NOVEL TECHNOLOGIES FOR IN VIVO IMAGING (SBIR/STTR)

RELEASE DATE:  May 19, 2003

PA NUMBER: PAR-03-125 (see replacement PA-04-094)

EXPIRATION DATE: December 1, 2003, unless reissued.

National Cancer Institute (NCI) 
 (http://www.nci.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS) 
 (http://www.niehs.nih.gov/)
National Institute for Biomedical Imaging and Bioengineering (NIBIB) 
 (http://www.nibib.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
 (http://www.niddk.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  93.394, 93.395, 93.396, 
93.286, 93.287
 
LETTER OF INTENT RECEIPT DATES: June 23, 2003 and October 22, 2003.

APPLICATION RECEIPT DATES: July 21, 2003 and November 19, 2003.

This Program Announcement (PAR) replaces PAR-01-102, which was published in 
the NIH Guide on May 29, 2001.

THIS PAR CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PAR
o Research Objectives
o Mechanisms of Support
o Project Period and Amount of Award 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

NOTICE: This program announcement (PAR) must be read in conjunction with the 
current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, CENTERS FOR 
DISEASE CONTROL AND PREVENTION, AND FOOD AND DRUG ADMINISTRATION FOR SMALL 
BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER 
(STTR) GRANT APPLICATIONS.  The solicitation (see 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf) contains information 
about the SBIR and STTR programs, regulations governing the programs, and 
instructional information for submission. All of the instructions within the 
current SBIR/STTR Omnibus Solicitation apply, with exceptions:
o  Special Receipt Dates
o  Initial review convened by the NCI Division of Extramural Activities
o  Special time and budget limitations
o  Additional review considerations

PURPOSE OF THE PAR

The National Cancer Institute (NCI), the National Institute of Environmental 
Health Sciences (NIEHS), the National Institute for Biomedical Imaging and 
Bioengineering (NIBIB) and the National Institute of Diabetes and Digestive 
and Kidney Diseases (NIDDK) invite applications for the development and 
delivery of novel image acquisition or enhancement technology and methods for 
biomedical imaging and image-guided interventions and therapy, and which may 
incorporate limited pilot or clinical feasibility evaluations using either 
pre-clinical models or clinical studies.  This initiative is intended to 
facilitate the proof of feasibility, development and delivery of novel imaging 
technologies for early detection, screening, diagnosis, image-guided 
interventions and treatment of various diseases, and secondarily to facilitate 
limited evaluation studies to show proof of concept and functionality.

The interests of NCI focus on imaging in vivo for cancer pre-conditions, 
cancer screening, diagnosis, progression, treatment monitoring, recurrence, 
and surrogate endpoints.  NCI interests include the discovery, development and 
delivery of imaging technologies that are cancer specific, and optimization 
and validation of imaging technologies for cancer applications.  The scope 
includes system integration, contrast agents, pre- and post-processing 
algorithms and software for imaging, image understanding, and related 
informatics that are cancer specific.  However, the interests of the National 
Institute of Biomedical Imaging and Bioengineering (NIBIB) focus on the 
discovery, development and delivery of imaging platforms and related component 
technologies, contrast agents, image processing and related informatics that 
can be applied to disease and injury.  The interests of NIEHS focus on 
detection, screening or diagnosis of tissue and organ toxicity related to 
exposures to environmental agents.  These include initiation of toxicity or 
exacerbation of disease or dysfunction resulting from toxic exposure, 
treatment and recovery.  NIDDK interests focus on diabetes, digestive, and 
kidney diseases.

This PAR is directed toward the discovery, development, optimization and 
delivery of innovative image acquisition and enhancement methods, including 
high risk/high gain research on technologies, as follows:
(a) Novel single and multi-modality molecular imaging systems, methods, 
agents, and related software and informatics, including the integration of 
these technologies with emerging biomedical imaging methods for more effective 
health care delivery for cancer and other diseases; 
(b) Novel single and multimodality anatomical and functional imaging systems, 
methods, agents, and related software and informatics for more effective 
health care delivery for cancer and other diseases. 
(c) Research partnerships among academics investigators in device and drug 
industries are encouraged to more rapidly translate and deliver completed 
imaging system developments.

