Expired RFA-CA-05-004: INNOVATIONS IN CANCER SAMPLE PREPARATION

Department of Health
and Human Services (HHS)

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This notice has expired. Check the NIH Guide for active opportunities and notices.

EXPIRED

INNOVATIONS IN CANCER SAMPLE PREPARATION

RELEASE DATE: December 17, 2003

RFA Number: RFA-CA-05-004 (This RFA has been reissued, see RFA-CA-06-004)
(see NOT-CA-04-013)

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Cancer Institute (NCI)
(http://www.nci.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.392, 93.393, 93.394,
93.395, 93.396.

LETTER OF INTENT RECEIPT DATES: January 16, 2004; May 17, 2004; September 17,
2004

APPLICATION RECEIPT DATES: February 17, 2004; June 17, 2004; October 18, 2004

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirement
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The National Cancer Institute (NCI) invites applications for research
projects involving the development and significant enhancement or adaptation
of sample preparation methodologies and technologies, the development of
assays to assess sample quality, and studies designed to elucidate the
criteria by which to judge sample quality. The outcome will be products and
methods designed to optimize sample utility. Samples may originate from
residual material not necessary for patient care or from cell lines, model
organisms, or other sources relevant to cancer research.

The development of new and/or improved cancer sample preparation
methodologies and technologies, the development of assays to assess sample
quality, and studies to elucidate the criteria needed to judge sample quality
covers a wide range of project sizes and innovation levels. This RFA will
allow the submission of applications involving R21, R21/R33, and R33
mechanisms. R21 applicants may propose small, highly innovative feasibility
studies or small, short-term exploratory studies to meet one of the RFA
goals. R21/R33 applicants should propose projects that require a small
feasibility study followed by a well-defined development plan. Successful
completion of the R21 feasibility study and the resulting transition to the
R33 phase will be judged by NCI staff per NCI R21/R33 policy. Projects for
which feasibility has already been established may be proposed as R33
applications. Feasibility means that some preliminary experiments have been
performed and that there is sufficient technical data to support proof-of-
principle of the technology/hypothesis.

This initiative is part of a broader technology development program within
the NCI. That program underscores the desire of NCI to develop and integrate
novel technologies focused on the molecular analysis of cancers and their
micro-environment in support of cancer research, diagnosis, and treatment.
In the research continuum of discovery, development, and delivery, this
program thus emphasizes the link between development and delivery. This
specific initiative aims to foster the development of sample preparation
techniques and methodologies that are essential for effective research,
technology development, and validation that will eventually lead to clinical
applications.

This RFA capitalizes on both the success and intent of the original NCI
sponsored Innovative Molecular Analysis Technologies (IMAT) program in
bringing together a multi-disciplinary group of scientists and engineers to
work on cancer and the expansion of interest in technology development across
the NCI and other NIH institutes. This continuation of the IMAT program
consists of the following three initiatives: Innovative Technologies for the
Molecular Analysis of Cancer; Innovations in Cancer Sample Preparation; and
Application of Emerging Technologies for Cancer Research. This RFA is
designed to support research focused on sample preparation methods. Projects
focused on the development of novel technologies may be most suitable for
RFA CA-05-002, Innovative Technologies for the Molecular Analysis of Cancer
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-002.html). Projects
focused on evaluating emerging technologies that are ready for initial
clinical or biological application in cancer research may be most suitable
for RFA CA-05-003, Application of Emerging Technologies for Cancer Research
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-003.html).
Applicants from small businesses are encouraged to submit applications to the
parallel RFA for each IMAT initiative, which utilizes the SBIR and STTR grant
mechanisms (see MECHANISMS OF SUPPORT).

RESEARCH OBJECTIVES

Background

High quality sample preparations are the foundation for effective technology
validation as well as for meaningful biological and clinical research.
Sample preparation covers the spectrum from preparation of molecules to cells
to tissues. Preparation of the highest quality samples can be hampered by
technical issues, lack of standards by which to judge quality, and lack of
standard practices. Sample preparation methods vary. Researchers often
develop sample preparation methodologies in an ad hoc fashion as part of
other projects. This lack of information and standardization affects the
quality and comparability of data across all fields of cancer research and
across all technological platforms.

