DIRECTOR'S CHALLENGE: TOWARD A MOLECULAR CLASSIFICATION OF TUMORS

Release Date:  January 20, 1999

RFA:  CA-98-027

P.T.

National Cancer Institute

Letter of Intent Receipt Dates:  March 23, 1999; October 5, 1999
Application Receipt Dates:  April 26, 1999; November 16, 1999

PURPOSE

The Director of the National Cancer Institute (NCI) challenges the scientific
community to harness the power of comprehensive molecular analysis technologies
to make the classification of tumors vastly more informative.  This challenge is
intended to lay the groundwork for changing the basis of tumor classification
from morphological to molecular characteristics.  The NCI Director invites
investigators to form multi-disciplinary research groups [National Cooperative
Tumor Signature Groups (NCTSGs)] and to submit applications proposing the
exploitation of one or a related set of comprehensive molecular analysis
technologies for the analysis of tumor specimens.  The NCTSGs will be expected
to define comprehensive profiles of molecular alterations in tumors that can be
used to identify subsets of patients.  These molecular profiles will provide the
basis for future studies to validate the clinical utility of molecular-based
classification schemes.  To achieve these goals, applicants may propose to
develop comprehensive molecular profiles using DNA, RNA or protein-based
technologies.  A further goal of this initiative is the development and
implementation of a plan for timely release of the extensive data sets expected
to result from these projects.  Access to these information rich data sets will
benefit the entire cancer research community and facilitate rapid progress toward
achieving the goals of the NCI.

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),
Director's Challenge: Toward a Molecular Classification of Tumors, 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), or at
http://www.crisny.org/health/us/health7.html

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.  NCTSGs may be formed by investigators from within a single
institution.  However, collaborations between companies developing molecular
technologies and other institutions with clinical resources and cancer expertise
are strongly encouraged.  Racial/ethnic minority individuals, women and persons
with disabilities are encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

Support for this program will be through the National Institutes of Health (NIH)
cooperative agreement grant (U01) and research project cooperative agreement
grant (U19) mechanisms. Applications for U01 support follow an R01 application
format while applications for U19 support have a program project grant (P01) 
structure and follow a P01 application format.  Like the P01, the U19  is an
assistance award for the support of a broadly based multidisciplinary research
program that has a well-defined central focus or objective (see APPLICATION
PROCEDURES and REVIEW CONSIDERATIONS sections below for additional information
specific to the multi-project format of the U19 application).

The cooperative agreement (U01/U19) is an "assistance" mechanism in which
substantial NIH scientific and/or programmatic involvement with the awardee is
anticipated during performance of the research.  Under the cooperative agreement
mechanism, the NIH purpose is to facilitate and/or coordinate the activities of
the successful grantees, but not to assume direction, prime responsibility, or
a dominant role in grant related activity.  Details of the responsibilities,
relationships and governance of the study to be funded under cooperative
agreement(s) are discussed under the section "Terms and Conditions of Award". 
The total project period for an application submitted in response to this RFA may
not exceed five years.  The anticipated award dates are September 30, 1999 (1st
application receipt date) and July 1, 2000 (2nd application receipt date).

FUNDS AVAILABLE

The NCI intends to commit approximately $10 million for the two application
receipt dates to fund a total of eight to ten new grants in response to this RFA. 
Awards and level of support depend on 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.  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.

RESEARCH OBJECTIVES

Background

Since its beginnings as a scientific discipline, diagnostic pathology has been
based on tumor morphology, the microscopic appearance of tumor tissue.  Tumor
morphology has served as the basis of tumor classification.  Advances in tissue
fixation, staining and imaging technologies have resulted in increasingly
informative images that have permitted substantial refinements in diagnostic
criteria for many cancers.  Current classification schemes have serious
limitations, however.  They often cannot discriminate between tumors with similar
histopathologic appearances that will follow significantly different clinical
courses.  The Director of the National Cancer Institute therefore invites the
scientific community to exploit contemporary molecular analysis technologies to
develop vastly more informative tumor classification systems.  This challenge is
intended to lay the groundwork for changing the basis of tumor classification
from morphological to molecular characteristics.

The Director's Challenge is based on the assumption that a comprehensive
knowledge of the molecules, or a relevant subset of molecules, expressed in a
tumor can be much more informative clinically than the morphological
characteristics of the tumor.  The knowledge that a specific molecular profile
correlates with important clinical parameters should allow physicians to base
management decisions on the molecular characteristics of an individual patient's
tumor.  Molecular profiles should also improve a physician's ability to determine
the primary tumor site for tumors of unknown origin at the time of their
detection.

