SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY 
TRANSFER (STTR) TO DEVELOP NEW THERAPIES FOR TYPE 1 DIABETES AND ITS 
COMPLICATIONS

RELEASE DATE:  August 28, 2003

RFA Number:  RFA-DK-03-020 (This RFA has been reissued, see RFA-DK-05-015)
                           (This RFA has been modified, see RFA-DK-05-010)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov/)
National Eye Institute (NEI)
 (http://www.nei.nih.gov/)
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov/)
National Institute of Allergy and Infectious Diseases (NIAID)
 (http://www.niaid.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)
National Institute of Nursing Research (NINR)
 (http://www.ninr.nih.gov/)
National Institute of Child Health and Human Development (NICHD)
 (http://www.nichd.nih.gov) 

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.847, 93.867, 98.837, 
93.855, 93.853, 93.361, 93.865

LETTER OF INTENT RECEIPT DATE:  January 19,2004

APPLICATION RECEIPT DATE: February 19, 2004 

THIS RFA CONTAINS THE FOLLOWING INFORMATION

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

NOTICE: This Request for Application (RFA) 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 ADMINISTRATION 
FOR SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY 
TRANSFER (STTR) GRANT APPLICATIONS.  The solicitation (see 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf) contains 
information about the SBIR and STTR programs, regulations governing the 
programs, and instructional information for submission. All of the 
instructions within the SBIR/STTR Omnibus Solicitation apply with the 
following exceptions: 

o This RFA is a one-time solicitation with the receipt date of 2/19/03. 
o Upon receipt applications will be reviewed by a Special Emphasis Panel  
organized by NIDDK.  

PURPOSE OF THIS RFA

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 
National Eye Institute (NEI), National Heart, Lung, and Blood Institute 
(NHLBI), National Institute of Allergy and Infectious Diseases (NIAID), 
National Institute of Neurological Disorders and Stroke (NINDS), National 
Institute of Nursing Research (NINR), National Institute of Child Health and 
Human Development (NICHD) invite the small business community to apply 
cutting edge technology to research to develop new approaches to prevent, 
treat, and cure type 1 diabetes and its complications.   

This RFA will utilize the Small Business Innovation Research (SBIR) and Small 
Business Technology Transfer (STTR) mechanisms, but will be run in parallel 
with other requests for applications (RFAs) of similar scientific scope 
(DK-03-015 for Innovative Partners and DK-03-001 for Bench to Bedside) that will 
utilize the traditional research project grant (R01), the 
exploratory/developmental grant (R21) or the exploratory/developmental grant 
phase II (R33) grant mechanisms. 

RESEARCH BACKGROUND AND OBJECTIVES:

Type 1 diabetes is an autoimmune disease that destroys the insulin-producing 
cells of the pancreas and affects an estimated one million Americans, usually 
with onset in childhood or young adulthood. The disease markedly impairs 
quality of life and shortens lifespan primarily through premature 
cardiovascular mortality.  Cardiovascular complications are increased four-
fold compared to the general population, and type 1 diabetes is associated 
with numerous complications including blindness, renal failure, painful nerve 
disorders, and amputation.  In addition to its devastating toll in human 
suffering, type 1 diabetes and its complications result in significant health 
care expenditures for families and constitute a major societal economic 
burden. 

Recent research progress in understanding and treating this disease has been 
dramatic.  Researchers can now accurately identify individuals at increased 
risk of type 1 diabetes based on genetic tests and antibody measurements.  
Clinical trials are ongoing in those with new onset disease to test new 
immunomodulatory agents that may have the potential to preserve residual 
function of the insulin producing beta cells.  Clinical trials have 
demonstrated dramatic reductions in complications of type 1 diabetes through 
intensive glycemic control.  However, dangerous episodes of hypoglycemia 
limit attempts to control blood glucose in many patients with type 1 
diabetes.  Recently researchers have reported success using islet 
transplantation to restore lost beta cell function.  However, the current 
immunosuppressive regimens required for transplant survival have significant 
immediate side effects and long term safety is uncertain.  The small business 
community in encouraged to contribute to the rapid progress toward developing 
safe and effective cell based beta cell replacement therapy, as well other 
new approaches to prevent, treat and cure type 1 diabetes and its macro- and 
micro-vascular complications.  

