Full Text CA-95-004

BREAST CANCER SURVEILLANCE RESEARCH

NIH GUIDE, Volume 24, Number 1, January 13, 1995

RFA:  CA-95-004

P.T. 34

Keywords: 
  0715036 
  Diagnosis, Medical 
  Biomedical Research, Multidiscipl 


National Cancer Institute

Letter of Intent Receipt Date:  February 14, 1995
Application Receipt Date:  April 21, 1995

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.  This is a follow-up
to a cooperative agreement in which three awards began in 1994.

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.  The intent of this RFA is to broaden the
current Surveillance projects in areas that have not as yet been
adequately covered, specifically among urban African-Americans and
rural areas.

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 NCI's Surveillance, Epidemiology, and End
Results (SEER) Program or members of the North American Association
of Central Cancer Registries (NAACCR) 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,
or a consortium of hospitals and/or clinics and/or physicians that
agree to work together with a Principal Investigator and a single
administrative focus.  Although a Health Maintenance Organization
(HMO) can be part of an application, it should not serve as the sole
population base for the surveillance activities.

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 $250,000 per year
per award.  The anticipated date of award is December 1995.  The
total project period for applications submitted in response to the
RFA may not exceed five years.

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 $8,000,000 in total costs for five years will be
committed to fund applications that are submitted in response to this
RFA.  It is anticipated that up to 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 a willingness to collaborate with
researchers working in the same research area, principally awardees
who have formed the working Consortium as a response to the previous
RFA.  First year costs may include development of computer systems
dedicated to this research, if needed.  Following is the estimated
total cost support available for all awards by fiscal year:

FY 96   $1,000,000
FY 97    1,500,000
FY 98    1,500,000
FY 99    2,000,000
FY 2000  2,000,000
Total   $8,000,000

This level of support is dependent on the receipt of a sufficient
number of applications of high scientific merit.  Although this
program is provided for in the financial plans of 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
1993, 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 1960s
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, 1992).

A review of the breast cancer screening data indicates an under
utilization of mammography in surveys conducted as late as 1979
(Howard, 1987).  Eight to eleven years later, breast cancer screening
with mammography had become an increasing part of the health care
picture.  Data from 1987 and 1990 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 1990 (compared to 45
percent in 1987), and 33 percent had a screening exam in the last
year (compared to 17 percent in 1987) (Kessler, Breen, 1992).
Although data from the 1992 NHIS show increases in screening across
all age and race groups, these increases are smaller than the
increases in the late 1980s (Breen and Kessler, unpublished data from
the 1992 NHIS public use data tapes).  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 1987 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 1973 and 1985 (Makuc, Freid, Kleinman, 1989).  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 1985, 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 to 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 1978-88 to
35-59 percent in 1991 across all five areas).  However, among women
who had a mammogram, the percent who also had a clinical breast
examination decreased between the 1978-88 survey and the 1991 survey
(p=.001 using logistic regression pooled across all sites) (Coleman,
Feuer, NCI Breast Cancer Screening Consortium, 1992).  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 is 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 groups for screening
o  rates of women screened
o  influence of screening on trends in breast cancer 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

Under the previous release of this RFA, three awards were made.
However, incomplete coverage of several key populations will limit
our understanding the current implementation of breast cancer
screening in the U.S.  Specifically, coverage of African-Americans
and rural populations is less than optimal.  This RFA encourages
applicants who can address one of these two groups, although
consideration will be given to applicants who can perform unique and
important research in other populations.

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
include CDC's projects in providing breast and cervical cancer
screening to low income populations, NCI's Specialized Programs of
Research Excellence in Breast Cancer (SPORES), the American College
of Radiology's mammography lexicon, and NCI's SEER Special Studies.

The applicant must establish the availability and potential of a
linked data base between breast cancer screening, registry, and
pathology data sources.  This data must serve as a foundation or
"core" for the conduct of health services and basic biologic
research.  The quality of this data base must be demonstrated in the
application clearly; however, this should be seen as a basic
component and not as research in itself.  The research topics
suggested in the paragraphs about objectives above must build on this
data base.  As such, an applicant may wish to limit their application
to one or two strong research proposals along with the establishment
of the data base to maintain a balance in the application and allow
for a reasonable budget.

SPECIAL REQUIREMENTS

Study Organization

The NCI will convene a meeting for new award recipients to join the
NCI's Breast Cancer Surveillance Consortium.  This Consortium
consists 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 awardees to this
Consortium will review the established group procedures and goals,
and work with other investigators to 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.