The application of high-throughput technologies to human tumors should make it
possible to generate comprehensive molecular profiles.  However, to date, the
technologies have primarily been applied to the analysis of model systems, cell
lines or lower eukaryotes.  A few of the most mature technologies are now being
applied to the analysis of clinical tissue specimens.  For example, serial
analysis of gene expression (SAGE) has been applied to the analysis of gene
expression patterns in colon tumors, lung tumors and tumors from several other
sites.  Studies have been initiated to correlate gene expression patterns
determined by SAGE with clinical parameters.  Oligonucleotide and cDNA arrays are
being used to analyze gene expression in colon, breast, and certain other tumors. 
Although these and other early studies are demonstrating the potential power of
these technologies, the extensive research needed to be able to routinely apply
molecular-based strategies to actual tumor specimens is just beginning.

This is an opportune time for NCI to facilitate the application of these
technologies to the analysis of tumor specimens.  The technologies have developed
to the point where translation to analysis of tumor specimens is feasible.  The
Cancer Genome Anatomy Project (CGAP) and other research efforts are providing the
resources and reagents needed to facilitate these efforts.  This initiative is
designed to bring  together the expertise and resources necessary to continue
development and application of these powerful new technologies.

Objectives and Scope

The specific purpose of this RFA is to support research projects focused on
identification of  patterns of molecular alterations in tumors that will become
the foundation of molecular-based tumor classification schemes.  Multi-
disciplinary groups will be funded to focus on the application of comprehensive
molecular technologies to the analysis of tumor specimens. These groups, National
Cooperative Tumor Signatures Groups (NCTSGs), will be expected to develop new
molecular classification schemes for a selected set of tumors based on patterns
of molecular alterations rather than on the classical histopathological criteria
currently in use.

NCTSG applicants should focus on one technology, or a set of related
technologies, for application to tumor specimens.  The selected technologies can
be for analysis of molecular changes in DNA, RNA or protein.  The DNA-based
technologies can be targeted to the comprehensive analysis of mutations, to the
determination of genome-wide cytogenetic changes or to changes in patterns of DNA
modifications such as DNA methylation.  Technologies can be targeted to the
analysis of patterns of gene expression at the level of mRNA.  Protein-based
technologies can be used to determine patterns of gene expression, changes in
protein composition in subcellular compartments, or changes in post-translational
modifications of proteins.  The selected technology should be able to generate
a comprehensive analysis of each tumor specimen.

Development of new molecular classification schemes for tumors will depend on a
rational approach to the selection of tumor specimens for analysis.  Applicants
should include a detailed rationale for selecting the class of tumors they plan
to analyze.  The design of the study should ensure that statistically significant
differences among profiles from subsets of tumors can be identified.  For
example, an applicant could propose to analyze specimens from node-negative
breast cancer patients.  There is known biological heterogeneity within this
group of patients since approximately 30% of these patients will have recurrences
and will die of their disease.  It is anticipated that molecular profiles can
successfully identify subgroups of these patients.  Other examples of groups of
cancer patients with known heterogeneity include, but are not limited to,
patients with multi-focal, organ-confined prostate cancer, stage C colon cancer
or anaplastic astrocytomas.

The analysis of the selected tumor specimens should be carried out without
further reference to morphology or clinical data.  The initial identification of
subsets of the tumors should result from analysis of molecular profile data. 
Established profiles can then be annotated with all of the available clinical
data, including histopathological data, to examine whether the subsets defined
molecularly are associated with clinical parameters.  These data can include
tumor stage and grade, demographic data and any clinical data that is available
such as response to therapy and disease outcome.

An additional benefit of developing molecular profiles of tumors is the potential
to aid in identifying the primary tumor sites for tumors of  unknown origin at
the time of diagnosis.  Development of schemes for identifying tumors of unknown
origin may require a different scientific approach such as establishing profiles
that uniquely identify all tumors from a given organ site.  In response to this
initiative, investigators may propose to identify unique profiles from a large
number of organ sites and then to evaluate the utility of these profiles for
identifying the primary site for metastatic tumors.

Each applicant should clearly document a strategy for obtaining access to high
quality tissue specimens that will be needed to carry out their programs. 
Applicants should also describe the demographic and clinical data that they
anticipate they will collect in order to ensure that the molecular profiles
obtained will be as informative as possible.  Applicants must specifically
describe plans to protect patient confidentiality.

During the course of the projects grantees may identify needs for additional
tissue specimens.  NCI program staff will assist grantees in obtaining access to
additional tissue resources by facilitating interactions and collaborations
between the NCTSGs and other NCI supported research efforts.  Appropriate
collaborations could be established between the NCTSGs and the clinical trials
groups, SPOREs, NCI supported collaborative research networks, NCI Cancer Centers
and other NCI supported specimen resources.  Establishing these collaborative
interactions will ensure that tumor specimens needed to develop molecular
profiles are available.

