EXPLORATORY GRANTS FOR CORRELATIVE LABORATORY STUDIES AND CLINICAL TRIALS

Release Date:  March 20, 1998

PA NUMBER:  PA-98-042

P.T.

National Cancer Institute

PURPOSE

The Division of Cancer Treatment and Diagnosis (DCTD) of the National Cancer
Institute (NCI) invites research grant applications from interested investigators
to conduct innovative therapeutic clinical trials or new correlative laboratory
studies using patient specimens from therapeutic clinical studies.

The exploratory/developmental (R21) grant mechanism is utilized for pilot
projects or feasibility studies to support creative, novel, high risk/high payoff
research that may produce innovative advances in science.  The objective of this
Program Announcement (PA) is to encourage applications from individuals who are
interested in testing novel or conceptually creative ideas that are
scientifically sound and may advance progress in human health.  This PA
supersedes PA-96 -040, Exploratory Grants to Stimulate Correlative Laboratory
Studies and Innovative Clinical Trials, which was published in the NIH Guide for
Grants and Contracts, Vol. 25, No. 12, April 19, 1996.  The exploratory grant
program provides limited funds (maximum of $100,000 direct costs per year not
including indirect costs of any collaborating institutions) for short-term (up
to two years) research projects.

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 PA, Exploratory Grants for Correlative
Laboratory Studies and Clinical Trials, 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 foreign and domestic, for-profit and non-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 be from a single institution or may include
arrangements with one or more institutions (e.g., consortia, clinical trials
cooperative group) if appropriate.  Applications from minority individuals,
women, and new investigators are encouraged.

MECHANISM OF SUPPORT

Support of this program will be through the National Institutes of Health (NIH)
exploratory/developmental grant (R21) mechanism.  Applicants will be responsible
for the planning, direction, and execution of the proposed project.  All PHS and
NIH grants policies will apply to applications received and awards made in
response to this program announcement.  Applicants may request up to $100,000 per
year in direct costs, not including indirect costs for collaborating
institutions, if any.  The total project period for applications submitted in
response to this PA may not exceed two years.  These grants are non-renewable and
continuation of projects developed under this program will be through the
traditional unsolicited investigator initiated grant program.

RESEARCH OBJECTIVES

Background

The NCI supports an extensive network of clinical and laboratory research studies
related to cancer therapy through grants and cooperative agreements.  At present,
there is no mechanism targeted to stimulate the communication of promising and
potentially relevant innovative developments between the laboratory and the
clinical setting.  It has been difficult for investigators to obtain
complementary funding through either the traditional basic research project grant
(R01) mechanism or through the cooperative agreement (U10) mechanism for either: 
(1) innovative clinical trials that take advantage of new developments in the
laboratory or (2) novel correlative laboratory studies to existing clinical
trials.  The R21 mechanism will provide investigators at all career levels with
a defined level of funding adequate for the initial feasibility testing of
innovative clinical oncology studies and for the generation of preliminary
results.  These clinical studies would not be developed fully enough for a
standard R01 and would therefore be considered high risk.  It is expected that
these R21 grants will serve as a basis for planning future clinical research
project grant applications (R01) or NCI cooperative clinical trial group studies.

Because the exploratory grant mechanism is designed to support innovative ideas,
preliminary data as evidence of feasibility are not required.  However, the
applicant does have the responsibility for developing a sound research plan. 
Originality of the approach and potential significance of the proposed research
are major considerations in the evaluation.

Research Goals and Scope

The major goal of this initiative is to promote translational and clinical
research through the support of two types of studies:  (1) new therapeutic
clinical trials or (2) new correlative studies relevant to therapeutic clinical
studies.  Applications should be focused on integrating clinical goals with
laboratory research areas.

This PA envisions funding new therapeutic clinical trials that move new treatment
strategies more rapidly from the laboratory into the clinic.  These clinical
studies must involve human subjects, be designed to ultimately improve cancer
treatment, and be based on a strong rationale.  Furthermore, the underlying
hypothesis should be supported by preclinical data.  The proposed clinical
protocol should be included in the Appendix of the application.

This PA has a second research goal of funding new correlative laboratory studies
that are relevant to therapeutic clinical studies.  The clinical correlates must
have a future clinical application such as development of new treatment
strategies or identification of patient subsets for specific treatment therapies. 
Examples of correlative studies include, but are not limited to, analysis of
prognostic markers, pharmacokinetic studies, studies of drug resistance, and
analyses of immune response.  This PA does not support research investigations
on diagnostic markers or clinical correlates which will have no impact on the
clinical treatment of patients (see PA 98-022 for support of cancer diagnostics). 
The laboratory assays must utilize patient specimens.  Where applicable, evidence
of statistical support should be included to ensure proper correlation of assay
parameters with clinical outcome.

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
policy results from the NIH Revitalization Act of 1993 (Section 4928 of Public
Law 103-43).

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 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.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95) and will be accepted at the standard application deadlines as indicated in
the application kit.  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: 
ASKNIH@od.nih.gov. The title and number of the program announcement must be typed
in line 2 on the face page of the application and the YES box must be marked.

Applicants from institutions that have a General Clinical Research Center (GCRC)
funded by the NIH National Center for Research Resources may wish to identify the
GCRC as a resource for conducting the proposed research.  If so, a letter of
agreement from either the GCRC program director or Principal Investigator must
be included with the application.

The completed original application and five legible copies must be sent or
delivered to:

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

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public Health Service
referral guidelines.  Applications will be reviewed for scientific and technical
merit by study sections of the Center for Scientific Review, NIH in accordance
with the standard NIH peer review procedures.  Following scientific-technical
review, the applications will receive a second-level review by the appropriate
national advisory council.

The five criteria to be used in the evaluation of grant applications are listed
below.

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.

1.  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?  In this case, what is the potential for translation of basic research to
clinical applications?

2.  Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  This includes, where applicable, the statistical rationale for the
study design and the choice of sample size.  Does the applicant acknowledge
potential problem areas and consider alternative tactics?

3.  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?

4.  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)?

5.  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?

The initial review group will also examine: the appropriateness of proposed
project budget and duration; 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 provisions
for the protection of human and animal subjects; and the safety of the research
environment.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding decisions:

-- Quality of the proposed research as determined by peer review
-- Program balance among research areas
-- Availability of funds
-- Responsiveness to the goals and objectives of the PA

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Ms. Diane Bronzert or Dr. Roy S. Wu
Division of Cancer Treatment Diagnosis and Centers
National Cancer Institute
6130 Executive Boulevard, Room 734, MSC 7432
Bethesda, MD  20892-7432
Telephone:  (301) 496-8866
FAX:  (301) 480-4663
Email:  BRONZERTD@CTEP.NCI.NIH.GOV or WUR@CTEP.NCI.NIH.GOV

Direct inquiries regarding fiscal matters to:

Ms. Kathleen Shino
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243, MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext. 248
FAX:  (301) 496-8601
Email:  SHINOK@GAB.NCI.NIH.GOV

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No
93.395, Cancer Treatment Research.  Awards are made under the authorization of
the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended,
Public Law 99-158, 42 USC 241 and 285) and administered under HHS grants
policies. 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.

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