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 
https://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 
https://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:  mm102i@nih.gov

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: dh48v@nih.gov 

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 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: GrantsInfo@nih.gov.

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 https://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 
https://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 
https://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 
https://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 
https://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: 
https://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 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html, a 
complete copy of the updated Guidelines are available at 
https://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 
https://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: 
https://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 https://grants.nih.gov/grants/stem_cells.htm and at  
https://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:
https://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

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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