RELEASE DATE:  June 9, 2003

PA NUMBER: PA-03-136

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 using 
the electronic SF424 (R&R) application. Replacement R01 (PA-06-254) and 
R21 (PA-06-255) funding opportunity announcements have 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)
National Institute of Aging (NIA)
Office of Research on Women's Health (ORWH)

93.849, 93.866


o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations


The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 
National Institute on Aging (NIA), in cooperation with the National 
Institutes of Health (NIH) Office of Research on Women's Health (ORWH), 
invite applications for research studies which focus on basic cellular, 
molecular, genetic and developmental mechanisms of the normal and abnormal 
function of the bladder and lower urinary tract. An important goal of this 
initiative is to attract new and established investigators from a variety of 
basic science research areas to apply their knowledge, skills, and tools to 
studies of the bladder and lower urinary tract. Areas of special interest 
include, but are not restricted to, basic cellular biology of bladder 
epithelial and smooth muscle cells and connective tissues; organ innervation, 
vascularization and physiology; genomics and proteomics, including studies of 
age-related changes in gene expression; development of animal models; 
pathogen-host interactions in infectious conditions of the bladder; and 
developmental biology of the lower urinary tract including sex differences. 
Studies proposing the development and application of novel tools and 
technologies including methods of in vivo functional assessment and imaging 
are encouraged. Also, basic science studies addressing sex/gender differences 
that may predispose women to bladder and lower urinary tract disorders are 
encouraged. Another important goal is to promote productive research 
collaborations for study of the lower urinary tract between clinicians and 
basic scientists. This Program Announcement (PA) is presented as part of the 
ongoing commitment of the NIDDK, NIA, and ORWH to biomedical research aimed 
at improving bladder and lower urinary tract health. 


A. Background

Disorders of the urinary bladder and associated structures including urinary 
incontinence, chronic pelvic pain, urinary tract infections (UTIs), 
interstitial cystitis (IC), vesicoureteral reflux, and dysfunctional bladder 
emptying are a major cause of morbidity and impaired quality of life. As many 
as 35 million Americans are estimated to suffer from disorders and diseases 
of the bladder, with bladder disease affecting all ages, races, and ethnic 
groups. While bladder and urinary tract illness affects both genders, women 
are the primary victims of urinary incontinence, IC, and UTIs, as well as 
other diseases of the urinary system. In addition, many disorders of the 
bladder, such as urinary incontinence, change with age. Disordered bladder 
function is a common complication of diabetes. While some progress has been 
made in the diagnosis, management, and treatment of diseases of the bladder 
and lower urinary tract disease, these problems frequently remain 
intractable. This initiative is undertaken with the expectation that improved 
bladder health will eventually result from better understanding of the basic 
biology of these organs under normal and pathological conditions. 

The goal of the NIDDK, NIA, and ORWH in developing this PA is to promote 
high-quality, basic research that will lead to important discoveries relevant 
to bladder and lower urinary tract biology. It is anticipated these 
discoveries will aid future development of predictive early markers of 
disease, preventive measures, and more effective treatments for a wide range 
of bladder and lower urinary tract conditions and diseases. Achieving the 
goals outlined in this PA was deemed a high-priority by the Bladder Research 
Progress Review Group 
( and the ORWH

B. Objectives and Scope

This PA encourages basic cellular, molecular, developmental and genetic 
research relevant to the bladder and lower urinary tract. Basic research 
studies that address age and gender differences in bladder and lower urinary 
tract function are also encouraged. New and established investigators from 
related fields of study are encouraged to apply their expertise to these 
problem areas. Investigators with diverse basic science and clinical 
backgrounds are encouraged to develop collaborative research relationships. 
Discoveries resulting from these studies may serve as the basis for the 
development of new agents, techniques, and strategies for detecting, 
preventing, and treating diseases of the bladder and lower urinary tract, as 
well as dealing with bladder complications resulting from other diseases, 
such as diabetes. 

Basic research in the following areas are examples of areas of high interest:

o Epithelial cell biology, including function, growth, and differentiation of 
bladder urothelium; interactions of epithelium with mesenchyme; and the 
cellular and molecular basis for epithelial dysfunction in disease.

o Smooth muscle cell biology, including neuromodulation and neuronal 
characteristics of bladder smooth muscle, smooth muscle receptor and cell-
signaling mechanisms, as well as studies addressing bladder striated muscle 
and detrusor biology.

o Developmental biology, including the biology and genetics of early 
organogenesis and lower genitourinary tract development and dysfunction in 

o Studies of bladder innervation, including the developmental biology of 
organ innervation, studies of motor and sensory neurophysiology, imaging 
methods to assess organ innervation and studies of pain modulation in the 
bladder and pelvis. 

o Connective tissue research, including cell-extracellular matrix 
relationships in cell signaling and overall bladder function, deposition of 
matrix components, and the role of connective tissues in bladder 

o Molecular genetics, including identification of genetic mutations affecting 
bladder and lower urinary tract function and susceptibility to disease. 

