RELEASE DATE:  October 31, 2003

RFA Number: RFA-AI-04-005

Department of Health and Human Services (DHHS)

National Institutes of Health (NIH) 

National Institute of Allergy and Infectious Diseases (NIAID) 

No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research



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

NOTICE: This Request for Application (RFA) must be read in conjunction with 
TRANSFER (STTR) GRANT APPLICATIONS.  The solicitation (see (see contains 
information about the SBIR and STTR programs, regulations governing the 
programs, and instructional information for submission. All of the 
instructions within the SBIR/STTR Omnibus Solicitation apply with the 
following exceptions: 

o Special receipt date and mailing instructions
o Additional eligibility and significance requirements
o Extended project period and amount of award
o Requirement for critical path and annual milestones
o Mandatory NIAID "Clinical Terms of Award" for clinical research
o Initial review convened by the NIAID Division of Extramural Activities
o Additional review considerations


This RFA invites applications for the competing continuation of eligible SBIR 
or STTR Phase II awardees to continue the process of developing a product 
that requires clinical evaluation and FDA approval. An "eligible application" 
must develop one of the following products: therapeutics (drugs or 
antibodies) to treat HIV or HIV-related opportunistic infections, anti-
inflammatory therapeutics, improved transplantation strategies, or other new 
or improved vaccines, antiviral or antimicrobial agents for infectious 

The progress from an eligible SBIR/STTR Phase II grant should be commensurate 
with previous support and indicate the merit of continued NIH research and 
development (R&D) funding.  Activities supported by a competing continuation 
of a Phase II SBIR/STTR grant may include additional pre-clinical R&D, 
clinical testing, and other R&D activities needed to meet requirements of the 
FDA. A competing continuation SBIR/STTR Phase II award may not be used to 
conduct early stage research (e.g., identifying targets for drugs, initial 
identification of lead compounds, etc.).


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 R&D needs.  An additional provision of these programs is 
the expected commercialization of the research.  Certain types of research 
require clinical evaluation and FDA approvals before the Phase III of the 
small business research pathway can 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 

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 research to commercialization 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, 
effectiveness, 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 
improvement of public health.  The intent of the NIAID SBIR/STTR Phase II 
competing continuation awards is to support such R&D.


Eligible to apply for NIAID SBIR/STTR Phase II competing continuation awards 
under this RFA 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 a product that requires 
clinical evaluation and FDA approval.  Only applications on one of the 
following products will be considered responsive to this RFA:  

o therapeutics (drugs or antibodies) to treat HIV infections
o therapeutics (drugs or antibodies) for HIV-related opportunistic infections
o anti-inflammatory therapeutics
o improved transplantation strategies
o new or improved vaccines, antiviral or antimicrobial agents for infectious 

Applications that are not considered responsive to one of these topics will 
be returned without review. Applications may be submitted either before or 
after expiration of the eligible Phase II budget period.


This RFA usually uses the Phase II SBIR (R44) and STTR (R42) grant 
mechanisms, which are set-aside programs. The application for the competing 
continuation must propose R&D that represents a logical extension of the 
previously supported Phase II research.  When awarded as a grant, the 
applicant is responsible for planning, directing, and executing the proposed 
project. When appropriate, NIAID may offer to award Phase II SBIR/STTR 
competing continuation applications using a small business cooperative 
agreement SBIR (U44) or STTR (U42) mechanism.  In the cooperative agreement 
mechanism, the Principal Investigator retains the primary responsibility and 
dominant role for planning, directing, and executing the proposed project, 
with NIAID staff being substantially involved as a partner with the Principal 

This RFA uses just-in-time concepts. This RFA does not use modular budget 

Cost-sharing arrangements are strongly encouraged since the SBIR/STTR 
programs cannot support all activities that may be required to advance a 
project to feasibility demonstration in a clinical trial.