This RFA is intended to support innovative research in the field of type 1 
diabetes and its complications, conducted by small business (SBIR) and small 
business in partnership with academia (STTR).  Examples of projects that this 
announcement intends to solicit include:

o Development of novel therapeutics, including beta cell replacement therapy, 
devices, biologics and other drugs for the treatment of type 1 diabetes and 
its complications.

o Development of methods to increase the yield of functional and successfully 
transplantable islets from pancreata including the development of alternative 
enzymatic approaches to isolate islets and methods to increase the duration 
for which a pancreas can be utilized.

o Development of methods to develop replenishible sources of islet like cells 
or to expand the number of human islets during culture while still retaining 
appropriate functional islet characteristics and the ability to be 
successfully transplanted.

o Development of pre-transplant islet testing approaches that are predictive 
of subsequent successful islet transplantation using functional genomics, 
proteomics or other methods.

o Development of methods to improve viability/function of islets prior to 
transplantation and the engraftment and long term function of islets after 
transplantation including gene transfer, encapsulation or immunoisolation, 
and the evaluation of alternative transplantation sites.

o Development of improved approaches to xenotransplantation as an unlimited 
source of islets that would reduce potential complications and enhance graft 
survival.

o Application of basic research in regenerative medicine to preclinical or 
clinical treatment of type 1 diabetes and its complications.  

o Application of gene therapy strategies to prevent or reverse complications.

o Development of novel approaches to immunomodulation or development of 
tolerance with relevance to type 1 diabetes and/or of methods to measure 
changes in immune status in type 1 diabetes, such as pathogenic T cell 
assays.

o The development of methodology or biomarkers to help understand the 
physiology or improve the diagnosis and treatment of type 1 diabetes and its 
complications (e.g. novel genetic screening methodologies, application of 
proteomic technologies). 

o The development of methods for measuring or imaging the pancreatic beta 
cell mass or inflammation.

o Development of methods for early detection, diagnosis and quantification of 
cardiovascular disease, neuropathy, retinopathy and nephropathy in type 1 
diabetes.

o Development of non-invasive or minimally invasive methods for continuous 
monitoring of blood glucose and/or approaches to linkage of monitoring 
devices to miniaturized insulin delivery systems for the development of a 
"closed loop" artificial pancreas.

o Identification of biomarkers for use in clinical trials that could serve as 
surrogate outcomes for monitoring the progression of type 1 diabetes and/or 
its complications or for quantitatively assessing response to therapy to 
prevent or reverse disease.

o Development of high throughput assays based on biologic pathways likely 
involved in the pathogenesis of type 1 diabetes complications or autoimmunity 
that could be used to screen molecular libraries for novel therapeutic 
agents. 

o The development of novel animal models for investigating type 1 diabetes 
and its complications 

MECHANISM(S) OF SUPPORT

This RFA uses the SBIR and STTR 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. The anticipated award date is October 2004. Applications that are 
not funded in the competition described in this RFA may be resubmitted as NEW 
SBIR/STTR applications using the standard receipt dates for NEW applications 
described in the current SBIR/STTR Omnibus Solicitation.

This RFA uses just-in-time concepts. It also uses the modular budgeting 
format. Specifically, if you are submitting an application budget of $100,000 
total costs (direct, F&A and fee) or less, use the modular format and 
instructions as described in the current SBIR/STTR Omnibus Solicitation. 
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 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.

Except as otherwise stated in this RFA, awards will be administered under NIH 
grants policy as stated in the NIH Grants Policy Statement, March 2001, 
available at http://grants.nih.gov/grants/policy/nihgps_2001.  

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; or the 
SBIR/STTR FAST-TRACK option as described in the SBIR/STTR Omnibus 
Solicitation.  Phase II applications in response to this RFA 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 RFA. Fast Track applications will benefit from expedited 
evaluation of progress following the Phase I feasibility study for transition 
to Phase II funding for expanded developmental work. 

PROJECT PERIOD AND AMOUNT OF AWARD

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 RFA, budgets up to $500,000 total costs per year 
and time periods up to 2 years for Phase I may be requested.  Budgets up to $ 
1,000,000 total costs per year and up to 3 years may be requested for Phase 
II.  Total costs include direct costs, F&A, and fee/profit.  

