kristoff@GENBANK.BIO.NET (Dave Kristofferson) (01/03/91)
REQUEST FOR APPLICATIONS
RFA NUMBER: CA-91-03
CLINICAL TREATMENT AND CORRELATES OF UPPER GI
CARCINOMA
P.T. 34; K.W. 0715035, 0715085
National Cancer Institute
Letter of Intent Date: February 25, 1991
Application Receipt Date: April 8, 1991
I. PURPOSE
The Division of Cancer Treatment (DCT) of the National Cancer
Institute (NCI) invites research grant applications (R01) from
interested investigators to assess new clinical correlates and
develop new treatment modalities in upper gastrointestinal (GI)
carcinoma by means of an integrated research program of
laboratory experimentation and concurrent clinical trials. New,
as well as experienced, investigators in relevant fields and
disciplines may apply to fund new therapeutic clinical trials or
new correlative laboratory studies that are related to clinical
trials.
The present Request for Applications (RFA) announcement is for a
single competition with a
specified deadline of April 8, 1991, for receipt of applications.
Applications should be prepared and submitted in accordance with
the aims and requirements described in the following sections:
I. PURPOSE
II. BACKGROUND INFORMATION
III. RESEARCH GOALS AND SCOPE
IV. MECHANISM OF SUPPORT
V. ELIGIBILITY
VI. REVIEW PROCEDURES AND CRITERIA
VII. METHOD OF APPLYING
VIII. LETTER OF INTENT
IX. INQUIRIES
II. BACKGROUND
Carcinoma of the organs of the upper GI tract
(esophagus and stomach) are lethal tumors. Development of
resistance to treatment (as manifested by tumor progression) is
rapid even when chemotherapy, with or without radiation therapy, is
effective. Taken collectively, the incidence of these tumors
represents a major health hazard to 35,000 patients per year.
Adenocarcinoma of the esophagus formerly was a rare tumor (8-11%
of esophageal cases), but recent clinical reports suggest that
approximately 30% of esophageal cancer patients annually are now
presenting with adenocarcinoma (associated with Barrett's
esophagus). If these figures are representative of a wider
epidemiologic shift, up to 3,000 cases of esophageal
adenocarcinoma may occur each year. In addition, there are
24,000 cases of gastric carcinoma and 8,000 cases of esophageal
squamous carcinoma annually. Except for the 11% of patients with
gastric cancer limited to the stomach, who are able to undergo
curative resection, and a similar group of patients with
esophageal cancer, the average life span for patients with these
cancers is 4 to 6 months. The reported response rates for
cytotoxic therapy range from 5% to 40%. Relatively few complete
responses are noted and no patient with metastatic disease is
cured. Recently, however, promising results utilizing
combinations of radiation or surgery and chemotherapy have been
reported for esophageal cancer.
The NCI supports basic research efforts to describe and
understand the tumor biology and treatment resistance of
malignancies. Such efforts form the basis for the development of
new treatment modalities. Relatively few investigations are
supported in upper gastrointestinal carcinoma to move new
advances in the laboratory into the clinic. This RFA encourages
applicants to address their research efforts towards the upper GI
carcinomas and the development of new clinical therapies. For
example, monoclonal antibodies directed against gastrointestinal
tumor-specific antigens have been developed, characterized, and
applied for diagnostic purposes. The potential of these
antibodies to improve clinical management and/or therapy of these
diseases needs further investigation. Clinical correlations of
oncogenes, growth factors, or markers of drug resistance may
prove useful in subsets of patients that would respond to
specific treatment therapies.
III. RESEARCH GOALS AND SCOPE
The major goal of this RFA is to foster interactions between
basic science laboratories and clinicians performing clinical
trials in upper GI carcinoma to improve treatment results and
clinical outcome. To accomplish this goal, two types of studies
will be supported: (1) the development of new therapeutic
clinical trials or (2) new correlative studies relevant to
clinical trials. Applications should be focused on integrating
clinical goals with laboratory research areas.
