Full Text CA-94-016

COMMUNITY CLINICAL ONCOLOGY PROGRAM

NIH GUIDE, Volume 23, Number 21, June 3, 1994

RFA:  CA-94-016

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Disease Prevention+ 
  Treatment, Medical+ 
  Disease Control+ 
  Community/Outreach Programs 


National Cancer Institute

Letter of Intent Receipt Date:  July 1, 1994
Application Receipt Date:  August 25, 1994

PURPOSE

The Division of Cancer Prevention and Control (DCPC), National Cancer
Institute (NCI), invites applications from domestic institutions for
cooperative agreements to the Community Clinical Oncology Program
(CCOP).  New community and research base applicants and currently
funded programs are invited to respond to this Request For
Applications (RFA).

Utilizing the national resource of highly trained oncologists in
community practice, the CCOP:  (1) provides support for expanding the
clinical research effort in the community setting; (2) stimulates
quality care in the community through participation in protocol
studies; (3) fosters the growth and development of a scientifically
viable community cancer network able to work closely with
NCI-supported clinical cooperative groups and cancer centers; (4)
supports development of and community participation in cancer
prevention and control intervention research, which includes
chemoprevention, early detection, patient management, rehabilitation,
and continuing care research; (5) involves primary care providers and
other specialists in cancer prevention and control clinical trials;
and (6) increases the involvement of minority and underserved
populations in clinical research.  Combining the expertise of
community physicians and other health care professionals with
NCI-approved treatment and cancer prevention and control clinical
trials provides the opportunity for the transfer of the latest
research findings to the community level.

This issuance of the CCOP RFA seeks to build on the strength and
demonstrated success of the CCOP over the past eleven years by:  (1)
continuing the program as a vehicle for supporting community
participation in treatment and cancer prevention and control clinical
trials through research bases (clinical cooperative groups and cancer
centers supported by NCI); (2) expanding and strengthening the cancer
prevention and control research effort; (3) utilizing the CCOP
network for conducting NCI-assisted cancer prevention and control
research; and (4) evaluating on a continuing basis CCOP performance
and its impact in the community.

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,
Community Clinical Oncology Program, 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 from domestic institutions for
cooperative agreements to continue the Community Clinical Oncology
Program (CCOP).  New applicants and currently funded programs are
eligible as described below.

A.  CCOP Applicants

1.  An applicant may be a hospital, a clinic, a group of practicing
physicians, a health maintenance organization (HMO), or a consortium
of hospitals and/or clinics and/or physicians and/or HMOs that agree
to work together with a principal investigator and a single
administrative focus.

2.  A university, military, or Veterans Administration hospital may
be included in an application as a member of a consortium led by a
community institution, but may not be the applicant organization or
the major contributor to accrual.  An unfunded, non-university
clinical trials cooperative group member is eligible to apply.

3.  Funded Cooperative Group Outreach Program (CGOP) participants are
eligible to apply, but should state in the application that CGOP
support will be relinquished if a CCOP award is received.

4.  Institutions not eligible to apply as a CCOP include:

a.  A comprehensive, consortial, or clinical cancer center holding an
NCI Cancer Center Support (CORE) grant;

b.  A university hospital that is the major teaching institution for
that university; or

c.  A university hospital clinical trials cooperative group member
funded by DCT, NCI.

B.  Research Base Applicants

An applicant may be:

1.  An NCI-funded clinical trials cooperative group;

2.  An NCI-funded clinical, consortia, or comprehensive cancer
center.

Cooperative groups must participate in both treatment and cancer
prevention and control clinical trials; cancer centers may
participate in treatment and cancer prevention and control studies or
cancer prevention and control research only.

MECHANISM OF SUPPORT

Support of this program will be through the Cooperative Agreement
(U10).  The Cooperative Agreement is an assistance mechanism in which
substantial NCI programmatic involvement with the recipient during
performance of the planned activity is anticipated to assist awardees
in the planning, direction, and execution of the proposed project.

The total project period for an application submitted in response to
this RFA may not exceed three years for new applicants, and five
years for applicants currently supported under this program.
Currently supported applicants will be funded for three, four, or
five years depending upon priority score/percentile, review committee
recommendations, and programmatic considerations.

FUNDS AVAILABLE

The NCI has determined that there is a continuing program need for
community participation in cancer clinical research trials, both
treatment and cancer prevention and control.  Although this RFA is a
one-time issuance, it is expected that a CCOP RFA will be published
in the NIH Guide for Grants and Contracts annually provided that
funds are available.

It is anticipated that up to $5.0 million in total costs per year for
five years will be committed to specifically fund applications that
are submitted in response to this RFA.  Approximately two research
base awards and 17 CCOP awards will be made.  This level of support
is dependent upon the 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.

RESEARCH OBJECTIVES

A.  Background

The CCOP was initiated in 1983 to bring the benefits of clinical
research to cancer patients in their own communities by providing
support for physicians to enter patients onto treatment research
protocols.  In the first three years of the CCOP, 62 community
programs in 34 states were funded.  During this time, approximately
14,000 patients were entered onto NCI-approved treatment clinical
trials through the CCOP.  The data from CCOP participants met or
exceeded all the quality control standards of the cooperative groups.
The CCOP evaluation indicated that patients on protocol and patients
treated by CCOP participating physicians received more appropriate
patterns of care than patients seen by physicians who never used
protocols.  The CCOPs also had an increase in the number of
physicians using protocols, the number of protocols used, and the
number of patient registrations.  It was further documented that
CCOPs with higher accruals were often associated with more
appropriate patterns of care.  All of these factors contribute to
establishing a framework that is critical to the diffusion process
and the widespread dissemination of state-of-the-art practices.

The CCOPs clearly were very effective in accruing patients to
treatment clinical trials.  The second CCOP RFA, issued in 1986,
expanded the focus to include cancer prevention and control research
based on the rationale that the multi-institutional clinical trials
model essential for testing new treatment regimens is also required
for conducting large-scale cancer prevention and control trials.  In
1993, there were 48 programs in 27 states involving over 300
hospitals and over 2,900 physicians.  Approximately 4,000 patients
were entered onto treatment trials and 4,400 subjects on cancer
prevention and control trials in 1993.

Cancer prevention and control research in the CCOPs is aimed at
reducing cancer incidence, morbidity, and mortality through the
identification, testing, and evaluation of interventions in
controlled clinical trials.  The development of cancer prevention and
control research in the CCOP network has been increasing steadily
since funding started in 1987.  Since that time nearly 120 cancer
prevention and control protocols have been reviewed and 80 have been
activated.   Protocols reviewed to date cover the full spectrum of
cancer prevention and control research, including chemoprevention,
marker studies for future prevention interventions, smoking cessation
studies, screening and early detection, and pain control and other
symptom management interventions.  Several large chemoprevention
trials have been implemented through the CCOP network, including the
breast cancer prevention trial with tamoxifen, the head and neck
chemoprevention trial with 13-cis retinoic acid (13-cRA), and the
prostate cancer prevention trial with finasteride.

