RELEASE DATE:  January 7, 2004
RFA Number:  RFA-CA-05-008 (This RFA has been reissued, see RFA-CA-06-007)
                           (see NOT-CA-04-013)

Department of Health and Human Services (DHHS)
National Institutes of Health (NIH) 

National Cancer Institute (NCI) 

LETTER OF INTENT RECEIPT DATES: February 10, 2004; May 17, 2004; 
September 17, 2004.
APPLICATION RECEIPT DATES: March 10, 2004; June 17, 2004; October 18, 2004. 

o Purpose of this RFA
o Research Objectives
o Mechanisms of Support 
o Project Period and Amount of Award
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirement
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
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 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 dates;    
o Initial review convened by the NCI Division of Extramural Activities;    
o Additional review considerations; and
o In certain cases, larger budgets and longer project periods than statutory 


This RFA will utilize the Small Business Innovation Research (SBIR) and Small 
Business Technology Transfer (STTR) mechanisms, but will be run in parallel 
with a RFA of identical scientific scope (CA-05-004, that will 
utilize the exploratory/developmental research Phase I (R21) mechanism, the 
exploratory/developmental research Phase II (R33) mechanism, and the phased 
innovation (R21/R33) mechanisms. 

The National Cancer Institute (NCI) invites applications for research 
projects involving the development and significant enhancement or adaptation 
of sample preparation methodologies and technologies, the development of 
assays to assess sample quality, and studies designed to elucidate the 
criteria by which to judge sample quality.  The outcome will be products and 
methods designed to optimize sample utility.   Samples may originate from 
residual material not necessary for patient care or from cell lines, model 
organisms, or other sources relevant to cancer research.

The development of new and/or improved cancer sample preparation 
methodologies and technologies, the development of assays to assess sample 
quality, and studies to elucidate the criteria needed to judge sample quality 
cover a wide range of project sizes and innovation levels.  This RFA will 
allow the submission of applications involving Phase I, Phase II, and Fast-
Track mechanisms.  Phase I (R41 or R43) applicants may propose small, highly 
innovative feasibility studies or small, short-term exploratory studies to 
meet one of the RFA goals.  Fast-Track applicants should propose projects 
that require a small feasibility study followed by a well-defined development 
plan.  Successful completion of the Phase I feasibility study and the 
resulting transition to Phase II will be judged by NCI staff according to 
Fast-Track review criteria.  Projects for which feasibility has already been 
established through the award of a Phase I grant (through this or another 
relevant RFA) may be proposed as Phase II (R42 or R44) applications.  
Feasibility means that some preliminary experiments have been performed and 
that sufficient technical data exist to support proof of principle of the 

This initiative is part of a broader technology development program within 
the NCI.  That program underscores the desire of NCI to develop and integrate 
novel technologies focused on the molecular analysis of cancers and their 
micro-environment in support of cancer research, diagnosis, and treatment.  
In the research continuum of discovery, development, and delivery, this 
program thus emphasizes the link between development and delivery.  This 
specific initiative aims to foster the development of sample preparation 
techniques and methodologies that are essential for effective research, 
technology development, and validation that will eventually lead to clinical 

This RFA capitalizes on both the success and intent of the original NCI-
sponsored Innovative Molecular Analysis Technologies (IMAT) program in 
bringing together a multi-disciplinary group of scientists and engineers to 
work on cancer and the expansion of interest in technology development across 
the NCI and other NIH institutes and centers.   This continuation of the IMAT 
program consists of the following three initiatives: Innovative Technologies 
for the Molecular Analysis of Cancer; Innovations in Cancer Sample 
Preparation; and Application of Emerging Technologies for Cancer Research.  
This RFA is designed to support research focused on sample preparation 
methods.  Projects focused on the development of novel technologies may be 
most suitable for RFA (CA-05-006), Innovative Technologies for the Molecular 
Analysis of Cancer SBIR/STTR 
Projects focused on evaluating emerging technologies that are ready for 
initial clinical or biological application in cancer research may be most 
suitable for RFA (CA-05-007), Application of Emerging Technologies for Cancer 
Research SBIR/STTR 



High quality sample preparations are the foundation for effective technology 
validation as well as for meaningful biological and clinical research.  
Sample preparation covers the spectrum from preparation of molecules to cells 
to tissues.  Preparation of the highest quality samples can be hampered by 
technical issues, lack of standards by which to judge quality, and lack of 
standard practices.  Sample preparation methods vary.  Researchers often 
develop sample preparation methodologies in an ad hoc fashion as part of 
other projects.  This lack of information and standardization affects the 
quality and comparability of data across all fields of cancer research and 
across all technological platforms.  