This RFA envisions funding new therapeutic clinical trials in
upper GI carcinomas that test and exploit basic findings
concerning drug resistance or cellular targets of treatment.
Clinical studies should be designed to improve cancer treatment.
New clinical studies dealing with treatment using
chemotherapeutic drugs, biologics, radiation, or surgery, whether
used as a single agent/modality or in combination, are
appropriate. Examples of clinical trials based on new
therapeutic approaches include: (1) treatment therapies for
overcoming drug or radiation resistance; (2) treatment therapies
based on novel mechanisms of action; (3) biologics in combination
with drug or radiation regimens; (4) immunotherapies including
monoclonal antibody therapy, radioimmunotherapy, and the use of
new immunotoxins; (5) new therapies combining endocrine
manipulations with chemotherapeutic agents; (6) more effective
combinations of chemotherapy and radiation therapy; or (7)
radiation modifiers to enhance cell kill or protect normal
tissue.
This RFA has a second research goal of funding new correlative
laboratory studies that are relevant to therapeutic clinical
trials. Some examples of therapeutic correlates include: (1)
phenotypic or genotypic alterations which appear to correlate
with the development of drug or radiation resistance; (2)
oncogenes, growth factors, and specific antigen expression on
tumor cells for antibody development; (3) pharmacokinetic and
pharmacodynamic measurements; and (4) biochemical pharmacologic
parameters. The therapeutic correlates must have a future
clinical application such as development of new treatment
strategies or identification of patient subsets for specific
treatment therapies. This RFA does not support research
investigations on diagnostic markers or clinical correlates which
will have no impact on the clinical treatment of patients. The
laboratory assays must utilize patient specimens from new or
ongoing clinical trials and have been demonstrated to be
applicable to tissue samples and/or body fluids, etc.
Investigators are encouraged to obtain patient specimens from
multi-institutional clinical trials to ensure adequate sample
size for statistical analysis.
Research investigators are not limited to the above areas of
potential studies. Clinical protocols should be included in the
Appendix of the application. A section on statistical support
should be included in the grant application to ensure proper
correlation of assay parameters with clinical outcome.
IV. MECHANISM OF SUPPORT
Support of the program will be through the National Institutes of
Health (NIH) grant-in-aid (RO1). Applicants will be responsible for
the planning, direction, and execution of the proposed project.
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.
Approximately $1,500,000 in total costs per year for three years
will be committed to specifically fund applications that are
submitted in response to this RFA. It is anticipated that 6 to 8
awards will be made. This funding level is dependent on the
receipt of a sufficient number of applications of high scientific
merit. The total project period for applications submitted in
response to the present RFA should not exceed three (3) years.
The earliest feasible start date for the initial award will be
December 1, 1991. Although this program is provided for in the
financial plans of the NCI, the award of grants pursuant to this
RFA is also contingent upon the continuing availability of funds
for this purpose.
V. ELIGIBILITY
Non-profit and for-profit, domestic organizations and
institutions, governments and their agencies are eligible to
apply.
Applications can be from single institutions or multiple
institutions (collaborating institutions, consortia, cooperative
groups). We encourage new, as well as experienced,
investigators to apply.
VI. REVIEW PROCEDURES AND CRITERIA
A. REVIEW PROCEDURE
Upon receipt, applications will be reviewed by the DRG for
completeness. Incomplete applications will be returned to the
applicant without further consideration. Applications will be
evaluated by NCI Program staff to determine whether they are
responsive to this RFA and meet the stated goals and objectives
of the program. Applications that are judged non-responsive
will be returned to the applicant. Questions concerning the
relevance of proposed research to the RFA should be directed to
program staff as described in the INQUIRIES section.
In cases where the number of applications is large compared to
the number of awards to be made, the NIH will conduct a
preliminary scientific peer review to eliminate those that are
clearly not competitive. The NIH 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 competitive and responsive
will be further evaluated, using 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.
B. REVIEW CRITERIA
The factors considered in evaluating the scientific merit of each
response to this RFA will be:
1. Extent to which the proposed research addresses the goals of
the RFA.
