Full Text CA-97-004
 
CANCER GENETICS NETWORK
 
NIH GUIDE, Volume 26, Number 17, May 23, 1997
 
RFA:  CA-97-004
 
P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Genetics 
  Social Psychology 
  Ethics/Values in Science & Technol 

 
National Cancer Institute
 
Letter of Intent Receipt Date: June 20, 1997
Application Receipt Date: September 12, 1997
 
PURPOSE
 
The Extramural Epidemiology and Genetics Program (EEGP), Division of
Cancer Epidemiology and Genetics (DCEG), National Cancer Institute
(NCI) invites applications from organizations with demonstrated
excellence in human cancer genetics for resource-related cooperative
agreements (U24s), a new mechanism for the National Cancer Institute.
The purpose of this solicitation is to support the formation of a
multi-center, interdisciplinary cooperative, the Cancer Genetics
Network.  This consortium will serve as an infrastructure for
collaborative research investigations into the genetic basis of human
cancer susceptibility, explore mechanisms for integrating this
information into medical practice, and identify means to address the
psychosocial, ethical and legal issues associated with human cancer
genetics.
 
To capitalize on advances in the area of hereditary cancer
predisposition requires scientific resources and study populations
which are currently unavailable to most human genetics programs.
Thus a new infrastructure is needed that is a hybrid between the
traditional models of Cancer Centers (with recognized scientific
excellence)  and the cooperative clinical trials groups (with
efficient multisite recruitment).  Funding through this RFA will be
used to support the development of this new model of research
infrastructure, the Cancer Genetics Network, in which potential study
populations are preassembled through multiple participating centers
and linked to a collective scientific expertise in cancer genetics.
Through the formation of the Cancer Genetics Network consortium it is
envisioned that participating groups will have access to resources,
information, and expertise which are beyond the scope of any single
institution or organization.
 
The Cancer Genetics Network will also facilitate the exchange of
human cancer genetics information and resources within the larger
cancer genetics community.  The Network will develop mechanisms to
broaden access to genetic services and educational materials by both
the public and health care professionals.  It will establish a
clearinghouse of human cancer genetics resources and develop means to
extend access to and connections between cancer genetics researchers,
providers of genetic services, and the general public.
 
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 Request
for Applications (RFA), the Cancer Genetics Network, is related to
the priority area  of cancer.  Potential applicants may obtain a copy
of  "Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (Telephone: 202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, non-profit and
for-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal Government.
Applications may represent a single organization or a consortium of
several institutions or organizations.  Collaborations which bring
together groups with individual expertise in basic human cancer
genetics research, clinical cancer genetics, epidemiology, genetic
counseling, and education are encouraged. Applications from existing
NIH-sponsored programs in clinical oncology, cancer epidemiology and
genetics, and related areas which meet the requirements above (e.g.,
NCI Clinical Trials Cooperative Groups, the Community Clinical
Oncology Program [CCOP], NCI-designated Comprehensive Cancer Centers,
NCI Cooperative Family Registries for Breast and Colon Cancer
Studies, and the NHGRI Cancer Genetics Studies Consortium) are
encouraged, but consideration will not be limited to these
applicants. Applications from minority individuals, women, and
persons with disabilities as Principal Investigators are also
encouraged.
 
MECHANISM OF SUPPORT
 
Support for this program will be through the resource-related
cooperative agreement (U24). Hypothesis-driven R01 applications are
NOT to be submitted in response to this RFA.  A single consortium
called the Cancer Genetics Network will be developed from the
individual cooperative agreement awards for participating centers.
As research resource, the Cancer Genetics Network will enhance the
capability of investigators to identify and recruit individuals for
genetic studies and will facilitate communication of scientific
information and research collaboration among participating centers.
 
Substantial NCI involvement with the recipients is anticipated during
Network development, implementation, and operation. Under the
cooperative agreement, NCI will support and/or stimulate the
recipient's activity, working jointly with the participating centers
in a partnership role. Participating organizations will be
responsible for planning and executing the proposed consortium.
Details of the responsibilities, relationship and governance of the
project to be funded under cooperative agreements are discussed later
in this document under the section "Terms and Conditions of Award."
 