Objectives and Scope

Sample preparation methods and technologies may be developed for sample 
collection, processing, isolation, storage, purification, preservation, and, 
in the case of stored tissues, reversal of adverse events resulting from 
storage and preservation.  Methods may be developed for preparation of 
molecules, fluids, tissues, or any other samples necessary for cancer 
research.  Researchers may propose to develop methods to isolate cells or 
sub-cellular components, such as classes of molecules, organelles, or sub-
cellular structures.  They may propose to isolate specific classes of 
molecules, such as membrane-bound proteins.  They may also propose studies to 
determine the effects of collecting, processing, and storage on molecular 
components of interest in stored specimens.  The goal is to develop products 
and methodologies that maximize the quality and utility of samples for 
research and, in the case of human specimens, maximize the quality of the 
samples for research and clinical needs without compromising patient care.

Sample preparation methods may impact the results or interpretation of 
biological studies.  Investigators may apply different methods of sample 
preparation using the same measurement technology.  In many cases of 
measuring biological response, no “gold standard” exists by which to compare 
research results obtained from the different sample preparation methods.  
There is a need for methods to assess the quality of samples prepared using 
different methodologies.   This RFA will support methods to assess sample 
quality and studies that elucidate the criteria needed to judge sample 
quality under different conditions.  This RFA will also support the 
development of technologies to make these assessments, such as the 
development of sample reference materials that can be used to calibrate the 
effectiveness of new fixatives or new detection methodologies. 

It is expected that many investigators who developed successful cancer sample 
preparation techniques under previous IMAT initiatives or under the new RFA 
(Innovative Technologies for Molecular Analysis of Cancer, RFA (CA-05-006) 
will propose projects for this RFA.  However, this RFA is not limited to 
techniques developed under the IMAT program.  Investigators are encouraged to 
use any sample preparation methodologies or techniques relevant to cancer.   

For all projects proposed, it will be important to substantiate the ultimate 
value of the innovation for analyzing samples, optimizing analysis, and/or 
evaluating sample quality for the purpose of research and eventually clinical 
applications.  Also of importance is the potential for ultimately 
transferring knowledge, technologies, and/or methodologies to other 
laboratories or the clinic.  In the case of technologies intended for use on 
clinical specimens or in patients, applications from or collaborations with 
investigators involved in the clinical research of cancer are encouraged.


This RFA uses the SBIR and STTR mechanisms, which are set-aside programs.  As 
an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project.  Future unsolicited, competing-continuation 
applications based on this project will compete with all SBIR/STTR 
applications and will be reviewed according to the customary peer review 
procedures. The anticipated award date is approximately nine months from the 
respective receipt date.  
This RFA uses just-in-time concepts. It also uses the modular budgeting 
format. Specifically, if you are submitting an application budget of $100,000 
total costs (direct, F&A, and fee) or less, use the modular budget format and 
instructions as described in the current SBIR/STTR Omnibus Solicitation. 
Otherwise follow the instructions for non-modular budget research grant 
applications.  This program does not require cost sharing as defined in the 
current NIH Grants Policy Statement at

Except as otherwise stated in this RFA, awards will be administered under NIH 
grants policy as stated in the NIH Grants Policy Statement, December 2003, 
available at. 

