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APPLICATIONS OF INNOVATIVE TECHNOLOGIES FOR THE MOLECULAR ANALYSIS OF CANCER:
PHASED INNOVATION AWARD
Release Date: May 31, 2001
PA NUMBER: PAR-01-106 (see replacement RFA-CA-05-003)
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-99-102, 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 evaluate the utility and pilot the application of molecular
analysis technologies in studies relevant to cancer research.
Molecular analysis technologies of interest include those that are
entirely novel, or emerging but not currently in broad scale use where
the technologies have not yet been demonstrated to be robust or
reproducible in supporting molecular analysis in cancer research, or
technologies currently in use for one application or set of
applications, that are being evaluated for utility for alternative
applications. The Program Announcement (PA) provides support for a
first phase for technology evaluation and a second phase for pilot
application of the technology in a study of biological interest to
cancer research. The first (evaluation) phase should include proof of
principle experiments that will demonstrate the utility of the
technology on samples comparable to those that will be used in the
second phase study. Applicants will be expected to demonstrate the
utility of all components of the process required for a fully
integrated system, including sample preparation, molecular analysis
assay, and data capture and analysis. The second (application) phase
supports the transition of the technology optimized in the first
(evaluation) phase to pilot application in a study of biological
interest to cancer research. The design of the second phase study
should allow the demonstration that the technology can reproducibly
obtain molecular data from the selected sample type and produce
information of biological interest to cancer research. Studies might
appropriately target analysis of precancerous, cancerous, or metastatic
cells, or host derived samples, from model cancer systems, preclinical
or clinical research, or from population based research.
Technologies suited for this solicitation, include those that enable
the detection of alterations and instabilities of genomic DNA;
measurement of expression of genes and gene products; analysis and
detection of gene and or cellular products including differential
expression, quantitation, post translational modification, and function
of proteins; identification of exogenous infectious agents in cancer;
and assaying the function or major signal transduction networks
involved in cancer. Additionally, technologies that will support
molecular analysis in vitro, in situ, or in vivo (by imaging or other
methods) are suitable for this PA. Technologies are defined as
instrumentation, techniques, devices and analytical tools (e.g.,
computer software) but are distinct from resources such as databases,
reagents, and tissue repositories.
This PA will expire on July 22, 2003, unless reissued.
BACKGROUND
Rapid molecular analysis tools will expedite the molecular
characterization of normal cells, precancerous, cancerous, and
metastatic cells, as well as, expand our understanding of the
biological basis of cancers. Comprehensive analysis of cancers at the
molecular level will facilitate cancer detection and diagnosis, as well
as identify new targets for therapeutic and preventative agents.
The definition of the molecular alterations in cancer will require the
continued development and dissemination of comprehensive molecular
analysis technologies as well as identification 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
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. A
complimentary program on "Innovative Technologies for the Analysis of
Cancer" to support technology development was announced in May 1998 and
has recently been reissued for the next two years.
This initiative, "Applications of Innovative Technologies for the
Molecular Analysis of Cancer" is intended to support the demonstration
that newly developed and emerging technologies have matured and are
suitable for use in cancer research, followed by the initial
application of these technologies in well-defined studies of biological
interest to cancer research using model cancer systems, preclinical or
clinical samples, or in population research. The routine use of
improved molecular analysis tools will lead to a better understanding
of the molecular basis of cancer, and will facilitate the
identification of molecular characteristics of individuals, that
influence cancer development and prognosis.
Molecular analysis technologies of interest include those that will
support:
--A more complete understanding of the biological basis of cancer.
--The identification of molecular variations between normal,
precancerous, cancerous, and metastatic cells that can serve as targets
for the detection, diagnosis, therapy, and prevention.
--An examination of genetic factors that influence an individual's
likelihood to develop cancer or their ability to respond to external
damaging agents, such as radiation and carcinogens.
--The molecular correlation between individuals with therapeutic or
toxic responses to treatment and prevention measures and genetic
factors that influence the efficacy and safety of these strategies and
agents (pharmacogenomics).
--Identification of molecular markers in the individual that correlate
with the body's response to the onset or clearance of disease and the
development of biomarkers to track and even image the efficacy of
therapy (therametrics) and prevention, as well as the onset of
secondary cancers.
--Tracking of the damage to the genome from exogenous agents such as
carcinogens, radiation and existence of exogenous infectious agents
resident in cancer cells.
The comprehensive molecular analysis of cancer will require:
--High through put analysis strategies to elucidate the processing and
expression of genetic material in the cell.
