and Human Services (HHS)
EXPIRED
INTESTINAL FAILURE, SHORT GUT SYNDROME AND SMALL BOWEL TRANSPLANTATION
RELEASE DATE: September 9, 2002
PA NUMBER: PA-02-163
This PA has been reissued as PA-06-230 (R01) and PA-06-229 (R21)
EXPIRATION DATE: AFTER 10/01/05, unless reissued.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov)
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS PA
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
seeks grant applications to study the pathogenesis, natural history,
treatment and complications of intestinal failure and its therapies,
including parenteral nutrition and small bowel transplantation. Intestinal
failure, which is defined as reduced absorption of nutrients from the
gastrointestinal tract resulting in the need for parenteral nutrition for
survival, has many causes, including primary defects of intestinal epithelial
absorption, motility disorders, and loss of large portions of the intestine
due to surgical resection for congenital defects, necrotizing enterocolitis,
ischemia, trauma, and inflammatory bowel disease. It is estimated that
20,000 individuals in the United States are supported by parenteral nutrition
for intestinal failure and that the economic and quality of life burden for
these patients is very high. A small fraction of these patients undergo
small bowel transplantation, a treatment with significant morbidity,
mortality, and high cost. Thus, new fundamental discoveries that lead to
ways to prevent intestinal failure or its complications, to improve existing
therapies, parenteral nutrition or small bowel transplantation, or to devise
novel therapies, could lead to a significant improvement in quality of life
and decreased cost of care for patients suffering from intestinal failure.
RESEARCH OBJECTIVES
The overall objective of this PA is to encourage basic and clinical research
into intestinal failure, short gut syndrome and intestinal transplantation.
There are many causes of intestinal failure, each of which has varying
degrees of information regarding etiology and pathogenesis. Intestinal
failure can be due to intrinsic diseases of the gastrointestinal tract or
result from major loss or resection of the intestine (short gut syndrome).
By definition, therapy for intestinal failure relies on parenteral nutrition,
usually in conjunction with oral nutritional support. While some patients
may survive indefinitely using parenteral and oral nutritional support,
others suffer multiple complications, such as recurrent infection,
dehydration, vascular thrombosis, or progressive liver disease that may
result in death. A small number of patients with these complications may be
rescued by small bowel transplantation, which itself is associated with
numerous potential complications and requirement for lifelong
immunosuppression.
The specific objectives of this PA are to encourage research addressing the
overall problem of intestinal failure, which may include, but is not
restricted to any of the following topics:
o Studies of the etiology and pathogenesis of intestinal failure where
the cause is not well understood, especially necrotising enterocolitis
in infancy, congenital developmental defects, motility disorders,
defects of transport such as microvillus inclusion disease, and early
childhood inflammatory disorders of the gut.
o Studies of the genetic and molecular basis of gut development in animal
models that may lead to novel insights into intestinal failure.
o Basic and clinical studies of gut adaptation to intestinal failure,
including the role of nutrients, endogenous factors such as growth
factors, intestinal flora, and therapeutic agents.
o Studies to define nutrient requirements, either oral or parenteral,
necessary to maintain optimal health for patients with intestinal
failure.
o Studies of the complications of intestinal failure and its therapy,
particularly the etiology, diagnosis and treatment of liver disease
associated with parenteral nutrition.
o Basic or clinical research in small bowel transplantation, either in
animal models or humans, that aim to improve multiple aspects of
transplantation, including patient selection, transplantation
procedures, nutritional support, immunosuppression, and tolerance
induction.
o Research to improve diagnosis or treatment of complications of small
bowel transplantation, including graft rejection, infections or
diarrhea of unknown etiology following transplantation.
MECHANISM OF SUPPORT
This PA will use the National Institutes of Health (NIH) research
project grant (R01) and the Exploratory/Development Research Grant
(R21) award mechanisms. Responsibility for the planning, direction,
and execution of the proposed project will be solely that of the
applicant. The total project period for an R01 application submitted
in response to this PA may not exceed 5 years.
The R21 awards are to demonstrate feasibility and to obtain preliminary
data testing innovative ideas that represent clear departure from ongoing
research interests. These grants are intended to 1) provide initial support
for new investigators, 2) allow exploration of possible innovative new
directions for established investigators, and 3) stimulate investigators from
other areas to lend their expertise to research within the scope of this
solicitation. Applicants for the R21 must limit their requests to $100,000
direct costs per year and are limited to two years. These R21 grants will not
be renewable, continuation of projects developed under this program will be
through the regular research grant (R01) program.
Investigators interested in submitting a proposal for a small clinical study
or planning proposal for a large clinical study should review the Program
Announcement PAR-01-056 (see
http://grants.nih.gov/grants/guide/pa-files/PAR-01-056.html).
This PA uses just-in-time concepts. It also uses the modular and non-
modular budget formats. (see
http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in each
year of $250,000 or less, use the modular format. Otherwise, use the
standard PHS 398 application instructions.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Investigators new to diabetes and
digestive and kidney diseases are encouraged to apply. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are encouraged to apply for NIH programs.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this PA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into two
areas: scientific/research, and financial or grants management issues.
o Direct inquiries regarding programmatic issues in digestive diseases and
nutrition to:
Dr. Michael K. May
Gastrointestinal Neuroendocrinology Program Director
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 663, MSC 5450,
Bethesda MD 20892-5450
Telephone: 301-594-8884
Fax: 301-480-8300
Email: [email protected]
o Direct inquiries regarding fiscal matters to:
Ms. Donna Huggins
Supervisory Grants Management Specialist
Grants Management Branch, DEA
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 711
MSC 5456
Bethesda, MD 20892-5456
(For Express Mail Use Zip Code 20817)
Telephone: (301) 594-8848
Fax: (301) 480-3504
Email: [email protected]
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). The PHS 398 is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone (301) 710-0267,
Email: [email protected].
