and Human Services (HHS)
EXPIRED
INNOVATIVE TECHNOLOGIES FOR THE MOLECULAR ANALYSIS OF CANCER: PHASED
INNOVATION AWARD
Release Date: May 31, 2001 (see addendum NOT-CA-03-007)
PA NUMBER: PAR-01-104
National Cancer Institute
Letter of Intent Date: June 15, 2001; October 17, 2001; February 14, 2002;
June 10, 2002; October 18, 2002; February 14, 2003;
and June 16, 2003
Application Receipt Date: July 20, 2001; November 21, 2001; March 21, 2002;
July 22, 2002; November 22, 2002; March 21, 2003;
and July 21, 2003
This Program Announcement (PA) replaces PAR-99-100, which was published
in the NIH Guide on May 14, 1999.
THE PA INCLUDES MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT
MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA. THIS
PA DOES NOT USE THE MODULAR GRANT CONCEPT.
PURPOSE
The National Cancer Institute (NCI) invites applications for research
projects to develop novel technologies that will support the molecular
analysis of cancers and their host environment in support of basic,
clinical, and epidemiological research. Technology encompasses methods
and tools that enable research including, but not limited to,
instrumentation, techniques, devices, and analysis tools (e.g.,
computer software). Technology is distinct from resources such as
databases, reagents, and tissue repositories. Applications for support
of such resources will not be considered to be responsive to this
Program Announcement (PA). Technologies solicited include those that
are suitable for the detection of alterations and instabilities of
genomic DNA; measurement of the expression of genes and gene products;
analysis and detection of gene and or cellular products including post
translational modification, and function of proteins; identification
and characterization of exogenous infectious agents in cancer; and
assaying the function of major signal transduction networks involved in
cancer. This PA is intended to support the development of all required
components of fully integrated systems for analysis including front end
preparation of sample materials from cells, bodily fluids, and tumor
specimens; novel chemistries or contrast agents; molecular detection
systems; data acquisition methods; and data analysis tools.
Technologies under consideration include those that will support
molecular analysis either in vitro, in situ, or in vivo (by imaging or
other methods) in the discovery process, as well as in pre-clinical
models and clinical research.
This PA will expire on July 22, 2003 unless reissued.
BACKGROUND
In the past several decades it has become clear that cancer is not one
disease but many, and that cancers arise as the result of the gradual
accumulation of genetic changes in single cells. Identifying which
subset of the genes encoded within the human genome can contribute to
the development of cancer remains a challenge. The identification of
these cancer genes and their associated gene products remains a high
priority in cancer research. Identifying the molecular alterations
that distinguish any particular cancer cell from a normal cell will
ultimately help to define the nature and predict the pathologic
behavior of that cancer cell, as well as the responsiveness to
treatment of that particular tumor. By understanding the profile of
molecular changes in any particular cancer it will become possible to
correlate the resulting phenotype of that cancer with molecular events.
Resulting knowledge will offer the potential for a better understanding
of cancer biology; the discovery of new tools and biomarkers for
detection, diagnosis, and prevention studies; and new targets for
therapeutic development.
The definition of the molecular profiles of cancer will require the
development and dissemination of enhanced molecular analysis
technologies, as well as elucidation of all of the molecular species
encoded in genomes of cancer and normal cells. The National Cancer
Institute implemented the Cancer Genome Anatomy Project (CGAP) to
create an information infrastructure of the molecular changes
associated with cancer development, and to develop technological tools
to support the analysis of molecular profiles of cancer cells and their
normal counterparts. The current CGAP program comprises Tumor Gene
Indices for the human and mouse (hTGI and mTGI), a Genetic Annotation
Initiative (GAI) and the Cancer Chromosome Aberration Project (cCAP).
The TGI and GAI, are focused toward building a catalog of annotated
genes associated with cancer. The third component, cCAP, is developing
resources to catalog and facilitate the molecular characterization of
cancer-related chromosomal aberrations. Complete information about CGAP
can be found at http://cgap.nci.nih.gov. The NCI is also targeting the
support for the development and dissemination to basic, preclinical,
and clinical researchers of novel technologies that will allow high-
throughput analysis of genetic alterations, expression of genome
products, and monitoring of signal transduction pathways in cancers.
