DEVELOPMENT OF NOVEL TECHNOLOGIES FOR IN VIVO IMAGING (PHASED INNOVATION AWARD)

Release Date:  May 29, 2001 (see replacement PAR-03-124)

PA NUMBER:  PAR-01-101

National Cancer Institute

Letter of Intent Receipt Dates:  June 11, 2001, February 11, 2002 and 
June 11, 2002

Application Receipt Dates:  July 16, 2001, March 18, 2002, and July 16,2002

This PAR is a reissue of PAR-00-089, which was published in the NIH 
Guide on April 27, 2000.

PURPOSE

The National Cancer Institute (NCI) invites applications for the 
development of novel image acquisition or enhancement methods for in 
vivo oncology, and which incorporate limited pilot or clinical 
feasibility evaluations using either pre-clinical models or clinical 
studies.  This initiative is primarily intended to facilitate the 
development of novel imaging technologies for early detection, 
screening, diagnosis or image guided treatment of cancer and to 
facilitate specifically limited evaluation studies to show proof of 
concept.  Specific emphasis of this PAR is directed at (a) the 
development of highly innovative image acquisition and enhancement 
methods, including high risk/high gain research on technologies that 
exploit our knowledge of the molecular basis of cancer, and (b) the 
development of other novel imaging methods and the integration of these 
technologies with emerging molecular imaging methods, where 
appropriate, for more effective health care delivery. 

The primary motivation for this Program Announcement (PA) is that 
current technologies for the molecular analysis of disease are largely 
restricted to in vitro methods and need to be extended to the in vivo 
situation. Furthermore, the use of molecular probes or tracers for 
imaging molecular events in pre-clinical and clinical investigations 
are essential for detection of molecular changes in vivo. Developments 
of innovative, high-resolution imaging methods at the cellular or 
molecular scales are needed, with particular emphasis on identification 
and characterization of processes in the early formation of disease or 
early molecular changes during intervention or therapy. Integrations of 
these emerging molecular imaging methods with advances in traditional 
imaging methods are also required for more effective cancer 
investigations in vivo.

This solicitation (Development of Novel Technologies for in vivo 
Imaging) will utilize the Phased Innovation Award Mechanism that is 
designed to encourage technology development.  Specific features of 
this mechanism include:

o  Single submission and evaluation of both the R21 and R33 phases as 
one application.  An R33 application also may be submitted alone.

o  Expedited transition from the R21 feasibility phase to the R33 
development phase, based on successful completion of negotiated 
quantitative Milestones.

o  Flexible staging of feasibility (R21) and development (R33) phases. 
Applications from industry or industrial partnerships with other groups 
are encouraged.

o Review of submissions by an NCI special study section, and expedited 
NCI program review for transition from the R21 to the R33 phase.

Small businesses are encouraged to respond to the parallel PA, PAR-01-
102 (see http://grants.nih.gov/grants/guide/pa-files/PAR-01-102.html). 
Its objectives are identical, but it uses the Small Business Innovation 
Research (SBIR) and Small Business Technology Transfer Research (STTR) 
granting mechanisms. The same expedited review and transition from 
Phase I to Phase II funding apply, as do the same cost and time limits 
as this program announcement for Phased Innovation Awards. 

The National Center for Research Resources (NCRR) has recently issued a 
PA for Technology Development for Biomedical Applications:  Phased 
Innovation Award (R21/R33), 
http://grants.nih.gov/grants/guide/pa-files/PAR-01-057.html.   
The NCRR phased innovation awards for medical 
technology developments include imaging developments that are not 
cancer or disease specific. 

BACKGROUND

Significant advances in medical imaging technologies have been made 
over the last 25 years in such areas as magnetic resonance imaging 
(MRI), computed tomography (CT), nuclear medicine and ultrasound. 
However, these advances largely focused on structural or anatomical 
imaging at the organ or tissue level. Now there is a clear need and 
opportunity to stimulate the development and integration of novel 
imaging technologies that exploit our current knowledge of the genetic 
and molecular bases of cancer.  Molecular biological discoveries have 
great implications for prevention, detection, and targeted therapy. 
Imaging technologies that can provide the same kinds of cellular and 
molecular information in vivo that are currently available only from 
techniques in vitro would be very useful. This is commonly known as in 
vivo molecular imaging. 

