APPLICATIONS OF INNOVATIVE TECHNOLOGIES FOR THE MOLECULAR ANALYSIS OF CANCER:  
SBIR/STTR
 
Release Date:  May 31, 2001
 
PA NUMBER:  PAR-01-107
 
National Cancer Institute

Letter of Intent Date:     June 15, 2001; October 17, 2001; February 14, 2002; 
                           June 10, 2002; October 18, 2002; February 14, 2003; 
                           and June 16, 2003

Application Receipt Date:  July 20, 2001; November 21, 2001; March 21, 2002; 
                           July 22, 2002; November 22, 2002; March 21, 2003; 
                           and July 21, 2003
						   
This Program Announcement (PA) replaces PA-99-103, which was published in the 
NIH Guide on May 14, 1999.
 
PURPOSE

The National Cancer Institute (NCI) invites applications for research projects 
to evaluate the utility and pilot the application of molecular analysis 
technologies in studies relevant to cancer research.  Molecular analysis 
technologies of interest include those that are entirely novel, or emerging 
but not currently in broad scale use where the technologies have not yet been 
demonstrated to be robust or reproducible in supporting molecular analysis in 
cancer research, or technologies currently in use for one application or set 
of applications, that are being evaluated for utility for alternative 
applications.  The Program Announcement (PA) provides support for a first 
phase for technology evaluation and a second phase for pilot application of 
the technology in a study of biological interest to cancer research. The first 
(evaluation) phase should include proof of principle experiments that will 
demonstrate the utility of the technology on samples comparable to those that 
will be used in the second phase study.  Applicants will be expected to 
demonstrate the utility of all components of the process required for a fully 
integrated system, including sample preparation, molecular analysis assay, and 
data capture and analysis.  The second (application) phase supports the 
transition of the technology optimized in the first (evaluation) phase to 
pilot application in a study of biological interest to cancer research.  The 
design of the second phase study should allow the demonstration that the 
technology can reproducibly obtain molecular data from the selected sample 
type and produce information of biological interest to cancer research.  
Studies might appropriately target analysis of precancerous, cancerous, or 
metastatic cells, or host derived samples, from model cancer systems, 
preclinical or clinical research, or from population based research.

Technologies suited for this solicitation, include those that enable the 
detection of alterations and instabilities of genomic DNA; measurement of 
expression of genes and gene products; analysis and detection of gene and or 
cellular products including differential expression, quantitation, post 
translational modification, and function of proteins; identification of 
exogenous infectious agents in cancer; and assaying the function or major 
signal transduction networks involved in cancer.  Additionally, technologies 
that will support molecular analysis in vitro, in situ, or in vivo (by imaging 
or other methods) are suitable for this PA.  Technologies are defined as 
instrumentation, techniques, devices and analytical tools (e.g., computer 
software) but are distinct from resources such as databases, reagents, and 
tissue repositories. 

This Program Announcement (PA) must be read in conjunction with the OMNIBUS 
SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH,  SMALL BUSINESS INNOVATION 
RESEARCH (SBIR) and SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT 
APPLICATIONS.
 
All of the instructions within the Omnibus Solicitation apply with the 
following exceptions:
  
o  Special receipt dates   
o  Opportunity for two years of Phase I support and three years of Phase II 
support    
o  Initial review convened by the NCI Division of Extramural Activities    
o  Additional review considerations
o  Modular grant concept is not used.

This PA will expire on July 22, 2003, unless reissued.  

BACKGROUND

Rapid molecular analysis tools will expedite the molecular characterization of 
normal cells, precancerous, cancerous, and metastatic cells, as well as, 
expand our understanding of the biological basis of cancers.  Comprehensive 
analysis of cancers at the molecular level will facilitate cancer detection 
and diagnosis, as well as identify new targets for therapeutic and 
preventative agents.  

