From: kristoff@NET.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 21, no. 42, pt. 4, 20 November 1992
Date: 21 Nov 92 04:22:02 GMT
Distribution: bionet


$$XID RFA CA9305 CA-93-05 P1O1 *****************************************

RESEARCH AND DEVELOPMENT PROJECTS IN CHEMOPREVENTION

NIH GUIDE, Volume 21, Number 42, November 20, 1992

RFA:  CA-93-05

P.T. 34; K.W. 0745003, 0715035

National Cancer Institute

Letter of Intent Receipt Date:  December 9, 1992
Application Receipt Date:  February 9, 1993

PURPOSE

The Division of Cancer Prevention and Control (DCPC), National Cancer
Institute (NCI), invites applications for cooperative agreements to
encourage coordinated submissions of projects from investigators
dedicated to developmental research in chemoprevention.

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 Request for
Applications (RFA), Research and Development Projects in
Chemoprevention, 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 "Healthy People 2000" (Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-783-3238).

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 individuals and women are encouraged.

Each application will be considered on its own merit as an individual
research project.  Applicants for Research and Development Projects
(RDPs) in Chemoprevention MAY NOT concurrently submit R01 applications
that represent significant duplication of the efforts described in the
applicant's RDP.

MECHANISM OF SUPPORT

This RFA will use the cooperative agreement mechanism (U01). The
cooperative agreement is an assistance mechanism in which substantial
NIH programmatic involvement with the recipient during performance of
the planned activity is anticipated.  The nature of the Program
Director's involvement is described in the section on Special
Requirements, D.1.  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the
applicant/awardee.  Except as otherwise stated in this RFA, awards will
be administered under PHS grants policy as stated in the PHS Grants
Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised
October 1, 1990.

This RFA is a one-time solicitation.  Future unsolicited competitive
continuation applications will compete with all other
investigator-initiated research applications and be peer reviewed by a
study section in the Division of Research Grants (DRG), NIH.  However,
if it is determined that there is a sufficient continuing need, the NCI
will invite recipients of awards made in FY 93 under this RFA to submit
competitive continuing applications for review according to procedures
described below in the APPLICATION PROCEDURES and REVIEW CONSIDERATIONS
sections.

An assistance relationship will exist between NCI and the awardees to
accomplish the purpose of the activity.  As more fully described later
in this announcement, the recipients will have primary responsibility
for the development and performance of the activity.  However, there
will be government involvement with regard to (1) assistance in
securing an Investigational New Drug (IND) approval from the Food and
Drug Administration (FDA), (2) coordination and assistance in obtaining
the chemopreventive agent, (3) monitoring of safety and toxicity and,
(4) quality assurance of the clinical chemistry aspects of the study.
Awards will not be made until all arrangements for obtaining the IND
and the agent are completed.  Final awards will also consider not only
the cost of the clinical trial but also the cost of the agent and, if
necessary, its formulation.  The anticipated direct cost will be in the
range of $150,000 to $250,000.

FUNDS AVAILABLE

Approximately $4.0 million in total costs for the first year for
project periods up to five years will be committed to specifically fund
applications which are submitted in response to this RFA.  It is
anticipated that 9 to 15 awards will be made.  This number of awards is
dependent on the receipt of a sufficient number of applications of high
scientific merit.  The earliest feasible start date for the initial
awards will be December, 1993.  Although this program is provided for
in the financial plans of the NCI, awards made pursuant to this RFA
will be contingent upon the continued availability of funds for this
purpose.

RESEARCH OBJECTIVES

Background

This RFA encourages submissions of applications from investigators
wanting to conduct collaborative translational research in cancer
chemoprevention.  Translational research moves the results of basic
research studies in the laboratory or developmental studies to clinical
research in human subjects or populations.  The research objectives of
these projects should be the development of intermediate biomarkers of
cancer risk and evaluation of the efficacy of individual biological
and/or molecular markers as intermediate endpoints in chemoprevention
trials.

