RELEASE DATE:  July 22, 2003

PA NUMBER:  PA-03-154 (The SBIR (R44) portion of this PA has been reissued, 
                       see PA-06-036)

EXPIRATION DATE:  December 7, 2005

National Institute on Drug Abuse (NIDA)



o Purpose of the PA
o Research Objectives
o Mechanisms 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


This PA solicits Small Business Innovation Research (SBIR) and Small 
Business Technology Transfer (STTR) grant applications that propose the 
advanced stage development of pharmacological treatment agents for drug 
and nicotine abuse and dependence.  This PA specifically invites 
applications for the competing continuation of previously funded Phase 
II SBIR and STTR grants, to take existing, promising compounds through 
the next step of drug discovery and development.  Only SBIR and STTR 
Phase II awardees are eligible to submit a competing continuation 
application.  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 solicitation.

This PA does not support early stage drug development such as the 
identification of new targets or lead compounds.  The expectation is 
that as a result of support from previous SBIR/STTR Phase I and Phase 
II grants, a promising new molecular entity (NME) or entities have been 
identified as potential pharmacological treatment agents for drug or 
nicotine abuse and dependence, and that the entities have gone through 
sufficient preclinical testing to justify their continued development.  
It is expected that each NME be in an advanced stage of preclinical 
development and ready to begin the process for translation into 
clinical trials (e.g., pharmacokinetic assays, large-scale production 
carried out under Good Manufacturing Practices (GMP), toxicity testing, 
formulation and analytical development, and clinical evaluation).  
These translational activities would be supported by the competing 
continuation of a Phase II SBIR/STTR grant.  



Transitioning a new molecular entity, or NME (a term which is applied 
by the Food and Drug Administration to new pharmaceutical and 
immunological agents) from the preclinical to clinical phase of 
development, requires large-scale production of the NME and toxicity 
testing, activities which are both costly and time consuming.  The cost 
and time constraints imposed by advanced stage development of an NME 
pose a significant obstacle for small businesses.   A recipient of an 
NIH SBIR/STTR Phase I and Phase II award normally receives under $1 
million, and less than three years of support.  Although Phase I and 
Phase II SBIR/STTR support is sufficient for initial discovery efforts 
(e.g., compound synthesis and some in vitro and in vivo preclinical 
pharmacological testing), it is not adequate to support either the kind 
of developmental work needed for compliance with the Food and Drug 
Administration's requirements for an investigational new drug (IND), or 
for clinical trials. 

This PA adds up to another three (3) years of support to small 
businesses for drug development by providing a second stage of Phase II 
SBIR/STTR funding through the mechanism of a SBIR/STTR Phase II 
competing continuation grant.  It is recognized that an award of this 
type may not support the entire medications development timeline for 
any given drug.  The competing continuation grant will, however, allow 
small businesses to carry a medication from the preclinical to the 
clinical stage, which will aid in attracting interest and investment by 
third parties, and provide an important resource for new 
pharmaceuticals for the treatment of substance abuse. 

Research topics

The following examples would make appropriate topics for proposed SBIR 
or STTR Phase II competing continuation projects.  These are meant for 
illustrative purposes only and are not exclusive of other appropriate 
activities.  Research and development efforts can be focused on 
medications for the treatment of cocaine, methamphetamine, and other 
stimulant abuse, as well as towards opiate, cannabis, PCP and club 
drugs.  The medications under development should be targeted towards 
attainment of abstinence, maintenance, and/or relapse prevention.

o  Preclinical studies, including pharmacology and toxicology, beyond 
those conducted under the initial SBIR Phase I and Phase II grants.  
The studies conducted under the previous grants should be sufficient to 
provide a sound rationale for continued development of the entity or 
o  Completion of studies as required by the FDA for an IND application.
o  Human laboratory clinical trials to determine a medication's safety 
profile, metabolism, cardiovascular effects, interaction with drugs of 
abuse, etc.
o  Clinical studies to assess the efficacy of the medication under 


This PA will use the NIH SBIR and STTR competing continuation award 
mechanisms, which is a set aside program (see   The 
applicant will be solely responsible for planning, directing, and 
executing the proposed project.  

Only competing continuations of previously funded NIH Phase II SBIR or 
STTR awards will be accepted under this PA.  The expectation is that, 
as a result of support from previous SBIR or STTR Phase I and Phase II 
grants, sufficient positive findings have been produced that provide a 
strong rationale for the continued development of the NME or NMEs under 
investigation, and that the development will ultimately lead to 
clinical investigations to support Federal regulatory approvals. 

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 of 
pharmacotherapies for the treatment of substance abuse, and must be a 
logical extension of the previously supported Phase II research.  


It is expected that applications will normally not exceed a project 
period of three years and total costs of $1,000,000 per year.


The total amount of all consultant costs and contractual costs normally 
may not exceed 50 percent of the total costs requested for Phase II 
SBIR or STTR applications.  Competing continuation grant applications 
submitted under this PA may exceed these guidelines, however, when well 
justified.  Examples of well-founded reasons for exceeding these 
guidelines include, but are not limited to, subcontracts to clinical 
research organizations to carry out aspects of clinical evaluation or 
subcontracts to assure compliance with GMP expectations of the FDA.


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


Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.  On an 
SBIR application, the principal investigator must have his/her primary 
employment (more than 50 percent) with the small business at the time 
of award and for the duration of the project.  The principal 
investigator on an STTR application may be employed with the small 
business concern or the participating non-profit research institution 
as long as s/he has a formal appointment with or commitment to the 
applicant small business concern, which is characterized by an official 
relationship between the small business concern and that individual.


