Full Text CA-93-025

COMMUNITY CLINICAL ONCOLOGY PROGRAM

NIH Guide, Volume 22, Number 18, May 7, 1993

RFA:  CA-93-025

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Clinical Trial 
  Disease Prevention+ 
  Community/Outreach Programs 


National Cancer Institute

Letter of Intent Receipt Date:  June 25, 1993
Application Receipt Date:  August 24, 1993

PURPOSE

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

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

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

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
Community Clinical Oncology Program, is related to the priority area of
cancer.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy People
2000" (Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington, DC
20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

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

A.  CCOP Applicants

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

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

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

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

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

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

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

B.  Research Base Applicants

An applicant may be:

1.  An NCI-funded clinical trials cooperative group;

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

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

MECHANISM OF SUPPORT

Support of this program will be through the clinical 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 applications submitted in response to this
RFA may not exceed three years for new applicants, and five years for
applicants currently supported under this program.  Currently supported
applicants will be funded for three, four, or five years depending upon
priority score/percentile, review committee recommendations, and
programmatic considerations.

FUNDS AVAILABLE

The NCI has determined that there is a continuing program need for
community participation in cancer clinical research trials, both
treatment and cancer prevention and control.  While 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 in the future provided
that funds are available.

It is anticipated that up to $4.2 million in total costs per year for
five years will be committed to specifically fund applications which
are submitted in response to this RFA.  Of the total, approximately
$1.8 million will be committed to research bases and approximately $2.4
million to CCOPs.  It is anticipated that up to three research base
awards and up to 15 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

Over 80 percent of patients with cancer are treated in the community.
The CCOP was initiated in 1983 to bring the benefits of clinical
research to cancer patients in their own communities by providing
support for physicians to enter patients onto treatment research
protocols.  In the first three years of the CCOP, 62 community programs
in 34 states were funded.  During this time, approximately 14,000
patients were entered onto NCI-approved treatment clinical trials
through the CCOP.  The data from CCOP participants met or exceeded all
the quality control standards of the cooperative groups.  The CCOP
evaluation indicated that patients on protocol and patients treated by
CCOP participating physicians received more appropriate patterns of
care than patients seen by physicians who never used protocols.  The
CCOPs also had an increase in the number of physicians using protocols,
the number of protocols used, and the number of patient registrations.
It was further documented that CCOPs with higher accruals were often
associated with more appropriate patterns of care.  All of these
factors contribute to establishing a framework that is critical to the
diffusion process and the widespread dissemination of state-of-the-art
practices.

The CCOPs clearly were very effective in accruing patients to treatment
clinical trials.  The second CCOP RFA, issued in 1986, expanded the
focus to include cancer prevention and control research based on the
rationale that the multi-institutional clinical trials model essential
for testing new treatment regimens is also required for conducting
large-scale cancer prevention and early detection trials.  In 1992,
there were 51 programs in 27 states involving over 300 hospitals and
over 2,800 physicians.  Approximately 5,000 patients per year were
entered onto treatment trials and 4,000 subjects per year on cancer
prevention and control trials.

Cancer prevention and control research in the CCOPs is aimed at
reducing cancer incidence, morbidity, and mortality through the
identification, testing, and evaluation of interventions in controlled
clinical trials.  The development of cancer prevention and control
research in the CCOP network has been increasing steadily since funding
started in 1987.  Since that time over 100 protocols have been reviewed
and 80 have been activated.   Protocols reviewed to date cover the full
spectrum of cancer prevention and control research, including
chemoprevention, marker studies for future prevention interventions,
smoking cessation studies, screening and early detection, and pain
control and other symptom management interventions.  Several large
chemoprevention trials have been implemented through the CCOP network,
including the breast cancer prevention trial with tamoxifen and the
head and neck chemoprevention trial with 13-cis retinoic acid (13-cRA).

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

B.  Goals and Scope

The CCOP initiative is designed to:

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

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

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

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

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

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

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

SPECIAL REQUIREMENTS

A.  Terms and Conditions of Award

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

1.  Community (CCOP) Awardees

a.  Nature of NCI Staff Involvement

(1) Protocol Review

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

The 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).

