DCTD CLINICAL TRIALS COOPERATIVE GROUPS

Release Date:  January 29, 1999

PA NUMBER:  PA-99-058

P.T.

National Cancer Institute

PURPOSE

The National Cancer Institute (NCI) is reannouncing its willingness to accept
applications from institutions interested in conducting multi-institutional
clinical trials in a Cooperative Group setting.  Awards will continue to be
made using the cooperative agreement mechanism (U10).  Potential applicants
are encouraged to contact the Cancer Therapy Evaluation Program staff to
discuss and/or clarify any issues or questions regarding this announcement.
The "CLINICAL TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES" and the Cooperative
Group Terms and Conditions of Award are available from the NCI Program
Director upon request (see INQUIRIES).  A copy of the Guidelines and the Terms
and Conditions of Award are available on the World Wide Web at
http://ctep.info.nih.gov/CGroupGuide/GuidelinesContents.htm.  This Program
Announcement (PA) replaces PAR-95-063, which was published in NIH Guide,
Volume 24, Number 19, May 26, 1995.

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 PA, DCTD Clinical Trials
Cooperative Groups, is related to the priority area of cancer.  Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0) or Summary Report: Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington, DC
20402-9325 (telephone 202-783-3238) or at
http://www.crisny.org/health/us/health7.html.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and
non-profit organizations (including consortia of institutions), public and
private, such as universities, colleges, hospitals, laboratories, units of
State and local governments, and eligible agencies of the Federal government. 
Racial/ethnic minority individuals, women, and persons with disabilities are
encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

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.
The "Terms and Conditions of Award," which detail the responsibilities,
relationships, and governance of the studies to be funded under these
cooperative agreement(s) are available from the program staff listed under
INQUIRIES.  Participation by NCI through the Associate Director for CTEP and
selected designees provides assistance in the nature of information on NCI
priorities and ongoing efforts elsewhere within the scientific community, as
well as oversight, through the protocol review process and the Clinical Trials
Monitoring Branch and Regulatory Affairs Branch, of methodology, feasibility,
and adherence to regulatory requirements.  Any subsequent updates to the terms
and conditions of award will apply to any awards made under this program
announcement.

Because the nature and scope of the research proposed in response to this
program announcement may vary, it is anticipated that the size of awards will
vary also.

RESEARCH OBJECTIVES

Background

The NCI's Clinical Trials Cooperative Groups (henceforth termed, "the Groups")
were conceived in 1955 when Congress appropriated funds to the National Cancer
Institute to establish the Chemotherapy National Service Center.  By 1958,
seventeen Groups were organized that operated under research grants from NCI;
their main thrust was the testing of new anticancer agents from the NCI drug
development program.  Over the intervening years the Group Program has evolved
into one that places major emphasis on definitive studies of combined modality
approaches to the treatment of cancer, and on the developmental efforts
preparatory to such trials.  Most recently, increasing attention has been give
to translational research, correlating biologic insights gained from the
laboratory with disease behavior and treatment outcome.

In 1980-81, the mechanism of support for the Clinical Trials Cooperative Group
Program was converted from the grant to the cooperative agreement.  The
purpose of this change was to define the involvement of NCI program staff in
the coordination of Group activities.

There are currently twelve NCI-funded Groups; approximately 20,000 new
patients are accrued into their treatment studies each year, and many times
that number are in follow-up.  Thousands of individual investigators
participate in Cooperative Group protocols.  Currently, over $100 million is
awarded annually by the NCI in support of Group research.

The Groups consist of researchers at institutions affiliated with the Groups,
who jointly develop and conduct cancer treatment clinical trials in
multi-institutional settings.  They are a major component of the extramural
research effort of the Division of Cancer Treatment and Diagnosis.  Each Group
is supported to continually generate new trials compatible with its particular
areas of interest and expertise, as well as with national priorities for
cancer treatment research.  Unlike most other major NIH cooperative clinical
trials efforts, Group structure and funding are not usually linked to any
specific clinical trial(s).  This mechanism thus has the potential for
considerable flexibility in resource allocation, and for the rapid testing of
promising new cancer therapies in large patient populations, since the
apparatus for conducting such trials is constantly in place.  The Groups have
been instrumental in the development of new standards of cancer patient
management and in the development of sophisticated clinical investigation
techniques.

The essential feature of the Clinical Trials Cooperative Group Program is the
support of organizations that continually generate and conduct new clinical
trials consistent with national priorities for cancer treatment research. 
Emphasis is placed on definitive, randomized Phase III studies and the
developmental efforts preliminary to them.  While a wide variety of
investigational efforts are therefore appropriate, this Program specifically
does not overlap with or replace funding mechanisms for more narrowly focused,
Research Project Grant activities (e.g., R01, P01, U01, U19).

The Cooperative Groups are heterogeneous in their research objectives and
their structures.  These Groups presently are of four major types: (1) Groups
that are specifically disease oriented (e.g., gynecologic oncology); (2)
Groups that are designed to deal primarily with high technology, single
modality studies (e.g., radiotherapy); (3) Groups in which the investigators
have a particular expertise (e.g., pediatricians); and (4) multimodality
Groups.  The common thread, however, is the development and conduct of
large-scale trials in a multi-institutional setting.