Objectives and Scope

Sample preparation methods and technologies may be developed for sample
collection, processing, isolation, storage, purification, preservation, and,
in the case of stored tissues, reversal of adverse events resulting from
storage and preservation. Methods may be for preparation of molecules,
fluids, tissues, or any other samples necessary for cancer research.
Researchers may propose to develop methods to isolate cells or sub-cellular
components, such as classes of molecules, organelles, or sub-cellular
structures. They may propose to isolate specific classes of molecules, such
as membrane-bound proteins. They may also propose studies to determine the
effects of collecting, processing, and storage on molecular components of
interest in stored specimens. The goal is to develop products and
methodologies that maximize the quality and utility of samples for research
and, in the case of human specimens, maximize the quality of the samples for
research and clinical needs without compromising patient care.

Sample preparation methods may impact the results or interpretation of
biological studies. Investigators may apply different methods of sample
preparation using the same measurement technology. In many cases of
measuring biological response, no gold standard exists by which to compare
research results obtained from the different sample preparation methods.
There is a need for methods to assess the quality of samples prepared using
different methodologies. This RFA will support methods to assess sample
quality and studies that elucidate the criteria needed to judge sample
quality under different conditions. This RFA will also support the
development of technologies to make these assessments, such as the
development of sample reference materials that can be used to calibrate the
effectiveness of new fixatives or new detection methodologies.

It is expected that many investigators who developed successful cancer sample
preparation techniques under previous IMAT initiatives or under the new RFA
(Innovative Technologies for Molecular Analysis of Cancer, RFA CA-05-002)
(http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-002.html) will
propose projects for this RFA. However, this RFA is not limited to
techniques developed under the IMAT program. Investigators are encouraged to
use any sample preparation methodologies or techniques relevant to cancer.

For all projects proposed, it will be important to substantiate the ultimate
value of the innovation for analyzing samples, optimizing analysis, and/or
evaluating sample quality for the purpose of research and eventually clinical
applications. Also of importance is the potential for ultimately
transferring knowledge, technologies, and/or methodologies to other
laboratories or the clinic. 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.

MECHANISMS OF SUPPORT

This RFA will use NIH Exploratory/Developmental Research Grant (R21),
Exploratory/Developmental Phase II (R33), and the Phased Innovation Award
(R21/R33) mechanisms. Applicants will be solely responsible for planning,
directing, and executing the proposed projects. This RFA is a one-time
solicitation. Future unsolicited, competing-continuation applications based
on this project will compete with all investigator-initiated applications and
will be reviewed according to the customary peer review procedures. The
anticipated award date is seven to nine months after the receipt date.
Applications that are not funded in the competition described in this RFA may
be resubmitted as amended applications for the receipt dates listed in this
RFA and its future issuances, if any.

This RFA uses just-in-time concepts. It also uses both the modular budgeting
as well as the non-modular budgeting formats (see
http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if
you are submitting an application with direct costs in each year of $250,000
or less, use the modular budget format. Otherwise, follow the instructions
for non-modular budget research grant applications. This program does not
require cost sharing as defined in the current NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

The total project period for an application submitted in response to this RFA
may not exceed the following durations: R21, 2 years; R33, 3 years; combined
R21/R33 application, 4 years. In the combined application, the R21 phase
cannot extend beyond 2 years.

For R21 and 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. 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, and to
discuss programmatic adherence of the proposed project to the RFA guidelines.
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 phases as one
application.

2. Minimal or no funding gap between R21 and R33 grants. 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.

An R21/R33 application must contain, within the R21 phase, well-defined
quantitative milestones that will be used to judge the success of the proposed
research, as well as a credible plan for the pilot application of the proposed
technology in the R33 phase. These must be presented in a section labeled
Milestones at the end of the Research Plan of the R21 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, should also be
presented in this section.

This program will run in parallel with a program of identical scientific scope
RFA CA-05-008 that will utilize the Small Business Innovation Research (SBIR,
R43 and R44) and Small Business Technology Transfer (STTR, R41 and R42)
mechanisms.

FUNDS AVAILABLE

NCI intends to commit approximately $1,000,000 in FY 2005 to fund four to
eight new and/or competitive continuation grants in response to this RFA. An
applicant may request a project period of up to two years for an R21, up to
three years for an R33, and up to four years for a combined R21/R33 of which
the R21 portion may be no more than 2 years. An applicant may request a
budget for direct costs of up to $100,000 per year for R21 and the R21
portion of R21/R33 applications. Budgets for R33 and the R33 portion of
R21/R33 grant applications should be appropriate for the science proposed.
Because the nature and scope of the proposed research will vary from
application to application, it is anticipated that the size and duration of
each award will also vary. Although the financial plans of the NCI provide
support for this program, awards pursuant to this RFA are contingent upon the
availability of funds and the receipt of a sufficient number of meritorious
applications.

