INNOVATIVE TECHNOLOGIES FOR MOLECULAR ANALYSIS OF CANCER (SBIR/STTR)
 
RELEASE DATE:  January 7, 2004
 
RFA Number:  RFA-CA-05-006 (This RFA has been reissued, see RFA-CA-06-005)
                           (see NOT-CA-04-013)

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATION:  
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:  
National Cancer Institute (NCI) 
 (http://www.nci.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.393, 93.394, 93.395, 
93.396
 
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 
                  
THIS RFA CONTAINS THE FOLLOWING INFORMATION

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 
the current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, 
CENTERS FOR DISEASE CONTROL AND PREVENTION, and FOOD AND DRUG ADMINISTRATION 
FOR SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY 
TRANSFER (STTR) GRANT APPLICATIONS.  The solicitation (see 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf) contains 
information about the SBIR and STTR programs, regulations governing the 
programs, and instructional information for submission. All of the 
instructions within the 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 
guidelines.

PURPOSE OF THIS RFA 

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-05-002, 
http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-002.html) that will 
utilize the exploratory/developmental research Phase I (R21) mechanism and 
the exploratory/developmental research Phase II (R33) mechanism . 

The National Cancer Institute (NCI) invites applications for research 
projects proposing the development of highly innovative cancer-relevant 
technologies.  Technology encompasses methods and tools that enable research, 
including, but not limited to, instrumentation, techniques, and devices.  
Technology is distinct from resources such as databases, reagents, and tissue 
repositories.  Applications for support of such resources will not be 
considered to be responsive to this RFA.  Technologies solicited include, but 
are not necessarily limited to, those that are suitable for the detection of 
alterations and instabilities of genomic DNA; measurement of the expression 
of genes and gene products, including proteins; analysis and detection of 
gene and/or cellular products, including post-translational modifications and 
functions of proteins; identification and characterization of exogenous 
infectious agents in cancer; and assaying the functions of major signal 
transduction networks involved in cancer.  Developing technologies would 
include those that will support molecular analysis in vitro, in situ, or in 
vivo in discovery processes as well as in pre-clinical models and clinical 
research.

This initiative is part of a broader technology development program within 
the NCI to harness technology in the fight against cancer.  The NCI 
technology program underscores the desire of NCI to develop and integrate 
novel and emerging technologies in the support of cancer research, diagnosis, 
and treatment.  In the research continuum of discovery, development, and 
delivery, this program accelerates development and delivery.  This specific 
initiative will serve as the discovery tool of the larger program by 
soliciting and funding highly innovative, high risk and cancer-relevant 
technology development projects associated with the molecular analysis of 
cancer.  

This initiative 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.  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 technology development projects.  Technologies developed 
or adapted for sample preparation methodology may be most suitable for RFA 
(CA-05-008), Innovations in Cancer Sample Preparation SBIR/STTR 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-008.html).  
Research projects to evaluate 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 (http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-007.html) 
(see MECHANISMS OF SUPPORT).  Researchers who emphasize the 
assessment of in vivo imaging technologies as the primary focus of their 
grant applications should contact the Cancer Imaging Program 
http://www3.cancer.gov/bip/) for information on appropriate funding 
opportunities.  Researchers focusing on applying new bioinformatics or 
statistical techniques as the primary focus of their applications should 
consider one of the BISTI initiatives 
(http://www.bisti.nih.gov/bistic_funding.cfm).  

RESEARCH OBJECTIVES

Background

In order to meet the goal of eliminating death and suffering due to cancer, 
the NCI will continue to support the development of creative methods to 
understand, prevent, diagnose, and treat cancer.  In the past several 
decades, basic discovery research has revealed that cancer is a complex 
disease involving myriad molecular and cellular processes, and that cancers 
arise as the result of the gradual accumulation of genetic changes in 
specific cells.  Identifying which subset of the genes encoded within the 
human genome can contribute to the development of cancer remains a challenge.  
Even more challenging is the subsequent understanding of the proteins and 
other functional products encoded by these genes.  The identification and 
characterization of these cancer genes and their associated gene products 
remains a high priority in cancer research.  New technologies and approaches 
not only address specific questions in basic research and clinical practice 
but are also beneficial in uncovering and developing new directions and 
paradigms in cancer research.  Taken together, these points highlight the 
leading and critical role technological advances play throughout the NCI’s 
mission.