The goals of the Groups are:

1.  IMPROVEMENT OF  THERAPY:  Therapeutic research aimed at improving the
survival and quality of life for persons with cancer is of highest priority.

2.  ADJUNCT STUDIES:  The database of patient information accumulated in the
course of treatment research, including the possibilities for large-scale
collection of tissue samples with subsequent correlation of biologic features
with patient outcome, provide the Groups with unique opportunities to address
scientific questions about genetics, etiology, epidemiology, pathology and
other cancer-related topics.  Such ancillary investigations can add
considerable strength to a Group's total scientific program, and are strongly
encouraged.  While certain studies may be eligible for inclusion in a Group
application for financial support, particularly when the laboratory efforts
are integral to the clinical trials proposed, a variety of other funding
mechanisms - including investigator-initiated grants (R01s, R03s, P01s) and
cooperative agreements for discrete projects (U01s, U19s) - may also be
appropriate.

3.  CANCER CONTROL:  Groups supported by NCI's Division of Cancer Treatment
and Diagnosis may  serve as research bases for treatment and cancer control
research performed by Community Clinical Oncology Program (CCOP) cooperative
agreement awardees supported by the NCI's Division of Cancer Prevention. While
this activity, when present, should be an integrated component of the Group's
total research program, peer-review of the CCOP research program including
cancer control research for the purposes of NCI financial support will be
advisory to the Division of Cancer Prevention, and generally will be conducted
separately from peer review advisory to the Division of Cancer Treatment and
Diagnosis.

4. CLINICAL TRIALS METHODOLOGY:  The Groups provide a unique framework for
research in clinical trials methodology.  While CTEP welcomes development of
and experimentation with new study designs within the Group framework, purely
statistical research is appropriately funded through other mechanisms.

SPECIAL REQUIREMENTS

Each Cooperative Group should consist of three major operational components
that collaborate to conduct the research agenda of the Group: the headquarters
(including the Group Chair's office), the central statistical/data management
office, and the participating investigators and institutions.  Each component
should have general responsibilities in meeting the goals and objective of the
Cooperative Group or in completing tasks necessary to accomplish those goals. 
Each Group must be governed by a constitution and bylaws, which describe
membership criteria, procedures for selecting group leadership and other
details of governance.  Each Group must be led by a chairperson who is
ultimately responsible for the content and conduct of the Group's research
program.  Beyond these requirements, the structure and management of the
individual Group is the responsibility of the Group itself to determine.  The
headquarters is the direct responsibility of the Group chairperson.  It should
provide executive leadership and day-to-day administrative management of the
Group.  Through this office the chairperson implements the Group's scientific
and organizational policies.  A Group's statistical and data management staff
must be integral collaborators in all stages of study  development, conduct,
analysis, and reporting.  It is anticipated that member institutions will be,
for the most part, academic centers and their affiliated institutions, or
large community practices supported through the CCOP programs.  In addition to
patient accrual, member institutions should provide scientific and
administrative contributions to the Group.  Each Group must establish its own
specific criteria for membership and a formal process for application for
Group membership.

Terms and Conditions of Award

Awards will include the "Terms and Conditions of Award," which detail the
responsibilities, relationships, and governance of the studies to be funded
under these cooperative agreement(s).  These terms and conditions are
available from the program staff listed under INQUIRIES and can be found at
URL:  http://ctep.info.nih.gov/CGroupGuide/Guidelines10.htm.

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

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which was reprinted in the Federal Register of March 28, 1994 (59
FR 14508-14513) to correct typesetting errors in the earlier publication, and
reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994, available on the web at the following URL address:
http://www.nih.gov/grants/guide/1994/94.03.18/notice-nih-guideline008.html.
Investigators also may obtain copies of the policy from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN
RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research conducted or supported by the
NIH, unless there are clear and compelling scientific and ethical reasons not
to include them.  This policy applies to all initial (Type 1 and Type 2)
applications submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address:  http://www.nih.gov/grants/guide/notice-files/not98-024.html.

Applicants for National Cancer Institute (NCI) funding who propose clinical
research for adults with cancer may use language similar to the following for
the "Participation of Children" section of their application:

"This protocol/project does not include children because the number of
children with cancer is limited and because the majority are already accessed
by a nationwide pediatric cancer research network.  This exemption is based on
Exclusion 4b of the NIH Policy and Guidelines on the Inclusion of Children as
Participants in Research Involving Human Subjects."

LETTER OF INTENT

It is strongly recommended that a letter of intent, which includes a
descriptive title of the proposed research, the name, address, and telephone
of the Principal Investigator, the identities of other key personnel and
participating institutions, and the number and title of this program
announcement be submitted at least six months in advance of the application
submission deadline.  A member institution that intends to apply or reapply
out of cycle with the parent Group should submit a letter of intent as early
as possible prior to the submission of the application.  A letter of intent is
not binding and is not a precondition for submission, review or award.