The CCOPs are a vital resource for conducting NCI cancer prevention
and control research because they provide access to:  (1) a national
network for cancer prevention and control trials which require large
sample sizes for completion; (2) geographic areas that include cross
sections of the population, providing mixes of patients/subjects not
always available in university or urban settings; (3) large
populations of cancer patients free of disease which provide a unique
resource for chemoprevention clinical trials; and (4) cancer
patients' family members and others who may be at increased risk of
developing cancer and thus be candidates for prevention and detection
studies.  Participation in cancer prevention and control research by
CCOPs also further expands the network of community physicians,
increasing the potential for diffusion of state-of-the-art cancer
prevention and control practices.

B.  Goals and Scope

The CCOP initiative is designed to:

o  Bring the advantages of state-of-the-art treatment and cancer
prevention and control research to individuals in their own
communities by having practicing physicians and their
patients/subjects participate in NCI-approved treatment and cancer
prevention and control clinical trials;

o  Provide a basis for involving a wider segment of the community in
cancer prevention and control research and investigate the impact of
cancer therapy and control advances in community medical practices;

o  Increase the involvement of primary health care providers and
other specialists (e.g., surgeons, family practitioners, urologists,
gynecologists) with the CCOP investigators in treatment and cancer
prevention and control research, providing an opportunity for
education and exchange of information;

o  Facilitate wider community participation, including minorities,
women, and other underserved populations, in treatment and cancer
prevention and control research approved by NCI; and

o  Reduce cancer incidence, morbidity, and mortality by accelerating
the transfer of newly developed cancer prevention, early detection,
treatment, patient management, rehabilitation, and continuing care
technology to widespread community application.

Participating community programs (CCOPs) will be required to enter
patients onto NCI-approved treatment and cancer prevention and
control clinical trials through the research base(s) with which each
CCOP is affiliated.  CCOPs may relate directly to NCI for assistance
and participation in selected cancer prevention and control
protocols.  CCOP performance will be evaluated on a continuing basis
by the NCI program director for its impact on community cancer
treatment and control practices.

Participating research bases will be required to continue providing
clinical research treatment and/or cancer prevention and control
protocols, as applicable, and as studies progress and findings
indicate, to develop new protocols.  Cancer prevention and control
research should be intervention- oriented and may include such areas
as cancer prevention, early detection, patient management,
rehabilitation, and continuing care.  Research bases will be expected
to monitor the quality of protocol conduct, follow CCOP accrual, and
participate in the continuing program evaluation.

SPECIAL REQUIREMENTS

A.  Terms and Conditions of Award

Under the cooperative agreement, a partnership will exist between the
recipient of the award and NCI, with assistance from NCI in carrying
out the planned activity.  The following terms and conditions
pertaining to the scope and nature of the interaction between NCI and
the investigators will be incorporated in the Notice of Award.  These
terms will be in addition to the customary programmatic and financial
negotiations which occur in the administration of grants.  The "Terms
and Conditions of Award:  Nature of NCI Staff Involvement" and "Terms
and Conditions: Responsibilities of Awardees" described in this
section are in addition to, and not in lieu of, otherwise applicable
OMB administrative guidelines; DHHS grant administration regulations
45 CFR 74; other DHHS, PHS, and NIH grant administration policy
statements; and other NCI administrative terms of award.

1.  Community (CCOP) Awardees

1.a.  Nature of NCI Staff Involvement

1.a.(1) Protocol Review

All protocols utilized by the CCOPs must be reviewed and approved for
CCOP use by the Cancer Control Protocol Review Committee (CCPRC),
Division of Cancer Prevention and Control (DCPC), and/or the Protocol
Review Committee (PRC), Division of Cancer Treatment (DCT), NCI,
prior to implementation.

NCI will not provide investigational drugs, permit expenditure of NCI
funds, or allow accrual credit for a protocol that has not been
approved, or that has been closed (except for patients already on
study).

1.a.(2) Monitoring

There will be periodic on-site audits of each CCOP by representatives
of its research base(s), NCI, or an NCI-designee, such as DCT's
current Clinical Trials Monitoring Service contractor.  Such on-site
audits may include review of the following:  use of investigational
drugs; compliance with regulations for Institutional Review Board
(IRB) approval and informed consent (compliance with 45 CFR 46);
compliance with protocol specifications; quality control and accuracy
of data recording; and completeness of reporting adverse drug
reactions.  Reports of such on-site audits will be reviewed by the
Clinical Trials Monitoring Branch (CTMB), Cancer Therapy Evaluation
Program (CTEP), DCT, and by the DCPC Program Director.  In addition,
NCI program and grants management staff will review protocol accrual,
fiscal and administrative procedures.

1.a.(3) Data Management

The DCPC Program Director will have access to all data generated
under this award and will periodically review the data management
procedures of the CCOP.  Data must also be available for external
monitoring if required by NCI's agreement with other federal
agencies, such as the Food and Drug Administration (FDA).

1.a.(4) Investigational Drug Management

The Drug Management and Authorization Section, Investigational Drug
Branch (IDB), CTEP, DCT and Chemoprevention Investigational Studies
Branch (CISB), DCPC staff will advise investigators of specific
requirements and changes in requirements about investigational drug
management that the FDA and NCI may mandate, either directly or
through the research bases.

1.a.(5) Organizational Changes

CCOPs must obtain prior written approval of the DCPC Program Director
for certain organizational changes.  These changes include the
addition/deletion of a participating physician or a health
professional other than a physician (entering patients/subjects in
cancer prevention and control research in the CCOP), an affiliate,
component, or research base.

A change in the principal investigator, or in any key personnel
identified on the "Notice of Award," must have the prior written
approval of the NCI Grants Management specialist, with the advice of
the DCPC Program Director.

1.a.(6) Program Review

Annual progress reports must be submitted to DCPC.  A suggested
format developed by the DCPC Program Director for this purpose will
be provided.  The DCPC Program Director will review the progress of
each CCOP through consideration of the CCOP annual report, program
site visits, and reports from affiliated research bases.  This review
may include, but not be limited to, overall accrual credits, percent
of available patients/subjects placed on study, eligibility and
evaluability of individuals entered on study, and timeliness and
quality of data reporting.  The inability of a CCOP to meet the
performance requirements set forth in the Terms and Conditions of
Award in the RFA, or significant changes in the level of performance,
may result in an adjustment of funding, withholding of support,
suspension or termination of the award.

1.a.(7) Strategy Sessions

The DCPC Program Director or designee will sponsor strategy sessions
when indicated, attended by principal investigators from the CCOPs
and appropriate DCPC/DCT staff.  At these meetings, information
relevant to the CCOPs will be reviewed and discussed, including such
issues as overall CCOP performance and the science of current or
proposed clinical trials.  Data will be analyzed and the outstanding
research questions established and prioritized into national research
goals by CCOP investigators and the DCPC/DCT attendees.  The
principal investigators will have the primary responsibility for
analyzing and prioritizing the research questions to be developed
into clinical trials.  The DCPC Program Director will also assist the
CCOP investigators in exploring mutual interests in cancer prevention
and control research.