o Development of animal models for basic science analyses of bladder and 
lower urinary tract function in vivo. 

o Immunology, including immune responses of the bladder and autoimmunity as a 
potential causal factor in bladder disease. 

o Host-pathogen interactions in urinary tract infections and latent 
infections and the role of latent infections as a potential causal factor in 
bladder disease. 

o Genomics and proteomics approaches to bladder biology and disease, 
including identification of disease markers (i.e. biomarkers) and genomic 
changes useful for prediction and diagnosis of disease or response to 

o Development and application of new and novel basic and clinical 
technologies, including cell and molecular imaging and techniques to separate 
and analyze individual, physiological relevant cell types and methods to 
study bladder function in vivo and to image whole organ function. 

o Molecular and cellular studies of bladder and lower urinary tract tissues 
that demonstrate how age related changes impact on the function of these 


This PA will use the National Institutes of Health R01 (Research Project) and 
R21 (Exploratory/Development Project) award mechanisms (for a description of 
R01 and R21 awards see  The R01 award 
represents an investigator-initiated research grant designed to support a 
discrete, specified research project performed by a principal investigator. 
R01 applications awarded through this PA will provide funds for a maximum 
period of five years and are renewable.  The R21 award represents an 
exploratory/developmental research grant for support of high-risk pilot and 
feasibility research designed to develop new ideas sufficiently to allow 
future submission of a full R01 application. R21 grants awarded through this 
PA will provide up to $275,000 for the two year period. No more than $200,000 
may be requested in any single year. The request should be tailored to the 
needs of the project.  Applicants are solely responsible for planning, 
directing, and executing the proposed project. 
This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  For applications with direct costs 
exceeding $250,000 follow the PHS 398 instructions for non-modular research 
grant applications. 

ELIGIBLE INSTITUTIONSYou 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


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. 

DATA SHARING: Data sharing achieves many important goals for the scientific 
community, such as reinforcing open scientific inquiry, encouraging diversity 
of analysis and opinion, promoting new research, testing of new or 
alternative hypotheses and methods of analysis, supporting studies on data 
collection methods and measurement, facilitating teaching of new researchers, 
enabling the exploration of topics not envisioned by the initial 
investigators, and permitting the creation of new data sets by combing data 
from multiple sources. Applications submitted in response to this PA must 
include a data sharing plan in the application. This plan will be reviewed 
for: 1) statements of willingness to share information fully; 2) adequate and 
clear strategies for sharing results, data, tools, and mice with the research 
community and/or websites maintained by the NIH; and 3) non-restrictive 
nature of included Material Transfer Agreements and Mouse Transfer Agreements 
In their applications investigators must acknowledge their willingness to 
fulfill these requirements. Additional, information regarding data sharing 
may be found at:


We encourage your inquiries concerning this PA and welcome the opportunity 
answer questions from potential applicants.  Inquiries may fall into two 
areas: scientific/research and financial or grants management issues.

o Direct your questions about scientific/research issues to:

Chris Mullins, Ph.D.
Director, Basic Cell Biology Programs
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Blvd., Room 637
Bethesda, MD. 20892-5458
Telephone: (301) 594-7717
FAX: (301) 480-3510

Leroy M. Nyberg, Jr., Ph.D., M.D.
Director, Urology Programs
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Blvd., Room 627
Bethesda, MD. 20892-5458
Telephone: (301) 594-7717
FAX: (301) 480-3510

Frank Bellino, PhD
Biology of Aging Program 
National Institute on Aging 
Gateway Building, Suite 2C231
Bethesda, MD  20892-9205
Telephone:  (301) 496-6402
FAX:  (301) 402-0010

Lisa Begg, Dr.P.H., R.N.
Director of Research Programs
Office of Research on Women's Health
Office of the NIH Director
National Institutes of Health/DHHS
Telephone: (301)496-7853
Fax: (301)402-1798

o Direct your questions about financial or grants management matters to:

Ms. Trude Hilliard
Grants Management Specialist
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Blvd., Room 717
Bethesda, MD. 20892
Telephone: (301) 594-8859
FAX: (301) 480-3504

Ms. Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone: (301)496-1472
FAX: (301)402-3672


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at  Application 
deadlines are also indicated in the PHS 398 application kit.

up to $250,000 per year in direct costs 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 includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at

Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:

o Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

o Obtain agreement from the IC staff that the IC will accept your application 
for consideration for award; and,
o 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  

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 mailed on or before the receipt 
dates described at 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 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.


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 
( 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 an appropriate advisory council or board.


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
The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application.  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.

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?

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?

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?

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)?

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?  

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
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 will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  


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.


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


HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained. 

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, 

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 "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 (
02-001.html); a complete copy of the updated Guidelines are available at
.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.

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 

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

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at and at  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see   
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 

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

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.

Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information", 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at

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  

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at

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

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