Subject: RFA CA-91-09 From the 5/3/9l NIH Guide
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Tue, 30 Apr 91 13:03 EST

Hi Paul,
   This is the third of seven.  Please post this to the listserver
as:   RFACA-91-09.910503
   Thanks.  dottie
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA CA9109 CA-91-09 P1O1 *****************************************
 
REQUEST FOR APPLICATIONS
 
COOPERATIVE NETWORK FOR EVALUATION OF PROGNOSTIC MARKERS
OF URINARY BLADDER CANCER
 
RFA:  CA-91-09
 
P.T. 34; K.W. 0715035, 0785220, 0765033
 
National Cancer Institute
 
Letter of Intent Receipt Date:  May 31, 1991
Application Receipt Date:  July 31, 1991
 
I.  Purpose
 
The Cancer Diagnosis Branch of the Division of Cancer
Biology, Diagnosis and Centers at the National Cancer
Institute (NCI) invites applications for cooperative agreements
from institutions capable of, and interested in,
participating in the "Cooperative Network for Evaluation
of Prognostic Markers of Urinary Bladder Cancer."  The
goal of the network is to test biochemical, immunologic,
genetic, and other quantifiable markers of urinary bladder
cancer.  The network will perform collaborative studies
requiring expertise in urology, pathology, and/or basic
cancer biology to evaluate appropriate quantifiable
markers of urinary bladder cancer and to define relevant
clinical applications.  This network will continue and
expand the collaborative studies of bladder cancer
markers currently supported by the Marker Network for
Bladder Cancer.
 
Awards will be made as cooperative agreements that
create an assistance relationship with substantial NCI
programmatic involvement with the recipients during the
performance of the project, as outlined in this request
for applications (RFA).  The cooperative agreement
mechanism is used when the NCI wishes to stimulate
investigator interest and proposes to advise or assist in
an important and opportune area of research.  The NCI
anticipates making four to six awards for project periods
of up to four years.  A total of $950,000 is expected to
be set aside for funding these activities in the initial
year.  Although this project is provided for in the
financial plans of the NCI, the award of cooperative
agreements pursuant to this RFA is contingent on the
availability of funds appropriated in fiscal year 1992.
 
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, "Cooperative Network
for Evaluation of Prognostic Markers of Urinary Bladder
Cancer," 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, D.C. 20402-9325 (telephone 202-783-3238).
 
II.  Background Information
 
Advances in immunology, molecular biology, and genetics
have opened new possibilities for developing markers to
detect cancer and its recurrence, invasion, and
metastasis.  This is expected to lead to new and more
effective approaches to improve diagnostic accuracy,
make prognostic and therapeutic decisions, more
effectively monitor response to therapy, detect cancer
at earlier stages, and identify high-risk populations.
Different cell markers appear to correlate with
particular biological behaviors of urinary bladder
tumors.  Separate markers may be useful for predicting
recurrence, progression, or metastasis in early stage
disease (Ta, T1) or for detecting carcinoma in situ.
Markers for prediction of treatment response may prove
useful in selecting the most appropriate treatment.  DNA
ploidy studies of exfoliated tumor cells have
demonstrated some utility in predicting tumor behavior.
The addition of other quantitative markers that can be
evaluated by flow cytometric or other techniques will
expand the range of diagnostic measurements and may add
to the accuracy and range of diagnostic information
available to the clinician.
 
A variety of immunological, biochemical, and genetic
markers are currently being evaluated by the "Marker
Network for Bladder Cancer."  While these activities are
expected to continue, activities of the proposed network
need not be confined to markers currently under study.
Investigators are encouraged to propose interesting
markers and appropriate studies for their evaluation.
 
III.  Research Goals and Scope
 
The objective of this RFA is to invite applications for
cooperative agreements to support a network of
laboratories to cooperatively evaluate promising
diagnostic and prognostic markers of urinary bladder
cancer.  The existing network has already demonstrated
the feasibility of an inter-institutional network for
collaborative clinical studies of urinary bladder cancer
markers.  Studies of new methods for cell
marker identification and analysis, including:
evaluation of additional genetic, biochemical, and
immunological markers of urinary bladder cancer;
evaluation of the most appropriate techniques for
quantitatively assaying these markers; and development of
tumor classification systems useful in patient
management, are needed.  Awardees will share clinical material and
develop a plan to optimize research opportunities offered
by the strengths of the participating institutions and
the patient populations available to the network.  The
cooperative approach will expand the available patient
resources, improve evaluation of potentially useful
markers and allow comparison of their utility in
different clinical and laboratory settings.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING
IMPLEMENTATION OF NIH POLICIES CONCERNING WOMEN AND
MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA
clinical research grants and cooperative agreements will
be 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 should be placed
on the need for inclusion of minorities and women in
studies of diseases, disorders or 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,
together with a rationale for its choice.  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 should be included in the form PHS 398 in
Section 2 A-D of the Research Plan AND summarized in
Section 2E Human Subjects.
 