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign institutions/organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.

SPECIAL REQUIREMENT

An annual meeting of all investigators funded through this program will be
held to share progress and research insights that may lead to 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.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into four
areas: scientific/research, intellectual property, peer review, and
financial or grants management issues:

o Direct your questions about scientific/research issues to:

Gregory J. Downing, D.O., Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
Building 31, Room 10A52
Bethesda, MD 20892
Telephone: (301) 496-1550
FAX: (301) 496-7807
Email: downingg@mail.nih.gov

o Questions regarding intellectual property management plans should be
directed to:

Wendy Patterson, J.D.
National Cancer Institute
Technology Transfer Branch
6120 Executive Boulevard, EPS Room 450
Bethesda, MD 20892-8329
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-0477
Email: pattersw@mail.nih.gov

o Direct your questions about peer review issues to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

o Direct your questions about financial or grants management matters to:

Ms. Catherine Blount
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda, MD 20892-7150
Rockville, MD 20852 (express/courier service)
Telephone: 301-496-3179
Fax: 301-496-8601
Email: blountc@mail.nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA

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 at least one month prior to the targeted
receipt date. The receipt dates and respective letter of intent dates are
listed at the beginning of this document. The letter of intent should be
sent to:

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). Applications must have a Dun and
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the
Universal Identifier when applying for Federal grants or cooperative
agreements. The DUNS number can be obtained by calling (866) 705-5711 or
through the web site at http://www.dunandbradstreet.com/. The DUNS number
should be entered on line 11 of the face page of the PHS 398 form. The PHS
398 document is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone: (301) 710-0267, Email: GrantsInfo@nih.gov.

SUPPLEMENTARY INSTRUCTIONS

SPECIFIC INSTRUCTIONS FOR PREPARING THE COMBINED R21/R33 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.

The R21/R33 application must include the specific aims for each phase and the
quantitative feasibility milestones that would, if successfully completed,
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, quantitative, and scientifically
justified. For funded applications, completion of the R21 negotiated
milestones (potentially modified in the light of peer review and further
discussion with the Program Director to whom the application is assigned) 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 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 Table of Contents form
page in the PHS 398 instructions 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 combined sections a-d and milestones for the R21 phase and sections a-d
for the R33 phase.

In preparing the R21/R33 application, investigators should consider the fact
that applications will be assigned a single priority score. In addition, the
initial review panel has the option of recommending only the R21 phase for
support. However, an R21/R33 application with an R33 Phase that is so
deficient in merit that it is not recommended for support will reflect upon
the judgment of the applicant. For these reasons, the clarity and
completeness of the R21/R33 application with regard to specific goals, and the
quality of the feasibility milestones for the R21 phase, are critical. The
presentation of milestones that are judged not to be sufficiently
scientifically rigorous for assessing progress in the R21 phase will reflect
upon the scientific judgment of the applicant.

1. Face Page of the application:

Item 2. Check the box marked YES and type the number and title of this
request for applications. Also indicate if the application is an R21 only, a
combined R21/R33, or an 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 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, both R21 and R33 years, in item 8a

2. Page 2 - Description:
As part of the description, identify concisely and completely 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 contain a modular budget for the
Initial Budget Period (form page 4), for each of the initial years of the R21
and R33 phases (or a detailed budget for R33 years that exceed $250,000 direct
costs), 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.

4. Research Plan:

Item a: Specific Aims

The applicant 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 RFA is to support the pilot application of innovative
technologies, hypothesis testing per se may not be the driving force in
developing such an application 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 phase and
the 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 are essential. In particular,
studies pursuing comprehensive analyses may result in hypothesis generation
rather than hypothesis testing.

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, quantitative, and scientifically justified and they should 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 should be provided.
The page number of the milestones 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 grant 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 PREPARING THE R21 APPLICATION (WITHOUT AN R33 PHASE)

Item d: Research Design and Methods

Follow the instructions in the PHS 398 booklet. In addition to sections a-d,
a one page section entitled Technical Vision should be included describing the
potential application of the proposed technology.

The R21 application must also include the quantitative feasibility milestones
that, when accomplished, would justify a future continuation to an R33 phase.

The milestones and Technical Vision sections must be contained within the
standard 25 page limit for sections a-d text for an R21 application.

Applications lacking these sections, as determined by the NCI program staff,
will be returned to the applicant without review.

SPECIFIC INSTRUCTIONS FOR PREPARING THE R33 APPLICATION (WITHOUT AN 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 the items below.