Products of this PA are intended to contribute to this goal.
This solicitation is intended to support the development of molecular
analysis tools that will allow for the more careful examination of the
molecular basis and profiles of cancer, and also provide the ability to
identify the molecular characteristics of individuals that influence
cancer development and prognosis. These tools will allow for an
examination of genetic factors that influence an individual’s
likelihood to develop cancer or their ability to respond to damaging
external agents, such as radiation, carcinogens, and therapeutic
regimes. Correlating the molecular variations between individuals with
therapeutic or toxic responses to treatment and prevention measures
should define genetic factors that influence the efficacy and safety of
these strategies and agents (pharmacogenomics). Identification of
molecular markers in the individual that characterize the body’s
response to the onset or clearance of disease will allow for the
development of biomarkers to track and even image the efficacy of
therapy (therametrics) and prevention, as well as the onset of
secondary cancers. The ability to completely screen the genome for
variations should enable tracking of the damage to the genome from
exogenous agents such as carcinogens, infectious agents, radiation, and
therapeutic regimes. Products of this PA such as molecular imaging in
situ are intended to contribute to this goal.
Modern molecular technology can contribute to detection and
characterization of nucleic acid sequences of novel exogenous
infectious agents including viruses, bacteria or other microscopic
forms of life that may be etiologic factors or co-factors in the
initiation and/or progression of human cancers. New technologies are
demonstrating that microorganisms may play a more important role in the
initiation of malignancies than was previously appreciated. New
molecular analysis tools resulting from this initiative are intended to
contribute to this goal.
In order to fully understand cancer and define the molecular response
of the host to cancer, it will be critical to not only have knowledge
at the DNA level, but to have a complete understanding of the
processing of genetic information in cellular function. Current
discoveries indicate that alterations in many of the cellular
processes, pathways, or networks may contribute to the genesis of
cancer and could be exploited for therapeutic or prevention
intervention. Therefore, it is important to put in place technologies
that can detect molecular changes in the cell without preconceived
ideas about which information will be most valuable to monitor or which
technologies will have the greatest impact. It is currently possible to
monitor very specific changes in the expression and function of genes
and gene products at the DNA, RNA, or protein level. However, many
existing technologies do not adequately address technical issues
specific to the study of cancer in vitro and in vivo, such as limited
cell number, sample heterogeneity, heterogeneity of specimen types
(i.e. bodily fluids and waste, tissues, cells), and cost effectiveness.
Adaptation of novel technologies to support use in cancer research,
including use on tumor specimens, and in patient imaging, is
encouraged.
In the discovery phase, it will be of great utility to have
technologies that can effectively scan variations or function, in many
or all members of the populations of DNA, RNA or protein molecules
present in cells through highly multiplexed analysis. Current
technologies for the multiplexed analysis of molecular species are at a
stage where the greatest utility exists for the analysis of large
numbers of relatively homogeneous cell populations that can be assayed
in vitro. While many of the existing technologies have relatively
sophisticated multiplexing capability in the assay format of the
system, none of the existing systems is comprehensive for any
particular molecular species (DNA, RNA or protein). In addition, none
of the existing systems for in vitro analysis have well integrated
sample preparation components that maintain the cost efficiencies of
the assay system and effectively accommodate human tumor specimens.
Similarly, data analysis tools for interpreting the information from
highly multiplexed molecular analyses have not been sufficiently
developed and tested for use in the context of basic, preclinical, and
clinical cancer research questions. Therefore, the opportunity exists
for further development to insure that resulting technologies provide
enhanced assay potential, adequate sensitivity and discrimination,
robust data analysis tools, and are easily adapted to the basic,
preclinical, and clinical research settings.