2. Significance and originality of the research from a scientific
and technical viewpoint.
3. Feasibility of proposed research.
4. Adequacy and appropriateness of the methodology and protocol
design.
5. Clinical experience, training, time availability, and research
competence of the investigators involved.
6. Adequacy of available resources and environment (facilities,
equipment, statistical collaboration, patient population, etc.).
7. Provision for the adequate protection of human subjects.
8. Documentation of support from collaborators and consultants
through letters of commitment.
The review group will critically examine the submitted budget and
will recommend an appropriate budget and period of support for
each approved application.
C. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN 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 women 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
women 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 women 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. 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 Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors 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 women 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 women 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 women 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.
VII. METHOD OF APPLYING
The research grant application form PHS-398 (revised 10/88)
must be used in applying for these grants. These forms are
available at most institutional business offices; the
Office of Grant Inquiries, Division of Research Grants, National
Institutes of Health, Room 449, Westwood Building, 5333 Westbard
Avenue, Bethesda, MD 20892; and the NCI Program Director
named below.
The RFA label available in the 10/88 revision of Application Form
398 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
should be typed on line 2 of the face
page of the application form.
Submit a signed, typewritten original of the application,
including the Checklist, and four (4) 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
Westwood Building, Room 240
Bethesda, MD 20892**
At the time of submission, two (2) additional copies of the
application should also be sent to:
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 848
5333 Westbard Avenue
Bethesda, MD 20892
Applications must be received by April 8, 1991. If an
application is received after the indicated date, it will be
returned. 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 which 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.
VIII. LETTER OF INTENT
Prospective applicants are asked to submit by February 25, 1991, a
letter of intent that includes a descriptive title of the
proposed research, the name and address of the Principal
Investigator, the names of other key personnel, the participating
institutions, 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 should be sent to:
BY US POSTAL
Ms. Diane Bronzert
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) 496-9384
BY DIRECT DELIVERY
Ms. Diane Bronzert
Program Director
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
6130 Executive Blvd.
Rockville, MD 20852
IX. INQUIRIES
Written or telephone inquiries concerning the objectives and
scope of this RFA or inquiries about whether or not specific
proposed research would be responsive are encouraged and should
be directed to Ms. Diane Bronzert at the above address. The
program director welcomes the opportunity to clarify any issues
or questions from potential applicants.
This program is described in the Catalog of Federal Domestic
Assistance No. 93.395, (Clinical Treatment Research). Awards are
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 Grant Policies and
Federal Regulations 42 CFR 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.
SPECIALIZED CENTERS OF RESEARCH IN RHEUMATOID ARTHRITIS (RA)
SPECIALIZED CENTERS OF RESEARCH IN OSTEOPOROSIS (OP)
SPECIALIZED CENTERS OF RESEARCH IN OSTEOARTHRITIS (OA)
RFA AVAILABLE: AR-91-01
P.T. 04; K.W. 0715010, 0705050, 0710030
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Letter of Intent Receipt Date: July 15, 1991 (RA and OP)
November 14, 1991 (OA)
Application Receipt Date: October 15, 1991 (RA and OP)
February 14, 1992 (OA)
The National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS) established 9 Specialized Centers of
Research (SCORs) in Fiscal Year 87, three each in
osteoarthritis, osteoporosis, and rheumatoid arthritis. The
purpose of this Request for Applications (RFA) is to recompete these
centers in an open
competition. The specific areas will remain osteoarthritis,
osteoporosis, and rheumatoid arthritis. Applications for
SCORs in rheumatoid arthritis and osteoporosis will be
accepted on October 15, 1991. Applications for SCORs in
osteoarthritis will be accepted on February 14, 1992. The
direct cost budget requested may not exceed $1 million each
year. The applications should present five years of work.
BACKGROUND
A SCOR consists of a cluster of individual, but
interrelated, basic and clinical research projects, each
with high scientific merit and clear research objectives
and, in the aggregate, devoted to a specific major health
area. Ongoing projects may be absorbed into the SCOR if
their original funding source is relinquished.