This solicitation utilizes the Small Business Innovation Research (SBIR R43 
and R44) and Small Business Technology Transfer (STTR R41 and R42) mechanisms, 
and runs in parallel with a program announcement of identical scope (PAR-03-
124) that utilizes the Phased Innovation Award (R21/33) mechanism for 
exploratory/developmental studies and which is open to a broad range of 
organizations. 

Fast Track applications are strongly encouraged in this solicitation because 
they benefit from expedited evaluation of progress following the Phase I 
exploratory/feasibility study for immediate decision on transition to Phase II 
funding for expanded developmental work.  

Applications are subject to cost and duration guidelines that are expanded 
over those stated in the OMNIBUS SOLICITATION of the National Institutes of 
Health, Small Business Innovation Research (SBIR) and Small Business 
Technology Transfer (STTR) Grant Applications (PHS 2003-2). 

RESEARCH OBJECTIVES

The overarching Research Objectives of this PAR are to stimulate discovery, 
development, optimization and delivery of novel imaging technologies and 
methods to capture, process, validate, present, interpret or understand in 
vivo imaging data that support the missions of the NCI, NIEHS, NIBIB, and 
NIDDK. 

Significant advances in medical imaging technologies have been made over the 
past 25 years in such areas as magnetic resonance imaging (MRI), computed 
tomography (CT), nuclear medicine, ultrasound, and optical imaging.  These 
advances largely focused on structural or anatomical imaging at the organ or 
tissue level. Now there is an opportunity to stimulate the development and 
integration of novel imaging technologies that exploit our current knowledge 
of the genetic and molecular bases of various diseases.  Molecular biological 
discoveries have great implications for prevention, detection, and targeted 
therapy. Imaging technologies able to provide cellular and molecular 
information in vivo molecular imaging similar to that currently available from 
histological or micro-array techniques in vitro would be very useful. 

The advances in molecular methods pose new requirements for the performance of 
conventional biomedical imaging systems. For example, molecular imaging 
systems may need to be optimized for a molecular probe or probes as well as 
anatomical imaging. The integration of molecular imaging methods into multi-
modality systems will affect data acquisition, processing, reduction, display, 
and archiving. Therefore there is a need to support advances in methods for 
both molecular and conventional anatomical and functional imaging. 

The need to encourage and support biomedical imaging and imaging technology 
development by academic and industrial researchers was stressed by 
participants at several NIH- and NCI-supported forums over the past few years 
[Imaging Sciences Working Group (ISWG) July 1997; Lung Imaging Workshop: 
Technology Transfer, Jan 1997; Computer Aided Diagnosis and 3D Image Analysis, 
Oct 1998; Quantitative in-vivo Functional Imaging in Oncology, Jan 1999; Focus 
Group on Magnetic Resonance Spectroscopy (MRS) in Clinical Oncology, April 
1999; NIH BECON Symposium, June 1999; Dynamic Contrast Enhancement Magnetic 
Resonance Imaging Workshop, Rockville, Maryland, November 2000; and NCI/ISMRM 
Workshop on Higher Field MR (1.5 T & Up) in Oncology: Strategic Frontiers in 
Cancer Diagnosis and Treatment, Glasgow, Scotland, April 2001].  The needs 
include promoting (a) the development of novel, high risk, high gain 
technologies, (b) supporting them to maturation, dissemination and full 
exploitation, (c) integration of new technologies into commercially available 
imaging systems for targeted applications, (d) harmonization of imaging 
methods across versions of a single platform or across multiple platforms to 
permit the image-based surrogate outcome metrics of the kind required for 
multi-site pre-clinical and clinical investigations, (e) funding a small 
number of copies of integrated system prototypes for placement, as required, 
for off-site research and clinical feasibility studies, and (f) improving 
technology transfer, delivery and dissemination by promoting early-stage 
partnerships between academia and industry to encourage sharing of research 
resources, including data sharing and validation studies necessary to meet 
Federal regulatory requirements.  Thus the aims of this initiative and the 
support mechanism (SBIR/STTR, especially Fast Track applications) are also 
directed at encouraging the discovery, development and delivery of imaging 
"tools" to support biomedical imaging in general for applications in oncology 
and other diseases.