Effective data management and analysis will be critical to the successful
development of new tumor classification schemes based on molecular profiles since
application of comprehensive analytical technologies generates very large
quantities of data.  The organization and management of the data and the
subsequent analysis of the data will constitute a significant challenge to the
successful grantees.  The NCTSGs will be expected to develop and apply innovative
bioinformatics and statistical tools to the management and analysis of  the data. 
Applicants should describe the informatics approaches they plan to develop and/or
use.  Applicants should provide a detailed description of the design of the
proposed studies and the associated statistical strategies that will be used to
identify and compare molecular profiles that may be useful for tumor
classification.

The application of the comprehensive molecular analysis technologies results in
the generation of large, information rich data sets.  These data sets will be
analyzed by the investigators who generated them in order to address the
scientific questions that were initially posed.  However, it is likely that only
a subset of the data used in the analyses will be included in publications
resulting from the research.  The complete primary data sets would be extremely
valuable resources for other researchers who could use them to test additional
hypotheses.  In order to maximize the return on the NCI's  investment in the
application of these technologies, NCI program staff will work with the funded
investigators to develop a strategy for public release of the data.  Applicants
should discuss potential strategies for making these valuable molecular data sets
available to the cancer research community.

Group Structure and Operations

Applicants to this initiative are expected to assemble a team of investigators
prior to submitting their application; this team will form the nucleus of their
NCTSG.  Each research team should include the expertise necessary to meet the
goals of the RFA.  The necessary expertise is expected to include technology
developers and engineers to support continued development and/or adaptation of
the selected technologies; basic cancer researchers; oncologists and/or
pathologists to provide the cancer expertise that will ensure the selection of
appropriate specimens for analysis; and statisticians and experts in
bioinformatics to provide the appropriate expertise in data management and
analysis.

It is anticipated that in some cases collaborations between investigators from
academic, government and commercial organizations may be necessary in order to
include all of the expertise required for the project.  This will be particularly
true if the technology selected is provided by a commercial organization and the
cancer expertise and resources are being provided by an academic institution. 
In addition, NCI is supporting new and ongoing intramural programs for the
comprehensive analysis of molecular alterations in tumors.  Where appropriate,
applicants are encouraged to take advantage of these resources through
collaborations with intramural investigators.  Either the academic or commercial
organization may take the lead in developing an application and the Principal
Investigator may be from either institution.  Intramural researchers may not
serve as Principal Investigators or Co-Investigators on these applications.  The
final structure of individual NCTSGs should be consistent with the requirements
of the proposed research project.

Collaborations among investigators from academic and commercial institutions can
be complicated by concerns over issues of intellectual property.  The intent of
this initiative is to minimize these problems by addressing them at the time the
application is submitted.  Applicants should provide evidence that these issues
are being addressed and that all collaborating institutions recognize that
intellectual properties issues should not interfere with research progress.  The
adequacy of the collaborating institutions' consideration of these issues will
be assessed during of review of the applications.

It is anticipated that unexpected scientific opportunities may arise during the
course of these projects.  These opportunities might include breakthroughs in
technology development or the appearance of unanticipated novel technologies that
could significantly enhance progress toward project goals or breakthroughs in our
understanding of cancer which might lead to a shift in research strategy.  In
order to provide flexibility that will enable the NCTSGs to respond to these new
scientific opportunities as they arise, applicants may request developmental
funds in their budget for the second through the fifth years of support.  These
funds will be restricted, and their use will have to be requested and justified
by the PI on a yearly basis.  Use of these funds will require approval by NCI
program staff.  These funds may also be used to offset unexpected administrative
costs associated with obtaining the clinical specimens.

SPECIAL REQUIREMENTS

In order to ensure  maximum progress in the projects funded by this initiative
and to realize the maximum benefit for the cancer research community and
ultimately for the ongoing battle against cancer, several special activities will
be required of the funded investigators.  An annual meeting of all funded
investigators will be held to share progress and research insights that may
benefit all of the projects.  Applicants should request travel funds in their
budgets for critical personnel to attend this annual meeting.  The annual meeting
will be initiated after the first year of funding.  As discussed earlier,
grantees will be required to develop a plan for the timely release of data to the
cancer research community.  Applicants should also request travel funds to attend
two meetings per year of the planning group.  This group will evolve into an
implementation and oversight committee as the projects mature.  Finally,
applicants should state in their applications their commitment to participating
in these intergroup activities and their commitment to the public release of
data.