The total project period for applications submitted in response to
the present RFA should not exceed five years. The anticipated award
date is March, 1998. Because the nature and scope of the research
proposed in response to this RFA may vary, it is anticipated that the
size of awards will vary also. Awards and level of support will
depend on the receipt of a sufficient number of applications of high
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.
 
This RFA is a one-time solicitation. At this time the NCI has not
determined whether or how this solicitation will be continued beyond
the present RFA.  It is anticipated that a re-issuance of this RFA
would include competitive renewal applications from the centers
participating in the pilot phase of the Network and new applications
from institutions and programs not funded through this first
solicitation.
 
FUNDS AVAILABLE
 
Approximately $5 million in total costs per year for five years will
be committed to fund applications that are submitted in response to
this RFA.  This funding level is dependent on the receipt of a
sufficient number of applications of high merit. It is anticipated
that up to eight individual Network Center awards will be made.
 
RESEARCH OBJECTIVES
 
Background
 
Since the retinoblastoma gene was identified in 1986, the number of
cloned familial cancer susceptibility genes has increased rapidly.
In aggregate the genes identified to date affect a large number of
patients with cancer.  For example, germline mutations at the BRCA1
and BRCA2 loci are thought to account for 5-10% breast cancer
incidence and 2-5% ovarian cancer incidence. Genetic and
epidemiologic studies suggest that other genes of markedly lower
penetrance may also be important in determining cancer risk. These
genes may modulate individual response to environment and explain
variability in risk associated with different exposures.  This latter
category of  susceptibility genes may have very large attributable
risks for cancer and may be very common in the general population.
 
Genetic testing for an increasing number of cancer susceptibility
genes is becoming widely available in spite of the often uncertain
clinical, legal, ethical, and psychosocial implications of these
tests.  However, testing and counseling even for the rare, familial
susceptibility genes would exceed the capacity of the current health
care delivery infrastructure.  As predictive genetic testing becomes
more widespread, there is a critical need to develop novel approaches
to communicate high-quality and up-to-date information about cancer
genetics and genetic testing to health care providers and potential
consumers.  The difficulty of this task is magnified by the rapid
expansion of scientific knowledge regarding genetic susceptibility
and cancer risk.
 
To obtain answers to the next generation of questions in human cancer
genetics, studies of unprecedented size and complexity will be
required.  By providing a research infrastructure to support
multi-institutional collaboration, the Cancer Genetics Network will
further understanding of the genetics of cancer susceptibility,
facilitate the translation of cancer genetics into medical practice,
and address pressing public health issues. Ultimately, research
conducted using the Network infrastructure should be able to address
critical questions, such as:
 
(1)  The Genetics of Cancer Susceptibility.  The identification of
cancer susceptibility genes is still in its infancy, and it is likely
that the majority of susceptibility genes have yet to be identified.
Even for the genes identified to date, there are still many questions
to be addressed.
 
What is the prevalence of germline mutations of familial cancer
susceptibility genes in different populations?
 
What is the penetrance of germline mutations in these genes?
Is a single germline mutation in a familial cancer susceptibility
gene sufficient for increased risk?
Do all germline mutations in familial cancer susceptibility genes
have the same phenotype?
What is the risk conferred by genes of the lower penetrance class?
Do the low penetrance genes modify the risk associated with germline
mutations in cancer susceptibility genes?
What are the environmental exposures that interact with
susceptibility genes to cause cancer?
 
(2)  The Translation of Genetics into Medical Practice.  The
integration of genetic susceptibility information into medical
practice holds significant promise of new approaches for cancer
prevention and treatment.  Unfortunately, many of the most basic
questions concerning the clinical significance of germline mutations
in familial cancer susceptibility genes are unanswered, and it is
unclear how to use genetic susceptibility information to alter
outcomes.
 
Can adherence to public health cancer prevention strategies alter
cancer morbidity and mortality among individuals with genetic
susceptibility to cancer?
Does prophylactic surgery to remove target risk organs improve
survival?
Do carriers of cancer susceptibility genes benefit equally from
screening technologies such as mammography and PSA testing?
Does genetic constitution influence response to cancer treatment?
Can specialized prevention and treatment strategies be identified
that take advantage of the knowledge of constitutional genotype?
 
(3) Public Health Issues in Genetic Susceptibility.  The
opportunities afforded by advances in cancer genetics also raise
enormous challenges.  The consequences of widespread access to
individual genetic information about susceptibility, even of
uncertain clinical significance, are largely unknown.
 