1.a.(8) Federally Mandated Regulatory Requirements

The DCPC Program Director or designee and DCT staff will review
mechanisms established by each CCOP to meet the Department of Health
and Human Services (DHHS)/Public Health Service (PHS) regulations for
the protection of human subjects and FDA requirements for the conduct
of research using investigational agents.  At a minimum, these
include:

o  methods for assuring that each institution at which CCOP
investigators are conducting clinical trials has a current, approved
assurance on file with the Office for Protection from Research Risks
(OPRR); that each protocol is reviewed by the responsible IRB prior
to patient entry; and that each protocol is reviewed annually by the
IRB so long as the protocol is active;

o  methods for assuring or documenting that each patient (or
patient's parent/legal guardian) gives fully informed written consent
to participation in a research protocol prior to the initiation of
the experimental intervention;

o  a system for assuring timely reporting of all serious and
unexpected toxicities to the IDB, CTEP, DCT, according to DCT
guidelines and/or to DCPC according to DCPC guidelines; and

o  implementation of DCPC/DCT requirements for storage and accounting
for investigational agents provided under DCPC/DCT sponsorship.

1.a.(9) Arbitration Process

The Terms and Conditions of Award require that the DCPC Program
Director make post-award administrative decisions related to program
performance,programmatic decisions on scientific-technical matters,
and funding adjustments.  NCI will establish an arbitration process
when a mutually acceptable agreement cannot be obtained between the
awardee and the DCPC Program Director.  An arbitration panel (with
appropriate expertise) composed of one member of the recipient group,
one NCI nominee, and a third member chosen by the other two will be
formed to review the NCI decision and recommend a course of action to
the Director, DCPC.  These special arbitration procedures in no way
affect the awardee's right to appeal an adverse action in accordance
with PHS regulations 42 CFR Part 50, Subpart D, and DHHS regulations
45 CFR Part 16.

1.  Community (CCOP) Awardees

1.b.  Responsibilities of Awardees

1.b.(1) Protocols

All protocols utilized by the CCOPs must have been reviewed and
approved for CCOP use by the CCPRC, DCPC, and/or the PRC, DCT, NCI,
prior to implementation.

The research base is responsible for the development and
implementation of high quality treatment and cancer prevention and
control clinical trials, and for evaluation of the results of such
studies.  To be eligible to receive credit for accrual to a research
base protocol, the CCOP must have an affiliation agreement with the
research base responsible to NCI for that protocol.

1.b.(2) Research Base Affiliation(s)

Each CCOP must affiliate with a national multi-specialty cooperative
group having a spectrum of treatment and cancer prevention and
control clinical trials.  Each CCOP can affiliate with four or fewer
additional research bases.

Note:  A list of currently eligible research bases may be obtained
from the program official listed in the Letter of Intent Section.

If participation in the protocols of one group competes with that of
another group with which the CCOP is affiliated, the CCOP must
prioritize the protocols in order to avoid bias in the allocation of
patients to competing protocols.

Initial affiliations should be maintained during the funding cycle.
When circumstances require changes in research base affiliations,
prior written approval from the DCPC Program Director is required.

1.b.(3) Accrual

Each CCOP is required to accrue a minimum of 50 credits* per year to
treatment clinical trials that have been approved by the PRC, DCT,
NCI.  (For applicants whose specialty is pediatrics, the 50 credit
minimum requirement may be waived for those applicants who are able
to place a majority of their eligible patients on protocols.)  As one
measure of performance, it is expected that at least 10 percent of
patients for whom protocols are available will be placed on clinical
trials by CCOP physicians.

Each CCOP is required to accrue a minimum of 50 credits* per year to
cancer prevention and control clinical trials that have been approved
by the CCPRC, DCPC.

The CCOPs ability to meet projected accrual goals to both cancer
treatment and cancer prevention and control clinical trials will also
be assessed.

*  Each protocol approved for CCOP use will be assigned a credit
value. Credits will be based on the complexity of the intervention,
the amount of data management required, and the duration of
follow-up.  For example, each patient accrued to an average Phase II
or Phase III treatment protocol will count 1 credit; an
NCI-designated high-priority treatment protocol 1.5 credits; and a
childhood acute lymphocytic leukemia protocol 2 credits.  Cancer
prevention and control protocols will be assessed for credit using a
similar approach.  For example, a randomized Phase III
chemoprevention protocol will be assigned a value of 1 credit per
subject entered.  Cancer control protocols involving administration
of questionnaires receive an average assignment of 0.3
credits/subject.

1.b.(4) Quality Control

The CCOP must follow the procedures required by each of its research
bases and the CTMB, CTEP, DCT/DCPC Program Director.

1.b.(5) Data Management

The CCOP must provide the DCPC Program Director with access to all
data generated under this award for periodic review of data
management  procedures of the CCOP.  Data must also be available for
external monitoring if required by NCI's agreement with other federal
agencies, such as the FDA and with NCI's agreements with
pharmaceutical companies for the co-development of investigational
agents.  The awardees will retain custody of and primary rights to
their data.

1.b.(6) Investigational Drug Management

Investigators performing trials under cooperative agreements will be
expected, in cooperation with NCI, to comply with all FDA monitoring
and reporting requirements for investigational agents.

1.b.(7) Organizational Changes

Certain CCOP organizational changes must have the prior written
approval of the DCPC Program Director.  These include the
addition/deletion of a participating physician, a health professional
other than a physician (who actively enters patients to cancer
prevention and control trials), an affiliate, component, or research
base.

A change in the principal investigator, or in any key personnel
identified on the "Notice of Award," must have the prior written
approval of the NCI Grants Management specialist, with the advice of
the DCPC Program Director.

1.b.(8) Radiotherapy Equipment

Radiotherapy equipment must have its calibration verified according
to standards set by the Radiologic Physics Center (RPC) in order for
institutions to participate in protocols requiring radiation therapy,
as required by the affiliated research base(s).

1.b.(9) Monitoring

Each CCOP must agree to periodic on-site audits by representatives of
its research base(s), NCI, or an NCI-designee.

1.b.(10) Reporting Requirements

Annual progress reports must be submitted to DCPC.  A suggested
format developed by the DCPC Program Director for this purpose will
be provided.  The DCPC Program Director will review the progress of
each CCOP.  The inability of a CCOP to meet the performance
requirements set forth in the Terms and Conditions of Award in the
RFA, or significant changes in the level of performance, may result
in an adjustment of funding, withholding of support, suspension or
termination of the award.

1.b.(11) Network Participation

CCOPs are part of a national network for conducting treatment and
cancer prevention and control clinical trials.  As such, each CCOP
may be asked to participate in strategy sessions or workshops and in
the continuing evaluation of the program and its impact in the
community.

1.b.(12) Patient Log

Each CCOP may be asked to periodically maintain a new patient log or
minimal registry to include age, sex, race, insurance status, primary
site of cancer, stage of disease, and treatment disposition for the
potentially eligible patient pool seen by the CCOP investigators.

1.b.(13) Federally Mandated Regulatory Requirements

Each CCOP must establish mechanisms to meet DHHS/PHS regulations for
the protection of human subjects.

1.b.(14) Publications

Timely publication of major findings is encouraged.  Publication or
oral presentation of work done under this agreement requires
acknowledgement of NCI support.

