Full Text CA-95-015

COMMUNITY CLINICAL ONCOLOGY PROGRAM

NIH GUIDE, Volume 24, Number 21, June 9, 1995

RFA:  CA-95-015

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Community/Outreach Programs 
  Disease Control+ 


National Cancer Institute

Letter of Intent Receipt Date:  July 10, 1995
Application Receipt Date:  August 29, 1995

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).  Applicants for new and currently funded Community Clinical
Oncology Programs (CCOP) and research bases are invited to respond to
this Request For Applications (RFA).

Using 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, biomarkers and 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 cancer treatment and 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 twelve years by:  (1)
continuing the program as a vehicle for supporting community
participation in cancer treatment and 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 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 the CCOP applicant
organization 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 cancer treatment and
prevention and control clinical trials; cancer centers as CCOP
research bases may participate in both cancer treatment and
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
cancer treatment and 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, if funds are
available.

It is anticipated that up to $4.0 million in total costs per year for
five years will be committed to specifically fund applications that
are submitted in response to this RFA.  An additional $13.0 million
in total costs per year for five years will be committed to
specifically fund several large chemoprevention trials that have been
implemented through the CCOP network.  Approximately seven research
base awards and eight CCOP awards will be made.  This level of
support is dependent on the receipt of a sufficient number of
applications of high scientific merit.  Although this program is
provided for in the financial plans of 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 and accrued 14,000 patients to NCI
approved treatment clinical trials.

The CCOPs were clearly 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
1994, there were 50 programs in 29 states involving over 300
hospitals and over 3,000 physicians.  Approximately 3,800 patients
were entered onto treatment trials and 5,000 subjects on cancer
prevention and control trials in 1994.

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.  Protocols cover the full spectrum of
cancer prevention and control research, from chemoprevention and the
validation of biomarkers screening and early detection, pain control
and symptom management, and other rehabilitation and continuing care
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 that 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 cancer treatment and
prevention and control research to individuals in their own
communities by having practicing physicians and their
patients/subjects participate in NCI-approved cancer treatment and
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 cancer treatment and
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 cancer treatment and
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 cancer treatment and 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.

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 on a continuing basis in program evaluation.

SPECIAL REQUIREMENTS

A.  Terms and Conditions of Award

The administrative and funding instrument used for this program is a
cooperative agreement (U10), an "assistance" mechanism (rather than
an "acquisition" mechanism) in which substantial NIH scientific
and/or programmatic involvement with the awardee is anticipated
during performance of the activity.  Under the cooperative agreement,
the NIH purpose is to support and/or stimulate the recipient's
activity by involvement in and otherwise working jointly with the
award recipient in a partner role, but it is not to assume direction,
prime responsibility, or a dominant role in the activity.  Consistent
with this concept, the dominant role and prime responsibility for the
activity resides with the awardee(s) for the project as a whole,
although specific tasks and activities in carrying out the studies
will be shared among the awardees and the NCI Program Staff.

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. Responsibilities of Awardees

The awardee's programmatic responsibilities for the conduct of the
research supported by this cooperative agreement are described in the
INVESTIGATOR'S HANDBOOK, a Manual for Participants in Clinical Trials
of Investigational Agents Sponsored by the Division of Cancer
Treatment, National Cancer Institute, the CANCER PREVENTION AND
CONTROL HANDBOOK, and the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING
OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES and
any subsequent modifications of these documents.  These documents are
hereby incorporated by reference as term of award and are available
on request from the Cancer Therapy Evaluation Program (CTEP) or the
CORB/DCPC.

1.a.(1) Protocols

All protocols used 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.

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

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

Each CCOP must affiliate with a national multi-specialty cooperative
group having a spectrum of cancer treatment and prevention and
control clinical trials.  Each CCOP can affiliate with a maximum of
four 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 for the duration of the
funding cycle.  When circumstances require changes in research base
affiliations, prior written approval from the DCPC Program Director
is required.

1.a.(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 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 limited
interventions will receive credit that is commensurate with the
amount of data management effort required, usually an assignment of
0.3 or 0.5 credit per subject entered.