--Detection of molecular changes in the cell without preconceived ideas
about which information will be most valuable to monitor.
--Adequate adaptations to accommodate technical issues specific to the
study of cancer in vitro and in vivo, such as limited cell number,
sample heterogeneity, and heterogeneity of specimen types (i.e., bodily
fluids and waste, tissues, cells).
--Adaptation of novel technologies for use in cancer research,
including use on tumor specimens, in patient imaging, and in population
research.
--Integration of sample preparation components that maintain the
efficiencies of the assay system and effectively accommodate human
tumor specimens.
--Data analysis tools for interpreting the information from highly
multiplexed molecular analyses.
Novel technologies for comprehensive molecular analysis are being
developed. Many of these technologies have not yet been demonstrated
to have utility or cost effectiveness in application to cancer model
systems, cancer specimens, or in population-based research. It will be
necessary to demonstrate that relevant technologies have adequate
sensitivity to discriminate differences between tumors and normal
tissues, and tumors of different stages. Therefore, the need exists to
demonstrate the ability of emerging molecular analysis technologies to
provide routine assay performance, adequate sensitivity and
discrimination, and associated robust data analysis tools, that can be
adapted to basic, pre-clinical, and clinical research settings for the
purpose of cancer research.
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, potentially including but not
limited to, expertise in 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
clinical and 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 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
application of high-resolution imaging at the cellular or molecular
levels to, tissue samples, pre-clinical models, or human investigations
is therefore considered to be an important extension of molecular
analysis methods. Similarly, the application 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 modifications 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. Investigations of tumor models that do not target
molecular species are not responsive to this application.
Investigators are encouraged to contact NCI program staff for further
information.
RESEARCH OBJECTIVE
The National Cancer Institute (NCI) invites applications for research
projects to evaluate the utility and pilot the application of newly
developed molecular analysis technologies in studies relevant to cancer
research. The Program Announcement (PA) provides support for a first
phase for technology evaluation and a second phase for pilot
application of the technology in a study of biological interest to
cancer research. The first (evaluation) phase should include proof of
principle experiments that will demonstrate the utility of the
technology on samples comparable to those that will be used in the
second phase study. Applicants will be expected to demonstrate the
utility of all components of the process required for a fully
integrated system, including sample preparation, molecular analysis
assay, and data capture and analysis. The second (application) phase
supports the transition of the technology optimized in the first
(evaluation) phase to pilot application in a study of biological
interest to cancer research. The design of the second phase study
should allow the demonstration that the technology can reproducibly
obtain molecular data from the selected sample type and produce
information of biological interest to cancer research. Studies might
appropriately target analysis of precancerous, cancerous, or metastatic
cells, or host derived samples, from model cancer systems, preclinical
or clinical research, or from population based research.
The application of new tools that support the comprehensive molecular
characterization of normal, precancerous, cancerous, and metastatic
cells, as well as the identification of new targets for detection,
diagnosis, preventative, and therapeutic strategies, is needed to
support the basic discovery process and the translation of basic
discoveries to pre-clinical and clinical research. Application of
improved molecular analysis technologies 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 as well as the identification of exogenous infectious
agents that may be associated with the development of cancer. Examples
given below are not intended to be all-inclusive, but are illustrative
of the types of molecular analysis capabilities that are of interest
for evaluation and pilot application in response to this solicitation.
--In vitro identification and characterization of sites of chromosomal
aberrations, which arise from inherited 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, detecting rare variants in
mixed populations, or identifying infrequently represented mutations in
mixed populations of DNA molecules.
--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.
-- 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, of identifying
infrequently represented mutations in mixed populations of DNA
molecules.
-- Highly specific and sensitive detection of specific mutations in
multiplexed high through put analysis.
-- Detection of mismatch and recombinational DNA repair anomalies
related to cancer susceptibility, cancer progression, 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 post-
translationally 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.
--Assaying 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 members of a
complete genetic pathway.
Translation of the utility of the technologies described above and
basic research findings into tools for pre-clinical and clinical
applications requires additional technological innovation with regard
to sample preparation, enhanced sensitivity, and expanded data analysis
tools. Of interest is the application of technologies suitable for:
-- Detection, quantification and analysis of DNA mutations and
polymorphisms and functional proteins in clinical specimens (e.g.
tissue, serum, plasma, nipple aspirates, bronchioalveolar lavage,
sputum, urine, pancreatic juice, colonic wash, and bladder wash).