Applicants are urged to assess carefully the feasibility
of including the broadest possible representation of
minority groups.  However, the NIH recognizes that it may
not be feasible or appropriate in all research projects
to include representation of the full array of the United
States racial/ethnic minority populations (i.e. Native
Americans (including American Indians, or Alaskan
Natives), Asian/Pacific Islanders, Blacks, Hispanics).
The rationale for studies on single minority population
groups should be provided.
 
For the purpose of this policy, clinical research
includes human biomedical and behavioral studies of
etiology, epidemiology, prevention (and prevention
strategies), diagnosis or treatment of diseases,
disorders or conditions, including but not limited to
clinical trials.
 
The usual NIH policies concerning 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.
 
For foreign awards, the policy on inclusion of women
applies fully; since the definition of minority differs
in other countries, the applicant must discuss the
relevance of research involving foreign populations to
the United States' populations, including minorities.
 
If the required information is not contained within the
application, the application will be returned.
 
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.
 
IV.  Mechanism of Support
 
Support of this program will be through the cooperative
agreement, an assistance mechanism in which substantial
NIH programmatic involvement with the recipients during
performance of the planned activity is anticipated as
outlined in this RFA.  Applicants will be responsible for
the planning, direction, and execution of the proposed
project.  Except as otherwise stated in this
RFA, awards will be administered under PHS
grants policy as stated in the Public Health Service
Grants Policy Statement, DHHS Publication No. (OASH) 90-
50,000, revised October 1, 1990.
 
This RFA is a one-time solicitation.  Generally, future
unsolicited competitive continuation applications will
compete as research project applications with all other
investigator-initiated applications and be reviewed by
the Division of Research Grants (DRG).  However, should
the NCI determine that there is a sufficient continuing
program need, the NCI will invite recipients of awards
under this RFA to submit competitive continuation
cooperative agreement applications for review, according
to the procedures described in Section VII.
 
NCI anticipates making four to six awards for project
periods of up to four years and anticipates that a total
of $950,000 will be set aside for the initial year's
funding.  Funding in response to this RFA is dependent on
the receipt of a sufficient number of applications of
high scientific merit.  The earliest feasible start date
for the initial awards will be April 1, 1992.  Although this
program is provided for in the financial plans of the
NCI, the award of cooperative agreements pursuant to this
RFA is contingent on the availability of funds
appropriated for fiscal year 1992.
 
The purpose of the proposed awards is to stimulate
cooperative efforts to identify and evaluate diagnostic
and prognostic markers of urinary bladder cancer.  The
cooperative agreement funding mechanism was selected
because of substantial NCI programmatic involvement
required to coordinate activities among several
laboratories working toward a common goal.
 
V.  Terms of Cooperation
 
The cooperative agreements will require cooperation
between an NCI representative and the Principal
Investigators of the individual projects in order to
assure smooth interactions among the cooperating
institutions.  The NCI representative will assist in
coordinating the activities of the research groups and
in facilitating exchange of information.  Awardees will
retain custody and primary rights to their data developed
under these awards, subject to government, e.g., NCI, NIH,
or PHS, rights of access consistent with current DHHS,
PHS, and NIH policies.
 
A.  Responsibilities of the NCI Representative
 
The NCI representative will coordinate and facilitate the
programs supported by these cooperative agreements, will
attend and participate in all meetings as a member of the
Coordinating Committee, and will serve as a liaison between
the Coordinating Committee and participating research
groups.  The NCI representative will assist the
Coordinating Committee in developing operating policies,
quality control procedures, and consistent policies for
dealing with recurring situations that require
coordinated action.  To assure consistency and quality,
the NCI representative must concur in operating policies
and clinical protocols prior to their implementation.
The NCI representative may review the operations of
individual laboratories for compliance with protocols and
other operating policies developed by the Coordinating
Committee.  The NCI representative may recommend
withholding of support, suspension, or termination of an
award for lack of progress or failure to adhere to
policies established by the Coordinating Committee.
 
B.  Responsibilities of Awardees
 
Awardees are responsible for developing individual
research projects to facilitate the activities of the
network and to participate in the development of clinical
protocols for network studies.  All studies conducted
under this RFA by members of the network must be approved
by the Coordinating Committee.  Responsibility for
specific aspects of collaborative network studies, e.g.,
statistical design and analysis, will be determined by
the Committee at the time each study is planned.  Two
members of each research group are required to attend
meetings of the Committee (as detailed below), to help
formulate the Committee's policies (which will be
submitted to the NCI representative for approval), and to
implement those policies.  Awardees are required to have
access to appropriate tumor tissue and normal tissue.
They are required to submit progress reports at each
meeting of the Coordinating Committee.
 
