ENDOSCOPIC CLINICAL RESEARCH IN PANCREATIC AND BILIARY DISEASES  

RELEASE DATE:  November 21, 2002

PA NUMBER: PAR-03-033

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov  using 
the electronic SF424 (R&R) application. A replacement R03 (PAR-06-171) funding 
opportunity announcement has been issued for the submission date of June 1, 2006 
and submission dates thereafter. 

EXPIRATION DATE: After October 1, 2005, unless reissued. 

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov/)
National Cancer Institute (NCI)
 (http://www.nci.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 Submitting an Application
o Applications receipt dates
o Specific Instructions for Modular Grant Applications
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA  

The Division of Digestive Diseases and Nutrition (DDDN) of the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)  and  the  
Division of Cancer Prevention of the  National Cancer Institute encourage 
innovative clinical and epidemiological research into the role of Endoscopic 
Retrograde Cholangiopancreatography (ERCP) and other endoscopic and imaging 
techniques.  Acute and chronic pancreatic and biliary diseases are common in 
the United States and account for considerable morbidity, mortality and 
health care costs.  The spectrum of conditions includes those due to cancer 
of the exocrine and endocrine pancreas, gallstones, sludge, pancreatic and 
biliary malignancy, trauma, anatomic problems (pancreas divisum), alcohol and 
drugs and idiopathic syndromes such as idiopathic pancreatitis and sphincter 
of Oddi dysfunction. The recently held National Institutes of Health State-
of-the-Science Conference Statement on ERCP indicated that while ERCP and 
other advanced endoscopic and imaging techniques have gained widespread 
application in clinical practice,  there is little evidence based on rigorous 
clinical trials to guide the use of advanced diagnostic and therapeutic 
technologies in clinical practice decisions. The small grants (R03) may be 
used as planning grants for full-scale multi-center clinical trials or for 
pilot studies that could lead to full-scale multi-center clinical trials 
designed to provide evidence for or against changes in the current standard 
of care.  Pilot epidemiological studies are encouraged that could lead to 
more extended research that would provide evidence for or against changes in 
health policy, especially as related to disease and cancer prevention.  It is 
expected that these R03 grants will serve as a basis for planning future 
multi-center research project grant applications (R01) or cooperative 
agreement (U01) awards.  New and experienced investigators in relevant fields 
and disciplines may apply for these small grants.  Investigators are 
encouraged to take advantage of  recent  endoscopic and laboratory 
developments.  In addition, the small grant is a good mechanism for new and 
experienced investigators to become better equipped to perform clinical and 
epidemiological research.

RESEARCH OBJECTIVES

Background

Diseases of the gallbladder, pancreas, and liver are conditions that are 
frequently encountered in clinical practice.  Examination of the biliary and 
pancreatic ducts is often required for the appropriate diagnosis and 
management of patients with pancreatic and hepatobiliary diseases. Over the 
last three decades, the dramatic improvement of flexible endoscopes has 
established endoscopy as the primary method to diagnose and treat many 
pancreatic and biliary diseases.

Although ERCP first came into use about 30 years ago and has been applied to 
the diagnosis and management of a variety of gastrointestinal disorders, the 
value of ERCP relative to other means for diagnosing and treating these 
diseases has not been firmly established. Over the last two decades, there 
has been the development of new diagnostic and therapeutics tools – 
ultrasound, standard and helical computer tomography, magnetic resonance 
imaging (MRI), magnetic resonance cholangiography (MRCP), endoscopic 
ultrasound, and intraoperative cholangiography with potential usefulness in 
management of pancreatic and hepatobiliary diseases. Each of these tools has 
variable detail and accuracy.  A recent State-of-the-Science Conference on 
ERCP in diagnosis and therapy was held at the NIH on January 14-16, 2002 
(http://consensus.nih.gov/ta/020/020sos_intro.htm) Several of the 
recommendations of the conference included the need to improve the quality of 
clinical trials for the study of pancreaticobiliary diseases as well as to 
evaluate ERCP and other and newer technologies in assessing 
pancreaticobiliary diseases.    

The goal of this small grants program is to provide flexibility for 
initiating preliminary, short-term studies, thus allowing new ideas to be 
investigated in a more expeditious manner without requirements for 
preliminary data.  Such support is needed to encourage experienced 
investigators as well as new investigators to pursue new approaches, 
underdeveloped topics, or more risky avenues of research.  If successful, 
these awards should lead to significant scientific advances in defining the 
role of  Endoscopic Retrograde Cholangiopancreatography (ERCP) and other 
advanced endoscopic interventional and imaging techniques in the prevention, 
diagnosis and management of  pancreatic and biliary diseases.

This PA will encourage clinical research in a number of areas:  

Comparisons of  interventional endoscopic procedures vs. interventional 
radiological approaches vs. surgery for treatment of different complications 
of chronic pancreatitis.  

Studies of the role of endoscopic interventions for acute pancreatitis, 
chronic pancreatitits or its complications.  

Studies of the role of ERCP in sphincter of Oddi dysfunction  (biliary or 
pancreatic sphincter) 

Clinical studies of early detection and diagnosis, prognostication, 
prevention and treatment of  acute and chronic pancreatitis as well as 
pancreatic cancer 

The clinical significance, natural history, and management of microlithiasis 
or "biliary sludge"  in the pathogenesis of pancreatitis.  

Clinical studies of the role of endoscopic and other advanced technologies in 
early diagnosis, staging or treatment of biliary or pancreatic malignancy; 
including but not limited to the collection of pancreatic juice for the 
chemical analysis, cytopathology, proteomics, and gene expression 
microarrays. .   