--Imaging in situ or in vivo in order to extend molecular analysis to
early cancer formation. The application of high-resolution imaging at
the cellular or molecular levels to, tissue samples, pre-clinical
models, or clinical investigations are therefore considered to be an
important extension of molecular analysis methods. Similarly, the
application 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
modifications of gene expression are considered critical to improve the
sensitivity of detection of molecular changes in vivo. The molecular
imaging methodologies proposed, include 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.
The R21 proposal supports a first phase for technology evaluation.
Applicants should describe proof of principle experiments that will
demonstrate the utility of the technology. The applicant should:
--Demonstrate performance of the selected technology on samples
comparable to those to be used in the proposed study in the R33 phase.
--Have a detailed plan to optimize and troubleshoot the technology for
complete adaptation of the technology for the R33 pilot application.
--Discuss how they will evaluate cost effectiveness of the technology
relative to existing and competing technologies.
--Specifically address approaches to sample preparation, molecular
analysis assays, data collection, and data management.
Applicants must include in a separate section the milestones to be
accomplished in the first phase of the application. Milestones are
separate from specific aims. They provide a clear measure of the
success of the R21 application which is necessary to proceed to the
second phase, therefore they should be clearly stated and presented in
a manner that is easily quantifiable.
The R33 study is intended to support the pilot application of
technology evaluated and refined in the R21 proposal, to a study of
biological interest to cancer research. Technology developers are
strongly encouraged to seek collaborations with qualified cancer
researchers. In the R33 phase the applicants should:
--Describe how they will assess the performance of the technology in
providing useful molecular data relative to existing technologies.
--Address plans to refine study design parameters based on R21 results.
--Provide a more refined plan detailing the biological questions to be
asked by the study and how the forthcoming data will be translated,
either directly or indirectly, into information relevant to the study
of cancer.
--Comment in detail on the suitability of the study design (i.e.
numbers, types of samples) for asking the biological questions posed by
the study. This should be discussed in the context of information and
data to be obtained from R21 studies. The study design parameters (i.e.
number of samples, data analysis, etc.) should be of a scale to
reflect that this is a pilot application of the technologies.
--Clearly define what is considered to be a high quality sample for the
technology to be used.
--Document a strategy for obtaining access to high-quality samples that
will be needed to carry out the study.
--Discuss the ease of transition of the technology from R21 to R33
application with respect to scaling up the technology and implications
related to sample cost, availability, and sample through-put.
Effective data management and analysis will be critical to the
successful and productive application of the proposed technology.
Therefore applications must:
--Address the ability to acquire, store, analyze, and extract
information from data collected through the course of the study.
--Demonstrate capabilities to capture the data and to perform the
complex multiplex analysis on data a acquired through the course of the
study.
--Describe bioinformatics, other analytical systems, and approaches
that will be used to interpret data obtained from the study.
Applicants are encouraged to discuss potential strategies for making
resulting molecular data sets available to the cancer research
community in both peer reviewed-publications as well as in complete
electronically accessible data sets.
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 pilot application 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-01-107.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: carol_dahl@nih.gov
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: shinok@gab.nci.nih.gov
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: tf12w@nih.gov
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 applied, its innovative nature, its relationship to
presently available capabilities, and its expected impact on the
molecular analysis of cancer, as well as the study in which the
technology will be applied.
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 support the pilot
application of 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 supports
the pilot application of 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.
Studies pursuing comprehensive analysis in particular may result in
hypothesis generation, rather than hypothesis testing.
Item b: Background and Significance
Elaborate on the innovative nature of the proposed research. Clarify
how the technology proposed for evaluation 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. Describe the significance of the second phase
pilot biological study in terms of relevance to cancer research.
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 applied, its innovative nature, its relationship to
presently available capabilities and its expected impact on the
molecular analysis of cancer, as well as the pilot biological study in
which the technology will be applied.
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 pilot
the application of innovative technologies, hypothesis testing per se
may not be the driving force in developing such a proposal and,
therefore, may not be applicable. Studies pursuing comprehensive
analysis in particular may result in hypothesis generation rather than
hypothesis testing.
Item b: Background and Significance
Elaborate on the innovative nature of the proposed research. Clarify
how the technology proposed for evaluation 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, and how these proposed
technologies would differ from existing technologies. Discuss the
significance of the pilot biological application to be undertaken in
terms of relevance for cancer research.
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 application 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. Preliminary data relevant to both the technology
evaluations and the pilot biological study should be presented.
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?
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,
Applications of Innovative Technologies for the Molecular Analysis of
Cancer, 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.
Return to NIH Guide Main Index
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