PREVALENCE AND DIAGNOSIS OF CELIAC DISEASE
Release Date: June 10, 1999
RFA: DK-99-015
P.T.
National Institute of Diabetes and Digestive and Kidney Diseases
Letter of Intent Receipt Date: June 22, 1999
Application Receipt Date: July 22, 1999
THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. THIS RFA INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS RFA.
PURPOSE
The Division of Digestive Diseases and Nutrition of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) wishes to encourage
experienced and new investigators to pursue research that will establish the
prevalence and diagnosis of celiac disease in various at risk populations in
the United States. This information should lead to increased awareness of the
disorder and encourage proper diagnosis and treatment.
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),
PREVALENCE AND DIAGNOSIS OF CELIAC DISEASE, is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2000" at http://www.crisny.org/health/us/health7.html
ELIGIBILITY REQUIREMENTS
Applications may be submitted by 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. Foreign organizations are not eligible to apply;
however, domestic organizations may have a foreign component, but it should
not be the major research site. Racial/ethnic minority individuals, women, and
persons with disabilities are encouraged to apply as principal investigators.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) research project
grant (R01) award mechanism), interactive research project grants (IRPG), and
the exploratory/developmental grant (R21) award mechanism. The total project
period for a research project grant (R01) application submitted in response to
this RFA may not exceed 5 years. The maximum dollar request for R01
applications is limited to $500,000 in direct costs for any one year. The
Exploratory/Developmental Grant (R21) award provides funds for exploratory
research projects (maximum of $100,000 in direct costs per year for two
years). Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant. These grants are non-
renewable, but continuation of projects developed under this program can be
supported by the investigator-initiated research project grant (R01).
All applications submitted in response to this RFA must be submitted in the
MODULAR GRANT and JUST-IN-TIME formats. Specific application instructions
have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining
efforts being examined by the NIH. The modular grant concept establishes
specific modules in which direct costs may be requested as well as a maximum
level for requested budgets. Only limited budgetary information is required
under this approach. The just-in-time concept allows applicants to submit
certain information only when there is a possibility for an award. It is
anticipated that these changes will reduce the administrative burden for the
applicants, reviewers and Institute staff. Complete and detailed instructions
and information on Modular Grants can be found at
http://www.nih.gov/grants/funding/modular/modular.htm.
The IRPG mechanism encourages interaction and collaboration among independent
scientists with common goals. It is intended to bring together research
projects from investigators who wish to collaborate but who do not require
extensive shared resources. There should be constructive interchange of
ideas, data and/or materials. A minimum of two independent investigators are
encouraged to submit concurrent, collaborative, cross-referenced individual
regular research (R01) applications. These applications must be free-standing
and contain independent hypotheses and aims. An application that provides
only a service to other applicants is not acceptable. Applicants may be from
one or several institutions. Potential applicants contemplating the
submission of an IRPG should contact the program official listed under
INQUIRIES as early as possible. Guidelines for preparing IRPG applications
are available from the program official or from the internet at:
https://grants.nih.gov/grants/guide/pa-files/PA-96-001.html
Applicants will request direct costs in $25,000 modules, up to a total direct
cost request of $500,000 per year for an R01 application and $100,000 per
year for an R21 application. A typical modular grant application will request
the same number of modules in each year.
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. If so,
a letter of agreement from either the GCRC program director or principal
investigator should be included with the application.
This RFA is a one-time solicitation. Future unsolicited competing
continuation applications will compete with all investigator-initiated
applications and be reviewed according to the customary peer review
procedures. Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant. The anticipated award
date is April 1, 2000.
FUNDS AVAILABLE
It is anticipated that for FY 2000, approximately $1,000,000 total costs will
be available for the first year of support for this initiative. However, this
funding level is dependent upon the receipt of a sufficient number of
applications of high scientific merit. Although this program is provided for
in the financial plans of the NIDDK, the award of grants pursuant to this RFA
is also contingent upon the availability of funds for this purpose. It is
anticipated that up to 3 to 5 new grants will be awarded under this program.