Except as otherwise stated in this RFA, awards will be administered according 
to the NIH Grants Policy Statement (NIHGPS), currently available at


The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines of 
funding support and project duration periods for SBIR and STTR Phase I and 
Phase II awards.  Competing continuation applications for SBIR/STTR Phase II 
awards may be for a project period of up to three years and a budget not to 
exceed a total cost of $1 million per year (including direct cost, F&A, and 
fee/profit) provided the time period and amount are well justified.


NIAID intends to commit approximately $4 million to fund 4-6 SBIR competing 
continuation awards and $1 million to fund 1-2 STTR competing continuation 
awards in FY2004 or FY2005. Although the financial plans of the NIAID provide 
support for this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 

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 RFA 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 for safety, 
toxicity, or efficacy testing in animals, 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 competing Phase II applications, the small business MUST perform at 
least 30% of the R&D and the partnering research institution must perform at 
least 40% of the proposed R&D.


Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation. 
See (PDF) 
or (MS 
Word).  Only 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 criteria as described in the SBIR/STTR 
Omnibus Solicitation.  The competing continuation application must be a 
continuation of a previously funded Phase II (R44) SBIR or Phase II STTR 
(R42) grant focusing on R&D of a product or products ultimately requiring 
clinical testing and Federal regulatory approval.  


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. Individuals from underrepresented racial and ethnic 
groups, as well as individuals with disabilities, are encouraged to apply for 
NIH programs. The Principal Investigator (PI) on an SBIR application 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 PI on 
an STTR application may be employed with the small business concern or the 
participating non-profit research institution as long as she or 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.


Follow the Instructions for the Significance Section of an NIH SBIR/STTR 
Phase II Application.  In addition, include the following in this section:

Item b. Significance Section 

o Describe what makes the project eligible for a competing continuation Phase 
II award.
o Describe a critical path(s) to product approval with detailed milestones to 
be reached during each year of the proposed project period.  A milestone is 
defined as a specific R&D achievement that either demonstrates an essential 
product attribute or completes a step necessary to advance the product 
towards completion. Examples of milestones include, but are not limited to:  
passing toxicity studies; demonstrating sufficient bio-availability; showing 
efficacy in an animal model; completion of a prototype of a diagnostic tool; 
FDA submission and acceptance of an Investigational New Drug Application 
(IND) or an Investigational Device Exemptions (IDE); initiation of a clinical 
trial; and follow-on funding.

o  List in table format the milestones that have been achieved to date and 
those for each grant year of the proposed project. Include in the table the 
remaining milestones after the proposed grant period and estimated timeline 
to complete the product R&D. 

Additional milestones may be suggested by the review committee.  The review 
committee may also suggest which, if any, of the milestones should be 
identified in the Terms of Award as essential for annual non-competitive 
renewal.  Failure to achieve annual milestones may be grounds for not 
continuing future years of an award.

Item c. Phase II Final Report

Label this section, "Phase II Final Report."  Follow the Instructions for the 
Phase I Final Report of an NIH SBIR/STTR Phase II Application except replace 
all references to "Phase I" with "Phase II."   

Clinical Terms of Award

When human clinical studies or trials are a component of the research 
proposed, NIAID policy requires that studies be monitored commensurate with 
the degree of potential risk to study subjects and the complexity of the 
study.  Terms and Conditions of Award will be included with awards.  AN 
UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is 
available at:  
The full policy, including terms and conditions of award, is available at:

A mandatory milestone for projects involving humans is the approval of the 
final clinical protocol by NIAID prior to the accrual of subjects into the 
trial.  Applications that contain or comprise a clinical trial should also 
include a budget item for preparation of a clinical protocol.  Protocol 
development must be consistent with Federal and NIAID specific regulations 
governing the conduct of human subjects research 
(  Potential applicants are 
encouraged to contact appropriate NIAID program staff concerning this policy.