1.a.(4) Quality Control

The CCOP must establish and follow procedures for the assurance of
data quality and quality control in accordance with research base
guidelines and NCI policies.  The CCOP must follow NCI- approved
procedures developed by the research base for the prevention and/or
identification of false or otherwise unreliable data and for quality
assurance of data collected by the research base.

The CCOP must follow policies developed by the research base and
approved by the NCI for auditing the accuracy of scientific data
submitted to them by the research base participants.

1.a.(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.a.(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.a.(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.

1.a.(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.a.(9) Monitoring

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

CCOP members/affiliate performance sites and/or participating and/or
individual investigators participating or collaborating on NCI funded
and  unfunded, who are participating or collaborating in the CCOPs on
NCI-supported multi-institutional clinical trials must be in
compliance with the monitoring  standards established by the research
base.  They should include the following standards

o  Medical records submitted in support of NCI multi- institutional
trials must conform to usual standard for the maintenance of clear,
accurate, and unambiguous medical records.  White-outs on medical
records are unacceptable.

o  If it is the usual and customary practice of a department,
laboratory, clinic or office to prepare or issue official reports,
then only that department, laboratory, clinic or office can change
the report, and alterations of the medical record must be initialed
and dated by the person making such alterations. For clinical
progress notes, the change must be dated and initialled by the person
making the change.  Only one line should be placed through the
initial entry, so that both the original entry and the change are
legible.

o  The improper modification of important patient records will result
in additional investigations by the NCI Clinical Trials Monitoring
Branch (CTMB) and may lead to suspension of accrual and funding.

1.a.(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 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.(11) Network Participation

CCOPs are part of a national network for conducting cancer treatment
and 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.a.(12) Patient/Subject Log

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

1.a.(13) Federally Mandated Regulatory Requirements

Each CCOP must establish mechanisms to meet DHHS/PHS regulations for
the protection of human subjects.  At a minimum, these include:

o  methods for assuring that each facility 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 Investigational Drug Branch, 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.(14) Publications

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

1.  Community (CCOP) Awardees

1.b.  Nature of NCI Staff Involvement

1.b.(1) Protocol Review

All protocols used by the CCOPs must be reviewed and approved for
CCOP use by the Cancer Control Protocol Review Committee Protocol
Review Committee (CCPRC), (DCPC), and/or the Protocol Review
Committee (PRC), 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.b.(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.

The DCPC and CTMB/CTEP will review and provide advice regarding
mechanisms established for study monitoring including the on-site
auditing program.

DCPC/CTEP and/or its contractor staff may attend, the on-site audits
conducted by the Research Base or its NCI designee as observers.

1.b.(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.b.(4) Investigational Drug Management

The Regulatory Affairs Branch (RAB), PMB, CTEP, DCT, and
Chemoprevention Investigational Studies Branch (CISB),
Chemoprevention Research Program (CPRP), and DCPC staff will advise
investigators of specific requirements and changes in requirements
about investigational drug management that the FDA and NCI may
mandate.

1.b.(5) Organizational Changes

The DCPC program director will review requests for certain
organizational changes and provide written approval.  These changes
include the addition/deletion of a participating physician or other
health professional entering patients/subjects in cancer prevention
and control research in the CCOP, an affiliate, component, or
research base.

1.b.(6) Program Review

The DCPC program director will review the annual progress report
submitted by each CCOP.  A suggested format will be developed by the
DCPC Program Director for this purpose.  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.b.(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.b.(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.

1.b.(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.

B.  Terms and Conditions of Award

2.  Research Base Awardees

2.a.  Responsibilities of Awardees

It is the responsibility of the Research Base in accordance with its
constitution, bylaws, policies and procedures to develop the details
of the research design, including definition of objectives and
approaches, planning, implementation, analysis, and publication of
results, interpretations and conclusions of studies.  The research
base shall designate research base investigators to serve as Protocol
Chairpersons for each proposed study.  Protocols will be developed in
accordance with the instructions in the GUIDELINES CLINICAL TRIALS
COOPERATIVE GROUP PROGRAM and the INVESTIGATOR'S HANDBOOK, and CANCER
PREVENTION AND CONTROL HANDBOOK.