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. Research Plan:

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 applicant must clearly describe how the
exploratory/developmental study is ready to be scaled up to an expanded
application stage. In the event that an applicant feels that the technology
is too proprietary to disclose, the applicant must at a minimum 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.

INTELLECTUAL PROPERTY MANAGEMENT PLAN: Certain research plans will require
collaboration and coordination between investigators at different
institutions, some of whom may not be NIH funding recipients and who may have
pre-existing intellectual property obligations to third parties. It is
anticipated that commercial embodiments of the results of such research may
incorporate single inventions shared by several institutions, or multiple
inventions each from a separate institution. Therefore, prior to funding,
R33 grant applicants must address how they will coordinate patent prosecution
and licensing activities, if necessary to enable a licensee to access the
bundle of intellectual property needed to take a product to market on
commercially viable terms. Suggested strategies include: (1) assigning
intellectual property rights to related inventions to an invention management
firm; (2) designating one organization to take the lead on patenting and
licensing related inventions; and (3) agreeing in advance that if multiple
parties are to independently license related inventions, the total of stacked
royalties will not exceed a predetermined percentage rate.

The technology transfer/intellectual property management/licensing officer or
equivalent of the principal investigator’s institution is to submit an
intellectual property management plan including at least those elements
above. Alternatives to the suggested strategies, which accomplish the same
goals, will be considered. Intellectual property management plans are a
just-in-time requirement; it is not necessary to include the plan in the
grant application but plans will be required before an R33 grant can be
awarded.

The applicant’s institution should avoid exclusively licensing those
inventions that are research tools, unless either: (1) the field of use of
the exclusive license is restricted to commercial use, or (2) the exclusive
licensee will make the research tool available on reasonable terms.
Applicants are directed to the NIH policy on the dissemination of biological
research resources ( research tools ), which can be found at
http://www.ott.nih.gov/policy/rt_guide_final.html.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting
up to $250,000 per year in direct costs must be submitted in a modular grant
format. The modular grant format simplifies the preparation of the budget in
these applications by limiting the level of budgetary detail. Applicants
request direct costs in $25,000 modules. Section C of the research grant
application instructions for the PHS 398 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step
guidance for preparing modular grants. Additional information on modular
grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001)
application form must be affixed to the bottom of the face page of the
application. Type the RFA number on the label. Failure to use this label
could result in delayed processing of the application such that it may not
reach the review committee in time for review. In addition, the RFA title
and number must be typed on line 2 of the face page of the application form
and the YES box must be marked. The RFA label is also available at:
http://grants.nih.gov/grants/funding/phs398/labels.pdf.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the Checklist, and three signed photocopies in one
package to:

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

At the time of submission, two additional copies of the application and all
copies of the appendix material must be sent to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Rockville, MD 20852 (for express/courier service)

Appendices should be comprised of single-sided, unbound materials, with
separators between documents.

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE
WILL NO LONGER BE ACCEPTED. This policy does not apply to courier deliveries
(i.e., FEDEX, UPS, DHL, etc.)
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html).
This policy is similar to and consistent with the policy for applications
addressed to Centers for Scientific Review as published in the NIH Guide
Notice (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html).

APPLICATION PROCESSING: Applications must be received on or before the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the applicant
without review.

Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and funding
assignment within 8 weeks.

The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application. This
does not preclude the submission of a substantial revision of an unfunded
version of an application already reviewed, but such an application must
include an Introduction addressing the previous critique. An application
through this RFA that is unsuccessful may be resubmitted as amended at the
next subsequent receipt date.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NCI. Incomplete and/or non-responsive applications
will not be reviewed.

Applications that are complete and responsive to the RFA will be evaluated
for scientific and technical merit by an appropriate peer review group
convened by the Division of Extramural Activities of the NCI in accordance
with the review criteria stated below. As part of the initial merit review,
all applications will:

o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications under
review, will be discussed and assigned a priority score;
o Receive a written critique; and
o Receive a second level review by the National Cancer Advisory Board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to evaluate the application in
order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals. The scientific review
group will address and consider each of the following criteria in assigning
the application’s overall score, weighting them as appropriate for each
application.

o Significance
o Approach
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be judged
likely to have major scientific impact and thus deserve a high priority
score. For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field
forward.

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?

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?

INNOVATION: Does the project employ novel concepts, approaches or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

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)?