Candidate chemical, biological, molecular, and dietary cancer
chemopreventive agents have been identified from in vivo studies in
animal model systems and epidemiological studies.  The efficacy of each
of these agents individually or in concert in modulating cancer risk
can best be evaluated through prevention clinical trials.  Limitations
of the usefulness of such trials is the long duration and large sample
populations generally needed to achieve statistical significance.  This
limitation could be overcome by identification of biological or
molecular markers suitable for use as intermediate endpoints in the
process of carcinogenesis.  Ideally, such markers would be expressed in
an abnormal form in tumor tissue or washings or in serum of high-risk
individuals, but revert to the normal form when exposed to the
chemopreventive agent.

Our evolving understanding of the molecular biology of carcinogenesis
has identified possible oncogene and suppressor gene candidates and
molecular alterations in these candidates, and their interactions with
other cellular components, that could serve as intermediate markers in
cancer chemoprevention trials.  Examples would include sequential
genetic alterations in oncogenes HER-2/neu, C-myc, c-abl; in tumor
suppressors RB, p53 and APC; markers for increased risk for cancer
(Li-Fraumeni-p53, NF-1, APC, and early onset 17q21); and interactions
between oncogenes, suppressor genes and the cyclin P34 complex.  New
developments in the understanding of cellular function and metabolites
have provided information on possible candidate markers for cell
growth, proliferation, differentiation, and neoplastic transformation.
Included among these candidates are abnormal cytology, nuclear
aberrations (micronuclei), ornithine decarboxylase and/or
prostaglandins synthetase, DNA ploidy, and colonic mucosal
proliferation.

Cancer chemoprevention trials responsive to this RFA will examine
modulation of candidate markers in response to administration of
chemopreventive agents.  Additionally, these markers could be used to
identify human populations at high risk for cancer, and therefore
useful as sample populations for these trials.

SPECIAL REQUIREMENTS

A.  General

This RFA represents a single competition, with a specified deadline,
February 9, 1993, for receipt of applications.  It is expected that
each application will describe plans for a mixture of basic,
developmental, and clinical research from an investigator wanting to
focus on a particular study in cancer chemoprevention.  Each submission
should have a general focus on study outcomes and the application of
basic research and development to human subjects and populations.

If not contained within the investigator's own research project, plans
should be cited for establishing contacts with investigators with
complementary interests that would fulfill the broader goals of
translational chemoprevention studies.

B.  Special Emphasis

The studies described should be developed with preclinical and clinical
phases that may include a pilot phase in humans that could later
proceed to a full scale intervention.  One or more intermediate
endpoints might be initially evaluated to determine baseline parameters
and subsequently to serve as a follow-up after the administration of
the preventive measure or the chemopreventive agent in vivo and/or in
vitro.  The main emphasis should be on small, efficient studies aimed
at improving future research designs, providing a molecular basis for
the action of the chemopreventive agent(s), or providing improved
intermediate endpoint biomarkers.  After successful completion of the
pilot phase (i.e., demonstrated modulation of endpoint markers),
subsequent studies could include a clinical trial monitoring the test
system, a cancer incidence or mortality endpoint, and a designated
agent.  Studies that develop and evaluate new technologies for
identification of new genes, gene products, and DNA probes to identify
human disease and individuals at high risk or predisposition to cancer
are encouraged.

For the initial human phase, the proposed study might describe the
relevance of the marker test system to clinical or public health cancer
prevention, the rationale for the selection of the study population,
and potential intervention agent or procedure.  The project could
result later in the markers and agent being evaluated in a full scale,
double-blind, randomized, risk reduction clinical trial.

C.  Terms of Cooperation

The special award terms and conditions as described in section C.1-2
below will be incorporated in the Notice of Grant Award and are in
addition to, and not in lieu of, otherwise applicable HHS
Administrative Regulations at 45 CFR 74; other DHHS, PHS and NIH Grant
Administration Policy Statements and other NCI administrative terms of
award.

1.  Program Staff Involvement

a.  Study/Protocol Plan

The NCI Program Director (cited in the LETTER OF INTENT section below)
will assist the awardees in the study and protocol design by providing
information regarding a) the nature of concurrent studies in the area
of research, pointing out possible duplication of effort, b)
availability of necessary drugs.  The NCI Program Director will also
offer advice regarding the scientific rationale, priority, design, and
implementation of the proposed studies.  A safety and protocol review
will be undertaken by the NCI Program Director on all clinical trials
from proposals which are ultimately funded.  Such a review is legally
required by the FDA to assure that all safety, toxicity, monitoring,
and reporting issues are in conformance with Investigational New Drug
guidelines.  The awardee institutions and Principal Investigator must
agree to comply with the recommendations of the review.

