PROTEOMIC AND METABOLOMIC APPROACHES TO DIAGNOSE DIABETES AND PRE-DIABETES
RELEASE DATE: March 18, 2004
PA NUMBER: PAR-04-076 (see addendum NOT-DK-04-008)
Department of Health and Human Services (DHHS)
EXPIRATION DATE: July 21, 2004
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov/)
COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov/)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.847
LETTER OF INTENT RECEIPT DATE: June 18, 2004
APPLICATION RECEIPT DATE: July 20, 2004
THIS PAR CONTAINS THE FOLLOWING INFORMATION
o Purpose of this PAR
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
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 PAR
Over 5 million adults in the U.S. have undiagnosed type 2 diabetes, and
another 38 million with pre-diabetes are at increased risk for developing
diabetes. The lack of a simple and reliable way to detect diabetes and pre-
diabetes has hindered identification of these individuals and provision of
effective therapies. The National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) encourages the application of proteomic and other
novel technology to develop new diagnostic tests and/or to identify new
biomarkers for the diagnosis of pre-diabetes and/or diabetes that do not
require fasting or glucose administration.
RESEARCH BACKGROUND AND OBJECTIVES
Diabetes is a metabolic disease characterized by hyperglycemia that in 2002
affected nearly 9% of U.S. adults. Over 90% of the people with diabetes have
type 2 diabetes. The symptoms of type 2 diabetes develop gradually. Some
people have no symptoms until after they develop complications, which could
have been prevented or delayed with early diagnosis and effective treatment.
Additionally, 38 million U.S. adults aged 40-74 have pre-diabetes. Pre-
diabetes is defined as impaired fasting glucose or impaired glucose tolerance
(http://www.diabetes.org/diabetes-prevention/pre-diabetes.jsp). These
individuals have glucose levels above normal but below the level needed for
diagnosis of diabetes. They are at increased risk of cardiovascular disease
compared to those with normal glucose tolerance and at substantial risk for
developing diabetes.
Clinical trials have demonstrated effective interventions for preventing or
delaying complications in those with diabetes and for preventing or delaying
onset of diabetes in those with pre-diabetes. However, millions of Americans
are not receiving effective therapy, in part due to the limitations of
current methods of diagnosing diabetes and pre-diabetes. The oral glucose
tolerance test (OGTT), the gold standard for diagnosis of diabetes and pre-
diabetes is inconvenient requires fasting and is not highly reproducible. The
fasting blood glucose (FBG) is less burdensome but much less sensitive,
particularly in older Americans who have the highest prevalence of diabetes
and pre-diabetes. The quantitation of Hemoglobin A1c (a glycated form of
hemoglobin) from blood has been widely used as test for assessing the
adequacy of glycemic control and risk of complications in diabetic patients,
but this test is not sufficiently sensitive to detect the range of glucose
values typically seen in pre-diabetes or new onset type 2 diabetes.
Furthermore, there are many variants of hemoglobin present in blood,
particularly in minority populations disproportionately affected by diabetes,
and this adds additional uncertainty to the use of this test.
A simplified, less burdensome approach to the diagnosis of diabetes and pre-
diabetes would facilitate increased recognition and improved care of these
conditions. Many proteins and other blood components may be modified in
individuals with elevated blood glucose. Identification of these molecules
or of identifiable correlates of hyperglycemia would facilitate development
of potential new laboratory tests for diagnosis of diabetes and pre-diabetes.
With this initiative we are encouraging scientists with expertise in
proteomics and metabolomics to develop new tests to detect pre-diabetes and
diabetes that correlate with the results of the OGTT but do not require
fasting or administration of glucose.
Proteomic and metabolomic approaches have been successfully used for studying
complex biological problems and for the identification of disease markers.
Recent developments indicate that these technologies could be used or
appropriately modified for developing new methods to diagnose diabetes and
pre-diabetes. For example mass spectrometry has been successfully used for the
identification and quantitation of large number of proteins from plasma.
Similar studies were performed for quantifying large number of metabolites. In
some cases fractionation prior to the mass spectrometric analysis was shown to
be very effective for increasing the number of proteins and metabolites that
could be identified and perhaps further development in fractionation
methodologies could be the key for the identification of novel biomarkers. The
use of isotopically labeled reagents recently made many proteomic
methodologies usable for quantitative studies and further development of these
reagents might also lead to a more comprehensive analysis of the sera proteome
and possible identification of novel biomarkers.
