Full Text CA-95-020

NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS

NIH GUIDE, Volume 24, Number 33, September 22, 1995

RFA:  CA-95-020

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Chemotherapeutic Agents 
  Biomedical Research, Multidiscipl 


National Cancer Institute

Letter of Intent Receipt Date:  October 1, 1995
Application Receipt Date:  December 20, 1995

PURPOSE

The Developmental Therapeutics Program, Division of Cancer Treatment,
National Cancer Institute (NCI) invites applications for the
continuance of the National Cooperative Drug Discovery Group (NCDDG)
and National Cooperative Natural Products Drug Discovery Group
(NCNPDDG) Programs for the discovery of new and more effective
anticancer treatments.  Applications are sought from both recompeting
NCDDGs and NCNPDDGs as well as from new applicant Groups.

This Request for Applications (RFA) will support broad, innovative,
multidisciplinary approaches to the discovery of new, rationally
based (NCDDG) or natural-source derived (NCNPDDG) anticancer
treatments.  A multi-institutional approach involving academic,
nonprofit, and/or commercial/industrial institutions is envisioned
because the creative talents in the required scientific disciplines
will rarely be available in only one institution.  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.

The present RFA is a reissuance of CA-94-007 and CA-94-008, which
were released on June 3, 1994.  The "Research Objectives" of the RFA
require that an NCDDG or NCNPDDG has the capacity within itself to
discover and evaluate new entities and strategies for the treatment
of cancer.  Biological or molecular targets for drug discovery, and,
for the NCNPDDG program, the sources and types of natural products to
be investigated, will be selected by the applying Group.  For the
NCDDG program either mechanism of action or disease-oriented
approaches are being solicited.  Although this RFA does not support
clinical trials, a timely evaluation of products discovered by the
Groups is encouraged.

Subsequent studies required for development of new treatments and
progression to clinical trial (e.g., formulation development,
large-scale production for clinical trials, or toxicology in support
of Investigational New Drug Applications, etc.) are beyond the scope
of this RFA.  The development of analogs of established anticancer
agents is not responsive to this RFA.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
National Cooperative Drug Discovery Groups, is related to the
priority area of cancer.  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Applications from minority and women investigators are encouraged.

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for support of
awards will be 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. Under the
cooperative agreement, the NCI 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.  Details of the responsibilities, relationships and
governance of the study to be funded under cooperative agreement(s)
are discussed later in this document under the section "Terms and
Conditions of Award."

Assistance via cooperative agreement differs from the research
project grant in that the Government component (NCI) awarding the
cooperative agreement anticipates substantial programmatic
involvement during performance of the award.  This partnership
relationship will facilitate technology transfer from
Government-owned data bases and the use of appropriate NCI-derived
resources to enhance the efficiency and effectiveness of a Group's
efforts.  The nature of NCI staff participation is described below
under "Terms and Conditions of Award".  There is no intent, real or
implied, for NCI staff to direct Group activities or to limit the
freedom of investigators.

Award will be made only to the Principal Investigator's institution.
All Group activities will be coordinated through an administrative
core located at the Principal Investigator's institution.

The total project period for applications submitted in response to
the present RFA may not exceed five years.  The earliest anticipated
award date is August 1, 1996.  Because the nature and scope of the
research proposed in response to this RFA may vary, it is anticipated
that the size of awards will vary also.

The number of awards and the level of support depend on receipt of a
sufficient number of applications of high scientific merit.  Although
this program is provided for in the financial plans of the NCI,
awards pursuant to this RFA are contingent upon the availability of
funds for this purpose.

At this time, the NCI anticipates that there will be a renewed
competition of this program.  However, if the NCI does not continue
the program, awardees may submit grant applications through the usual
investigator-initiated grants program.

FUNDS AVAILABLE

The NCI has set aside approximately $3.5 million total costs (direct
plus indirect costs) for the first year of funding.  This level of
support is dependent on the receipt of a sufficient number and
diversity of applications with high scientific merit.  It is
anticipated that three or four NCDDG and one or two NCNPDDG awards
will be made for periods up to five years.

Awards are subject to a first year limit of $900,000 in total costs.
Budget requests should be carefully justified and commensurate with
the needs of the project.  Applications in excess of $900,000 total
costs for the first year will be returned without review.  Annual
budgets for years two to five cannot exceed $900,000 plus a four
percent yearly increase.