What are the ethical and psychosocial issues that will affect healthy
individuals and their families who may carry cancer susceptibility
gene mutations?
How can people be helped to make informed decisions about testing for
genetic susceptibility?
How can information about genetic information be effectively and
responsibly communicated to individuals, health professionals, and
the general public?
How can the nation's health care infrastructure be extended to
accommodate the responsible delivery of wide spread genetic testing
for cancer susceptibility genes?
 
Goals and Scope
 
The goal of the Cancer Genetics Network is to enable investigations
addressing the broad range of outstanding issues in human cancer
genetics outlined above.  Through the formation of the Network,
participating groups will have access to resources, information, and
expertise that are beyond the scope of a single institution.  The
Network will operate as a cooperative, providing a framework for
research designed by the consortium members and executed using the
joint resources of the centers.
 
To facilitate formation and effective operation of the Cancer
Genetics Network, this RFA will provide a broad base of support for
participating center activities relevant to Network implementation
and function. Applicants may request support for operating basic
registry and informatics systems and for expanding laboratory
capabilities and other support functions to meet increased needs
arising from Network participation.  Administrative supplements will
also be made available to the Network Participating Centers for
innovative small projects and pilot studies, as described below.
 
(1)  Support of Basic Network Activities
 
Basic activities of the Network include developing a collective data
base or registry of potential research participants and establishing
the ability to collect and store tissues for specific Network
projects.  Substantial effort should be directed towards basic
activities such as:
 
Recruitment of eligible individuals into the Network data system;
Collection of core data from recruited participants;
Tracking and follow-up of participants;
Collection of biological specimens for specific Network projects;
Maintenance of local informatics and communications capabilities;
Interactive participation in the Network-wide informatics system.
 
Thus budget requests should include personnel and consultant efforts
that provide multidisciplinary support for these Network functions,
particularly for areas of participant recruitment and follow-up,
health education, genetic counseling, data management and quality
assurance, and computer systems development and maintenance.
 
(2) Expansion of Research Capabilities to Support Network
Participation
 
To enable investigators to answer urgent questions in cancer genetics
such as those described above, applicants are encouraged to request
support for activities which create and/or expand the submitting
applicant's capacity to perform locally-based studies as well as the
cooperative Network projects that use joint resources.  Activities
which may be supported include, but are not limited to:
 
Support for personnel with expertise in laboratory-based genetic
analysis, health education, family studies, molecular epidemiology,
informatics, mathematical genetics, behavioral research, clinical
genetics, and/or genetic counseling;
 
Expansion of capability to collect, process, store, and exchange
biological specimens and reagents;
 
Development or expansion of informatics capacity, particularly in the
areas of data management/analysis and electronic information capture,
exchange, or distribution;
 
Travel to support training and collaborative interactions within and
between institutions;
 
Support for consultants with relevant expertise from outside the
Network participating center;
 
Acquisition of equipment and instrumentation to expand the ability to
perform genetic analyses;
 
Development of educational materials and resources.
 
(3) Developmental Activities and Pilot Research Studies
 
Following implementation of the Network consortium, the Participating
Centers will be allowed to request administrative supplements.  These
funds will be used to enhance activities of the Network as a whole
and will be awarded for specific developmental activities and pilot
studies as recommended by the Advisory Committee and approved by the
Steering Committee.  Examples of activities covered by the
supplements include, but are not limited to:
 
Development of high-priority Network-wide pilot studies.  These may
be extensions of pilot projects proposed in the applications of
individual Network centers, or rapidly emerging new priorities which
arise as a consequence of developments within the field;
 
Workshops addressing problems in the area of cancer genetics;
 
Consultants to provide expertise outside that contained within the
cooperative;
 
Sharing of education and information resources from within the
Network and outside sources;
 
Technology transfer between Network centers and from other relevant
sources;
 
Expansion of the basic Network infrastructure, e.g., to support
referral and outreach activities.
 
SPECIAL REQUIREMENTS
 
Applicants must have existing programs of scientific excellence in
human cancer genetics and ongoing clinical programs in genetic
evaluation and counseling which provide access to a broad spectrum of
individuals with expressed interest in predictive genetic testing for
cancer risk.
 
