Full Text CA-92-25

INTERACTIVE R01S FOR CLINICAL STUDIES OF SYSTEMIC THERAPIES

NIH GUIDE, Volume 21, Number 30, August 21, 1992

RFA:  CA-92-25

P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Clinical Medicine, General 
  Treatment, Medical+ 


National Cancer Institute

Letter of Intent Receipt Date:  October 22, 1992
Application Receipt Date:  December 22, 1992

PURPOSE

The Cancer Therapy Evaluation Program, Division of Cancer Treatment, at
the National Cancer Institute (NCI) invites Interactive Research
Project Grant (IRPG) applications (R01s) to perform research projects
designed to conduct clinical studies of innovative systemic therapies
investigating promising therapeutic approaches in a single tumor type
or focused on a single class of novel compounds or a mechanism of
action.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
Interactive R01s for Clinical Studies of Systemic Therapies, 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
"Healthy People 2000" (Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202/783-3238).

ELIGIBILITY REQUIREMENTS

Domestic and foreign for-profit and non-profit organizations,
governments and their agencies are eligible to apply.  Applications can
be from single institutions and multiple institutions (collaborating
institutions, consortia, cooperative groups).  New and experienced
investigators are encouraged to apply.  Applications from minority
individuals and women are encouraged.  Applicants proposing to perform
phase I clinical trials that address issues on the mechanisms of action
of immunologically active agents are not eligible for this RFA and
should apply for an RFA that will be issued by the Biological Response
Modifiers Program in the near future.

MECHANISM OF SUPPORT

Support of this program will be through the IRPG, an assistance
mechanism composed of three or more investigator-initiated research
grant applications (R01s) that will be reviewed for independent merit
but that share a theme and resource(s) and that require concurrent
funding to maximize the effectiveness of the resource or to allow
maximal creative interaction between researchers.  Except as otherwise
stated in this RFA, awards will be administered under PHS grants policy
as stated in the Public Health Service Grants Policy Statement, DHHS
Publication No. (OASH) 90-50,000, revised October 1, 1990.

This RFA is a one-time solicitation for FY 93.  However, the NCI has
plans to re-issue this RFA for funding in 1994.  If it is determined
that there is a sufficient continuing program need, the NCI will invite
recipients of awards under this RFA to submit competitive continuation
applications for review according to the procedures described below.

FUNDS AVAILABLE

Approximately $4,000,000 in total costs per year for four years will be
committed to fund applications submitted in response to this RFA.  This
funding level is dependent on the receipt of a sufficient number of
applications of high scientific merit.  The total cost for each IRPG
(consisting of three or more R01s) is limited to $750,000 per year.
Thus it is anticipated that five to six IRPGs will be funded in FY 93.
In FY 93 it is anticipated that this RFA will be re-advertised and an
additional three IRPGs will be funded in FY 94.  The total project
period for applications submitted in response to the RFA may not exceed
four years.  The earliest feasible start date for the initial awards
will be August 1993.  Although this program is provided for in the
financial plans of the NCI, the award of R01 grants pursuant to this
RFA is also contingent upon the availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

Investigator-initiated grant support is by far the largest single
entity in the NCI research budget.  The NCI utilizes a range of funding
mechanisms to support clinical research efforts of differing scale and
scope.  For the conduct of large-scale, multi-institutional clinical
trials, the Cancer Therapy Evaluation Program has established a program
of integrated national networks of clinical investigators and
institutions (Clinical Trials Cooperative Groups).  The primary
responsibility of the cooperative groups is to perform definitive
evaluation of clinical treatment programs.  These groups have limited
involvement with pilot studies and ancillary laboratory studies, which
bridge the gap between the laboratory and the clinic.  Currently,
translational research and preliminary clinical studies are supported
by grants (R01, P01, and U01 awards) under the Research Project Grant
category.  This smaller scale clinical research is usually done within
single institutions or in small consortia of institutions interested in
a particular area of therapeutic investigation.  These investigator
initiated mechanisms support early clinical development of new
therapeutic agents and treatment modalities.  They support
pharmacokinetics studies, studies of mechanisms of action and
resistance of therapeutic agents, and all types of clinical correlative
studies.  This effort is the essence of translational research, which
brings the basic science to the bedside and provides leads for
definitive treatment trials.

An unprecedented number of new therapeutic agents are ready for
evaluation in pilot clinical studies.  In addition, insights into the
biologic function and clinical relevance of growth factors, genes that
promote and suppress neoplasia, mechanisms of treatment sensitivity and
resistance, and function of the immune system provide important new
clinical research opportunities for investigators.  The NCI is
interested in expanding support for clinical research.  Under this IRPG
RFA, the NCI encourages the coordinated submission of related research
project grant applications from investigators who want to collaborate
on a common cancer research theme, but do not require extensive shared
physical resources or multiple core functions.  This mechanism is not
meant to replace the program project (P01) mechanism but to support a
level of collaboration between that of the P01 and that available
through an individual R01.