(2) Monitoring

There will be periodic on-site audits of each CCOP by representatives
of its research base(s), NCI, or an NCI-designee, such as DCT's current
Clinical Trials Monitoring Service contractor.  Such on-site audits may
include review of the following:  use of investigational drugs;
compliance with regulations for Institutional Review Board (IRB)
approval and informed consent (compliance with 45 CFR 46); compliance
with protocol specifications; quality control and accuracy of data
recording; and completeness of reporting adverse drug reactions.
Reports of such on-site audits will be reviewed by the Quality
Assurance and Compliance Section (QACS), Regulatory Affairs Branch
(RAB), 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.

(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).

(4) Investigational Drug Management

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

(5) Organizational Changes

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

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

(6) Program Review

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

(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.

(8) Federally Mandated Regulatory Requirements

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

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

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

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

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

(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.  The 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.  Responsibilities of Awardees

(1) Protocols

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

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

(2) Research Base Affiliation(s)

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

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

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

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

(3) Accrual

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

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

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

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

(4) Quality Control

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

(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.

(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.

(7) Organizational Changes

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

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

(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).

(9) Monitoring

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

(10) Reporting Requirements

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

(11) Network Participation

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

(12) Patient Log

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

(13) Federally Mandated Regulatory Requirements

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

(14) Publications

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

B.  Terms and Conditions of Award

1.  Research Base Awardees

a.  Nature of NCI Staff Involvement

(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
Branch (CB), DCPC, staff, through the DCPC Program Director, will
provide updated information on the efficacy, toxicity and availability
of all Investigational New Drugs (INDs) supplied by NCI to the research
base.  The Principal Investigators will have primary control over
making decisions derived from meetings with the additional staff named
above.

(2) 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.

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

(3) Protocol Review

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

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

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

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

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

(4) Data Management and Analysis

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

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

(5) Quality Control and Monitoring

The Quality Assurance and Compliance Section (QACS), Regulatory Affairs
Branch (RAB), CTEP, DCT/DCPC Program Director may review quality
control and monitoring procedures of the research base for consistency
with policies and procedures established by DCT/DCPC for awardees
conducting treatment and cancer prevention and control clinical trials.

(6) Investigational Drug Management

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

(7) Organizational Changes

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

(8) Program Review

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

(9) Protocol Closure

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

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

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

(10) Federally Mandated Regulatory Requirements

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

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

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

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

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

(11) CCOPs/Minority-Based CCOPs

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

(12) Arbitration Process

The Terms and Conditions of Award require that the DCPC Program
Director make post-award decisions related to protocol review, program
performance and adjustments in funding.  The 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.

b.  Responsibilities of Awardees

(1) Protocol Development

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

(2) Protocol Review

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

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

(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.

*  The NCI Program Director will assign a patient/subject credit value
to each NCI approved protocol.  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 protocol will count 1 credit; an NCI-designated
high-priority protocol 1.5 credits; and a childhood acute lymphocytic
leukemia protocol 2 credits.  Cancer control protocols will be assessed
for credit using a similar approach.

(4) Data Management and Analysis

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

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

(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.

(6) Investigational Drug Management

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

(7) Organizational Changes

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

(8) Audits

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

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

(9) Reporting Requirements

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

(10) Network Participation

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

(11) Federally Mandated Regulatory Requirements

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

(12) CCOPS/Minority-Based CCOPs

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

(13) Publications

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

STUDY POPULATIONS

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

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

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives of the
study.  This information must be included in the form PHS 398 in the
Research Plan 1-4, AND summarized in 5, Human Subjects.  If the
required information is not contained within the application, the
application will be returned.  Applicants are urged to assess carefully
the feasibility of including the broadest possible representation of
minority groups.  However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority populations
(i.e., Native Americans (including American Indians or Alaskan
Natives), Asian/Pacific Islanders, Blacks, Hispanics).  To address the
informational request, it is recommended that a breakdown by percentage
of the gender and minority composition of the study population be
provided.  This information may be based on the institutional records
and/or prior experience.

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

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but limited to clinical trials.

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

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

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

LETTER OF INTENT

Prospective applicants are asked to submit, by June 25, 1993, 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 Dr. Leslie G. Ford at the address
listed under INQUIRIES.