All applications must address the following questions in a clear and
organized manner, as described below:  (1) What existing resources,
capabilities, and expertise does the applicant bring to the Network?
(2) How will the support requested for expansion of capabilities
enhance the applicant's ability to participate in Network functions?
(3) What unique resources, capabilities, or expertise does the
applicant bring to the Network?
 
(1) Existing Resources, Capabilities, and Expertise
 
Applications should include, at a minimum, descriptions of the
following resources:
 
The clinical program(s) in predictive genetic testing and clinical
genetics on which the application is based;
 
The clinic catchment population (source of participants) and
potential for outreach beyond this group;
 
Pre- and post-test counseling protocols;
 
Laboratory testing procedures;
 
Methods for assuring privacy and maintaining confidentiality of
participant records, including specific protections for
Internet-based data systems;
 
Informed consent procedures; and
 
Capabilities for collection, processing, and storage of biological
materials.
 
Relevant to the educational objectives of the Network, applicants
should describe:
 
Educational materials and interventions, in use or to be developed,
particularly in the area of risks and benefits of testing for genetic
susceptibility for cancer;
 
Methods in place or planned for providing user-friendly access to
rapidly changing scientific information and/or resource directories;
 
Post-marketing' surveillance strategies for medical or social harms
associated with pharmaceuticals or medical devices, particularly in
relation to cancer genetic predisposition testing.
 
Applicants should provide evidence of their capability and
willingness to collaborate in development of common protocols during
the first six months of the award and to participate in the conduct
of collaborative research studies.  They should present plans and/or
approaches for fostering scientific collaborations through the Cancer
Genetics Network.  Applicants must also demonstrate their willingness
to allow non-Network investigators to have access to Network data for
high-priority research studies approved by the Steering Committee and
Advisory Committee.
 
Applicants are also encouraged to describe briefly (in 1 or 2 pages
per project, in addition to the usual 25-page limit) at least one
pilot study that they would envision as addressing important
questions utilizing the unique resources that will be available
through the Network consortium.  While support for these pilot
studies will not be provided through this solicitation, these studies
may be funded through administrative supplements to be made available
to the Network cooperative at a later date.
 
(2) How Expansion of Resources will Enhance Network Participation
 
Applicants should list the resources requested for expansion of
existing facilities or capabilities (see "Goals and Scope" above) and
provide a clear and detailed description of how these resources will
impact the scope and/or function of the existing facility.  This
section should emphasize how the expansion of capabilities will
contribute to the general functions of the larger Network system and
how it will enhance the research potential of the Network as a whole.
Applicants should also describe provisions to continue Network
activities and collaborations should federal support terminate
following the initial (pilot) phase of this initiative.
 
(3)  Unique Capabilities
 
Applicants should highlight the aspects of their existing and
proposed programs that offer unique expertise and/or unusual
opportunities for Network projects.  Examples include, but are not
limited to:
 
Expertise in highly specialized areas with potential applications in
genetic testing and counseling, such as psychosocial aspects
(including quality of life), risk communication and/or
decision-making, and medical outcomes research (including costs and
cost-effectiveness);
 
Innovative laboratory procedures or analytic technologies;
 
Experience in regulatory affairs, such as FDA approval of reagents
(devices), laboratory certification, and surveillance for adverse
effects;
 
Access to special participant populations, such as ethnically diverse
groups, cohorts with unique mutations (such as ATM heterozygotes);
and
 
Experience and/or expertise in state-of-the-art communications
technology (such as informatics, telemedicine).
 
Study Organization and Function
 
A maximum of eight Network participating centers will be funded in
the initial offering of this initiative. NIH intramural laboratories
and/or clinical programs may be included as Network participating
centers, as described below.  Each participating center shall be
headed by a single Principal Investigator who will provide scientific
and administrative leadership for the Network functions and
responsibilities.
 
A Steering Committee (SC) will serve as the main governing board of
the Network (see "Terms and Conditions of Award").  It will be
responsible for the design and execution of Network-wide research
protocols and the assembly of study populations which are required
for their conduct.  Its membership will include the Principal
Investigators of the Network Participating Centers, the NCI Program
Coordinator, directors of other coordinating groups, and a consumer
representative.  Additional members may be appointed by mutual
agreement of the SC membership.
 