RESEARCH OBJECTIVES

Background

Important new discoveries in molecular biology, embryology and
related fields, together with major technological advances, permit
the design of highly selective and specific approaches to discovery
of new cancer therapies.  Exploitation of 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
utilize facilitating resources of NCI's drug development program
within these teams, the NCI established, in 1983, on advice of a
special subcommittee of the Division of Cancer Treatment's Board of
Scientific Counselors, the National Cooperative Drug Discovery
(NCDDG) program.  The NCDDG was initiated by Requests for
Applications (RFAs) issued in July 1983 and August 1984 for the
exploitation of mechanistically based differences between normal and
cancer cells.  October 1986 reissuances established groups focused on
exploitation of specific and unique characteristics of lung and
colorectal cancers.  The NCDDG approach to modern drug discovery was
broadened further in August 1987 by RFAs inviting applications for
the creation and evaluation of both the general mechanism of action
based and the specific disease oriented anticancer treatments as well
as for the development of innovative preclinical models.  Combined
RFAs were issued in August 1991 and March 1994 for general mechanism
of action and specific disease oriented research.

National Cooperative Natural Products Drug Discovery Groups
(NCNPDDGs) were established through RFAs issued in September 1988 and
October 1989 with a reissuance in March 1994, to enhance discovery of
novel chemotypes from natural sources for subsequent development as
anticancer agents.

NCDDGs and NCNPDDGs are peer-reviewed projects funded as cooperative
agreements.  The cooperative agreement is 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, provide advice and guidance in the area of drug discovery and
development and facilitate access to NCI resources including
repositories, chemical searches, and screens.  Resources for advanced
development including scale-up synthesis, pharmaceutics, toxicology,
Investigational New Drug Applications (INDAs) to the Food and Drug
Administration (FDA), and clinical trials support can be made
available through the NCI Decision Network process (M.R. Grever, S.A.
Schepartz, and B.A. Chabner, Seminars in Oncology, Vol. 19, No. 6
(December), 1992: pp 622-638) or through private venture capital.

Objectives and Scope

The purpose of this RFA is to encourage the discovery of novel
therapies and therapeutic strategies to improve the survival of
cancer patients.  Projects organized for both the NCDDG and NCNPDDG
programs should utilize, to the extent possible, novel and innovative
approaches to drug discovery based on recent advances in tumor
biology and the molecular understanding of cancer.  Approaches to
targets specifically altered in tumor cells 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.  Applications with relevance to high
priority diseases, such as breast and prostate cancer, are
encouraged, but this RFA is not meant to exclude any approach or
disease type.  Rather, the emphasis is on creative ideas.

Applications could include approaches to chemical modification of
leads, but it should be emphasized that discovery of new agents and
not modification of known structures should be the primary focus of
the Group activities.  Preclinical evaluation that will facilitate
decisions regarding potential clinical efficacy of agents discovered
should be included.

NCDDG projects should emphasize new drug design strategies based on
recent advances in tumor biology and new technology appropriate for
cancer drug discovery.  Specific approaches could encompass a wide
range of topics such as new combinatorial libraries or computer
modelling of receptor targets.  Other examples appropriate for the
NCDDG program include, but are not limited to, gene therapies,
monoclonal antibodies, and vaccines; design of agents to interfere
with transcription factors, signal transduction, cell adhesion
factors, angiogenesis, intracellular 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.

NCNPDDG projects should focus on the discovery and evaluation of new
entities from natural sources for the treatment of cancer.  Programs
should utilize to the extent possible, novel and innovative
approaches to drug discovery based on recent advances in tumor
biology and the molecular understanding of cancer.  Programs
appropriate to fulfillment of these objectives include, but are not
limited to, discovery of natural products which selectively inhibit
specific tumor types, products that may affect oncogene expression in
tumors, signalling pathways, or the actions of hormones or growth
factors on proliferation.  The development or use of preclinical
models based on their ability to discriminate for antitumor activity
and to test the rationale for natural product selection and isolation
are encouraged. Projects for random collection and screening of
natural products extracts without strong rationales for material
selection or testing models and projects designed to produce analogs
of known antitumor natural products are not responsive to this RFA.
Applications should stress novelty of approach and strong rationale
both in terms of the cancer target and the natural products to be
evaluated.