C.  Coordinating Committee
 
The NCI representative and the participating research
groups will be responsible for forming a Coordinating
Committee as defined below.  Operating policies will be
developed by the Coordinating Committee and submitted to
the NCI representative for concurrence prior to
implementation.  The NCI representative will facilitate
the review of operating policies and clinical research
protocols.  Results of the review will be discussed with
the Coordinating Committee and an arbitration system, as
detailed below, will be available to resolve disagreements
between the NCI representative and the other members of
the Coordinating Committee.
 
The Coordinating Committee will review the plans proposed
in the applications by the individual research groups
to ensure that they are compatible with the overall goals
of the RFA.  Members of the Coordinating Committee will
be responsible for redefining research objectives and
defining strategies for network studies to optimize
progress and efficient use of patient and tissue
resources.  The Coordinating Committee will also be
responsible for coordinating activities such as plans for
statistical design and analyses, developing forms,
distributing reagents and biological samples, data
collection and data analysis, monitoring the progress of
the network, and maintaining quality assurance.
 
The Coordinating Committee will consist of the NCI
representative and two members from each cooperating
institution, one of whom is the Principal Investigator.
The NCI representative will be appointed by the Chief of
the Cancer Diagnosis Branch, Division of Cancer Biology,
Diagnosis and Centers.  The Coordinating Committee will
be responsible for electing a Chairperson (who may not be
the NCI representative).  The Chairperson of the
Coordinating Committee will be responsible for
coordinating the Committee activities, preparing
meeting agendas, and scheduling and chairing
meetings.  The NCI representative will attend and
participate in all meetings of the Coordinating Committee
and should be informed of major inter-group interactions.
The Coordinating Committee will prepare an annual
progress report that will include individual reports
from each participating research group; each group is
responsible for timely preparation of its report.

The Coordinating Committee will meet initially to map
strategies and set up operating procedures.  The
Coordinating Committee will meet at least twice a year
thereafter.  Meetings may be held at any of the
participating institutions or at another convenient
location.  These meetings are aimed at coordinating the
activities of the participating laboratories,
establishing new policies and priorities, and reviewing
progress.  The NCI representative will participate in the
discussions at these meetings.  Travel funds for
Coordinating Committee meetings are to be set aside as a
budget line item in each project budget.
 
D.  Arbitration Procedure
 
An arbitration panel of external consultants will be
created as needed to resolve any irreconcilable
differences of opinion related to scientific/programmatic
matters between the NCI representative and the
Coordinating Committee with respect to implementation of
a proposed operating policy.  The panel will include one
member selected by the Coordinating Committee, one member
selected by the NCI, and a third member chosen by the
other two members of the arbitration panel.  The NCI
arbitration process for the cooperative agreement in no
way affects the rights of awardees to appeal selected
post award administrative decisions in accordance with PHS
regulations at 42 CFR part 50, subpart D and HHS
regulations at 45 CFR part 16.
 
VI.  Eligibility Requirements
 
Applicant organizations must be located in the United
States, Canada, or Mexico.  Non-profit and for-profit organizations and
institutions, and government agencies are eligible to
apply.
 
VII.  Special Instructions for Preparation of Cooperative
Agreement Applications
 
The grant application form PHS 398 (revised 10/88,
reprinted 9/89) must be used for the cooperative
agreement application.  The general instructions, e.g., for
format and budget issues, included in the application
packet must be followed.
 
Specific issues related to cooperative agreements must be
addressed as follows:  It is critical that each applicant
include specific plans for responding to the Terms of
Cooperation discussed in Section V above.  Plans must
describe how the applicant will comply with the
involvement of the NCI representative, as well as how all
the responsibilities of awardees will be fulfilled.
Individual proposals for both network studies and
individual studies must be included in order to provide
the Coordinating Committee with a basis for planning
network activites.  For competing renewal applications,
a complete description of past collaborative efforts
must be included in the progress report.
 
VIII.  Review Procedures and Criteria
 
A.  Review Procedures
 
Upon receipt, applications will be initially reviewed
by the DRG for
completeness.  Incomplete applications will be returned
to the applicant without further consideration.
Evaluation for responsiveness to the program requirements
and criteria stated in the RFA is an NCI program staff
function.  Applications that are judged to be
non-responsive will be returned to the applicant, but may be
submitted as investigator-initiated research
grant applications at the next receipt date.
 