The need for NCI to encourage and support bioengineering and 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; and NIH BECON Symposium, June 
1999].  The needs are to (a) promote the development of novel, high 
risk, high gain technologies, including continued support for their 
maturation and full exploitation, (b) promote system integration of 
technologies for targeted applications, including the development of a 
system prototype and small number of copies, as required, for research 
and clinical feasibility studies, and (c) improve technology transfer 
by promoting partnerships between academia and industry.  

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

RESEARCH OBJECTIVES

This initiative is primarily intended to facilitate the development of 
novel imaging technologies for early detection, screening, diagnosis or 
image guided treatment of cancer and to facilitate clinical evaluation 
studies of the development that are specifically limited to proof of 
concept. Specific emphasis of this PAR is directed at (a) developments 
of highly innovative image acquisition and enhancement methods, 
including high risk/high gain research on technologies that exploit our 
knowledge of the molecular basis of cancer, and (b) developments of 
other novel imaging methods and their integration with emerging 
molecular imaging methods, where appropriate, for more effective health 
care delivery.   In particular, developments of innovative, high-
resolution imaging methods at the cellular or molecular scales are 
needed for both pre-clinical models and clinical studies, with emphasis 
on identification and characterization of either the early formation of 
disease or early molecular changes during intervention or therapy. 
Methods that establish “ground truth” are required at appropriate 
levels of resolution to validate these emerging imaging methods.  They 
may include the imaging of excised tissue using protocols similar to 
those used for imaging in vivo.  Developments of probes or tracers are 
considered essential for detection of molecular changes in vivo to take 
better advantage of many technologies with potential for molecular 
imaging. 

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

o   Imaging to detect early changes.  Developments of innovative high-
resolution imaging methods at the cellular or molecular scales are 
encouraged, with a particular intent to identify and characterize pre-
malignant 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, 
contrast and temporal resolution are encouraged. Similarly, 
developments of contrast enhancement methods and imaging probes are 
also encouraged.

o   Large scale screening applications for cancer may include, but are 
not limited to: development and optimization of efficient, low-cost 
imaging systems for rapid and automated large-scale screening with the 
intent of achieving significantly higher sensitivity and specificity 
for cancer detection are encouraged.  Applications could address 
significant innovative improvements to current imaging methods or new 
emerging imaging sensors.  Research topics of interest include, but are 
not limited to, technologies for molecular imaging, means to 
significantly reduce imaging time or motion effects, use of novel 
contrast agents or imaging probes, and use of technologies that do not 
involve ionizing radiation.  System integration could include a variety 
of image processing techniques including temporal analysis of serial 
studies, close to real-time image processing, novel image display 
methods, and related imaging informatics and information reduction 
methods 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, allow deterministic methods or 
patient-specific staging, or measure early effects of therapy.  
Examples of system integration would include image fusion or 
registration from the different modalities employed, development of 
software methods that would estimate the probability of malignancy or 
of other specific disease identification, quantitative information for 
monitoring the effects of therapy, and close to real-time image 
analysis.

o   Image guided biopsy (IGB), therapy (IGT), and interventional 
procedures. Novel approaches using imaging technologies are needed to 
significantly improve specificity, to identify lesion extent and 
microscopic involvement, and to minimize the 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 information at the cellular or molecular level. Examples 
of system integration that are of interest include, but are not limited 
to, navigational systems, registration methods for several imaging 
modalities, real-time feedback mechanisms for controlling therapy or 
the use of methods that are adaptive or allow patient-specific 
optimization of treatment and computer-assisted surgery.

o  The production of a limited number of systems based on the prototype 
may be supported to facilitate research aims that require pre-clinical 
or clinical investigations.  Investigators anticipating this need are 
advised to contact program staff.
 
