COMPETING CONTINUATION AWARDS OF SBIR/STTR PHASE II GRANTS FOR PHARMACOLOGICAL 
AGENTS AND BIOMARKERS FOR ALCOHOLISM AND ALCOHOL-RELATED DISEASES

RELEASE DATE:  May 29, 2003   

PA NUMBER: PA-03-129

EXPIRATION DATE: This PA will expire on May 30, 2006, unless re-issued.

IMPORTANT CHANGE: The opportunity to apply for an NIAAA SBIR and STTR Phase II 
Competing Renewal is available from the PHS 2006-2 SBIR/STTR Omnibus Solicitation. 
(See Program Descriptions and Research Topics (PDF or MS Word)). Interested 
applicants must apply using the electronic application package from the parent 
SBIR (PA-06-120) or STTR (PA-06-121) Funding Opportunity Announcements (FOAs).  
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.273

APPLICATION RECEIPT DATE(S): NOTICE: This program announcement (PA) must be 
read in conjunction with the current Omnibus Solicitation of the National 
Institutes of Health, Centers for Disease Control and Prevention, and Food 
and Drug 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 current SBIR/STTR Omnibus Solicitation apply. 
 
THIS PA CONTAINS THE FOLLOWING INFORMATION:

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

PURPOSE OF THE PA 

The SBIR/STTR programs were initiated as a means for government agencies to 
use small businesses to stimulate technological innovation and to help 
agencies meet their research and development (R&D) needs.  An additional 
provision of these programs is the expected commercialization of the 
research. Certain types of research require clinical evaluation and Federal 
regulatory approvals before the Phase III of the small business research 
pathway can ever be realized.  A recipient of an NIH SBIR/STTR Phase I and 
Phase II award normally receives no more than $1 million. If the intended 
commercialized product is a medical device, drug, or biologic, the $1 million 
often represents a small fraction of the funds necessary to complete the 
studies required for approval and licensing by the Food and Drug 
Administration (FDA) or other Federal agencies.  

Moreover, a recipient of an NIH SBIR/STTR Phase I and Phase II award normally 
receives less than three years of support.  Yet, the process of moving 
promising new products from bench to bedside typically takes more than a 
decade.  The drug discovery timeline, for example, starts with identification 
of an agent or class of agents with particular activity, identification and 
optimization of lead compounds, and subsequent pre-clinical testing of these 
compounds for safety and toxicity.  Those agents still considered viable 
after such rigorous scrutiny are then brought to human subjects for clinical 
evaluation of a variety of aspects of the agent, including safety, efficacy, 
and dosage determination.   Similarly long timelines obtain for other 
products intended to understand, diagnose, prevent, or treat human health 
disorders (e.g., medical devices, vaccines).  

Despite the cost and the length of time required to move such products from 
the laboratory to the patient, these are precisely the products with 
potential to contribute significantly to the economy of the nation and to the 
health of her people. The intent of the SBIR/STTR Phase II competing 
continuation grants is to support such research and development.

The purpose of this Program Announcement (PA) is to solicit from Phase II 
SBIR/STTR awardees grant applications that propose to continue the process of 
developing products that ultimately require:  1) clinical evaluation and 2) 
approval of a Federal regulatory agency.  Such products include, but are not 
limited to:  drugs, vaccines, alcohol-sensitive biochemical markers, 
radioligands, medical implants, imaging protocols proposed for clinical use, 
and medical devices.  

RESEARCH OBJECTIVES

Background

During the past decade advances have been made in medications development to 
treat alcoholism. The fruits of these efforts have been highlighted by the 
FDA approval of naltrexone, the first medication approved for alcoholism in 
the 50 years since the introduction of disulfiram. Acamprosate has also been 
studied extensively in Europe and is currently approved for alcoholism 
treatment in over 24 countries.  Ondansetron and gabapentin are two more 
promising medications that are currently being evaluated in clinical trials.

Advances have also been made in understanding the biological mechanisms 
underlying alcohol drinking behavior. For example, it is now known that 
multiple neurotransmitter, neuromodulator, and hormonal systems can alter 
alcohol intake and are either directly or indirectly involved in problematic 
drinking. These include opioid, serotonin, dopamine, gamma-aminobutyric acid 
(GABA), glutamate, neuropeptide Y (NPY), cannabinoid, and hypothalamic-
pituitary-adrenal (HPA) systems. This recent knowledge has led to many 
biological targets for testing novel pharmacological agents. 