In addition, funding may also be requested for one or more
core resources devoted to performing specialized support
activities, such as biochemical analysis, electron
microscopy, or data management. A core is defined as a
resource shared by several investigators that should
enhance research productivity and increase the functional
capacity of the SCOR. The core is designed to provide an
added dimension generating a new accomplishment greater than
that obtained by the performance of the sum of the
individual projects alone. Developmental research (for
example, development of new assays or procedures) needed to
further research efforts of the SCOR investigators will be
permitted in a core.
NIAMS currently supports
SCORs in three areas of special importance to the
Institute: rheumatoid arthritis, osteoporosis, and
osteoarthritis. Each SCOR is envisioned as a national
resource associated with a major medical complex and
dedicated to working with the NIAMS in furthering the
research effort related to a given arthritis and
musculoskeletal disease area. The SCOR program complements
other programs in research and training supported by the
Institute. SCORs should foster a concerted research effort
that strongly emphasizes basic disciplines, but also
involves significant interaction between
basic research and clinical investigations of diseases
within the purview of the Institute.
OBJECTIVES AND SCOPE
SCOR programs must include both basic and clinical research.
Each program will provide for a mutually supportive
interaction between scientists conducting basic research and
those performing clinical investigation. The individual
projects and cores should be correlative or complementary in
the area selected for the SCOR.
The objective of this SCOR program is to expedite
development and application of new knowledge of specific
importance to arthritis and musculoskeletal diseases, to
learn more about the etiology of these diseases, and to
foster improved approaches to treatment and/or prevention.
Each SCOR should provide a multidisciplinary approach
utilizing both laboratory and clinical research to focus on
a particular health problem and provide for a mutually
supportive interaction between basic scientists and clinical
investigators. Although research programs will vary at each
institution according to local expertise, interests, and
resources, each SCOR should have a central theme related to
osteoarthritis, rheumatoid arthritis, or osteoporosis to
which individual projects relate and that serves as an
integrating force. Emphasis in proposed projects should be
on development of innovative approaches, elaboration of new
and significant hypotheses, and generation of improved
strategies for approaching current issues relating to
arthritis and musculoskeletal diseases.
Support for large clinical trials or for applications that
contain exclusively clinical or exclusively basic studies
will not be provided within this SCOR program.
Applicants from institutions which 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. In such a
case, a letter of agreement from either the GCRC program
director or Principal Investigator is requested with
the application.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN 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 women 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
women 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 women 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. 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 Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors 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 women 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 women 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 women 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.
PROGRAM ADMINISTRATION/INTERACTION
The NIAMS Centers Program Director will facilitate program
development, disseminate new findings, and increase
interaction among SCOR's. The program director will
coordinate plans for any special activities of mutual
interest to the Institute and the SCOR or, perhaps, to
several SCORs. The NIAMS program director may make periodic
visits to various Centers and will be responsible for
evaluating progress.
To foster cooperation among Centers, SCOR personnel may be
asked to meet periodically to review progress and plans for
future work. Applicants, therefore, should include a
request for travel funds for the Center Director and other
key staff members to travel to the Washington, D.C. area in
each year of their budget.
MECHANISM OF SUPPORT
The support mechanism will be the research grant-in-aid (P50).
The Direct Costs requested cannot exceed $1 million each
year. The number and size of any resultant awards will be
based upon the merit of the applications received and the
funds available. If sufficient applications are judged by
peer review to be of excellent to outstanding merit, NIAMS
anticipates funding 9 SCORs for 5 years, three for each of
the diseases listed. The grants may be renewable on a competitive
basis.
Applicants are expected to furnish estimates of the time
required to achieve specific objectives of the proposed work
and a schedule for completion of the work. The SCOR will
plan, direct, and implement its own research program. However, any
substantial modifications in the scope or objectives must be
agreed upon mutually by the SCOR institution and the NIAMS.