This initiative solicits the application of proteomic and metabolomic
technologies for the development of novel methodologies and/or identification
of new biomarkers for the diagnosis of pre-diabetes and of type 2 diabetes
that do not require fasting or glucose administration. To facilitate this
effort, plasma from well-characterized individuals of diverse racial and
ethnic backgrounds with normal glucose tolerance (NGT), impaired glucose
tolerance (IGT) and type 2 diabetes will be made available to investigators
for validation of potential new diagnostic tests.
The novel diagnostic test could ultimately be used in place of the OGTT, if
adequately validated, or for the identification of high-risk individuals who
should undergo testing for diabetes and pre-diabetes using a more functional
assay such as the OGTT. Focused deployment of the OGTT in appropriately
selected individuals would reduce costs, limit burden, and improve the yield
of diagnostic testing for diabetes and pre-diabetes.
The NIDDK will make available citrated plasma and blood cell samples from
individuals with normal glucose tolerance, impaired glucose tolerance and
newly diagnosed type 2 diabetes for use in the R21 and for the R33 phases to
all awardees. Applicants should specify how these samples will be used to
identify and validate new biomarkers that can distinguish among these
conditions.
The NIDDK will provide the following samples to all awardees of the R21 phase:
o 1ml (4X250 l) of sera from 10 patients with normal glucose tolerance (NGT)
o 1ml (4X250 l) of sera from 10 patients with impaired glucose tolerance (IGT)
o 1ml (4X250 l) of sera from 10 patients with newly diagnosed type 2 diabetes
o The corresponding blood cell pellet from each NGT, IGT and diabetic patient
will also be provided. The cell pellet for each patient will not be divided in
four aliquots as for the plasma but will be provided in a single vial.
The above conditions are diagnosed using the oral glucose tolerance test
(OGTT). Briefly, after a fast of 8 to 12 hours, a person’s blood glucose is
measured before and 2 hours after drinking a glucose-containing solution.
Determination of NGT is made when glucose rises to no higher than 140 mg/dl 2
hours after the drink. IGT is diagnosed when the glucose level is between 140
and 199 mg/dl 2 hours after the drink. Diabetes is diagnosed if blood glucose
rises to 200 mg/dl or above. For clinical diagnosis of diabetes this
measurement must be confirmed on a subsequent measurement.
A similar set of samples but from a larger population will be provided for the
R33 phase at the time of the award for this phase. We expect to be able to
provide plasma and blood cell samples from approximately 200 patients with
IGT, 200 patients with NGT and 50 diabetic patients.
To be considered for the transition to the R33 phase the applicant must show
that he/she has identified differences between the pre-diabetes, diabetes, and
normal patient samples provided by NIDDK for the R21 phase (i.e. have
identified at least one potential biomarker for pre-diabetes and/or diabetes).
These differences should be determined in a reproducible (analysis in
triplicate) and quantitative way and with a throughput that shows promise for
translation to a clinical setting. In addition the investigator can include in
the proposal the use of samples from other clinical studies for optimizing or
further validating the methodology.
For the purpose of assessing research progresses and facilitating interaction
between the 4-5 funded principal investigators a workshop will be held in
May/June 2006 in Bethesda, MD. All funded principal investigators are required
to attend and collaborators are encouraged to participate. Funds for
attending this meeting should be included in the budget proposal.
MECHANISMS OF SUPPORT
This special emphasis PAR will use the NIH Exploratory/Development Research
Grant (R21) combined with the Exploratory/Development Research Grant Phase 2
(R33). The R33 is an NIH grant mechanism that provides a second phase for the
support of innovative exploratory and development research initiated under the
R21 mechanism. The transition of the R21 to the R33 phase will be expedited
and is dependent on completion of negotiated milestones. As an applicant you
will be solely responsible for planning, directing, and executing the proposed
project. This PAR is a one-time solicitation. Future unsolicited, competing-
continuation applications based on this project will have to be submitted
using a standard RO1 or R21 mechanism, will compete with all investigator-
initiated applications and will be reviewed according to the customary peer
review procedures. The anticipated award date is April 1, 2005. Applications
that are not funded in the competition described in this PAR may be
resubmitted as NEW investigator-initiated applications using the standard
receipt dates for NEW applications described in the instructions to the PHS
398 application.
