RELEASE DATE:  January 16, 2003

PA NUMBER: PA-03-058 (see amendment in NOT-HL-04-105)

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 R21 (PA-06-418) funding 
opportunity announcements has been issued for the 
submission date of June 1, 2006 and submission dates thereafter.

EXPIRATION DATE: March 2, 2006  (see extension in NOT-EB-06-005) 

National Institute of Biomedical Imaging and Bioengineering (NIBIB)  
National Cancer Institute (NCI) 
National Center for Research Resources (NCRR) 
National Eye Institute (NEI) 
National Heart, Lung, and Blood Institute (NHLBI)  
National Human Genome Research Institute (NHGRI)  
National Institute on Aging (NIA) 
National Institute on Alcohol Abuse and Alcoholism (NIAAA) 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 
National Institute on Drug Abuse (NIDA) 
National Institute on Deafness and Other Communication Disorders (NIDCD) 
National Institute of Dental and Craniofacial Research (NIDCR)  
National Institute of Environmental Health Sciences (NIEHS)  
National Institute of General Medical Sciences (NIGMS) 
National Institute of Mental Health (NIMH) 
National Institute of Neurological Disorders and Stroke (NINDS) 


o Purpose of this PA
o Research Objectives
o Mechanism of Support 
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 Required Federal Citations

Participating Institutes and Centers (ICs) of the National Institutes 
of Health (NIH) invite applications for Exploratory/Developmental 
Bioengineering Research Grants (EBRG) to support innovative, high 
risk/high impact bioengineering research in new areas that are lacking 
preliminary testing or development. This research can explore 
approaches and concepts new to a particular substantive area; research 
and development of new technologies, techniques or methods; or initial 
research and development of data upon which significant future research 
may be built.

While this program announcement (PA) is intended to encourage 
innovation and high impact research, and while minimal preliminary data 
are expected to be described in the application, applications should 
clearly indicate the significance of the proposed work and that the 
proposed research and/or development is scientifically sound, that the 
qualifications of the investigators are appropriate, and that resources 
available to the investigators are adequate. 


The objective of this PA is to invite applications in exploratory or 
developmental bioengineering research (EBRG).  The EBRG can support: 1) 
innovative, high-risk research, for which preliminary results have not 
yet been obtained; 2) exploration of new approaches or concepts to a 
particular substantive area; 3) research and development of new 
technologies, techniques or methods; or 4) initial research and 
development of data upon which significant future research may be 

The EBRG will support exploratory or developmental bioengineering 
research that is not appropriate for the R01 grant mechanism. While the 
core review criteria of 'significance', 'approach', 'innovation', 
'investigator', and 'facilities' are retained, the balance between 
risk, benefit, and the cost of the research is shifted toward accepting 
a significant risk of failure for a potential great benefit. The EBRG 
is appropriate for early stages of research or for investigating new 
ideas where risk is high but potential significance is also high and 
where the research needed to make a decision about proceeding to a 
larger scale R01 effort is moderate in terms of time and money.  A 
simple scenario would be a situation in which an investigator studying 
gene delivery conceives of a completely new, but unproven way to 
deliver genes. If the justification for the idea is solid, the 
feasibility of the idea can be effectively evaluated (with the EBRG), 
and if the potential significance is high then the feasibility could be 
supported in the absence of extensive preliminary results.  

Areas of Bioengineering Research for an EBRG

Bioengineering is defined as follows:  Bioengineering integrates 
physical, chemical, or mathematical sciences and engineering principles 
for the study of biology, medicine, behavior, or health.  It advances 
fundamental concepts, creates knowledge from the molecular to the organ 
systems level, and develops innovative biologics, materials, processes, 
implants, devices, and informatics approaches for the prevention, 
diagnosis, and treatment of disease, for patient rehabilitation, and 
for improving health. A few examples of bioengineering areas of 
relevance to the mission of Institutes and Centers (ICs) are identified 
below.  This list is illustrative only; it is not intended to be 