REVIEW PROCEDURES AND CRITERIA
Applications for Arthritis and Musculoskeletal Diseases SCORs
will be first screened for completeness, responsiveness, and
scientific merit. Applications that are incomplete for review or
nonresponsive to this RFA will be screened out by the Division of
Research Grants and NIAMS staff upon receipt. Applications that
are complete and responsive may be subjected to a preliminary
evaluation by a peer review group to determine their scientific
merit relative to the other applications received in response to
this RFA (triage); the NIH will withdraw from further
consideration applications judged to be noncompetitive and
promptly notify the Principal Investigators and the official
signing for the applicant organization. Those applications
judged to be competitive will be further evaluated for scientific
merit by an ad hoc review group. This phase of peer review will
be conducted by a group of expert consultants convened by the
Review Branch of the NIAMS. Each proposal should be complete in
itself. Site visits are not anticipated. A second level of
review will be performed by the National Arthritis and
Musculoskeletal and Skin Diseases Advisory Council.
Major factors to be considered in evaluation of applications
will include the:
1. Scientific merit of each proposed project, including
the originality and feasibility of the project and the
adequacy of the experimental design;
2. Scientific merit of combining the component parts into
a SCOR;
3. Technical merit and justification of each core unit;
4. Competence and commitment of the investigators to accomplish the
proposed research goals, and the time they
will devote to the research program;
5. Adequacy of facilities to perform the proposed
research, including laboratory and clinical facilities,
instrumentation, and data management systems, when needed;
6. Adequacy of plans for interaction among investigators,
and the integration of the various projects and core units;
7. Qualifications, experience, and commitment of the SCOR
Director and his/her ability to devote time and effort to
provide effective leadership;
8. Scientific and administrative structure, including
internal and external procedures for monitoring and
evaluating the proposed research and for providing ongoing
quality control and scientific review;
9. Institutional commitment to the program, and the
appropriateness of resources and policies for the
administration of a SCOR;
10. Appropriateness of the budget for the proposed program
and its individual components.
METHOD OF APPLICATION
Program Guidelines and Letter of Intent
Program guidelines, developed by NIAMS for its SCOR Program,
are available by contacting the Centers Program Director
below. It is especially important that applicants obtain
and follow these supplemental NIAMS guidelines that
require certain information in addition to the usual
instructions.
To facilitate Institute planning, applicants are requested
to submit a letter of intent by July 15, 1991 for the RA and
OP SCOR and by November 14, 1991 for the OA SCOR.
The letter
should include a descriptive title, the name
and address of the Principal Investigator and other key
investigations, and the names and address of any other
participating institutions.
The letter of
intent, and any inquiries about the program, should be
directed to:
Julia B. Freeman, Ph.D.
Centers Program Director, EP, NIAMS
Westwood Building, Room 403
5333 Westbard Avenue
Bethesda, MD 20892
Telephone: (301) 496-7495
FAX: (301) 480-7881
The Institute requests such letters for the purpose of
obtaining an indication of the number and scope of
applications to be received. A letter of intent is not
binding, will not enter into the review of any proposal
subsequently submitted, and is not a requirement for
application.
The letter of intent, however, may be useful as a basis for
consultation prior to submission of an application.
Applicants should make arrangements for such consultation
early in the application preparation process. Applicants
should not construe advice given by Institute staff as
assurance of a favorable review or funding. The program
staff will not evaluate or discuss the merit of the
proposal.
Application Procedure
Type in the RFA number and title of this announcement on line 2
of the application face page.
The RFA label (found in the 10/88 revision of application form
PHS 398) must be affixed to the bottom of the face page of the
original copy of the application. Failure to use this label
could result in delayed processing of your application such that
it will not reach the review committee in time for review.
The signed, completed, original application and four (4)
signed, exact photocopies, should be sent or delivered to:
Application Receipt Office
National Institute of Health
Division of Research Grants
Westwood Building, Room 240
Bethesda, MD 20892**
Applications must be received by the dates listed in this
announcement for each specific competition. An application
not received by this date will be considered ineligible.
In addition to mailing the application to the Division of
Research Grants, send two (2) copies of the application to:
Tommy Broadwater, Ph.D.