MECHANISM OF SUPPORT

The following are points to note about the mechanism of support and its 
implementation:

o    Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  

o   Awards will be administered under NIH grants policy as stated in 
the NIH Grants Policy Statement, March 2001, available at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/index.htm. Hard copies 
are not available.  Support for this program will be through the 
National Institutes of Health (NIH) Exploratory/Developmental Research 
Grant (R21) and the Exploratory/Developmental Research Grant Phase 2 
(R33).  The R33 is a relatively new NIH granting mechanism that 
provides a second phase of support to continue innovative exploratory 
and developmental research initiated under the R21 mechanism.  
Transition from the R21 to R33 phase will be expedited, and will depend 
on satisfactory completion of negotiated, quantitative R21 Milestones.

o    Under this PA, applicants can submit either a combined R21/R33 
application (Phased Innovation Award application), or an R33 
application alone if feasibility can be documented, as described in the 
APPLICATION PROCEDURES section, below. 

o    Applications for R21 support alone will not be accepted, but may 
be eligible for submission under PA-01-030 (see 
http://grants.nih.gov/grants/guide/pa-files/PA-01-030.html). 

o    The total project period for an application submitted in response 
to this PA may not exceed 4 years.  Its components are limited as 
follows: R21, up to 2 years; R33, up to 3 years; combined R21/R33 
application, up to 4 years.  

o    For a combined R21/R33 application, the R21 phase may not exceed 
$100,000 direct costs per year.  R21 budgets may exceed this cap to 
accommodate facilities and administrative costs to subcontracts to the 
project.  

The combined R21/R33 application offers two advantages over the regular 
application process:

1.  Single submission and evaluation of both the R21 and R33 components 
as one application.

2.  Minimal or no funding gap between the R21 and R33 budget awards.  
The award of R33 funds will depend upon program priorities, the 
availability of funds, and successful completion of negotiated, 
quantitative Milestones, as determined by NCI staff, who will take peer 
review recommendations into consideration.

The R21 phase of the Phased Innovation Award must include (1) well-
defined, quantifiable Milestones that will be used to judge the success 
of the proposed work to demonstrate the feasibility of the proposed 
technology development, and (2) a credible plan for the development of 
technology in the R33 phase. Include a separate section labeled 
“Milestones” at the end of the Research Plan of the R21 application. In 
addition to well-defined, quantifiable Milestones, include a discussion 
of the suitability of the proposed Milestones for assessing the success 
of the R21 phase, and a discussion of the implications of successful 
completion of these Milestones for the proposed R33 study. Examples of 
quantifiable milestones would be performance specifications of an 
imaging system, or anticipated characteristics required for suitable 
contrast agent performance, so that objective evaluations can be made 
of progress at the end of the R21 phase.

Potential applicants are encouraged to access the PHS SBIR and STTR 
Omnibus Solicitation for information on eligibility requirements at the 
following website: http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf   

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and 
non-profit organizations, public and private, such as universities, 
colleges, hospitals, laboratories, companies, units of State and local 
governments, and eligible agencies of the Federal government.  
Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as principal investigators.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Houston Baker, Ph.D. 
Biomedical Imaging Program 
National Cancer Institute 
6130 Executive Plaza, Suite 6000 
Bethesda MD   20892-7412 
Rockville MD  20852 (for express/courier service)  
Telephone:  (301) 496 9531 
FAX:  (301) 480 3507 
Email:  bakerhou@mail.nih.gov

Direct inquiries regarding fiscal matters to:

Kathleen J. Shino, M.B.A.
Grants Administration Branch
National Cancer Institute
6120 Executive Blvd, EPS 243
Bethesda MD  20892-7150
Rockville MD  20852 (for express/courier service)
Telephone:  (301) 846 1016
FAX:  (301) 846 5720
Email: ks48e@nih.gov

Direct inquiries regarding review matters to:

Ms. Toby Friedberg. 
Referral Officer 
National Cancer Institute 
6116 Executive Boulevard, Room 8109, MSC 8236 
Bethesda MD  20892-8236 
Rockville MD  20852 (for overnight/courier service)  
Telephone:  (301) 496 3428 
FAX:  (301) 402 0275 
Email: tf12W@nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit a Letter of Intent by the 
date listed at the beginning of this PA.  It should provide the number 
and title of this program announcement, a descriptive title of the 
proposed research, the name, address, telephone number, and e-mail 
address of the Principal Investigator, and identify other key personnel 
and participating institutions.