An Advisory Committee (AC) will be composed of senior scientists with
multidisciplinary expertise in cancer genetics research and will be
responsible for reviewing, evaluating and prioritizing all research
proposals involving use of Network resources or developmental funds.
The AC will also provide advice to the SC on scientific matters, as
appropriate and as needed.  AC members may be nominated by SC members
and will be appointed by the NCI for a two-year tenure.
 
To facilitate the analyses of genetic testing information and to
enhance the ability to conduct interdisciplinary research with
clinical, population-based, and laboratory components, the Network
will develop on-site databases and a central data repository as key
Network resources.  Recruitment of individual participants to the
databases will target persons who express an interest in genetic
testing for cancer predisposition, for any of a broad range of
cancer-related gene mutations and polymorphisms. The databases will
include both tested individuals (mutation carriers and non-carriers)
and those who have considered testing but decided against it at the
present time.  Consent for inclusion in the databases will be
obtained from participants in a manner independent of informed
consent for genetic testing.  The databases will be built using
state-of-the-art informatics technology and will be designed to
maximize confidentiality of information.  Core information will
likely include demographic, family history, environmental exposures
and other risk factor data, and information on cancer occurrence and
preventative practices. Individual participants will be followed
annually to provide updates and will be asked to release genetic
information to the Network if such information becomes available.
The Network will provide registrants with periodic updates on the
latest scientific findings about cancer genetics and new research
protocols and projects for which they may be eligible through
newsletters, electronic information transfer, or other approaches.
 
The Network will directly support and coordinate the development and
implementation of educational resources and programs in cancer
genetics, both for health care providers and for the general public.
Network sites will also be charged with developing innovative
approaches to education and community outreach.
 
An Informatics and Information Technology Group will be supported
through a separate RFA and will serve as a resource to help meet the
information management needs and requirements of the Network and its
various functions.  This group will develop and maintain an
Internet-based data management system and a central data repository,
expanding and enhancing the heterogeneous computer capabilities of
the individual participating centers.  Data security and
confidentiality will be of primary importance in the design and
implementation of this information system.  Individual participating
centers must demonstrate competency in the management and exchange of
electronic data that will become part of the larger Network
repository.
 
Research proposals requiring Network resources may be submitted by
Network investigators or by investigators unaffiliated with the
Network. All proposals must be reviewed and considered to be of high
priority by the AC and must be approved by the SC.  Except for
developmental activities and pilot studies supported through
administrative supplements, funding for investigator-initiated
research is not included in this RFA and should be sought from other
sources.
 
NIH intramural laboratories and/or clinical programs may participate
as Network centers but may not receive salary, equipment, supplies,
or other remuneration from this program.  The intramural principal
investigator must obtain appropriate NIH clearances.  The Principal
Investigator must incorporate into the application, in the usual
format, a full description of the collaborative project, including
technical details and methodology. The participation of an intramural
scientist is independent of and unrelated to the role of the NCI
Program Coordinator as described under "Terms and Conditions of
Award."  An intramural Network center will participate in a manner
analogous to the Network center awardees and will be subject to the
same requirements.
 
Terms and Conditions of Award
 
The Terms and Conditions of Award, below, 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.
These special Terms of Award are in addition to and not in lieu of
otherwise applicable OMB administrative guidelines, HHS grant
administration regulations in 45 CFR Part 74 and 92, and other HHS,
PHS and NIH grant administration policy statements.
 
The administrative and funding instrument used for this program is a
resource-related cooperative agreement (U24).  This is an assistance
mechanism for support of a research resource in which substantial NIH
scientific and/or programmatic involvement with the awardee is
anticipated during performance of the activity.  Under the
cooperative agreement, the NIH purpose is to support and/or stimulate
the recipient's activity by involvement in and otherwise working
jointly with the award recipient in a partner role. Consistent with
this concept, the prime responsibility for the activity resides with
the awardee(s) for the project as a whole.
 