Developments of novel imaging technologies usually require multidisciplinary 
approaches and teams with broad expertise in a variety of research areas.  
Such varied expertise might include imaging physics, chemistry, molecular and 
cellular biology, signal and image processing, computer vision, informatics 
and biostatistics, and clinical sciences. The coordination and collaboration 
of investigators with the necessary variety of disciplines to demonstrate the 
utility and applicability of new imaging methods is encouraged.

This initiative is to facilitate the development of novel imaging technologies 
for risk assessment, early detection, screening, diagnosis or image guided 
treatment of cancer and other diseases and to facilitate clinical evaluation 
and optimization studies that are specifically limited to proof of concept and 
pilot data on clinical functionality of the development. Clinical trials for 
clinical validation of emerging imaging technologies are beyond the scope and 
not responsive to this PAR. 

Studies with pre-clinical models and clinical studies to demonstrate the 
feasibility of developments are encouraged, including multi-site evaluations, 
where appropriate.  Methods that establish "ground truth" are required at 
appropriate levels of resolution to validate these emerging imaging methods, 
e.g., imaging excised tissue using protocols similar to those used in vivo, or 
correlation of molecular imaging results with micro-array library analyses.  
Developments of molecular probes or targeted contrast agents are considered 
important approaches to detection of molecular changes in vivo to take better 
advantage of many technologies with potential for molecular imaging. 

The following topics would make appropriate proposed projects. This list is 
not meant to be all-inclusive. 

o Early Disease Detection:  Developments may address innovative high-
resolution imaging methods, with a particular intent to identify and 
characterize abnormalities or other early changes, including molecular events 
on the path to disease. Novel solutions for in vivo microscopic imaging 
systems, or microscopic implanted devices with high spatial and/or temporal 
resolution, which may use either intrinsic or exogenous contrast agents 
represent possible topics. 

o Disease Screening:  These methods may include, but are not limited to 
development and optimization of efficient imaging systems for screening, with 
the intent of achieving improved sensitivity and specificity for disease 
detection.  Applications could address innovative improvements to current 
imaging methods, including hardware and/or software upgrades, or emerging 
imaging sensors and methods.  Research topics of interest include a means to 
significantly reduce imaging time or effects of motion, use of novel contrast 
agents or imaging probes, and use of technologies that reduce or do not 
involve ionizing radiation, or use of novel contrast agents and imaging 
probes.  System integration and software methods could include a variety of 
image processing and data reduction techniques including temporal analysis of 
serial studies, close to real-time image processing, novel image display 
methods, and related imaging informatics for more cost-effective solutions for 
screening. 

o Imaging for Diagnosis, Staging, or Monitoring the Effects of Therapy:  This 
initiative encourages, but is not limited to the development of novel imaging 
methods such as functional or molecular imaging or spectroscopy methods that 
would significantly improve the specificity of diagnosis of cancer and other 
diseases, allow deterministic methods or patient-specific staging, or measure 
early effects of therapy.  Examples of system integration would include multi-
modality imaging, image fusion or registration of the different modalities 
employed, development of software methods that would estimate the probability 
of malignancy or other specific disease identification, quantitative 
information for monitoring the effects of therapy, and close to real-time 
image analysis.

o Image Guided Biopsy (IGB), Therapy (IGT), and Interventional (IGI) 
Procedures:  This initiative encourages novel approaches using imaging 
technologies needed to significantly improve specificity, to identify lesion 
extent and microscopic involvement, and to minimize tissue damage accompanying 
biopsy and therapy. Of particular interest are innovative approaches to IGB, 
IGT or interventional methods that include novel imaging systems that provide 
molecular target information or information at the cellular or molecular level 
sufficient for image guidance and treatment. Examples of system integration 
that are of interest include, but are not limited to multi-modality imaging, 
navigational systems, registration methods, real-time feedback mechanisms for 
controlling therapy (including radiation therapy) or the use of methods that 
are adaptive or allow patient-specific optimization of treatment and computer-
assisted surgery.