Examples of Bioengineering Research:

o Development of molecular probes for imaging of structure or function
o Development of new imaging modalities
o Development of organ culture systems
o Development of biomaterials or engineered tissues
o Development or evaluation of prostheses 
o Development of medical implants, biomembranes, or sensors 
o Development of tools for robotic or non-invasive surgery
o Development of microarrays or other tools for genomics
o Development of combinatorial or other techniques for high-throughput 
o Development of techniques for bioprocessing
o Research on the biomechanics of tissue injury or repair, and standing 
or walking
o Research on the interactions between biomaterials and living systems
o Research on drug, gene, or cellular therapeutic delivery systems
o Research on the interaction of magnetic or other fields with 
biological systems


This PA will use the NIH R21 award mechanism.  As an applicant, you 
will be solely responsible for planning, directing, and executing the 
proposed project. Under this program announcement, applicants for the 
EBRG award may request direct costs of up to $275,000 distributed over 
two years.  The EBRGs are in addition to a related program announcement 
(PA) PA-02-011 for Bioengineering Research Grants [(BRGs) 
http://grants.nih.gov//grants/guide/pa-files/PA-02-011.html].  The 
BRGs differ from the EBRGs in that the BRG utilizes the R01 grant 
mechanism and requires strong preliminary data for hypothesis-driven, 
discovery-driven, developmental, or design-directed research.  The 
EBRG cannot be renewed; if sufficient results are generated during the 
term of the award, investigators are encouraged to apply for further 
funding through the Bioengineering Research Grant (BRG) R01 mechanism.

This PA uses just-in-time concepts.  It also uses the modular budgeting 
format. (see http://grants.nih.gov/grants/funding/modular/modular.htm).   
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular format.


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
o Faith-based or community-based organizations 


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.   


We encourage your inquiries concerning this PA 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 NIH BECON scientific and financial contacts listed at the following 
Web site should be contacted for answers to questions about 
scientific or financial issues:


o Direct your questions about peer review issues to:

Dr. Eileen Bradley
Center for Scientific Review
6701 Rockledge Drive
Bethesda, MD  20892
TEL:  301-435-1179
FAX:  301-480-2241
E-mail:  bradleye@csr.nih.gov


Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email: 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. (Note: per NOT-HL-03-007,
NHLBI will accept applications for this PA for the June 1, 2003 deadline
only.  Thereafter, NHLBI will not participate in this PA.)

requesting 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 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at 

All PHS 398 requirements should be followed, with the exception of 
those items affected by the following instructions.  Applications not 
conforming to the requested format will be returned to the applicant 
without review

o FACE PAGE- Item 2, Check the box marked "Yes" and type the number 
GRANTS) of this program announcement.

o Item 6:  Up to a total of two years of support may be requested.  

o RESEARCH PLAN- Do not exceed a total of 15 pages inclusive of the 
following sections:  Specific Aims; Background and Significance; 
Preliminary Studies/Progress Report (evidence of feasibility); and 
Research Design and Methods.  Tables, figures and photographs are 
included in the 15-page limitation. 

o Item a, SPECIFIC AIMS- The applicant should begin with a statement 
that justifies the designation of  the application as an 
Exploratory/Developmental Research Grant as defined under the PURPOSE 
section of this program announcement.

o Item b, BACKGROUND AND SIGNIFICANCE- In this section it is important 
to provide enough information to give the reviewers an understanding of 
the potential significance of this work and to identify clearly how the 
application addresses the specific objectives of this program 
announcement.  Briefly review the relevant state-of-the-art, and 
concisely describe the substantial advance beyond state-of-the-art that 
would be achieved if the project is successful. Indicate how this 
advance might impact on human health.  For innovations that involve 
multiple steps justify that the proposed research will investigate the 
highest-risk critical step of the process. Identify briefly how this 
application relates to the purpose of the R21 mechanism as stated in 
this program announcement (i.e., highly innovative, high risk/high 
impact research; exploration of the use of approaches and concepts new 
to a particular substantive area; research and development of new 
technologies, techniques or methods; or initial research and 
development of a body of data upon which significant future research 
may be built).