Chief, Review Branch, EP, NIAMS
Room 5A-07 Westwood Building
5333 Westbard Avenue
Bethesda, MD 20892
FAX: (301) 480-7881
This program is described in the Catalog of Federal Domestic
Assistance, No. 93.846. Grants are awarded under the
authority of the Public Health Service Act, Section 301 (42
USC 241) and administered under PHS grant policies and
Federal Regulations, most specifically at 42 CFR Part 52 and
45 CFR Part 74. This program is not subject to review by a
Health Systems Agency.
REQUEST FOR APPLICATIONS
RFA: DK-91-05
DIABETES INTERDISCIPLINARY RESEARCH PROGRAM
P.T. 34; K.W. 0715075, 0710030, 1002019, 0710070, 1002004, 1002008
National Institute of Diabetes and Digestive and Kidney Diseases
Letter of Intent Receipt Date: March 15, 1991
Application Receipt Date: May 17, 1991
INTRODUCTION
The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) and the Juvenile Diabetes Foundation
International (JDFI) invite investigator-initiated program
project grant applications that incorporate an
interdisciplinary research approach to the etiology and
pathogenesis of insulin-dependent diabetes mellitus (IDDM)
or to the genetic susceptibility for the long-term
complications of diabetes. This solicitation is intended to
stimulate the application of advances in basic molecular
biology, genetics, immunology, cell biology, and biophysics
to the study of IDDM and its complications.
Applications will be submitted to the NIH and will be
reviewed by NIH according to the usual NIH peer review
procedures. Applications judged meritorious but not funded
by the NIH may be considered by the JDFI for possible
funding. Applicants wishing to have their application
considered by the JDFI must authorize the NIDDK to provide a
copy of their letter of intent, application, and NIH-
prepared summary statement of the initial review to the
JDFI.
GENERAL BACKGROUND
In 1987, the National Diabetes Advisory Board (NDAB) formulated a
National Long-Range Plan to Combat Diabetes. A
number of significant recommendations were made by the NDAB
in this plan. One of these was to establish Diabetes
Interdisciplinary Research Programs (DIRPs) to be supported
by NIDDK. The DIRPs would promote the integration of new
research methodologies into diabetes research. As a result
of establishing these programs, young as well as established
scientists with research commitments to diabetes would be given
the opportunity to immerse themselves in new technologies at
the cutting edge of modern science.
In order to implement this recommendation, the NIDDK
convened three colloquia on "Genetics and Diabetes," "Gene
Regulation and Cellular Signaling in Diabetes" and
"Immunology and Diabetes Mellitus" during 1988. The
discussions and presentations focused on interdisciplinary
dialogue between investigators in new and rapidly evolving
areas of biomedical research (i.e., molecular biology and
immunology) and biomedical research areas related to
diabetes.
The NIDDK is coordinating efforts with the JDFI to implement
DIRPs in areas of research that appear particularly relevant
to the cure, prevention, and improved treatment of IDDM.
Toward this end, the JDFI has recently embarked on a major
long-term capital fund raising campaign targeted at
establishing programs of excellence in diabetes research.
SCIENTIFIC BACKGROUND
It has been established that IDDM is an autoimmune disease
with major genetic influences. Much has been learned about
the nature of the immunologic process involved but many
questions remain. Informative animal models of IDDM (i.e.,
BB/W rat and NOD mouse) continue to be a central focus of
research. Specific genes in the HLA locus have been
associated with IDDM, but the molecular or genetic roles of
these genes or closely linked genes in the diabetic process
have not been clearly defined.
There is a great deal of epidemiologic, clinical, and
physiologic information on the long-term microvascular,
macrovascular, and neurologic complications of diabetes.
There are biochemical theories of causation that have
prompted research during the last decade as well. At this
time, however, the molecular pathophysiology of diabetic
complications is still unclear. Despite the epidemiologic
and clinical evidence of genetic factors in the development
of complications, very little is known about the identity or
function of specific genes in these processes.