The definition of the molecular alterations in cancer will require the 
continued development and dissemination of comprehensive molecular analysis 
technologies as well as identification of all of the molecular species encoded 
in genomes of cancer and normal cells. The National Cancer Institute 
implemented the Cancer Genome Anatomy Project (CGAP) to create an information 
infrastructure of the molecular changes associated with cancer development, 
and to develop technological tools to support the analysis of molecular 
profiles of cancer cells and their normal counterparts. The current CGAP 
program comprises Tumor Gene Indices for the human and mouse (hTGI and mTGI), 
a Genetic Annotation Initiative (GAI) and the Cancer Chromosome Aberration 
Project (cCAP). The TGI and GAI, are focused toward building a catalog of 
annotated genes associated with cancer. The third component, cCAP, is 
developing resources to catalog and facilitate the molecular characterization 
of cancer-related chromosomal aberrations. Complete information about CGAP can 
be found at http://cgap.nci.nih.gov/.  The NCI is also targeting support for 
the development and dissemination to basic, preclinical, and clinical 
researchers of novel technologies that will allow high-throughput analysis of 
genetic alterations, expression of genome products, and monitoring of signal 
transduction pathways in cancers.  A complimentary program on "Innovative 
Technologies for the Analysis of Cancer" to support technology development was 
announced in May 1998 and has recently been reissued for the next two years. 
   
This initiative, "Applications of Innovative Technologies for the Molecular 
Analysis of Cancer" is intended to support the demonstration that newly 
developed and emerging technologies have matured and are suitable for use in 
cancer research, followed by the initial application of these technologies in 
well-defined studies of biological interest to cancer research using model 
cancer systems, preclinical or clinical samples, or in population research. 
The routine use of improved molecular analysis tools will lead to a better 
understanding of the molecular basis of cancer, and will facilitate the 
identification of molecular characteristics of individuals, that influence 
cancer development and prognosis.

Molecular analysis technologies of interest include those that will support:

--A more complete understanding of the biological basis of cancer.

--The identification of molecular variations between normal, precancerous, 
cancerous, and metastatic cells that can serve as targets for the detection, 
diagnosis, therapy, and prevention.

--An examination of genetic factors that influence an individual's likelihood 
to develop cancer or their ability to respond to external damaging agents, 
such as radiation and carcinogens. 

--The molecular correlation between individuals with therapeutic or toxic 
responses to treatment and prevention measures and genetic factors that 
influence the efficacy and safety of these strategies and agents 
(pharmacogenomics). 

--Identification of molecular markers in the individual that correlate with 
the body's response to the onset or clearance of disease and the development 
of biomarkers to track and even image the efficacy of therapy (therametrics) 
and prevention, as well as the onset of secondary cancers. 

--Tracking of the damage to the genome from exogenous agents such as 
carcinogens, radiation and existence of exogenous infectious agents resident 
in cancer cells.
     
The comprehensive molecular analysis of cancer will require:

--High through put analysis strategies to elucidate the processing and 
expression of genetic material in the cell.

--Detection of molecular changes in the cell without preconceived ideas about 
which information will be most valuable to monitor.

--Adequate adaptations to accommodate technical issues specific to the study 
of cancer in vitro and in vivo, such as limited cell number, sample 
heterogeneity, and heterogeneity of specimen types (i.e., bodily fluids and 
waste, tissues, cells).

--Adaptation of novel technologies for use in cancer research, including use 
on tumor specimens, in patient imaging, and in population research.

--Integration of sample preparation components that maintain the efficiencies 
of the assay system and effectively accommodate human tumor specimens.

--Data analysis tools for interpreting the information from highly multiplexed 
molecular analyses.
   
Novel technologies for comprehensive molecular analysis are being developed.  
Many of these technologies have not yet been demonstrated to have utility or 
cost effectiveness in application to cancer model systems, cancer specimens, 
or in population-based research. It will be necessary to demonstrate that 
relevant technologies have adequate sensitivity to discriminate differences 
between tumors and normal tissues, and tumors of different stages. Therefore, 
the need exists to demonstrate the ability of emerging molecular analysis 
technologies to provide routine assay performance, adequate sensitivity and 
discrimination, and associated robust data analysis tools, that can be adapted 
to basic, pre-clinical, and clinical research settings for the purpose of 
cancer research.

Translation of new in vitro technologies for the multiplexed analysis of 
molecular species in clinical specimens will require a multidisciplinary team 
approach with broad expertise in a variety of research areas.  Such varied 
expertise, potentially including but not limited to, expertise in pathology, 
specimen acquisition and preparation, informatics and biostatistics exists in 
ongoing cancer centers and clinical trials cooperative groups. The 
coordination and collaboration of investigators from these various disciplines 
to demonstrate the utility and applicability of new analytical tools in 
clinical and population based studies is considered to be a high priority.

