DIAGNOSTIC IMAGING AND GUIDED THERAPY IN PROSTATE CANCER: SBIR/STTR INITIATIVE

Release Date:  August 19, 1999

PA NUMBER:  PAR-99-149

National Cancer Institute
National Institute on Aging

Letter of Intent Receipt Date:  October 20, 1999
Application Receipt Date:  November 17, 1999

PURPOSE

The National Cancer Institute (NCI) and the National Institute on Aging (NIA)
invite Small Business applications on the development, risk assessment, and
application of improved imaging methods for the localization, biopsy and image
guided biopsy or therapy of prostate cancer.  Relevant investigations could
include technology development, in vitro laboratory work, pre-clinical animal
studies, or early feasibility testing in humans depending on the maturity of
the methods proposed, or evaluation of the effects of age-associated changes
and co-morbid conditions as they affect imaging diagnosis and treatment
techniques.  The development of several methodologies and their optimization
for this particular organ system is required.  The specific goals include the
development and application of one or more of the following inter-related
components:  (a) means for measuring local extent of disease using anatomic,
metabolic or alternative novel imaging methods, (b) means for improved image
guided biopsy, staging or identification of aggressive cancers by metabolic or
alternative novel imaging methods, and (c) means for navigation, control of
image guided therapy or measurement of early biological effects of therapy. 
Research is also encouraged on how age-associated differences in tumor
characteristics and age-related changes in the prostate and adjacent tissues
may affect the sensitivity, specificity, prognostic value, or the efficacy of
imaging techniques in guiding therapy.  The development of methods to increase
sensitivity, specificity, prognostic value, and therapeutic applicability of
these techniques across the full range of ages in which prostate cancer most
frequently occurs, and in the presence of age-related co-morbid conditions in
the prostate, other organs, and systems, is of particular interest.

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 Innovation Award mechanism RFA CA-99-015 (see
http://www.nih.gov/grants/guide/rfa-files/RFA-CA-99-015.html).  The
SBIR and STTR applications received in response to this program announcement
will undergo expedited review, 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.  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)
http://www.nih.gov/grants/funding/sbir.htm, and the OMNIBUS SOLICITATION OF
THE NATIONAL INSTITUTES OF HEALTH FOR SMALL BUSINESS TECHNOLOGY TRANSFER GRANT
APPLICATIONS (PHS 99-3) http://www.nih.gov/grants/funding/sttr1/toc.htm.  SBIR
Phase II Grant Application (PHS Form 6246-2) are available at
http://www.nih.gov/grants/funding/sbir2/index.htm.  All of the instructions
within the OMNIBUS SOLICITATIONS apply with the following exceptions:

o  Special receipt dates
o  Initial review convened by the NCI Division of Extramural Activities
o  Additional review considerations
o  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 program announcement (PA), Imaging
Techniques for Early Prostate 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 is a one-time 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 as stated in
the NIH Grants Policy Statement, NIH Publication Number 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 date 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 development plan
for the Phase II (R42/44) application. The FAST-TRACK must have a section
labeled Milestones at the end of the Research Plan for 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 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, the Phase I applications cannot exceed two years
duration.  Applications should contain budgets and justification for all
years.

Applications over $500,000.  Although the FAST TRACK application has no
official budgetary limit, applications requesting excess of $500,000 dollars
direct cost in any single year of the grant period require prior approval
before submission.  Applicants who plan to submit a FAST TRACK 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.

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 following the directions for Phase I
SBIR/STTR applications as described in the NIH OMNIBUS SOLICITATION.  The NIH
OMNIBUS SBIR SOLICITATION and NIH OMNIBUS STTR SOLICITATION are available on
the Internet at: http://www.nih.gov/grants/funding/sbir.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) 206-9696
FAX:  (301) 206-9722
Email:  [email protected]

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.

BACKGROUND

The ability to diagnose early prostate cancer has outpaced imaging methods for
accurate localization and staging of the disease, and for delivering the most
appropriate form of therapy.  This is reflected in the specific research needs
identified by the Prostate Cancer Clinical Guidelines Panel of the AUA as
early as 1995.  Needs include improved  methods for: (a) identification of the
boundary of the prostate and localization of the extent of the disease, (b)
staging and determination of biologic aggressiveness, and (c) minimally
invasive treatment of localized prostate cancer.  Within the past year, the
NCI Prostate Portfolio Review Group (PRG) and the NCI Imaging Sciences Working
Group (ISWG) made similar recommendations.

Accurate determination of the extent of local disease in the prostate is
difficult.  Current imaging techniques include transrectal ultrasound (TRUS),
endorectal coil magnetic resonance imaging (MRI), and proton magnetic
resonance spectroscopic imaging (MRSI).  The reported accuracy of TRUS for
determining if prostate cancer is confined within the capsule varies widely
from 58% to 90%.  However, preliminary data from recent studies of endorectal
MRI show higher accuracy (75-90%) than TRUS, and better consistency.  Further
technical advances in high-resolution ultrasound and MRI are feasible and
would result in localization and staging of local prostate cancer that is more
accurate than current methods.