o Item c, PRELIMINARY STUDIES/PROGRESS REPORT- Minimal preliminary data 
are expected for an Exploratory/Developmental Grant application. 
However, if data are available they can be included in this section.  
Particularly in the absence of preliminary data, describe the 
theoretical or conceptual underpinnings of the proposed project.  If 
substantial preliminary data are available the investigator should 
consider submitting a BRG application. 

o Item d, RESEARCH DESIGN AND METHODS- Fully describe the research 
design and methods. In many cases, an Exploratory/Developmental Grant 
mechanism will support novel research in an area or the research and 
development of new technologies.  Where appropriate, specific criteria 
by which to judge the feasibility of novel approaches (including 
milestones that will mark progress) should be explicitly described in 
this section. Milestones should be as quantitative as possible.  
Identify the key technical challenges and propose highest priority 
alternative solutions.

o APPENDIX  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 five signed 
photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING:  Applications must be received by or mailed on 
or before the receipt dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR 
will not accept any application in response to this PA that is 
essentially the same as one currently pending initial review unless the 
applicant withdraws the pending application.  The CSR will not accept 
any application that is essentially the same as one already reviewed.  
This does not preclude the submission of a substantial revision of an 
application already reviewed, but such application must include an 
Introduction addressing the previous critique.


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines. An appropriate scientific review 
group that includes bioengineering expertise will evaluate applications 
for scientific and technical merit convened in accordance with NIH peer 
review procedures (http://www.csr.nih.gov/refrev.htm). 

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 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
These NIH review criteria have been expanded to reflect the exploratory 
and bioengineering focus of an EBRG application.  The score should 
reflect the overall impact that the EBRG award could have on the 
selected area of bioengineering research based on consideration of the 
five criteria, with the emphasis on each criterion varying from one 
application to another, depending on the nature of the application and 
its relative strengths.  Note that an application need not be strong in 
all categories to be judged likely to have major scientific impact and 
thus deserve a high priority score.  The review criteria are:

(1) Significance.  If the Specific Aims of the EBRG are achieved, will 
they provide significant advances in the selected area of 
bioengineering research? Is the research likely to provide a foundation 
for a new research area or have potential for wide applicability? Does 
this represent a groundbreaking, precedent setting research topic that 
clearly requires additional preliminary data for its potential to be 

(2) Approach.  Are the EBRG approaches and methods adequately 
developed, well integrated, and appropriate to the aims of the project? 
Does the applicant acknowledge potential problem areas and consider 
alternative tactics?  For technology development projects, are the 
milestones sufficiently specific and quantitative to guide both the 
research and subsequent evaluation of success or failure of the 
proposed concept?

(3) Innovation.  Does the EBRG propose new approaches or explore new 
research paradigms or new concepts that will affect bioengineering, 
basic or clinical sciences? Are extant approaches or concepts applied 
to new scientific problems in novel ways?

(4) Investigators.  Are the PI and key personnel appropriately trained 
in their disciplines and capable of conducting the proposed research?

(5) Environment.  Does the scientific and technological environment in 
which the work will be done contribute to the probability of success? 
Does the proposed research take advantage of unique features of the 
scientific environment or employ useful collaborative arrangements? Is 
there evidence of other support that will contribute to the success of 
the research?

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)

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


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: 

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 
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 

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 

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 
http://grants.nih.gov/grants/stem_cells.htm 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 
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. 

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.

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 

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 Nos. 93.286, 93.287, 93.394, 93.395, 
93.396, 93.306, 93.867, 93.172, 93.837, 93.838, 93.839, 93.866, 93.273, 
93.855, 93.856, 93.846, 93.864, 93.865, 93.929, 93.279, 93.173, 93.121, 
93.847, 93.848, 93.849, 93.113, 93.821, 93.859, 93.862, 93.242, 93.853, 
93.361, and 93.879.  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 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 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.

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