Full Text CA-93-013

BREAST CANCER SURVEILLANCE RESEARCH

NIH Guide, Volume 22, Number 16, April 23, 1993

RFA:  CA-93-13

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Diagnosis, Medical 
  Biomedical Research, Multidiscipl 


National Cancer Institute

Letter of Intent Receipt Date:  May 13, 1993
Meeting of Interested Applicants:  May 26, 1993
Application Receipt Date:  July 27, 1993

PURPOSE

The Division of Cancer Prevention and Control (DCPC), National Cancer
Institute (NCI), invites applications from domestic institutions for
cooperative agreements to the Surveillance Program (SP).  New
applicants and applicants currently funded under SP initiatives are
invited to respond to this Request For Applications (RFA) to design and
conduct breast cancer surveillance research.

Cancer surveillance research requires a strong interface between
methodologic techniques and cancer control initiatives in prevention,
early detection, and treatment.  The purpose of the Breast Cancer
Surveillance Research initiative outlined in this RFA is to examine
thoroughly the operational aspects of breast cancer screening practices
in the United States by conducting analytic research designed to assess
the effectiveness, efficiency, and cost of screening programs as they
relate to the reduction of breast cancer mortality.  This may include
studies of medical decision models for workup of women with positive
screening tests, studies of utilization of emerging new technologies in
breast cancer screening and diagnosis, and studies of biological
differences among cancer related to detection methods.

This initiative also encourages interdisciplinary approaches to
research on the basic biology and immunobiology of breast cancer to
determine if there is a difference in screened detected and
non-screened detected cases.  It is not only important to determine the
need for change in screening practices but to stimulate other breast
cancer research.  In order to more fully understand the effect of
breast cancer screening on cancer outcome, data on breast cancer
screening practices and tumor biologic characteristics need to be
collected and linked to data from quality controlled population-based
tumor registry programs.  Examples of such registry programs are those
affiliated with the NCIs Surveillance, Epidemiology, and End Results
(SEER) Program or members of the American Association of Central Cancer
Registries (AACCR) who meet comparable standards for completeness,
quality, and timeliness of reporting and registry operations.  A
description of the NCI guidelines for these standards is available upon
request from the program staff listed under INQUIRIES.  Responses to
this RFA would initiate mechanisms to accomplish these goals, study the
utilization of state-of-the-art and emerging new technologies in breast
cancer screening, and increase knowledge of the differences in basic
biology and immunology of breast cancer by method of detection.

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,
Breast Cancer Surveillance Research, is related to the priority area of
cancer surveillance and data systems. This information (surveillance
and data systems) is used to understand the health status of the
population and to plan, implement, describe and evaluate public health
programs that control and prevent adverse health events.  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 by domestic for-profit and non-profit
organizations, public and private, such as universities, colleges,
cancer centers, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Applications from minority and women investigators are encouraged.
Since this RFA concerns breast cancer surveillance research in the
United States, a domestic application may not include an international
component.  New applicants and those with currently funded programs are
eligible as described below.

A Breast Cancer Surveillance Research applicant may be, but is not
limited to, 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.

It is essential that an applicant show evidence of the ability to
access and organize data collection from at least three different
facilities, which include:  mammography facilities, pathology
laboratories, and a quality-controlled, population-based cancer
registry.  If this expertise does not reside within one institution, an
applicant may put together a group with the necessary expertise, which
may involve the use of several institutions and/or organizations.  Each
applicant must have access to a resource unit that supports research
data management and statistical analyses locally.

MECHANISM OF SUPPORT

Support of this program will be through the National Institutes of
Health (NIH) cooperative agreement mechanism (U01).  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 anticipated
average amount of the direct cost awards will be $233,000.  The nature
of NCI staff involvement is described below.

The total project period for applications submitted in response to the
RFA may not exceed five years.  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.  Future unsolicited competing
continuation applications will compete with all other unsolicited
applications and be reviewed by a standing Division of Research Grants
(DRG) study section.  If the NCI determines that there is a sufficient
continuing program need, a request for new and competitive continuation
applications will be announced.