b.  Data Access

The NCI Program Director will have access to the data to review
toxicity and safety aspects of the project, prepare IND applications
and monitor any trial aspects required by other federal agencies.  This
information is necessary to satisfy FDA regulations with regard to Code
of Federal Regulations (CFR) 21.  The awardees, however, will retain
custody of and primary rights to their data.  The NCI Program Director
may encourage and facilitate sharing of data between investigators when
this is in the mutual interest of the investigators and the NCI.

c.  Investigational New Drug (IND)

The NCI will have the option to cross file or independently file an IND
on investigational drugs evaluated in trials supported under the
cooperative agreements.

The NCI will advise investigators of specific requirements and changes
in requirements concerning investigational drug management for
compliance with NCI and the FDA guidelines and regulations.
Investigators conducting trials under cooperative agreements will be
expected, in cooperation with the NCI, to comply with all FDA
monitoring and reporting requirements for investigational agents, for
reporting adverse reactions, and for maintaining necessary records of
drug receipt and distribution.

d.  Assistance with Obtaining or Purchasing Investigational Drugs

The NCI Program Director will assist the investigator to obtain the
agent to be used in the proposed study.  Once the application is
recommended for funding by the peer review committee, the NCI, and the
National Cancer Advisory Board, the NCI Program Director may begin
discussions with the principal investigators and pharmaceutical
industry with regard to obtaining the drug.  In the event a suitable
agent is not available at no cost, the NCI may proceed to purchase the
agent through normal procurement mechanisms.  Purchase of the agents is
only undertaken after measures to obtain the drug at no cost have been
exhausted.  Awards will not be made until all arrangements for
obtaining the agent are complete.  Final awards by the NCI will also
consider not only the cost of the trial but also the cost of the agent,
including its formulation, encapsulation and packaging, if these costs
are to be borne by the Government.

e.  Protocol Modification

No protocol modifications will be implemented without approval from the
NCI Program Director, consistent with FDA requirements.

f.  Protocol Termination

The NCI Program Director may request that a protocol study be
terminated.  Reasons for this request may be:  (a) insufficient
accrual, (b) further accrual will not add information of scientific
value, and/or (c) consideration of patient safety.  The NCI will not
provide drugs or IND sponsorship for a study after requesting
termination.  Investigators who wish to challenge protocol termination
may do so according to the arbitration process described below.  In
addition, the NCI may withdraw funding for such a protocol if the
grounds for termination are patient safety and toxicity.  The
Arbitration Mechanism is described in g. below.

g.  Description of Arbitration Mechanism

When mutually acceptable agreements on the safety of research
protocols, protocol disapproval or protocol termination cannot be
obtained between investigators and the NCI Program Director, as
described above, an arbitration panel will be formed composed of one
award recipient designee, one NCI designee, and a third designee with
appropriate expertise chosen by the other two members of the panel.
These special arbitration procedures in no way affect the awardee's
right to appeal an adverse action in accordance with PHS regulations at
42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

h.  Clinical Trials Progress Review

Progress will be evaluated semi-annually by the NCI Program Director
from material presented in the awardee's semi-annual report (as
described below).  Recommendations of the NCI Program Director will be
communicated by letter to the investigator to which he/she is expected
to respond.

Insufficient numbers of patients accrued to attain the stated delta
value (d=difference between treatments to be detected divided by
standard deviation), unsatisfactory progress, or non-compliance with
terms of award may result in a reduction of the budget, withholding of
support, suspension or termination of the award.

i.  Quality Assurance

(1) The NCI has established a clinical chemistry quality assurance
program with the National Institutes of Standards and Technology,
Gaithersburg, Maryland which will provide chemical standards for some
of the agents that will be used and assayed for in the clinical trials.
These standards will contribute to the quality control of selected
laboratory determinations.  The awardee will participate in the
laboratory quality control activity when so notified.

(2) Periodically, the NCI Program Director will review the mechanisms
established by each awardee for quality control of clinical studies.
These mechanism must conform with FDA regulations.

j.  Other Terms

No patients may be enrolled in this study without the prior written
approval of the NCI Program Director for this cooperative agreement.
Such approval is contingent upon submission to and approval by the FDA
of an IND application and satisfactory response to the recommendations
of the safety and protocol review.

