluated for the extent of progress on prior 
award (RECOMPETING GROUPS) or preliminary results (NEWAPPLICANTS).  
Groups will be evaluated for extent of effectiveness of cooperation 
with the NCI (RECOMPETING GROUPS) and adequacy of plans for cooperation 
with the NCI (ALL APPLICANTS).

SIGNIFICANCE: Does the applicant address an important problem in 
anticancer drug discovery and/or development? If the aims of the 
application are achieved, what is the likelihood of a new cancer 
therapy or strategy for clinical evaluation?  Is the development plan 
adequate to bring the agent to clinical trial?

APPROACH: Are the overall conceptual frameworks, designs, methods, and 
analyses adequatelydeveloped, well-integrated, and appropriate?  Are 
the scientific disciplines represented in Programs and Scientific Cores 
adequate to achieve Group objectives?  Does the applicant acknowledge 
potential problem areas and consider alternate tactics? Are targets and 
screens relevant to the neoplastic process?  Are plans adequate for 
ensuring effective intra-Group communication and for assuring Group 
cohesiveness?  Is the plan to optimize lead structures, from both 
synthetic and natural sources, adequate to ensure that the most 
efficacious drug will result?  Are plans for decision-making regarding 
identification and pursuit of lead candidates reasonable and 
appropriate?

INNOVATION: Does the NCDDG employ novel concepts, approaches, or 
methods?  Are the aims original and innovative?  Does the NCDDG 
challenge existing paradigms or develop new methodologies or 
technologies?  Is the target under investigation for drug discovery 
novel?  Will new paradigms for drug discovery emerge?

INVESTIGATORS: Are the Principal Investigator and Program/Core Leaders 
appropriately trained and well suited to carry out this work?  Is the 
time commitment for each sufficient to achieve goals?  Has the 
Principal Investigator demonstrated leadership in development, 
implementation and management of comprehensive research programs?

ENVIRONMENT: Does the scientific environment in which the Programs will 
be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
expertise and foster effective collaborations?  Is there evidence of 
institutional support and competence of the applying Institution to 
serve as the Administrative Core for the Group?

Review Criteria for Programs SIGNIFICANCE:  Does this program address 
an important problem in anticancer drug discovery and/or development?  
If the aims of the program 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 program?  Does the applicant acknowledge potential problem areas 
and consider alternative tactics?

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

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

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

Review Criteria for Cores

The utility of the Core to the NCDDG.  Each Core must provide essential 
facilities or services for two or more programs judged to have 
substantial merit.  

The quality of the facilities or services provided by the Core 
(including procedures, techniques, and criteria for prioritizing 
activities).

The qualifications, experience, and commitment of the personnel 
involved in the Core.

For an Administrative Core:  Resources and plans provided for Group 
communication and coordination of Group activities.

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).  The four items 
described in PHS 398 must be included in each program or core that uses 
human subjects.
 
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 any program or core, the five items described under 
Section f of the PHS 398 research grant application instructions (rev. 
5/2001) will be assessed.  The five items must be included in each 
program or core that uses animals.

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.  Instructions concerning this policy are listed 
below under REQUIRED FEDERAL CITATIONS. 

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:  April 19, 2004
Application Receipt Date:  May 19, 2004
Peer Review Date:  October 2004
NCAB Review:  February 2005 
Earliest Anticipated Start Date:  May 1, 2005

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 $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.

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.

VERTEBRATE ANIMALS: The PHS Policy on Humane Care and Use of Laboratory 
Animals requires that applicant organizations proposing to use 
vertebrate animals file a written Animal Welfare Assurance with the 
Office for Protection from Research Risks, establishing appropriate 
policies and procedures to ensure the humane care and use of live 
vertebrate animals involved in research activities supported by the 
PHS.  The PHS policy stipulates that an applicant organization, whether 
domestic or foreign, bears responsibility for the humane care and use 
of animals in PHS-supported research activities.  Additional 
information in outlined in the PHS 398 instructions and available at: 
http://grants.nih.gov/grants/olaw/references/phspol.htm.

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 that 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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