Existing technologies for molecular analysis are also largely restricted to in 
vitro analysis.  While these systems are suitable for discovery and many basic 
and clinical research questions, they are limited in their ability to offer 
information relative to molecular changes in real time and in the appropriate 
context of the intact cell or body.  Imaging in situ or in vivo is becoming 
increasingly important for extending molecular analysis of early cancer 
formation.  The application of high-resolution imaging at the cellular or 
molecular levels to, tissue samples, pre-clinical models, or human 
investigations is therefore considered to be an important extension of 
molecular analysis methods.  Similarly, the application of molecular probes 
for imaging molecular events is also of interest for pre-clinical and human 
investigations.  Finally, the use of molecular contrast enhancement 
techniques, such as contrast modifications of gene expression are considered 
critical to improve the sensitivity of detection of molecular changes in vivo. 
The molecular imaging methodologies proposed, including hardware and software, 
are specifically understood as being within the context of molecular analysis 
tools.  They include specialized high resolution or microscopic imaging 
methods dedicated to detection and analysis of molecular events related to 
cancer formation or as applied to pre-clinical drug discovery.  Improvements 
in these areas will bring capabilities for real time molecular analysis at 
whole body levels.  Investigations of tumor models that do not target 
molecular species are not responsive to this application.  Investigators are 
encouraged to contact NCI program staff for further information.

RESEARCH OBJECTIVE

The National Cancer Institute (NCI) invites applications for research projects 
to evaluate the utility and pilot the application of newly developed molecular 
analysis technologies in studies relevant to cancer research.  The Program 
Announcement (PA) provides support for a first phase for technology evaluation 
and a second phase for pilot application of the technology in a study of 
biological interest to cancer research. The first (evaluation) phase should 
include proof of principle experiments that will demonstrate the utility of 
the technology on samples comparable to those that will be used in the second 
phase study.  Applicants will be expected to demonstrate the utility of all 
components of the process required for a fully integrated system, including 
sample preparation, molecular analysis assay, and data capture and analysis.  
The second (application) phase supports the transition of the technology 
optimized in the first (evaluation) phase to pilot application in a study of 
biological interest to cancer research.  The design of the second phase study 
should allow the demonstration that the technology can reproducibly obtain 
molecular data from the selected sample type and produce information of 
biological interest to cancer research.  Studies might appropriately target 
analysis of precancerous, cancerous, or metastatic cells, or host derived 
samples, from model cancer systems, preclinical or clinical research, or from 
population based research.

The application of new tools that support the comprehensive molecular 
characterization of normal, precancerous, cancerous, and metastatic cells, as 
well as the identification of new targets for detection, diagnosis, 
preventative, and therapeutic strategies, is needed to support the basic 
discovery process and the translation of basic discoveries to pre-clinical and 
clinical research. Application of improved molecular analysis technologies 
will also allow a more thorough examination of the variations that influence 
predisposition to cancer, and individual variability in response to 
therapeutic and prevention agents as well as the identification of exogenous 
infectious agents that may be associated with the development of cancer.  
Examples given below are not intended to be all-inclusive, but are 
illustrative of the types of molecular analysis capabilities that are of 
interest for evaluation and pilot application in response to this 
solicitation.

--In vitro identification and characterization of sites of chromosomal 
aberrations, which arise from inherited or somatic alterations resulting from 
aging or oxidation, or exposure to radiation or carcinogens, including those 
that are suitable for scaling for use across whole genomes, detecting DNA 
adducts, detecting rare variants in mixed populations, or identifying 
infrequently represented mutations in mixed populations of DNA molecules.

--Detection and characterization of nucleic acid sequences of novel exogenous 
infectious agents including viruses, bacteria or other microscopic forms of 
life that may be etiologic factors or co-factors in the initiation and/or 
progression of human cancers.  New technologies are demonstrating that 
microorganisms may play a more important role in the initiation of 
malignancies than was previously appreciated. 

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

-- Highly specific and sensitive detection of specific mutations in 
multiplexed high through put analysis.

-- Detection of mismatch and recombinational DNA repair anomalies related to 
cancer susceptibility, cancer progression, and drug sensitivity.

-- In vitro multiplexed analysis of the expression of genes.

-- Computer assisted quantitation of gene expression. 

-- In vitro detection of expression of proteins and their post-translationally 
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.

--Assaying 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 members of a 
complete genetic pathway.
 