FUNDS AVAILABLE 

The total funds available will be approximately $4,000,000 in FY2004. 
The participating institutes intend to fund 6-10 phase I, Phase II or Fast 
Track SBIR projects and 1-2 phase I, Phase II or Fast Track STTR projects. 
Although the financial plans of the sponsoring Institutes provide support for 
this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 
applications. 

ELIGIBLE INSTITUTIONS:

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.  
Only small business concerns are eligible to submit SBIR/STTR 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 
current SBIR/STTR Omnibus Solicitation.

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 his/her 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. 

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA 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 questions about scientific/research issues to:

Dr. Sanford Garfield
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 685 
Bethesda, MD  20892-5460
TEL:(301) 594-8803 
Fax: (301) 480-6271 
Email: sg50o@nih.gov

Peter Dudley, Ph.D.
Division of Extramural Activities
National Eye Institute
6120 Executive Boulevard
Executive Plaza South, Suite 350
Bethesda, MD  20892-7164
TEL:(301) 451-2020 
Fax: (301) 402-0528 
Email: pad@nei.nih.gov 

Cristina Rabadan-Diehl, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
Rockledge II, Room 10186
6701 Rockledge Drive
Bethesda, MD 20892-7956
Phone: (301) 435-0550
FAX: (301) 480-2858
E-mail: cr601i@nih.gov 

Dr. John Paul Ridge
Division of Allergy, Immunology and Transplantation Research
National Institute of Allergy and Infectious Disease
6610 Rockledge Drive, Room 3027
Bethesda, MD 20892
Phone: (301) 496-7104
FAX: (301) 480-1450
E-mail: jr34g@nih.gov 

Paul L. Nichols, Ph.D. 
National Institute of Neurological Disorders and Stroke 
Neuroscience Center, Room 2108 
6001 Executive Blvd. 
Bethesda, MD 20892 
Phone: 301-496-9964 
FAX: 301-401-2060 
E-mail: pn13w@nih.gov

Dr. Nell Armstrong
Office of Extramural Programs
National Institute of Nursing Research
6701 Democracy Boulevard, Room 710
Bethesda, MD  20892-4870
Telephone:  (301) 594-5973
FAX:  (301) 480-8260
Email: na21f@nih.gov 

Dr. Gilman D. Grave 
Center for Research for Mothers and Children 
National Institute of Child Health and Human Development 
6100 Executive Boulevard; Suite 4B-11 
Bethesda, MD 20892-7510 
Telephone: 301-496-5593 
Fax: 301-480-9791 
e-mail: gg37v@nih.gov 

o Direct questions about peer review issues to:  

Francisco O. Calvo, Ph.D.
Chief, Review Branch 
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505
Email: fc15y@nih.gov

o Direct questions about financial or grants management matters to:

Kathleen Shino
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 708
Bethesda, MD 20892-5452
Telephone:  (301) 594-8869
FAX: (301) 480-3504
Email: ks48e@nih.gov

William W. Darby
Grants Management
National Eye Institute
6120 Executive Boulevard
Executive Plaza South, Suite 350
Bethesda, MD  20892-7164
TEL:(301) 496-5884
Fax: (301) 496-9997 
Email: wwd@nei.nih.gov  

Susan Lowenthal
Grants Management
National Heart, Lung, and Blood Institute
Rockledge II, Room 7155
6701 Rockledge Drive
Bethesda, MD 20892-7926
Phone: (301) 435-0159
FAX: (301) 480-3310
E-mail: sl262k@nih.gov

John Paul Ridge
Grants Management
National Institute of Allergy and Infectious Disease
6610 Rockledge Drive, Room 3027
Bethesda, MD 20892
Phone: (301) 496 7104 phone
FAX: (301) 480 1450 fax
E-mail: jridge@niaid.nih.gov

Karen Shields
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 3290
6001 Executive Blvd.
Bethesda, MD 20892
Phone: 301-496-9231
FAX: 301-402-0129
E-mail: ks26n@nih.gov