FUNDS AVAILABLE

The NCI has determined that it will continue its support of programs
that monitor progress against cancer through breast cancer screening.
Approximately $5,242,000 in total costs for five years will be
committed to fund applications that are submitted in response to this
RFA.  It is anticipated that at least three awards will be made to
applicants who successfully demonstrate that they can develop a
"multi-institutional group" with the ability to access mammography and
pathology facilities, and a cancer registry.  Awards will be made to
applicants who demonstrate their ability to work with other awardees in
the formation of a Consortium to establish a centralized database and
then use that data to conduct scientifically sound breast cancer
research.  Following is the estimated total cost support available for
all awards by fiscal year.  First year costs include development of
computer systems dedicated to this research, if needed:

FY 93   $2,000,000
FY 94      750,000
FY 95      790,000
FY 96      830,000
FY 97      872,000
Total   $5,242,000

This level of support is dependent on the receipt of a sufficient
number of applications of high scientific merit.  The anticipated date
of award is September 30, 1993.  Although this program is provided for
in the financial plans of the NCI, awards pursuant to this RFA are
contingent upon the availability of funds for this purpose.

For purposes of budgeting, funds should be requested for up to three
persons to attend two meetings in Bethesda, Maryland, during each of
the five years of award.

RESEARCH OBJECTIVES

A.  Background

Breast Cancer is the second leading cause of death among women.  In
l993, an estimated 46,000 women will die of breast cancer, while
182,000 new female cases will be diagnosed.  Approximately one woman in
every eight will develop breast cancer in her lifetime (Miller, Ries,
Hankey et al, 1992).

Screening for breast cancer can reduce mortality among women aged 50
and older.  A controlled trial that started in the early l960s
demonstrated a 30 percent reduction in breast cancer mortality among
women screened by mammography and clinical breast examinations
(Shapiro, Venet, Strax, Venet, 1988).  More recent studies confirmed
the effectiveness of screening mammography in reducing breast cancer
mortality, (DHHS, PHS, "Healthy People 2000") notwithstanding the
recent conflicting results from the Canadian study (Miller, Baines, To,
Wall, l992).

A review of the breast cancer screening data indicates an under
utilization of mammography in surveys conducted as late as l979
(Howard, l987).  Eight to eleven years later, breast cancer screening
with mammography had become an increasing part of the health care
picture.  Data from l987 and l990 National Health Interview Surveys
(NHIS) showed that screening with mammography had reached 59 percent of
women over 40 years of age at some time by l990 (compared to 45 percent
in l987), and 33 percent had a screening exam in the last year
(compared to l7 percent in l987) (Kessler, Breen, l992).  These
percentages were higher than previous surveys, and were part of an
increasing trend that suggested annual mammography was as high as 40
percent in surveys of the Behavioral Risk Factor Surveillance System
(BRFSS) of the Centers for Disease Control (CDC).  In addition,
analyses of the l987 BRFSS data showed considerable state-to-state
variation in screening rates.  Rates of participation by population
characteristics are also obtained.  This project will provide the
opportunity to investigate differences in the actual provision of
screening services, and by doing so, assist in evaluating the
population benefit of these increased screening activities.

Data on another critical component of breast cancer screening, the
physical examination, are also available from the NHIS.  Makuc, Freid,
and Kleinman reported on breast physical examination rates from l973
and l985 (Makuc, Freid, Kleinman, l989).  They showed a substantial
increase in prevalence of examinations during this interval for black
women in the U.S. but virtually no change among white women.  By l985
approximately 70 percent of white and black women had received a breast
physical examination within the past two years.  Recent survey results
indicate that while the usage of mammography is increasing, the usage
of clinical breast exam along with mammography may be declining.  A
comparison of mammography utilization rates among white women 64-75
years of age in five communities of the NCI Breast Cancer Screening
Consortium showed that rates had increased significantly (from 19-33
percent in l978-88 to 35-59 percent in l991 across all five areas).
However, among women who had a mammogram, the percent who also had a
clinical breast examination decreased between the l978-88 survey and
the 1991 survey (p=.001 using logistic regression pooled across all
sites) (Coleman, Feuer, NCI Breast Cancer Screening Consortium, l992).
Since clinical breast exam, along with mammography, is recommended as
a screening test for breast cancer detection, data need to be collected
on this screening test as well when feasible.