Translation of the utility of the technologies described above and basic 
research findings into tools for pre-clinical and clinical applications 
requires additional technological innovation with regard to sample 
preparation, enhanced sensitivity, and expanded data analysis tools.  Of 
interest  is the application of technologies suitable for:

-- Detection, quantification and analysis of DNA mutations and polymorphisms 
and functional proteins in clinical specimens  (e.g. tissue, serum, plasma, 
nipple aspirates, bronchioalveolar lavage, sputum, urine, pancreatic juice, 
colonic wash, and bladder wash).

--Imaging in situ or in vivo in order to extend molecular analysis to early 
cancer formation.  The application of high-resolution imaging at the cellular 
or molecular levels to, tissue samples, pre-clinical models, or clinical 
investigations are therefore considered to be an important extension of 
molecular analysis methods.  Similarly, the application of molecular probes 
for imaging molecular events is also of interest for pre-clinical and human 
investigations.  Finally, the use of molecular contrast enhancement 
techniques, such as contrast modifications of gene expression are considered 
critical to improve the sensitivity of detection of molecular changes in vivo. 
The molecular imaging methodologies proposed, include hardware and software, 
are specifically understood as being within the context of molecular analysis 
tools.  They include specialized high resolution or microscopic imaging 
methods dedicated to detection and analysis of molecular events related to 
cancer formation or as applied to pre-clinical drug discovery.  Improvements 
in these areas will bring capabilities for real time molecular analysis at 
whole body levels.

The Phase I component of the proposal supports a first phase for technology 
evaluation.  Applicants should describe proof of principle experiments that 
will demonstrate the utility of the technology. The applicant should: 

--Demonstrate performance of the selected technology on samples comparable to 
those to be used in the proposed study in Phase II.

--Have a detailed plan to optimize and troubleshoot the technology for 
complete adaptation of the technology for the Phase II pilot application.

--Discuss how they will evaluate cost effectiveness of the technology relative 
to existing and competing technologies.

--Specifically address approaches to sample preparation, molecular analysis 
assays, data collection, and data management.
   
Applicants must include in a separate section the milestones to be 
accomplished in the first phase of the application.  Milestones are separate 
from specific aims.  They provide a clear measure of the success of the Phase 
I application which is necessary to proceed to the second phase, therefore 
they should be clearly stated and presented in a manner that is easily 
quantifiable.

The Phase II study is intended to support the pilot application of technology 
evaluated and refined in the Phase I proposal, to a study of biological 
interest to cancer research.  Technology developers are strongly encouraged to 
seek collaborations with qualified cancer researchers. In the Phase II the 
applicants should:

--Describe how they will assess the performance of the technology in providing 
useful molecular data relative to existing technologies.

--Address plans to refine study design parameters based on Phase I results.

--Provide a more refined plan detailing the biological questions to be asked 
by the study and how the forthcoming data will be translated, either directly 
or indirectly, into information relevant to the study of cancer.

--Comment in detail on the suitability of the study design (i.e. numbers, 
types of samples) for asking the biological questions posed by the study. This 
should be discussed in the context of information and data to be obtained from 
Phase I studies. The study design parameters (i.e. number of samples, data 
analysis, etc.)  should be of a scale to reflect that this is a pilot 
application of the technologies.

--Clearly define what is considered to be a high quality sample for the 
technology to be used.

--Document a strategy for obtaining access to high-quality samples that will 
be needed to carry out the study.

--Discuss the ease of transition of the technology from Phase I to Phase II 
application with respect to scaling up the technology and implications related 
to sample cost, availability, and sample through-put.
   
Effective data management and analysis will be critical to the successful and 
productive application of the proposed technology. Therefore applications 
must:

--Address the ability to acquire, store, analyze, and extract information from 
data collected through the course of the study.

--Demonstrate capabilities to capture the data and to perform the complex 
multiplex analysis on data a acquired through the course of the study.

--Describe bioinformatics, other analytical systems, and approaches that will 
be used to interpret data obtained from the study.

Applicants are encouraged to discuss potential strategies for making resulting 
molecular data sets available to the cancer research community in both peer 
reviewed-publications as well as in complete electronically accessible data 
sets.

MECHANISM OF SUPPORT 

Support for the PA is through the SBIR and STTR mechanisms, which are set-
aside programs.  

Applications can 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 under 
the SBIR/STTR FAST-TRACK option as described in the OMNIBUS SOLICITATION  
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).  Phase II 
applications in response to this PAR will only be accepted as competing 
continuations of previously funded NIH Phase I SBIR/STTR awards.  The Phase II 
proposal must be a logical extension of the Phase I research.

