NOVEL TECHNOLOGIES FOR IN VIVO IMAGING (SBIR/STTR)

RELEASE DATE:  April 19, 2004

PA NUMBER: PA-04-094 (This PA has been reissued, see PA-06-045 and PA-06-046) 
                     (Expiration date extended, see NOT-CA-05-026) 

EXPIRATION DATE: November 3, 2005
 
Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Cancer Institute (NCI)
 (http://www.nci.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS)
 (http://www.niehs.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  NCI: 93.394, 93.395, 93.396; 
NIEHS: 93.113, 93.114, 93.115; NIDDK: 93.847, 93.848, 93.849; NINDS: 93.853

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadline (April 1, 
August 1, December 1)

This Program Announcement (PA) replaces PAR-03-125, which was published in
the NIH Guide on May 19, 2003.

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
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 Where to Send Inquiries
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Award Criteria
o Receipt and Review Schedule
o Required Federal Citations

NOTICE: This program announcement (PA) 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 [PDF] or 
http://grants.nih.gov/grants/funding/sbirsttr1/index.doc [MS Word] 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. 

PURPOSE OF THE PA

The National Cancer Institute (NCI), the National Institute of Environmental 
Health Sciences (NIEHS), the National Institute of Diabetes and Digestive and 
Kidney Diseases (NIDDK), and the National Institute of Neurological Disorders 
and Stroke (NINDS) invite applications for the development and delivery of novel 
in vivo image acquisition or enhancement technologies and methods for biomedical 
imaging and image-guided interventions and therapy. Applications may incorporate 
limited pilot or clinical feasibility evaluations using either pre-clinical 
models or clinical studies.  This initiative is primarily intended to facilitate 
the proof-of-feasibility, development, and delivery of novel imaging 
technologies for early detection, screening, diagnosis, image-guided 
interventions and treatments 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 image-
based surrogate end points.  NCI’s interests include 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.  The interests of NIEHS focus on detection of intracellular events 
including gene expression and signal transduction pathway alterations, screening 
or diagnosis of tissue and organ toxicities related to exposures to 
environmental agents.  These areas of interest include initiation of toxicity or 
exacerbation of disease or dysfunction resulting from toxic exposure, treatment, 
and recovery.  The interests of NIDDK focus on diabetes, digestive, and kidney 
diseases.  The interests of NINDS focus on development and delivery of 
neuroimaging technologies that can be applied to diagnosis and treatment of 
neurological disorders.  

This PA is directed toward the development, optimization, and delivery of 
innovative image acquisition and enhancement methods, including high risk/high 
gain research on technologies such as: (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 and (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.  In addition, research partnerships among investigators in both 
academia and device and drug industries are encouraged to more rapidly translate 
and deliver completed imaging system developments.

This PA will utilize the Small Business Innovation Research and Small Business 
Technology Transfer Mechanisms but will be run in parallel with a NCI program 
announcement of nearly identical scope PA-04-095 
(http://grants.nih.gov/grants/guide/pa-files/PA-04-095.html) that utilizes the Phased 
Innovation Award (R21/33) and the R33 mechanisms for exploratory/developmental 
studies and which is open to a broad range of organizations. 

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

RESEARCH OBJECTIVES

The overarching Research Objectives of this PA are to stimulate 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, NIDDK, and/or NINDS.

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 similar kinds of cellular and 
molecular information (i.e. in vivo molecular imaging) similar to that currently 
available from histological or micro-array techniques use for in vitro studies 
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 for 
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: (a) 
promoting the development of novel, high-risk, high-gain technologies; (b) 
supporting these technologies to maturation, dissemination, and full 
exploitation; (c) integrating new technologies into commercially available 
imaging systems for targeted applications; (d) harmonizing 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.  Therefore, the aims of this initiative and the support mechanism 
(SBIR/STTR, especially Fast Track applications) are also directed at encouraging 
the 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.

The purpose of 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 PA.

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 that 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 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 
the use of ionizing radiation or 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), Image-Guided Therapy (IGT), and Image-Guided 
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 
research purposes, namely 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, harmonize imaging methods, or collaborate with NCI 
funded centers are advised to contact the NIH program staff listed in the 
section of this document that is entitled “Where to Send Inquiries.”

o Research Resources:  Developments of publicly accessible research resources 
that facilitate a consensus process for optimization and validation of emerging 
imaging technologies are 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 
NIH program staff.

MECHANISMS OF SUPPORT

This PA uses the SBIR and STTR mechanisms, which are set-aside programs. As an 
applicant, you will be solely responsible for planning, directing, and executing 
the proposed project. Future unsolicited, competing-continuation applications 
based on this project will compete with all SBIR/STTR applications and will be 
reviewed according to the customary peer review procedures.