The Innovative Molecular Analysis Technologies (IMAT) program was originally 
designed in 1999 with three objectives:  to focus technology development on 
cancer, to solicit highly innovative technology development projects, and to 
accelerate the rate of maturation of meritorious technologies from 
feasibility through development of the technology.  Through solicitation, 
outreach, and communication with the investigator community, the IMAT program 
has been successful in focusing a diverse spectrum of new and emerging 
technologies onto cancer applications.  The program has focused on both the 
inception and development of cancer-related technologies.  Some of the 
technologies originally generated with IMAT funding have gone on to support 
the acquisition of basic knowledge about cancer, which feeds the discovery 
pipeline.  Other IMAT-supported technologies have been applied to questions 
of clinical importance.  Through the R21/R33 Phased Innovation Award, 
originally created and piloted by this program, IMAT has also been successful 
in accelerating meritorious technology development projects by minimizing the 
funding gap between the feasibility and development phases.  While the 
overall NCI technology program maintains these general goals, this initiative 
will be more focused on the Phase I or high-risk portion of an investigator’s 
scientific effort, with emphasis on the extent to which the idea is novel and 
innovative.  Therefore, this RFA will not support Fast-Track awards, but only 
separate Phase I and Phase II applications, as outlined in the Mechanism of 
Support section.

This solicitation is intended to support the development of molecular 
analysis tools that will not only allow for the more careful examination of 
the molecular basis and profiles of cancer but will also provide the ability 
to identify the molecular characteristics of individuals that influence 
cancer development and prognosis.  These tools will allow for an examination 
of genetic factors that influence individuals’ risk of developing cancer or 
their ability to respond to damaging external agents such as radiation, 
carcinogens, and therapeutic regimes.  

In order to fully understand cancer and define the molecular responses of the 
host to cancer, it will be critical not only to have knowledge at the DNA 
level, but also to have a complete understanding of the processing of genetic 
information in cellular function. Current discoveries indicate that 
alterations in many of the cellular processes, pathways, or networks may 
contribute to the genesis of cancer and that these alterations could be 
exploited for therapeutic or prevention intervention.  Therefore, it is 
important to invoke technologies that can detect molecular changes in the 
cell without preconceived ideas about what changes would be the most valuable 
to monitor.  In the discovery phase, the emphasis will be on technologies 
that can effectively scan, through highly multiplexed analyses, structural 
variations or functional changes in many or all members of the populations of 
DNA, RNA, or proteins present in cells.  Current technologies for the 
multiplexed analysis of molecular species are at a stage where the greatest 
utility exists for the analysis of large numbers of relatively homogeneous 
cell populations that can be assayed in vitro. While many of the existing 
technologies have relatively sophisticated multiplexing capabilities in the 
assay format, none are comprehensive for any particular molecular species 
(DNA, RNA, or protein).  Therefore, opportunities exist for further 
development to insure that the resulting technologies provide enhanced assay 
potential, adequate sensitivity and discrimination, robust data analysis 
tools, and easy adaptations to the basic, preclinical, and clinical research 
settings.

Objectives and Scope

The purpose of this RFA is to encourage applications from individuals and 
groups interested in developing novel technologies suitable for the molecular 
analysis of cancers and their host environment in support of basic, clinical, 
and epidemiological research.  Technologies to support research in the 
following areas are considered to be appropriate.  Examples given below are 
not intended to be all-inclusive but are illustrative of the types of 
capabilities that are of interest.

New tools that allow development of more complete molecular profiles of 
normal, precancerous, and cancerous cells, as well as of tissues undergoing 
the process of carcinogenesis, are needed to support the basic discovery 
process.  The same sort of technological approaches will also be needed to 
examine the tumor micro-environment, including tumor, stromal, and vascular 
interactions.  These tools will also allow more thorough examination of the 
variations that influence predisposition to cancer and individual variability 
in response to therapeutic and prevention agents.  Of interest are 
technologies and data analysis tools for:

o  In vitro scanning for and identification of the sites of chromosomal 
aberrations that reflect inherited aberrations or somatic alterations 
resulting from aging, oxidation, or exposure to radiation or carcinogens, 
including those that are suitable for scaling for use across whole genomes, 
detecting DNA adducts, or detecting rare variants in mixed populations;