In addition to morphologic extent, directed biopsy and assessment of tumor
aggressiveness are important for accurate staging and treatment for prostate
cancer when there is an elevated PSA.  Current biopsy techniques are based on
random spatial sampling and have a lower than desired sensitivity (60-70%) for
identification of carcinoma of the prostate.  Early preliminary studies of
combined MRI/MRSI demonstrated localization of cancer to a sextant of the
prostate with sensitivity up to 95% and specificity up to 91%.  However,
localization more specific than to a sextant would be desirable.  New contrast
agents or metabolic markers measurable by MRI, MRS, TRUS, nuclear medicine or
other imaging sensors (e.g., optical technologies) may contribute to improved
image guidance and tumor staging.

Early metabolic studies of prostate cancer by 3D proton MRSI show an ability
to predict tumor aggressiveness equal to or better than other markers such as
tumor grade or peak serum PSA.  Preliminary results for spectral analysis of
ultrasound images suggest a similar role for this modality; spectral
differences have been found to correlate with histopathology of certain tumors
located in other organ systems.  Optical spectra and chemical diagnostic
imaging probes need to be investigated as indicators of biologic
aggressiveness as well.

The clinical management of localized prostate cancer remains controversial. 
The two generally accepted methods of treatment for clinically localized
prostate cancer, namely radical prostatectomy and external beam radiation
therapy, have significant, but different, morbidity.

A variety of local therapies are being developed that can potentially treat
prostate cancer without major surgery.  They include brachytherapy,
hyperthermia, cryosurgery, interstitial laser therapy, focused ultrasound,
focused microwaves, or local delivery of therapeutic agents such as gene
therapy vectors.  Treatment of localized prostate cancer with one of these
alternative methods has several potential advantages.  Image-guidance systems
are essential to the successful application of these and other local
therapies.  Image guided therapy is the use of images obtained either during
or prior to treatment, coupled with the use of computers, sensors, graphics,
or other technologies to assist or guide the administration of treatment.

As image guidance of therapy improves, wider dissemination of the techniques
will be possible because they will become less operator-dependent.  For
technologies where great skill is required, practitioners outside of centers
with large numbers of patients may not be able to attain the level of skill
necessary to achieve successful intervention and cure.

The opportunity to make significant advances in image guided therapy now is
great because of technological breakthroughs in several areas.  "Open" MRI
magnets, developed to reduce patient discomfort, make it possible for
radiologists, surgeons and others to perform interventional procedures while
the patient is being imaged.  The digital architecture of current ultrasound
machines, and advances in ultrasound transducer manufacture have opened new
possibilities for ultrasound guidance.  Translation of discoveries in
fiberoptic and laser technologies to medical applications make optical
techniques an exciting new area for image guided procedures.  Increasing
computer power at lower cost makes image-processing techniques possible in
real-time.

RESEARCH OBJECTIVES

The purpose of this PA is to stimulate research into the development and
application of improved imaging methods for the localization, risk assessment,
and minimally invasive biopsy or delivery of therapy for prostate cancer. 
Prostate cancer incidence increases as a function of age to a magnitude
unparalleled by all other tumors.  Aging men are diverse in overall health and
physiologic and physical functioning.  These factors may impact on diagnosis
and therapy.  Research is particularly encouraged on how age-associated
changes in the prostate and adjacent tissues and co-morbid conditions may
affect imaging techniques' sensitivity, prognostic value, or their utility in
guiding therapy.  Relevant investigations could include technology
development, in vitro laboratory work, pre-clinical animal studies, or early
feasibility testing in humans depending on the maturity of the methods
proposed, and the evaluation of age-associated changes or co-morbid conditions
on imaging techniques for prostate diagnosis and treatment.  Image guided
therapy requires the development of several methodologies and their
optimization for this particular organ system.  The specific goals therefore
include the following inter-related components:  (a) means for measuring local
extent of disease using anatomic, metabolic or alternative novel imaging
methods, (b) means for improved image guided biopsy or other image guided
tissue sampling methods and staging or identification of aggressive cancers by
metabolic or alternative novel imaging methods, and (c) means for navigation,
control of image guided therapy or measurement of early biological effects of
therapy.

One key issue is that the navigational device requires the virtual object to
be accurately registered to the therapeutic object, ideally during the full
course of therapy, with improved navigational accuracy for the small scale of
the prostate gland.  Considerable bioengineering expertise must be combined
with basic science and clinical input in designing and developing image guided
therapy systems. The response to the PA should therefore address one or more
of the following four broad areas and development phases.