2.  Responsibilities of Awardees

Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant/awardee.

a.  Safety and Toxicity Review

Each awardee institution and principal investigator agree to comply
with the recommendations of the safety and protocol review to assure
that all FDA requirements are satisfied.

b.  Quality Control and Adverse Reaction Reporting

(1) The awardee will be required by the NCI Program Director to set up
mechanisms for quality control.  Some or all of the following may be
relevant:  compliance with protocol requirements for eligibility;
treatment and follow-up; laboratory data; dietary data; pathological
materials; and operative reports.

(2) The awardee agrees to perform the study according to the approved
protocol.  Any proposed changes in the protocol must receive the
advance permission of the NCI Program Director for this award.

(3) The awardee is required to conform to NCI guidelines for the use of
investigational drugs including investigator registration (FDA Form
1573), maintaining a record of drug receipt and reporting of adverse
drug reactions.  Life threatening or unexpected toxicity MUST be
reported by the investigator IMMEDIATELY by telephone to the NCI
Program Director shown on the Notice of Grant Award and confirmed with
details in writing within two weeks.  The investigator will be
responsible for amending protocols and consent forms based on new
toxicity information sent to the investigators by NCI staff.

c.  Data Management and Reporting Requirements

Data acquisition and analysis is the responsibility of the
investigator.  Each awardee institution will retain custody and primary
rights to their data developed under these Cooperative Agreements.

Investigators will be required to submit reports to the NCI using the
following schedule and format as required by FDA Investigational Drug
Regulations, CFR 21 312.23.

(1) Semi-annual Reports

Semi-annual scientific reports should report on the progress of the
project during the previous six months and the cumulative progress of
the study.

(a) Individual Study Information.  The summary is required to include
the following information for each study:

o  The title of the study (with any appropriate study identifiers such
as protocol number), its purpose, a brief statement identifying the
patient population and the inclusion of women and minorities, and a
statement as to whether the study is completed.

o  The total number of subjects initially planned for inclusion in the
study, the number entered into the study to date, the number whose
participation in the study was completed as planned, and the number who
dropped out of the study for any reason.

o  If the study has been completed, or if interim results are known, a
brief description of the study results.

(b) Summary Information.  Information obtained during the previous six
months' clinical and nonclinical investigations, including:

o  A narrative or tabular summary showing the most frequent and most
serious adverse experiences by body system.

o  A list of subjects who died during participation in the
investigation, with the cause of death for each subject.

o  A list of subjects who dropped out during the course of the
investigation in association with any adverse experience, whether or
not thought to be drug related.

o  A brief description of what, if anything, was obtained that is
pertinent to an understanding of the drug's actions, including for
example, information about dose response, information from controlled
trials, and information about bioavailability.

o  A list of the preclinical studies (including animal studies)
completed or in progress during the past year and a summary of the
major preclinical findings.

(c) A description of the general investigational plan for the coming
year to replace that submitted one year earlier.

(d) A description of any significant pilot trial protocol modifications
made during the previous year and not previously reported to the IND in
a protocol amendment.

(e) A brief summary of significant foreign marketing developments with
the drug during the past year, such as approval of marketing in any
country or withdrawal or suspension from marketing in any country.

Due Dates for Reports

January 1 and July 1 for the semiannual report.

(2) Final Study Report

The final report of a completed study shall consist of detailed
analyses of results and toxicity, plans for publications, a
comprehensive list of all previous publications related to the project,
and plans for archiving and storing the study records.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements will be required to include minorities and women
in study populations so that research findings can be of benefit to all
persons at risk of the disease, disorder or condition under study;
special emphasis should be placed on the need for inclusion of
minorities and women in studies of diseases, disorders and conditions
which disproportionately affect them.  This policy is intended to apply
to males and females of all ages.  If women or minorities are excluded
or inadequately represented in clinical research, particularly in
proposed population-based studies, a clear compelling rationale should
be provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues should be addressed in developing a research
dosing and sample size appropriate for the scientific objectives of the
study.  This information should be included in the form PHS 398 in
Sections 1-4 of the Research Plan AND summarized in Section 5, Human
Subjects.  Applicants are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., Native
Americans (including American Indians or Alaskan Natives),
Asian/Pacific Islanders, Blacks, Hispanics).