o Copies of Prototype Imaging Systems:  Support may be requested to make one 
or more copies of the prototype for placement in collaborating facilities for 
pre-clinical or clinical feasibility investigations, including harmonization 
across versions of a single platform or across multiple platforms to enable 
multi-center comparison studies.  Collaboration with NCI funded centers may be 
possible, such as the NCI Network for Translational Research in Optical 
Imaging, http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-03-002.html, or 
the Lung Image Database Consortium, http://www3.cancer.gov/bip/steercom.htm.  
Investigators anticipating need for funds to build system copies, 
harmonization of imaging methods or collaboration with NCI funded centers are 
advised to contact program staff.

o Research Resources:  The development of research resources that facilitate a 
consensus process for optimization and validation of emerging imaging 
technologies is encouraged. Examples include the development of open source 
software, image processing software and related informatics that can be ported 
onto different platforms, methods and image databases required for validation 
of software performance, and other hardware or informatics methods that assist 
in more efficient delivery of imaging technologies for screening, diagnosis 
and treatment for cancer and other diseases.  Investigators interested in 
development of research resources and related research are advised to contact 
program staff.

MECHANISMS OF SUPPORT 

This PAR uses the R43 and R44 SBIR and R41 and R42 STTR mechanisms funded by 
Small Business set-aside funds.  Applicants are solely responsible for 
planning, directing, and executing the proposed project.  Current and future 
unsolicited, competing-continuation applications based on this project will 
compete with all SBIR/STTR applications for funds, and if not submitted to a 
re-issuance of this (or similar) PAR, will be reviewed according to 
established peer review procedures.

This PAR uses just-in-time concepts described in the current SBIR/STTR Omnibus 
Solicitation.  It does not use the modular budgeting format.  Full budget 
presentations and justifications are required.  Follow the instructions for 
non-modular research grant applications.  This program does not require cost 
sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_I_1.htm.

Except as otherwise stated in this PAR, 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/part_I_1.htm.

Applications may be submitted for Phase I STTR (R41) or Phase I SBIR (R43) 
grant support; Phase II STTR (R42) or Phase II SBIR (R44) grant support; or as 
a pair of Phase I and II applications under the SBIR/STTR FAST TRACK option 
described in the Omnibus Solicitation.  Phase II applications in response to 
this PAR will be accepted only 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, but the Phase I project does not need to 
have been supported in response to this PAR.

Fast track applications will benefit from expedited evaluation of progress 
following Phase I feasibility work for faster transition to Phase II funding 
for development work, with minimal or no funding gap between the Phase I and 
Phase II work.  This PAR has features intended to enhance success rates for 
Fast Track applications.  

PROJECT PERIOD AND AMOUNT OF AWARD: 

The SBIR/STTR Omnibus Solicitation describes statutory guidelines on levels of 
funding support and periods of project duration for SBIR and STTR Phase I and 
Phase II awards.  Guidelines for this PAR are up to $100,000 total costs per 
Phase I year and time periods up to two years.  Phase II applications 
submitted to this PAR have no budget limitations and may request up to four 
years of support.  For a Phase I-Phase II pair of Fast Track applications the 
total duration of support cannot exceed five years.  NCI grantees who have 
successfully completed their Phase II aims may submit a competitive renewal of 
their Phase II project requesting support up to an additional three years for 
research activities that must include steps necessary to meet Federal 
regulatory requirements, e.g., good practice requirements, validation, early 
stage clinical safety, efficacy and feasibility studies, pre-marketing 
approval (PMA), investigational device exception (IDE), etc.  All Phase II 
provisions stated in this PAR apply to a competing continuation application.  