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 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.  Awardee Rights and Responsibilities

a.  Nature of Involvement with Consortium

The award recipients must be willing to join the established NCI
Breast Cancer Surveillance 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.  Within this framework, the awardees will
have primary and lead responsibility for the project as a whole,
including research design and protocol development, and the planning,
conduct, analysis, publication and interpretation of their studies.
Data from these collaborative projects will be pooled for joint
analysis, interpretation and publication of results in accord with
policies and procedures 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

The awardee must agree to send at least one representative to each of
the Consortium meetings.  In most cases, two representatives will be
necessary because of the wide range of substantive and methodological
discussions during these strategy sessions.

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 programs 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.

2.  NCI Staff Responsibilities

a.  Establishment of Consortium

The NCI Program Director will convene a meeting for the recipients of
this RFA to join 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 Program Director may
designate a staff person in the Surveillance Program to assume some
duties of this role as needed.

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.

c.  Data Management

Each awardee will retain custody of and primary rights to their data
and is 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.

3.  Collaborative Responsibilities

Awardees to this request must agree to join the existing Breast
Cancer Surveillance 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)
have established administrative procedures (i.e., meeting dates,
guidelines for reporting, etc.) and methods by which all
scientific/analytic requirements of the RFA will be met.  The new
awardees will review these procedures and work with the Consortium to
determine the need for any changes.  Awardees will be required to
accept and implement the common protocol and procedures approved by
the Consortium.

The Consortium will convene as needed to discuss collaborative study
progress and address scientific-technical aspects of implementation.
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.

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.

4.  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 16.

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.

Investigators proposing research involving human subjects should read
the "NIH Guidelines For Inclusion of Women and Minorities as Subjects
in Clinical Research," which have been published in the Federal
Register of March 28, 1994 (FR 59 14508-14513) 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.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 14, 1995, 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 K. Edwards at the
address listed under INQUIRIES.

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.  This 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 must submit at least one research plan separate
from the construction of the research data base in the application,
with an additional five page limit being allowed to describe each
additional study.

11.  In the event several projects or components are proposed, the
format of the program project grant should be used in which separate
budgets are used.

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for cooperative agreements.  These forms are available at
most institutional offices of sponsored research; from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone
(301) 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 1996.

Applications must be received by April 21, 1995.  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 RFA 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 DRG
and responsiveness by the NCI.  Incomplete and/or non-responsive
applications will be returned to the applicant without further
consideration.  Applications that are complete and responsive to the
RFA will be evaluated for scientific and technical merit in
accordance with the review criteria stated below by an appropriate
peer review group convened by the NCI.

As part of the initial merit review, a process (triage) may be used
by the initial review group in which applications will be determined
to be competitive or non-competitive based on their scientific merit
relative to other applications received in response to the RFA.
Applications judged to be competitive will be discussed and be
assigned a priority score.  Applications determined to be non-
competitive will be withdrawn from further consideration and the
Principal Investigator and the official signing for the applicant
organization will be notified.

Review Criteria

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

1.  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.

2.  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.

The development of a data base linking breast cancer screening
facilities to registries and pathology laboratories will be
considered as a basic requirement of the application.  The
establishment of this data base is necessary for the research
priorities for this RFA to be completed.  Establishment of this data
base must be described succinctly so that reviewers can determine its
viability.  However, the mere establishment of the data base is not
equivalent to responsiveness to the RFA.

3.  Scientific, technical, or medical significance and originality of
proposed breast cancer research that uses the database; i.e., whether
or not new technologies are employed in breast cancer screening and
diagnosis, basic biology and immunobiology of screened detected
versus non-screened detected breast cancer, genetic alterations among
women with breast cancer detected through screening versus 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.

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

5.  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.

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

7.  Availability of resources necessary to perform the research.

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

9.  Availability of a population for surveillance coverage and
research which complements the existing projects.  Current studies
sponsored by NCI include the ethnically diverse population in and
around San Francisco, a Health Maintenance Organization in the
Seattle area, a relatively homogeneous population although
representative of the catchment area, and the area surrounding
Denver, Colorado, which has a sizable Hispanic population.  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.

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 December 1995.  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:  (301) 496-8506
FAX:  (301) 402-0816
Email: edwardsb@dcpceps.nci.nih.gov

Direct inquiries regarding fiscal matters to:

Robert E. Hawkins
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 213

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.

The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

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;117:961-966.

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;79:21-26.

Miller AB, Baines CJ, To T, Wall C.  Canadian National Breast
Screening Study.  Can Med Assoc J. 1992;147:1459-1488.

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.

.

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	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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