The rationale for studies on single minority population groups should
be provided.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual policies concerning research on human subjects also apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded.  However, every
effort should be made to include women and racial/ethnic minorities
when it is important to apply the results of the study broadly, and
this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies. If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.

All applications for clinical research submitted to NIH are required to
address these policies.  NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by December 9, 1992, a
letter of intent that includes a descriptive title of the proposed
research, the name and address of the Principal Investigator, the names
of other key personnel, the participating institutions, and the number
and title of the RFA in response to which the application may be
submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, it is requested
in order to provide an indication of the number and scope of
applications to be reviewed.

The letter of intent is to be sent to:

Marjorie Perloff, M.D.
Program Director, Chemoprevention Branch
National Cancer Institute
Executive Plaza North, Suite 201
Bethesda, MD  20892-4200
Telephone:  (301) 496-8563
FAX:  (301) 402-0553

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these cooperative agreements.  These forms are
available at institutional sponsored research or business offices; from
the Office of Grants Inquiries, Division of Research Grants, National
Institutes of Health, Room 449, Westwood Building, 5333 Westbard Avenue
Bethesda, Maryland 20892; and from the NCI Program Director named
above.

The RFA label available in the PHS 398 must be affixed to the bottom of
the face page.  Failure to use this label could result in delayed
processing of the application such that it may not reach the review
committee in time for review.  In addition, the title of the
application, Research and Development Projects in Chemoprevention, and
the RFA number, CA-93-05, must be typed in block 2a of the face page of
the application form.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed, exact, clear, single-sided photocopies, in
one package to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At time of submission, two additional copies of the application must
also be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
Room 848, Westwood Building
5333 Westbard Avenue
Bethesda, MD  20892

If the application submitted in response to this RFA is substantially
similar to a research grant application already submitted to the NIH
for review, and has been or has not yet been reviewed, the applicant
will be asked to withdraw either the pending application or the new
one.  Simultaneous submission of identical applications will not be
allowed, nor will essentially identical applications be reviewed by
different review committees.  This does not preclude the submission of
substantial revisions of applications already reviewed, but such
applications must include an Introduction addressing the previous
critique.

Preparation of the Application

The general instructions for preparation of the applications contained
in the grant application form PHS 398 (rev. 9/91) are to be used in
preparing cooperative agreement applications.  Because of the award
terms and conditions included in the section under SPECIAL
REQUIREMENTS, C. Terms of Cooperation, it is important that applicants
indicate in the Research Plan how they will meet the requirements
stated in the RFA for staff involvement.  To ensure that the
cooperative agreement remains the appropriate instrument, awardees
submitting competing continuation and supplemental applications must
describe how they have met the established terms and conditions.

The following items apply to new as well as to competing continuation
applications:

1.  The study should clearly address a pilot trial and optionally a
definitive trial.  The pilot trial must involve the application of a
biological and/or biochemical marker and its modulation by the study
agent.  The definitive trial involves the implementation of a full
scale randomized, double-blind, risk reduction, prevention clinical
trial.  For applicants seeking to conduct only a pilot trial, the study
must describe relevance to a clinical trial application including a
marker, agent, and target group that might be appropriate for a full
scale intervention after completion of the pilot study.

2.  The applicant should provide a rationale for selection of the
biological or biochemical marker, its relevance to risk identification
or modulation, and its relevance to the intervention agent and the
target population.

3.  The applicant should provide the rationale for selection of the
proposed intervention agent.  This should include relevant
epidemiologic and laboratory data.  Preclinical and clinical data on
any potential untoward effects of the intervention agent should also be
presented.  In circumstances where there might be some doubt as to the
availability or the safety of the agent, the applicant may wish to
consult with the pharmaceutical company and the NCI Program Director
prior to preparing the application.  The applicant should thus present
a reasonable case for the "readiness" of the proposed intervention
agent for a clinical trial.

