CHEMICAL SCREENS FOR NEW INDUCERS OF FETAL HEMOGLOBIN (SBIR/STTR)

RELEASE DATE:  December 30, 2002

PA NUMBER:  PA-03-049

EXPIRATION DATE: December 1, 2005, unless reissued 

APPLICATION RECEIPT DATES:  Applications submitted in response to this PA 
will be accepted on the standard SBIR/STTR application deadlines (April 1, 
August 1, and December 1).

National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov)

THIS PA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE OF THIS PA

The National Heart, Lung, and Blood Institute (NHLBI) and the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite grant 
applications for Small Business Innovation Research (SBIR) and Small Business 
Technology Transfer (STTR) awards to support research and development of new 
drugs to increase fetal hemoglobin levels for the treatment of beta-chain 
hemoglobinopathies such as sickle cell disease (SCD) and Cooley's anemia (CA; 
beta-thalassemia). The goal of this Program Announcement (PA)is to encourage 
the use of SBIR and STTR mechanisms to support new chemical activity screens 
and drug design efforts for new pharmacologic inducers of fetal hemoglobin. 
The ultimate long-term objective will be to bring new fetal hemoglobin 
inducers to clinical practice to improve upon drugs such as hydroxyurea, the 
only FDA-approved drug for treatment of sickle cell disease. Hydroxyurea is 
thought to work in part through fetal hemoglobin induction, but does not 
benefit all patients. It is well established that SCD and CA can be cured 
with adequate reactivation of endogenous fetal hemoglobin genes silenced 
during development. Initial drug activity screens that are high-throughput in 
nature are encouraged. These screens should include but not be limited to 
compounds in the short chain fatty acid and carbonic acid classes, which have 
shown great promise in this area.  As commercial activity in this area has 
decreased significantly in the last decade, it is hoped that this PA will 
stimulate and renew interest within the small business community to develop 
new pharmacologic and/or combined pharmacologic-genetic approaches to fetal 
hemoglobin induction, to cure SCD and CA. 

RESEARCH OBJECTIVES

Background

Since the late 1970s, strong epidemiologic evidence has been gathered that 
shows high levels of fetal hemoglobin are curative for SCD and CA. Over the 
last two decades, this knowledge has provided a strong rationale to search 
for drugs that modify expression of fetal hemoglobin. Historically, 
pharmacologic induction of fetal hemoglobin has been attempted with two 
approaches. One is the use of cytotoxic drugs. This method is based on the 
observation that production of fetal hemoglobin can be stimulated by rapid 
regeneration of erythropoiesis. Cytotoxic drugs produce rapid erythroid 
regeneration following the killing of cycling hematopoietic cells. The 
induction of fetal hemoglobin by hydroxyurea, currently approved for 
treatment of SCD patients in acute vaso-occlusive crisis, is based on that 
principle (though it has still not been conclusively proven that the 
therapeutic effect of hydroxyurea is mediated through fetal hemoglobin 
induction). Significant variation in the level of induction of fetal 
hemoglobin synthesis is characteristic of treatment with hydroxyurea, and in 
about one-third of patients this treatment is ineffective. Furthermore, 
hydroxyurea (and other cytotoxic drugs) are ineffective in severe homozygous 
CA and they are only slightly effective in intermediate severity CA. The 
second approach is the induction of fetal hemoglobin by compounds that most 
likely act at the level of chromatin. Two types of compounds fall in this 
category:  5-azacytidine, and short chain fatty acids. 5-azacytidine 
stimulates fetal hemoglobin synthesis by affecting the level of DNA 
methylation and indirectly increasing fetal hemoglobin gene transcription by 
modulating DNA/protein interactions and chromatin remodeling. Short chain 
fatty acids probably act by increasing the level of chromatin acetylation 
because of inhibition of the activity of histone deacetylase. 5-azacytidine 
induces fetal hemoglobin in patients with SCD and CA, but its clinical use is 
very limited because this compound is considered to be carcinogenic.  
Butyrate induces fetal hemoglobin in patients with SCD and CA, but the 
therapeutic usefulness of this treatment is limited by the need of 
administration of this drug through intravenous infusions that last for 
several hours. 

A significant development of the last ten years has been the realization that 
the potential of induction of fetal hemoglobin synthesis is shared by a large 
number of compounds. Thus, all short chain fatty acids with 2-9 carbon atoms, 
as well as short chain fatty acid derivatives and analogues have been shown 
to act as fetal hemoglobin inducers. Other categories of organic chemicals 
have shown to have this property in vitro or in vivo. These findings permit 
the prediction that potent inducers of fetal hemoglobin synthesis can be 
discovered through empirical screening of chemicals. Thus, there is solid 
clinical, cell biological and biochemical evidence that the induction of 
fetal hemoglobin can cure SCD and CA, and there is proof of principle that 
fetal hemoglobin can be induced with pharmacological means, but there are 
severe limitations to the effectiveness of the currently used fetal 
hemoglobin inducers. It is therefore necessary to launch a focused research 
effort to discover new approaches for therapeutic induction of fetal 
hemoglobin synthesis. Compounds that can be taken orally and are effective in 
both SCD and CA are required.  