Research is needed on the effectiveness, efficiency, and cost of breast
cancer screening programs in the United States, on the medical decision
models for workup of women with abnormal screening tests, and on the
utilization of emerging new technologies in breast cancer detection.
Of major interest is whether or not there are differences in biology,
clinical management, and outcome between screened detected and
non-screened detected cases.  These areas of cancer surveillance
research require a strong interface between methodologic techniques and
cancer control initiatives in prevention, early detection, and
treatment.  Investigators affiliated with mammography facilities,
pathology laboratories, and a population-based cancer registry are
encouraged to work together to answer these questions.

B.  Goals and Scope

The objectives of this RFA are to foster research collaborations and
interactions among basic researchers, clinical investigators, and
applied researchers affiliated with quality-controlled population-based
tumor registries.  The focus of these collaborations are to advance
research in breast cancer screening methods, technology, clinical
work-up of women with abnormal screening tests, and differentials in
the biology and immunobiology of breast cancers in relationship to
detection methods.

Specifically, the objectives of the Breast Cancer Surveillance Research
Project are to conduct analytic research on breast cancer screening in
order to assess the operation (including cost) of screening programs
and policies in the U.S., and associated decision models for workup of
women with positive screening tests.  The research must be amenable to
extending implementation in a multi-group setting using comparable
data, which may include, but is not limited to, the following:

o  recommended screening policies
o  target gresps for screening
o  rates of women screened
o  influence of screening on trends in breast incidence and
intermediate outcomes (e.g., stage)
o  quality assurance procedures
o  use of state-of-the-art technology
o  results of screening examinations, including predictive values,
sensitivity, and specificity
o  follow-up of screened women
o  effect of screening on changes in breast cancer prognosis

Secondary objectives of the Breast Cancer Surveillance Research Project
extend the operational focus of breast cancer screening programs to
incorporate basic and clinical research on emerging technologies in
breast cancer detection and on biological differences of tumors
associated with detection modality.  Specifically, these objectives are
to conduct research such as, but not limited to, the following:

1.  Studies of the utilization of state-of-the-art and emerging new
technologies in breast cancer screening and diagnosis.  Technologies of
interest include, but are not limited to,

o  improvement in conventional mammography such as technological
development in grid design and composition

o  magnetic resonance and stereotactic fine needle aspiration and
biopsy

o  cytology of nipple aspirate

2.  Studies designed to determine whether or not there are differences
in biology, clinical management, and outcome between screened detected
and non-screened detected cases.  Studies may include, but are not
limited to,

o  basic biology and immunology of breast cancer to determine whether
there is a difference in screened detected cases and non-screened
detected cases

o  genetic alterations among women with breast cancer detected through
screening and those with breast cancer which was non-screened detected.

The above research topics are given as examples.  Each applicant may
submit more than one research plan, and each research plan, depending
upon the nature of the proposed study, may or may not be a
collaborative study.  However, the potential for extension to a
multi-institutional setting should be addressed.  An additional
five-page limit will be allowed for each additional research plan.

The Breast Cancer Surveillance Research Project by its very nature will
bring together multidisciplinary health professionals to accomplish the
goals and objectives of the proposal.  Thus, it is important that
applicants for this project demonstrate a track record of
interdisciplinary activity and interactive "know-how."  Furthermore,
this concept builds on several ongoing efforts related to data
collection in breast cancer screening programs.  Examples are CDCs
demonstration projects in breast cancer screening, NCIs Specialized
Programs of Research Excellence in Breast Cancer (SPORES), the American
College of Radiology's mammography lexicon, and NCI's SEER Special
Studies.