Because medications mentioned above produce small to medium effects to reduce 
or prevent drinking, development and evaluation of new and more potent 
medications remain a high priority. Several promising pharmacological agents 
could lead to clinical testing. These include, but are not limited to, 
memantine, a non-competitive NMDA antagonist; kudzu and its purified active 
components (e.g., puerarin); corticotropin-releasing factor (CRF) 
antagonists; opioid receptor subtype antagonists such as delta2 antagonist 
naltriben; 6-beta naltrexol, an active metabolite of naltrexone; synthetic 
neurosteroids; 1-aminocyclopropanecarboxylic acid (ACPC), a NMDA partial 
agonist; FG 5974 (and its analogues), a 5-HT1A agonist/5-HT2A antagonist; and 
agents with selective affinity to GABAA alpha1 or GABAA alpha5 receptor 
subunits. 

As basic research reveals promising targets relevant to alcohol abuse and its 
consequences, analogs acquired from existing libraries, or newly-synthesized 
analogs developed through computational and combinatorial chemistry can be 
screened in vitro or in standardized behavioral assays for potential 
therapeutic efficacy.

Advances in molecular genetics (e.g., microarray analysis, targeted 
mutations, and proteomics) offer a powerful approach for broad-spectrum 
scanning of participants in the adaptive process.  Individual gene clusters 
or functionally-related proteins can be identified in specific brain regions 
in temporal relation to alcohol exposure.  Such studies may identify 
biochemical pathways and brain circuits which are preferentially recruited as 
alcohol dependence develops.  Receptors or pathways involved in alcohol 
drinking and other alcohol effects can be disabled selectively with targeted 
knockout strategies. 

Progress has also been made in elucidating the mechanisms of alcohol-induced 
organ damage. In particular, several primary factors underlying the 
pathogenesis of alcoholic liver disease have been identified including 
cytokines and reactive oxygen species (ROS). For example, antioxidants, such 
as S-adenosyl-L- methionine (SAMe), have been shown to reduce alcohol-induced 
liver injury in animals. Potential new treatments of alcoholic liver disease 
include antioxidants, such as SAMe and vitamin E; as well as other types of 
agents including phosphatidylcholine, a phospholipid; pirfenidone, a new 
anti-fibrotic agent; and metformin, an insulin-sensitizing agent.  

The development of effective biochemical markers represents a powerful means 
for early diagnosis and treatment of alcohol dependent/abuse patients and for 
the identification of individuals who have a predisposition for alcoholism.  
There are two different types of alcohol-sensitive biochemical markers: trait 
markers and state markers.  

Trait biomarkers have the ability to detect inborn characteristics of 
individuals who are vulnerable for alcoholism.  This type of marker would be 
invaluable for screening of high-risk individuals (e.g., children of 
alcoholics) and targeting them with preventive or early treatment 
interventions.  In addition, trait markers might assist practitioners in 
identifying subpopulations of alcoholics who may need different treatment 
strategies. An ideal trait marker should have several features.  First, it 
should display validity in detecting people susceptible to alcoholism, 
particularly before the onset of alcoholism or during periods of stable 
abstinence. Second, it should be measured easily and reliably.  Third, it 
should be specific for only alcoholism and not affected by other medical or 
psychiatric disorders or drugs.  Since alcoholism is a complex disease, it is 
likely that more than one type of gene and protein exist as a trait marker.

State markers or markers of alcohol consumption serve several important 
purposes.  First, they can assist physicians in diagnosing individuals with 
chronic drinking problems, particularly patients who deny excessive drinking. 
Moreover, they may also identify individuals in early stages of heavy 
drinking, thus avoiding the long-term medical, psychological, and social 
consequences of chronic alcoholism.  Second, state biomarkers can aid in the 
diagnosis and treatment of other diseases (liver diseases, pancreatitis, and 
cardiovascular diseases) that were, at least, caused by excessive drinking. 
Biomarkers that detect alcohol-induced tissue/organ damage would be 
particularly valuable.  Third, they are useful in alcohol treatment and 
prevention programs. Since the goal of many programs is abstinence, 
monitoring relapse is important in gauging success.  Last, state biomarkers 
are important in clinical alcohol trials.  Although measurement of self-
report has become more sophisticated (e.g., Timeline Followback), it still 
relies on accurate reporting. These biomarkers would be essential in at least 
confirming the self-report. 

There are several ideal features of a state marker.  These include high 
validity, reliability, stability, reasonable cost, practicability, 
acceptability to both practitioners and patients, and transportability in 
different settings.  Several biomarkers are currently being used including 
carbohydrate-deficient transferrin (CDT), gamma glutamy transferase (GGT), 
aspartate aminotransferase (AST), alanine aminotransferase (ALT), and mean 
corpuscular volume (MCV).  Many of these markers are elevated due to alcohol-
induced tissue damage.  Unfortunately, these markers have limitations, and 
thus new markers need to be developed.