Because the length of time and cost of research involving advanced technology 
projects often exceeds that normally awarded for SBIR/STTR grants, NCI will 
entertain well-justified Phase I applications with a project period up to two 
years and a budget not to exceed $100,000 per year direct cost (maximum of 
$200,000 direct costs for to 2 years excluding subcontractor Facility and 
Administrative costs).  Phase II applications with a project period up to 
three years with well-justified budget levels appropriate for the work 
proposed would also be accepted.  Applications submitted through the FAST-
TRACK option are subject to the same direct costs limits per year as when 
submitted outside of the FAST-TRACK option: Phase I R41/43, not to exceed 
$100,000 per year total direct costs excluding subcontractor indirect costs; 
Phase II R42/44, no dollar limit.  However, the total duration (Phase I plus 
Phase II applications) cannot exceed four years.  In any case, Phase I 
applications cannot exceed two years duration.

This program will run in parallel with a program of identical scientific scope 
(http://grants.nih.gov/grants/guide/pa-files/PAR-01-106.html) that will 
utilize the newly created Phased Innovation Award mechanism.  The SBIR and 
STTR applications received in response to this announcement will have the 
opportunity for expedited transition of successful technology research into an 
expanded development phase, and will be subject to cost and duration limits 
comparable to the parallel Phased Innovation Award applications.

Except as otherwise stated in this program announcement, 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/.  Hard copies are not 
available.

ELIGIBILITY REQUIREMENTS

Eligibility requirements are described in the OMNIBUS SOLICITATION.  Any small 
business, independently owned by United States citizens and located in the 
United States, may apply.  Partnerships and collaborations are encouraged.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions 
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Carol A. Dahl, Ph.D. 
Office of Technology and Industrial Relations
National Cancer Institute
31 Center Drive, Room 11A03
Bethesda, MD  20892-2590
Telephone:  (301) 496-1550
FAX: (301) 496-7807
Email:  carol_dahl@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Kathleen J. Shino
Grants Administration Branch
National Cancer Institute
6120 Executive Blvd. Room 243
Bethesda, MD  20892-7150
Telephone:  (301) 846-1016
FAX:  (301  846-5720
Email:  shinok@gab.nci.nih.gov 

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8109, MSC 8326
Bethesda, MD  20892-8326
Rockville, MD  20852 (for express/courier service)
Telephone: (301) 496 -3428
FAX: (301) 402-0275 
Email: tf12w@nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit, by the dates indicated on the 
front page, a Letter of Intent that includes a descriptive title of the 
proposed research, the name, address, and telephone number of the Principal 
Investigator, the identities of other key personnel and participating 
institutions, and the number and title of the PA in response to which the 
application may be submitted.  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 IC staff to estimate the potential 
review workload and plan the review.
 
The Letter of Intent is to be sent to Dr. Carol Dahl listed under INQUIRIES by 
the Letter of Intent receipt date. 

 APPLICATION PROCEDURES

Application forms, requirements and procedures are the same as listed in the 
Omnibus Solicitation for Phase I SBIR/STTR Grant applications 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf), with the following 
exceptions:

o  Type the title and number of this PA on line 2 on the face page of the 
application.

o  The Omnibus Solicitation states levels of Phase I and Phase II budgets that 
are guidelines, not ceilings. Under this PA the NCI will consider larger 
budgets for longer periods of time that are well-justified and necessary to 
complete the proposed research and development.  Phase I budgets are limited 
to project periods up to a two year ceiling, and up to a guideline of $100,000 
direct costs per year, excluding subcontractor facilities and administrative 
costs.  Include a second budget page, and expand the narrative budget 
justification page(s) to provide second year justification if there are 
significant line item differences.  If second year changes reflect only cost 
of living factor(s), include a statement to that effect, the factor(s) used, 
and omit repetition of detail already provided for first year line items.

o  There are no dollar limitations under this PA for Phase II budgets, but 
requested amounts are subject to peer review recommendations, availability of 
funds, and program priority.  Under this PA, budget proposals for direct costs 
of $500,000 or more in any one year require a letter of justification and 
approval of the NCI prior to submission. 

o  A flexible SBIR/STTR Phase I budget period of one or two years (versus the 
Omnibus Solicitation guideline of 6 months for the SBIR and 1 year for the 
STTR).

o  A flexible SBIR/STTR Phase II budget period of one to three years (versus 
the Omnibus Solicitation guideline of up to two years).

o  A four-year limit to funding for a Fast Track, or five year limit to 
funding for a Phase I and renewal Phase II application.