SPECIAL REQUIREMENTS

Terms and Conditions of Award

Under the cooperative agreement, a partnership will exist between the
recipient of the award and the NCI, with assistance from the NCI in
carrying out the planned activity.  The following terms and conditions
pertaining to the scope and nature of the interaction between the NCI
and the investigators will be incorporated in the Notice of Grant
Award.  These terms will be in addition to the customary programmatic
and financial negotiations which occur in the administration of grants.
The "Nature of NCI Staff Involvement" and "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; DHHS grant administration
regulations 45 CFR 92; other DHHS, PHS, and NIH grant administration
policy statements; and other NCI administrative terms of award.

The NCI will convene a meeting to establish a Consortium consisting of
one voting member from each award recipient (the Principal Investigator
or designee) and one voting member from the NCI (the Program Director
or designee).  The Consortium will establish group procedures and
goals, and plan and set priorities for cooperative group studies.  The
NCI Program Director will coordinate and facilitate the interactions of
the Consortium institutions and will review their activities for
relevance to the objectives of the RFA and programmatic considerations.

The inability of an awardee 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 award.

1.  Nature of NCI Staff Involvement

a.  Establishment of Consortium

The NCI Program Director will convene a meeting to establish the
Consortium, when the awards have been made.  Principal Investigators
from each of the award recipients will meet with the NCI Program
Director to build a cooperative organizational unit, referred to as the
Consortium.  The Consortium members will establish a leader (Consortium
Coordinator, chosen from awardees) who will administratively preside at
all Consortium meetings.  The Consortium Coordinator, other members of
the Consortium, and the NCI Program Director (Associate Director,
Surveillance Program, DCPC) will establish administrative procedures
(i.e., meeting dates, guidelines for reporting, etc.) and methods by
which all scientific/analytic requirements of the RFA will be met.

b.  Strategy Sessions

The NCI Program Director or designee, in cooperation with the
Consortium Coordinator, will sponsor strategy sessions when indicated,
attended by Principal Investigators and other appropriate staff from
the Consortium and appropriate NCI staff.  At these meetings,
information relevant to collaborative studies will be reviewed and
discussed, including such issues as overall Consortium performance and
the science of current or proposed collaborative studies.  Data will be
analyzed and the outstanding research questions established and
prioritized into national research goals by the Consortium
investigators and the NCI Program Director.  The Principal
Investigators will have the primary responsibility for analyzing and
prioritizing the research questions to be developed into collaborative
studies.  The NCI Program Director will provide assistance and guidance
as needed, for example, in developing shared study protocols, selecting
data elements, obtaining cooperation from the three types of
facilities, linking databases, and analyzing pooled data on the
operational aspects of screening.  Communication at the various stages
of protocol development is encouraged.

c.  Data Management

Each awardee will retain custody of and primary rights to their data
and are responsible for statistical analysis of local data, computer
processing and statistical interpretations.  However, for any
collaborative studies among the Consortium members, the NCI is willing
to assist in providing data analysis and statistical evaluation from
existing resources for pooled analyses.  For these collaborative
studies, the Consortium members will be responsible for the study
design, planning and interpretation of the data.  The NCI Program
Director will have access to all data generated under this award and
will periodically review the data management and analysis procedures
for the Consortium.  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).

d.  Monitoring and Program Review

In addition to normally prescribed duties of program and grants staff,
an on-site program review will occur as early as 10 months but no later
than 18 months after award.  The program review will be conducted to
evaluate progress of the Consortium, particularly the collaborative
projects.  The inability of a Consortium member to meet the performance
requirements set forth in the Terms of Cooperation 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.

e.  Arbitration Process

The Terms and Conditions of Award require that the NCI Program Director
make post-award decisions related to program performance and
programmatic decisions on scientific-technical matters.  NCI will
establish an arbitration process when a mutually acceptable agreement
cannot be obtained between the awardee and the NCI Program Director.
An arbitration panel (with appropriate expertise) composed of one
member selected by 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, NCI.  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 l6.

