APPLICATIONS OF INNOVATIVE TECHNOLOGIES FOR THE MOLECULAR ANALYSIS OF CANCER:  
(SBIR/STTR) INITIATIVE

Release Date:  May 14, 1999

PA NUMBER:  PAR-99-103

P.T.

National Cancer Institute

Letter of Intent Receipt Dates: June 18, October 18, 1999; February 18, June 19,
October 19, 2000 and February 20, 2001
Application Receipt Dates: July 21, November 21, 1999; March 21, July 21,
November 21, 2000 and March 21, 2001

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, 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 and tissue repositories.

This program will utilize the Small Business Innovation Research (SBIR) and Small
Business Technology Transfer (STTR) mechanisms, but will be run in parallel with
a program of identical scientific scope that will utilize the newly created
Phased Technology Application Award (PAR-99-102).  The SBIR and STTR applications
received in response to this announcement will undergo expedited review, have the
opportunity for expedited transition of successful Phase I proof of principle
into an expanded technology application phase, and will be subject to cost and
duration limits comparable to the parallel Phased Technology Application Award
applications. This program announcement must be read in conjunction with the
Omnibus Solicitation of the Public Health Service for Small Business Innovation
Research Grant Applications (PHS 99-2), and the Omnibus Solicitation of the
National Institutes of Health for Small Business Technology Transfer Grant
Applications  (PHS 99-3).  All of the instructions within the Omnibus
Solicitations apply with the following exceptions:

Special receipt dates

Initial review convened by the NCI Division of Extramural Activities

Additional review considerations

Opportunity for 2 years of Phase I support

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of Healthy People 2000, a PHS-led national
activity for setting priority areas.  This PA, Innovative Technologies for the
Molecular Analysis of Cancer: SBIR/STTR Initiative, is related to the priority
area of cancer.  Potential applicants may obtain a copy of "Healthy People 2000"
(Full Report: Stock No. 017-001-00474-0 or Summary Report:  Stock No. 017-001-
00473-1) through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800), or at
http://www.crisny.org/health/us/health7.html.

ELIGIBILITY REQUIREMENTS

Eligibility requirements for SBIR and STTR are described in the NIH Omnibus
Solicitation for SBIR/STTR grant applications.  As stated in the REVIEW
CONSIDERATIONS section, applications submitted in response to this PA will be
reviewed by one or more NCI Special Emphasis Panels convened especially for this
solicitation.

MECHANISM OF SUPPORT

This PA will expire two years from the initial receipt date as indicated by the
dates on the front of this solicitation.  Responsibility for the planning,
direction and execution of the proposed project will be solely that of the
applicant.  Awards will be administered under NIH grants policy stated in the NIH
Grants Policy Statement, NIH publication 99-8 October 1998.

A.  FAST-TRACK APPLICATIONS.  Applications may be submitted for the FAST-TRACK
review option.  Information on the FAST-TRACK process may be found at:
http://www.nih.gov/grants/funding/sbir.htm.  Applications will be accepted only
on the receipt dates listed on the first page of this document.

To be eligible for the FAST-TRACK option, the Phase I (R41/43) application must
include well defined quantifiable milestones that will be used to judge the
success of the proposed research, as well as a credible plan to apply the
selected technology in a pilot study of biological interest to cancer research
for the Phase II R42/44 application. The FAST-TRACK must have a section labeled
Milestones at the end of the Research Plan Phase I R41/43. This section must
include well-defined quantifiable milestones for completion of Phase I R41/43,
a discussion of the suitability of the proposed milestones for assessing the
success in Phase I R41/43, and a discussion of the implications of successful
completion of these milestones on the proposed Phase II R42/R44.

Applications submitted through the FAST-TRACK option are subject to the same
direct cost 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, the Phase I application cannot exceed two years duration.

B.  INDIVIDUAL  PHASE I APPLICATIONS.  Phase I applications in response to this

PA will be funded as Phase I SBIR Grants R43 or STTR Grants R41 with
modifications as described below. Applications for Phase I grants should be
prepared following the directions for Phase I SBIR/STTR applications as described
in the NIH Omnibus Solicitation.  The NIH Omnibus SBIR Solicitation is available
on the Internet at: http://www.nih.gov/grants/funding/sbir1/sbir.htm.  The NIH
OMNIBUS STTR Solicitation is available at:
http://www.nih.gov/grants/funding/sttr1/toc.htm.

A limited number of hard copies of the NIH Omnibus SBIR and STTR Solicitations
are available from:

PHS SBIR/STTR Solicitation Office
13685 Baltimore Avenue
Laurel, MD  20707-5096
Telephone:  301-206-9385
FAX:  (301) 206-9722
Email:  a2y@cu.nih.gov

Project Period and Amount of Award.  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 indirect costs).