RESEARCH OBJECTIVES
Celiac disease (celiac sprue) is an autoimmune, gastrointestinal disorder
characterized by intolerance to dietary gluten. The large majority of
patients with celiac disease have at least one copy of the MHC type 2 HLA-DQ2
gene, but only a minority of persons with this genotype develop celiac
disease. The "classic" presentation is among children who present with
chronic diarrhea, bloating, anemia, and failure to gain weight. More
recently, this disease has been diagnosed increasingly among adults, who may
have minimal gastrointestinal symptoms and mild manifestations of
malabsorption. Relatives of celiac patients are at increased risk as are
persons with other autoimmune diseases such as type 1 diabetes mellitus and
primary biliary cirrhosis. Celiac disease is commonly diagnosed in Western
Europe, but is rarely identified in the United States, even among persons
descended from European immigrants. The possible reasons for this difference
in clinical recognition include: U.S. physicians may often fail to detect
typical celiac disease; celiac disease may be common but causes atypical or
mild symptoms; or the disease may actually be uncommon due to the influence of
unknown environmental factors. Recently, specific and sensitive serological
markers for celiac disease have been developed that allow for screening of
patients and special populations. These tests include antigliadin antibody,
IgA endomysium antibody, and the newer IgA tissue transglutaminase (tTG)
antibody. Application of specific serological assays to particular patient
populations should facilitate a better understanding of celiac disease in the
U.S.
The role of serological testing in either screening or evaluation of high-risk
populations has not been defined. It is also not clear how HLA testing should
be applied to diagnosis. Of primary interest are studies that will define the
prevalence of celiac disease in high-risk groups. These groups could include,
but are not limited to, relatives of patients with celiac disease, persons
with autoimmune conditions such as insulin dependent diabetes mellitus and
primary biliary cirrhosis, patients with diarrhea predominant functional bowel
disease, persons with IgA deficiency, and persons with early onset
osteoporosis. Such studies would require diagnostic confirmation of celiac
disease using standard tests, including small bowel mucosal biopsy. For
persons with antibody markers but not meeting criteria for diagnosis, despite
full diagnostic evaluation, clinical characterization and natural history are
of interest. Also of interest are population-based studies across the age
range of different sex and ethnic groups that would determine antibody
presence and association with other immunological markers, including HLA
genotypes.
It is anticipated that through systematic studies, this research will
determine whether celiac disease is as rare as sometimes perceived in the
United States and will define the utility of diagnostic testing in various
populations. A goal of this RFA is to obtain information on celiac disease
across as many identifiable groups as possible.
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 492B 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, Vol. 23,
No. 11, March 18, 1994 available on the web at the following URL address:
http://www.nih.gov/grants/guide/1994/94.03.18/notice-nih-guideline008.html
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 scientific and ethical reasons not to include them. 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:
http://www.nih.gov/grants/guide/notice-files/not98-024.html
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
LETTER OF INTENT
Prospective applicants are asked to submit, by June 22, 1999, a letter of
intent that includes a descriptive title of the proposed research; the name,
address, and telephone number of the Principal Investigator; the identities of
other key personnel and participating institutions; and the number and title
of the RFA in response to which the application may be submitted. Although a
letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows
NIDDK staff to estimate the potential review workload and avoid conflict of
interest in the review.
The letter of intent is to be mailed or faxed to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-37F, MSC 6600
Bethesda, MD 20892-6600
Telephone: (301) 594-8885
FAX: (301) 480-3505
APPLICATION PROCEDURES
Applications are to be submitted on the grant application form PHS 398 (rev.
4/98). Application 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,
email: GrantsInfo@nih.gov.
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 (PREVALENCE AND DIAGNOSIS OF CELIAC DISEASE) and number (DK-99-015) must
be typed on line 2 of the face page of the application form and the YES box
must be marked.
The modular grant concept establishes specific modules in which direct costs
may be requested as well as a maximum level for requested budgets. Only
limited budgetary information is required under this approach. The
just-in-time concept allows applicants to submit certain information only when
there is a possibility for an award. It is anticipated that these changes will
reduce the administrative burden for the applicants, reviewers and Institute
staff. The research grant application form PHS 398 (rev. 4/98) is to be used
in applying for these grants, with the modifications noted below.
BUDGET INSTRUCTIONS
The total direct costs must be requested in accordance with the program
guidelines and the modifications made to the standard PHS 398 application
instructions described below:
PHS 398
o FACE PAGE - Items 7a and 7b should be completed, indicating Direct Costs
(in $25,000 increments up to a maximum of $500,000) and Total Costs [Modular
Total Direct plus Facilities and Administrative (F&A) costs] for the initial
budget period. Items 8a and 8b should be completed indicating the Direct and
Total Costs for the entire proposed period of support.
o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4
of the PHS 398. It is not required and will not be accepted with the
application.
o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the
categorical budget table on Form Page 5 of the PHS 398. It is not required
and will not be accepted with the application.
o NARRATIVE BUDGET JUSTIFICATION - Use a Modular Grant Budget Narrative page.
