RELEASE DATE:  May 16, 2003

PA NUMBER:  PA-03-123 (This PA has been reissued, see PA-06-033 and PA-06-034)

EXPIRATION DATE: October 27, 2005

National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


APPLICATION RECEIPT DATES: Applications submitted in response to this 
program announcement will be accepted at the standard SBIR/STTR 
application deadlines: April 1, August 1, and December 1.

NOTICE: This program announcement (PA) must be read in conjunction with 
the current Omnibus Solicitation of the National Institutes of Health, 
Centers for Disease Control and Prevention, and Food And Drug Food and 
Drug Administration for Small Business Innovation Research (SBIR) and 
Small Business Technology Transfer (STTR) Grant Applications. (see The 
solicitation contains information about the SBIR and STTR programs, 
regulations governing the programs, and instructional information for 
submission. All of the instructions within the current SBIR/STTR 
Omnibus Solicitation OMNIBUS SBIR/STTR SOLICITATION apply, with the 
following exceptions:


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


This announcement invites grant applications for Small Business 
Innovation Research (SBIR) and Small Business Technology Transfer 
Research (STTR) projects to develop a non-invasive or minimally 
invasive, rapid, and practical diagnostic screening test for salt 
sensitivity of blood pressure.  Ideally, such a test correlates with 
long-term changes in blood pressure resulting from a high salt intake.  
It must be feasible for use in the general population, both in terms of 
low cost and use on an out-patient basis.



More than 50 million Americans have hypertension, which is a major risk 
factor for stroke and heart disease.  Excess dietary sodium is one of 
the most important environmental risk factors for hypertension.  
Besides increasing blood pressure, emerging scientific evidence 
indicates that excess sodium intake also can have deleterious effects 
on organs such as the kidney and heart, as well as increase the 
mortality rate later in life, even in the absence of hypertension.

Therefore, strategies to reduce salt intake in the general population 
are of the utmost importance to public health.  General dietary 
guidelines from the National Heart, Lung, and Blood Institute and from 
the American Heart Association include the recommendation to limit 
dietary sodium chloride intake to six grams per day.  This 
recommendation is especially important for individuals with excessive 
salt-sensitivity, i.e., with exaggerated blood pressure responses to 
variations in sodium intake.  Presently there is no easy test to 
identify these susceptible individuals.  

Research in animals and humans has made great strides in understanding 
the complex molecular pathways that underlie salt sensitivity of blood 
pressure.  Molecular and genetic studies support the decades-old 
concept that sodium is a major contributing factor to blood pressure.  
Family studies suggest a heritable contribution to salt sensitivity.  
Despite an intensive search in recent years for candidate genes for 
essential hypertension and salt sensitivity, identification of 
significant effects by single gene polymorphisms remains elusive.  
Similar to blood pressure itself, salt sensitivity is now known to be a 
continuous, multigene, multifactorial variable.  Among recently 
discovered molecular markers for salt sensitivity are GRK4gamma gene 
variants that reduce kidney dopamine activity and the N-terminal 
fragment of atrial natriuretic peptide prohormone (proANP1-30).  Using 
modern proteomic methodologies, major sodium channel and transporter 
proteins expressed along the renal tubule, such as the amiloride-
sensitive epithelial sodium channel (ENaC), the sodium hydrogen 
exchanger (NHE3), the thiazide-sensitive sodium chloride cotransporter 
(NCC), and the bumetanide-sensitive sodium potassium 2chloride 
cotransporter (NKCC2), have been detected in human as well as rat 
urine; furthermore, the amount of excreted proteins reflect changes in 
kidney tissue.  Thus, urinalysis of the sodium channel and transporters 
has the potential to be developed for the clinical detection of 
disorders of sodium excretion or reabsorption. 

In hypertension research, the usual method of measuring salt 
sensitivity is dietary manipulation which typically takes about two 
weeks.  It compares blood pressure after a week of low salt intake to 
blood pressure after a week of high salt intake, under carefully 
controlled conditions.  A shorter, three-day "acute" clinical test for 
salt sensitivity includes the infusion of an isotonic saline solution 
for four hours followed by the administration of a diuretic accompanied 
by a low salt diet the next day.  Blood pressures are measured before, 
during, and after this procedure.  The difference in blood pressure 
between the salt-replete and salt-deplete states defines the level of 
salt sensitivity.  Both methods are neither practical nor feasible as 
screening tests for the general population. Further, some studies of 
such protocols suggest limited reproducibility.  

