INNOVATIVE TECHNOLOGIES FOR THE MOLECULAR ANALYSIS OF CANCER: PHASED
INNOVATION AWARD

Release Date:  May 8, 1998

PA NUMBER:  PAR-98-067

P.T.

National Cancer Institute

Letter of Intent Receipt Dates:  July 2, November 5, 1998 and March 5, 1999
Application Receipt Dates:  August 7, December 10, 1998 and April 9, 1999

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 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;
monitoring of the expression of genes and gene products; analysis and
detection of the cellular localization, post-translational modification, and
function of proteins; and monitoring 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 clinical application.  This program will utilize the
Phased Innovation Award mechanisms (R21 and/or R33) to allow expedited review
of applications and expedited transition of successful technology research to
an expanded development phase.  Small businesses are encouraged to consider a
parallel program announcement (PAR-98-066) of identical scientific scope that
utilizes the SBIR and STTR mechanisms with accelerated review and transition,
as well as cost and duration requirements comparable to the Phased Innovation
Awards.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This PA, 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 2000" (Full Report: 
Stock No. 017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202- 512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, 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

MECHANISM OF SUPPORT

Support for this program will be through the National Institutes of Health
(NIH) Exploratory/Developmental Research Grant (R21) and the
Exploratory/Developmental Research Grant Phase 2 (R33).  The R33 is a newly
established NIH grant mechanism to provide a second phase for the support of
innovative exploratory and development research initiated under the R21
mechanism.  Conversion of the R21 to the R33 phase will be expedited and based
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.  Although the R33 application
has no official budgetary limit, 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 responsiveness of the proposed project.  Early contact with NCI
staff is particularly critical relative to this PA since it utilizes a new
grant mechanism (R33) as well as 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 release 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
measurable milestones that will be used to judge the success of the proposed
research, as well as a credible development plan for phase  R33. In place of a 
Preliminary Studies/Progress Report, the R33 application must include a
discussion of the R21 milestones and their implications for the R33.

Through a separate program announcement, (PA-98-066) the NCI is inviting
applications for SBIR and STTR support, focusing on the identical research
areas as described in the RESEARCH OBJECTIVES section of this solicitation. 
For SBIR/STTR solicitation, the expedited NCI review and cost allowance
policies and procedures will be identical to this PA.  Qualified applicants
are strongly encouraged to consider responding to the SBIR/STTR program
announcement.  SBIR and STTR application information is available on the web
at: http://www.nih.gov/grants/funding/sbir.htm

Potential applicants who believe that they may be eligible for the SBIR/STTR
award should discuss their eligibility with NCI staff listed under INQUIRIES.

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 PHS grants policy
as stated in the PHS Grants Policy Statement, DHHS Publication No (OASH)
90-50,000 revised April 1, 1994

RESEARCH OBJECTIVES

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 þcancer genes' 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. To this end, the NCI has established the Cancer
Genome Anatomy Project (CGAP), which will put in place the tools that will
allow deciphering of the molecular anatomy of a cancer cell at the DNA, RNA
and protein levels. The NCI is currently targeting two objectives in the CGAP. 
The first is the establishment of an index (Tumor Gene Index) identifying
genes that are expressed in normal, precancerous, and cancerous cells. This
project is well under way and further information about the Index can be found
at:  http://www.ncbi.nlm.nih.gov/ncicgap/.  The second objective is the
support for the development and dissemination to basic 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.

Improved molecular analysis tools will not only allow for the more careful
examination of the molecular basis and profiles of cancer, but will 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 and carcinogens.  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 and radiation.

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.  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 both basic 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 both the basic 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 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. Therefore, the development of technologies
such as imaging that will support the in situ and in vivo monitoring of
molecular activity is considered to be essential.

Objectives and Scope

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 epidemiologic 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 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

-- Highly specific and sensitive detection of specific  mutations

-- Detecting mismatch and recombinational DNA repair related to cancer
susceptibility

-- In vitro multiplexed analysis of the expression of genes

-- Computer assisted quantitation of gene expression in histological samples

-- 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 in vitro tools for clinical research and clinical
application 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.

-- Detecting DNA mutations and polymorphisms, and functional proteins in
biologic fluids such as serum, plasma, nipple aspirates, bronchioalveolar
lavage, sputum, urine, pancreatic juice, colonic wash, and bladder wash.

During the basic discovery process, enhanced capability is needed to determine
the influence of various molecular alterations or factors in the context of
viable whole cells or whole body analysis of model organisms. Similarly,
substantial opportunity exists for improvements in approaches to monitor
molecular events non-invasively in humans in support of both clinical research
and patient care.  Of interest are  technologies suitable for:

-- Delineating molecular expression or function in situ including imaging
technologies related to the energy source-detector, contrast agents, and data
analysis tools.

-- Delineating molecular expression or function at the cellular level in the
context of the whole body, including imaging technologies related to the
energy source-detector, contrast agents, and 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  demonstrating
the utility of the technology is appropriate.