APPLICATION PROCEDURES

A. Preparation of Application

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

1.  CCOP Applicants

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

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

a.  Each applicant must delineate its catchment area.  A map of the
service area, designating counties or zip codes from which
approximately 80 percent of the patients will be drawn, should be
provided.  A description of other cancer care resources in the
catchment area (i.e., hospitals, clinics, physicians, cancer centers)
that are not part of the application should be included.

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

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

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

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

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

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

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

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

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.

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

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

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

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.

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 that will serve as a focus for data management, quality
control, and communication.

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).
Physician compensation is only an allowable cost for the Principal
Investigator (PI) and Co-PI, specifically for time spent on CCOP
organizational/administrative tasks.  Justification must be provided
for personnel time, effort and funds requested.

2.  Research Base Applicants

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

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

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

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

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

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.

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

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.

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.

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.

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.

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).

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.

i.  Requests for funds must reflect headquarters operational, quality
control and data management add-on costs for CCOP participation in
protocols, based on the expected accrual credits of affiliated
CCOPs/Minority-Based CCOPs and for member/affiliate accrual credits in
cancer prevention and control. CCOP-research base affiliation
agreements must be included.  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 Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone
301/435-0714; and from the NCI program official listed under INQUIRIES.

A suggested format will be sent to all applicants 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 application form must be affixed
to the bottom of the face page.  Failure to use this label could result
in delayed processing of the application such that it may not reach the
review committee in time for review.  In addition, the RFA title and
number must be typed on line 2a of the face page of the application
form and the YES box must be marked.

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

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

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

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Boulevard
Rockville, MD  20852

Applications must be received by August 24, 1993.  If an application is
received after that date, it will be returned to the applicant.  The
Division of Research Grants (DRG) will not accept any application in
response to this announcement that is essentially the same as one
currently pending initial review, unless the applicant withdraws the
pending application.  The DRG will not accept any application that is
essentially the same as one already reviewed.  This does not preclude
the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction addressing
the previous critique.

REVIEW CONSIDERATIONS

A.  Review Procedures

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

If the number of applications is large compared to the number of awards
to be made, applications may receive a preliminary scientific peer
review (triaged) to determine their relative competitiveness.  The NCI
will withdraw from further competition those applications judged to be
non- competitive for award and notify the applicant Principal
Investigator and institutional official.  Those applications judged to
be competitive will undergo further scientific merit review in
accordance with the criteria stated below for scientific/technical
merit by an appropriate peer review group convened by the Division of
Extramural Activities, NCI.  The second level of review will be
provided by the National Cancer Advisory Board.

B.  Review Criteria

1.  CCOP Applicants

a.  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.  The accrual requirement may be
waived for applicants whose specialty is pediatrics.  Each applicant's
ability to access the appropriate populations, professional
disciplines, and facilities to participate with affiliated research
bases in at least two DCPC approved cancer prevention and control
intervention protocols will be appraised.  Any prior participation in
treatment and cancer prevention and control research will be
considered.

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

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

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

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

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

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

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

i.  For competitive continuations, adequacy of progress during the
funding period, including ability to meet the minimum accrual credits
in cancer treatment and cancer prevention and control, progress made as
a CCOP, and evaluation of CCOP performance by affiliated research
bases(s).  Consideration will be given to previous accrual and the
ability to meet the previous accrual projections for which the CCOP was
funded.  The research base evaluation report(s) must be provided in the
application.  The review group will critically examine the submitted
budget and will recommend an appropriate budget and period of support
for each favorably recommended application.

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

2.  Research Base Applicants

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

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

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

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

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

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

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

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

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

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

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

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

AWARD CRITERIA

The anticipated date of award is June 1, 1994.  NCI program staff will
take into account demographic and geographic distribution of applicants
in the final funding selection process to assure inclusion of minority
and underserved populations.  Multiple CCOP applicants for funding who
are competing for the same patient population will be considered, but
all may not be awarded unless warranted by the population density.

INQUIRIES

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

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

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

Direct inquiries regarding fiscal matters to:

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

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 13.399, Cancer Control.  Awards are made under authorization of the
Public Health Service Act, Title IV, Part A (Public Law 78-410 as
amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45
CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency
review.

.

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