This PA uses just-in-time concepts. It also uses the modular budgeting format. 
Specifically, if you are submitting an application budget of $100,000 total 
costs (direct, F&A and fee) or less, use the modular format and instructions as 
described in the current SBIR/STTR Omnibus Solicitation. Otherwise follow the 
instructions for non-modular budget research grant applications.  This program 
does not require cost sharing as defined in the current NIH Grants Policy 
Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

Applications may be submitted for support as Phase I STTR (R41) or Phase I SBIR 
(R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) grants; or the 
SBIR/STTR FAST-TRACK option as described in the SBIR/STTR Omnibus Solicitation.  
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 but not 
necessarily a Phase I project supported in response to this PA.

PROJECT PERIOD AND AMOUNT OF AWARD: 

The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines on levels 
of funding support and periods of project duration for SBIR and STTR Phase I and 
Phase II awards.  For this PA, budgets up to $1M total costs per year and time 
periods up to 3 years for Phase II Competing Continuations for NCI and NINDS 
grantees may be requested.  For Phase I-Phase II Fast Track applications, the 
total duration of support cannot exceed 5 years.  Total costs include direct 
costs, F&A, and a profit/fee.  

ELIGIBLE INSTITUTIONS

Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation.  
Only small business concerns are eligible to submit applications. A small 
business concern is one that, on the date of award for both Phase I and Phase II 
agreements, meets ALL of the criteria as described in the SBIR/STTR Omnibus 
Solicitation.

A parallel NCI program announcement, PA-04-095 
(http://grants.nih.gov/grants/guide/pa-files/PA-04-095.html), is available for 
institutions ineligible for small business grants. 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues:

For NCI
Guoying Liu, Ph.D., Keyvan Farahani, Ph.D., James A. Deye, Ph.D., or Houston 
Baker, Ph.D.
National Cancer Institute
6130 Executive Plaza, Suite 6000
Bethesda, MD   20892-7412
Rockville, MD  20852 (for express/courier service)
Telephone:  301-496-9531 for GL, KF, or HB; 301-496-6111 for JAD
Fax:  301-480-3507
Email:  
guoyingl@mail.nih.gov
farahank@mail.nih.gov
deyej@mail.nih.gov.
bakerhou@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 NINDS
Daofen Chen, Ph.D.
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard 
Bethesda, MD 20892-9523 
Rockville, MD 20852 (courier service only) 
Telephone: (301) 496-1917
Fax:  (301) 402-1501 
Email: daofen.chen@nih.gov 

For NIDDK
Sanford A. Garfield, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/DDDN)
6707 Democracy Blvd, Room 685
Bethesda MD 20892-5450
Rockville, MD  20852 (for express/courier service)
Telephone:  301-594-8803
Fax: 301-420-6271
E-mail:  garfields@ep.niddk.nih.gov

o Direct your questions about financial or grants management matters to:

Ted Williams
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda MD 20892
Rockville MD  20852 (for express/courier service)
Telephone: 301-496-8785
Fax: 301-496-8601
Email: tw133b@nih.gov

SUBMITTING AN APPLICATION

The PHS 398 research grant application must be used for all SBIR/STTR Phase I, 
Phase II and Fast-Track applications (new and revised.)  Effective October 1, 
2003, applications must have a Dun and Bradstreet (D&B) Data Universal Numbering 
System (DUNS) number as the Universal Identifier when applying for Federal 
grants or cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. The 
DUNS number should be entered on line 11 of the face page of the PHS 398 form. 
The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  Prepare your 
application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 
398. Helpful information for advice and preparation of the application can be 
obtained at http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf. The NIH 
will return applications that are not submitted on the 5/2001 version of the PHS 
398.  For further assistance, contact GrantsInfo; Telephone: (301) 435-0714; 
Email: GrantsInfo@nih.gov. 

The title and number of this PA must be typed on line 2 of the face page of the 
application.
 
SUPPLEMENTARY INSTRUCTIONS 

o  For Phase II, 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.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the 
application, including the checklist, and five 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)

APPLICATION PROCESSING:  Applications must be received by or mailed on or before 
the receipt dates described on the first page of this program announcement. The 
CSR will not accept any application in response to this PA that is essentially 
the same as one currently pending initial review unless the applicant withdraws 
the pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed. This does not preclude the 
submission of a substantial revision of an unfunded version application already 
reviewed, but such application must include an Introduction addressing the 
previous critique.

