PA-04-094: NOVEL TECHNOLOGIES FOR IN VIVO IMAGING (SBIR/STTR)

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/grants/policy/nihgps_2003/NIHGPS_Part2.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

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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