Example of Research Topics

These examples are meant for illustrative purposes and are not exclusive of 
other appropriate activities:

o  Preclinical studies, including pharmacology and toxicology, beyond those 
conducted under the Phase I (R43) and initial Phase II (R44) grants.  Some in 
vivo or in vitro studies would be expected to have been carried out in Phase 
I or the initial Phase II grant.  

o  Completion of studies as required by the Food and Drug Administration 
(FDA) for Investigational New Drug (IND) or Radioactive Drug Research 
Committee (RDRC) application.  

o  Development and clinically evaluation of new alcohol-sensitive biomarkers

o  Assessment of devices with regard to performance standards related to the 
FDA approval process.

o  Safety and effectiveness studies of novel medical devices.

o  Biocompatibility studies of surface materials of putative medical implants.

o  Evaluation of novel imaging approaches for diagnostic purposes.

o  Clinical studies in support of New Drug Application approval by the FDA.

o  Clinical studies in support of Pre-Market Approval for biomarkers/medical 
devices by the FDA.

MECHANISM(S) OF SUPPORT

Unsolicited SBIR/STTR competing continuation applications will not be 
accepted. That is, an SBIR/STTR Phase II competing continuation application 
must be in response to this PA, and the application will only be accepted as 
a competing continuation of a previously funded NIH Phase II SBIR or STTR 
award (R44 mechanism, R42 mechanism.)  The previously funded NIH Phase II 
grant need not have been submitted in response to any particular 
solicitation, but the application for the competing continuation must propose 
research and development that represents a logical extension of the 
previously supported Phase II research as described in the announcement.  The 
applicant will be solely responsible for planning, directing, and executing 
the proposed project.  

The SBIR/STTR Phase II competing continuation would represent a continuation 
of support for research/research and development of such previous work funded 
by the original Phase II R44 grant.  The expectation is that as a result of 
support from a previous SBIR/STTR Phase I (R43) and Phase II (R44) grant, 
promising results had been produced that indicate not only the merit of 
further research and development, but also that clinical investigations and 
Federal regulatory approvals will ultimately be required to realize the 
potential of the product being researched and developed.

Activities supported by a competing continuation of a Phase II SBIR/STTR 
grant may include an extension and expansion of preclinical research and 
development, clinical testing, and other scientific research and development 
activities that would ultimately be useful in meeting the requirements and 
expectations of Federal regulatory processes.  

A competing continuation Phase II award should not, however, be used to 
conduct very early stage research (e.g., identifying targets for drugs, 
initial identification of lead compounds, etc.).  In addition, like a Phase I 
and initial Phase II grant, the competing continuation Phase II award will 
not support costs for legal consultation, marketing efforts, etc.  

PROJECT PERIOD AND AMOUNT OF AWARD

Awards routinely will be in the range of $750,000 to $1,000,000 total costs 
per year for up to three years. 

Because the length of time and cost of drug discovery and development 
represents a long term research and development commitment, a project period 
of up to three years and a budget not to exceed total costs of $1,000,000 per 
year (including direct costs, indirect costs and fee/profit) will be 
considered under this PA if the time period and amount are well justified.
Consultant and Contractual Costs

The total amount of all consultant costs and contractual costs normally may 
not exceed 50% of the total costs requested for initial SBIR Phase II 
applications.  SBIR Phase II competing continuation grant applications 
submitted under this PA may exceed this guideline, however, when well 
justified and when those costs are necessary to support clinical studies or 
trials and related expenses. Examples of well founded reasons for exceeding 
this guideline include, but are not limited to, subcontracts to clinical 
research organizations to carry out aspects of clinical evaluation or 
subcontracts to assure compliance with Good Manufacturing Practices (GMPs) 
expectations of the FDA. 

For STTR Phase II applications, the small business MUST perform at least 30% 
of the research/R&D and the partnering research institution must perform at 
least 40% of the proposed research/R&D.  

Commercialization Plan

All Phase II grant applications, including this competing continuation 
application, require a "Commercialization Plan [formerly "Product Development 
Plan,"] as described in Item j of the SBIR/STTR Phase II instructions (PDF or 
MS Word).  The Commercialization Plan is meant in part to demonstrate the 
commercial viability of the product researched and developed with SBIR 
support.  Since this Phase II competing continuation application mechanism 
supports a more advanced stage of research and development than the R44 Phase 
II mechanism, the Commercialization Plan should reflect more advanced plans 
and arrangements for commercialization than what might be submitted for an 
R44 application.  For example, part of a Commercialization Plan that would be 
appropriate to drug development supported by a Competing Continuation 
application would be a clear indication of an arrangement (e.g., strategic 
alliance, letters of support) with another party through which the final 
stages of the work might be supported or carried out, including additional 
clinical trials, FDA submissions, drug manufacturing and drug 
commercialization.  This example is meant for illustrative purposes; the 
details of any Commercialization Plan will depend upon the particular 
circumstances represented in a given application.