Terms and Conditions of Award

These special Terms of Award are in addition to and not in lieu of otherwise
applicable OMB administrative guidelines, HHS Grant Administration Regulations
at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant Administration
policy statements.  [Part 92 applies when state and local governments are
eligible to apply as a "domestic organization."]

The administrative and funding instrument used for this program is a cooperative
agreement [(U01)/(U19)], an "assistance" mechanism (rather than an "acquisition"
mechanism) in which substantial NIH scientific and/or programmatic involvement
with the awardee is anticipated during performance of the activity. Under the
cooperative agreement, the NIH purpose is to support and/or stimulate the
recipient's activity by involvement in and otherwise working jointly with the
award recipient in a partner role, but it is not to assume direction, prime
responsibility, or a dominant role in the activity.  Consistent with this
concept, the dominant role and prime responsibility for the activity resides with
the awardee(s) for the project as a whole, although specific tasks and activities
will be carried out as a collaboration among the awardees with coordination and
facilitation by NCI Program Staff.

1.  Awardee Rights and Responsibilities

Awardees will have primary responsibility for the project as a whole, including
research design and conduct, data collection, data quality control, data analysis
and interpretation and preparation of publications, as well as collaborations
with other awardees.  An NCI Program Staff member will coordinate and facilitate
interactions and collaborations among the awardees (see section 3 below).

Awardees will retain primary rights to the data developed under these awards,
subject to Government rights of access consistent with current HHS, PHS, and NIH
policies.  However, awardees must commit to the release of the data to the cancer
research community through a mechanism to be planned and implemented by the
awardees and the NCI.  It is anticipated that the release of data will occur
after the individual investigators have had a reasonable period of time to
evaluate their results and realize the appropriate benefits of their own research
efforts.  Awardees must also commit to sharing research results at the annual
meeting of investigators.

2.  NCI Staff Responsibilities

Program staff will work closely with individual investigators to facilitate
collaborations with other NCI-funded research groups to ensure that all
investigators have access to the tumor specimens and other resources that may be
necessary to successfully achieve their research goals.  The NCI program
directors responsible for the individual awards will assist in the coordination
of activities that involve all of the awardees such as the annual meetings, but
only a single NCI program staff member, as described below, will be a member of
the Data Release Planning and Oversight Committee.

3.  Collaborative Responsibilities

Program staff will participate in and facilitate the development of the strategy
for making research data widely available to the cancer research community.  The
Data Release Planning and Oversight Committee, composed of the PI of each NCTSG,
a second member from each NCTSG selected by the PI and one NCI Program Staff
member, will be responsible for developing a plan for making the data from the
comprehensive analysis publicly available in a format that will facilitate use
of the data by the cancer research community.  The Committee will continue to
monitor the implementation of the data release plan for the life of the awards. 
A chairperson for the Committee will be selected by the participants.  The NCI
Program Staff member will be a voting member of the Committee but cannot serve
as chair and will coordinate and facilitate the work of the Committee.

4.  Arbitration

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 Data Release Planning Committee (with the NCI member not voting)
or by the individual awardee in the event of an individual disagreement, a second
member selected by NCI, and the third member selected by the two prior selected
members.  This special arbitration procedure in no way affects the awardee's
right to appeal an adverse action that is otherwise appealable in accordance with
the PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation 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
sub-populations 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
policy results from the NIH Revitalization Act of 1993.

All 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 in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

Investigators may also obtain copies of the policy from the program staff listed
under INQUIRIES.  Program staff may also provide additional relevant information
concerning the policy.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are clear and compelling scientific and ethical reasons not to
include them.  This policy applies to all initial (Type 1) applications submitted
for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for Grants
and Contracts, March 6, 1998, and is available at the following URL address:
https://grants.nih.gov/grants/guide/notice-files/not98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent by March 23, 1999
or October 5, 1999.  The letter of intent should include a descriptive title of
the proposed research, name, address, and telephone number of the Principal
Investigator, identities of other key personnel and participating institutions,
and 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 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 the program staff listed under INQUIRES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in applying
for these grants.  Applications kits are available at most institutional offices
of sponsored research and may be obtained from the Division of Extramural
Outreach and Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, E-mail:
grantsinfo@nih.gov.  For those applicants with internet access, the 398 kit may
be found at https://grants.nih.gov/grants/forms.htm

In addition to the PHS 398, applicants submitting U19 applications are to use the
NCI program project grant (P01) guidelines (available from the NCI Referral
Officer listed under INQUIRIES or at http://deainfo.nci.nih.gov/awards/P01.PDF),
in the preparation of applications.