Commercialization Plan

All Phase II SBIR/STTR grant applications, including Phase II competing 
continuation applications, require a Commercialization Plan, described in 
item J of the Instructions for Preparation of Phase II Applications. These 
Instructions describe the contents to be included in the following sections:

1.  Value of the SBIR/STTR Project, Expected Outcomes, and Impact.  
2.  Company. 
3.  Market, Customer, and Competition. 
4.  Intellectual Property (IP) Protection.
5.  Finance Plan. 
6.  Production and Marketing Plan.
7.  Revenue Stream.

If relevant, applicants may replace sections 5 with licensing, mergers or 
acquisition plans, section 6 with the milestones necessary for one of the 
section 5 events, and section 7 with a description of commitments, if any, 
from potential partners or buyers.  Although applicants may consider this new 
section 7 too confidential to include, when provided it may enhance the 
enthusiasm of reviewers.


We encourage your inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into three 
areas:  general SBIR issues, specific scientific research and development 
issues, review issues, and financial or grants management issues.

Frequently asked "Questions and Answers" about this RFA may be found at

General SBIR Issues

Potential applicants are strongly encouraged to contact Dr. Gregory Milman 
before proceeding with an NIAID competing continuation SBIR/STTR Phase II 

Gregory Milman, Ph.D.  
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 2153, MSC-7610
6700-B Rockledge Drive
Bethesda, MD 20892-7610 (US Mail) 
Rockville, MD 20817-7610 (Delivery Services) 
Telephone (301) 496-8666
Fax: (301) 402-0369 

Specific Scientific Research and Development Issues

Applicants are directed to a list of research areas and program staff for 
each area at

Review Issues

Madelon Halula, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive 
Bethesda, MD 20892-7616 (US Mail) 
Rockville, MD 20817-7616 (Delivery Services) 
Telephone (301) 402-2636
Fax: (301) 402-2638 

Financial or Grants Management Issues

Ms. Pamela Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2119, MSC 7614
6700-B Rockledge Drive 
Bethesda, MD 20892-7614 
Bethesda, (MD 20817-7614 for express/courier service)
Telephone: (301) 402-6580 
FAX: (301) 480-3780 


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

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

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

The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

Madelon Halula, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive 
Bethesda, MD 20892-7616 (US Mail) 
Rockville, MD 20817-7616 (Delivery Services) 
Telephone (301) 402-2636
Fax: (301) 402-2638 


The PHS 398 research grant application must be used for all SBIR/STTR Phase 
I, Phase II and Fast-Track applications (new and revised.)  Effective October 
1, 2003, applications must have a DUN and Bradstreet (D&B) Data Universal 
Numbering System (DUNS) number as the Universal Identifier when applying for 
Federal grants or cooperative agreements. The DUNS number can be obtained by 
calling (866) 705-5711 or through the web site at The DUNS number should be entered on line 
11 of the face page of the PHS 398 form. The PHS 398 is available at  Prepare your 
application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 
398. Helpful information for advice and preparation of the application can be 
obtained at: 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) 
710-0267, Email: 

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

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and three signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710 (for USPS EXPRESS or REGULAR MAIL)

At the time of submission, two additional copies of the application must be 
sent to:

Madelon Halula, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3116, MSC-7616
6700-B Rockledge Drive 
Bethesda, MD 20892-7616 (US Mail) 
Rockville, MD 20817-7616 (Delivery Services) 
Telephone (301) 402-2636
Fax: (301) 402-2638 

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

This policy does not apply to courier deliveries  (i.e. FEDEX, UPS, DHL, 
etc.) (  
This policy is similar to and consistent with the policy for applications 
addressed to Centers for Scientific Review as published in the NIH Guide 

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

The Center for Scientific Research (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. However, when a previously unfunded application, originally 
submitted as an investigator-initiated application, is to be submitted in 
response to an RFA, it is to be prepared as a NEW application.  That is, the 
application for the RFA must not include an Introduction describing the 
changes and improvements made, and the text must not be marked to indicate 
the changes from the previous unfunded version of the application. 