(See http://www.nih.gov/grants/funding/modular/modular.htm for sample pages.)
At the top of the page, enter the total direct costs requested for each year.
o PERSONNEL - Under Personnel, list key project personnel, including their
names, percent of effort, and roles on the project. No individual salary
information should be provided. However, the applicant should use the NIH
appropriation language salary cap and the NIH policy for graduate student
compensation in developing the budget request.
For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the nearest
$1,000. List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of key personnel,
and the role on the project. Indicate whether the collaborating institution
is foreign or domestic. The total cost for a consortium/contractual
arrangement is included in the overall requested modular direct cost amount.
Provide an additional narrative budget justification for any variation in the
number of modules requested.
o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual's qualifications for a specific
role in the proposed project, as well as to evaluate the overall
qualifications of the research team. A biographical sketch is required for
all key personnel, following the instructions below. No more than three pages
may be used for each person. A sample biographical sketch may be viewed at:
http://www.nih.gov/grants/funding/modular/modular.htm
- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;
o CHECKLIST - This page should be completed and submitted with the
application. If the F&A rate agreement has been established, indicate the
type of agreement and the date. It is important to identify all exclusions
that were used in the calculation of the F&A costs for the initial budget
period and all future budget years.
o CONTACT - The applicant should provide the name and phone number of the
individual to contact concerning fiscal and administrative issues if
additional information is necessary following the initial review.
APPLICATIONS NOT CONFORMING TO THESE GUIDELINES WILL BE CONSIDERED
UNRESPONSIVE TO THIS RFA AND WILL BE RETURNED WITHOUT FURTHER REVIEW.
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 time of submission, two additional copies of the application must be sent
to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-37F, MSC 6600
Bethesda, MD 20892-6600
Applications must be received by July 22, 1999. If an application is received
after that date, it will be returned to the applicant without review.
Similarly, supplemental documents containing significant revision or additions
will not be accepted after that date, unless applicants are notified by the
Scientific Review Administrator. 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 substantial revisions of applications previously reviewed, but
such applications must include an introduction addressing the previous
critique.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by NIDDK. Incomplete and/or non-responsive applications will
be returned to the applicant without further consideration. Applications that
are complete and responsive will be evaluated for scientific and technical
merit by an appropriate scientific review group convened by the NIDDK in
accordance with the standard NIH peer review procedures. As part of the
initial merit review, all applications will 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 applications under review, will be
discussed, assigned a priority score, and receive a second level review by the
National Diabetes and Digestive and Kidney Diseases Advisory Council.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to discuss the following aspects
of the application 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 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 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?
(2) Approach: Are the conceptual framework, design, methods, 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?
(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?
All applications will also be evaluated for their ability to achieve the
stated goals of the RFA.
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also be
evaluated.
o The reasonableness of the proposed budget and duration in relation to the
proposed research
o The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.
The personnel category will be reviewed for appropriate staffing based on the
requested percent effort. The direct costs budget request will be reviewed
for consistency with the proposed methods and specific aims. Any budgetary
adjustments recommended by the reviewers will be in $25,000 modules. The
duration of support will be reviewed to determine if it is appropriate to
ensure successful completion of the requested scope of the project.
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit as determined by peer review
o Availability of funds
o Programmatic priorities
o The distinction from other meritorious proposals in regards to the study
populations
Schedule
Letter of Intent Receipt Date: June 22, 1999
Application Receipt Date: July 22, 1999
Date of Initial Review: October - November 1999
Review by Advisory Council: February 2, 2000
Anticipated Award Date: April 1, 2000
INQUIRIES
Inquiries are encouraged. The opportunity to clarify any issues or questions
from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
James Everhart, M.D., M.P.H.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AN-12J, MSC 6600
Bethesda, MD 20892-6600
Telephone: (301) 594-8878
FAX: (301) 480-8300
Email: je17g@nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Sharon Bourque
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-49, MSC 6600
Bethesda, MD 20892-6600
Telephone: (301) 594-8846
FAX: (301) 480-3504
Email: bourques@ep.niddk.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.848. 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 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.
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, and 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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