The RFA label available in the PHS 398 (rev. 4/98) 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 2 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 photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must also be
sent to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636, MSC-7399
Bethesda, MD  20892-7399
Rockville, MD  20850 (for express/courier service)

Applications must be received by April 26, 1999 or November 16, 1999.  If an
application is received after that date, it will be returned to the applicant
without review.  The Center for Scientific Review (CSR) 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 CSR will not accept any application that is essentially the same as one
already reviewed.  This does not preclude the submission of a substantial
revision of an application already reviewed, but such an application must follow
the guidance in the PHS Form 398 application instructions for the preparation of
revised applications, including an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR 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 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, a process will be used by the initial review group in which
applications receive a written critique and undergo a process in which only those
applications deemed to have the highest scientific merit, generally the top half
of the 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 encouraged to submit a research plan describing their own ideas
about how best to meet the goals of the RFA.  Applicants are expected to address
issues identified in the section on SPECIAL REQUIREMENTS of the RFA.

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered by the reviewers in assigning the
overall score weighting them as appropriate for each application.  Note that the
application does not need to be strong in all categories to be judged likely to
have a major scientific impact and thus deserve a high priority score.  For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.

Significance:  Does this study address an important problem?  If the aims of the
application are achieved, how will scientific knowledge be advanced?  What will
be the effect of these studies on the concepts or methods that drive this field?

Approach:  Are the conceptual framework, design, method, and analyses adequately
developed, well-integrated, and appropriate to the aims of the project?  Does the
applicant acknowledge potential problem areas and consider alternative tactics?

Innovation:  Does the project employ novel concepts, approaches or method?  Are
the aims original and innovative?  Does the project challenge existing paradigms
or develop new methodologies or technologies?

Investigator:  Is the investigator appropriately trained and well suited to carry
out this work?  Is the work proposed appropriate to the experience level of the
principal investigator and other researchers (if any)?

Environment:  Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?

Additional review criteria specific for this initiative include:

-- access to appropriate tissue resources with the associated clinical data
necessary to perform the research;

--  demonstrated willingness to collaborate with other funded investigators and
with NCI Program Staff  in the development of a plan for the release of data and
a stated commitment to the timely release of data;

--  evidence that the intellectual properties issues are being addressed by the
collaborating institutions and will not interfere with productive collaboration;

--  appropriateness of the proposed budget and duration in relation to the
proposed research.

The initial review group will also examine: the adequacy of plans to include both
genders and minorities and their subgroups as appropriate for the scientific
goals of the research and plans for the recruitment and retention of subjects;
the adequacy of plans for including children as appropriate for the scientific
goals of the research, or justification for exclusion; the provisions for the
protection of human and animal subjects; and the safety of the research
environment.

For U19 applications, all of the above criteria apply, as well as the review
considerations outlined in the NCI program project guidelines (available from the
NCI Referral Officer listed above or at http://deainfo.nci.nih.gov/awards/P01.PDF.)  
In applications for U19 support, interrelationships between component projects are 
expected to result in greater contribution to the program goals than if each project 
were pursued separately.

AWARD CRITERIA

The following criteria will be considered in making funding decisions: the
quality of the proposed projects as determined by peer review; the responsiveness
of the proposed project to the goals of the RFA; and the availability of funds.

SCHEDULE

Letter of Intent Receipt Dates:   March 23, 1999      October 5, 1999
Application Receipt Dates:        April 26, 1999      November 16, 1999
Review by Advisory Board (NCAB):  September 1999      May 2000
Earliest Anticipated Start Date:  September 30, 1999  July 1, 2000

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:

James W. Jacobson, Ph.D.
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, Room 700, MSC 7388
Bethesda, MD  20892-7388
Telephone:  (301) 402-4185
FAX:  (301) 402-7819
Email:  jj37d@nih.gov

Direct inquiries regarding review issues to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636, MSC-7399
Bethesda, MD  20892-7399
Rockville, MD  20850 (for express/courier service)
Telephone:  (301) 496-3428
FAX:  (301) 402-0275
Email:  tf12w@nih.gov

Direct inquiries regarding fiscal matters to:

E.C. Melvin
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243, MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext. 258
FAX:  (301) 496-8601
Email:  melvine@gab.nci.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.394, Cancer Detection and Diagnosis Research.  Awards are made under
authorization of the Public Health Service Act, Title IV, Part A (Public Law
78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR Parts 52 and 45 CFR Part
74 [and Part 92 when applicable for State and Local governments]. This program
is not subject to the intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities ( or in some cases, any portion of a facility) in which regular or
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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Department of Health and Human Services

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