Full Text PAR-95-063

DCT CLINICAL TRIALS COOPERATIVE GROUPS

NIH GUIDE, Volume 24, Number 19, May 26, 1995

PA NUMBER:  PA-95-063

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Clinical Trial 


National Cancer Institute

Application Receipt Dates:  June 1, October 1, and February 1

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).

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, DCT
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).

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.

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 nine 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 $75 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.
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.  IMPROVE 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 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 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 and Control. 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 Control, and
generally will be conducted separately from peer review advisory to the
Division of Cancer Treatment.

4. CLINICAL TRIALS METHODOLOGY:  The Groups provide a unique framework
for research in clinical trials methodology.  While CTEP encourages
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.  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.

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.

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.

APPLICATION PROCEDURES

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

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 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.

Applications are to be submitted on the grant application form PHS 398
(rev. 9/91).  Application kits are available at most institutional
offices of sponsored research and may be obtained from the Office of
Grants Information, Division of Research Grants, National Institutes of
Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-
7762, telephone 301/435-0714.

The title and number of the program announcement must be typed in
Section 2a of the face page of the application.  The code U10 must be
entered in section 2b.  The applicant must provide a statement
acknowledging and agreeing to NCI staff post-award involvement in
conducting the Cooperative Group's clinical trials, and must describe
plans to accommodate this involvement.

The completed original application and three legible copies must be
sent or delivered to:

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

At the time of submission, two additional copies and all appendix
material must also be sent to:

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

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

Applications will be assigned to the National Cancer Institute.
Applications will be reviewed for scientific and technical merit by the
NCI's Cancer Clinical Investigations Review (CCIRC) Committee, 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).  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 CCIRC 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 CCIRC 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 by the CCIRC in accordance with the following review criteria.

A.  GROUP HEADQUARTERS

1.  Merit of Specific Research Plans  - How meritorious are the
research plans and strategies for each of the major areas of study?
Are they appropriate in the context of national priorities?  Are
guidelines for the inclusion of women and minorities as research
subjects being followed?

2.  Research Methodology - How well designed are the Group's planned
clinical trials?  Will their design allow clinically important
conclusions to be drawn?

3.  Efficiency of Study Development - Will the process of study
development proceed in an efficient and timely manner?  Will important
studies be rapidly developed and implemented?

4.  Timeliness of Study Completion - Will the Group be able to carry
out its planned studies in a reasonable period of time?

5.  Overall Group Priorities - Are the proposed priorities of the Group
appropriate?  Are its resources well directed?

6.  Developmental Fund Plans - Are the specific plans for the
developmental fund appropriate and consistent with the Group's overall
goals and priorities? Has the fund been well managed and wisely used in
the past?

7.  Group Structure and Administration - Will the Group be well
administered by the Chairperson and the Headquarters staff?   Does its
organization and infrastructure allow it to meet its major objectives
and goals?

8.  Publication Record - Is the Group's prior research (if relevant)
published in a timely manner and in quality peer reviewed journals?

9.  Group Cohesiveness - Will the Group function as a cohesive research
team?

10. Interdisciplinary Coordination -   Is there adequate
interdisciplinary participation in protocol development and design?  Do
protocol investigators reflect the modalities utilized?

11. Quality Control - Are the Group's proposed mechanisms of quality
control adequate and functioning in a manner which ensures accurate
data?

12. Membership - Are the criteria for initial and continuing membership
adequate?  Do the Group's periodic evaluations of its members result in
an optimal membership roster?

13. Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

B.  STATISTICAL AND DATA MANAGEMENT OFFICE

This portion of the evaluation involves 2 facets: 1) the performance
and capabilities of the statistical and data management office; and 2)
the Group's integration of the statistical and data management offices'
roles and responsibilities into the overall research program.

1.  Collaboration in Research - Is there adequate statistical and data
management collaboration in the development and conduct of the Group's
research?

2.  Adequacy of Study Design - Are the protocols properly designed
statistically?  Are the sample sizes adequate to detect realistic and
medically important differences?  Are the assumptions adequately
justified? Is the expected accrual rate carefully estimated?  Are the
designs used appropriate for the study questions?  Are endpoint
selections and sequential monitoring plans adequately described and
justified?

3.  Adequacy of Procedures - Are data management procedures adequate,
appropriate, and consistent with accepted standards?  Are procedures
for the verification of data accuracy in place?  Is there clinical
review of study data?

4.  Statistical Analyses -  Are analytical techniques, procedures, and
policies adequate, appropriate, and consistent with accepted standards?
Do publications demonstrate thorough and state-of-the-art methodology,
awareness of problems of multiple analyses, and sufficient independence
and lack of bias of statistical collaborators?

5.  Adequacy of Staff - Are the statistical and data management staff
capable of carrying out their special responsibilities?

6.  Independent Research - While not required, involvement in research
related to the design, conduct and analysis of cancer clinical trials
is a strength.

7.  Computing resources - Are computing resources adequate and
appropriate to support Group activities as needed?

Participating Institutional Applications

Both scientific contributions to the Group, and patient accrual and
data quality enter into this evaluation.

1.  Contributions to Group Science - What are the contributions of the
institution's investigators to the Group's research strategies and
plans?  Do the investigators chair research committees and studies?

2.  Participation in Group Activities and Administration - Do the
institution's investigators participate in Group activities and
meetings?

3.  Interdisciplinary Coordination - To the extent required by the
Group's research, is there adequate interdisciplinary cooperation and
coordination?

4.  Patient Accrual - Is the record of patient accrual appropriate in
the context of Group standards? Are projections for the future
reasonable and adequate?

5.  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

6.  Data Quality - Are the recent data complete, accurate, and
submitted in a timely fashion?

7.  Protocol Compliance -  What is the recent record of the quality of
protocol participation?

8.  Data Management - Are the institution's data management practices
and procedures adequate and appropriate?

9.  Publication - Do the institution's investigators contribute to
publication of Group studies?

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, 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.

The receipt dates and review schedule are as follows:

Application Receipt Dates:         Feb 1      Jun 1        Oct 1
Site Visit  (if applicable):       Apr/May     Aug/Sep     Dec/Jan
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

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
National Cancer Institute
Executive Plaza North, Suite 741
6130 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (if using express mail)
Telephone:  (301) 496-6056
FAX:  (301) 402-0557
Email:  UNGERLER@DCT.NCI.NIH.GOV

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:  WOLFREYC@GAB.NCI.NIH.GOV

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.395, Cancer Treatment Research.  Awards are made under the
authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grant policies and Federal Regulations
42 CFR 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems agency review.

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

.

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