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIAID. Incomplete and/or nonresponsive applications 
will not be reviewed. Applications that are complete and responsive to the 
RFA will be evaluated for scientific and technical merit by an appropriate 
peer review group convened by the NIAID in accordance with the review 
criteria stated below.  As part of the initial merit review, all applications 

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


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 evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals within the context of the 
SBIR/STTR Program.  The scientific review group will address and consider 
each of the following criteria in assigning the application’s overall score:

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

1.  Significance:  Does this study address an important public health 
problem? Is the proposed project in one of the NIAID Small Business Highest 
Priority Areas?  Does the proposed project have commercial potential to lead 
to a marketable product or process that requires FDA approval? 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., vaccine 
platforms) for further discoveries? Will the technology have a competitive 
advantage over existing/alternate technologies or products. 

2.  Approach:  Does the proposed project describe a critical path for FDA 
approval and licensing with milestones and a timeline for those milestones to 
be achieved during each year of the proposed project period; milestones that 
will remain after the proposed funding period to complete the product R&D? 
Are there additional milestones that the review committee suggests be 
included? The review committee may suggest which, if any, of the milestones 
and timelines should be included in the Terms of Award.  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 

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

4.  Investigators: Is the Principal Investigator capable of coordinating and 
managing the proposed R&D? Are the work and management activities proposed 
appropriate to the experience level of the Principal Investigator and other 
researchers, including consultants and subcontractors (if any)? Are the roles 
and relationships of the Principal Investigator, key personnel, consultants, 
and contractors appropriate for the work proposed? 

5.  Environment:  Do the proposed contracts, if any, have the capability of 
producing the expected product or service in the time frame proposed?  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?  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 (cost-sharing) that 
would enhance the likelihood for commercialization? 

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

COMMERCIALIZATION PLAN:  The Commercialization Plan (formerly the Product 
Development Plan) should be used to evaluate the probability that the product 
will eventually receive FDA approval and become available.  If licensing, 
mergers or acquisition plans are anticipated in order to produce the product, 
are the milestones for these events described and reasonable?

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).

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

Human Subjects: 

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 

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? 

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?
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? 

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? 

be used in the project, the required five items described under Vertebrate 
Animals (section f of the Research Plan instructions) will be assessed. If 
vertebrate animals are involved, are adequate plans proposed for their care 
and use? Are the applicant's responses to the five required points 
appropriate? Will the procedures be limited to those that are unavoidable in 
the conduct of scientifically sound research? 

BIOHAZARDS:  Is the use of materials or procedures that are potentially 
hazardous to research personnel and/or the environment proposed? Is the 
proposed protection adequate? 

ADDITIONAL REVIEW CONSIDERATIONS: The following items may be also be 
considered by reviewers but will not be included in the determination of 
scientific merit.

SHARING RESEARCH DATA:  Applicants requesting more than $500,000 in direct 
costs in any year of the proposed research must include a data sharing plan 
in their application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the reviewers. 
However, reviewers will not factor the proposed data sharing plan into the 
determination of scientific merit or priority score.
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.


Letter of Intent Receipt Date:    December 14, 2003
Application Receipt Date:         January 16, 2004
Peer Review Date:                 June/July 2004
Council Review:                   September 2004
Earliest Anticipated Start Date:  September/October 2004


Applications submitted in response to a RFA will compete for available funds 
with all other recommended SBIR and STTR applications but NIAID paylines for 
other SBIR or STTR applications do not apply to applications in response to 
this RFA. 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 for applications in response to this RFA
o  Relevance to NIAID priorities


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.

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.  (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998:  

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible. Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score. 

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 
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 

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

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

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

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at 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, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s) for the hESC line(s) to be used in the proposed research.  
Applications that do not provide this information will be returned without 

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

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

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

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

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 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

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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