1. Awardee Rights and Responsibilities
 
Awardees and NIH intramural laboratories/programs participating as
Network centers will have primary rights and responsibilities to
define projects and approaches and to plan and conduct the project
including:
 
a.  The Awardee is responsible for enrollment and follow-up of
Network participants, and for establishment and maintenance of
mechanisms to ensure that data collection and management procedures
have necessary quality control and assure confidentiality of data.
 
b.  The Principal Investigator will serve as a permanent member of
the SC and will participate in the development of Network protocols
and procedures.  The awardee will be required to implement and comply
with the common policies and procedures approved by the SC.
 
c.  The awardee will participate in common Network protocols and
procedures.  In addition, individual awardees may conduct single site
(e.g., pilot) studies using their unique program and resources.
Single site projects involving resources supported by Network funds
must be reviewed and approved by the SC and AC, as described below.
 
d.  The Awardee must implement core data collection methods and
strategies agreed upon by the SC. Each awardee/site must ensure that
data will be submitted in a timely way to the central Network
database.
 
e.  The Awardee must agree to provide access to Network resources to
Network-affiliated and non-affiliated investigators, based on review
and prioritization of the research proposals by the AC and approval
by the SC.
 
f.  The Awardee must provide a semi-annual progress report to the NCI
Program Coordinator.  This report should include progress during the
reporting period (including accrual and follow-up), staffing changes,
a summary of project expenditures, manuscripts prepared during the
reporting period, and priorities for the coming reporting period.
 
g.  The Awardee will cooperate in the scientific reporting of Network
findings.  The NCI will have access to and may periodically review
all data generated under an award.  Plans for joint publication with
NCI extramural program staff of pooled data will be reviewed and
approved by the Steering Committee.  NIH policies governing
co-authorship of publications with NCI extramural program staff will
apply in all cases.
 
h.  The awardee(s) will retain custody of and have primary rights to
the data developed under these awards, subject to Government rights
of access consistent with current HHS, PHS and NIH policies.
However, publication or oral presentation of results obtained under
this Cooperative Agreement will require appropriate acknowledgment of
NCI support.
 
2.  NCI Staff Responsibilities
 
The role of the Program Coordinator is to assist and facilitate, but
not to direct, the activities supported by the Network.
 
The NCI Program Coordinator will:
 
a.  Serve as liaison from the NCI, helping to coordinate activities
among the awardees;
 
b.  Serve as scientific liaison between the awardees and other
program staff at NCI with experience in multicenter studies, cancer
genetics, and social and behavioral research;
 
c.  Serve as a full participant and voting member of the SC, and, as
appropriate, SC subcommittee(s); serve as liaison between the SC and
the AC, attending AC meetings in a non-voting liaison member role;
 
d.  Assist in the monitoring of field data collection, helping to
ensure standardization in methods across Network participating
centers; and assist in developing operating guidelines, quality
control procedures, and consistent policies for dealing with
recurrent situations that require coordinated action.
 
The NCI reserves the right to reduce the budget, to withhold support,
and to suspend, terminate or curtail a study or an award in the event
of substantial shortfall in accrual, data reporting, inadequate
quality control of data collection, refusal to carry out the
recommendations of the SC and AC, or substantial failure to comply
with the terms of the award.  Periodic external progress reviews of
the program will be carried out as NCI deems appropriate.
 
3. Collaborative Responsibilities
 
a.  Steering Committee (SC).  The SC will serve as the main governing
board of the Network.  The SC will be responsible for development and
implementation of the Network at the participating centers and for
the design and execution of Network-wide research protocols. Its
membership will include the Principal Investigators of the Network
Participating Centers, the NCI Program Coordinator, directors of
other coordinating groups, and a consumer representative.  Additional
members may be appointed by mutual agreement of the SC membership.
 
This Committee will develop uniform policies and procedures for (a)
data collection,  management, and quality control; (b) access to
Network resources for research purposes by Network and non-Network
investigators (including policies governing authorship for research
reports); and (c) dissemination of educational materials and
scientific information.  The SC will develop the criteria for review
and prioritization of research proposals requiring the use of Network
resources.
 
The Committee will elect a Chairperson (other than the NCI Program
Director) who will be responsible for coordinating the Committee's
activities, for preparing meeting agendas, and for scheduling and
chairing subsequent meetings. The NCI Program Coordinator will attend
and participate in all meetings.  At least three meetings will be
held during the first year of operation, and two meetings a year
thereafter, one of which will be with the AC.  Applicants must
request sufficient funds in their budgets to accommodate travel
expenses for the PIs.  Subcommittees will be established by the SC as
it deems appropriate.
 