Translation of new in vitro technologies for the multiplexed analysis
of molecular species in clinical specimens will require a
multidisciplinary team approach with broad expertise in a variety of
research areas. Such varied expertise including but not limited to
pathology specimen acquisition and preparation, informatics, and
biostatistics, exists in ongoing cancer centers and clinical trials
cooperative groups. The coordination and collaboration of investigators
from these various disciplines to demonstrate the utility and
applicability of new analytical tools in preclinical, clinical and in
population based studies is considered to be a high priority.
Existing technologies for molecular analysis are also largely
restricted to in vitro analysis. While these systems are suitable for
discovery and many basic, preclinical, and clinical research questions,
they are limited in their ability to offer information relative to
molecular changes in real time and in the appropriate context of the
intact cell or body. Imaging in situ or in vivo is becoming
increasingly important for extending molecular analysis of early cancer
formation. The development of high-resolution imaging at the cellular
or molecular scales in tissue samples, pre-clinical models, or human
investigations is considered to be an important extension of molecular
analysis methods. Similarly, the development of molecular probes for
imaging molecular events is also of interest for pre-clinical and human
investigations. Finally, the use of molecular contrast enhancement
techniques, such as contrast modification of gene expression are
considered critical to improve the sensitivity of detection of
molecular changes in vivo. The molecular imaging methodologies
proposed, including hardware and software, are specifically understood
as being within the context of molecular analysis tools. They include
specialized high resolution or microscopic imaging methods dedicated to
detection and analysis of molecular events related to cancer formation
or as applied to pre-clinical drug discovery. Improvements in these
areas will bring capabilities for real time molecular analysis at whole
body levels.
RESEARCH OBJECTIVES
The purpose of this program announcement is to encourage applications
from individuals and groups interested in developing novel technologies
suitable for the molecular analysis of cancers and their host
environment in support of basic, clinical, and epidemiological
research. Technologies to support research in the following areas are
considered to be appropriate. Examples given below are not intended to
be all-inclusive, but are illustrative of the types of capabilities
that are of interest.
New tools that allow development of a more complete molecular profile
of normal, precancerous, and cancerous cells, as well as the process of
carcinogenesis, are needed to support the basic discovery process.
These tools will also allow a more thorough examination of the
variations that influence predisposition to cancer, and individual
variability in response to therapeutic and prevention agents. Of
interest are technologies and data analysis tools for:
--In vitro scanning of or identification of the sites of chromosomal
aberrations which reflect inherited aberrations or somatic alterations
resulting from aging or oxidation, or exposure to radiation or
carcinogens, including those that are suitable for scaling for use
across whole genomes, detecting DNA adducts, or detecting rare variants
in mixed populations.
--In vitro scanning for and identification of sites of mutations and
polymorphisms which reflect inherited aberrations or variations, or
somatic alterations resulting from aging or oxidation, or exposure to
radiation or carcinogens, including those that are suitable for scaling
for screening whole genomes, detecting DNA adducts, or identifying
infrequently represented mutations in mixed populations of DNA
molecules.
--Technologies for detection and characterization of nucleic acid
sequences of novel exogenous infectious agents that may be present in
human cancer.
--Highly specific and sensitive detection of specific mutations.
--Detecting mismatch and recombinational DNA repair related to cancer
susceptibility and drug sensitivity
--In vitro multiplexed analysis of the expression of genes.
--Computer assisted quantitation of gene expression.
--In vitro detection of expression of proteins and their modified
forms, including technologies suitable for expansion to profiling of
all proteins expressed in cells, detecting rare variants in mixed
populations, and detecting protein adducts involved in chemical
mutation.
--Monitoring the function of proteins and genetic pathways, including
measurement of ligand-protein complexes and technologies for monitoring
protein function of all members of a class of proteins or a complete
genetic pathway.
Translation of the utility of the technologies described above and
basic research findings into tools for preclinical, and clinical
research; requires additional technological innovation with regard to
sample preparation, enhanced sensitivity, and expanded data analysis
tools. Of interest are technologies for:
--In vitro sample and specimen preparation that is suitable for human
tissues and tumor (including solid tumor) specimens that interface with
molecular analysis tools of the type listed above.