2.a.(1) Protocol Development

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

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.

2.a.(2) Concept/Protocol Submission

All research base protocols utilized by the CCOPs must have been
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.  Treatment and cancer
prevention and control protocols should be submitted to the protocol
Information Office (PIO), CTEP, DCT for review by the appropriate
committee.

All cancer prevention and control protocols must be preceded by the
submission of a concept proposal for review by the DCPC Cancer
Control Concept Review Committee (CCCRC).  The CCCRC considers
scientific merit and the feasibility of implementing prospective
cancer control protocols in the CCOP research network.  Similarly,
concept proposals for cancer treatment protocols must precede
protocol development.  Cancer treatment concepts are reviewed by the
CTEP Protocol Review Committee (PRC) in the Division of Cancer
Treatment.  All concept and protocol documents should be submitted to
the PIO, CTEP, DCT.  DCT may also require a letter of intent for new
cancer treatment trials.

2.a.(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 limited
interventions will receive credit that is commensurate with the
amount of data management effort required, usually an assignment of
0.3 or 0.5 credit per subject.

2.a.(4) Data Management and Analysis

The research base shall establish and implement mechanisms for data
management and analysis that ensure that data collection and
management procedures are:  (a) adequate for quality control and
analysis; (b) as simple as appropriate in order to encourage maximum
participation of physicians entering patients and to avoid
unnecessary expense; and (c) sufficiently uniform across research
bases.  CCOP members/affiliate performance sites are required to
follow procedures for 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.

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.a.(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.

The research bases shall establish mechanisms for quality control of
all procedures and modalities employed in its trials.  CCOP
member/affiliates are required to follow research base procedures for
quality control.

The research base shall establish mechanisms for study monitoring.
CCOP Members/Affiliates are required to follow the awardee procedures
for study monitoring.

The research base is responsible for assuring accurate and timely
knowledge of the progress of each study through:

o  tracking and reporting of patient accrual and adherence to defined
accrual goals;

o  ongoing assessment of case eligibility and evaluability;

o  timely medical review and assessment of patient data;

o  rapid reporting of treatment-related morbidity and measures to
ensure communication of this information to all parties;

o  interim evaluation and consideration of measures of outcome as
consistent with patient safety and good clinical trials practice;

o  timely communication of results of studies; and

o  an on-site monitoring program.

The research base is responsible for ensuring that all performance
sites have routine audits which are reported to the NCI in accordance
with the NCI/CTMB GUIDELINES FOR ON-SITE MONITORING OF CLINICAL
TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES.  In the event
that the NCI determines that the awardee failed to comply with these
guidelines, the accrual of new patients/subjects to the research
base's protocols at the affected performance site shall be suspended
immediately upon notice of the NCI determination.  The suspension
will remain in effect until the awardee conducts the required audit
and the audit report is accepted by the NCI.

The research base will be responsible for notifying any affected
performance site of the suspension.  During the suspension period, no
funds from this award may be provided to the performance site for new
accruals, and no changes to the award for new accruals will be
permitted.  The NCI will also notify an institution that is the
direct recipient of a cooperative agreement from the NCI if it is
necessary to suspend accrual at that institution.

2.a.(6) Quality Assurance of Data

The research base must develop and follow procedures for the
assurance of data quality and quality control in accordance with
research base guidelines and NCI policies.  The research base must
follow NCI-approved procedures for the prevention and/or
identification of false or otherwise unreliable data and for quality
assurance of data collected.

The research base must develop and implement NCI-approved policies
for auditing the accuracy of scientific data submitted to them.

In the event that there is a finding through the quality assurance
and/or quality control programs of any indication of a pattern of
non-compliance with protocol or regulatory requirements or a finding
of possible alteration of data, these findings must be reported in
accordance with the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF
CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES.

2.a.(7) Data and Safety Monitoring Committees

The research base must establish and maintain Data and Safety
Monitoring Committees (DSMCs) for Phase III prevention and control
clinical trials.  The policies and procedures of the DSMC must be
approved by the NCI.  The research base must comply with the approved
policies and procedures of the DSMC.