o  In vitro scanning for and identification of sites of mutations and 
polymorphisms that reflect inherited aberrations or variations, or somatic 
alterations resulting from aging, oxidation, or exposure to radiation or 
carcinogens, including those that are suitable for scaling for screening 
whole genomes, detecting DNA adducts, or identifying infrequently represented 
mutations in mixed populations of DNA molecules;

o  Technologies for detection and characterization of nucleic acid sequences 
of novel exogenous infectious agents that may be present in human cancer;

o  Highly specific and sensitive detection of specific mutations;

o  Detecting mismatch and recombinational DNA repair related to cancer 
susceptibility and drug sensitivity;

o  In vitro multiplexed analysis of the expression of genes;

o  In vitro detection of expression of proteins and their modified forms, 
including technologies suitable for expansion to profiling of all proteins 
expressed in cells, detecting rare variants in mixed populations, and 
detecting protein adducts involved in chemical mutation;

o  Monitoring the function of proteins and genetic pathways, including 
measurement of ligand-protein complexes and technologies for monitoring 
protein function of all members of a class of proteins or a complete genetic 
pathway;

o  Delineating molecular expression, function, and analysis at the cellular 
level in the context of both the whole body and in situ, including molecular 
imaging technologies suitable at this scale, contrast agents, gene 
amplification techniques, and related data analysis tools;

o  Detection technologies and sensors, including signal to noise optimization 
and rare cell/molecule detection, of cancer and the structures and molecules 
important in its development and diagnosis;

o  Technologies to elucidate molecular modifications of macromolecules that 
may be indicative of and critical to the transformation process;

o  Delivery technologies and approaches to enable faster and more accurate 
delivery of molecular and cellular labels and drugs to and within cells for 
research and treatment, the overall goals being speed, accuracy, and 
biocompatibility; and/or

o  Development of high-throughput, quantitative assays for epigenetic 
alternations, e.g., acetylation and methylation in promoter region of genes 
and histone proteins isolated from biological fluids and tissues.

For all technologies proposed, it will be important to substantiate the 
ultimate value of and role for the technology in deciphering the molecular 
anatomy of cancer cells or analyzing the molecular profile of the individual.  
It is also important for applicants to discuss the ultimate potential for the 
transfer of ensuing technology to other laboratories or the clinic and, for 
more mature technologies, plans to ensure dissemination of the technology.  
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.

MECHANISMS OF SUPPORT

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 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.

Except as otherwise stated in this RFA, awards will be administered under NIH 
grants policy as stated in the NIH Grants Policy Statement, March 2001, 
available at http://grants.nih.gov/grants/policy/nihgps_2001.  

Applications may be submitted for support as Phase I STTR (R41) or Phase I 
SBIR (R43) grants; or Phase II STTR (R42) or Phase II SBIR (R44) grants, 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.  
Phase I/Phase II Fast-Track applications will not be accepted.  

This initiative will employ separate discovery (Phase I) and development 
(Phase II) awarding mechanisms.  The Phase I application will emphasize the 
high risk, high innovation feasibility phase and potential impact.  The Phase 
II development application will have to contain proof of the feasibility of 
the proposed technology.  In addition, the Phase II application will contain 
an outline of a plan for further development of the technology towards its 
ultimate use and application.

Unlike the previous IMAT announcements of 1999 and 2002 (PAR-01-104) and the 
other two RFA solicitations of the current program, this RFA does not solicit 
and will not accept Phase I/ Phase II Fast-Track applications.  Under this 
RFA, applicants must submit either a Phase I application or a fully developed 
Phase II application, according to the guidelines below.  

The Phase I application will emphasize the innovative and high-risk nature of 
the proposed research and be conceptual in nature, with no preliminary data 
required.  In addition to the concept and discussion of the proposed 
technology that is common to all Phase I applications, the application must 
also include a brief section describing the potential use and impact of the 
proposed technology.  The specifics of the Phase I application are described 
in the SUPPLEMENTARY INSTRUCTIONS section of this RFA.  

Under this RFA, small business Phase I awardees may also submit a Phase II 
application if feasibility can be documented, as described in the 
SUPPLEMENTARY INSTRUCTIONS section of this RFA. Phase II applicants must 
present detailed preliminary data in support of the feasibility of the 
proposed technology or approach that is proposed for development.  These 
applications will also have the added burden of demonstrating the innovation 
of the particular technology or approach.  