This PA encourages the use of the National Institutes of Health (NIH) SBIR 
and STTR grant mechanisms to explore various approaches to high-throughput 
screening of synthetic chemical or natural product libraries, to identify new 
drugs with fetal hemoglobin induction activity and develop them for clinical 
application (e.g. file an Investigational New Drug application with the FDA, 
and carry out Phase I-III clinical trials). The NHLBI has supported through a 
cooperative agreement since 1997 a Reference Laboratory to Evaluate New 
Therapies for Sickle Cell Disease, that is located at the Children's Hospital 
of Philadelphia and that carries out small-scale drug screening for fetal 
hemoglobin inducers. Applicants planning to respond to this PA are encouraged 
to consult with this Reference Laboratory before preparing an application 
(contact NHLBI Program representative listed below). In addition, the NHLBI 
and NIDDK are co-sponsoring an active Request for Applications(RFA) on 
transactivation of fetal hemoglobin genes, and the NHLBI is soon to sponsor a 
second RFA on fetal hemoglobin gene silencing. Grantees funded in response to 
this PA are encouraged to attend the joint RFA investigator meetings to be 
held for these two RFAs in the Fall (contact NHLBI Program representative 
listed below for details). It is expected that the high-throughput initial 
screening portion of this research will be carried out primarily, but not 
exclusively using in vitro cell culture systems. Toxicology studies, 
pharmacokinetic, and late stage efficacy studies may be carried out in rodent 
models engineered to contain a human fetal hemoglobin gene, and/or in large 
animal models (e.g. non-human primates). 

Research Goals and Topics

The following research areas are examples of appropriate topics for 
applications in response to this PA. This list is meant to be representative 
and not all-inclusive:

o Develop new automated, high-throughput assays or chemical activity screens 
for classical drug discovery efforts based on fetal hemoglobin induction 
activity. Assay methods that employ robotics, and that are physiologically 
relevant are needed.

o Screen synthetic or natural product chemical libraries of high complexity 
for fetal hemoglobin induction activity using new or existing rapid assays. 
The application of new assay methods to existing chemical libraries published 
in the scientific literature is encouraged. New chemical libraries with well-
documented diversity and complexity may also be useful. 

o Screen synthetic or natural product chemical libraries of low complexity 
and limited to compounds in the short chain fatty acid and carbonic acid 
classes (many examples of which are known to possess fetal hemoglobin 
induction activity). 

o Using rational drug design, study, refine, and optimize the structure-
activity relationships of candidate fetal hemoglobin-inducing drugs 
identified in initial screens. 

o Develop genetic approaches to drug discovery focused on fetal hemoglobin 
induction. Methods that might be employed include the construction and 
screening of artificial transcription factors that activate gamma-globin, 
interfering RNAs (RNAi), or catalytic RNAs, all coupled with gene transfer 
methods. 

o Pursue signal transduction pathway-based drug discovery for fetal 
hemoglobin inducers by screening for drugs that modify or modulate the 
activity of specific regulatory proteins known to participate in the 
activation of fetal hemoglobin expression. 
 
o Advance to large animal studies candidate inducers of fetal hemoglobin that 
have shown promise in vitro, and/or in small animal studies.

o Advance to clinical studies in hemoglobinopathy subjects inducers that have 
shown promise in large animal studies or prior pilot clinical studies.

o Develop genetic or pharmacologic means to specifically inhibit the gamma-
globin gene silencing that occurs in the neonatal period of human 
development. Therapeutic agents developed from such approaches could 
potentially be used for treatment of newborns diagnosed with homozygous 
sickle cell disease or Cooley's anemia, in order to inhibit the gamma- to 
beta-globin gene switch and thus continue synthesis of fetal hemoglobin into 
infancy. Either genetic or non-genetic approaches may be feasible.

o Develop pharmacologic or genetic means to inhibit the gamma-globin gene 
silencing that takes place during the process of maturation of adult 
erythroid progenitors.

o Use combined pharmacologic-genetic approaches to fetal hemoglobin 
induction.
 
MECHANISM OF SUPPORT–SBIR AND STTR

This PA will use the NIH Small Business Innovation Research (SBIR) and Small 
Business Technology Transfer (STTR) award mechanisms. As an applicant, you 
will be solely responsible for planning, directing, and executing the 
proposed project.  