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows NCI staff to estimate the potential review 
workload and plan the review.  The letter of intent is to be sent to 
Dr. Houston Baker at the address listed under INQUIRIES, above. 

SCHEDULE

Letter of Intent Receipt:                  June 11, 2001; February 11, 2002; 
                                           June 11, 2002
Application Receipt Date:                  July 16, 2001; March 18, 2002; 
                                           July 16, 2002
Peer Review Date:                          Oct-Nov, 2001; June-July, 2002; 
                                           Oct-Nov, 2002
Review by National Cancer Advisory Board:  February, 2002; September, 2002; 
                                           February, 2003
Earliest Anticipated Start Date:           March 2002; October, 2002; March 2003

APPLICATION PROCEDURES

SPECIFIC INSTRUCTIONS FOR PREPARING THE COMBINED R21/R33 PHASED 
INNOVATION AWARD APPLICATION:

Applications for R21/R33 grants are to be submitted on the grant 
application form PHS 398 and prepared according to the instructions 
provided unless specified otherwise within this section.  Application 
kits are available at most institutional offices of sponsored research 
and may be obtained from the Division of Extramural Outreach and 
Information Resources, 6701 Rockledge Drive, MSC 7910, Bethesda MD 
20892-7910, telephone 301 435 0714, email: grantsinfo@nih.gov.  See 
also the website for PHS 398: 
http://grants.nih.gov/grants/funding/phs398/phs398.html

The R21/R33 application must include specific aims for each phase and 
quantitative Milestones for the R21 component that would later help 
justify transition to the R33 phase.  See below, Item d., "Research 
Design and Methods" for directions for including Milestones in the 
application.  After funding and completion of the R21 phase, a 
comparison of progress with the R21 Milestones in an NCI expedited 
review will determine whether or not the R33 continuation grant should 
be awarded. Funds for R33 developments are contingent on program 
priorities, the availability of funds, and satisfactory completion of 
the negotiated Milestones. The expedited review may result in 
additional negotiations of award.  

The R21/R33 Phased Innovation Award application must be submitted as a 
single application, with one face page.  Although it is submitted as a 
single application, it should be clearly organized into two phases.  To 
provide a clear distinction between the two phases, applicants are 
directed to complete Sections a-d of the Research Plan twice: one 
write-up of Sections a-d and Milestones for the R21 phase, and Sections 
a-d again for the R33 phase.  The Form 398 Table of Contents should be 
modified to show Sections a-d for each phase as well as the Milestones.  
There is a page limit of 25 pages for the composite a-d text (i.e., 
Sections a-d and Milestones for the R21 and Sections a-d for the R33 
phase all must be contained within the 25-page limit).  The initial 
review group will assign a single priority score to the combined 
R21/R33 application.  Therefore, the clarity and completeness of the 
R21/R33 application with regard to the R21 feasibility Milestones and 
the specific goals of each phase are crucial. A weak R33 component will 
impact the evaluation of both phases of the R21/R33 application.  
Presentation of Milestones that are not sufficiently rigorous, and not 
quantitative, such as procedural research plans, may not permit 
adequate validation of the R21 feasibility studies and adversely affect 
reviewer opinions of the merit of the application.

Page 1.  Face Page of the application: 
Item 2.  Check the box marked "YES" and type the number and title of 
this PA. Also indicate if the application is an R21/33 or R33.  If for 
an R21/R33, follow the next set of instructions.  If for an R33 alone, 
see instructions further below.