Diane E. Drew  
Grants Management 
National Institute of Nursing Research  
6701 Democracy Boulevard, Room 710  
Bethesda, MD  20892-4870  
Telephone:  (301) 594-2807  
FAX:  (301) 451-5651 or (301) 402-4502  
Email:  dd276v@nih.gov  

Dr. Gilman D. Grave 
Center for Research for Mothers and Children 
National Institute of Child Health and Human Development 
6100 Executive Boulevard; Suite 4B-11 
Bethesda, MD 20892-7510 
Telephone: 301-496-5593 
Fax: 301-480-9791 
e-mail: gg37v@nih.gov 

LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch 
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505 
Email: fc15y@nih.gov

SUBMITTING AN APPLICATION 

The PHS 398 research grant application must be used for all SBIR/STTR Phase 
I, Phase II and Fast-Track applications (new and revised.)  Effective October 
1, 2003, applicants must have a DUN and Bradstreet (D&B) Data Universal 
Numbering System (DUNS) number as the Universal Identifier when applying for 
Federal grants or cooperative agreements. The DUNS number can be obtained by 
calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com. The DUNS number should be entered on line 
11 of the face page of the PHS 398 form. The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare your 
application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 
398. Helpful information for advice and preparation of the application can be 
obtained at: http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.  The 
NIH will return applications that are not submitted on the 5/2001 version of 
the PHS 398.  For further assistance contact GrantsInfo, Telephone: (301) 
435-0714, Email: GrantsInfo@nih.gov. 

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: If you are submitting 
an application budget of $100,000 total costs (direct, F&A and fee) or less, 
you must use the modular format and instructions as described in the 
SBIR/STTR Omnibus Solicitation. 

USING THE RFA LABEL: The RFA label available in the PHS 398 application form 
must be affixed to the bottom of the face page of the application. Type the 
RFA number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.doc or 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.  

The title and number of this RFA 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 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 (for USPS EXPRESS or REGULAR MAIL)
Bethesda, MD  20817 (for EXPRESS/COURIER NON-USPS SERVICE)

At the time of submission, two additional copies of the application and 
five sets of appendices must be sent to:

Francisco Calvo, Ph.D.
Chief, Review Branch 
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505
Email: fc15y@nih.gov

APPLICATION PROCESSING: Applications must be received on or before the 
receipt date listed on the first page of this announcement. If an application 
is received after that date, it will be returned to the applicant without 
review.

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.

The Center for Scientific Research (CSR) will not accept any application in 
response to this RFA 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. However, when a previously unfunded application, originally 
submitted as an investigator-initiated application, is to be submitted in 
response to an RFA, it is to be prepared as a NEW application.  That is the 
application for the RFA must not include an Introduction describing the 
changes and improvements made, and the text must not be marked to indicate 
the changes.  While the investigator may still benefit from the previous 
review, the RFA application is not to state explicitly how.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIDDK. Incomplete applications will not be reviewed.  If 
the application is not responsive to the RFA, NIH staff may contact the 
applicant to determine whether to return the application to the applicant or 
submit it for review in competition with unsolicited applications at the next 
appropriate NIH review cycle.

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIDDK in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will:
 
o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by an appropriate national advisory council 
or board. 

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals within 
the context of the SBIR/STTR Program: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

ALL SBIR/STTR APPLICATIONS

o 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? 

o 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? 

o Innovation:  Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies? Are the aims original and 
innovative? 

o 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? 

o 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 considered in the determination of scientific merit and the 
priority score:

RELEVANCE TO THE GOALS OF THIS RFA:  Does the proposed project have the 
potential to open new avenues to the prevention, treatment and cure of type 1 
diabetes and its complications?  For Fast Track applications, are there clear 
milestones that will be achieved and evaluated at the end Phase I that are 
directly relevant to the goals of the RFA?  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of 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).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: 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 additional information and Inclusion Criteria in the sections 
on Federal Citations, below).