Applications may be submitted for support as Phase I STTR (R41) or Phase I 
SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) grants; or the 
SBIR/STTR Fast-Track option as described in the SBIR/STTR Omnibus 
Solicitation.  The Phase II application must be a logical extension of 
previously funded Phase I SBIR/STTR research but not necessarily a Phase I 
project supported in response to this RFA.  Fast Track applications will 
benefit from expedited evaluation of progress following the Phase I 
feasibility study for transition to Phase II funding for expanded 
developmental work. 

The Phase I portion of the Fast-Track application must contain well-defined 
quantitative milestones that will be used to judge the success of the 
proposed research, as well as a credible plan for the pilot application of 
the proposed technology in Phase II.  


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.  Under this RFA, an applicant may request a project period 
of up to 2 years for Phase I, up to 3 years for Phase II, and up to 4 years 
for a combined Phase I/Phase II Fast-Track, of which the Phase I portion may 
be no more than 2 years.  An applicant may request a budget for total costs 
of up to $100,000 per year for Phase I and the Phase I portion of Fast-Track 
applications.  .  Phase I budgets can exceed this cap to accommodate indirect 
costs to subcontracts to the project, but funds for such may not be 
rebudgeted.  Budgets for Phase II and the Phase II portion of Fast-Track 
grant applications should be appropriate for the science proposed.  Because 
the nature and scope of the proposed research will vary from application to 
application, NCI will consider budgets that exceed the statutory guidelines.  
Total costs include direct costs, F&A, and fee/profit.  


The NCI intends to commit approximately $1,250,000 in FY 2005 to fund 8-12 
Phase I, Phase II, and/or Fast-Track applications under the SBIR/STTR set-
aside funding mechanism. Although the financial plans of the NCI provide 
support for this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 
applications. At this time, it is not known if competing renewal applications 
will be accepted and/or if this RFA will be reissued. 


Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.  
Only small business concerns are eligible to submit SBIR/STTR applications.  
A small business concern is one that, on the date of award for both Phase I 
and Phase II agreements, meets ALL of the criteria as described in the 
current SBIR/STTR Omnibus Solicitation.  Also, for eligibility clarification 
see the July 25, 2003 Notice in the NIH Guide for Grants and Contracts 


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. 


An annual meeting of all investigators funded through this program will be 
held to share progress and research insights that may lead to further 
progress in the program.  Applicants should request travel funds in their 
budgets for the principal investigator and one additional senior investigator 
to attend this annual meeting.


We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into four 
areas:  scientific/research, intellectual property, peer review, and 
financial or grants management issues:

o Direct your questions about scientific/research issues to:

Gregory J. Downing, D.O., Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
Building 31, Room 10A52
Bethesda, MD  20892
Rockville, MD 20652 (or express/courier service)
Telephone:  (301) 496-1550
FAX:  (301) 496-7807

o Direct your questions regarding intellectual property management plans to:
Wendy Patterson, J.D. 
Technology Transfer Branch
National Cancer Institute, NIH, DHHS
6120 Executive Boulevard, EPS Room 450
Bethesda, MD 20892 
Rockville, MD 20652 (or express/courier service)
Telephone:  (301) 496-0477

o Direct your questions about peer review issues to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Telephone: (301) 496-3428
FAX: (301) 402-0275 

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

Ted Williams  
Grants Administration Branch 
National Cancer Institute 
6120 Executive Boulevard, EPS Room 243 
Bethesda, MD 20892 (for regular mail)
Rockville, MD 20852 (for express mail) 
Telephone:  (301) 496-8785 
FAX:  (301) 496-8601 

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

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

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows NCI staff to estimate the potential review workload and plan 
the review.
The letter of intent is to be sent at least one month prior to the targeted 
receipt date.  The receipt dates and respective letter of intent dates are 
listed at the beginning of this document.  The letter of intent should be 
sent to:

Gregory J. Downing, D.O., Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
Building 31, Room 10A52
Bethesda, MD  20892
Rockville, MD 20652 (or express/courier service)
Telephone:  (301) 496-1550
FAX:  (301) 496-7807


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 document 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:  For 
further assistance contact GrantsInfo, Telephone: (301) 710-0267, Email: 


Applications may be submitted for Phase I or Phase II support, or as a 
combined Phase I and II (Fast-Track).  The Phase II proposal must be a 
logical extension of previously funded Phase I SBIR/STTR research but not 
necessarily a Phase I project supported in response to this initiative.  
The total duration for a Phase I/Phase II Fast-Track application cannot 
exceed 4 years.