2.  Responsibilities of Awardees

a.  Nature of Involvement with Consortium

The award recipients must be willing to form a Consortium for the
purpose of planning, developing, and conducting collaborative projects
which share a common protocol, study design and research objectives,
and comparable data collection procedures.  Data from these
collaborative projects will be pooled for joint analysis,
interpretation and publication of results in accord with policies and
procedures which have been established by the Consortium.  The
Consortium will convene as needed to discuss collaborative study
progress and address scientific-technical aspects of implementation.
In addition, when relevant, the award recipients will provide reports
on progress of other funded projects external to the collaborative
activities.

The award recipients (Principal Investigator or designee) must attend
Consortium strategy session meetings and cooperate fully as active
participants in the development and implementation of collaborative
projects.

Each awardee must access three different kinds of facilities for the
purpose of data collection and analysis regarding breast cancer
screening practices.  Access to existing records and collection of new
information is required for:  mammography facilities, pathology
laboratories, and a quality-controlled, population-based cancer
registry.  Since this project includes substantial involvement in the
use of the facilities' records and practices, the awardee must ensure
collaboration among the three facilities throughout the award for
purposes of this research project.

b.  Strategy Sessions and Meeting Attendance

At Consortium meetings, members will strive to develop collaborative
protocols and comparable standards for data collection and management,
examine the areas of commonality, and discuss progress toward the
agreed upon goals in all of the RFA scope of activities.  These range
from development of data collection instruments to more complex
procedures such as the study protocol required to answer research
questions in the collaborative studies proposed by the Consortium.
Timelines will be established, revised and refined; Consortium members
will collectively address and solve problems within the project;
outstanding research questions will be defined and existing ones will
be prioritized; data will be analyzed and prepared for "pooled"
statistical analyses to answer agreed upon research questions requiring
pooled analyses.

c.  Data Collection and Management

Award recipients:

1.  Must cooperate in the establishment of comparable data collection
techniques for collaborative studies;

2.  Ensure that the tripartite multi-institutional group is able to
implement the data collection procedures to be developed by the
Consortium members;

3.  Ensure that the population-based registry data are compatible with
SEER Program standards; and

4.  Make all data required by any collaborative Consortium study
available for pooled analyses.

Awardees are required to collect prospective detailed data directly
from breast cancer screening facilities and from pathology records, and
to link these data to population-based cancer registry data.  These
unique linkages are required in order to conduct research on breast
cancer screening program and to facilitate investigator initiated
research on the immunobiology, cell biology, molecular genetics and
endocrinology of breast cancer.

The awardees will retain custody of and primary rights to their data.
However, the NCI Program Director or designee will have access to all
data generated under collaborative studies conducted under this award.
The NCI Program Director or designee may review data management and
analysis procedures for collaborative studies 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.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
(Note:  Since this RFA addresses female breast cancer research, the
following statements deal only with minorities in clinical research
studies.)

NIH policy states that applicants for NIH clinical research grants and
cooperative agreements are required to include minorities 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 in
studies of diseases, disorders and conditions which disproportionately
affect them.  If minorities are excluded or inadequately represented in
clinical research, particularly in proposed population-based studies,
a clear and compelling rationale must be provided.

The composition of the proposed study population must be described in
terms of racial/ethnic group.  In addition, racial/ethnic issues must
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 (rev. 9/91) in
Sections 1-4 of the Research Plan and summarized in Section 5, 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 United
States racial/ethnic minority populations (i.e., Native American
[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 project, 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 not 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 racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this should be addressed by applicants.

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
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 the 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 May 13, 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 conflict of interest in the review.

The letter of intent is to be sent to Dr. Brenda Edwards at the address
listed under INQUIRIES.