4.  The applicant should provide a rationale for selection of a
specific target group and provide an estimate of the number of
participants required for the completion of the study.  Criteria and
calculations used to estimate sample size should be included.  The
applicant should provide a description of the target population or
group chosen and should justify the selection of this group.  The group
should be defined, as appropriate, by age, sex, race, dietary customs,
education, geographic location, occupational or life style risk
factors, and relevancy to a specific cancer problem or to its possible
prevention by the designated inhibitor(s).  The accrual rate should be
estimated.  If multiple institutions are involved, the proposal should
include verification of the coinvestigators' willingness to
participate, and pertinent additional information regarding the
cooperating institutions' staff qualifications, resources, research
plans, including patient availability and data flow, as well as
corresponding budget requirements.

5.  The applicant should clearly indicate the clinical chemistry and
biologic aspects of the study to include collection, storage, handling,
analysis, and quality control of biological or biochemical samples.
The methods and equipment to be used and the technical qualifications
and experience of the personnel involved must be addressed.  If these
aspects of the study are to be conducted by groups other than at the
applicant's institution, a letter from the cooperating institutions
indicating their willingness to participate should be included.

6.  The applicant should elucidate any known or potential safety or
toxicity considerations, the techniques and procedures to monitor and
report any adverse health effects and appropriate dose modifications
based on toxicity monitoring.

7.  The applicant should specify the methods to be used to document
nutrient intake, if indicated, and adherence to the prescribed
intervention during the course of the trial.

8.  The applicant must indicate a willingness to work cooperatively
with the assistance of the NCI Program Director in the implementation
and conduct of the study.

9.  Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research.  If so, a letter of agreement from either the GCRC program
director or Principal Investigator could be included with the
application.

10.  Availability of the chemopreventive agents or dietary factors.

REVIEW CONSIDERATIONS

A.  Review Procedure

Upon receipt, applications will be administratively reviewed
(initially) by the Division of Research Grants (DRG) for completeness.
Incomplete applications will be returned to the applicant without
further consideration.  Evaluation for responsiveness to the RFA is an
NCI program staff function.  Applications will be judged to determine
if they meet the goals and objectives of the program as described in
the RFA.  Applications that are judged non-responsive will be returned,
but may be submitted for investigator initiated grant competition at
the next receipt date.  Questions concerning the relevance of proposed
research to the RFA may be directed to the NCI Program Director.

If the number of applications is large compared to the number of awards
to be made, the NCI may conduct a preliminary scientific peer review to
identify those that are clearly not competitive for awards.

Those applications judged to be both competitive and responsive will be
further evaluated, using the review criteria shown below, for
scientific and technical merit by an appropriate peer review group
convened by the Division of Extramural Activities, NCI.  The second
level of review by the National Cancer Advisory Board considers the
special needs of the Institute and the priorities of the National
Cancer Program.

B.  Review Criteria

The following factors will be considered in evaluating the scientific
merit of each response to the RFA:

1.  Scientific merit of the study objective(s), design, and methodology
to include considerations of toxicity, safety and quality assurance.

2.  Basic and clinical scientific significance as well as originality
of the proposed research.

3.  Research experience and/or competence of the Principal Investigator
and other key personnel to conduct the proposed studies.

4.  Adequacy of time (effort) which the Principal Investigator and
staff would devote to conduct the proposed studies.

5.  Relevancy and appropriateness of the specific target population
along with assurance as to its accessibility.

6.  Identity of sources of data, tissues, fluids, and other materials
procedures for their collection and analysis, and assurances of their
accessibility.

7.  Adequacy of plans for NCI program staff involvement with the
proposed studies.

8.  Adequacy of plan for inclusion of women and minorities

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

AWARD CRITERIA

The earliest feasible start date for the initial awards will be
December 1, 1993.  In addition to the technical merit of the
applications, NCI will consider how well the applicant institutions
meet the goals and objectives of the program as described in the RFA,
availability of resources, and study populations.

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 to Dr. Perloff at the
address listed under LETTER OF INTENT.

Direct inquiries regarding fiscal matters to:

Ms. Eileen Natoli
Division of Cancer Prevention and Control
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, Ext. 56

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.399, Cancer Control.  Awards will be made under the authority of
the Public Health Service Act, Title IV, Section 301 (Public Law
78-410,; 42 U.S.C. 241, and Section 412, as amended by Public Law
99-158, 42 U.S.C. 258a-1); and administered under PHS grants policies
and Federal regulations 42 CFR Part 52 and 45 CFR Part 74.  This
program is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.