--Detection, quantification and analysis of DNA mutations,
polymorphisms and functional proteins in clinical specimens (e.g.
tissues, urine, serum, plasma, nipple aspirates bronchioalveolar
lavage, sputum, pancreatic juice, colonic wash and bladder wash).
During the basic discovery process enhanced capability is critically
needed for the following:
--Delineating molecular expression, function and analysis at the
cellular level in the context of both the whole body and in situ,
including molecular imaging technologies suitable at this scale,
contrast agents, gene amplification techniques and related data
analysis tools.
Applications may request support for the development of individual
components of the final system, for example, front-end sample
preparation components for in vitro systems, molecular detection
systems, data acquisition systems, and data analysis tools. Issues
related to the integration of the entire analysis process should be
discussed particularly in the context of the R33 application.
For all technologies proposed it will be important to substantiate the
ultimate value of and role for the technology in deciphering the
molecular anatomy of cancer cells or analyzing the molecular profile of
the individual. It is also important for applicants to discuss the
ultimate potential for the transfer of ensuing technology to other
laboratories or the clinic, and for more mature technologies, plans to
ensure dissemination of the technology. In the case of technologies
intended for use on clinical specimens or in patients, applications
from or collaborations with investigators involved in the clinical
research of cancer are encouraged.
The focus of this Program Announcement is technology development.
Support for mechanistic studies of basic questions will not be
provided, although testing on biological samples or in whole organisms
in the course of enhancing the utility of the technology is
appropriate. Support for the pilot applications of new technologies to
questions of interest to cancer research is outside the scope of this
PA, but is the subject of another solicitation entitled Application of
Innovative Technologies for the Molecular Analysis of Cancer.
MECHANISM OF SUPPORT
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant. Except as
otherwise stated in this program announcement, awards will be
administered under NIH grants policy as stated in the NIH Grants Policy
Statement, March 2001, available at:
http://grants.nih.gov/grants/policy/nihgps_2001/. 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
mechanism provides a second phase for the support of innovative
exploratory and development research initiated under the R21 mechanism.
Transition of the R21 to the R33 phase will be expedited and is
dependent on completion of negotiated milestones.
Under this PA, applicants can submit either a combined R21/R33
application (Phased Innovation Award application) or the R33
application alone, if feasibility can be documented, as described in
the APPLICATION PROCEDURES section of this program announcement.
Applications for R21 support alone will not be accepted. The total
project period for an application submitted in response to this PA may
not exceed the following duration: R33, 3 years; combined R21/R33
application, 4 years. In the combined application the R21 phase cannot
extend beyond 2 years.
For combined R21/R33 applications, the R21 phase may not exceed
$100,000 direct costs per year. R21 budgets can exceed this cap to
accommodate indirect costs to subcontracts to the project. R33
applications requesting in excess of $500,000 dollars direct costs in
any single year of the grant period require prior approval before
submission. It is strongly recommended that applicants contact NCI
staff at an early stage of application development to convey critical
information, such as potentially large budget requests or to discuss
programmatic adherence to the guidelines of the proposed project.
Early contact with NCI staff is particularly critical relative to this
PA because it uses an expedited review procedure. Refer to the
INQUIRIES sections of this program announcement for NCI staff contacts.
The combined R21/R33 application offers two advantages over the regular
application process:
1. Single submission and evaluation of both the R21 and the R33 as one
application.
2. Minimal or no funding gap between R21 and R33. The award of R33
funds will be based on program priorities, on the availability of funds
and on successful completion of negotiated scientific milestones as
determined by NCI staff in the context of peer review recommendations.
To be eligible for the Phased Innovation Award, the R21 phase must
include well-defined quantifiable milestones that will be used to judge
the success of the proposed research, as well as a credible plan for
the development of technology for the R33 phase. The Phased Innovation
Award must have a section labeled Milestones at the end of the Research
Plan of the R21 application. This section must include well-defined
quantifiable milestones for completion of the R21 part of the
application, a discussion of the suitability of the proposed milestones
for assessing the success in the R21 phase, and a discussion of the
implications of successful completion of these milestones for the
proposed R33 study.