In cases where the number of applications is large
compared to the number of awards to be made, the NCI may
conduct a preliminary scientific peer review to eliminate
those that clearly are not competitive for award.  The
NCI will remove from further competition those
applications judged to be noncompetitive and notify the
applicant Principal Investigator and institutional
official.
 
Those applications judged to be both competitive and
responsive will be further evaluated according to the
review criteria stated below for scientific and technical
merit by an appropriate peer review group convened by the
Division of Extramural Activities, NCI.  The second level
of review by the National Cancer Advisory Board considers
the special needs of the Institute and the priorities of
the National Cancer Program.
 
B.  Review Criteria
 
Factors considered to be important for review include:
demonstrated expertise in urology, pathology, and/or basic
cancer biology applied to the diagnosis and treatment of
urinary bladder cancer; expertise and an active research
program in cell marker studies; availability of an
appropriate population of patients for study; good
interaction among collaborating researchers;
demonstration of adequate facilities; and willingness to
interact within the terms of a cooperative agreement as
outlined in this document.
 
Reviewers will be asked to review the grant applications
by considering the following criteria:
 
1) Scientific merit, feasibility, and relevance of the
proposed project to the overall goals and objectives
of the RFA;
 
2) Demonstration of availability of, and access to,
appropriate patients (including representative numbers
of women and minorities or sufficient justification
for their exclusion), archival tissue, and appropriate
clinical data;
 
3) Proposed collaborations among urologists,
pathologists, basic cancer biologists, and other key
personnel;
 
4) Qualifications, experience, and proposed
responsibilities of the Principal Investigators and of
key support personnel;
 
5) Facilities and resources, and their availability for
this project;
 
6) Plans for effective interaction and coordination among
cooperating projects and with the NCI, including a
proposed timetable; and
 
7) Plans to protect the rights of human subjects.
 
The review group will recommend an appropriate budget and
period of support for each approved application.
 
IX.  Method of Applying
 
The most recent revision of the research grant
application form PHS 398 (revised 10/88, reprinted 9/89)
must be used in applying for cooperative agreements.
These forms are available at most institutional business
offices and from:
 
Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 449
5333 Westbard Avenue
Bethesda, MD  20892-4500
 
and from the NCI Program Director named below.
 
The RFA label available in the application form PHS 398
(revised 10/88, reprinted 9/89) must be affixed to the
bottom of the face page.  Failure to use this label could
result in delayed processing of your application such
that it may not reach the review committee in time for
review.  In addition, the RFA number and title must be
typed on line 2 of the face page of the application form.
 
Submit a signed, typewritten original of the application,
including the checklist, and four signed exact
photocopies, in one package to the Division of Research
Grants at the address below.  Photocopies must be clear
and single sided.
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892-4500**
 
At the time of submission send two additional copies of
the application to:
 
Referral Officer
Division of Extramural Activities, DEA, NCI
Room 838, Westwood Building
5333 Westbard Avenue
Bethesda, MD  20892-9912
 
Applications must be received by July 31, 1991.  If an
application is received after this date, it will be
returned.
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one.  Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this
RFA that is essentially identical to one that has already been
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.
 
X.  Letter of Intent
 
Prospective applicants are asked to submit by May 31,
1991, a letter of intent that includes a descriptive title
of the proposed project, the name and address of the
Principal Investigator, the names of other key personnel,
the participating institutions, and the number and title
of the RFA in response to which the application is being
submitted.  Although a letter of intent is not required,
is not binding, and does not enter into the review of
subsequent applications, it is requested in order to
provide an indication of the number and scope of the
applications to be reviewed.
 
The letter of intent is to be sent to:
 
Roger L. Aamodt, Ph.D.
Program Director for Pathology and Cytology
Cancer Diagnosis Branch, DCBDC, NCI
Executive Plaza South, Room 638
6120 Executive Boulevard
Rockville, MD  20892-9904
Telephone:  (301) 496-7147
FAX:  (301) 496-8656
 
XI.  Inquiries
 
Written and telephone inquiries concerning the objectives
and scope of this RFA, about the activities of the
currently funded marker network, or inquiries about
whether specific proposed research would be
responsive, are encouraged and should be directed to Dr.
Roger L. Aamodt at the above address.  The program
director welcomes the opportunity to clarify any issues
or questions from potential applicants.
 
This program is described in the Catalog of Federal
Domestic Assistance No. 93.394, Cancer Detection and
Diagnosis Research.  Awards are made under authorization of
the Public Health Service Act, Title IV, Part A (Public
Law 78-410 as amended: 42 USC 241) and administered under
PHS grant policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.