ELIGIBILITY

Eligible to apply for SBIR/STTR Phase II competing continuation awards are 
NIH SBIR/STTR Phase II awardees that meet the definition of a small business 
concern (as described in the NIH SBIR/STTR Phase II instructions) and whose 
projects are developing products that would ultimately require clinical 
studies and Federal regulatory approval.  The previously funded Phase II 
SBIR/STTR grant need not have been submitted in response to a particular 
solicitation, as long as the research is appropriate to the purpose of this 
PA.
  
ELIGIBLE INSTITUTIONS

The competing continuation application must be a continuation of a previously 
completed Phase II (R44) SBIR/ Phase II STTR (R42) grant focusing on research 
and development of a product or products ultimately requiring clinical 
testing and Federal regulatory approval.  To maintain eligibility to seek a 
Phase II competing continuation grant, a Phase II grantee organization should 
submit an application for the Phase II competing continuation grant within 
the first six receipt dates following the expiration of the initial Phase II 
budget.  Other eligibility requirements for a Phase II competing continuation 
grant are identical to those for the initial Phase II (R44) applications and 
can be found at 
http://grants.nih.gov/grants/funding/sbirsttr2/PhaseII_SBIRSTTR.pdf (PDF) or 
http://grants.nih.gov/grants/funding/sbirsttr2/PhaseII_SBIRSTTR.doc (MS Word)

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.  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 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:

Joanne B. Fertig, Ph.D.
Division of Clinical and Prevention Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 505 MSC 7003
Bethesda, MD 20892-7003 (for courier, use Rockville, MD 20852)
Telephone: (301) 443-0635
Fax: (301) 443-8774
Email: [email protected]

Peter B. Silverman, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402
Bethesda, MD 20892-7003 (for courier, use Rockville, MD 20852)
Tel. 301-402-6966
FAX  301-594-0673
Email: [email protected]

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

Judy Fox (formerly Simons)
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 505 MSC 7003
Bethesda, MD 20892-7003 (for courier, use Rockville, MD 20852)
Telephone: (301) 443-2434
Email: [email protected]

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.)  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 on the 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 using the PHS 398 grant 
application. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].
  
All Phase II SBIR/STTR grant applications, including this competing 
continuation application, require a "Commercialization Plan," as described in 
item J of the Phase II SBIR Instructions 
http://grants.nih.gov/grants/funding/sbir.htm). The Commercialization Plan is 
meant, in part, to demonstrate the commercial viability of the product 
researched and developed with SBIR support.  Since this Phase II competing 
continuation application mechanism supports a more advanced stage of research 
and development than the R44 Phase II mechanism, the Commercialization Plan 
should reflect more advanced plans and arrangements for commercialization 
than what might be submitted for an initial R44 application.

For purposes of identification and processing, enter the following title and 
number of this PA in item 2 on the face page of the application: PA-03-129; 
"COMPETING CONTINUATION PHASE II SBIR/STTR   NIAAA" 

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. 

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 must be received by or mailed on or before the receipt dates 
described on the first page of this program announcement. The Center for 
Scientific Research (CSR) will not accept any application in response to this 
PA that is essentially the same as one currently pending initial review 
unless the applicant withdraws the pending application.  The CSR will not 
accept any application that is essentially the same as one already reviewed. 
This does not preclude the submission of a substantial revision of an 
application already reviewed, but such application must include an 
Introduction addressing the previous critique.

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

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 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 second level review by the 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: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

ALL SBIR/STTR APPLICATIONS

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

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

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

Investigators: Is the Principal Investigator capable of coordinating and 
managing the proposed SBIR/STTR? Is the work proposed appropriate to the 
experience level of the Principal Investigator and other researchers, 
including consultants and subcontractors (if any)? Are the relationships of 
the key personnel to the small business and to other institutions appropriate 
for the work proposed?

Environment:  Is there sufficient access to resources (e.g., equipment, 
facilities)? Does the scientific and technological environment in which the 
work will be done contribute to the probability of success? Do the proposed 
experiments take advantage of unique features of the scientific environment 
or employ useful collaborative arrangements? 

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

o  Does the activity as proposed address issues related to Federal regulatory 
approval processes?
o  What will be the effect of these studies on the concepts or methods that 
drive this field?

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.)

Protection of Human Subjects from Research Risks - for all studies involving 
human subjects.  See instructions and "Guidance for Preparing the Human 
Subjects Research Section." 

o  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? 

o  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? 

o  Are the plans proposed for the protection of human subjects adequate? 

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.)

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?

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.  

o  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? 

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.
Amended Applications

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

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended SBIR and STTR applications.  The following will be 
considered in making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

RECEIPT AND REVIEW SCHEDULE  
See http://grants.nih.gov/grants/funding/sbirsttr_receipt_dates.htm 

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 

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 "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.

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.

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 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.

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