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 http://grants.nih.gov/grants/policy/nihgps_2001.  

Applications can be submitted for support as Phase I STTR (R41) or Phase I 
SBIR (R43) grants; or under the SBIR/STTR FAST-TRACK option as described in 
the SBIR/STTR Omnibus Solicitation. 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 proposal must be a logical extension 
of the Phase I research.

ELIGIBLE INSTITUTIONS 

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation. 
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 following criteria: 

o is organized for profit, with a place of business located in the United 
States, which operates primarily within the United States or which makes a 
significant contribution to the United States economy through payment of 
taxes or use of American products, materials, or labor;

o is in the legal form of an individual proprietorship, partnership, limited 
liability company, corporation, joint venture, association, trust or 
cooperative, except that where the form is a joint venture (as defined in 
this section) there can be no more than 49 percent participation by foreign 
business entities in the joint venture;

o is at least 51 percent owned and controlled by one or more individuals who 
are citizens of, or permanent resident aliens in, the United States; has, 
including its affiliates, not more than 500 employees, and meets the other 
regulatory requirements found in 13 CFR Part 121. Business concerns, other 
than investment companies licensed, or state development companies qualifying 
under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are 
affiliates of one another when either directly or indirectly, (a) one concern 
controls or has the power to control the other; or (b) a third party/parties 
controls or has the power to control both. Control can be exercised through 
common ownership, common management, and contractual relationships. The term 
"affiliates" is defined in greater detail in 13 CFR 121.3-2(a). The term 
"number of employees" is defined in 13 CFR 121.3-2(t). 

Business concerns include, but are not limited to, any individual (sole 
proprietorship), partnership, corporation, joint venture, association, or 
cooperative. Further information may be obtained by contacting the Small 
Business Administration Size District Office at http://www.sba.gov/size/. For 
both Phase I and Phase II, the R&D must be performed in its entirety in the 
United States.  For both Phase I and Phase II, the proposed work must be 
performed in its entirety in the United States.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.  

WHERE TO SEND INQUIRIES

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:

Pankaj Qasba, Ph.D.
Blood Diseases Program
National Heart Lung and Blood Institute
6701 Rockledge Dr, MSC 7950
Bethesda MD 20892-7950
Telephone: 301-435-0050 
Fax: 301-480-0868 
Email: qasbap@nhlbi.nih.gov

David G. Badman, Ph.D.  
Hematology Program Director  
Deputy Director for Basic Program Administration  
DKUHD, NIDDK, NIH  
2 Democracy Plaza, Room 621 MSC 5458  
6707 Democracy Blvd.  
Bethesda, MD 20892-5458  
Telephone: 301-594-7717  
Fax: 301-480-3510  
Email: db70f@nih.gov 

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 Dr, MSC 7926
Bethesda MD 20892-7926
Telephone: 301-435-0166 
Fax: 301-480-3310 
Email: ortizs@nhlbi.nih.gov

SUBMITTING AN APPLICATION

The PHS 398 research grant application (rev. 5/2001) must be used for all 
Phase I, Phase II and Fast-Track applications (new and revised.)  
Instructions and forms are available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare your 
application in accordance with the SBIR/STTR Omnibus Solicitation and Chapter 
VI of the PHS 398. 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 PHASE I APPLICATIONS:  Application forms, 
requirements, and procedures are the same as listed in the Omnibus 
Solicitation for Phase I SBIR/STTR Grant applications 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf), except for the 
following:

o Type the title and number of this PA on line 2 on the face page of the 
application.

o The Omnibus Solicitation states levels for Phase I and Phase II budgets 
that are guidelines, not ceilings.  SBIR applications requesting up to 
$100,000 in total costs (direct costs, indirect costs, and fee) 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. Section VI of the research grant application instructions 
for the PHS 398 at  
http://grants.nih.gov/grants/funding/phs398/instructions2/p1_preparing
_SBIR_STTR_app.htm includes 
step-by-step guidance for preparing modular grants. Additional information on 
SBIR modular grants is available at
http://grants.nih.gov/grants/funding/phs398/instructions2/p1_SBIRSTTR
_general_instructions.htm. 
Applications for over $100,000 total costs must include a detailed budget and 
budget justification (Form Pages 4 and 5).

SPECIFIC INSTRUCTIONS FOR Phase II Applications:  Phase II applications will 
be accepted only as competing continuations of previously funded NIH Phase I 
SBIR or STTR awards.  The Phase II application must be for developmental work 
that is a logical extension of the feasibility research conducted during 
Phase I.  When preparing an application for a Phase II award, you should 
follow the instructions for NIH Phase II SBIR or STTR applications. The 
instructions and forms for a Phase II SBIR and STTR award are available at
http://grants.nih.gov/grants/funding/phs398/phs398.html.