APPLICATION PROCEDURES

Potential applicants (proposed Chairperson) are strongly encouraged to contact
NCI staff (See INQUIRIES) prior to the preparation and submission of an
application to discuss NCI's programmatic interest in supporting the proposed
Cooperative Group.  Copies of the Cooperative Group Guidelines and additional
information that will be helpful in preparing applications should be requested
at that time.

Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted on the standard application deadlines as indicated
in the application kit. Application kits are available at most institutional
offices of sponsored research and may be obtained from the Division of
Extramural Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267, email: [email protected].  The title and number of the program
announcement must be typed in Section 2 on the face page of the application.
The code U10 must be entered in section 2b.  For those applicants with
internet access, the 398 kit may be found at
http://www.nih.gov/grants/forms.htm

Applicants planning to submit an investigator-initiated new (type 1),
competing continuation (type 2), competing supplement, or any amended/revised
version of the preceding grant application types requesting $500,000 or more
in direct costs for any year are advised that he or she must contact the
Institute or Center (IC) program staff before submitting the application, i.e,
as plans for the study are being developed.  Furthermore, the application must
obtain agreement from the IC staff that the IC will accept the application for
consideration for award. Finally, the applicant must identify, in a cover
letter sent with the application, the staff member and Institute or Center who
agreed to accept assignment of the application.

This policy requires an applicant to obtain agreement for acceptance of both
any such application and any such subsequent amendment. Refer to the NIH Guide
for Grants and Contracts, March 20, 1998 at
http://www.nih.gov/grants/guide/notice-files/not98-030.html.

The receipt dates and review schedule are as follows:

Application Receipt Dates:   Feb 1     Jun 1     Oct 1
Site Visit (if applicable):  May/Jun   Sep/Oct   Jan/Feb
Review Committee Meeting:    Jun/Jul   Oct/Nov   Feb/Mar
NCAB Meetings:               Sep/Oct   Jan/Feb   May
Earliest Possible Funding:   Dec 1     Apr 1     Aug 1

Each applicant for a U10 cooperative agreement shall submit a signed,
typewritten original of the application, including the checklist and three
signed photo copies in one package to:

Center for Scientific Review
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 exact copies of the grant
application and all copies of appendix material must be sent to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636
Bethesda, MD  20892
Rockville, MD  20852 (for express/courier service)

Because of the interrelatedness of various components, all of the individual
applications from a particular Cooperative Group must be submitted and
reviewed at the same time; similarly, funding recommendations for all of the
components are usually of the same duration and time frame.  Exceptions
include competing supplement applications and applications from individual
members submitted out of sequence with the remainder of the Group.  Even in
these cases, however, adjustments are made in the award such that funding
periods coincide with those of the remainder of the Group.

REVIEW CONSIDERATIONS AND REVIEW CRITERIA

Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NCI.  Applications will be reviewed for scientific and
technical merit by the Clinical Groups Subcommittee, Subcommittee H of the NCI
Initial Review Group, Division of Extramural Activities, in accordance with
the standard NIH peer review procedures and in accordance with the "CLINICAL
TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES" available from the NCI Program
Director upon request (see INQUIRIES) and available at
http://ctep.info.nih.gov/CGroupGuide/GuidelinesContents.htm.  Because of their
interrelatedness, all applications from all components of a particular
Cooperative Group are reviewed simultaneously (except in the case of member
applications submitted out-of sequence with the parent Group).  The full IRG
review is usually preceded by a site visit to the Group's statistical and data
management facilities.  The site visit team generally consists of a subset of
Subcommittee H members plus ad hoc reviewers as indicated by the proposed work
scope.  Following scientific-technical review, the applications will receive a
second- level review by the National Cancer Advisory Board.

Review Criteria

The three components of each proposed Cooperative Group will be reviewed in
accordance with the Review Criteria found in the "CLINICAL TRIALS COOPERATIVE
GROUP PROGRAM GUIDELINES" and available at
http://ctep.info.nih.gov/CGroupGuide/Guidelines8.htm.

AWARD CRITERIA

Applications will compete for available funds with all other approved
Cooperative Group U10 applications assigned to the Cancer Therapy Evaluation
Program, Division of Cancer Treatment and Diagnosis, NCI.  The following will
be considered in making funding decisions:  Quality of the proposed project as
determined by peer review, availability of funds, and program priority.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Richard S. Ungerleider, M.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Executive Plaza North, Suite 741
6130 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (if using express mail)
Telephone:  (301) 496-2522
FAX:  (301) 402-0557
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Ms. Crystal Wolfrey
Grants Management Branch
National Cancer Institute
Executive Plaza South, Room 242
6120 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (if using express mail)
Telephone:  (301) 496-7800, ext. 282
FAX:  (301) 496-8601
Email:  [email protected]

Direct inquiries regarding review issues to:

Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Blvd., MSC-7399
Rockville, MD 20850 (express courier)
Bethesda MD 20892-7399
Telephone (301) 496-3428
Fax: (301) 402-0275
Email: [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.395.  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 52 and 45 CFR Part 74 and part 92.  This program is not
subject to the inter governmental 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 routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

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