Other studies of pancreatic and biliary diseases that compare ERCP, 
diagnostic imaging or surgical approaches.

Studies to  enhance and evaluate training for laparoscopic common bile duct 
exploration (and other surgical techniques) and to improve training for 
advanced endoscopy. 

Development of endoscopic and laparoscopic  simulators and other new 
technologies to facilitate training, maintenance  and objective assessment of  
procedural performance.

MECHANISM OF SUPPORT 

This PA will use the NIH small grant (R03) award mechanism.  Responsibility 
for the planning, direction, and execution of the proposed project will be 
solely that of the applicant.  This PA uses just-in-time concepts.  It also 
uses the modular budgeting format.

The total project period for an application submitted in response to this PA 
may not exceed two years.  The budget may be submitted for direct costs up to 
$100,000 per year, in modules of $25,000. 

Complete and detailed instructions and information on Modular Grant 
applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.  

Only one revision is permitted.  These grants may not be renewed. 

Replacement of the Principal Investigator on the grant is not permitted.

Applications submitted in response to this PA will compete for funds with all 
other R03 and regular research project grant (R01) applications. The award of 
grants in response to this PA is also contingent upon the availability of 
funds.  

Applicants from institutions that have a General Clinical Research Center 
(GCRC) funded by the 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.

Applicants are encouraged to collaborate with the Directors of the Silvio O. 
Conte Digestive Diseases Centers, Clinical Nutrition Research Centers, and 
Obesity/Nutrition Research Centers for consultation in experimental design, 
intervention, and methodology, as well as usage of core facilities 
appropriate for carrying out their projects.  Information describing the 
centers and their cores can be requested from individuals listed under 
scientific/research INQUIRIES.

ELIGIBLE INSTITUTIONS 

Foreign Institutions are not eligible to submit applications in response to 
this PA.

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 

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. Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

This PA for small grant support is for new projects only; competing 
continuation applications will not be accepted.  Submission of an application 
under this PAR precludes concurrent submission of any other Public Health 
Service application containing substantially the same research proposal.  In 
addition, these R03 awards may not be used to supplement research projects 
currently supported by Federal or non-Federal funds, or to provide interim 
support of projects under review by the Public Health Service.

To be eligible for this award, the proposed Principal Investigator must be an 
independent researcher.  New investigators are eligible, but they must be 
independent of a mentor and have strong institutional support.  Small grant 
support may not be requested for thesis or dissertation research.  
Investigators who have questions about eligibility should contact one of the 
officials listed under INQUIRIES.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PAR and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

Frank Hamilton M.D., M.P.H.
Gastrointestinal Motility Program Director
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 669
Bethesda, MD  20817-5450
Phone: 301-594-8877
FAX:   301-480-8300
Email:  fh14e@nih.gov 

Jose Serrano M.D., Ph.D.
Liver and Biliary Diseases Program Director
Division of  Digestive Diseases and Nutrition
National Institute of  Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 657
BETHESDA MD 20892-5450
Phone: 301  594-8871 
FAX:   301 480-8300
EMAIL: js362q@nih.gov

William F. Anderson, MD MPH
GI and Other Cancers Research Group
National Cancer Institute, Division of Cancer Prevention
EPN 2144
6130 Executive Blvd
Bethesda, MD 20892-7317
Phone: 301-594-7672
FAX: 301 435-6344
EMAIL: wa31i@nih.gov

o Direct your questions about peer review issues to:

Francisco Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of  Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 752
Bethesda, MD  20892-5452
Phone: 301-594-8897
FAX:   301-480-3505
Email:  fc15y@nih.gov
 
o Direct your questions about financial or grants management matters to:

Ms. Donna Huggins
Grants Management Specialist
Division of Extramural Activities
National Institute of  Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 711 
Bethesda, MD  20892-5456
Pone: 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 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact Grants Info, Telephone (301) 435-
0714, Email: GrantsInfo@nih.gov.

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

Instructions outlined in the PHS 398 application kit are to be followed, with 
the modifications noted below.

o The title, "Endoscopic Clinical Research in Pancreatic and Biliary Diseases  
(R03)" and number of this PA must be typed on line two of the face page and 
the YES box must be marked.

o Items a - d of the Research Plan [Specific Aims, Background and 
Significance, Preliminary Studies (not required), and Research Design and 
Methods] may not exceed a total of ten pages.  Detailed descriptions of 
protocols for the proposed involvement of human subjects and/or vertebrate 
animals, literature cited, consortium/contractual arrangements and consultant 
letters are not included in the ten-page limit.

o Professional credentials of the participating center investigators in the 
clinical problem and in clinical trial participation.  Verification of the 
cooperating investigators and their institutions will be required later if 
considered for funding.

o Publications may not be submitted, but color/glossy photographs and other 
appendix material (surveys, questionnaires, etc.) is permitted.

SENDING AN APPLICATION TO THE NIH: 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 the time of submission, two additional copies of the application must be 
submitted to:

Francisco Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 752
Bethesda, MD  20892-5452
Phone: 301-594-8897
FAX:   301-480-3505
Email:  fc15y@nih.gov

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 by the NIDDK. 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 Institutes of 
Health 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 your 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
  
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, you 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 your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
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? Note: The R03 mechanism does not require that preliminary data be 
submitted.

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your 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?

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. 

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program 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 CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating 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 clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," 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: 
The NIH maintains a policy 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 
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. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

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.   Furthermore, 
we caution reviewers 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 and 93.395 (NCI) and is not subject to 
the intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  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 described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files.