The IRPG is defined in PA-92-29 (NIH Guide for Grants and Contracts,
Vol. 21, No. 1, January 10, 1992) as three or more investigator-
initiated research grant applications that are reviewed for independent
merit but that share a theme and resource(s), and that require
concurrent funding to maximize the effectiveness of the resource or to
allow maximal creative interaction between researchers.  Applicants
will benefit from use of the IRPG mechanism by establishing a larger
framework of reference for the proposed work, by facilitating formal
collaborations tailored to achieving research objectives, by providing
a record of independently acquired awards credited to each funded
investigator, and by allowing retention of research autonomy by the
named Principal Investigator on each of the interactive grants.

Research Goals And Scope

The aims of this RFA are two-fold:  (1) to provide support for
translational research that brings innovative basic research findings
into the clinic and (2) to foster the development of interactions
between basic science laboratories of different disciplines and
clinicians performing clinical trials to advance therapeutic clinical
research.

This RFA is soliciting applications to perform IRPGs with the goal of
developing new clinical studies involving systemic therapies with a
therapeutic intent.  The IRPGs may have as their key focus either:  (1)
clinical studies investigating promising therapeutic approaches in a
single tumor type or (2) the development of new clinical treatment
strategies focused on a single class of novel compounds or mechanism of
action.  Each project supported in the IRPG is expected to contribute
to and be directly related to the common theme of the IRPG application.
The application must clearly explain how the projected integrated R01
research grants can be expected to accomplish the stated goal more
efficiently and effectively than they could without the anticipated
interactions.  At least one clinical trial protocol must be proposed in
one of the grant applications.  The clinical trials should be well
integrated with the laboratory studies proposed within the same R01
application or in separate R01 applications.

Support will be provided to institutions with established clinical,
laboratory, and statistical resources.  Some examples of research areas
that individual R01 grant applications would focus on include:  (1)
pre-clinical drug development studies, utilizing in vitro or in vivo
models, leading to new clinical trials; (2) studies to elucidate or
exploit the mechanism of action or resistance of therapeutic agents;
(3) pharmacokinetics and pharmacodynamic studies of new agents or in
combination; (4) clinical correlative studies designed to improve
therapeutic approaches; (5) clinical trials of new systemic therapies
utilizing therapeutic agents alone or in combination with other
modalities.  Investigators are not limited to the above examples of
potential studies.  The NCI encourages investigators to propose other
scientific approaches that suit the interactive R01 mechanism and the
requirements of this RFA.

SPECIAL REQUIREMENTS

Definitions

Principal Investigator (PI) - The person who submits the single R01
grant application in response to this RFA and who is responsible to the
applicant/awardee institution for the scientific and administrative
direction and proper conduct of all aspects of the R01 grant.

Project Coordinator -  The person designated by the PIs of the
interactive R01 grants who is responsible for the overall coordination
of the scientific direction of the interactive R01 grants.

Responsibilities of Each Awardee

Each awardee is responsible for his/her own proposed research
project(s) to advance the goals of the RFA and to define its approaches
to attain these goals.  It is the primary responsibility of the PI to
state clearly the objectives of the research project, to direct the
research stipulated in the application, and to ensure that the results
obtained are published in a timely manner.  It is anticipated that
decisions on the overall scientific direction of the package of
interactive R01s will be reached by consensus of the collaborating PIs.

Responsibilities of the Project Coordinator

In addition to the responsibilities stated above for each awardee, the
Project Coordinator has the responsibility of providing coordination of
the overall scientific direction of the interactive R01s.  He/she will
accomplish this role by facilitating scientific collaborations among
the various investigators.  The Project Coordinator will also be
responsible for establishing mechanisms to facilitate regular
communication and coordination among investigators.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF FEMALES AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and females in study populations so that research findings
can be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis should be placed on the need
for inclusion of minorities and females in studies of diseases,
disorders and conditions which disproportionately affect them.  This
policy is intended to apply to males and females of all ages.  If
females or minorities are excluded or inadequately represented in
clinical research, particularly in proposed population-based studies,
a clear compelling rationale should be provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group, together with a rationale for
its choice.  In addition, gender and racial/ethnic issues should be
addressed in developing a research design and sample size appropriate
for the scientific objectives of the study.  This information should be
included in the form PHS 398 in the Research Plan, 1-4, AND summarized
in Section 5, Human Subjects.

Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However, NIH
recognizes that it may not be feasible or appropriate in all research
projects to include representation of the full array of United States
racial/ethnic minority populations (i.e., Native Americans (including
American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks,
Hispanics).  The rationale for studies on single minority population
groups should be provided.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.  However,
every effort should be made to include human tissues from females and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of females applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
females or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.

All applications for clinical research submitted to NIH are required to
address these policies.  NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by October 22, 1992, a
letter of intent that includes a descriptive title of the proposed
research, the names and addresses of the Principal Investigators, the
names of other investigators and key personnel, the participating
institutions, and the number and title of the RFA in response to which
the application is being submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, it is requested
in order to provide an indication of the number and scope of
applications to be reviewed.