2.a.(8) Protocol Closure

The research base shall establish a mechanism for interim monitoring
of results and monitoring protocol progress.  If the 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 staff for review and concurrence
prior to closure.  It is recommended that statistical guidelines for
early closure be presented as explicitly as possible in the protocol
in order to facilitate these decisions.  In the event that the DMSC
has recommended early closure, DSMC procedures regarding notification
of DCPC must be followed.

2.a.(9) Protocol Reporting Requirements

Reporting requirements will be in agreement with FDA regulations and
NCI procedures.  Interim reports of each activated and ongoing study
shall appear in the minutes of each research base meeting and shall
include specific data on patient/subject accrual as well as, when
appropriate, detailed reports of treatment-associated morbidity.
Quarterly accrual reports must be provided as appropriate to CTEP for
all active studies.  A system for providing such information in a
timely manner should be in place.

2.a.(10) Annual Progress Report

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.

The annual report will include, at 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 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.(11) Adverse Event Procedures

In order to be in compliance with FDA regulations, all recipients of
NCI support for clinical trials, including research bases responsible
for coordinating and monitoring such trials, must promptly report
adverse events (including adverse drug reactions) to the NCI and any
other trial sponsors according to directions provided in the adverse
event reporting section of the protocol.

The awardee will notify all institutions/investigators participating
in this project, funded or unfunded, about the above requirement and
about the institutions'/investigators' responsibility to report
adverse events as specified in the protocol.  The awardee will also
notify the Investigational Drug Branch (IDB), Drug Monitor for
DCT-sponsored investigational agents and the Program Director for
other agents, of serious or life-threatening events, as specified in
the protocol.

2.a.(12) Performance Review

The research base shall establish policies and procedures for
credentialing participating CCOPS and conducting periodic review of
the performance and membership status of each performance site
conducting prevention and control clinical trials.  This review
should examine scientific contributions, patient accrual, data
accuracy and timeliness, protocol compliance, and audit results.

2.a.(13) Data Files Available to NCI Upon Request

Upon the request of the Grants Management Officer, NCI, true copies
of data files and supporting documentation for all NCI- supported
protocols that have a major impact on patterns of care, as determined
by the NCI, shall be made available to the NCI in a timely manner.

2.a.(14) 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.a.(15) Network Participation

Research bases are part of a national network for conducting cancer
treatment and 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.a.(16) 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.  These regulations include, but are not limited to,
Title 21 CFR 50, 56 and 312 and Title 45 CFR 46.  At a minimum the
research base must be able to:

o  demonstrate that each participant has a current approved assurance
number on file with the NIH Office for Protection from Research Risks
(OPRR).

o  demonstrate that each protocol and informed consent is approved by
the responsible Institutional Review Board (IRB) prior to patient
entry, that each investigator has a current FDA Form 1572 and
curriculum vitae on file with the Pharmaceutical Management Branch,
(PMB), CTEP.

o  demonstrate that each patient (or legal representative) gives
written informed consent prior to entry on study.

o  implement the CTEP requirement for storage and accounting for
investigational agents provided under DCPC/DCT sponsorship.

o  establish 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  provide a method, upon DCPC/DCT request, of summarizing 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 all serious and unexpected
toxicities.

2.a.(17) 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.a.(18) Publications

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

2.a.(19) Procedures in the Event of Scientific Misconduct

If a duly authorized governmental or institutional body issues a
final determination that scientific misconduct has occurred or if the
awardee determines that other events have occurred which have
significantly affected the quality or integrity of the Group data or
patient safety, the awardee is responsible for notifying the Group
Data and Safety Monitoring Committee (DSMC), the CTMB, the
collaborating investigators, the appropriate Institutional Review
Boards (IRBs), and other sponsors of the affected work.

The awardee is also responsible, if the events describe above have
occurred, for ensuring that submitted but unpublished abstracts and
manuscripts are corrected, if possible.  If publication deadlines
have passed or if abstracts and/or manuscripts containing the
affected data have already been published, the awardee is
responsible, within 90 days after learning of the event(s)
significantly affecting the quality of the Group data or patient
safety, for submitting to NCI a re-analysis of the results deleting
the false or otherwise unreliable data, and disclosing within the
text the reason(s) for the reanalysis.  The awardee must submit the
reanalysis for publication.  The NCI may disseminate information
about the reanalysis as broadly as it deems necessary.