Applications for NCDDG and NCNPDDG should stress creative approaches
to the discovery of effective anticancer therapies and should
emphasize the following:

o  Objectives of the proposed NCDDG or NCNPDDG project.

o  Research approaches to the realization of objectives and the
provision of comprehensive information (including citations) in
support of the rationale(s) for the proposed approaches.

o  Specific relevance to cancer treatment.

o  The scientific and technical areas of expertise (Program Leaders)
required to attain Group objectives.

Funds for projects or cores that depend on the successful completion
of other activities, such as the availability of certain reagents or
scale up synthesis, could be included, but use of such funds will be
restricted and released only on specific approval of the NCI Program
Director.  Inclusion of such funds cannot exceed the total costs cap
of $900,000 plus four percent annual increase.

Definitions

ADMINISTRATIVE CORE.  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.

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 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 and NCNPDDG, below.

LABORATORY PROGRAM.  A research component headed by a Program Leader
within an NCDDG or NCNPDDG with a separate, detailed research plan
and budget.

NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG).  A unit consisting
of a Principal Investigator, Program Leaders, Core Leaders (if any),
their respective programs, and an NCI Coordinator (appointed after
award) which functions as a unit with a common goal:  the
conceptualization, invention, and evaluation of new entities and
strategies for treatment and cure of cancer.  In this RFA, the terms
NCDDG and Group are used synonymously.

NATIONAL COOPERATIVE NATURAL PRODUCTS DRUG DISCOVERY GROUP (NCNPDDG):
A number of Laboratory Programs representing diverse scientific
disciplines and usually multiple organizations which consist of a
Principal Investigator, Program Leaders, Core Leaders (if any) and
the NCI Coordinator which functions as a unit with a common goal: the
rational selection, isolation, and evaluation of new entities from
natural sources for treatment of cancer.  As with the NCDDG (above),
the terms NCNPDDG and Group are used synonymously.

NATURAL PRODUCT:  In the context of the NCNPDDG program, a term used
broadly to encompass any naturally occurring chemical or biological
entity of non-human origin selected and evaluated preclinically
against cancer.  This, of course, excludes materials which are
synthesized de novo by the investigators and also excludes
semi-synthetic derivatives of known antitumor agents.

NCI COORDINATOR.  A scientist from the NCI extramural program staff,
appointed after award by the NCI Program Director, 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
Director also may serve as the NCI Coordinator for a Group.

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

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.

SCIENTIFIC CORE.  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.

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 or NCNPDDG requirements, criteria, and NCI involvement.

B.  All proposed Groups must consist of at least three interrelated
projects, which are called Laboratory Programs in this RFA. While no
maximum number of programs is stipulated, when an award exceeds five
programs the overall Group becomes more difficult to manage. Groups
may also have scientific cores which provide essential services to
two or more Laboratory Programs, but a core cannot serve as one of
the three Laboratory Programs.

C.  The Principal Investigator and each Program Leader should 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 provided for those developmental activities
required for introduction of an agent into clinical trial but not
supported by this RFA for those agents identified as potentially
worthy of clinical evaluation.

E.  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 applicants provide plans to assure
such coverage.  The situation could be complicated since multiple
institutions are likely to be involved.  Each 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 institution.  Procedures must be described for resolution of
legal problems should they arise.  Your attention is drawn to P.L.
96-517 as amended by P.L. 98-620 and 37 CFR Part 401.  Instructions
were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol.
19, No. 23, June 22, 1990.

NOTE:  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 is preferred with the application. If this signed
agreement is not included in the application, it must be submitted to
the Scientific Review Administrator, Division of Extramural
Activities, NCI prior to peer review.  For NCNPDDG applications a
formal statement of agreement should be provided signed by authorized
representatives of all institutions in the Group, assuring that an
equitable portion of royalties or profits arising from drugs
discovered, 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 drug was derived.  If this signed agreement is not
included with the application, it must be submitted to the Scientific
Review Administrator prior to peer review.