SPECIFIC INSTRUCTIONS FOR FAST TRACK APPLICATIONS: The NIH Fast-Track 
mechanism expedites the decision and award of SBIR and STTR Phase II funding 
for scientifically meritorious applications that have a high potential for 
commercialization.  Fast Track incorporates a submission and review process, 
in which complete Phase I and Phase II grant applications are submitted 
simultaneously and reviewed together. The FAST-TRACK must have a section 
labeled Milestones at the end of the Phase I Research Plan. This section must 
include well-defined quantifiable milestones for completion of Phase I, a 
discussion of the suitability of the proposed milestones for assessing the 
success in Phase I, and a discussion of the implications of successful 
completion of these milestones on the proposed Phase II. Failure to provide 
such information in the Phase I application and/or sufficient detail in the 
Phase II application may be sufficient reason for the peer review committee 
to exclude the Phase II from consideration. If so, the applicant may apply 
later for Phase II support. Such applications will be reviewed by an 
appropriate scientific review group convened by the NIH. 

In addition, the Phase II portion of a Fast Track application must include a 
concise Commercialization Plan (Product Development Plan), which is limited 
to ten pages. Label this section clearly and include it in Section J of the 
Phase II Research Plan. More detailed instructions on the preparation of a 
Fast Track application are described in the PHS 398 at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf#page=21.

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)

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE CENTER FOR SCIENTIFIC 
REVIEW WILL NO LONGER BE ACCEPTED.  This policy does not apply to 
courier deliveries (i.e. FEDEX, UPS, DHL, etc.) 
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-012.html)

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

PEER REVIEW PROCESS

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

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the National Heart, Lung and Blood 
Advisory Council and the National Diabetes and Digestive and Kidney Diseases 
Advisory Council.

Review Criteria

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

o Significance 
o Approach 
o Innovation
o Investigator
o Milestones and Proof of Principle
o Environment
  
The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.

ALL SBIR/STTR APPLICATIONS

1.  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? 

2.  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? 

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

4.  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?

5.  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? 

In accordance with NIH policy, the following criteria will be applied to ALL 
applications:

Budget:  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? 

Human Subjects: 

1.  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? 

2.  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? 

3.  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? 

4.  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? 

5.  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? 
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? 

Phase II Application Review Criteria:  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 (Product 
Development Plan) that adequately addresses the 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? 

Phase I/Phase II Fast-Track Application Review Criteria
For Phase I/Phase II Fast Track applications, the following criteria also 
will be applied:

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

2.  Did the applicant submit a concise Commercialization Plan (Product 
Development Plan) that adequately addresses the areas described in the 
Research Plan, item J? 

3.  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? 

4.  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.

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 appropriateness of the proposed budget and duration in relation 
to the proposed research. The following evaluation criterion will be 
presented in an administrative note in the Summary Statement and will not 
factor into the numerical score: 

DATA SHARING: The adequacy of plans to make the methods and materials 
generated in the project widely available in a timely fashion to the 
scientific community, given the proposed plan to exercise (or not to 
exercise) intellectual property rights. 

AWARD CRITERIA 

Applications will compete for available funds with all other recommended SBIR 
and STTR applications. Funding decisions for Phase I or Phase II applications 
will be based on quality of the proposed project as determined by peer 
review, availability of funds, and relevance to program priorities. 

Phase II applications will be selected for funding based on the initial 
priority score, assessment of the Phase I progress and determination that 
Phase I goals were achieved, the project's potential for commercial success, 
and the availability of funds. 

FAST-TRACK Phase II applications may be funded following submission of the 
Phase I progress report and other documents necessary for continuation. 

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures. In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). 

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43). 

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community. The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences. 

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998. 

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED 

EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy 
requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects. 
You will find this policy announcement in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. 

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). 
It is the responsibility of the applicant to provide the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research. 
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances. Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA. It is important for applicants to understand the basic scope of 
this amendment. NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. 
Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time. If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award. 

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites. Furthermore, we 
caution reviewers that their anonymity may be compromised when they directly 
access an Internet site. 

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance No. 93.839 (NHLBI, DBDR), and No. 93.848 (NIDDK, 
DKUHD) and is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.  Awards are made under 
authorization of Sections 301 and 405 of the Public Health Service Act as 
amended (15 USC 638 and 42 USC 241 and 284) and administered under NIH grants 
policies described at http://grants.nih.gov/grants/policy/policy.htm and 
under Federal Regulations 42 CFR 52 and 45 CFR Parts 74.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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