This program will run in parallel with a program of identical
scientific scope
(http://grants.nih.gov/grants/guide/pa-files/PAR-01-105.html) that will utilize
the Small Business Innovation Research (SBIR) and Small Business Technology
Transfer (STTR) mechanisms.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by foreign and domestic, for-profit and
not-for-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, 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:
Carol A. Dahl, Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
31 Center Drive, Room 11A03
Bethesda, MD 20892-2590
Telephone: (301) 496-1550
FAX: (301) 496-7807
Email: [email protected]
Direct inquiries regarding fiscal matters to:
Ms. Kathleen J. Shino
Grants Administration Branch
National Cancer Institute
6120 Executive Blvd. Room 243
Bethesda, MD 20892-7150
Telephone: (301) 846-1016
FAX: (301) 846-5720
Email: [email protected]
Direct inquiries regarding review matters to:
Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8109, MSC 8326
Bethesda, MD 20892-8326
Rockville, MD 20852 (for express/courier service)
Telephone (301) 496-3428
Fax: (301) 402-0275
Email: [email protected]
LETTER OF INTENT
Prospective applicants are asked to submit, by the dates listed on the
first page of this PA, a Letter of Intent that includes a descriptive
title of the proposed research, the name, address, and telephone number
of the Principal Investigator, the identities of other key personnel
and participating institutions, and the number and title of the PA in
response to which the application may be submitted. Although a Letter
of Intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains
allows NCI staff to estimate the potential review workload and plan the
review.
The Letter of Intent is to be sent to Dr. Carol Dahl, listed under
INQUIRIES, by the Letter of Intent receipt date.
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 on the Internet at:
http://grants.nih.gov/grants/funding/phs398/phs398.html.
The R21/R33 application must include the specific aims for each phase
and the feasibility milestones that would justify transition to the R33
phase. Applications must include a specific section labeled Milestones
following the Research Plan of the R21 phase. Milestones should be
well described, quantifiable and scientifically justified. A
discussion of the milestones relative to the progress of the R21 phase,
as well as, the implications of successful completion of the milestones
for the R33 phase should be included. This section should be indicated
in the Table of Contents. Applications lacking this information as
determined by the NCI program staff, will be returned to the applicant
without review. For funded applications, completion of the R21
negotiated milestones will elicit an NCI expedited review that will
determine whether or not the R33 should be awarded. The release of R33
funds will be based on successful completion of negotiated scientific
milestones, program priorities, and on the availability of funds. 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
accomplish 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.,
section a-d and milestones for the R21 and sections a-d for the R33
phase must be contained within the 25 page limit.)
In preparing the R21/R33 application, investigators should consider the
fact that applications will be assigned a single priority score. In
addition, as discussed in the REVIEW CONSIDERATIONS section, the
initial review panel has the option of recommending only the R21 phase
for support. However, a Phased Innovation Award Application with an
R33 Phase that is so deficient in merit that it is not recommended for
support will reflect upon the judgement of the applicant. For these
reasons, the clarity and completeness of the R21/R33 application with
regard to specific goals and feasibility milestones for each phase are
critical. The presentation of milestones that are not sufficiently
scientifically rigorous to be valid for assessing progress in the R21
phase will reflect upon the scientific judgement of the applicant in
this proposal.
1. Face Page of the application:
Item 2. Check the box marked YES and type the number and title of this
program announcement. Also indicate if the application is a R21/33 or
R33.
Item 7a, DIRECT COSTS REQUESTED FOR INITIAL PERIOD OF SUPPORT:
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
and the award may not be used to supplement an ongoing project. The
requested budgets can exceed this cap to accommodate for indirect costs
to subcontracts to the project. Insert the first year of R21 support
in item 7a.
Item 8a, DIRECT COSTS REQUESTED FOR PROPOSED PERIOD OF SUPPORT:
For the R21 phase, direct costs requested for the proposed period may
not exceed $200,000 for two years of support. The statement in item 7a
above pertaining to subcontract costs also applies here. Insert sum of
all years of requested support in item 8a
2. Page 2 - Description:
As part of the description, identify concisely the technology or
methodology to be developed, its innovative nature, its relationship to
presently available capabilities, and its expected impact on the
molecular analysis of cancer.