Meeting of Interested Applicants for the RFA

A meeting will be held in Bethesda, Maryland, on Wednesday, May 26,
1993, for the purpose of responding to questions from interested
applicants.  The meeting will also be announced through direct mailing
to cancer center directors, current grantee and contractors conducting
research in breast screening and cancer registration, and to the
American College of Radiology.  All other interested applicants should
contact the NCI program director listed under INQUIRIES for details
regarding arrangements for this RFA preapplication conference.  All
costs incurred by those attending are the responsibility of the
attendee and can not be recovered by budget requests in the
application.

APPLICATION PROCEDURES

Because the Terms of Cooperation (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.

1.  In addition to providing a complete research plan based on the kind
of resources immediately available to the applicant, each applicant
must delineate its catchment area for each of the three facilities
(mammography, pathology, and tumor registry).  Each applicant will
project how the research plan could be expanded as resources within the
Consortium become available.

2.  A designated Principal Investigator is required.  An associate
Principal Investigator should be named to assure continuity in the
event of resignation of the Principal Investigator.  The qualifications
and experience of both, must be described.

3.  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.

4.  Multiple research affiliations and related funded research are
permitted provided they are not conflicting.  The affiliation
agreements must state specifically how the problem of competing
projects will be resolved.

5.  Quality control procedures must be described in detail.  It is
essential that the quality control of the cancer registry be described.

6.  The availability of facilities, including mammography facilities,
pathology laboratories, and quality controlled population-based cancer
registries, must be described.  A statement of commitment from each
participating institution or organization and/or documentation of
collaborative arrangements must be provided.  Each applicant must have
a defined space for administrative activities and administrative
personnel which will serve as a focus for data management, quality
control, and communication.

7.  Each applicant's capability and expertise to manage the data 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.  Statistical data
collection comparability must exist among the tripartite local
facilities and the collaborative research project.  Each applicant must
provide evidence of their willingness to pool statistical data for
analysis as required for collaborative studies.  Each applicant's
ability to manage data from local facilities and to participate in
multi-institutional collaborative studies must be described.

8.  Applicants need to demonstrate that they can successfully develop
a tripartite organization of local facilities and show evidence that
they will successfully participate in a Consortium and conduct
collaborative studies which will be the primary mechanism by which the
NCI program Director will relate to all principal award recipients over
the duration of the period of the RFA.

9.  The applicant must describe how the issue of confidentiality will
be addressed, describing how the records of patients will be protected.
The applicant must include evidence and knowledge of legal issues
pertaining to the collection and analysis of data.  Specific state laws
and their impact on the project must be fully explained.

10.  Each applicant is encouraged to submit more than one research plan
in a single application, with an additional five page limit being
allowed to describe each additional study.

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
(30l) 710-0267; and from the NCI program official named below.

The RFA label available in the PHS 398 application form must be affixed
to the bottom of the face page of the application.  Failure to use this
label could result in delayed processing of the application such that
it may not reach the review committee in time for review.  In addition,
the RFA title and number must be typed on line 2a of the face page of
the application form and the YES box must be marked.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed, 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, Referral Officer
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
Bethesda, MD  20892

Failure to submit these copies may delay the review and consideration
of an application for award in FY 1994.

Applications must be received by July 27, 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

Review Procedures

Upon receipt, applications will be reviewed for completeness by the DRG
and by the NCI 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 the
application to the applicant.

Applications may be triaged by an NCI peer review group on the basis of
relative competitiveness.  The NCI will remove from further competition
those applications judged to be non-competitive for award and notify
the applicant Principal Investigator and institutional official.  Those
applications that are complete and responsive will be evaluated 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.

Review Criteria

The following factors will be considered in evaluating the scientific
merit of each response to the RFA:

1.  Scientific, technical, or medical significance and originality of
proposed breast cancer research that uses the database; i.e., whether
or not new technologies in breast cancer screening and diagnosis, basic
biology and immunobiology of screened detected and non-screened
detected breast cancer, genetic alterations among women with breast
cancer detected through screening and those with breast cancer that was
non-screened detected, economics of breast cancer screening techniques,
or some other area of breast cancer research which uses the database.
The scientific merit of the study objective(s), design, and methodology
to include considerations for quality assurance.