Human Subjects: 

o Protection of Human Subjects from Research Risks - for all studies 
involving human subjects. See instructions and "Guidance for Preparing the 
Human Subjects Research Section." If an exemption is claimed, is it 
appropriate for the work proposed? If no exemption is claimed, are the 
applicant's responses to the six required points appropriate? Are human 
subjects placed at risk by the proposed study? If so, are the risks 
reasonable in relation to the anticipated benefits to the subjects and 
others? Are the risks reasonable in relation to the importance of the 
knowledge that reasonably may be expected to be gained? Are the plans 
proposed for the protection of human subjects adequate? 

o Inclusion of Women Plan - for clinical research only.  Does the applicant 
propose a plan for the inclusion of both genders that will provide their 
appropriate representation? Does the applicant provide appropriate 
justification when representation is limited or absent? Does the applicant 
propose appropriate and acceptable plans for recruitment/outreach and 
retention of study participants? 

o Inclusion of Minorities Plan - for clinical research only.  Does the 
applicant propose a plan for the inclusion of minorities that will provide 
their appropriate representation? Does the applicant provide appropriate 
justification when representation is limited or absent? Does the applicant 
propose appropriate and acceptable plans for recruitment/outreach and 
retention of study participants? 

o Inclusion of Children Plan- for all studies involving human subjects.  Does 
the applicant describe an acceptable plan in which the representation of 
children of all ages (under the age of 21) is scientifically appropriate and 
recruitment/retention is addressed realistically? If not, does the applicant 
provide an appropriate justification for their exclusion? 

o Data and Safety Monitoring Plan – for clinical trials only.  Does the 
applicant describe a Data and Safety Monitoring Plan that defines the general 
structure of the monitoring entity and mechanisms for reporting Adverse 
Events to the NIH and the IRB? 
 
CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals 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. 
 
Animal Welfare: If vertebrate animals are involved, are adequate plans 
proposed for their care and use? Are the applicant's responses to the five 
required points appropriate? Will the procedures be limited to those that are 
unavoidable in the conduct of scientifically sound research?
 
Biohazards: Is the use of materials or procedures that are potentially 
hazardous to research personnel and/or the environment proposed? Is the 
proposed protection adequate? 

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.
For all applications, is the percent effort listed for the PI appropriate for 
the work proposed? On applications requesting up to $100,000 total costs, is 
the overall budget realistic and justified in terms of the aims and methods 
proposed? On applications requesting over $100,000 in total costs, is each 
budget category realistic and justified in terms of the aims and methods? 

PERIOD OF SUPPORT: The appropriateness of the requested period of support in 
relation to the proposed research.
Phase II Application Review Criteria:  In addition to the above criteria:
o 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?
 
o 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? 

o 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.

o Are the responses to comments from the previous SRG review adequate? 

o Are the improvements in the revised application appropriate?
 
Phase I/Phase II Fast-Track Application Review Criteria 
For Phase I/Phase II Fast Track applications, the following criteria also 
will be applied:

o Does the Phase I application specify clear, appropriate, measurable goals 
(milestones) that should be achieved prior to initiating Phase II? 

o 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?

o To what extent was the applicant able to obtain letters of interest, 
additional funding commitments, and/or resources from the private sector or 
non-SBIR/ STTR funding sources that would enhance the likelihood for 
commercialization? 

o Does the project carry a high degree of commercial potential, as described 
in the Commercialization Plan? 

Phase I and Phase II Fast-Track applications that satisfy all of the review 
criteria will receive a single rating. Failure to provide clear, measurable 
goals may be sufficient reason for the scientific review group to exclude the 
Phase II application from Fast-Track review.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    January 19, 2004
Application Receipt Date:         February 19, 2004
Peer Review Date:                 June/July 2004
Council Review:                   September 2004
Earliest Anticipated Start Date:  October 2004

AWARD CRITERIA

Applications submitted in response to an RFA 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

For FAST-TRACK applications, the Phase II portion may not be funded until a 
Phase I final report and other documents necessary for continuation have been 
received and assessed by program staff that the Phase I milestones have been 
successfully achieved. 

REQUIRED FEDERAL CITATIONS 

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.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants. (NIH Policy for Data and Safety 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 "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://stemcells.nih.gov/index.asp 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://stemcells.nih.gov/registry/index.asp).   It is the responsibility of 
the applicant to provide, in the project description and elsewhere in the 
application as appropriate, 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 RFA 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.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  
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 
(http://www.hhs.gov/ocr/) 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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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 
RFA is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/. 

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ 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 
http://grants.nih.gov/grants/policy/policy.htm 

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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