Item 7a, DIRECT COSTS REQUESTED FOR INITIAL PERIOD OF SUPPORT: Insert 
the amount requested for first year R21 support in Item 7a.  This PA 
does NOT use the "Modular Grant" and "Just-in-time" concepts.  For the 
R21 phase of the combined R21/R33 application, direct costs are limited 
to a maximum of $100,000 per year for a maximum of two years.  The 
award may not be used to supplement an ongoing project.  The requested 
budget may exceed this cap to accommodate for Facilities and 
Administrative costs to subcontracts of the project. 

Item 8a, DIRECT COSTS REQUESTED FOR PROPOSED PERIOD OF SUPPORT:  Insert 
the sum of all years of requested support for direct costs in Item 8a.  
For the R21 phase, direct costs requested for the proposed period may 
not exceed $100,000 per year for either one or two years of phase one 
R21 feasibility study support.  The statement in item 7a above 
pertaining to subcontract costs also applies here.  

2.  Budget: The application should provide a detailed budget on Form 
Page 4, Initial Budget Period, for each of the initial years of the R21 
and R33 phases (use two Form Page 4s, one for each phase) as well as a 
budget on Form Page 5 for the entire proposed period of support. 
Indicate on the Form pages which years are for R21 and which are for 
R33 support. All budgets should include written justifications for line 
items requested. 

An annual meeting of all investigators funded through this program will 
be held to share progress and research insights that may further 
progress in the program.  Applicants should request travel funds in 
their budgets for the principal investigator and one additional senior 
investigator to attend this annual meeting. 

3.  Research Plan:  A combined R21/R33 application should present two 
sets of research plans (items a through d), one of them for R21 
feasibility studies, and the other for R33 developmental work.  The 
entire Research Plan, consisting of two sets of items a through d, must 
fit within a 25-page limit.

Item a., Specific Aims.
The application must present specific aims that the applicant considers 
technically or scientifically appropriate for the relevant phases of 
the project. The PHS 398 instructions for this section of research 
grant applications suggest that the applicant state the hypotheses to 
be tested.  Since the goal of this PA is the development of innovative 
imaging technologies, hypothesis testing per se may not be the driving 
force in developing such a proposal, and therefore, may not be 
applicable. For the R21 portion of the grant application, preliminary 
data are not required, although they should be included when available.  

Item d., Research Design and Methods.  Follow the PHS 398 instructions.  
In addition, for the R21 phase only, the following information must be 
included as a final section of Item d:  Applications must include a 
specific section labeled Milestones following the Research Design and 
Methods section of the R21 component of the application. Milestones are 
to be appropriate measures of whether the specific aims have been 
accomplished and proof of principle established upon completion of the 
R21 phase of work.  Milestones should be well described, quantifiable, 
and technically or scientifically justified.  They are not to be simply 
a restatement of the specific aims or be procedural in nature. A 
discussion of the Milestones relative to the success of the R21 phase, 
as well as the implications for successful completion of the Milestones 
for the R33 phase, should be provided. The page number of the 
Milestones section should be listed on the Table of Contents page. 
Applications lacking adequate Milestone information, as determined by 
the NCI program staff, will be returned to the applicant without 
review.

SPECIFIC INSTRUCTIONS FOR PREPARATION OF THE R33 APPLICATION WHEN 
SUBMITTED WITHOUT THE R21 PHASE.

Applications for R33 grants are to be submitted on the grant 
application form PHS 398 and prepared according to the instructions 
provided unless specified otherwise within items 1-5 below.  
Application kits are available at most institutional offices of 
sponsored research and may be obtained from the Division of Extramural 
Outreach and Information Resources, 6701 Rockledge Drive, MSC 7910, 
Bethesda, MD 20892-7910, telephone 301/435-0714, email: 
grantsinfo@nih.gov.  See also the website for PHS 398: 
http://grants.nih.gov/grants/funding/phs398/phs398.html

Face Page of the application:
Item 2.  Check the box marked "YES," type the number and title of this 
PA, and indicate R33.