ELIGIBLE INSTITUTIONS

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.  
Only small businesses are eligible to submit applications.  A small business 
is one that meets ALL of the criteria described in the SBIR/STTR Omnibus 
Solicitation on the date of award for both Phase I and Phase II grants.  There 
is a parallel NCI program announcement for institutions ineligible for small 
business grants that is being reissued concurrently as PAR-03-124 (see 
http://grants.nih.gov/grants/guide/pa-files/PAR-03-124.html).  

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with his or her institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.  The SBIR Principal Investigator must 
have primary employment (more than 50%) with the small business at the time of 
award and for the duration of the project.  The STTR Principal Investigator 
may be employed with the small business or the participating non-profit 
research institute so long as she or he has a formal appointment with or 
commitment to the applicant small business and which is characterized by an 
official relationship between the small business and the Principal 
Investigator.  

SPECIAL REQUIREMENTS 

o  The Research Plan of R41 and R43 FAST-TRACK applications must conclude with 
a section on Objective Performance Targets (Milestones), quantitative if 
appropriate, to serve as one approach to judging the success of Phase I work 
after completion.  Milestones are recommended for other Phase I applications, 
but not required.

o  If a copy or copies of a prototype will be needed for placement in one or 
more sites for pre-clinical or clinical testing, include a clear written 
justification for the funds requested in the Budget Justification Section, and 
make written reference to this instruction. 

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to the following:

For NCI
Houston Baker, Ph.D., Guoying Liu, Ph.D., or Keyvan Farahani, Ph.D.   
Biomedical Imaging Program
James A. Deye, Ph.D.
Radiation Research Program 
National Cancer Institute 
6130 Executive Plaza, Suite 6000 
Bethesda MD   20892-7412 
Rockville MD  20852 (for express/courier service)  
Telephone:  301-496-9531 for BIP; 301-496-6111 for RRP 
FAX:  301-480-3507 
Email:  bakerhou@mail.nih.gov
guoyingl@mail.nih.gov
farahank@mail.nih.gov
deyej@mail.nih.gov.

For NIEHS
Jerrold (Jerry) J. Heindel, Ph.D.
Organs and Systems Toxicology Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233 
(for express/courier service: 79 T.W. Alexander Drive, 4401 Research Commons, 
3rd Floor)
Research Triangle Park, NC  27709
Telephone:  919-541-0781
FAX:  919-541-5064
Email:  heindelj@niehs.nih.gov

For NIBIB
John W. Haller, Ph.D.
Health Scientist Administrator
National Institute of Biomedical Imaging and Biomedical Engineering
6707 Democracy Blvd., Suite 200
Bethesda MD 20892-5469
Telephone:  301-451-4780
Fax:  301-480-4973
Email: hallerj@mail.nih.gov

For NIDDK
Judith Podskalny, Ph.D.
Program Director for Training and Career Development, Digestive Diseases 
Centers, and SBIR/STTR
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/DDDN)
6707 Democracy Blvd, Suite 667
Bethesda MD 20892-5450
Telephone:  301-594-8876
Fax: 301-480-8300
E-mail:  jp53s@nih.gov

o Direct your questions about peer review issues to

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda MD 20892-8329
Telephone: 301-496-3428
FAX: 301-402-0275 
Email:  ncirefof@dea.nci.nih.gov

o Direct your questions about financial or grants management matters to

Brian E. Martin
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda MD 20892
Rockville MD  20852 (for express/courier service)
Telephone: 301-496-1014
Fax: 301-846-5720
Email:  martinbr@nih.gov 

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

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

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 
provides allows NCI staff to estimate the potential review workload and plan 
the review.
 
Send the letter of intent to:

Houston Baker, Ph.D. 
Biomedical Imaging Program 
National Cancer Institute 
6130 Executive Plaza, Room 6060 
Bethesda MD   20892-7412 
Rockville MD  20852 (for express/courier service)  
FAX: 301-480-3507
Email: bakerhou@mail.nih.gov

SUBMITTING AN APPLICATION

All SBIR/STTR Phase I, Phase II, and Fast-Track applications must be prepared 
using the PHS 398 research grant application instructions and forms, available 
at http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare your 
application in accordance with instructions in the PHS 398, instructions in 
the SBIR/STTR Omnibus Solicitation, and instructions in this PAR for a new or 
revised SBIR or STTR Phase I or Phase II application, or pair of Fast-Track 
applications.  Helpful information for advice and preparation of the 
application is available at:  
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.  The NIH will 
return applications that are not submitted using the 5/2001 version of PHS 398 
grant application forms.  For further assistance contact GrantsInfo, Telephone 
301 710-0267, email GrantsInfo@nih.gov. 