It is strongly recommended that applicants contact NCI staff at an early 
stage of application development to convey critical information, such as 
potentially large budget requests, or to discuss programmatic adherence of 
the proposed project to the RFA guidelines. Refer to the INQUIRIES sections 
of this program announcement for NCI staff contacts.

PROJECT PERIOD AND AMOUNT OF AWARD

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 two years for Phase I and up to three years for Phase II.  An 
applicant may request a budget for total costs of up to $100,000 per year for 
Phase I.  Phase I budgets can exceed this cap to accommodate F&A/indirect 
costs to subcontracts to the project, but funds for such may not be 
rebudgeted. Budgets for Phase II 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.  

FUNDS AVAILABLE

The NCI intends to commit approximately $1,000,000 in FY 2005 to fund 3-5 
Phase I and/or Phase II 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. 

ELIGIBLE INSTITUTIONS:

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 
(NOT-OD-03-053) SMALL BUSINESS ELIGIBILITY REQUIREMENTS FOR APPLICANTS TO THE 
SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY 
TRANSFER (STTR) PROGRAMS.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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

SPECIAL REQUIREMENT

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.

WHERE TO SEND INQUIRIES

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 management, 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
E-mail: downingg@mail.nih.gov

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
E-mail:  pattersw@mail.nih.gov

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 
E-mail:  ncirefof@dea.nci.nih.gov

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 
E-mail:  tw133b@nih.gov 

LETTER OF INTENT
 
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
E-mail: downingg@mail.nih.gov

SUBMITTING AN APPLICATION

The PHS 398 research grant application must be used for all SBIR/STTR Phase I 
and Phase II 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 http://www.dunandbradstreet.com/. 
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 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare your 
application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 
398. Helpful information for advice and preparation of the application can be 
obtained at: http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.   
For further assistance contact GrantsInfo, Telephone: (301) 435-0714, 
E-mail: GrantsInfo@nih.gov. 

SUPPLEMENTARY INSTRUCTIONS

Applications may be submitted for Phase I or Phase II support, but NOT as a 
Phase I/Phase 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.  

Applicants should elaborate on the innovative nature of the proposed 
research.  Clarify how the technology development proposed in this project is 
a significant improvement over existing approaches.  Explain the potential of 
the proposed technology for having a broad impact on cancer research.  
Clearly identify how the project, if successful, would result in new 
capabilities for research, the immediacy of the opportunity, and how these 
proposed technologies would differ from existing technologies.

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 is expected that technology feasibility will be 
established.  If two 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 innovation 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 two and three, if requested, 
is dependent upon Institute programmatic review of progress and achievement 
of the proposed milestones. 

All Phase II 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 
http://grants.nih.gov/grants/funding/sbirsttr2/PhaseII_SBIRSTTR.pdf or 
http://grants.nih.gov/grants/funding/sbirsttr2/PhaseII_SBIRSTTR.doc.     

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, the total of stacked royalties will not exceed a 
predetermined percentage rate. 

The technology transfer/IP management/licensing officer or equivalent at the 
small business concern is to submit an 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 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 should refer to the 
NIH policy on the dissemination of biological research resources (“research 
tools”), which can be found at 
http://www.ott.nih.gov/policy/rt_guide_final.html.   

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:  
http://grants.nih.gov/grants/funding/phs398/labels.pdf. 

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.

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE 
WILL NO LONGER BE ACCEPTED.  This policy does not apply to courier deliveries 
(i.e., FEDEX, UPS, DHL, etc.) 
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html).  
This policy is similar to and consistent with the policy for applications 
addressed to Centers for Scientific Review as published in the NIH Guide Notice 
at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

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.  

PEER REVIEW PROCESS  
 
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.
 
REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to 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
 
ALL SBIR/STTR APPLICATIONS

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 
innovative? 

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

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

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 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?  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below.)
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below.)

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? 

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
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? 

RECEIPT AND REVIEW SCHEDULE

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

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.

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained. See
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

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.  See NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html.  

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: 
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.  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: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.  
Information concerning essential elements of data safety monitoring plans for 
clinical trials funded by the NCI is available:  
http://www.cancer.gov/clinical_trials/.

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 
(http://grants.nih.gov/grants/policy/data_sharing).  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.

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

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

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

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

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

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, 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 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this 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.

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

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on “Am I a covered 
entity?”  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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 
http://www.health.gov/healthypeople.

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

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


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NIH Funding Opportunities and Notices


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