Recent breakthroughs in basic biomedical research have
revolutionized our ability to study complex diseases such as
diabetes. Limited but highly successful application of the
new capabilities of molecular biology, genetics, immunology,
cell biology, and biophysics to diabetes research has been
evident. Importantly, the increased utilization of these
technologies and approaches promise an improved
understanding and enhanced development of potential
preventative and therapeutic strategies.
OBJECTIVE AND SCOPE
It is the intention of the NIDDK and JDFI to further
stimulate the integration of the most current basic
biomedical research approaches into diabetes-related
research. It is expected that this will be accomplished by
bringing to the diabetes arena those who are skilled in
these approaches by the support of meritorious, synergistic,
multidisciplinary research program project applications.
Proposals should include the involvement of both basic and
applied scientists in collaborative endeavors. Research
proposals should be in the broad areas of IDDM or molecular
and genetic aspects of complications of the disease.
Relevant topics listed below are examples and should not be
construed as required or limiting.
o Identification and functional characterization of genes
for IDDM or IDDM susceptibility
o Identification of initial instigating events or factors
in the development of IDDM
o Molecular mechanisms of beta cell destruction in IDDM
o Genetic regulation of beta cell differentiation and its
role in diabetes
o Identification and characterization of targets for the
autoimmune process in IDDM
o Genetic manipulation of beta cells or surrogate cells to
replace physiologic insulin secretion capacity that has been
destroyed in IDDM
o Immunoalteration of beta cells or the immune response in
an attempt to prevent or ameliorate autoimmune destruction
of beta cells
o Molecular mechanisms of rejection of grafted tissue and
other causes of transplanted pancreas or islet failure
o Identification and characterization of genes influencing
the development of long-term diabetic complications
o Molecular mechanisms responsible for tissue destruction
or dysfunction in the long-term complications of diabetes
o Interventions in basic molecular or cellular processes to
prevent or halt the progression of long-term complications
of diabetes.
MECHANISM OF SUPPORT
The mechanism of support will be the program project grant
award (PO1). A program project grant is for the support of a
broadly-based multidisciplinary or multifaceted research
program that has a specific major objective or central
theme. The award may support research components and core
functions. Collectively, these components should
demonstrate essential elements of unity and interdependence
and result in a greater contribution to program goals than if each
activity were pursued individually.
The NIDDK plans to make one or two awards in FY 1992
contingent on the receipt of highly meritorious applications
in response to this solicitation. The JDFI plans to make
two to four awards. With respect to post-award
administration, the current policies and requirements that
govern the research grant programs of the NIH or the JDFI
will prevail depending on the funding source. Applicants
should note that grants funded by the JDFI will be subject
to the indirect cost policy of JDFI.
Although this solicitation is included in the funding plans
for Fiscal Year 1992 for NIDDK, the award of grants pursuant
to this RFA is contingent upon the receipt of appropriated
funds for this purpose. The duration of proposed projects
may be up to five years. Projects may be extended through
competing continuation applications. A monetary cap on
applications specific to this RFA has been set by the NIDDK.
A program project application may request up to $3.75 million
in direct costs over a 5-year period.
$5 million in total costs).
Upon initiation of this program, the NIDDK and the JDFI plan
to sponsor periodic meetings to encourage exchange of
information among investigators, to foster collaborative
efforts between program grantees, and to identify resources
that would enhance the productivity of several grantees.
For this purpose, requests for travel funds for
a two-day meeting each year, probably to be held in
Bethesda, Maryland, should be included in the budget section
of the application. Applicants should also include a
statement in their applications indicating their willingness
to participate in such meetings and to cooperate with other
researchers at other diabetes interdisciplinary research
program sites.
REVIEW PROCEDURES AND CRITERIA
In the event that the number of applications is large
compared to the number of awards to be made, the NIH may
conduct a preliminary scientific peer review to eliminate
those applications that are clearly not competitive. The
NIH will administratively withdraw from competition those
applications judged to be noncompetitive and notify the
applicant and institutional business official.