The awardee must use its best efforts to notify all scientists,
research laboratories, and other organizations to which the awardee
has sent research materials affected by false or otherwise unreliable
data.

True copies of data files and other supporting documentation from
studies affected by scientific misconduct or other findings affecting
the quality or integrity of data or patient safety shall be made
available to the NCI in a timely manner upon the request of the
Grants Management Officer, NCI.  The NCI reserves the right to
reanalyze, to publish, or to distribute its analyses of these data
when it is in the interest of public health.  Prior to release,
publication or distribution of such analyses, the NCI will provide
such analyses to the awardee.

2.a.(20) Data Files Available to NCI Upon Request

Upon the request of the Grants Management Officer, NCI, true copies
of data files and supporting documentation for all NCI-supported
protocols that have a major impact of patterns of care, as determined
by the NCI, shall be made available to the NCI in a timely manner.

2.a.(21) Notification of Patients by the Awardee During Patient's
Lifetime

In order for there to be an appropriate response in the event the NCI
determines, either while a protocol is active or (if relevant) during
the lifetime of the subjects following protocol closure, that a
medically important toxicity or side effect is associated with
protocol-directed treatment or that the medical care of one or more
subjects may have been compromised by scientific misconduct or other
finding affecting the integrity of the data or patient safety at the
awardee institution or at a third-party institution, funded or
unfunded, the awardee shall assure that the institution(s)
responsible for these subject(s') accrual, whether funded or
unfunded, will have procedures in place to; (a) contact each subject
individually at his or her last known address on file with the
institution and which give each subject contacted appropriate
information and the right to communicate with an appropriate
institutional representative and, in the event of misconduct, to meet
with a physician not connected with the clinical trial or study in
which the subject has participated; and (b) encourage subjects to
notify the institution of any changes of address.  The procedure must
provide for informing the subjects fully of; the consequences of the
toxicity or misconduct for their care and well-being, if any, and the
availability of follow-up; and their opportunity to examine any
portion of their medical records relevant to the potential effect of
the toxicity or side effect upon them or that may be affected by
scientific misconduct or other findings affecting the quality or
integrity of the data or patient safety.

It is understood that under regulations at 45 CFR Section 74.53, NCI
has a right of access to research records pertinent to the NCI
funding.  In exceptional circumstances, such as a public health
emergency, the institutions will be required to provide subject names
and treatments to the NCI in a format that allows direct notification
of the patient by the NCI.

2.  Research Base Awardees

2.b.  Nature of NCI Staff Involvement

2.b.(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.

2.b.(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 which
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.

2.b.(3) Concept/Protocol Review

All research base protocols utilized by the CCOPs must be reviewed
and approved for CCOP use by the (CCPRC), DCPC, and/or the (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 proposed; 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 the 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,
reasons 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.b.(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 cancer
treatment and 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.b.(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 including the on-site auditing program for consistency
with policies and procedures established by DCT/DCPC for awardees
conducting cancer treatment and prevention and control clinical
trials.

2.b.(6) Review of Quality Control and Study Monitoring

The DCPC and CTMB/CTEP will review and provide advice regarding
mechanisms established for study monitoring including the on-site
auditing program.

DCPC/CTEP and/or its contractor staff may attend as observers, the
on-site audits conducted by the Research Base or its NCI designee.
The frequency of participation by an NCI representative as observer
will be determined by the NCI.

2.b.(7) Data and Safety Monitoring Committees

The NCI Staff will assess the research base compliance with NCI
established policies on Data and Safety Monitoring Committees for
Phase III trials.  One or more DCPC/CTEP staff will serve as non-
voting members on the DSMC.

2.b.(8) Investigational Drug Management

The Regulatory Affairs Branch, 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.b.(9) Program Review

Annual progress reports, including an annual performance report on
each affiliated CCOP, must be submitted to DCPC.  DCPC staff will
provide a suggested format for this purpose.  The DCPC Program
Director will review the progress of each research base through
consideration of the research base quarterly accrual reports, annual
report and program site visits.