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

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and three signed photocopies in one 
package to

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda MD  20892-7710
Bethesda MD  20817 (for express/courier service)

To expedite the review process, at the time of submission send two additional 
copies of the applications to: 

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

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

RECEIPT OF APPLICATIONS:  Applications must be received on or before the 
receipt dates listed at the top of the first page of this PAR.  If an 
application is received after that date, it will be retuned to applicant 
without review.  The Center for Scientific Review (CSR) will not accept any 
application in response to this PAR 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 a 
substantive revision of an application already reviewed, but such application 
must include an Introduction that addresses the previous critiques.    

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are usually notified of the review and funding 
assignments within 8 weeks.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by CSR staff and 
responsiveness by NCI or another participating Institute.  Incomplete 
applications and applications not adhering to instructions described above may 
be returned to the applicant without further consideration.  If a complete 
application is not responsive to the PAR, NCI staff may contact the applicant 
to determine if the application should be returned un-reviewed or submitted 
for review in competition with unsolicited applications at the earliest 
appropriate NIH review cycle.

Applications that are complete and responsive to this PAR will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the Division of Extramural Activities of the NCI in accordance 
with the peer review criteria listed below.  As part of the initial merit 
review, all applications will

o  Receive a written critique;
o  Undergo a process in which those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed and assigned a priority score.
o  Receive second level review by appropriate National Advisory Boards or 
Councils of the NCI, NIEHS, NIBIB, and/or NIDDK.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  The 
goals of NCI include Discovery, Development, and Delivery of knowledge, 
methods, devices and systems to prevent, screen, diagnose, treat, and monitor 
the health progress of patients.  NIEHS, NIBIB and NIDDK embrace similar 
goals.  In their written comments, reviewers will be asked to discuss the 
following criteria in evaluating the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. 

o Significance 
o Approach  
o Innovation
o Investigators
o Environment
  
The scientific review group will consider each of these criteria in assigning 
your application's overall score, weighting them as appropriate for each 
application.  Your application does not need to be strong in all categories to 
be judged likely to have major impact and thus deserve a high priority score.  
For example, you may propose to carry out important work that by its nature is 
not innovative but is essential to move a field forward.

SIGNIFICANCE:  Does the study address an important problem?  Does the proposed 
project have commercial potential to lead to a marketable product or process?  
What may be the anticipated commercial and/or societal benefits of the 
proposed activity?  If the aims of the application are achieved, how will 
imaging technology, methods or knowledge be advanced?  Does the proposal lead 
to enabling technologies (instrumentation, software, etc.) for further 
discoveries?   Will the technology have a competitive advantage over existing 
alternative technologies that can meet market needs?

APPROACH:  Are the conceptual framework, design, methods, and scientific and 
engineering analyses adequately developed, well-integrated, and appropriate to 
the aims of the project?  Is the proposed plan a sound approach to 
establishing technical and commercial feasibility?  Does the applicant 
acknowledge potential problem areas and consider alternative strategies?  Is a 
time frame described for developing and delivering the proposed technology and 
methods, and is it suitable to meeting the needs of the community?  Are plans 
adequate for the proposed development, its integration as a useful, effective 
solution to the problem, and its implementation and dissemination for multi-
site evaluation?  

INNOVATION:  Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies?  Are the aims original and 
innovative?  What useful purpose can be expected of the proposed technology or 
methods developments?