PHASE I:  Demonstration of feasibility of the innovative approach.  Research 
should be proposed with quantitative feasibility milestones that, when 
accomplished, would provide sufficient reason to continue the technology 
development in Phase II.  It would be expected that technology feasibility 
would be established.  If 2 years of support are requested, the goals for the 
first year should be clearly stated and not be simply a reiteration of 
specific aims.  Support for the second year will be contingent upon Institute 
programmatic evaluation to ensure that investigators are reaching milestones 
and accomplishing the goals presented.  

PHASE II:  Development of approach to a stage at which the sample preparation 
technology can be piloted for implementation.  Extensive studies designed to 
validate the approach would be expected.  Goals and milestones for each year 
of support should be clearly presented.  Support for years 2 and 3, if 
requested, is dependent upon Institute programmatic review of progress and 
achievement of the proposed milestones. 

FAST-TRACK: Applications may be submitted for combined Phase I and Phase II, 
Fast-Track consideration as described in the OMNIBUS SOLICITATION.  

The Phase I part of Fast-Track applications must specify clear, quantitative 
milestones that should be achieved prior to Phase II funding.  These must be 
presented in a section labeled “Milestones” at the end of the Research Plan.  
A discussion of the suitability of the proposed milestones for assessing 
success in Phase I, and a discussion of the implications of successful 
completion of these milestones for the proposed Phase II, should also be 
presented in this section.  Failure to provide such information in the Phase 
I application and/or sufficient detail in the Phase II application may be 
sufficient reason for the peer review committee to exclude the Phase II from 
consideration.  If so, a Phase I grantee may apply later for Phase II 
support.  Such applications will be reviewed by an appropriate scientific 
review group convened by the NIH. 

Special provisions described in this RFA pertaining to Phase I and Phase II 
applications also apply to FAST TRACK applications.

All Phase II and Fast-Track applications must include a succinct 
Commercialization Plan (limited to 15 pages).  The Commercialization Plan 
must be included as part of the Research Plan. Refer to Phase II grant 
application instructions for more specific details and instructions. See or    

Potential applicants are encouraged to contact program staff for guidance and 
to read the advice and information on the web sites.  However, responsibility 
for planning, direction, and execution of the proposed research will be 
solely that of the applicant.

INTELLECTUAL PROPERTY MANAGEMENT PLAN:  Certain research plans will require 
collaboration and coordination between investigators at different 
institutions, some of whom may not be NIH funding recipients and who may have 
pre-existing intellectual property (IP) obligations to third parties.  It is 
anticipated that commercial embodiments of the results of such research may 
incorporate single inventions shared by several institutions, or multiple 
inventions each from a separate institution.  Therefore, prior to funding, 
Phase II grant applicants must address how they will coordinate patent 
prosecution and licensing activities, if necessary to enable a licensee to 
access the bundle of IP needed to take a product to market on commercially 
viable terms.  Suggested strategies include: (1) assigning IP rights to 
related inventions to an invention management firm; (2) designating one 
organization to take the lead on patenting and licensing related inventions: 
(3) agreeing in advance, that if multiple parties are to independently 
license related inventions, that the total of stacked royalties will not 
exceed a predetermined percentage rate. 

The technology transfer/IP management/licensing officer or equivalent at the 
principal investigator’s institution is to submit an intellectual property 
(IP) management plan, including at least those elements above.  Alternatives 
to the suggested strategies, which accomplish the same goals, will be 
considered.  IP management plans are a just-in-time requirement; it is not 
necessary to include the plan in the grant application, but plans will be 
required before a Phase II grant can be awarded.

