RESEARCH STUDIES ON THE HEREDITARY CALCIUM OXALATE STONE DISEASES
Release Date: April 27, 2000
PA NUMBER: PA-00-091
National Institute of Diabetes and Digestive and Kidney Diseases
THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA.
PURPOSE
Urinary tract stone disease constitutes a major health care burden for the
United States population. Calcium oxalate is the major constituent of these
urinary tract stones. Studies suggest that a subset of persons who have
chronic, recurrent urinary tract stone disease have a familial predisposition
to the disease. The etiology and the genetic abnormality in these persons
are not known. However, there is a group of individuals with known inherited
disorders who develop recurrent calcium oxalate stones at a very early age.
These persons have a genetic metabolic disorder known as primary
hyperoxaluria in which a genetic defect causes excessive excretion of oxalate
in the urine. These primary hyperoxaluria disorders have been shown to be
due to a defect in the regulation of oxalate synthesis in the liver,
resulting in an accumulation of excess oxalate. The purpose of this Program
Announcement is to increase investigator interest in research into the
genetics and heritability of oxalate regulation and the oxalate stone
diseases. The Division of Kidney and Urologic and Hematologic Diseases of
the NIDDK has set aside specific funds for pilot and feasibility studies
which utilize new and innovative approaches to the study of these disorders.
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, for-profit and
nonprofit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal Government. Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as principal
investigators.
MECHANISM OF SUPPORT
This PA will use the National Institutes of Health (NIH) pilot and
feasibility project grant (R21) award mechanism. Responsibility for the
planning, direction, and execution of the proposed project will be solely
that of the applicant. The total project period for an application submitted
in response to this PA may not exceed two years. The total amount of direct
costs to be requested for each of the two years may not exceed $100,000 per
year.
Specific application instructions have been modified to reflect "MODULAR
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH.
Complete and detailed instructions and information on Modular Grants can be
found at http://grants.nih.gov/grants/funding/modular/modular.htm
DURATION OF PROGRAM ANNOUNCEMENT
This PA will remain active for two years, until October 2002, at which time
applications may no longer be submitted in response to this program
announcement.
RESEARCH OBJECTIVES
Although calcium oxalate stone disease is a very common health problem in the
United States, there is very little new, innovative research being applied to
the understanding of the etiology, risk factors, or genetic basis of this
chronic disease. This announcement focuses on the heritable oxalate stone
disorders in an attempt to better understand the metabolic and genetic
defects responsible for the disease and to eventually develop more effective
treatment and preventive strategies. The calcium oxalate stone disease that
is most commonly identified in adults is poorly understood from a basic
science point of view. It is known that this disease tends to occur within
families but pedigrees have not been well established or studied.
A rare, heritable cause of nephrolithiasis has been identified and
characterized. This disorder results in the onset of oxalate stone disease
early in childhood and can frequently lead to renal failure. This disease
(primary hyperoxaluria) is due to a defect in the liver peroxisomes of the
enzyme alanine-glyoxylate aminotransferase (AGT), which catalyzes the
transamination of glyoxylate to glycine. The non-catalized glyoxylate is
oxidized to oxalate and is excreted in excess in the urine.
To address these issues and others related to calcium oxalate stone disease,
the following are some areas in which it is suggested that applications be
submitted:
o develop strategies to replace the gene defect in oxalosis and
hyperoxaluria,
o develop strategies for development of new animal models for the study of
the calcium oxalate stone diseases,
o develop strategies to assemble and investigate family pedigrees with
calcium oxalate stone disease for risk factors, genetic defects, and other
related factors.
Research applications need not be limited to those areas listed above. All
innovative proposals related to the subject are encouraged.
Summary
It is anticipated that, as a result of the grants funded with this PA, new
and innovative approaches will have been developed addressing the genetics
and heritability of oxalate regulation and the oxalate stone diseases, and
that the data obtained from these pilot studies will be effectively utilized
by the investigators to submit competitive investigator-initiated R01
research grant applications.