B.  Terms and Conditions of Award

2.  Research Base Awardees

2.a.  Nature of NCI Staff Involvement

2.a.(1) Scientific Resource

The Division of Cancer Prevention and Control (DCPC) and Division of
Cancer Treatment (DCT) staff will serve as a resource for specific
scientific information on cancer prevention and control clinical
trials, treatment regimens, and clinical trial design.  The DCPC
Program Director will assist the research base as appropriate in
developing information concerning the scientific basis for specific
trials and will also be responsible for advising the research base of
the nature and results of relevant trials being carried out
nationally or internationally.  The DCPC Program Director will
sponsor strategy sessions when indicated, attended by leading
investigators from the research bases, other extramural scientists,
and appropriate experts to discuss specific research initiatives.
The Investigational Drug Branch (IDB), Cancer Therapy Evaluation
Program (CTEP), DCT, Chemoprevention Investigational Studies Branch
(CISB), DCPC, staff, through the DCPC Program Director, will provide
updated information on the efficacy, toxicity and availability of all
Investigational New Drugs (INDs) supplied by NCI to the research
base.  The principal investigators will have primary control over
making decisions derived from meetings with the additional staff
named above.

2.a.(2) Protocol Development

The protocol should be a document mutually acceptable to the research
base and to DCPC/DCT.  Communication at the various stages of
development is encouraged.  DCPC/DCT will assist the research base in
protocol design as appropriate by providing information regarding:
(a) the existence and nature of concurrent clinical trials in the
area of research, with an emphasis on preventing duplication of
effort; (b) relevant pharmacokinetic and pharmacodynamic data on
investigational agents; (c) availability of investigational agents,
including biologic response modifiers; (d) feasibility and
appropriateness of the research for use by the CCOPs and/or in a
community setting; and (e) basic research in cancer centers and other
NCI-funded programs that may be ready for clinical trials.  DCPC/DCT
will also comment on the scientific rationale, programmatic
relevance, priority, design, statistical requirements, and
implementation of the proposed study.

All cancer prevention and control protocols proposed for use by the
CCOPs must be preceded by a concept for review by DCPC.  All cancer
prevention and control concepts and protocols should be submitted to
the Protocol Information Office (PIO), CTEP, DCT, for review by the
Cancer Control Protocol Review Committee, DCPC.  DCT may require a
letter of intent for cancer treatment trials.  All treatment
protocols should be submitted to the PIO, CTEP, DCT.

2.a.(3) Protocol Review

All research base protocols utilized by the CCOPs must be reviewed
and approved for CCOP use by the Cancer Control Protocol Review
Committee (CCPRC), DCPC, and/or the Protocol Review Committee (PRC),
DCT, NCI, prior to implementation.

The major considerations in protocol review by DCPC/DCT include:  (a)
strength of the scientific rationale supporting the study; (b)
importance of the question being posed; (c) avoidance of undesirable
duplication with ongoing clinical trials; (d) appropriateness and
feasibility of study design; (e) satisfactory projected accrual rate
and follow-up period; (f) patient/subject safety; (g) compliance with
NIH and other federal regulatory requirements; (h) adequacy of data
management; and (i) appropriateness of patient/subject selection,
evaluation, assessment of toxicity, response to intervention, and
follow-up.

The DCPC/DCT review committee chairperson will provide the research
base with a consensus review that describes recommended modifications
and other suggestions as appropriate.  If a protocol is disapproved,
the specific reasons for lack of approval will be communicated to the
research base principal investigator as a consensus review within a
reasonable time.

The DCPC Program Director will work with the research base, where
appropriate, to develop a mutually acceptable protocol compatible
with the research interests, abilities, and needs of the base, its
affiliates, and NCI.  Credit will be assigned following final
approval of the protocol.

NCI will not provide investigational drugs, permit expenditure of NCI
funds, or allow accrual credit for a protocol that has not been
approved.

2.a.(4) Data Management and Analysis

The awardees will retain custody of and primary rights to their data;
however, DCPC/DCT will have access to all data generated under this
award.  The DCPC Program Director or a DCT representative may review
data management and analysis procedures of the research base, under
mutually agreeable circumstances, for consistency with policies and
procedures established by DCPC/DCT for awardees conducting treatment
and cancer prevention and control clinical trials.

Data must also be available for external monitoring if required by
NCI's agreement with other federal agencies, such as the Food and
Drug Administration (FDA) and by NCI's agreements with pharmaceutical
companies for the co-development of investigational agents.

2.a.(5) Quality Control and Monitoring

The Clinical Trials Monitoring Branch (CTMB), CTEP, DCT/DCPC Program
Director may review quality control and monitoring procedures of the
research base for consistency with policies and procedures
established by DCT/DCPC for awardees conducting treatment and cancer
prevention and control clinical trials.

2.a.(6) Investigational Drug Management

The Drug Management and Authorization Section, IDB, CTEP, DCT, and
CISB, CPRP, DCPC, staff will advise investigators of specific
requirements and changes in requirements concerning investigational
drug management that the FDA may mandate.

2.a.(7) Organizational Changes

A change in the research base principal investigator, or in any key
personnel identified in the "Notice of Award," must have the prior
written approval of the NCI Grants Management specialist, with the
advice of the DCPC Program Director.

2.a.(8) Program Review

Annual progress reports, including an annual performance report on
each affiliated CCOP, must be submitted to DCPC.  A suggested format
developed by the DCPC Program Director for this purpose will be
provided.  The DCPC Program Director will review the progress of each
research base through consideration of the research base annual
report and program site visits.  The annual report will include, as a
minimum, information on:  overall case accrual credits; cancer
prevention and control research, existing or planned; eligibility and
evaluability of patients/subjects entered on study; timeliness and
quality of data reporting; and results of quality control review and
audits if performed during that year.  Research base funding is
contingent on accrual from affiliated CCOPs/Minority-Based CCOPs and
annual adjustments in funding may be made.  The inability of a
research base to meet the performance requirements set forth in the
Terms and Conditions of Award in the RFA, or significant changes in
the level of performance, may result in an adjustment of funding,
withholding of support, suspension or termination of the award.

2.a.(9) Protocol Closure

DCPC/DCT will review research base mechanisms for interim monitoring
of results and will monitor protocol progress.  DCPC/DCT may request
that a protocol study be closed for reasons including:  (a)
insufficient accrual rate; (b) accrual goal met; (c) poor protocol
performance; (d) patient/subject safety; (e) already conclusive study
results; and (f) emergence of new information which diminishes the
scientific importance of the study question.

NCI will not provide investigational drugs, permit expenditure of NCI
funds, or allow accrual credit for a study after requesting closure
(except for patients already on study).

If a research base wishes to close accrual to a study prior to
meeting the initially established accrual goal, the interim results
and other documentation should be made available to NCI for review
and concurrence prior to implementation of the decision by the
research base.  It is recommended that statistical guidelines for
early closure be presented as explicitly as possible in the protocol
in order to facilitate these decisions.