2.  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research.

3.  Appropriateness of plans to develop or modify current data
collection practices to conform to standards set by Consortium members
which should include:

o  evidence of obtaining cooperation of radiologists, pathologists,
surgeons, tumor registrars, etc., necessary for data collection
efforts;
o  description of how data systems in the area will be linked to cancer
registry and plans to solve anticipated problems with data linkage.

4.  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the area
of the proposed research should include:

o  demonstration of a track record of interdisciplinary activity and
interactive "know-how";

o  experience in the management of large data sets.

o  personnel with credentials and experience in cancer registration,
breast cancer pathology, mammography and other breast cancer screening
technology, breast cancer biology, biostatistics, and computer
programming.

5.  Adequacy of time (effort) that the Principal Investigator and staff
would devote to establishing the database and conducting the proposed
studies.

6.  Availability of resources necessary to perform the research.

7.  Commitment to conduct pooled analyses of combined data across
cooperative agreements in the Consortium for research objectives that
require pooled analyses of data.

8.  Scientific merit of each research plan within the application that
includes analytic research on breast cancer screening plus one or more
of the following:  utilization of state-of-the-art and emerging new
technologies in breast cancer screening and diagnosis, biology of
screened detected and non-screened detected cases, and other
investigator proposed studies.

Subsequent to the scientific merit of the proposed projects,
consideration will be given to the appropriateness of the proposed
budget and duration in relation to the proposed research as part of the
review process.

AWARD CRITERIA

The anticipated date of award is April 1994.  In addition to the
technical merit of the application, the NCI will consider how well the
proposed research meets the goals and objectives of the program as
described in the RFA, as well as the level of total costs requested.
Awards will be given to Principal Investigators/applicants who
demonstrate they can successfully develop the essential elements
required in a tripartite local organization, which shows evidence that
they will successfully participate in collaborative studies conducted
by the Consortium.  The Consortium is the primary entity by which the
NCI Program Director will relate to all principal award recipients over
the duration of the period of the project.  Funding criteria will be
weighted toward those applications that demonstrate a capability for
collaborative studies involving all three facilities
(clinical/radiology, pathology/laboratory science, and population-based
quality controlled cancer registry) and scientifically meritorious
research studies that address the full scope of the RFA.  Strong
consideration will be given to the potential of having geographical and
racial representation in the study population within the Consortium.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Brenda K. Edwards, Ph.D.
Surveillance Program
National Cancer Institute
Executive Plaza North, Room 343
Bethesda, MD  20892
Telephone:  (30l) 496-8506
FAX:  (301) 402-0816

Direct inquiries regarding fiscal matters to:

Marie N. Moyer
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 243
Bethesda, MD  20892
Telephone:  (30l) 496-7800, ext. 25

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93,399.  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; DHHS
grant regulations at 45 CFR part 92.  This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.

References

Coleman EA, Feuer EJ, NCI Breast Screening Consortium.  Breast cancer
screening among women 65-74 years of age in 1987-88 and 1991.  Ann
Intern Med. 1992;117:961-6.

Howard J. Using mammography for cancer control:  an unrealized
potential.  Cancer.  1987;37:33-48.

Kessler LG, Breen N. Screening mammography doubles between 1987 and
1990.  1992;in review.

Makuc DM, Freid VM, Kleinman JC.  National trends in the use of
preventive health care by women.  Am J Public Health.  1989;79:21-6.

Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening
Study.  Can Med Assoc J. 1992;147:1459-88.

Miller BA, Ries LAG, Hankey BF, Kosary CL, Edwards BK (eds).  Cancer
Statistics Review:  1973-1989, National Cancer Institute.  NIH Pub. No.
92-2789, 1992.

Shapiro S, Venet W, Strax P, Venet L. Periodic Screening of Breast
Cancer:  the Health Insurance Plan Project and its Sequelae, 1963-1986.
Baltimore, MD:  The Johns Hopkins University Press; 1988.  review.

.

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