Applicants’ institutions should avoid exclusively licensing those inventions 
that are research tools unless either: (1) the field of use of the exclusive 
license is restricted to commercial use, or (2) the exclusive licensee will 
make the research tool available on reasonable terms.  Applicants’ attention 
is directed to the NIH policy on the dissemination of biological research 
resources (“research tools”), which can be found at   

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.   The RFA label is also available at: 

The title and number of this RFA must be typed on line 2 of the face page of 
the application and the YES box must be marked.

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
Bethesda, MD  20817 (for express/courier service)
To expedite the review process, at the time of submission, two additional 
copies of the application and all copies of the appendix material must be 
sent to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Rockville, MD  20852 (for express/courier service)

Appendices should be comprised of single-sided, unbound materials, with 
separators between documents.

WILL NO LONGER BE ACCEPTED.  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 

RECEIPT OF APPLICATIONS: Applications must be received on or before the 
application receipt dates listed in the heading of this RFA.  If applications 
are received after those dates, they will be returned to the applicant 
without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
The Center for Scientific Review (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. This 
does not preclude the submission of a substantial revision of an unfunded 
version of an application already reviewed, but such an application must 
include an Introduction addressing the previous critique. An application 
through this RFA that is unsuccessful may be resubmitted as amended by the 
October receipt date.  

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NCI.  Incomplete and non-responsive 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 Division of Extramural Activities of the NCI in accordance 
with the review criteria stated below.  As part of the initial merit review, 
all applications will:

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

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, 
weighting them as appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

1.  Significance:  Does this 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 will 
scientific knowledge be advanced? Does the proposal lead to enabling 
technologies (e.g., instrumentation, software) for further discoveries? Will 
the technology have a competitive advantage over existing/alternate 
technologies that can meet the market needs? 

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

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

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

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

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:

MILESTONES: In the case of Phase I or Fast-Track applications, are 
appropriate and quantitative scientific milestones included that will show, 
when completed by the end of Phase I, whether or not the project has shown 
feasibility to pursue Phase II aims?  

subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See 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 Inclusion Criteria in the sections on Federal Citations, 

Human Subjects:

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

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

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

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

5. Data and Safety Monitoring Plan – for clinical trials only.  Does the 
applicant describe a Data and Safety Monitoring Plan that defines the general 
structure of the monitoring entity and mechanisms for reporting Adverse 
Events to the NIH and the IRB? 

be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

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.

PHASE II APPLICATIONS:  In addition to the above review criteria:

1.  How well did the applicant demonstrate progress toward meeting the Phase 
I objectives, demonstrating feasibility, and providing a solid foundation for 
the proposed Phase II activity? 

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

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

AMENDED APPLICATIONS: In addition to the above criteria, the following 
criteria will be applied to revised applications.

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

Are the improvements in the revised application appropriate? 


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

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

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

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

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

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


Letter of Intent Receipt Dates: February 10, 2004; May 17, 2004; September 
17, 2004.

Application Receipt Dates: March 10, 2004; June 17, 2004; October 18, 2004. 

Peer Review Dates: June 2004; November 2004; March 2005.

Council Reviews: September 2004; February 2005; June 2005.

Earliest Anticipated Start Dates: December 2004; April 2005; July 2005.


Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic 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 to determine whether 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.  See 

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:  

Clinical trials supported or performed by NCI require special considerations.  
The method and degree of monitoring should be commensurate with the degree of 
risk involved in participation and the size and complexity of the clinical 
trial.  Monitoring exists on a continuum from monitoring by the principal 
investigator/project manager or NCI program staff or a DSMB.  These 
monitoring activities are distinct from the requirement for study review and 
approval by an Institutional Review Board (IRB).  For details about the 
Policy for the NCI for Data and Safety Monitoring of Clinical trials see:  For Phase I and II 
clinical trials, investigators must submit a general description of the data 
and safety monitoring plan as part of the research application.  See NIH 
Guide Notice on “Further Guidance on a Data and Safety Monitoring for Phase I 
and II Trials” for additional information:  
Information concerning essential elements of data safety monitoring plans for 
clinical trials funded by the NCI is available:

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  A 
continuing education program in the protection of human participants in 
research is available online 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
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Bethesda, Maryland 20892
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and Human Services (HHS) - Government Made Easy

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