Budget: The application should provide a detailed budget on Form Page 
4, Initial Budget Period, for the initial year of the R33 phase as well 
as a budget on Form Page 5 summarizing the initial year and any 
subsequent years (for up to three years). All budgets should include 
written justifications for line items requested. 

Research Plan:
Item a., Specific Aims.
The PHS 398 instructions for this section of research grant 
applications suggest that the applicant state the hypotheses to be 
tested. Because the goal of this PA is to develop innovative 
technologies, hypothesis testing per se may not be the driving force in 
developing such a proposal, and therefore, may not be applicable.  

Item c., Preliminary Studies/Progress report
This section must document that feasibility (proof of principle) 
studies have been completed, and progress achieved that is equivalent 
to that expected through the support of an R21 project.  The 
application must clearly describe how the exploratory/developmental 
work already performed is ready to scale up to an expanded 
developmental stage. In the event that an applicant feels that the 
technology is too proprietary to disclose, at a minimum the application 
should provide a demonstration (results) of the capabilities of the 
proposed technology development. Ideally, performance capabilities of 
the proposed technology, or quantitative performance characteristics, 
that may be objectively evaluated should be provided, and compared with 
the published literature.

Item d., Research Design and Methods
Follow the PHS 398 instructions.

FOR ALL APPLICATIONS

Clinical Trials:  All clinical trials supported by any NIH Institute or 
Center require some form of safety monitoring plan.  The method and 
degree of monitoring to be included in the plan should be commensurate 
with the degree of risk involved, and the size and complexity of the 
clinical trial.  Monitoring exists on a continuum from monitoring by 
the principal investigator/project manager or NCI program staff to a 
Data and Safety Monitoring Board (DSMB).  These monitoring activities 
are distinct from and in addition to the requirement for human subject 
study review and approval by an Institutional Review Board (IRB).  For 
details about the Policy of the NCI for Data Safety Monitoring of 
Clinical Trials, see http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. 
For additional information, see 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html and 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed photocopies, in one package to: 

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

At the time of submission, two additional copies of the application 
must be sent to:

Ms. Toby Friedberg 
Referral Officer 
National Cancer Institute 
6116 Executive Boulevard, Room 8109, MSC 8236 
Bethesda MD  20892-8236 
Rockville MD  20852 (for overnight express or courier service) 
Telephone:  (301) 496 3428 
FAX:  (301) 402 0275

The Center for Scientific Review (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 substantial revisions of applications already 
reviewed, but such applications must include an introduction addressing 
the previous critique.

REVIEW CONSIDERATIONS

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

Applications that are complete and responsive to the PA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NCI in accordance with the review criteria 
stated below. As part of the initial merit review, all applications 
will receive a written critique and undergo a process in which only 
those applications deemed to have the highest scientific merit, 
generally the top half of the applications under review, will be 
discussed, assigned a priority score, and receive a second level review 
by the 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 aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals. Each of these criteria will be addressed and 
considered in assigning the overall score, weighting them as 
appropriate for each application. Note that the application does not 
need to be strong in all categories to be judge likely to have major 
scientific impact and thus deserve a high priority score. For example, 
an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

1.  Significance.  Does this study address an important problem? If the 
aims of the application are achieved, how will in vivo imaging 
technology or scientific knowledge be advanced?  What will be the 
effect of these studies on the concepts or methods that drive this 
field?  To what degree does the technology support the needs for the 
targeted disease? 

2.  Approach.  Are the conceptual framework, design, and methods 
adequately developed, well integrated, and appropriate to the aims of 
the project?  Does the applicant acknowledge potential problem areas 
and consider alternative tactics? What is the time frame for developing 
the proposed technologies, and suitability of this time frame for 
meeting the community's needs?  How easy will it be to use the proposed 
technology?  Are the plans adequate for the proposed technology, its 
integration as an effective solution for implementation, and 
dissemination? If industrial partnerships are proposed, how will they 
facilitate the development and integration of system components? 