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 are 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
http://grants.nih.gov/grants/guide/notice-files/not94-100.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.
This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators may also obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
APPLICATION PROCEDURES
Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted at the standard application deadlines as indicated
in the application kit. Application kits are available at most institutional
offices of sponsored research, or 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.
Competing continuation (type 2), competing supplement, or any amended/revised
version of the preceding grant application types are not relevant
applications for submission under the guidelines of this PA.
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
Modular Grant applications will request direct costs in $25,000 modules, up
to a total direct cost request of $100,000 per year. 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 $100,000) 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: Prepare a Modular Grant Budget Narrative
page. (See http://grants.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. This is not a Form page.
o 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.
Include the Letter of Intent to establish a consortium. Indirect costs for
subcontracts are included in the total cost budget for the R21 applications
submitted in response to this PA. The subcontract costs should not be in
modular format but should be rounded to the nearest $1000.
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://grants.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. All appropriate exclusions must be applied in
the calculation of the F&A costs for the initial budget period and all future
budget years.
o 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. The program announcement title
and number must be typed on line 2 of the face page of the application form
and the YES box must be marked.
Submit the signed, original, single-sided application, including the
Checklist, along with five signed photocopies and five collated sets of
appendix materials 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)
The Center for Scientific Review (CSR) will not accept any application in
response to this PA 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, however, amended applications either investigator initiated
or previously submitted in response to the PA may be submitted in response to
this RFA, but must meet the guidelines delineated in this announcement.
REVIEW CONSIDERATIONS
Applications will be assigned on the basis of established Public Health
Service referral guidelines. Applications will be evaluated for scientific
and technical merit by an appropriate scientific review group convened 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 appropriate national advisory council or board.
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.
o 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?
o 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?
o Innovation: Does the project employ novel concepts, approaches, or
methods? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies?
o 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)?
o 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?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o 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. The
reasonableness of the proposed budget and duration to the proposed research
will also be reviewed..
o The adequacy of the proposed protection of humans, animals, or the
environment, to the extent that they may be adversely affected by the project
proposed in the application.
o Availability of special opportunities for furthering research programs
through the use of unusual talent resources, populations, or environmental
conditions in other countries which are not readily available in the United
States or which provide augmentation of existing U.S. resources.
AWARD CRITERIA
Applications will compete for available funds with all other approved
applications assigned to the National Institute of Diabetes and Digestive and
Kidney Diseases. The following will be considered in making funding
decisions:
o Quality of the proposed project as determined by peer review,
o Availability of funds,
o Program priority.
INQUIRIES
Inquiries are encouraged. The opportunity to clarify any issues or questions
from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Leroy M. Nyberg, Jr., Ph.D., M.D., Urology Programs
DKUHD/NIDDK
6707 Democracy Blvd, rm 627
Bethesda, MD 20892-5458
Telephone: (301) 594-7717
FAX: (301)-480-3510
E-mail: NybergL@extra.niddk.nih.gov
or
Monica Liebert, Ph.D., Urology Programs
DKUHD/NIDDK
6707 Democracy Blvd, rm 623
Bethesda, MD 20892-5458
Telephone: (301) 594-7717
FAX: (301)-480-3510
E-mail: liebertm@extra.niddk.nih.gov
Direct inquiries regarding fiscal and administrative matters to:
Ms. Trude Hilliard
Division of Extramural Activities
NIDDK
6707 Democracy Blvd, rm 643
Bethesda, MD 20892
Telephone: (301) 594-5452
E-Mail: HilliardT@extra.niddk.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93. 93.849. 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 NIH grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not
subject to the intergovernmental review requirements of Executive Order 12372
or Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products. In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
|
|
|
|
Department of Health and Human Services (HHS)
|
|
|
|
NIH... Turning Discovery Into Health®
|