SPECIFIC INSTRUCTIONS FOR R21 APPLICATIONS
All application instructions outlined in the PHS 398 application kit are to
be followed, with the following requirements for R21 applications:
1. R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME"
concepts, with direct costs requested in $25,000 modules, up to the total
direct costs limit of $100,000 per year.
2. Although preliminary data are not required for an R21 application, they
may be included.
3. Sections a-d of the Research Plan of the R21 application may not exceed
15 pages, including tables and figures.
4. R21 appendix materials should be limited, as is consistent with the
exploratory nature of the R21 mechanism, and should not be used to circumvent
the page limit for the research plan. Copies of appendix material will only
be provided to the primary reviewers of the application and will not be
reproduced for wider distribution. The following materials may be included
in the appendix:
o Up to five publications, including manuscripts (submitted or accepted
for publication), abstracts, patents, or other printed materials
directly relevant to the project. These may be stapled as sets.
o Surveys, questionnaires, data collection instruments, and clinical
protocols. These may be stapled as sets.
o Original glossy photographs or color images of gels, micrographs, etc.,
provided that a photocopy (may be reduced in size) is also included
within the 15 page limit of items a-d of the research plan
APPLICATION RECEIPT DATES: Applications submitted in response to this program
announcement will be accepted at the standard application deadlines, which
are available at http://grants.nih.gov/grants/dates.htm. Application
deadlines are also indicated in the PHS 398 application kit.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications with
direct costs in each year of $250,000 or less must be submitted in a modular
grant format. The modular grant format simplifies the preparation of the
budget in these applications by limiting the level of budgetary detail.
Applicants request direct costs in $25,000 modules. Section C of the
research grant application instructions for the PHS 398 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step
guidance for preparing modular grants. Additional information on modular
grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.
SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER
YEAR:
Applications requesting $500,000 or more in direct costs for any year must
include a cover letter identifying the NIH staff member who has agreed to
accept assignment of the application.
Applicants requesting more than $500,000 must carry out the following steps:
1) Contact the IC program staff at least 6 weeks before submitting the
application, i.e., as you are developing plans for the study,
2) Obtain agreement from the IC staff that the IC will accept your
application for consideration for award, and
3) Identify, in a cover letter sent with the application, the staff member
and IC who agreed to accept assignment of the application. This policy
applies to all investigator-initiated new (type 1), competing continuation
(type 2), competing supplement, or any amended or revised version of these
grant application types. Additional information on this policy is available
in the NIH Guide for Grants and Contracts, October 19, 2001 at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the checklist, and five 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)
APPLICATION PROCESSING: Applications must be received by or mailed on or
before the receipt dates described at
http://grants.nih.gov/grants/funding/submissionschedule.htm. The 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.
This does not preclude the submission of a substantial revision of an
application already reviewed, but such application must include an
Introduction addressing the previous critique.
PEER REVIEW PROCESS
Applications submitted for this PA will be assigned on the basis of
established PHS referral guidelines. An appropriate scientific review group
convened in accordance with the standard NIH peer review procedures
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific
and technical merit.
As part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o 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:
o Significance
o Approach
o Innovation
o Investigator
o Environment
(1) Significance: Does this study address an important problem? If the aims
of your 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? Do you 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: Are you appropriately trained and well-suited to carry out
this work? Is the work proposed appropriate to your experience level as the
principal investigator and to that of other researchers (if any)?
(5) Environment: Does the scientific environment in which your work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
support?
The scientific review group will address and consider each of these criteria
in assigning your application"s overall score, weighting them as appropriate
for each application. Your 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.
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
PROTECTIONS: 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.
INCLUSION: The adequacy of plans to include subjects from both genders, all
racial and ethnic groups (and subgroups), and children as appropriate for the
scientific goals of the research. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria included in the
section on Federal Citations, below).
DATA SHARING: The adequacy of the proposed plan to share data.
BUDGET: The reasonableness of the proposed budget and the requested period
of support in relation to the proposed research.
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
REQUIRED FEDERAL CITATIONS
MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components
involving Phase I and II clinical trials must include provisions for
assessment of patient eligibility and status, rigorous data management,
quality assurance, and auditing procedures. In addition, it is NIH policy
that all clinical trials require data and safety monitoring, with the method
and degree of monitoring being commensurate with the risks (NIH Policy for
Data Safety and Monitoring,
NIH Guide for Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
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
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," published in the NIH Guide for
Grants and Contracts on October 9, 2001
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html, a
complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of
clinical research, updated racial and ethnic categories in compliance with
the new OMB standards, clarification of language governing NIH-defined Phase
III clinical trials consistent with the new PHS Form 398, and updated roles
and responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable,
and b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
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 is available at
http://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:
NIH policy requires education on the protection of human subject participants
for all investigators submitting NIH proposals for research involving human
subjects. You will find this policy announcement in the NIH Guide for Grants
and Contracts Announcement dated June 5, 2000, at the following website:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding (see
http://escr.nih.gov). It is the responsibility of the applicant to provide
the official NIH identifier(s)for the hESC line(s)to be used in the proposed
research. Applications that do not provide this information will be returned
without review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency in
support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for applicants to
understand the basic scope of this amendment. NIH has provided guidance at:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm
Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and
proposals for NIH funding must be self-contained within specified page
limitations. Unless otherwise specified in an NIH solicitation,
internet addresses (URLs) should not be used to provide information
necessary to the review because reviewers are under no obligation to
view the Internet sites. Reviewers are cautioned that their anonymity
may be compromised when they directly access an Internet site.
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. This PA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.848. Awards are made under authorization of sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284)
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, 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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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