The DCPC program director will make funding recommendations based 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.b.(10) 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).

2.b.(11) 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.

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

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

2.b.(13) 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.

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 Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations) which
have been in effect since 1990.  The new policy contains some new
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines on the Inclusion of Women and Minorities as
Subjects in Clinical Research," which was reprinted in the Federal
Register of March 29, 1994 (59 FR 14508-14513) to correct type
setting errors, and reprinted in the Federal Register of March 28,
1994 (59 FR 14508-14513) and reprinted in the NIH GUIDE FOR GRANTS
AND CONTRACTS, Volume 23, Number 11, March 18, 1994.

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 10, 1995, 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 may be 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:

Leslie G. Ford, M.D.
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Room 300-D
6130 Executive Boulevard, MSC-7340
Bethesda, MD  20892-7340
Telephone:  (301) 496-8541

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.  Accrual tables from previous annual progress reports should
be included.  A summary of accrual to all cancer treatment and a
summary of accrual to all cancer prevention and control protocols by
gender and ethnicity must be provided; progress in meeting DCPC's
established accrual goals must be presented; (2) a plan for
continuing to meet prevention and control accrual requirements
including plans for follow-up of subjects from the large prevention
trials as well as plans for implementation of additional cancer
control protocols; (3) tables of the current budget and FTEs with a
justification for any request for additional resources; (4) an
evaluation of CCOP performance by affiliated research base(s); and
(5) a complete description of how the applicant has met the special
cooperative agreement terms and conditions of the award.

ALL Applications

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)
which are not part of the application should be included.  In
describing the study population, a breakdown by percentage of the
gender and minority composition of the study population should 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
total 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 the projected accrual to each must be
provided.  Plans for recruiting women and minority participants must
be included.

1.c.  Each applicant must demonstrate the potential and plans for
accrual of 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 total number of patients and
credits accrued to NCI approved cancer prevention and control
clinical trials.  A list of the NCI approved prevention and control
protocols in which the applicant expects to participate and the
projected accrual must be provided.  Plans for recruiting women and
minority subjects must be included.

New applicants must provide at least two examples of NCI-approved
intervention cancer prevention and control protocols appropriate for
the CCOP's participation.  The applicant should describe their
implementation, including specifics on patient/subject recruitment,
compliance and follow-up.  These studies must come from research
base's that they propose to affiliate.

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

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 cancer
treatment and 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 cancer treatment and 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
cancer treatment and prevention and control research protocols.
Evidence must be provided that an affiliation has been established
with at least one NCI-approved research base that has the capacity to
provide both clinical cancer treatment and 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 in the Letter of Intent Section.

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 research base 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 to cancer treatment and annual accrual to cancer prevention
and control protocols (gender and racial/ethnic minority composition)
from affiliated CCOPs over the funding period; 2) progress in
developing and implementing a cancer prevention and control research
program.  Include the process and organizational structure for
protocol development and implementation, selection and evaluation
(auditing) of performance sites, data management, quality control,
statistical analysis, and study safety monitoring; 3) a clear
presentation of annual accrual to each NCI-approved prevention and
control clinical trial for CCOPs, and research base members and
affiliates; (4) status of concepts and protocols under development;
(5) a description of how the applicant has met the special
cooperative agreement terms and conditions of the award.

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

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.a.  Each applicant must demonstrate the ability to design and
implement multi-institutional treatment clinical trials (if
applicable).

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

2.b.  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.

New research base applicants must also provide a least two examples
of active or proposed cancer prevention and control intervention
clinical trial 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.

2.c.  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.d.  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.e.  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.f.  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.g.  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.h.  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.i.  Each applicant must describe their plans for independent data
and safety monitoring for all phase III prevention and control
clinical trials.

2.j.  Requests for funds must reflect operations/statistical costs
for quality control and data management costs for CCOP participation
in protocols.  This estimate is 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 and auditing 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, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD
20892-7762; and from the NCI program official listed under INQUIRIES.