This PAR uses just-in-time concepts. It also uses the modular 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 format. Otherwise follow the instructions for non-
modular research grant applications. This program does not require cost
sharing as defined in the current NIH Grants Policy Statement at
http://odoerdb2.od.nih.gov/gmac/nihgps_2003/index.htm.
Specific features of this Phased Innovation Award (R21/33) Program
Announcement include:
o The total project period for an application in response to this PAR may not
exceed 2 years for the R21 phase and 3 years for the R33 phase.
o Single submission and evaluation of both a feasibility/pilot phase (R21) and
an expanded development phase (R33) as one application.
o Expedited transition of the R21 feasibility phase to an R33 development
phase. However, the award of the R33 funds will be based on program
priorities, the availability of funds and the successful completion of
negotiated scientific milestones as determined by program staff in the context
of peer review recommendations
o Responsibility for the planning, direction and execution of the proposed
research project will be solely that of the applicant. Except as otherwise
stated in this PAR, awards will be administered under the NIH grants policy
as stated in the NIH Grants Policy Statement, December 2003, available from
the internet only at http://odoerdb2.od.nih.gov/gmac/nihgps_2003/index.htm.
o 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 the completion of the R21 portion 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 the milestones for the proposed R33
study.
FUNDS AVAILABLE
The NIDDK intends to commit approximately $1 million in direct cost for FY
2005 to fund 4 to 5 new grants in response to this PAR. An applicant may
request a project period of 2 years for the R21 phase and 3 years for the R33
phase. The R21 phase may not exceed $250,000 direct costs per year. The R21
budgets can exceed this cap to accommodate F&A costs to subcontracts to the
project, in which case a non-modular budget format must be used. The R33
application has a budgetary limit of $500,000 direct costs for each year. This
limit cannot be exceeded to accommodate F&A to subcontracts. Awards pursuant
to this PAR 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 REQUIREMENTS
Applicants from institutions, which have a General Clinical Research Center
(GCRC) funded by the NIH National Center for Research Resources, may wish to
identify the GCRC as a resource for conducting the proposed research. In such
a case, a letter of agreement from either the GCRC program director or
principal investigator should be included with the application.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this PAR and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into three
areas: scientific/research, peer review, and financial or grants management
issues:
o Direct your questions about scientific/research issues to:
Salvatore Sechi, Ph.D.
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd. Rm. 611
Bethesda, MD 20892-5460
Telephone: (301) 594-8814
FAX: (301) 480-2688
E-mail: ss24q@nih.gov
o Direct your questions about peer review issues to:
Francisco O. Calvo, Ph.D.
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 752
Bethesda, MD 20892-5452
Telephone: (301) 594-8897
FAX: (301) 480-3505
E-mail: fc15y@nih.gov
o Direct your questions about financial or grants management matters to:
Ms. Kathleen Shino
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Rm.708
Bethesda, MD 20892-5460
Telephone: (301) 594-8869
FAX: (301) 594-9523
E-mail: ks48e@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 PAR
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 IC staff to estimate the potential review workload and plan
the review.
The letter of intent is to be sent by the date listed at the beginning of this
document. The letter of intent should be sent to:
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8885
FAX: (301) 480-3505
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.
The title and number of this program announcement must be typed on line 2 of
the face page of the application form and the YES box must be checked.
SUPPLEMENTARY INSTRUCTIONS:
I. SPECIFIC INSTRUCTIONS FOR PREPARING THE COMBINED R21/R33 PHASED INNOVATION
AWARD APPLICATION:
The R21/R33 application must include the specific aims for each phase and
clear measurable goals (milestones) that would demonstrate feasibility and
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
and not simply a restatement of the specific aims. 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.
The Milestones section should be indicated in the Table of Contents.
Applications lacking this information, as determined by the NIH program staff,
will be returned to the applicant without review. For funded applications,
completion of the R21 milestones will elicit an NIH 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 combined applications 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 of
all applications (i.e., section a-d and milestones for the R21 phase plus
sections a-d for the R33 phase must be contained within the 25 page limit for
R21/R33 applications.)