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

PEER REVIEW PROCESS

Applications submitted for this PA that are complete will be assigned on the 
basis of established PHS referral guidelines.  Appropriate scientific review 
groups convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

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 a written critique
o  Receive second level review by the appropriate national advisory council or 
board.  

REVIEW CRITERIA

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

ALL SBIR/STTR APPLICATIONS 

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

2. Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Is the proposed plan a sound approach for establishing technical and 
commercial feasibility? Does the applicant acknowledge potential problem areas 
and consider alternative strategies? Are the milestones and evaluation 
procedures appropriate? 

3. Innovation:  Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies? Are the aims original and innovative? 

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

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

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be applied to ALL applications 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 criteria 
included in the section on Federal Citations, below). 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

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

Human Subjects: 

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

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

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

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

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

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

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

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

SHARING RESEARCH DATA:
Applicants requesting $500,000 or more in direct costs in any year of the 
proposed research must include a data sharing plan in their application. The 
reasonableness of the data sharing plan or the rationale for not sharing 
research data will be assessed by the reviewers. However, reviewers will not 
factor the proposed data sharing plan into the determination of scientific merit 
or priority score.

BUDGET:
The reasonableness of the proposed budget 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?  

PERIOD OF SUPPORT: The appropriateness of the requested period of support in 
relation to the proposed research.

PHASE II APPLICATIONS

In addition to the above review criteria;

1.  How well does the application demonstrate progress toward meeting the Phase 
I objectives, demonstrate feasibility and provide a solid foundation for the 
proposed Phase II activity?  

2.  Did the applicant submit a concise Commercialization Plan that adequately 
addresses the seven areas described in the Research Plan item J?

3.  Does the project carry a high degree of commercial potential, as described 
in the Commercialization Plan?

AMENDED APPLICATIONS

In addition to the above criteria, the following criteria will be applied to 
revised applications.

1.  Are the responses to comments from the previous SRG review adequate?

2.  Are the improvements 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 clear, appropriate, measurable goals 
(milestones) that should be achieved prior to initiating Phase II? 
2. Did the applicant submit a concise Commercialization Plan that adequately 
addresses the seven areas described in the Research Plan, item J? 
3. To what extent was the applicant able to obtain letters of interest, 
additional funding commitments, and/or resources from the private sector or non-
SBIR/ STTR funding sources that would enhance the likelihood for 
commercialization? 
4. Does the project carry a high degree of commercial potential, as described in 
the Commercialization Plan? 
Phase I and Phase II Fast-Track applications that satisfy all of the review 
criteria will receive a single rating. Failure to provide clear, measurable 
goals may be sufficient reason for the scientific review group to exclude the 
Phase II application from Fast-Track review.

TYPE 2 PHASE II COMPETING CONTINUATION APPLICATIONS  

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?

AWARD CRITERIA

Applications submitted in response to this PA 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; and
o Relevance to program priorities.

For FAST-Track applications, the Phase II portion may not be funded until a 
Phase I final report and other documents necessary for continuation have been 
received and assessed by program staff that the Phase I milestones have been 
successfully achieved. 

RECEIPT AND REVIEW SCHEDULE  

See http://grants.nih.gov/grants/funding/sbirsttr_receipt_dates.htm. 

REQUIRED FEDERAL CITATIONS

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities involving 
live, vertebrate animals must comply with PHS Policy on Humane Care and Use of 
Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as 
mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal 
Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as 
applicable.

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. See 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all 
types of clinical trials, including physiologic, toxicity, and dose-finding 
studies (phase I); efficacy studies (phase II); and efficacy, effectiveness and 
comparative trials (phase III). The establishment of data and safety monitoring 
boards (DSMBs) is required for multi-site clinical trials involving 
interventions that entail potential risk to the participants.  (See the NIH 
Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 
12, 1998 at http://grants.nih.gov/grants/guide/notice-files/not98-084.html.)  

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking 
$500,000 or more in direct costs in any single year are expected to include a 
plan for data sharing (http://grants.nih.gov/grants/policy/data_sharing) or 
state why this is not possible. Investigators should seek guidance from their 
institutions, on issues related to institutional policies, local IRB rules, as 
well as local, State, and Federal laws and regulations, including the Privacy 
Rule. Reviewers will consider the data sharing plan but will not factor the plan 
into the determination of the scientific merit or the priority score.

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

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts on 
October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html ); 
a complete copy of the updated Guidelines 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. 
All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

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

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project description 
and elsewhere in the application as appropriate, the official NIH identifier(s) 
for the hESC line(s) to be used in the proposed research.  Applications that do 
not provide this information will be returned without review. 

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

Applicants may wish to place data collected under this PA 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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