F.  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.

Terms and Conditions of Award

NOTE:  Failure to abide by any of the Terms 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 of Award are in addition to and not in lieu of
otherwise applicable OMB administrative guidelines, HHS Grant
Administration Regulations at 45 CFR parts 74 and 92, and other HHS,
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.  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, 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 staff may not chair Group meetings.

b.  The Government, via the NCI Coordinator, will have access to data
generated under this cooperative agreement and may periodically
review the data.  However, the awardee will retain rights to the
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 acknowledgement 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.

c.  For NPNCDDGs, ownership of natural product samples acquired
during the course of the research rests with the Group.  The Group
should formulate a policy for final disposition of the samples and
ownership rights in the event that the samples are transferred to the
other parties who make discoveries using them.  In order that the
samples be fully evaluated for anticancer potential and anti-AIDS
activity 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 will arrange for review
of these lists by NCI staff involved in the Developmental Therapeutic
Program's screening for anticancer and anti-AIDS activities.  Should
selected samples be of interest to the NCI, the Group is requested to
provide these to the NCI for evaluation before release of samples for
other purposes.

d.  The NCI recognizes that most countries, and in particular
developing countries, retain interests in samples collected in their
domains.  All applicants who propose foreign collections of natural
products must provide a plan, signed by authorized representatives of
all Group member institutions, for equitable return of a portion of
any profits or royalties derived from NCNPDDG discoveries to
indigenous peoples, research collaborators, cooperating institutions
or Governmental entities in the countries of origin, as appropriate
to their contributions.

2.  NCI Staff Responsibilities

NCI shall participate as a member of the Group and will be
represented by a Coordinator. The NCI Coordinator will be selected
after award by the NCI Program Director for the NCDDG Program from
the extramural but not the intramural senior staff.  During
performance of the award, NCI may provide appropriate assistance by
participating in the design of activities; advising in the selection
of sources for resources, staff, etc.; advising in management and
technical performance; and participating in the preparation of
publications.  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 in support of Group research activities when
such resources may be required on an occasional basis.  The following
is a list of some resources that might 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 of materials, chemical structures and
biological activity, 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.

g.  Computer processing and statistical evaluations if costs are not
excessive.

These "Terms and Conditions of Award" require that the NCI Program
Director approve the following:  changes in the Principal
Investigator or Program Leaders; reports intended for inclusion in
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

a.  The principal end product of NCDDG and NCNPDDG 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, such as the NCI
Decision Network Committee.

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 will be submitted
promptly by the Principal Investigator to the NCI Coordinator upon
request.  Such reports will 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), 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 HHS
regulations at 45 CFR Part 16.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH-supported
biomedical and behavioral research projects involving research.  This
new policy results from the NIH Revitalization Act of 1993 (Section
492B of Public Law 103-43) and supersedes and strengthens the
previous policies (Concerning the Inclusion of Women in Study
Populations, and Concerning the Inclusion of Minorities in Study
Populations) which have been in effect since 1990.  The new policy
contains some new provisions that are substantially different from
the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines on the Inclusion of Women and Minorities as
Subjects in Clinical Research," which was reprinted in the Federal
Register of March 28, 1994 (59 FR 14508-14513), and reprinted in the
NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23,
Number 11.

Investigators may obtain copies from these sources or from the
program staff or contact person listed under INQUIRIES.  Program
staff may also provide additional relevant information concerning the
policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by October 1, 1995, a
letter of intent that includes a descriptive title of the overall
proposed research; the name, address, telephone number, and
institution of the Principal Investigator; names of prospective
Program Leaders, other key investigators, and their respective
institutions; title and Program Leader for each Group Program; and
the number and title of the RFA in response to which the application
may be submitted.

Although the letter of intent is not required, is not binding, and is
not a factor in the peer review of the application, the information
it contains is helpful in planning for the review of applications.
It allows NCI staff to estimate the potential review workload and to
avoid conflict of interest in the review process.

The letter of intent is to be sent to:

George S. Johnson, Ph.D.
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Suite 832
6130 Executive Boulevard, MSC 7450
Bethesda, MD  20892-7450
Bethesda, MD  20852 (for express/courier service)

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these awards.  These forms are available at most
institutional offices of sponsored research or from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD
20892-7762, telephone (301) 435-0714.

Because of the multidisciplinary and likely multi-institutional
nature of an NCDDG or NCNPDDG and the special requirements in this
RFA, additional written suggestions regarding format will be provided
by Dr. George S. Johnson at the address listed under INQUIRIES.
Potential applicants are urged to obtain the "Special Instructions to
Applicants" to avoid omitting essential information and to expedite
review.  If required information is not contained within the
application, the application will be returned without review.