There is a great need for an easily administered screening test for 
salt sensitivity, which could be included in a routine physical 
examination to identify salt sensitive individuals for targeted 
preventive efforts.  New genomic and proteomic approaches, in addition 
to recently discovered molecular markers for salt sensitivity, provide 
evidence that a more concerted effort at developing a sophisticated, 
practical test has a high likelihood of success.

Accurate diagnostic screening test results would provide strong 
incentives for susceptible individuals to decrease their salt intake.  
Moreover, a simple screening test could be very useful as a research 
tool, especially for clinical investigations of the biologic mechanisms 
underlying salt sensitivity and its pathophysiological consequences.  
Therefore, this initiative seeks new ideas and approaches from the 
entrepreneurial, small business community to develop a practical, acute 
clinical test to diagnose salt sensitivity. 

Research Topics

Examples of research topics that would be considered responsive to this 
PA include, but are not limited to, the following:

o A practical test that can rapidly determine salt sensitivity by 
demonstrating precise blood pressure changes between states of high and 
low salt in the body

o A test using blood, urine, or buccal tissue to examine a panel of 
gene variants, proteins, peptides or chemicals that can be used as 
surrogate markers for salt sensitivity, such as:
o Sodium channel and transporter proteins or gene variants, e.g., ENaC, 

o Regulators of sodium excretion, e.g., proteins that modulate dopamine 
activity in the kidney and proteins that reflect levels of natriuretic 

o Regulators of sodium reabsorption, e.g., aldosterone and vasopressin 
or their modulators


This PA uses the NIH SBIR and STTR award mechanisms, which are set-
aside programs. As an applicant, you will be solely responsible for 
planning, directing, and executing the proposed project.  Future 
unsolicited, competing-continuation applications based on this project 
will compete with all SBIR/STTR applications and will be reviewed 
according to the customary peer review procedures.  This PA uses just-
in-time concepts.  It also uses the modular as well as the non-modular 
budgeting formats specifically for SBIR and STTR grant applications as 
described in the current SBIR/STTR Omnibus Solicitation.  Specifically, 
if you are submitting an application budget of $100,000 or less in 
total costs (direct, F&A and fee) each year, use the modular format.  
Otherwise follow the instructions for non-modular research grant 
applications.  This program does not require cost sharing as defined in 
the current NIH Grants Policy Statement at
Except as otherwise stated in this PA, awards will be administered 
under NIH grants policy as stated in the NIH Grants Policy Statement, 
March 2001, available at  

Applications may be submitted for support as Phase I STTR (R41) or 
Phase I SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) 
grants.  Phase II applications in response to this PA will only be 
accepted as competing continuations of previously funded NIH Phase I 
SBIR/STTR awards.  The Phase II application must be a logical extension 
of the Phase I research but not necessarily a Phase I project supported 
in response to this PA.  


The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines 
of funding support and project duration periods for SBIR and STTR Phase 
I and Phase II awards.  For this PA, budgets up to $150,000 total costs 
per year and time periods up to 2 years may be requested for Phase I.  
Budgets up to $500,000 total costs per year and up to 3 years may be 
requested for Phase II.  Total costs include direct costs, F&A, and a 


Eligibility requirements are described in the SBIR/STTR Omnibus 
Solicitation.  Only small business concerns are eligible to submit 
applications. A small business concern is one that, on the date of 
award for both Phase I and Phase II agreements, meets ALL of the 
criteria as described in the SBIR/STTR Omnibus Solicitation.


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.  On an 
SBIR application, the principal investigator must have his/her primary 
employment (more than 50%) with the small business at the time of award 
and for the duration of the project. The PI on an STTR application may 
be employed with the small business concern or the participating non-
profit research institution as long as s/he has a formal appointment 
with or commitment to the applicant small business concern, which is 
characterized by an official relationship between the small business 
concern and that individual. 