Page Limitations.  The requirements for normal Phase I applications apply (see
NIH OMNIBUS Solicitation).

C.  INDIVIDUAL PHASE II APPLICATIONS

Phase II applications in response to this PA will be awarded as Phase II SBIR
Grants R44 or STTR Grants R42 with modifications as described below.  Phase II
applications in response to this PA will only be accepted as competing
continuations of previously funded NIH Phase I SBIR/STTR awards.  The Phase II
application must be a logical extension of the Phase I research.

Applications for Phase II awards should be prepared following the instructions
for NIH Phase II SBIR/STTR applications.  The Phase II SBIR instructions and
application may be found on the Internet at:
http://www.nih.gov/grants/funding/sbir2/index.htm.

The Phase II STTR instructions and application may be found on the Internet at:
http://www.nih.gov/grants/funding/sttr2/index.html

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 a project
period up to three years with no budget limitation.  Applications over $500,000. 
Although the Phase II application has no official budgetary limit, applications
requesting in excess of $500,000 dollars direct costs in any single year of the
grant period require prior approval before submission.  Applicants who plan to
submit a Phase II SBIR/STTR application requesting $500,000 or more in any year
are advised that it is important that they contact program staff listed under
INQUIRIES as they begin to develop plans.  Applications requesting more than
$500,000 received without prior staff contact may be delayed in the review
process or returned to the applicant without review (NIH GUIDE, Volume 22, Number
45, December 17, 1993).

BACKGROUND

Rapid molecular analysis tools will expedite the molecular characterization of
normal cells from 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.  To this end, the NCI has established the Cancer Genome
Anatomy Project (CGAP), which will put in place the research infrastructure that
will allow deciphering of the molecular anatomy of a cancer cell at the DNA, RNA
and protein levels.  The NCI has established the Tumor Gene Index, an index
identifying the genes that are expressed in normal, precancerous, and cancerous
cells. This project is well under way and further information about the Index can
be found at http://www.ncbi.nlm.nih.gov/ncicgap.  The NCI has also begun a
project to identify cancer chromosome aberrations (Cancer Chromosome Aberration
Project, CCAP).  The NCI has started the generation of a public repository of a
standardized set of bacterial artificial chromosome (BAC) clones anchored across
the whole human genome at 1 megabase intervals, for the identification of cancer
chromosomal aberrations and reference points/landmarks clones for the integration
of cancer chromosome aberrations and genomic data.  Information on the repository
and reagent access will be released on CCAP homepage
(http://www.ncbi.nlm.nih.gov/).  The NCI is also targeting the
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, preclincial 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,
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 OBJECTIVES

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 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 evaluation
and 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 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 Phase II study.

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 proposal the
applicants should:

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

Provide a more refined plan detailing the 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 a 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 the 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 utilize databases and to perform the complex
mutliplex analysis an a data 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 s
reviewed-publication as well as in complete electronically accessible data sets.

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
subpopulations 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 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
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

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.

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://www.nih.gov/grants/guide/notice-files/not98-024.html

As part of the scientific and technical merit evaluation of the research plan,
reviewers will be instructed to address the adequacy of plans for including
children as appropriate for the scientific goals of the research.

LETTER OF INTENT

Prospective applicants are asked to submit, by the dates listed at the beginning
of this program announcement, 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 NCI staff to estimate the potential review
workload and avoid conflict of interest in the review.  The letter of intent is
to be sent to Dr. Jay George at the address listed under INQUIRIES.

APPLICATION PROCEDURES

OMNIBUS SOLICITATIONS for both the SBIR and STTR programs are available
electronically through the NIH, Office of Extramural Research Small Business
Funding Opportunities web site at http://www.nih.gov/grants/funding/sbir.htm. 
Hard copies, subject to availability, may be obtained from the PHS SBIR/STTR
Solicitation Office, phone (301) 206-9385; FAX (301) 206-9722; email
a2y@cu.nih.gov.  Helpful information for preparation of the application can be
obtained: https://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf

Applications are to be submitted on the grant application form PHS 6246-1 (1/99)
(SBIR) and PHS 6246-3 (STTR) (3/99) located in the back pages of the OMNIBUS
SOLICITATIONS, and will be accepted at the application deadlines as indicated on
the first page of this document.

THE TITLE AND NUMBER OF THIS PA MUST BE TYPED IN LINE 2 ON THE FACE PAGE OF THE
APPLICATION.