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 subpopulations 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 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
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

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.

NIH POLICY AND GUIDELINES ON THE 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.  Therefore, the policy does
not apply to applications submitted on the August 7, 1998 receipt date.

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://www.nih.gov/grants/guide/notice-files/not98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit, by the dates listed at the
beginning of this program announcement, 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 avoid conflict of interest in the review.  The
letter of intent is to be sent to Dr. Carol Dahl at the address listed under
INQUIRIES.

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 (rev. 5/95) and prepared according to the instructions provided
unless specified otherwise within this section.  Application kits are
available at most institutional offices of sponsored research and may be
obtained from the Division of Extramural Outreach and Information Resources,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone
301/435-0714, email:  grantsinfo@nih.gov.

The R21/R33 application must include the specific goals for each phase and the
feasibility milestones that would justify expansion to the R33 phase. 
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 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 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 writeup of Sections a-d for the
R21 phase and again for the R33 phase.  The Form 398 Table of Contents should
be modified to show sections a-d for each phase.  There is a page limit of 25
pages for the composite a-d text (i.e., Sections a-d for both the R21 and 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.

1.  Face Page of the application:

Item 2.  Check the box marked "YES" and type the number and title of this
program announcement..

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.

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.

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, the immediacy of the opportunity and its expected
impact on the molecular analysis of cancer.

3.  Research Plan:

Item a., Specific Aims.

The applicants must present scientific milestones that the applicant considers
to be scientifically appropriate for determining proof of feasibility and
warrants expansion of the R21 to the R33 development phase.

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

In Item c of the R33 phase, a description of the scientific milestones can be
included in lieu of preliminary studies.

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 (rev. 5/95) and prepared according to the instructions provided unless
specified otherwise within items 1-5 below.  Application kits are available at
most institutional offices of sponsored research and may be obtained from the
Division of Extramural Outreach and Information Resources, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: 
grantsinfo@nih.gov.

1.  Face Page of the application:

Item 2.  Check the box marked "YES" and type the number and title of this
program announcement

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." 
Since 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.

FOR ALL APPLICATIONS

Appendix:   All instructions in the Form 398 application kit apply.

The completed original application and three legible copies must be sent or
delivered 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
6130 Executive Boulevard, Room 636a, MSC 7405
Bethesda, MD 20892-7405
Rockville, MD 20852 (for overnight/courier service)
Telephone:    (301) 496-3428
FAX:    (301) 402-0275

Applications must be received by the receipt dates listed at the beginning of
this PA.

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established PHS referral
guidelines.  Upon receipt, applications will be reviewed by the CSR for
completeness and by NCI program staff for responsiveness. Applications not
adhering to application instructions described above and those applications
that are incomplete or non-responsive as determined by CSR or by NCI program
staff will be returned to the applicant without review.

Applications will be reviewed for scientific and technical merit by an initial
review group convened by the NCI Division of Extramural Activities.  Following
scientific-technical review, the applications will receive a second-level
review by the National Cancer Advisory Board.

As part of the initial merit review, a process may be used by the initial
review group in which applications will be determined to be competitive or
non-competitive based on their scientific merit relative to other applications
received in response to the PA.  Applications judged to be competitive will be
discussed and be assigned a priority score.  Applications determined to be
non-competitive will be withdrawn from further consideration and the Principal
Investigator and the official signing for the applicant organization will be
notified.

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 field 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?  What is the immediacy of the research opportunity?  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? How appropriate are the proposed milestones against which
to evaluate the demonstration of feasibility for transition to the R33
development phase? 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

For the R21/R33 Phased Innovation Award Application, the initial review group
will evaluate the specific goals for each phase and the feasibility milestones
which 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's specific goals and the
feasibility milestones justifying expansion to the R33 phase.  Deletion of the
R33 phase by the review panel 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 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.  In addition, for applications submitted for the
December 10, 1998 and April, 9 1999 receipt dates, reviewers will address the
adequacy of plans for including children as appropriate for the scientific
goals of the research, or justification for exclusion. (See section on NIH
POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH
INVOLVING HUMAN SUBJECTS).

AWARD CRITERIA

Applications will compete for available funds with all other approved
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.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Carol Dahl, Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
Building 31, Room 11A03
31 Center Drive, MSC 2590
Bethesda, MD  20892-2590
Telephone:  (301) 496-1550
FAX:  (301) 496-7807
Email:  carol_dahl@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Theresa Mercogliano
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243, MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800 ext. 243
FAX:  (301) 496-8601
Email:  mercoglt@gab.nci.nih.gov

Direct inquiries regarding review matters to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636
Bethesda, MD  20892-7150
Telephone:  (301) 496-3428
FAX:  (301) 402-0275

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.394.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC
241 and 285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74 and part 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 and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.  In
addition, Public Law 103-227, the Pro- Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.


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