2.a.(10) Federally Mandated Regulatory Requirements

The DCPC Program Director and a DCT representative will review
mechanisms established by each research base to meet Department of
Health and Human Services (DHHS)/Public Health Service (PHS)
regulations for the protection of human subjects and FDA requirements
for the conduct of research using investigational agents.  At a
minimum, these include:

o  a method for assuring that local IRB approval has been obtained
before patients are registered on each study.

o  an on-site audit program for periodic data verification and review
of regulatory responsibilities at each CCOP, cooperative group
member, and Cooperative Group Outreach/cancer center affiliate
institution.

o  a method of providing, upon DCPC/DCT request, summary efficacy and
toxicity data to be included in DCPC/DCT's annual reports to the FDA
for each investigational agent.

o  a method for the timely reporting of serious adverse reactions.

2.a.(11) CCOPs/Minority-Based CCOPs

The DCPC Program Director will notify research bases when
CCOPs/Minority-Based CCOPs are funded.

2.a.(12) Arbitration Process

The Terms and Conditions of Award require that the DCPC Program
Director make post-award decisions related to protocol review,
program performance and adjustments in funding.  NCI will establish
an arbitration process when a mutually acceptable agreement cannot be
obtained between the awardee and NCI staff.  An arbitration panel
(with appropriate expertise) composed of one member of the recipient
group, one NCI nominee, and a third member chosen by the other two
will be formed to review the NCI decision and recommend an
appropriate course of action to the Director, DCPC.  These special
arbitration procedures in no way affect the awardee's right to appeal
an adverse action in accordance with PHS regulations 42 CFR Part 50,
Subpart D, and DHHS regulations 45 CFR Part 16.

2.  Research Base Awardees

2.b.  Responsibilities of Awardees

2.b.(1) Protocol Development

The research base is responsible for the development and
implementation of high quality treatment and cancer prevention and
control clinical trials, and for evaluation of the results of such
clinical trials.

2.b.(2) Protocol Review

All research base protocols utilized by the CCOPs must have been
reviewed and approved for CCOP use by the CCPRC, DCPC, and/or the
PRC, DCT, NCI, prior to implementation.

Treatment and cancer prevention and control protocols must be
submitted to the PIO, CTEP, DCT, for review by the appropriate
committee.  DCT may require a letter of intent for treatment
protocols.  All cancer prevention and control protocols must be
preceded by a concept review by DCPC.

2.b.(3) Accrual

A research base for treatment research is required to accrue a
minimum of 50 credits* per year from affiliated CCOPs to treatment
clinical trials that have been approved by the PRC, DCT, NCI.

A research base for cancer prevention and control research is
required to accrue a minimum of 50 credits* per year from affiliated
CCOPs to cancer prevention and control clinical trials that have been
approved by the CCPRC, DCPC.

*  Each protocol approved for CCOP use will be assigned a credit
value. Credits will be based on the complexity of the intervention,
the amount of data management required, and the duration of
follow-up.  For example, each patient accrued to an average Phase II
or Phase III treatment protocol will count 1 credit; an
NCI-designated high-priority treatment protocol 1.5 credits; and a
childhood acute lymphocytic leukemia protocol 2 credits.  Cancer
prevention and control protocols will be assessed for credit using a
similar approach.  For example, a randomized Phase III
chemoprevention protocol will be assigned a value of 1 credit per
subject entered.  Cancer control protocols involving administration
of questionnaires receive an average assignment of 0.3
credits/subject.

2.b.(4) Data Management and Analysis

Data generated is the property of the awardee; however, the research
base must provide DCPC/DCT with access to all data generated under
this award.  The DCPC Program Director or a DCT representative may
review data management and analysis procedures of the research base
under mutually agreeable circumstances.

Data must also be available for external monitoring if required by
NCI's agreement with other Federal agencies, such as the FDA and by
NCI's agreements with pharmaceutical companies for the co-development
of investigational agents.

2.b.(5) Quality Control

A DCPC/DCT-funded research base must follow all the policies and
procedures for quality control established by NCI.  Similar policies
and procedures for quality control will be expected from cancer
centers.

2.b.(6) Investigational Drug Management

Investigators performing trials under cooperative agreements will be
expected, in cooperation with DCPC/DCT to comply with all FDA
distribution, monitoring, and reporting requirements for
investigational agents.

2.b.(7) Organizational Changes

A change in the research base principal investigator, or in any key
personnel identified in the "Notice of Award," must have the prior
written approval of the NCI Grants Management specialist, with the
advice of the DCPC Program Director.

2.b.(8) Audits

Each research base will be responsible for auditing its affiliated
CCOPs/Minority-Based CCOPs.  Cooperative group research bases will be
responsible for on-site audits of affiliated CCOPs according to the
established guidelines for monitoring its other members and/or
affiliates. Cancer center research bases may initiate their own audit
programs following guidelines established by the CTMB, CTEP, DCT.  As
an alternative, they may choose to include CCOP records in the audits
of center studies conducted by CTEP.  If this latter option is
chosen, the center must prospectively assure that medical charts and
other records from the affiliated CCOPs will be brought to the center
for audit when they are requested.  Results of CCOP audits will be
reported to the CTMB, CTEP, DCT, and the DCPC Program Director.

Cancer centers approved as research bases for only cancer prevention
and control research must have audit procedures for affiliated CCOPs.
Results of these CCOP audits will be reported to the DCPC Program
Director.

2.b.(9) Reporting Requirements

Annual progress reports, including an annual performance report on
each affiliated CCOP, must be submitted to DCPC.  A suggested format
developed by the DCPC Program Director for this purpose will be
provided.  The DCPC Program Director will review the performance of
each research base. Research base funding is contingent on accrual
from affiliated CCOPs/Minority-Based CCOPs and annual adjustments may
be made.  The inability of a research base to meet the performance
requirements set forth in the Terms and Conditions of Award in the
RFA, or significant changes in the level of performance, may result
in an adjustment of funding, withholding of support, suspension or
termination of the award.

2.b.(10) Network Participation

Research bases are part of a national network for conducting
treatment and cancer prevention and control clinical trials.  As
such, each research base may be asked to participate in strategy
sessions or workshops and the continuing evaluation of the program
and its impact in the community.

2.b.(11) Federally Mandated Regulatory Requirements

Each research base must establish mechanisms to meet FDA regulatory
requirements for clinical trials involving DCPC/DCT-sponsored
investigational agents and DHHS/PHS regulations for the protection of
human subjects.

2.b.(12) CCOPS/Minority-Based CCOPs

Research bases must agree to affiliate with CCOPs/Minority-Based
CCOPs when they are funded, according to guidelines established by
each research base for its affiliates, and as appropriate.

2.b.(13) Publications

Timely publication of major findings is encouraged.  Publication or
oral presentation of work done under this agreement requires
acknowledgement of NCI support.

STUDY POPULATIONS

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 human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and superseded and strengthens the previous policies
(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) to correct typesetting
errors in the earlier publication, 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 below.  Program staff may also
provide additional relevant information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit by July 1, 1994, a letter
of intent that includes a descriptive title of the proposed research,
the name, address, and telephone number of the principal
investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application is being submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains is helpful in planning for the review of
applications.  It allows NCI staff to estimate the potential review
workload and to avoid possible conflict of interest in the review.