A suggested format will be sent to all applicants requesting an RFA
or 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 (rev. 9/91) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application 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 photocopies, in one package to
DRG at the address below.  The photocopies must be clear and single
sided.

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

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

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
Executive Plaza North - Room 636
6130 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (for express/courier 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 on or before the designated receipt date.

Applications must be received by August 29, 1995.  If an application
is received after that date, it will be returned to the applicant
without review.  The Division of Research Grants (DRG) will not
accept any application in response to this RFA that is essentially
the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The DRG will not accept
any application that is essentially the same as one already reviewed.
This does not preclude the submission of 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 for completeness by DRG
and responsiveness by the NCI staff.  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, all
applicants will receive a written critique and may undergo a process
in which only those applications deemed to have the highest
scientific merit will be discussed, assigned a priority score, and
received a second level review by the appropriate National Cancer
Advisory Board.

B.  Review Criteria

1.  CCOP Applicants

1.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.

1.b.  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 performance in meeting these accrual goals.  The minimum 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 NCI-approved cancer prevention and
control intervention protocols will be appraised.  Any prior
participation in cancer treatment and prevention and control research
will be considered.

1.c.  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
cancer treatment and prevention and control research and related
activities.

1.d.  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.e.  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
cancer treatment and prevention and control research and related
activities will be considered.

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

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

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

1.j.  For competitive continuations, adequacy of progress during the
funding period, including ability to meet the accrual goals in cancer
treatment and 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.  Plans for continued accrual and follow-up of subjects
on protocols will be evaluated.

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.

The initial review group will also examine the provisions for the
protection of human subjects, recruitment plans for the inclusion of
women, minorities and sub-populations to clinical trials, and the
safety of the research environment.

2.  Research Base Applicants

All research base applicants will be evaluated on the following
criteria:

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.  Experience in conducting multi-institutional clinical trials;
demonstrated ability to develop such studies and act as a
coordinating and statistical center; adequate facilities to conduct
the clinical trials; adequate procedures to collect, monitor, and
analyze the data and assure the safety of patients/subjects.

2.c.  Quality and availability of cancer treatment and/or prevention
and control protocols, as applicable, which are appropriate for CCOP
participation, or the potential for developing such clinical trials.
For new applications, a detailed description of at least two examples
of actual or planned cancer prevention and control protocols, with
professional expertise to assure the quality of the proposed
intervention clinical trial will be evaluated.

2.d.  The ability to accrue a minimum of 50 credits per year from
affiliated CCOPs/Minority-Based CCOPs to treatment clinical trials.

The 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.

2.e.  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 the designation of protocol chairpersons and its
relationship to other clinical trial committees and activities will
be assessed.

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

2.h.  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 use of mechanisms for
periodic review of quality control, quality assurance, and data
management procedures, safety monitoring, including procedures for
data safety and monitoring committee and on-site auditing program
will be assessed.

2.i.  For competitive continuations, adequacy of progress in
implementing a prevention and control clinical trials program
including; cancer prevention and control protocol development and
implementation, accrual, data management, evaluation of performance
sites; current status of each protocol and progress towards meeting
planned accrual goals from CCOPs and members/affiliates; summary of
prior activities with a clear presentation of annual accrual;
completion of clinical trials, interim analyses, publication of
findings, or other dissemination of trial findings throughout the
research base; and other progress in meeting the requirements for a
CCOP research base.

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 operations/statistical costs for
quality control and data management costs for CCOP participation in
protocols.  This estimate is 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 include a budget for monitoring and auditing costs.  Funding
may be requested for scientific development and pilot testing of new
cancer prevention and control research initiatives, other costs
related to implementation of specific cancer prevention and control
protocols (include support of 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.

The initial review group will also examine the provisions for the
protection of human subjects, the plans for the accrual of women,
minorities and sub-populations to clinical trials, and the safety of
the research environment.

AWARD CRITERIA

The anticipated date of award is June 1, 1996.  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

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:

Leslie G. Ford, M.D.
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Room 300-D
6130 Executive Boulevard, MSC-7340
Bethesda, MD  20892-7340
Telephone:  (301) 496-8541

Direct inquiries regarding fiscal matters to:

Ms. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7800, Ext. 282

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

.

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