We encourage your inquiries concerning this PA and welcome the 
opportunity to answer questions from potential applicants.  Inquiries 
may fall into two areas:  scientific/research and financial or grants 
management issues:

o Direct your questions about scientific/research issues to:

Cathrine Sasek, Ph.D.
SBIR/STTR Coordinator
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 5237
Bethesda, MD  20892-9591
Telephone:  (301) 443-6071
Fax:  (301) 443-

o Direct your questions about financial or grants management matters 

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
FAX:  (301) 594-6847


Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at in 
an interactive format.  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:  For further 
assistance contact GrantsInfo, Telephone (301) 710-0267, Email:

APPLICATION RECEIPT DATES: Applications submitted in response to this 
PA will be accepted at the standard application deadlines, which are 
available at  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)

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

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


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group convened in accordance with the standard NIH peer review 
procedures ( will evaluate 
applications for scientific and technical merit.  

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

o Receive a written critique
o Undergo a selection process in which only those applications deemed 
to have the highest scientific merit, generally the top half of 
applications under review, will be discussed and assigned a priority 
o Receive a second level review by an appropriate advisory council or 


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


SIGNIFICANCE:  Does the study address an important problem?  Does the 
proposed project have commercial potential to lead to a marketable 
product or process?  What may be the anticipated commercial and 
societal benefits of the proposed activity?  If the aims of the 
application are achieved, how do they advance scientific knowledge?  
Does the proposal lead to enabling technologies (instrumentation, 
software, etc.) for further discoveries? What is the throughput and 
cost effectiveness of the proposed assay(s)? Will the technology have a 
competitive advantage over existing/alternative technologies that can 
meet the market needs? What will be the impact on future clinical 
trials or on clinical practice?

APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project?  This includes the statistical rationale for the study 
design and the choice of sample size. Is the proposed plan a sound 
approach for establishing technical and commercial feasibility?  Does 
the applicant acknowledge potential problem areas and consider 
alternative strategies?  Has the applicant considered how the Phase II 
study, if promising, could proceed into eventual definitive testing of 
the diagnostic strategy? 

INNOVATION:  Does the project challenge existing paradigms or employ 
novel technologies, approaches, or methods?  Are the aims original and 
innovative?  How is the proposed diagnostic strategy superior to 
existing alternatives?  What additional uses can be projected for the 
proposed assay(s), or what additional groups of patients might benefit 
from the new diagnostics strategy? 

INVESTIGATOR:  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 sub-contractors  (if any)?

ENVIRONMENT:  Is there sufficient access to resources (equipment, 
facilities, etc.)?  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?  Are the planned statistical and data management 
resources adequate?

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

human subjects and protections from research risk relating to their 
participations in the proposed research will be assessed. (See 
additional information and criteria included in the section on Federal 
Citations, below).
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research will be assessed.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See additional 
information and Inclusion Criteria in the sections on Federal 
Citations, below).

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

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 

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 of the medical safety and the 
validity and integrity of the trial including mechanisms for reporting 
Adverse Events and Serious 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 

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.  
Is the percent effort listed for the PI appropriate for the work 
proposed?  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.

In addition to the above criteria, the following criteria will be 

1.  Does the activity as proposed address issues related to Federal 
regulatory approval processes?

2.  What will be the effect of these studies on the concepts or methods 
that drive this field?

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 

2.  Are the improvements in the revised application appropriate?


Applications submitted in response to a PA will compete for available 
funds with all other recommended SBIR and STTR applications.  Portions 
of the SBIR and STTR allotments will not be designated for this 
initiative.  The following will be considered in making funding 

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.


HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained. 

components involving Phase I and II clinical trials must include 
provisions for assessment of patient eligibility and status, rigorous 
data management, quality assurance, and auditing procedures.  In 
addition, it is NIH policy that all clinical trials require data and 
safety monitoring, with the method and degree of monitoring being 
commensurate with the risks (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998:  

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

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
a complete copy of the updated Guidelines are available at
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 

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

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 

policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at

DRUG ABUSE:  Researchers funded by NIDA who are conducting research in 
community outreach settings, clinical, hospital settings, or clinical 
laboratories and have ongoing contact with clients at risk for HIV 
infection, are strongly encouraged to provide HIV risk reduction 
education and counseling.  HIV counseling should include offering HIV 
testing available on-site or by referral to other HIV testing service 
for persons at risk for HIV infection including injecting drug users, 
crack cocaine users, and sexually active drug users and their sexual 
partners.  For more information see

Council on Drug Abuse recognizes the importance of research involving 
the administration of drugs to human subjects and has developed 
guidelines relevant to such research.   Potential applicants are 
encouraged to obtain and review these recommendations of Council before 
submitting an application that will administer compounds to human 
subjects.  The guidelines are available on NIDA's Home Page at under the Funding, or may be obtained by calling (301) 

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of 
research on hESCs can be found at and at  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see   It is the responsibility of the applicant to 
provide the official NIH identifier(s)for the hESC line(s)to be used in 
the proposed research.  Applications that do not provide this 
information will be returned without review. 

The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

The Department of Health and Human Services (DHHS) issued final 
modification to the "Standards for Privacy of Individually Identifiable 
Health Information", the "Privacy Rule," on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on "Am 
I a covered entity?"  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at

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

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

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92.  All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at

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

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
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