The OMNIBUS SOLICITATIONS give the normal levels of support and period of time
for SBIR and STTR Phase I and II awards.  However, these award levels are
guidelines and not ceilings.  Therefore, larger budgets with longer periods of
time may be requested if required to complete the proposed research.  As stated
under MECHANISM OF SUPPORT section, Phase I applications submitted in response
to this PA can have a project period of up to two years and a budget not to
exceed $100,000 per year direct cost excluding subcontractor indirect costs.

The second year of the Phase I budget should be included on the Budget
Justification page, using categorical totals if costs deviate significantly from
the first year of the budget, with narrative justifications for the increase(s). 
If the second year simply escalates due to cost of living factors, a statement
to that effect with the escalation factor should be included rather than
categorical totals. Phase II applications submitted in response to this PA have
no budget limitations.  The total duration (Phase I and Phase II application)
cannot exceed four years.

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.

In order to apply for the FAST-TRACK option, applications for both Phase I and
Phase II must be submitted together according to the instructions for FAST TRACK
applications as described in the OMNIBUS SOLICITATIONS.  The Phase I application
must specify clear, 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 measurable milestones and sufficient
detail may be sufficient reason for the peer review committee to exclude the
Phase II application from FAST-TRACK review. If so, at a later date, the
applicant may apply for Phase II support through normal application procedures. 
Such applications will be reviewed by a standard Study Section of the Center for
Scientific Review or by a special review group convened in response to a re-
issuance of this PAR, if applicable.

An additional requirement of the FAST-TRACK mechanism is the Product Development
Plan.  The small business must submit a concise Product Development Plan (limited
to five pages) as an Appendix to the Phase II application addressing the four
areas described in the instructions for FAST-TRACK applications in the OMNIBUS
SOLICITATIONS.  In the event that an applicant feels that technology is too
proprietary to disclose, applicants at a minimum should provide a demonstration
(e.g., results) of the capabilities of the proposed technology.

The completed original application and one legible copy must be sent or delivered
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 one additional
copy of the application to:

Ms. Toby Friedberg
Referral Officer
National Cancer Institute
6130 Executive Boulevard, Room 636a, MSC 7405
Bethesda, MD 20892-7405
Rockville, MD 20852 (for overnight/courier service)
Telephone:  (301) 496-3428
FAX:  (301) 402-0275

Applications must be received by the receipt dates listed at the beginning of
this program announcement.

REVIEW CONSIDERATIONS

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

Applications that are complete and responsive to the 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.

Review criteria are described in the NIH Omnibus Solicitation and are as follows:

1.  The soundness and technical merit of the proposed research. (Preliminary data
are not required for Phase I proposals.

2.  The qualifications of the proposed principal investigator, supporting staff,
and consultants.

3.  The scientific, technical, or technological innovation of the proposed
research.

4.  The potential of the proposed research for commercial application or societal
impact.

5.  The appropriateness of the budget requested.

6.  The adequacy and suitability of the facilities and research environment.

7.  Where applicable, the adequacy of assurances detailing the proposed means for
safeguarding human or animal subjects and/or (b) protecting against or minimizing
any adverse effect on the environment.

For Fast-Track, Phase I application should specify clear, well defined
quantifiable milestones that should be achieved prior to initiating Phase II.
Failure to provide clear, measurable milestones may be sufficient reason for the
study section to judge the application non-competitive.

In addition to the standard review criteria as described in the NIH Omnibus
Solicitation, the reviewers will comment on the six following aspects of the
application in their written critiques 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 by the reviewers 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 a 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.

Significance.  Does this study address an important problem? If the aims of the
application are achieved, how will scientific knowledge be advanced?  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?

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?

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

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 or expanded capabilities of the proposed technology?

Investigator.  Is the investigator appropriately trained and well suited to carry
out this work?  Is the work proposed appropriate to the experience level of the
principal investigator and other researchers (if any)?

Environment.  Does the scientific 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? Is there evidence of institutional support?

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 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 as well as the adequacy of plans for including children as
appropriate for the scientific goals of the research, or justification for
exclusion (see section on NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN
AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS).

AWARD CRITERIA

Applications will compete for available funds with all other approved SBIR and
STTR applications.  Funding decisions for Phase I 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
milestones were achieved, programmatic relevance the project potential for
commercial success, and the availability of funds.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

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

Direct inquiries regarding fiscal matters to:

Ms. Kathleen Shino
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Boulevard
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext. 248
FAX:  (301) 496-8601
Email:  shinok@gab.nci.nih.gov

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636
Bethesda, MD  20892-7150
Telephone:  (301) 496-3428
FAX:  (301) 402-0275
Email:  tf12w@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.394, Cancer Detection and Diagnosis Research.  Awards are made under
authorization of the Sections 301 and 405 of the Public Health Service Act, as
amended (42 USC 241 and 284) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74 and part 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 and contract 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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	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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