The SC will be responsible for confirming the availability and
accessibility of data for use by investigators requesting the use of
Network resources for approved research proposals.  The SC may
nominate members for the AC.  The SC will pay particular attention to
conflict of interest issues in the conduct of all business matters
and will bring such matters to the attention of the AC and of the NCI
Program Coordinator.
 
b.  Advisory Committee (AC): The AC will be composed of senior
scientists with multidisciplinary expertise in cancer genetics
research.  AC members may be nominated by SC members and will be
appointed by the NCI for a two-year tenure. At least 75% of AC
members will be non-government.
 
The AC will be responsible for reviewing, evaluating and prioritizing
all research proposals involving use of Network resources or
developmental funds.  The AC will evaluate all research proposals
(those from Network investigators as well as from the research
community) which require Network resources.  All reviews will be held
according to rules pertaining to the conduct of reviews for NIH
grants, contracts, and cooperative agreements and to review
procedures developed by the SC, with special attention to issues of
conflict of interest (whether real or apparent).  The AC will provide
a recommendation to the SC as to the priority of the proposed
research projects. The AC will also provide advice to the SC on
scientific matters, as appropriate and as needed.  The AC will meet
jointly with the SC at least once yearly.  Support for AC meetings
and other AC functions will be provided by NCI through a mechanism
outside this RFA.
 
4. Arbitration Procedures
 
Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award) between award recipients and the NCI
may be brought to arbitration. An arbitration panel will be composed
of three members -- one selected by the awardee, a second member
selected by NCI, and the third member selected by the two previously
selected members. These special arbitration procedures in no way
affect the awardee's right to appeal an adverse action that is
otherwise appealable in accordance with PHS regulations at 42 CFR
Part 50, Subpart D, and HHS regulations at 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 new
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines on the Inclusion of Women and Minorities as
Subjects in Clinical Research" which have been published in the
Federal Register of March 28, 1994 (59 FR 14508-14513) and reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS, Volume 23, Number 11,
March 18, 1994.
 
Investigators may obtain copies of the policy from these sources or
from the program staff or the contact person listed below. Program
staff may also provide additional relevant information concerning the
policy.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by June 20, 1997, a
letter of intent that includes a descriptive title of the proposed
project, the name, address and a telephone number of the Principal
Investigator, the names 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 is helpful in planning
for the review of applications. It allows NCI staff to estimate the
potential review workload and to avoid conflicts of interest in the
review. The letter of intent is to be sent to Susan G. Nayfield,
M.D., M.Sc. at the address listed under INQUIRIES below.
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants. These forms are available at most
institutional offices of sponsored research and may be obtained from
the Office of Extramural Outreach and Information Resources, Division
of Research Grants, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267,
e-mail [email protected].
 
The RFA label available in the application form PHS 398 (rev. 5/95)
must be affixed to the bottom of the face page. 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 number and title of the RFA must be typed on line 2a of
the face page of the application and YES must be checked.
 
Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact photocopies in one package to
the Division of Research Grants at the address below. The photocopies
must be clear and single sided.
 
Division of Research Grants
National Institutes of Health
Suite 1040
6701 Rockledge Drive MSC 7710
Bethesda, MD 20892-7710
 
At the time of submission, two additional copies of the application
must by sent to:
 
Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Blvd.
Rockville, MD 20850 (if hand delivered or delivery service)
Bethesda MD 20892-7399 (if using U.S. Postal Service)
 
It is important to send these copies at the same time that the
original and three copies are sent to DRG; otherwise, the NCI cannot
guarantee that the application will be reviewed in competition with
other applications received on or before the designated receipt date.
 
Applications must be received by September 12, 1997. If an
application is received after that date, it will be returned to the
applicant without review. 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.
 
Funds requested by this RFA should be directed to support basic
Network activities and for other personnel and activities that extend
the capacity of an applicant site to meet the goals of the Network,
as described above under "Goals and Scope."  The costs of clinical
genetic testing and counseling, beyond the counseling required for
the Network recruitment and informed consent process, will not be
covered under this award.
 
Routine collection and storage of biospecimens from all Network
participants will not be covered through this solicitation.  Funds
for expansion of tissue repository capabilities may be requested as
an infrastructural resource for future Network research projects, as
described under "Goals and Scope." The costs of collection,
processing, and storing tissues for investigator-initiated research
and for Network-wide projects must be covered by funds from other
sources and should be included in the budgets for R01 (or other)
applications which rely upon Cancer Genetic Network resources on a
fee-for-service basis.  The costs of collecting, processing, and
storing specimens for developmental activities (e.g., development and
standardization of new laboratory procedures) and for pilot studies
will be covered by the Network through administrative supplements,
also described under "Goals and Scope."
 