PHASE I APPLICATIONS.  Because the length of time and cost of research 
involving advanced technology projects may exceed that normally awarded for 
SBIR/STTR grants, NCI will entertain well-justified Phase I applications with 
a project period up to two years and a budget guideline that may not exceed 
$100,000 per year direct costs (maximum of $200,000 direct costs for up to 2 
years, excluding subcontractor facilities and administrative costs).

PHASE II APPLICATIONS.  Phase II applications in response to the PA will only 
be accepted as competing continuations of previously funded NIH Phase I SBIR 
or STTR awards.  The Phase II application must be for developmental work that 
is a logical extension of the Phase I feasibility research.  Because the 
length of time and cost of research often exceeds that normally awarded for 
SBIR grants, NCI will entertain well-justified Phase II applications for this 
SBIR/STTR award with project periods up to three years with well-justified 
budget levels appropriate for the work proposed.  Applications for Phase II 
awards should be prepared following the instructions for NIH Phase II SBIR or 
STTR applications.   The Phase II SBIR instructions and application may be 
found on the Internet at: http://grants.nih.gov/grants/funding/phs398/phs398.html.

The Phase II STTR instructions and application may be found on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

Helpful information for preparation of the application(s) can be obtained at: 
http://grants.nih.gov/grants/funding/sbir_policy.htm.

FAST-TRACK APPLICATIONS.  Applications may be submitted for the Fast Track 
review option.  Information on the Fast Track option may be found at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.

Phase I Milestones:  The R41 or R43 phase of a Fast Track application must 
include well-defined, quantifiable milestones that should be achieved prior to 
Phase II funding.  Milestones should be located in a separate section at the 
end of the Research Plan of the Phase I and should be indicated in the Table 
of Contents.  Failure to provide such information for 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, at a later date, the applicant will be reviewed by standard Study Section 
of the Center for Scientific Review or by a special review group convened in 
response to this PAR, if applicable.

Project Period and Amount of Award.   Because the length of time and cost of 
research often exceeds that normally awarded for SBIR grants, NCI will 
entertain well-justified Phase II applications for this SBIR/STTR award with 
project periods up to three years with budget levels appropriate for the work 
proposed (subject to the four year funding limit for Phase I and Phase II 
grants).

Both Phase II applications and Fast Track applications must include a succinct 
commercialization plan, also referred to as a "Product Development Plan" 
(PDP). The PDP is limited to ten pages and must be included as part of the 
Research Plan.  Refer to Phase II grant application instructions 
http://grants.nih.gov/grants/funding/phs398/phs398.html or the Fast-Track 
instructions contained in the Omnibus SBIR/STTR solicitation  
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf) for more specific 
details and instructions.  In the event that an applicant feels their 
technology is too proprietary to disclose, applicants at a minimum should 
provide a demonstration (e.g., results) of the capabilities of the proposed 
technology.  

An annual meeting of all investigators funded through this program will be 
held to share progress and research insights that may 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

FOR ALL APPLICATIONS

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, send two copies  of 
the application to:  

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8109, MSC 8236
Bethesda, MD  20892-8236
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-3428
FAX:  (301) 402-0275

Applications must be received by the receipt dates listed at the beginning of 
this PA.
The Center for Scientific Review (CSR) will not accept any application in 
response to this PA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by the CSR for completeness and by 
the NCI program staff for adherence to the guidelines.  Applications not 
adhering to application instructions described above and those applications 
that are incomplete as determined by CSR or by NCI program staff will be 
returned to the applicant without review.  

Applications that are complete and adhere to the guidelines of this PA will be 
evaluated for scientific and technical merit by an appropriate peer review 
group convened by the NCI in accordance with the review criteria stated below.  
As part of the initial merit review, all applicants will receive a written 
critique and may undergo a process in which only those applications deemed to 
have the highest scientific merit generally the top half of the applications 
will be discussed, assigned a priority score, and receive a second level 
review by the National Cancer Advisory Board (NCAB).
    
Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. In the 
written comments reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application. Note that the application 
does not need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score. For example, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

Review criteria as described in the NIH OMNIBUS SOLICITATION have been 
included in the following:

1.  Significance.  Does this study address an important problem? If the aims 
of the application are achieved, how will scientific knowledge be advanced?  
What may be the anticipated commercial and societal benefits of the proposed 
activity? What will be the effect of these studies on the concepts or methods 
that drive this field?  To what degree does the technology support the needs 
of the targeted research community?  For systems intended for clinical 
research the additional criteria will be considered: to what degree is the 
analysis system appropriate for clinical research and likely to have utility 
for the analysis of clinical specimens or patients? Does the proposed project 
have commercial potential to lead to a marketable product or process? 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?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics? What is the time frame for developing the proposed 
technologies and suitability of this time frame for meeting the scientific 
community’s needs?  How easy will it be to use the proposed technology?  Are 
the plans for proposed technology dissemination adequate?  Is the proposed 
plan a sound approach for establishing technical and commercial feasibility?  

3. Milestones.  How appropriate are the proposed milestones against which to 
evaluate the demonstration of feasibility for transition to the Phase II 
development phase?

4.  Innovation.  Does the project employ novel concepts, approaches, or 
method? Are the aims original and innovative? Does the project challenge 
existing paradigms or develop new methodologies or technologies? What is the 
throughput and cost effectiveness of the proposed technology?  What additional 
uses can be projected for the proposed technology?

5.  Investigator.  Is the investigator appropriately trained and well suited 
to carry out this work?  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 subawardees (if any)?
  
6.  Environment.  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? Does not make sense 
for small business.  Is there sufficient access to resources (e.g. equipment, 
facilities)?  
        
In addition to the above criteria, the following will also be considered for 
Phase II applications and Phase I/Phase II FastTrack applications.  

1. To what degree was progress toward the Phase I objectives met and 
feasibility demonstrated in providing a solid foundation for the proposed 
Phase II activity?  

2.  Did the applicant submit a concise Product Development Plan that 
adequately addresses the four areas described in the Omnibus SBIR/STTR 
solicitation? 

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 
commercialization?  

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

The initial review group will also examine: the appropriateness of the 
proposed project budget and duration; the adequacy of plans to include both 
genders and minorities and their subgroups, and children as appropriate for 
the scientific goals of the research and plans for the recruitment and 
retention of subjects; the provisions for the protection of human and animal 
subjects; and the safety of the research environment.
    
AWARD CRITERIA

Applications will compete for available funds with all other recommended SBIR 
and STTR applications.  Funding decisions for Phase I or Phase II applications 
will be based on quality of the proposed project as determined by peer review, 
availability of funds, and program priority.

FAST-TRACK, Phase II applications may be funded following submission of the 
Phase I progress report and other documents necessary for continuation.  Phase 
II applications will be selected for funding based on the initial priority 
score, NCI’s assessment of the Phase I progress and determination that Phase I 
goals were achieved, the project’s potential for commercial success, and the 
availability of funds.

SCHEDULE

Letter of Intent Receipt Dates:   June 15, 2001; October 17, 2001; 
                                  February 14, 2002; June 10, 2002; 
                                  October 18, 2002; February 14, 2003; 
                                  and June 16, 2003
Application Receipt Dates:        July 20, 2001; November 21, 2001; 
                                  March 21, 2002; July 22, 2002; 
                                  November 22, 2002; March 21, 2003; 
                                  and July 21, 2003
NCAB Review Dates:                February 2002; May 2002; September 2002; 
                                  February 2003;  May 2003; September 2003; 
                                  February 2004
Earliest Anticipated Award Date:  April 1, 2002; July 1, 2002; November 1, 2002; 
                                  April 1 2003; July 1, 2003; November 1, 2003; 
                                  April 1, 2004

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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 biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and 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 research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000  
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to 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) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH 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 clear and compelling 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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address:  http://grants.nih.gov/grants/guide/notice-files/not98-024.html. 

Investigators also may obtain copies of the policy from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
NIH policy on education in the protection of human research participants now 
required for all investigators, which is published in the NIH Guide for Grants 
and Contracts, June 5, 2000 (Revised August 25, 2000), available at the 
following URL address 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.  
A continuing education program on the protection of human 
participants in research is now available online at http://cme.nci.nih.gov/.

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.  Reviewers are cautioned 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 PA, Applications of Innovative 
Technologies for the Molecular Analysis of Cancer: SBIR/STTR  is related to 
the priority area of cancer.  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 No. 
93.394.  Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-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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