The letter of intent is to be sent to Dr. Leslit G. Ford at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

A. Preparation of Application

General instructions for the preparation of the cooperative agreement
application are contained in the grant application form PHS 398 (rev.
9/91).  Responses to the instructions concerning "Human Subjects"
verification must be provided when the application is initially
submitted.

1. CCOP Applicants

Because the Terms and Conditions of Award (discussed in the SPECIAL
REQUIREMENTS Section above) will be included in all awards issued as
a result of this RFA, it is critical that each applicant include
specific plans for responding to these terms.  Plans must describe
how the applicant will comply with NCI staff involvement as well as
how all the responsibilities of awardees will be fulfilled.

An application from a currently funded program will be a competitive
continuation and must include a progress report, which at a minimum
consists of: (1) a summary of prior CCOP activities/accomplishments,
including a clear presentation of annual accrual over the funding
period such as accrual tables from previous annual progress reports
(progress in meeting DCPC accrual goals must be presented); (2) an
evaluation of CCOP performance by affiliated research base(s); and
(3) a complete description of how the applicant has met the special
cooperative agreement terms and conditions of the award.

1.a.  Each applicant must delineate its catchment area.  A map of the
service area, designating counties or zip codes from which
approximately 80 percent of the patients will be drawn, should be
provided.  A description of other cancer care resources in the
catchment area (i.e., hospitals, clinics, physicians, cancer centers)
that are not part of the application should be included.  In
describing the study population, it is recommended that a breakdown
by percentage of the gender and minority composition of the study
population be provided.  This information may be based on the
institutional records and/or prior experience.

1.b.  Each applicant must demonstrate the potential and stated
commitment to accrue a minimum of 50 credits per year to treatment
clinical trials (except if waived for applicants whose specialty is
pediatrics).  Documentation must include any prior participation in
treatment research clinical trials with a clear presentation of the
number of patients and credits accrued to NCI approved treatment
clinical trials.

A list of the NCI-approved treatment protocols in which the applicant
expects to participate and projected accrual to each must be
provided.

1.c.  Each applicant must demonstrate the potential and stated
commitment to accrue a minimum of 50 credits per year to cancer
prevention and control protocols.  Documentation must include any
prior participation in cancer prevention and control research
clinical trials with a clear presentation of the number of patients
and credits accrued to NCI-approved cancer prevention and control
clinical trials.

The CCOP applicant must document experience in cancer prevention and
control activities and research, ability to access the appropriate
physicians and patient/subject populations, and adequate facilities
to participate in the proposed clinical trials.

The ability of CCOPs and research bases to collaborate in cancer
prevention and control research must be demonstrated by each
applicant.  Working with affiliated research bases, the applicant
must provide at least two examples of DCPC approved intervention
cancer prevention and control protocols appropriate for the CCOP's
participation, and should describe their implementation, including
specifics on patient/subject recruitment, compliance, and follow-up.

A list of the NCI approved cancer prevention and control protocols in
which the applicant expects to participate and projected accrual to
each must be provided.

1.d.  A designated Principal Investigator is required.  An associate
principal investigator should also be named to assure continuity in
the event of resignation of the principal investigator.  The
qualifications and experience of both, in terms of ability to
organize and manage a community oncology program that includes
treatment and cancer prevention and control research and related
activities, must be described.

1.e.  Each applicant is expected to have a committed
multidisciplinary professional group appropriate for its expected
protocol participation.  This team may include medical oncologists,
surgeons, radiation oncologists, pathologists, oncology nurses, data
managers, health educators, and other disciplines (e.g., gynecology,
urology, pediatrics, internal medicine, family practice) as
appropriate.  The training and experience of participating physicians
must be provided, along with a description of working relationships.
Any experience working together as a group, particularly in
implementing clinical treatment and cancer prevention and control
research and related activities, should be included.  An
organizational chart showing how the group will function must also be
included.

1.f.  Each applicant must provide the qualifications and experience
of all proposed support personnel as well as a description of the
proposed duties for each position.

1.g.  Through formal affiliations with a maximum of five research
bases, only one of which may be a national multi-specialty
cooperative group, each applicant must demonstrate access to both
treatment and cancer prevention and control research protocols.
Evidence must be provided that an affiliation has been established
with at least one NCI-funded research base which has the capacity to
provide both clinical treatment and cancer prevention and control
protocols.  In addition, affiliations with research bases offering
only cancer prevention and control protocols are appropriate.  The
conditions of affiliation must be provided in the CCOP-research base
affiliation agreement(s).  Initial affiliations should be maintained
during the funding cycle.

Multiple research base affiliations are permitted provided they are
not conflicting.  The affiliation agreements must state specifically
how the problem of competing protocols will be resolved.

NOTE:  A list of currently eligible research bases may be obtained
from the program official listed under INQUIRIES.

1.h.  Quality control procedures must be described in detail.
Assurance of quality is the joint responsibility of the CCOP and its
research base(s). Quality control procedures of the research base
will be applied to the CCOPs and should be specified in the
CCOP-research base affiliation agreement.

Procedures for investigational drug monitoring and data management
must also be described.

1.i.  The availability of facilities, including laboratories,
inpatient and outpatient resources, cancer registries, etc., must be
described.  A statement of commitment from each participating
institution or organization and/or documentation of consortium
arrangements must be provided.  Evidence of involvement with
community-based voluntary organizations may be submitted.  In
addition, each applicant must have a defined space for administrative
activities and administrative personnel, which will serve as a focus
for data management, quality control, and communication.

1.j.  Allocation of funds to support community costs for receipt,
handling, and quality control of patient data must be specified.
Allowable items in the budget are requests for full or part-time
administrative personnel, data managers, and study assistants;
supplies and services directly related to study activities (e.g.,
processing and sending material for pathology review, processing and
sending port films for radiation therapy quality control); and
appropriate travel to meetings directly related to study activities
(e.g., research base meetings, NCI-sponsored strategy
sessions/workshops, local travel).  Funding is not allowed for
clinical care provided to patients (e.g., reimbursement of patient
care expenses; transportation costs).  Funding is not allowed for
clinical support personnel (e.g. pharmacist, physicist, clinical
psychologist, dosimetrist).  Physician compensation is only an
allowable cost for the Principal Investigator (PI) and Co-PI,
specifically for time spent on CCOP organizational/administrative
tasks.  Justification must be provided for personnel time, effort and
funds requested.

2.  Research Base Applicants

Because the Terms and Conditions of Award (discussed in the SPECIAL
REQUIREMENTS Section above) will be included in all awards issued as
a result of this RFA, it is critical that each applicant include
specific plans for responding to these terms.  Plans must describe
how the applicant will comply with NCI staff involvement as well as
how all the responsibilities of awardees will be fulfilled.

An application from a currently funded program will be a competitive
continuation and must include a progress report, which at a minimum
consists of:  (1) a summary of prior research base
activities/accomplishments, including a clear presentation of annual
accrual (by study, gender and racial/ethnic minority composition)
from affiliated CCOPs over the funding period; (2) progress in
developing and implementing DCPC-approved cancer prevention and
control clinical trials; (3) a description of how the applicant has
met the special cooperative agreement terms and conditions of the
award; and (4) a summary of participation of members and affiliates
in cancer prevention and control research.