A.  Improved localization, image guided biopsy or tissue sampling, or staging
methods for early prostate cancer.

Important areas for investigation should be specific to the prostate gland,
and may include, but are not limited to:

o  Improvements in MRI and MRSI methods, such as: (a) specialized radio
frequency (RF) transmit and receive coils, RF pulse sequencing and 3D imaging
methods to improve signal to noise (S/N) and image contrast, and (b)
development and application of novel MR contrast materials for identification
of prostate cancer.
o  Improvements in ultrasound, such as novel probe design, RF pulse
sequencing, contrast materials, 3D imaging methods, and multi-spectral imaging
to improve S/N and image contrast.
o  Advances in PET or SPECT imaging, such as using novel radio-ligands
specific for prostate cancer to improve tumor localization and staging.
o  Other novel imaging methods, such as optical imaging, spectroscopy, and
contrast enhancement methods, to improve image-guided biopsy or tissue
sampling and staging of cancer.
o  Image processing methods for improved image registration, image fusion,
image contrast and resolution.
o  Innovative tissue sampling methods to improve localization and the adequacy
of tissue samples for diagnosis of prostate cancer.
o  Improved and, ideally, automatic image segmentation techniques for the
prostate gland and surrounding tissues for determining the boundary of the
prostate gland, connective tissues and proposed treatment area.
o  Multi-spectral analysis or computer classification methods as applied to
MRI, MRS, ultrasound, radio frequency (RF) or other sensor images/spectra are
important to explore for classification of tissues as normal or cancer, or to
determine the level of cancer aggressiveness.
o  Combination of the above  methods with PSA or other markers for improved
staging of prostate cancer and patient selection for image guided therapy.

B.  Image Guided Therapy Methods.

All the minimally invasive locally ablative therapies are still under
development and should not be pre-judged as to their effectiveness relative to
each other or to existing standard therapies.  Thus, new approaches to image
guided local therapy will be responsive to this PA.

Therapy methods specific for the prostate may include, but are not limited to:

o  Heating the tissue directly, to coagulate cellular proteins, with
controlled temperature probes or lasers, or killing  cellular proteins by
freezing with small probes (cryosurgery).
o  Administration of chemotherapeutic agents, such as gene therapy vectors, or
toxic chemicals, either delivered directly into tumors by small catheter-based
tools, or administered systemically and deposited locally by the addition of
externally applied energy such as focused ultrasound.
o  Focused ultrasound waves, radiowaves, or microwaves  used to heat tissue
and cause protein coagulation.  Externally focused energy methods are
particularly attractive in that no needle or probe has to be inserted into the
tissue, of more control over the distribution and amount of heat generated
throughout the treatment volume.

C.  Image Guidance and Control of Therapy

All the above  therapeutic methods require image guidance, both to steer the
focal point of the therapy and to provide a means to control degree of local
therapy.

Technical problems that need to be addressed, specifically for the prostate
include, but are not limited to:

o  Design of the navigational system.  Image guided therapy systems need to be
developed for specific application to the prostate, and to address the
navigational and control scales required for this small gland and associated
surrounding critical tissue structures. Similarly, for instances where
physical probe insertions are required, the integration of models for
incorporating soft tissue deformation characteristics into the image guided
therapy system needs to be investigated. The image guided therapy system also
needs to address all registration issues that influence the accuracy of
navigation. The use of robotics for improved navigation and reproducible
controlled probe insertion is also an area of interest.
o  Means for controlling therapy delivery.  Control of the various forms of
therapy may require modeling of the therapy response (which may be non-linear)
to ensure patient-specific local spatial control and control of the total
therapy dose delivered.  There is a need to explore  physical  methods to
control localized therapy.  For example, MRI can provide both high spatial
resolution and tissue temperature measurement. There is a need to further
develop and model such temperature measurement methods and feed back
mechanisms and integrate these components into the image guided therapy
system, to assure accurate spatial delivery of thermal exposure throughout the
gland.
o  Monitoring of early biological effects and feedback mechanisms for the
image guided therapy system.  Novel methods for measurement of early
biological effects, such as for non-thermal therapies, are considered
important; feed back mechanisms may provide a basis for therapy control.  For
example, photo-dynamic therapy (PDT) is one local therapy that has been
proposed and an early biologic marker of successful response to PDT would be
useful.
o  Imaging as a follow up to therapy treatment.  There is a need to understand
and quantitate the changes in the images following therapy and to relate the
image differences to tissue changes.  Imaging can be used to follow treated
patients, especially if the changes expected to be caused by therapy are
known.
o  Optimization and validation of all the engineering components of the
navigational system. There is a need to develop metrics to determine the
performance of the image guided therapy system components and overall
integrated system performance.