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 REVIEW CRITERIA: In addition to the above criteria, the following
items will be considered in the determination of scientific merit and the
priority score:

MILESTONES: In the cases of R21 alone and R21/R33 applications, are
appropriate and quantitative scientific milestones included that will show,
when completed by the end of the R21 period, whether or not the project has
shown feasibility to pursue the R33 portion of the project?

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human
subjects and protections from research risk relating to their participation
in the proposed research will be assessed. (See criteria included in the
section on Federal Citations, below.)

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups
(and subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria in the sections on
Federal Citations, below.)

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to
be used in the project, the five items described under Section f of the PHS
398 research grant application instructions (rev. 5/2001) will be assessed.

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of the
proposed research must include a data sharing plan in their application. The
reasonableness of the data sharing plan or the rationale for not sharing
research data will be assessed by the reviewers. However, reviewers will not
factor the proposed data sharing plan into the determination of scientific
merit or priority score.

BUDGET: The reasonableness of the proposed budget and the requested period
of support in relation to the proposed research will be assessed after the
determination of the priority score.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Dates: January 16, 2004; May 17, 2004; September 17,
2004

Application Receipt Dates: February 17, 2004; June 17, 2004; October 18,
2004

Peer Review Dates: June 2004; November 2004; March 2005

Council Reviews: September 2004; February 2004; June 2005.

Earliest Anticipated Start Dates: December 2004; April 2005; July 2005.

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review);
o Availability of funds; and
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and
others, and the importance of the knowledge gained or to be gained. See
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); and efficacy,
effectiveness and comparative trials (phase III). The establishment of data
and safety monitoring boards (DSMBs) is required for multi-site clinical
trials involving interventions that entail potential risk to the
participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for
Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html.)

Clinical trials supported or performed by NCI require special considerations.
The method and degree of monitoring should be commensurate with the degree of
risk involved in participation and the size and complexity of the clinical
trial. Monitoring exists on a continuum from monitoring by the principal
investigator/project manager or NCI program staff or a Data and Safety
Monitoring Board (DSMB). These monitoring activities are distinct from the
requirement for study review and approval by an Institutional Review Board
(IRB). For details about the Policy for the NCI for Data and Safety
Monitoring of Clinical trials see:
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. For Phase I and II
clinical trials, investigators must submit a general description of the data
and safety monitoring plan as part of the research application. See NIH
Guide Notice on Further Guidance on a Data and Safety Monitoring for Phase I
and II Trials for additional information:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.
Information concerning essential elements of data safety monitoring plans for
clinical trials funded by the NCI is available:
http://www.cancer.gov/clinical_trials/.

SHARING RESEARCH DATA: Starting with the October 1, 2003, receipt date,
investigators submitting an NIH application seeking $500,000 or more in
direct costs in any single year are expected to include a plan for data
sharing or state why this is not possible
(http://grants.nih.gov/grants/policy/data_sharing). Investigators should
seek guidance from their institutions, on issues related to institutional
policies, local IRB rules, as well as local, state, and Federal laws and
regulations, including the Privacy Rule. Reviewers will consider the data
sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of
the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research -
Amended, October, 2001," published in the NIH Guide for Grants and Contracts
on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable;
and b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported
by the NIH, unless there are scientific and ethical reasons not to include
them. 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 is available at
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH proposals for research involving human
subjects. You will find this policy announcement in the NIH Guide for Grants
and Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. A
continuing education program in the protection of human participants in
research is available online at: http://cme.nci.nih.gov/.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research
on hESCs can be found at http://stemcells.nih.gov/index.asp and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only
research using hESC lines that are registered in the NIH Human Embryonic Stem
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide, in the project
description and elsewhere in the application as appropriate, the official NIH
identifier(s) for the hESC line(s) to be used in the proposed research.
Applications that do not provide this information will be returned without
review.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope
of this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The
Department of Health and Human Services (DHHS) issued final modification to
the Standards for Privacy of Individually Identifiable Health Information ,
the Privacy Rule, on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable
health information, and is administered and enforced by the DHHS Office for
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified
under the Rule as covered entities ) must do so by April 14, 2003 (with the
exception of small health plans which have an extra year to comply).

Decisions about applicability and implementation of the Privacy Rule reside
with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including
a complete Regulation Text and a set of decision tools on Am I a covered
entity? Information on the impact of the HIPAA Privacy Rule on NIH
processes involving the review, funding, and progress monitoring of grants,
cooperative agreements, and research contracts can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This
RFA is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284)
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All
awards are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement. The NIH Grants
Policy Statement can be found at
http://grants.nih.gov/grants/policy/policy.htm.

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

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NIH Funding Opportunities and Notices