Cooperative groups must participate in both treatment and cancer
prevention and control clinical trials; cancer centers may
participate in treatment and cancer prevention and control clinical
trials or cancer prevention and control research only.

2.a.  In describing the study population, it is required that a
description of the gender and minority population and subpopulation
served be provided, as well as an outreach plan.  This information
may be based on the institutional records and/or prior experience.

2.b.  Each applicant must demonstrate the ability to design and
implement multi-institutional treatment clinical trials, if
applicable as stated above.

A list of treatment protocols available for CCOP participation must
be provided.

2.c.  Each applicant must demonstrate the ability to design and
implement multi-institutional cancer prevention and control clinical
trials.

A list of cancer prevention and control protocols available for CCOP
participation must be provided.

The research base applicant must also provide at least two examples
of NCI-approved cancer prevention and control protocols and describe
plans for study design, intervention(s), and statistical
considerations; access to potential patients/subjects to be studied;
and procedures for data management, quality control, and follow-up.
The availability of appropriate expertise to design, implement, and
analyze the results of the proposed clinical trials must be
documented.  New applicants must provide at least two detailed
examples of proposed cancer prevention and control intervention
clinical trials.

2.d.  Each applicant must have an organizational structure for
involving appropriate personnel in the design and implementation of
treatment and/or cancer prevention and control research.  An
organizational chart and a description of the research base
operations showing the relationship(s) between the scientific and
administrative functional units of the research base, vis-a-vis the
conduct of treatment and/or cancer prevention and control clinical
trials, must be provided.

The organizational focus within the research base for cancer
prevention and control research must be described, including the
composition and activities of the research base cancer prevention and
control committee, or equivalent, and its relationship to other
clinical trial committees and activities.

2.e.  Collaboration with affiliated CCOPs/Minority-Based CCOPs in
treatment and/or cancer prevention and control research, as
applicable, is required. CCOP-research base affiliation agreements
must be included in the application.

For treatment research, each applicant must demonstrate the ability
to accrue a minimum of 50 credits per year from affiliated
CCOPs/Minority-Based CCOPs to treatment clinical trials.

For cancer prevention and control research, each applicant must
demonstrate the ability to accrue a minimum of 50 credits per year
from affiliated CCOPs/Minority-Based CCOPs to cancer prevention and
control clinical trials.

It is expected that selected cooperative group members and/or
Cooperative Group Outreach/cancer center affiliates other than the
CCOPs will participate in cancer prevention and control research.
The applicant must indicate the participants and their expected level
of participation, and describe their ability to participate.

2.f.  A designated Principal Investigator is required and his/her
qualifications and experience must be described.  An individual must
be designated to coordinate cancer prevention and control research.
His or her qualifications and experience within the research base
structure should also be described.  Each applicant must also
demonstrate the ability to access professionals with the appropriate
expertise to design and implement the proposed treatment and/or
cancer prevention and control clinical trials. Basic scientists,
medical, surgical, radiation and other oncology specialists, nurse
oncologists, epidemiologists, health educators and/or other public
health professionals may be included.

2.g.  Each applicant's ability to manage the data from
multi-institutional treatment and/or cancer prevention and control
clinical trials must be described.  Data management includes
development of data collection forms, procedures for data
transmittal, procedures for data entry, data editing, compilation,
and analysis, as well as procedures for quality control and
verification of submitted data.  Standards should exist for
determining eligibility and evaluability of patients/subjects entered
on protocols. Statistical capability must exist to develop protocol
statistical parameters, analyze the data, and report results.

2.h.  Each applicant must demonstrate the ability to initiate
procedures for training and maintaining the proficiency of personnel
from affiliated CCOPs/Minority-Based CCOPs on techniques for
successful management of treatment and/or cancer prevention and
control clinical trials research. Depending on the clinical trials
initiated and the interventions involved, this will include training
for data managers/nurses and any other individuals responsible for
data collection, monitoring, or carrying out the intervention(s).

2.i.  Each applicant's ability to provide mechanisms for periodic
review of the performance of affiliated CCOPs/Minority-Based CCOPs,
including on-site monitoring (auditing) and written procedures and
criteria for continued affiliations, must be described.  Similar
measures must be described for other member/affiliates participating
in cancer prevention and control research.

2.j.  Requests for funds must reflect headquarters operational,
quality control and data management add-on costs for CCOP
participation in protocols, based on the expected accrual credits of
affiliated CCOPs/Minority-Based CCOPs and for member/affiliate
accrual credits in cancer prevention and control. CCOP-research base
affiliation agreements must be included.  Each applicant should
include a budget for monitoring activities.  Funding can be requested
for scientific development and pilot testing of new cancer prevention
and control research initiatives (including support of a cancer
prevention and control committee for the research base), and funds
can also be requested  for appropriate travel to meetings directly
related to study activities (such as NCI-sponsored strategy
sessions/workshops).  Specific justification must be provided.

B.  Method of Applying

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for cooperative agreements.  These forms are available at
most institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/435-0714; and from the NCI program official listed
under INQUIRIES.

A suggested format will be sent to all applicants submitting a letter
of intent.  All applicants are encouraged to obtain and use the
suggested format instructions for organizing the specific information
concerning the RFA programmatic requirements in the PHS 398.

The RFA label available in the PHS 398 application form 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 RFA title and number must be typed on line 2a of the face page of
the application form and the YES box must be marked.

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

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

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

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Boulevard
Rockville, MD  20852   (If hand-delivered or delivery service)
Bethesda, MD  20892    (If using U.S. Postal Service)

It is important to send these copies at the same time that the
original and three copies are sent to DRG; otherwise, the NCI cannot
guarantee that the applications will be reviewed in competition with
other applications received by the designated receipt date.

Applications must be received by August 25, 1994.  If an application
is received after that date, it will be returned to the applicant.
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 substantial revisions of applications already
reviewed, but such applications must include an introduction
addressing the previous critique.

REVIEW CONSIDERATIONS

A.  Review Procedures

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

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, a
process (triage) may be used by the initial review group in which
applications will be determined to be competitive or non-competitive
based on their scientific merit relative to other applications
received in response to the RFA.  Applications judged to be
competitive will be discussed and be assigned a priority score.
Applications determined to be non-competitive will be withdrawn from
further consideration and the principal investigator/program director
and the official signing for the applicant organization will be
promptly notified.  The second level of review will be provided by
the National Cancer Advisory Board.

B.  Review Criteria

1.  CCOP Applicants

1.a.  Each applicant should demonstrate the ability to accrue a
minimum of 50 credits per year to treatment clinical trials and a
minimum of 50 credits per year to cancer prevention and control
clinical trials.  Established CCOPs will be funded at a yearly
accrual goal that may be higher than 50 credits for treatment
clinical trials and 50 credits for cancer prevention and control
clinical trials.  These established CCOPs will be evaluated for their
past preformance in meeting these accrual goals.  The accrual
requirement may be waived for applicants whose specialty is
pediatrics.  Each applicant's ability to access the appropriate
populations, professional disciplines, and facilities to participate
with affiliated research bases in at least two DCPC approved cancer
prevention and control intervention protocols will be appraised.  Any
prior participation in treatment and cancer prevention and control
research will be considered.