D.  Image Guided Therapy Systems: Development Phases for Fully Integrated
Systems.
Development and optimization of the image guided therapy for the prostate may
require several phases of technology development and pre-clinical evaluation
as outlined above.  For example, we anticipate that applications may be
received for two levels of effort.  First, investigators who have image guided
therapy experience with totally integrated systems for another organ system
may seek support for the translation of research and development for an fully
integrated image guided therapy system specifically for the prostate.  Such
applications may propose development of the integrated system within 2-3
years, with performance specifications and pre-clinical or preliminary
clinical testing to be completed by the end of the grant period.  It is
anticipated that clinical trials would be performed after this grant period. 
Second, requests are anticipated for the development and integration of
several key components, but not necessarily all, outlined above, and for
limited evaluation of performance specifications or pre-clinical evaluation,
where the image guided therapy components are optimized for the scale of
measurement and application to the prostate gland.

Partnership of institutions having medical expertise and patient access with
medical device manufacturers will permit a joint approach to the integration
of system components for image guided diagnosis and therapy of the prostate.

E.  Effects of age-related changes on sensitivity, specificity, prognostic
value, or therapeutic applicability of new imaging techniques.

Age-associated differences in tumor characteristics, and age-related changes
in the prostate and adjacent tissues, may affect imaging techniques'
sensitivity, specificity, prognostic value, or therapeutic applicability. 
Applicants are encouraged to examine these aspects of new imaging techniques
across the full range of ages in which prostate cancer most frequently occurs,
including advanced ages in which incidence and mortality rates are the very
highest.  Applicants are asked to consider how non-malignant age-related
changes in the prostate (e.g., benign prostatic hypertrophy), and other age-
related changes and co-morbid conditions may affect the sensitivity,
specificity, prognostic value, or therapeutic applicability of imaging
techniques.  Applicants are encouraged to develop and test methods to optimize
these aspects of imaging techniques in the presence of age-related changes or
co-morbid conditions.

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, available on the web at the following URL address: 
http://www.nih.gov/grants/guide/1994/94.03.18/notice-nih-guideline008.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.

Applications received in response to this PA are expected to focus on
scientific issues related to prostate cancer.  In describing the plan to
recruit human subjects, investigators may cite a focus on prostate cancer as
the justification for why women will be excluded.  In this regard applicants
may use Justification 1 from the policy announcement.

LETTER OF INTENT

Prospective applicants are asked to submit, by the date listed at the
beginning of this PA, 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 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. Barbara Croft 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:
[email protected].  Helpful information for preparation of the application can be
obtained: https://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf

Phase I applications are to be submitted on the grant application form PHS
6246-1(SBIR) (1/99) 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.  Phase II applications are to
be submitted on grant application form PHS 6246-2 (SBIR) (1/99) and PHS 6246-4
(STTR) (3/99).

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.

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.

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.

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.  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 PA, 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 ten 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 copies 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 7399
Bethesda, MS 20892-7405
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-3428
FAX:  (301) 402-0275

Applications must be received by the receipt date 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 technology forward.

1.  Significance.  Does this study address an important problem? If the aims
of  the application are achieved, how will clinical treatment and 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 clinical community?  To what degree is the
image guided therapy system appropriate for clinical research and likely to
have utility for the physicians and patients?

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 clinical
community's needs?  How easy will it be to use the proposed technology?  Are
the plans for proposed technology dissemination adequate?

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 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 work proposed appropriate to the experience
level of the principal investigator and other researchers (if any)?

6.  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
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.

Additional Considerations

For the SBIR/STTR Fast Track applications, the initial review group will
evaluate the specific goals for each phase and the feasibility Milestones that
would justify expansion to phase II. A single priority score will be assigned
to each scored application.  As with any grant application, the initial review
group has the option of recommending support for a shorter duration than that
requested by the applicant, and basing the final merit rating on the
recommended portion of the application.  For the Fast Track application, this
may result in a recommendation that only the phase I be supported, based on
concerns related to the applicant specific goals and the feasibility
Milestones justifying expansion to  phase II.  Deletion of phase II by the
review panel or inadequate Milestones will affect the merit rating of the
application.

AWARD CRITERIA

Applications will compete for available funds with all other recommended 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.  Criteria for continuing to
Phase II in a Fast Track grant are available at the following website:
https://grants.nih.gov/grants/funding/sbirsttr1/6method.htm#6g

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Barbara Y. Croft, Ph.D.
Diagnostic Imaging Program
National Cancer Institute
6130 Executive Boulevard, Room 800
Bethesda, MD 20892
Telephone:  (301) 496-9531
FAX:  (301) 480-5785
Email: [email protected]

Direct inquiries regarding fiscal matters to:

Ms. Kathleen Shino
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD  20892-7150
Telephone:  (301) 496-8635
FAX:  (301) 496-8601
Email:  [email protected]

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: [email protected]

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 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 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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