In preparing the R21/R33 application, investigators should consider the fact
that applications will be assigned a single priority score. For this reason,
the clarity and completeness of the 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 judgment
of the applicant in this application.
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 $250,000 per year for a maximum of two years and the
award may not be used to supplement an ongoing project. The non-modular budget
format must be used for the combined R21/R33 application. The requested
budgets can exceed this cap to accommodate for F&A costs to subcontracts to
the project only for the R21 phase. Insert the first year of R21 support in
item 7a.
Item 8a, DIRECT COSTS REQUESTED FOR PROPOSED PERIOD OF SUPPORT.
Insert sum of all years of requested support in item 8a.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 research team, the
fundamental research to be performed or the technology/tool to be developed,
its innovative nature, its relationship to presently available knowledge or
capabilities, and its expected impact on the diagnosis, treatment or
prevention of type 2 diabetes or its complications.
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 justification for each item requested.
Funds for attending a meeting in May/June 2006 in Bethesda, MD should be
included in the budget proposal.
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. Furthermore for the R21 phase, preliminary data are not required,
although they should be included when available.
The applicant must include a plan for analyzing the samples provided by NIDDK
for the R21 and for the R33 phase (see research background and objectives
section at the beginning of this PAR). The applicant might also include a plan
for the analysis of additional samples from other patients but a plan for
analyzing the samples provided by NIDDK is the minimum requirement.
Similarly, one of the milestones must be the identification of a potential
biomarker for pre-diabetes and/or diabetes using the samples provided by
NIDDK. The investigator can include additional milestones. For examples,
additional milestones could be related to methodology developments or to the
analysis of samples from other patients.
Item b, Background and Significance:
Elaborate on the innovative nature of the proposed research. Clarify how the
fundamental research or tools/technologies to be developed as proposed in this
project will result in a significant improvement over existing approaches.
Explain the potential of the proposed studies for having a broad impact on a
compelling area of type 2 diabetes research. Clearly identify how the project,
if successful, would result in new capabilities for the treatment and
prevention of type 2 diabetes and its complications.
Item c, Preliminary Studies/Progress Report:
While preliminary data are not required for the submission of the R21 phase,
this section should provide current thinking or evidence in the field to
substantiate the feasibility of the R33 phase. While preliminary data are not
required for submission of the R21 phase, easily understandable data that
provide relevant information to aid the review should be included when
available. The R33 phase need not repeat information already provided in the
R21 phase.
Item d, Research Design and Methods:
Follow the instructions in the PHS 398 booklet. In addition a specific
section labeled Milestones must follow the Research Design and Methods section
of the R21 phase. Milestones should be well described, quantifiable, and
scientifically justified and not be simply a restatement of the specific aims.
The milestones should not be a reiteration of the Specific Aims of the
research project, but should be tangible accomplishments. 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.
For funded applications, completion of the R21 milestones will elicit an
Institute 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.
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
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:
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
APPLICATION PROCESSING: Applications must be received on or before the
application receipt date listed in the heading of this PAR. 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 PAR 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 a substantial
revision of an unfunded version of an application already reviewed, but such
application must include an Introduction addressing the previous critique.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIDDK. Applications lacking the milestones section and
description, as indicated in the Supplementary instruction section of this
PAR, will not be reviewed. Incomplete and/or non-responsive applications will
not be reviewed. Applications that are complete and responsive to the PAR will
be evaluated for scientific and technical merit by an appropriate peer review
group convened by the NIDDK 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
o Receive a second level review by the National Diabetes and Digestive and
Kidney Advisory Council.
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: Are 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:
The initial review group will evaluate the specific goals for each phase and
the feasibility of the milestones that would justify expansion to the R33
phase. The initial review group will evaluate how appropriate, realistic and
quantifiable the proposed research milestones are, and whether the milestones
are adequate for the demonstration and feasibility for transition to the R33
development phase. The initial review group will also assess the timeframe
for achieving the milestones and whether they are appropriate. 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.
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. 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 CONSIDERATIONS
BUDGET: The reasonableness of the proposed budget and the requested period of
support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: June 18, 2004
Application Receipt Date: July 20, 2004
Peer Review Date: October/November 2004
Council Review: February 2005
Earliest Anticipated Start Date: April 1, 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
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.
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); 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).
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 are 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.
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 PAR 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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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