INVESTIGATORS:  Is the Principal Investigator capable of coordinating and 
managing the proposed SBIR/STTR technology development?  Are the researchers 
appropriately experienced, trained, or otherwise well suited to perform this 
work?  Is the work proposed appropriate to the backgrounds of the Principal 
Investigator and other researchers, including consultants and sub-contractors 
(if any)?  Are the relationships of the key personnel to the small business 
and to other institutions appropriate for the work proposed?

ENVIRONMENT:  Does the technical and scientific environment in which the work 
will be performed contribute to the probability of success?  Do the proposed 
developments take advantage of unique features of the intellectual environment 
or employ useful collaborative arrangements?  Is there sufficient access to 
resources, e.g., equipment, facilities, etc?  

ADDITIONAL REVIEW CRITERIA: 
In addition to the above criteria, the following items will be considered in 
the determination of scientific merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:    
The involvement of human subjects and protections from research risk relating 
to their participation in the proposed research will be assessed.  (See 
additional information and Inclusion Criteria in the sections on Federal 
Citations, below).

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans 
to include subjects from both genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

Human Subjects:

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

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

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

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

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

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH:
If vertebrate animals are to be used in the project, the required five items 
described under Vertebrate Animals (section f. of the Research Plan 
instructions) will be assessed.

If vertebrate animals are involved, are adequate plans proposed for their care 
and use?  Are the application's responses to the five required points 
appropriate?  Will the procedures be limited to those that are unavoidable in 
the conduct of scientifically sound research?

BIOHAZARDS:
Is the use of materials or procedures that are potentially hazardous to 
research personnel and/or the environment proposed?  Is the proposed 
protection adequate?

ADDITIONAL CONSIDERATIONS:  The following items may be considered by reviewers 
but will not be included in the determination of scientific merit.

BUDGET:  
The reasonableness of the proposed budget and the requested period of support 
in relation to the proposed research may be considered.  For all applications, 
is the percent effort listed for the PI appropriate for the work proposed?  On 
applications requesting up to $100,000 total costs, is the overall budget 
realistic and justified in terms of the aims and methods proposed?  On 
applications requesting over $100,000 in total costs, is each budget category 
realistic and justified in terms of the aims and methods?  Is the requested 
period of support appropriate in relation to the proposed research?

PHASE II APPLICATION REVIEW CRITERIA:   

In addition to the above criteria, apply the following:

1.  How well does the application demonstrate progress toward meeting the 
Phase I objectives, demonstrate feasibility and provide a solid foundation for 
the proposed Phase II work?  Is there a detailed plan to validate the 
development?  

2.  Does the application provide a concise Commercialization Plan [formerly 
Product Development Plan] that adequately addresses the seven areas described 
in the Research Plan item J?

3.  Does the project have appropriate commercial potential, as described in 
the Commercialization Plan?  

MILESTONES: Are there objective performance targets (Milestones) and other 
procedures proposed with which to evaluate successful completion of the Phase 
I project, including feasibility of the proposed development, which would be 
adequate to justify transition to funding for the Phase II development and 
delivery phase?  Are there changes, additions or deletions that should be 
recommended to improve the milestones?

AMENDED APPLICATIONS

In addition to the above criteria, the following apply to revised 
applications:

1.  Are adequate responses provided to points raised in the Summary Statement 
of the prior review?

2.  Are amendments in the revised applications appropriate?

PHASE I/PHASE II FAST TRACK REVIEW CRITERIA

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

1.  Does the Phase I application specify appropriate, clear, objective 
performance targets (milestones)--quantitative if appropriate, that are 
suitable for judging investigator performance and success in meeting Phase I 
objectives?  If the milestones were to be met, would Phase I work have 
demonstrated feasibility and provided a solid foundation for the proposed 
Phase II work?  Are there changes, additions or deletions that should be 
recommended to improve the milestones?  Does the Phase II application provide 
a detailed plan to validate the development?

2.  Does the Phase II application provide a concise Commercialization Plan 
[formerly Product Development Plan] that adequately addresses the seven areas 
described in the Research Plan item J? 

3.  Does the Phase II application include letters of interest, additional 
funding commitments and/or resources from private sector or non-SBIR/STTR 
funding sources that would enhance the likelihood for commercialization?  