The letter of intent is to be sent to:

Dr. Roy S. Wu
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663

APPLICATION PROCEDURES

The PHS 398 (rev. 9/91) research grant application form is to be used
in applying for this RFA.  These forms are available at most
institutional business offices; from the Office of Grants Inquiries,
Division of Research Grants, National Institutes of Health, Room 449,
Westwood Building, 5333 Westbard Avenue, Bethesda, MD 20892, telephone
(301) 496-7441; and from the NCI Program Director named below.

A short narrative of the interactive nature of the research
applications should be included in the Research Plan of each of the R01
applications.  The exact nature of the interactions should be clearly
detailed under the consortium section of the respective R01
applications.

The RFA label available in the PHS 398 research application form 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
RFA number and title must be typed on line 2a of the face page of the
application form.

Submit the signed, typewritten original application, including the
Checklist, and three signed, exact photocopies of each R01.  The
photocopies must be clear and single sided.

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, send two additional copies of each
application to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 838
5333 Westbard Avenue
Bethesda, MD  20892

Applications must be received by December 22, 1992.  If an application
is received after that date, it will be returned without review.  If
the application submitted in response to this RFA is substantially
similar to a research grant application already submitted to the NIH
for review, but has not yet been reviewed, the applicant will be asked
to withdraw either the pending application or the new one.
Simultaneous submission of identical applications will not be allowed,
nor will essentially identical applications be reviewed by different
review committees.  Therefore, an application cannot be submitted in
response to this RFA that is essentially identical to one that has
already been reviewed.  This does not preclude the submission of
substantial revisions of applications already reviewed, but such
applications must include an introduction addressing the previous
critique.

REVIEW CONSIDERATIONS

Review Procedure

Upon receipt, applications will be reviewed by the Division of Research
Grants for completeness.  Incomplete applications will be returned to
the applicant without further consideration.  Evaluation for
responsiveness to the program requirements and criteria stated in the
RFA is an NCI program staff function.  Applications that are judged
non-responsive will be returned to the applicant.  An application
judged to be non-responsive to this RFA may be submitted as an
investigator-initiated IRPG at the next receipt date for unsolicited
applications.  Questions concerning the responsiveness of proposed
research to the RFA are to be directed to program staff (see
INQUIRIES).

If the number of applications submitted is large compared to the number
of awards to be made, the NCI may conduct a preliminary scientific peer
review to eliminate those that are clearly not competitive.  The NCI
will remove from competition those applications judged to be
noncompetitive for award and notify the applicant and institutional
business official.

Those applications judged to be both responsive and competitive will be
further evaluated according to the review criteria stated below for
scientific and technical merit by an appropriate peer review group
convened by the Division of Extramural Activities, NCI.  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.

Review Criteria

The factors considered in evaluating the scientific merit of each
application will be:

o  Extent to which the proposed research addresses the goals of the RFA

o  Scientific, technical, or medical significance and originality of
proposed research within each R01 application;

o  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  Research or clinical experience, training, time availability, and
qualifications of the investigators involved;

o  Adequacy of plans for effective collaboration among laboratory,
clinical, and statistical investigators within each R01;

o  Adequacy of the available resources and environment (e.g.,
facilities, equipment, statistical resources, patient population)

o  Adequacy of the mechanisms for quality control, study monitoring,
data management and reporting, and data analysis;

o  Adequacy of provisions for the protection of human subjects;

o  Adequacy of the plans for inclusion of females and minorities.

The reviewers will also judge the appropriateness of the proposed
budget and duration in relation to the proposed research.  For each
application that is given a priority score, the review group will
assign an adjectival descriptor that reflects the extent and
effectiveness of its collaboration(s) with other applications included
in the IRPG.  This assessment will be documented in a brief
administrative note in the summary statement to assist the NCI in
making final decisions on each application in the context of the
overall IRPG.

AWARD CRITERIA

The anticipated date of award is August 1, 1993.  In addition to the
technical merit of the application, NCI will consider how well the
applicant institution meets the goals and objectives of the program as
described in the RFA, availability of resources, and study populations.

INQUIRIES

Written and telephone inquires concerning the objectives and scope of
this RFA and inquires about whether or not specific proposed research
would be responsive are encouraged and are to be directed to NCI
Program Directors at the addresses below.  The NCI Program Directors
welcome the opportunity to clarify any issues or questions from
potential applicants.

For technical information:

Dr. Roy S. Wu
Ms. Diane Bronzert
NCI Program Director
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663

For business information:

Ms. Sara Stone
Grants Management Specialist
National Cancer Institute
Executive Plaza South, Room 242
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 66
FAX:  (301) 496-8601

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 Sections 301,
410, and 411, Part A (Public Law 78-410, 42 USC 241 as amended, Public
Law 99-158, 42 USC 285a) and administered under PHS grants policies and
Federal Regulations at 42 CFR Part 52 and 45 CFR Part 74.  This program
is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.

.

Return to RFAs Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.