We encourage your 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 your questions about scientific/research issues to:

Winnie Barouch, Ph.D.
Division of Heart and Vascular Diseases 
National Heart, Lung, and Blood Institute 
6701 Rockledge Drive, Suite 10193 MSC 7956
Bethesda, MD 20892-7956
Bethesda, MD 20817 (for express/courier service)
Telephone:  (301)435-0560
FAX:  (301)480-2849

Marva Moxey-Mims, M.D., F.A.A.P.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 639, MSC 5458
Bethesda, MD  20892-5458
Phone:  (301) 594-7717   
Fax:  (301) 480-3510

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

Shelia Ortiz
Division of Extramural Affairs
National Heart, Lung, and Blood Institute 
6701 Rockledge Drive, Room 7171, MSC 7926
Bethesda, MD  20892-7926
Bethesda, MD  20817 (for express/courier service)
Telephone:  (301)435-0166
FAX:  480-3310


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, Email:  The PHS 
398 research grant application must be used for all SBIR/STTR Phase I 
and Phase II applications (new and revised.)  Prepare your application 
in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 398.  
Helpful information on the preparation of the application can be 
obtained at: 

The title and number of this PA must be typed on line 2 of the face 
page of the application.

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 critique.  

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 
o Receive a second level review by the appropriate national 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.

SIGNIFICANCE:  Does the proposed project have commercial potential to 
lead to a marketable product or process? Does this study address an 
important problem? What may be the anticipated commercial and societal 
benefits of the proposed activity? If the aims of the application are 
achieved, how will scientific knowledge be advanced? Does the proposal 
lead to enabling technologies (e.g., instrumentation, software) for 
further discoveries? Will the technology have a competitive advantage 
over existing/alternate technologies that can meet the market needs?

APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project? Is the proposed plan a sound approach for establishing 
technical and commercial feasibility? Does the applicant acknowledge 
potential problem areas and consider alternative strategies? Are the 
milestones and evaluation procedures appropriate?

INNOVATION:  Does the project challenge existing paradigms or employ 
novel technologies, approaches or methodologies? Are the aims original 
and innovative?
INVESTIGATORS: Is the Principal Investigator capable of coordinating 
and managing the proposed SBIR/STTR? Is the work proposed appropriate 
to the experience level of the Principal Investigator and other 
researchers, including consultants and subcontractors (if any)? Are the 
relationships of the key personnel to the small business and to other 
institutions appropriate for the work proposed?
ENVIRONMENT: Is there sufficient access to resources (e.g., equipment, 
facilities)? Does the scientific and technological 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? 
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be applied to ALL applications in the 
determination of scientific merit and the priority score:

human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See 
additional information and criteria included in the section on Federal 
Citations, below).
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 additional information and 
Inclusion Criteria in the sections on Federal Citations, below).

are to be used in the project, the required five items described under 
Vertebrate Animals (section f of the Research Plan instructions) will 
be assessed.  

ADDITIONAL CONSIDERATIONS: The following items may be also be 
considered by reviewers but will not be included in the determination 
of scientific merit.

BUDGET:  The reasonableness of the proposed budget may be considered.

PERIOD OF SUPPORT: The appropriateness of the requested period of 
support in relation to the proposed research.


In addition to the above criteria:

1.   How well did the applicant demonstrate progress toward meeting the 
Phase I objectives, demonstrating feasibility, and providing a solid 
foundation for the proposed Phase II activity? 
2.   Did the applicant submit a concise Commercialization Plan 
[formerly Product Development Plan] that adequately addresses the seven 
areas described in the Research Plan item J? 
3.   Does the project carry a high degree of commercial potential, as 
described in the Commercialization Plan? 

Amended Applications

In addition to the above criteria, the following criteria will be 
applied to revised applications.
1. Are the responses to comments from the previous SRG review adequate?
2. Are the improvements in the revised application appropriate? 


Applications submitted in response to a PA will compete for available 
funds with all other recommended SBIR and STTR 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.

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 and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998:  

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 

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 
a complete copy of the updated Guidelines are available at http://  
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 

SUBJECTS: (if applicable) 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 review. 

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

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.

The 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

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

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
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Bethesda, Maryland 20892
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