3.   Innovation.  Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project 
challenge existing paradigms or develop new methodologies or 
technologies? What additional uses can be projected for the proposed 
technology?

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

5.   Environment.  Does the technical and scientific environment in 
which the work will be performed contribute to the probability of 
success?  Does the proposed work take advantage of unique features of 
the technical and scientific environment or employ useful collaborative 
arrangements? Is there evidence of institutional support?

Additional Considerations

Milestones (for R21/R33 applications) and Proof of Principle (for R33 
applications).  For the R21/R33 applications, how appropriate are the 
proposed Milestones against which to evaluate the demonstration of 
feasibility for transition to the R33 development phase?  For the R33 
applications, how well has feasibility or proof of principle been 
demonstrated? 

For the R21/R33 Phased Innovation Award Application, the initial review 
group will evaluate the specific goals for each phase and the 
feasibility Milestones that would justify progression to the R33 phase. 
A single priority score will be assigned to each scored application.  
As with any grant application, the initial review group has the option 
of recommending support for a shorter duration than that requested by 
the applicant, and basing the final merit rating on the recommended 
portion of the application.  This may result in a recommendation that 
only the R21 phase of the combined R21/R33 application be supported, 
based on the relative merit of the two research plans, adequacy of the 
milestones for determining the success of Phase I feasibility studies 
and capacity to provide easily assessed justification for progression 
to the R33 phase without further peer review.  The Initial Review Group 
may recommend modifications to or the addition of milestones.  Deletion 
of the R33 phase by the review panel or inadequate Milestones may 
affect the merit rating of the application.

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:
o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research. Plans for the recruitment and retention of subjects will also 
be evaluated.
o  The reasonableness of the proposed budget and duration in relation 
to the proposed research.
o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.

AWARD CRITERIA

Applications recommended by the National Cancer Advisory Board will be 
considered for award on the basis of (a) quality of the proposed 
project as determined by peer review; (b) availability of funds; and 
(c) program priority.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups 
and their sub- populations must be included in all NIH-supported 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification is provided 
to indicate that inclusion is inappropriate with respect to the health 
of the subjects or the purpose of the research.  This policy results 
from the NIH Revitalization Act of 1993 (Section 492B of Public Law 
103-43). 

All investigators proposing research involving human subjects should 
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities 
as Subjects in Clinical Research," published in the NIH Guide for 
Grants and Contracts on August 2, 2000  
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a 
complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: 
The revisions relate to NIH defined Phase III clinical trials and 
require a) all applications or proposals and/or protocols to 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) all investigators to report accrual, 
and to conduct and report analyses, as appropriate, by sex/gender 
and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age 
of 21) must be included in all human subjects research conducted or 
supported by the NIH, unless there are clear and compelling scientific 
and ethical reasons not to include them.  This policy applies to all 
initial (Type 1) applications submitted for receipt dates after October 
1, 1998. 

All investigators proposing research involving human subjects should 
read the “NIH Policy and Guidelines on the Inclusion of Children as 
Participants in Research Involving Human Subjects” that was published 
in the NIH Guide for Grants and Contracts, March 6, 1998, and which is 
available at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators may also obtain copies of these policies from program 
staff listed under INQUIRIES.  Program staff may also provide 
additional relevant information concerning the policy.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should 
read the NIH policy on education in the protection of human research 
participants now required for all investigators, which is published in 
the NIH Guide for Grants and Contracts, June 5, 2000 (Revised August 
25, 2000), available at the following URL address 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.  A 
continuing education program on the protection of human participants in 
research is now available online at http://cme.nci.nih.gov/.

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 a 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.  Reviewers are cautioned 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 PA, 
Development of Novel Technologies for In Vivo Imaging (Phased 
Innovation Award), is related to the priority area of cancer. 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 
No. 93.394, Cancer Detection and Diagnosis Research (NCI). Awards are 
made under authorization of Sections 301 and 405 of the Public Health 
Service Act as amended (42 USC 241 and 284) and administered under NIH 
grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 
and 92. This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

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


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