Those applications judged to be both competitive and
responsive 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, NIDDK. It is not anticipated that
site visits will be part of the review process; therefore,
each proposal should be complete in itself and should be
prepared as if no visit is expected. Following the IRG
review, the applications will be reviewed by the National
Diabetes and Digestive and Kidney Diseases Advisory Council.
The criteria for review of applications will be those used
regularly for the review of program project grant
applications by the NIDDK. These criteria concern the
scientific and technical merit, originality, and feasibility
of the constituent individual research projects; the utility
and quality of the proposed core facilities; the
cohesiveness, synergy, significance, and overall scientific
and technical merit of the entire program project; and the
qualifications, experience, and commitment of the
participating personnel. A complete and detailed
description of these criteria is contained in the
publication entitled "NIDDK Program Project Grants:
Administrative Guidelines" that is available by request as
discussed below.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN 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 women 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
women 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 women 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. 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 Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors 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 women 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 women 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 women 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.
METHOD OF APPLYING
Applicants should request a copy of the publication entitled
"NIDDK Program Project Grants: Administrative Guidelines."
These guidelines contain important additional information on
the format of applications and review criteria. Prospective
applicants may obtain these guidelines from:
Dr. Robert D. Hammond
Chief, Review Branch
Division of Extramural Activities
NIDDK, NIH
Westwood Building, Room 406
Bethesda, MD 20892
Letter of Intent:
Potential applicants are strongly encouraged to submit a
letter of intent. The letter of intent need only include 1)
names of the Principal Investigator/program director and
principal collaborators, 2) descriptive title of the
potential application, and 3) identification of the
organization(s) involved. The letter of intent should be sent to
the Chief, Review Branch, NIDDK at the address noted above.
Letter of Authorization:
Applicants must submit a brief letter to the NIDDK
indicating whether or not they wish their applications to be
considered for funding by the JDFI. While applicants may
request that their applications be considered only by the
NIDDK and not by the JDFI, it is necessary that the record
indicate the applicant's consideration of this opportunity.
For those applicants who wish to have the JDFI consider
their application, all materials relating to the application
will be promptly forwarded to that organization by NIDDK,
and the summary statements for such applications will be
shared with the JDFI at the time of their availability. The
NIDDK will provide no information to the JDFI nor any other
non-governmental agency related to proposals from applicants
who request that the JDFI not consider their application.
Letters of authorization should be prepared by the Principal
Investigator and co-signed by the offfical signing for the
applicant organization. This letter may be combined with
Letters of Intent or may be submitted as cover letters
accompanying applications.
In all cases, the NIDDK will make its funding decisions
prior to those of the JDFI.
Format for Application:
Applications should be submitted on the PHS 398
(rev. 10/88 or 9/89) application form available at most
institutional business offices or from the Division of
Research Grants, NIH, (301) 496-7441. On item 2 of the face
page of the application, applicants should enter: RFA:
Diabetes Interdisciplinary Research Programs and the RFA
number, DK-91-05. The RFA label available in the current
revision of Application Form PHS 398 must be affixed to the
bottom of the face page. Failure to use this label could
result in delayed processing of the application to the
extent that it may not reach the review committee in time
for review.
Application Procedure:
Applications must be received by May 17, 1991, the original
and four copies of the application should be sent or
delivered to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
Two additional copies of the application should be sent to:
Review Branch
National Institute of Diabetes and Digestive and Kidney
Diseases
Westwood Building, Room 406
Bethesda, MD 20892
Timetable:
A letter of intent should be submitted no later than
March 15, 1991. Applications must be received by May 17,
1991. Any applications received after this date will be
considered ineligible for this special solicitation.
APPLICATION EARLIEST
RECEIPT DATE INITIAL REVIEW COUNCIL REVIEW START DATE
May 17, 1991 Sept. - Oct. Jan. - Feb. April 1, 1992
INQUIRIES
Inquiries regarding this announcement should be addressed
to:
Joan T. Harmon, Ph.D.
Executive Director, Diabetes Research Program
Diabetes Programs Branch
NIDDK, DDEM
Westwood Building, Room 622
Telephone: (301) 496-7731