1.b.  Qualifications and experience of the principal
investigator/associate principal investigator, in terms of ability to
organize and manage a community oncology program that includes both
treatment and cancer prevention and control research and related
activities.

1.c.  Training, experience, and commitment of participating
physicians for accruing individuals to protocols in which the
applicant has agreed to participate.  The experience of proposed
investigators in the entry and treatment of cancer patients on
research trials (gained from residency, fellowships, postdoctoral
training and/or subsequent practice) will be appraised.  For
multidisciplinary studies, evidence of the availability of
appropriate professional resources (e.g., radiotherapy, pediatrics,
surgery, gynecology, urology, pathology, internal medicine, family
practice, nursing, and nutrition) will be required.  Experience or
special skills in cancer prevention and control research and related
activities will be considered, together with availability of other
community resources and personnel for such clinical trials.

1.d.  Stability of the functional unit or group applying to become a
CCOP.  Preexisting organizational affiliations of at least a core of
the group applying, and evidence of stable working relationships,
will be appraised.  Examples of established consortium arrangements,
and committee structure which demonstrates the participation of
appropriate physicians and administrators, may be submitted.
Evidence of previous success as a group in implementing clinical
treatment and cancer prevention and control research and related
activities will be considered.

1.e.  Qualifications and experience of all proposed support personnel
relative to their position descriptions.  The relevant credentials
and expected contributions to the program of personnel resources not
fiscally supported by the award will be considered.

1.f.  Adequacy of quality assurance mechanisms for both treatment and
cancer prevention and control interventions, and adequacy of
procedures for investigational drug monitoring and data management.

1.g.  Adequacy of available facilities, including laboratories,
in-patient and outpatient resources, cancer registries, etc., and
adequacy of space for administrative activities and personnel.

1.h.  Appropriateness of research base affiliations and of the
treatment and cancer prevention and control research protocols
chosen.  Affiliation agreements must be provided in the application.

1.i.  For competitive continuations, adequacy of progress during the
funding period, including ability to meet the minimum accrual credits
in cancer treatment and cancer prevention and control, progress made
as a CCOP, and evaluation of CCOP performance by affiliated research
bases(s).  Consideration will be given to previous accrual and the
ability to meet the previous accrual projections for which the CCOP
was funded.  The research base evaluation report(s) must be provided
in the application.

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

Allowable items in the budget are requests for full or part-time
administrative personnel, data managers, and study assistants;
supplies and services directly related to study activities (e.g.,
processing and sending material for pathology review, processing and
sending port films for radiation therapy quality control); and
appropriate travel to meetings directly related to study activities
(e.g., research base meetings, NCI-sponsored strategy
sessions/workshops, local travel).  Funding is not allowed for
clinical care provided to patients (e.g., patient care reimbursement,
transportation costs).  Funding is not allowed for clinical support
personnel (e.g. pharmacist, physicist, clinical psychologist,
dosimetrist).  Physician compensation is only an allowable cost for
the Principal Investigator (PI) and Co-PI, specifically for time
spent on CCOP organizational/administrative tasks.  Justification
must be provided for personnel time and effort and funds requested.

2.  Research Base Applicants

2.a.  Experience in conducting multi-institutional clinical trials;
demonstrated ability to develop such studies and act as a
coordinating and statistical center; and adequate facilities to
conduct the clinical trials.

2.b.  Quality and availability of treatment and/or cancer prevention
and control protocols, as applicable, which are appropriate for CCOP
participation, or the potential for developing such clinical trials.
Documentation of DCPC cancer prevention and control protocols,
including a detailed description of at least two examples of
NCI-approved cancer prevention and control protocols, will be
evaluated as part of the application along with professional
expertise to assure the quality of the proposed intervention clinical
trials.  Two detailed examples of proposed cancer prevention and
control intervention clinical trials will be evaluated for new
applicants.

2.c.  For treatment research, ability to accrue a minimum of 50
credits per year from affiliated CCOPs/Minority-Based CCOPs to
treatment clinical trials.

For cancer prevention and control research, ability to accrue a
minimum of 50 credits per year from affiliated CCOPs/Minority-Based
CCOPs to cancer prevention and control clinical trials.  Experience
as well as the potential for developing future clinical trials will
be considered.

Documentation must include CCOP-research base affiliation agreements.
Prior CCOP assessments must be included.

2.d.  Organizational structure for involving appropriate personnel in
the design and implementation of treatment and/or cancer prevention
and control research.  The organizational focus within the research
base for cancer prevention and control research, including the
composition and activities of the cancer prevention and control
committee, and its relationship to other clinical trial committees
and activities will be assessed.

2.e.  Qualifications and experience of the principal investigator
and/or the individual responsible for directly relating to the CCOPs.
The availability and experience of multidisciplinary health
professionals and allied professionals with skills needed to develop,
utilize, and analyze treatment and/or cancer prevention and control
clinical trials will also be evaluated.

2.f.  Experience in working with community oncologists, orienting
community data personnel to protocol requirements, organizing
scientific and educational meetings for those participating in the
clinical trials, and participating in intergroup clinical trials.

2.g.  Ability to establish quality control, quality assurance, and
data management procedures.  Experience in data management and
analysis of multi- institutional clinical trials and adequacy of data
management staff will be appraised.  The availability of mechanisms
for periodic review of quality control, quality assurance, and data
management procedures will be assessed.

2.h.  For competitive continuations, adequacy of progress during the
funding period, including cancer prevention and control protocol
development, implementation and current status of each to meet
minimum accrual credits from affiliated CCOPs, and progress in
meeting the requirements of a research base for CCOP.

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

Requests for funds must reflect headquarters operational, quality
control and data management add-on costs for CCOP participation in
protocols, based on the expected accrual credits of affiliated
CCOPs/Minority-Based CCOPs and for member/affiliate accrual credits
in cancer prevention and control.  Research bases should request
funds for monitoring and auditing costs.  Funding may be requested
for scientific development and pilot testing of new cancer prevention
and control research initiatives (including a cancer prevention and
control committee for the research base), or for appropriate travel
to meetings directly related to study activities (such as
NCI-sponsored strategy sessions/workshops).  Specific justification
must be provided.

AWARD CRITERIA

The anticipated date of award is June 1, 1995.  NCI program staff
will take into account demographic and geographic distribution of
applicants in the final funding selection process to assure inclusion
of minority and underserved populations.  Multiple CCOP applicants
for funding who are competing for the same patient population will be
considered, but all may not be awarded unless warranted by the
population density.

INQUIRIES

Written and telephone inquiries concerning the objectives and scope
of this RFA or inquiries about whether or not specific proposed
research would be responsive are encouraged.  The program official
welcomes the opportunity to clarify any issues or questions from
potential applicants.

Direct inquiries regarding programmatic issues and address the letter
of intent to:

Leslie G. Ford, M.D.
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Room 300-D
Bethesda, MD  20892
Telephone:  (301) 496-8541

Direct inquiries regarding fiscal matters to:

Ms. Crystal Elliott
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, Ext. 19

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 13.399, Cancer Control.  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 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.

The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

.

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