3. Budget: The application should provide a detailed budget for
Initial Budget Period (form page 4), for each of the initial years of
the R21 and R33 phases as well as a budget for the entire proposed
period of support (form page 5). Form pages should indicate which
years are R21 and R33. All budgets should include a written
justification.
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.
4. Research Plan:
Item a., Specific Aims.
The applicants must present specific aims that the applicant considers
to be scientifically appropriate for the relevant phases of the
project.
The instructions in the PHS 398 booklet for this section of research
grant applications suggest that the applicant state the hypotheses to
be tested. Since 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.
Furthermore for R21 grant applications, preliminary data are not
required, although they should be included when available. For both
the R21 and R33 phase, research that develops new technologies is
likely to require the application of principles of fields such as
engineering, materials science, physics, mathematics, and computer
science. Clear statements of these underlying principles within this
section are essential.
Item b: Background and Significance
Elaborate on the innovative nature of the proposed research. Clarify
how the technology development proposed in this project is a
significant improvement over existing approaches. Explain the
potential of the proposed technology for having a broad impact on
cancer research. Clearly identify how the project, if successful,
would result in new capabilities for research, the immediacy of the
opportunity and how these proposed technologies would differ from
existing technologies.
Item c., Preliminary Studies/Progress Report
While preliminary data are not required for submission of the R21
phase, this section should provide current thinking or evidence in the
field to substantiate feasibility of the R21 phase. The R33 need not
repeat information already provided in the R21. In the event that an
applicant feels that technology is too proprietary to disclose,
applicants at a minimum should provide a demonstration (results) of the
capabilities of the proposed technology.
Item d., Research Design and Methods
Follow the instructions in the PHS 398 booklet. 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 of the R21 phase. Milestones
should be well described, quantifiable, and scientifically justified
and not be simply a restatement of the specific aims. A discussion of
the milestones relative to the success of the R21 phase, as well as the
implications of successful completion of the milestones for the R33
phase and the page number of the milestones section should be listed.
This section should be indicated in the Table of Contents.
Applications lacking this information as determined by the NCI program
staff, will be returned to the applicant without review. For funded
applications, completion of the R21 negotiated milestones will elicit
an NCI expedited review that will determine whether or not the R33
should be awarded. The release of R33 funds will be based on
successful completion of negotiated milestones, program priorities and
on the availability of funds. The expedited review may result in
additional negotiations of award.
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 on the Internet at:
http://grants.nih.gov/grants/funding/phs398/phs398.html.
1. Face Page of the application:
Item 2. Check the box marked a YES and type the number and title of
this program announcement and indicate R33.
2. Page 2 Description:
As part of the description, identify concisely the technology or
methodology to be developed, its innovative nature, its relationship to
presently available capabilities and its expected impact on the
molecular analysis of cancer.
3. Research Plan:
Item a., Specific Aims.
The instructions in the PHS 398 booklet for this section of research
grant applications suggest that the applicant state the hypotheses to
be tested. Because the goal of this program announcement 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 b: Background and Significance
Elaborate on the innovative nature of the proposed research. Clarify
how the technology development proposed in this project is a
significant improvement over existing approaches. Explain the
potential of the proposed technology for having a broad impact on
cancer research. Clearly identify how the project, if successful,
would result in new capabilities for research, the immediacy of the
opportunity, and how these proposed technologies would differ from
existing technologies.
Item c: Preliminary Studies/Progress report
This section must document that feasibility studies have been
completed, and progress achieved, equivalent to that expected through
the support of an R21 project. The application must clearly describe
how the exploratory/developmental study is ready to scale up to an
expanded development stage. In the event that an applicant feels that
the technology is too proprietary to disclose, applicants at a minimum
should provide a demonstration (results) of the capabilities of the
proposed technology.
FOR ALL APPLICATIONS
Appendix: All instructions in the Form 398 application kit apply.
Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided photocopies, in one
package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040 - MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
To expedite the review process, at the time of submission, send two
additional copies of the application to:
Ms. Toby Friedberg
Referral Officer
National Cancer Institute
6116 Executive Boulevard, Room 8109, MSC 8326
Bethesda, MD 20892-8326
Rockville, MD 20852 (for overnight/courier service)
Applications must be received by the receipt dates listed at the
beginning of this PA.
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. 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 adhere to the guidelines of this PA
will be evaluated for scientific and technical merit by an appropriate
peer review group convened by the Division of Extramural Activities,
NCI in accordance with the review criteria stated below. As part of
the initial merit review, all applicants will receive a written
critique and may undergo a process in which only those applications
deemed to have the highest scientific merit generally the top half of
the applications will be discussed, assigned a priority score, and
receive a second level review by the National Cancer Advisory Board
(NCAB).
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
The reviewers will comment on the following aspects of the application
in their written critiques in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of
these goals. Each of these criteria will be addressed and considered
by the reviewers in assigning the overall score weighting them as
appropriate for each application. Note that the application does not
need to be strong in all categories to be judged likely to have a major
scientific impact and thus deserve a high priority score. For example,
an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a technology forward.
1. Significance. Does this study address an important problem? If the
aims of the application are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the concepts or
methods that drive this field? To what degree does the technology
support the needs of the targeted research community? For systems
intended for clinical research the additional criteria will be
considered: to what degree is the analysis system appropriate for
clinical research and likely to have utility for the analysis of
clinical specimens or patients?
2. Approach. Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to the
aims of the project? Does the applicant acknowledge potential problem
areas and consider alternative tactics? What is the time frame for
developing the proposed technologies and suitability of this time frame
for meeting the scientific community’s needs? How easy will it be to
use the proposed technology? Are the plans for proposed technology
dissemination adequate?
3. Innovation. Does the project employ novel concepts, approaches, or
method? Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies? What is the throughput and cost effectiveness of the
proposed technology? What additional uses can be projected for the
proposed technology?
4. Investigator. Is the investigator appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the principal investigator and other researchers
(if any)?
5. Environment. Does the scientific environment in which the work
will be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment or employ useful collaborative arrangements? Is there
evidence of institutional support?
Additional Considerations
Milestones. How appropriate are the proposed milestones against which
to evaluate the demonstration of feasibility for transition to the R33
development phase?
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 expansion 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. For the R21/R33 application, this may
result in a recommendation that only the R21 phase be supported, based
on concerns related to the applicant specific goals and the feasibility
milestones justifying expansion to the R33 phase. Deletion of the R33
phase by the review panel or inadequate milestones will affect the
merit rating of the application.
The initial review group will also examine: the appropriateness of the
proposed project budget and duration; the adequacy of plans to include
both genders and minorities and their subgroups, and children as
appropriate for the scientific goals of the research and plans for the
recruitment and retention of subjects; the provisions for the
protection of human and animal subjects; and the safety of the research
environment.
AWARD CRITERIA
Applications will compete for available funds with all other
recommended applications assigned to the NCI. The following will be
considered in making funding decisions: quality of the proposed project
as determined by peer review, availability of funds, and program
priority.
SCHEDULE
Letter of Intent Receipt Dates: June 15, 2001; October 17, 2001;
February 14, 2002; June 10, 2002;
October 18, 2002; February 14, 2003;
and June 16, 2003
Application Receipt Dates: July 20, 2001; November 21, 2001;
March 21, 2002; July 22, 2002;
November 22, 2002; March 21, 2003;
and July 21, 2003
NCAB Review Dates: February 2002; May 2002; September 2002;
February 2003; May 2003; September 2003;
February 2004
Earliest Anticipated Award Date: April 1, 2002; July 1, 2002; November 1, 2002;
April 1 2003; July 1, 2003; November 1, 2003;
April 1, 2004
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
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 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 is
available at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.
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 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. 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,
Innovative Technologies for the Molecular Analysis of Cancer: 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. 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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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