On line 2 of the face page of the application form, the YES box must
be marked, the Number must be listed as RFA CA-95-020 and the Title
should be given as "National Cooperative Drug Discovery Groups"; a
personalized title more fitting for the application should be listed
on line 1.

The RFA label available in the PHS 398 (rev. 5/95) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application with the result that it may not reach the review
committee in time for review.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed, photocopies, in one package to:

Division of Research Grants
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
must also be sent to:

Ms. Toby Friedberg
Referral Officer
National Cancer Institute
6130 Executive Boulevard
Executive Plaza North, Room 636
Bethesda, MD  20892
Rockville, MD  20852 (for express/courier service)

Applications must be received by December 20, 1995.  If an
application is received after that date, it will be returned to the
applicant without review.  The Division of Research Grants (DRG) 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.  The DRG will not
accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of a substantial
revision of an application already reviewed, but such an application
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

General Considerations

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, it will not be the sole
criterion for selection. Other considerations, such as the likelihood
of identifying a clinical trial candidate, will be part of the
evaluation criteria. Applications should provide a plan for
development even though some of the activities will be beyond the
scope of the RFA.

Review Method

Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NCI.  Incomplete applications will be
returned to the applicant without further consideration.  If NCI
staff find that the application is not responsive to the RFA, it will
be returned without further consideration.

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NCI in accordance with the review
criteria stated below.  As part of the initial merit review, all
applicants will receive a written critique and may undergo a process
in which only those applications deemed to have the highest
scientific merit will be discussed, assigned a priority score, and
receive a second level review by the National Cancer Advisory Board.

Review Criteria

o  Scientific merit and originality of proposed research.

o  Extent of progress on prior award (RECOMPETING GROUPS) or
preliminary results (NEW APPLICANTS).

o  Extent and effectiveness of cooperation with the NCI (RECOMPETING
GROUPS) and adequacy of plans for cooperation with the NCI in the
event of an award (ALL APPLICANTS).

o  Technical merit of proposed methods for producing or obtaining
test materials and for their evaluation.

o  Adequacy of the developmental plan for recommending a new cancer
therapy or strategy for clinical trial.

o  Adequacy of the scientific disciplines and specific competencies
represented by the Principal Investigator and Program Leaders;
research experience, competence, commitment, and time availability of
Principal Investigator, Program Leaders, and other key personnel.

o  Leadership, scientific ability, and administrative experience and
competence of Principal Investigator in the development,
implementation, and management of comprehensive research programs.

o  Adequacy of plans for effective intra-Group communication and for
ensuring Group cohesiveness.

o  Evidence of approval and commitment of institutions represented by
Group members to Group goals.

o  Evidence of availability and competence of the applying
institution to serve as the Administrative Core for the Group.

o  Adequacy of existing physical facilities and resources of the
Principal Investigator and Program Leaders.

o  Justification and usefulness of cores to the overall Group.

o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

The review group will critically examine the budget requested and
will recommend an appropriate budget and period of support for each
approved application.

AWARD CRITERIA

Applications recommended by the National Cancer Advisory Board (NCAB)
will be considered for award based on scientific merit as reflected
in the priority score; on programmatic priorities and relevance; on
program balance; and on funds available.

Letter of Intent Receipt Date:  October 1, 1995
Application Receipt Date:       December 20, 1995
Scientific Review Date:         March 1996
NCAB Meeting Date:              May 1996
Earliest Award Date:            August 1, 1996

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues and requests for the
"Special Instructions to Applicants" on application format to:

George S. Johnson, Ph.D.
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Suite 832
Bethesda, MD  20892-7450
Telephone:  (301) 496-8783
FAX:  (301) 496-8333 or (301) 402-0831
Email:  johnsongpax2.ncifcrf.gov

Direct inquiries regarding fiscal or administrative matters to:

Ms. Joan Metcalfe
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 242
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, Ext. 228
Email:  metcalfj@gab.nci.gov

AUTHORITY AND REGULATIONS

This program is described in the catalog of Federal Domestic
Assistance No. 93.395, Cancer Treatment Research.  Awards are made
under authorization of the Public Health Service Act, Title IV, Part
A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants policies and Federal
Regulations 42 CFR Parts 52 and 45 CFR Parts 74 and 92.  This program
is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.

The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-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 case, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.

.

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