REVIEW CONSIDERATIONS
 
All applications will be judged on the basis of the scientific merit
of the proposed project and the documented ability of the
investigators to meet the OBJECTIVES of the RFA.  Although the
technical merit of the proposed protocol is important, it will not be
the sole criterion of evaluation of a proposal.
 
Review Method
 
Upon receipt, applications will be reviewed for completeness by the
DRG and for responsiveness to the RFA by the NCI. Incomplete
applications will be returned to the applicant without further
consideration.  If NCI staff find that the application is not
responsive to the RFA, it will be returned and will receive no
further consideration.
 
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NCI in accordance with the review
criteria stated below.  As part of the initial merit review, all
applications will receive a written critique and undergo a process by
which only those applications deemed to have the highest scientific
merit, generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the National Cancer Advisory Board.
 
Review Criteria
 
Applicants are expected to address all issues identified under
SPECIAL REQUIREMENTS of the RFA. The review group will assess the
scientific merit of the protocols and related factors, including:
 
1.  The scientific excellence of the application and extent to which
it addresses the goals and objectives of the RFA;
 
2.  Scientific and technical excellence of the applicant's existing
program in clinical cancer genetics, especially in the genetics of
cancer susceptibility, the translation of genetics into medical
practice, or public health issues in cancer genetics.
 
3.  Availability of and access to a suitable catchment population;
ability of proposed recruitment strategies to provide adequate
numbers of enrollees to support active Network participation;
adequacy of plans for inclusion of minority participants;
 
4.  Demonstrated ability in meeting generally accepted standards for
predictive genetic testing, including informed consent processes,
pre-and post-test counseling, and laboratory procedures for genetic
testing;
 
5.  Evidence that appropriate steps have been taken to ensure the
rights of human subjects including informed consent for genetic
testing and for Network participation; adequacy of plans for
maintaining privacy and confidentiality of participant information;
 
6.  Demonstrated ability and willingness to carry out common
protocols, and adequacy of plans for effective cooperation and
collaboration with other participating centers and the NCI Program
Coordinator;
 
7.  Adequacy of existing physical facilities and resources of the
applicants' Institution(s);how effectively the proposed resource
expansion will enhance the applicant's participation in Network
functions; and the unique resources and capabilities the applicant
will bring to the Network;
 
8.  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research; and the unique expertise the Principal
Investigator, Co-Investigators, and Consultants will bring to the
Network.
 
The review group will also examine the proposed budget and will
recommend an appropriate budget and period of support for each
application that is recommended for further consideration.
 
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.
 
AWARD CRITERIA
 
The earliest anticipated date of award is March 1, 1998. The
following will be considered for making funding decisions:
 
1.  Scientific and technical merit of the proposed project as
determined by peer review;
 
2.  Adequate effort to represent the minority groups in the
population sampled;
 
3.  Availability of funds;
 
4.  Program balance among geographic and research areas.
 
INQUIRIES
 
Written and telephone inquiries concerning the RFA and the
opportunity to clarify any issues or questions from potential
applications are welcome.
 
Direct inquiries regarding programmatic and scientific issues to:
 
Susan G. Nayfield, M.D., M.Sc.
Extramural Epidemiology and Genetics Program
National Cancer Institute
Executive Plaza North, Suite 535
6130 Executive Boulevard MSC 7395
Bethesda, MD 20892-7395
Telephone: (301) 496-9600
 
Direct inquiries regarding fiscal matters to:
 
Ms. Crystal Wolfrey
Grants Management Specialist
National Cancer Institute
Executive Plaza South, Suite 243
6120 Executive Boulevard MSC 7395
Bethesda, MD 20892-7395
Telephone: (301) 496-7800, ext. 282
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No.93.393, Cancer Cause and Prevention Research. 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 Part 52 and 45 CFR Part 74 and 92. This
program is not subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review. Unless
otherwise noted all PHS grants policies apply.
 
The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products. In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases any
portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development
services are provided to children. This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
.

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