4.  Does the project have appropriate commercial potential, as described in 
the Commercialization Plan?

TYPE 2 PHASE II COMPETING CONTINUATION APPLICATION REVIEW CRITERIA 

In addition to the above criteria, the following items will be applied to ALL 
Type 2 Competing Continuation Phase II Applications in the determination of 
scientific merit and the priority score:

o  Does the proposed activity address issues related to Federal regulatory 
approval processes?
o  How well does the application demonstrate progress toward meeting the Phase 
II objectives and provide a solid foundation for the proposed Phase II 
competitive continuation work?  
o  What will be the effect of these studies on the concepts, systems or 
methods that drive this field?

The initial review group will evaluate the specific goals for both Phase I and 
II Fast Track applications, and the objective Phase I performance targets 
(milestones) that would help justify continuing work into Phase II.  A single 
priority score will be assigned to the pair of Fast Track applications.  The 
initial review group has the option of recommending changes in milestones, 
requested support and time, and base the final merit rating on the recommended 
portion of the application.  This may result in a recommendation that only 
Phase I (R41 or R43) of a Fast Track application be supported. 

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Dates:  June 23, 2003 and October 22, 2003.
Application Receipt Dates:  July 21, 2003 and November 19, 2003.
National Advisory Board Review Dates:  February, 2004 and June, 2004.
Earliest Anticipated Award Date:  April, 2004 and July, 2004.

AWARD CRITERIA

Applications submitted in response to this PAR will compete with all other 
recommended SBIR and STTR applications for available Small Business set aside 
funds.  The following will be considered in making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

Phase II Fast Track applications may be funded following submission and 
program staff evaluation and approval of the Phase I Progress Report and other 
documents necessary for continuation.  Continuation funding will depend on a 
determination of successful completion of goals set for Phase I work (assessed 
in part on meeting performance targets negotiated as Phase I milestones), and 
the availability of funds.

REQUIRED FEDERAL CITATIONS 

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

MONITORING PLAN, and DATA AND SAFETY MONITORING BOARD:  Research components 
that involve Phase I and II clinical trials must include provisions for 
assessing patient eligibility and status, rigorous data management, quality 
assurance, and auditing procedures.  In addition, it is NIH policy that all 
clinical trials require data and safety monitoring, with the method and degree 
of monitoring commensurate with the risks (NIH Policy for Data and Safety 
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

Clinical trials supported or performed by NCI require special considerations.  
The method and degree of monitoring should be commensurate with the degree of 
risk involved in participation and the size and complexity of the clinical 
trial.  Monitoring exists on a continuum from monitoring by the Principal 
Investigator/Project Manager or Institute Program staff to a Data and Safety 
Monitoring Board (DSMB).  These monitoring activities are distinct from the 
requirement for study review and approval by an Institutional Review Board 
(IRB).  For details about the Policy for the NCI for Data and Safety 
Monitoring of Clinical trials see 
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.  

For Phase I and II clinical trials, investigators must submit a general 
description of the Data and Safety Monitoring Plan as part of the research 
application.  See NIH Guide Notice on "Further Guidance on a Data and Safety 
Monitoring for Phase I and II Trials" for additional information: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.  
Information concerning essential elements of data and safety monitoring plans 
for clinical trials funded by the NCI is available at 
http://www.cancer.gov/clinical_trials/.

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

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

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

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

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

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/guide/notice-
files//NOT-OD-02-005.html.  Guidance for investigators and institutional review boards 
regarding research involving human embryonic stem cells, germ cells, and stem 
cell-derived test articles can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-044.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).  
It is the responsibility of the applicant to provide the official NIH 
identifier(s) for the hESC line(s) to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review.

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

Applicants may wish to place data collected under this PAR in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the application.  
In addition, applicants should think about how to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data collected under this award.

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

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

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.  Furthermore, we 
caution reviewers that their anonymity may be compromised when they directly 
access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 
2010," a PHS-led national activity for setting priority areas. This PAR is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

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

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

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