and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National
Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National
Center for Complementary and Alternative Medicine (NCCAM), (http://nccam.nih.gov)
Office of Dietary Supplements (ODS), (http://dietary-supplements.info.nih.gov)
Title: Probiotics for Pediatric Illnesses (R21)
Announcement Type
This is a
reissue of PA-05-035 which was previously released December 28, 2004.
Update: The following update relating to this announcement has been issued:
NOTICE: Applications submitted in response to this FOA for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).
A registration process is necessary before submission and applicants are highly encouraged to start the process at least 4 weeks prior to the grant submission date. See Section IV.
Two steps are required for on time submission:
1) The application must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the submission date (see Key Dates below).
2) Applicants must complete a verification step in the eRA Commons within 2 business days of notification from NIH. Note: Since e-mail can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.
Program Announcement (PA) Number: PA-06-316
Catalog of Federal Domestic Assistance Number(s)
93.213
Key Dates
Release/Posted Date: April
5, 2006
Opening
Date: May 2, 2006 (earliest date an application may be submitted to Grants.gov).
Application Submission Date(s): See http://grants.nih.gov/grants
funding/submissionschedule.htm
Peer
Review Date(s): See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s):See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s):See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (Url
Activation Date): Not
applicable
Expiration Date: November 2, 2007 (now January 8, 2008 per NOT-OD-07-093)
Due
Dates for E.O. 12372
Not applicable
Additional Overview
Content
Executive Summary
Table of Contents
Part I
Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity
Description
1. Research Objectives
Section II. Award Information
1. Mechanism of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and
Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review and
Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the
NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review
Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review
Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration
Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information
- Required Federal Citations
Part II
- Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
The purpose of this Funding Opportunity Announcement (FOA) is to provide support for pilot research on mechanism(s) of action, safety and efficacy of probiotics, as well as for more robust probiotic intervention studies for the prevention and treatment of pediatric illnesses for which more convincing preliminary data are available.
The NIH defines children as individuals under the age of 21. While the intent of this FOA is to focus on conditions unique to or prevalent in children, studies of individuals aged 21 or over may be justified as a precursor to studies in children.
Probiotics are defined as microorganisms that when administered in sufficient quantities may improve health. Prebiotics (nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of bacterial species already established in the colon) and synbiotics (mixtures of pro- and prebiotics) are distinct from probiotics and not the focus of this FOA. However, their inclusion in studies focused on probiotics is acceptable.
Background
Use and Efficacy:
Probiotics have traditionally been thought to be useful in the treatment of various gastrointestinal diseases. One of the primary areas of research in children has been in the treatment and prevention of diarrhea, e.g., antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, rota-viral diarrhea, and traveler's diarrhea). Some studies in adults show a reduction of symptoms associated with irritable bowel syndrome. Newer areas of research include systemic immune responses (including atopic eczema) that accompany food-related allergies in children. In addition, there is some evidence that probiotics enhance antibody response to vaccines, and decrease occurrence of respiratory and ear infections. Other potential indications for use in children include the treatment of inflammatory bowel disease, necrotizing enterocolitis, small bowel bacterial overgrowth, juvenile rheumatoid arthritis, and vaginitis, as well as the prevention of mother-baby transmission of HIV, recurrent urinary tract infections and tumors preceding the development of cancer.
Common side effects of oral antibiotics relate to the intestinal tract and include nausea, abdominal cramps, diarrhea, and loose stools. Published studies of children receiving probiotics concurrent with antibiotics report reduction of the intestinal side effects. The effects of probiotics in minimizing the nutritional and intestinal side effects of antibiotics used in treating or preventing infections, including ones associated with bioterrorism, are not known.
Safety:
Some microorganisms have a long history of use as probiotics without established risk to humans. Nevertheless, probiotics may theoretically be responsible for: (1) systemic infections; (2) deleterious metabolic activities; (3) excessive immune stimulation in susceptible individuals; or (4) gene transfer. Probiotic organisms may be inherently resistant to antibiotics, and the concern has been raised that probiotics might transfer drug-resistance genes to pathogenic microbes.
Administration:
Careful consideration should be given to the matrix in which probiotics are administered, whether one provides viable or inactivated organisms, and the dosage and schedule of administration, as these may impact critically on efficacy and/or safety. Probiotics can be administered orally as dietary supplements and in yogurt, fermented and unfermented milk, infant formula, bacterial lyophilizates, juices, and even candy. They may be applied topically and as suppositories. Probiotics in dietary supplements or foods may be live, heat treated, irradiated, spray dried, or freeze dried. Inactivated probiotics may be as effective as live probiotics in certain conditions and may be favorable because of lower risks (especially in infants whose gut defense barrier is immature). The best possible way to administer probiotics and the appropriate dose for each probiotic organism for its intended use are understudied. For example, some areas of controversy and lack of data include: (1) the impact of administration in different parts of the life-cycle or in infants vs. mothers late in pregnancy; (2) the impact of administration in food vs. as a dietary supplement; and 3) the effect of continuous (every day for a defined period of time) vs. pulsed (few days on, few days off, few days on, etc.) dosing.
Product Quality:
The quality of probiotics has received little attention. Quality issues for probiotic supplements can include the following: (1) the types of microorganism in the product; (2) the viability of microorganisms in the product; (3) stability of different strains under different storage conditions and in different product formats; and (4) enteric protection of the product. Viability of live organisms is an important factor, the importance of which may be different in different situations. In vitro test protocols can be readily adopted to examine the maintenance of a strain's ability to tolerate acidic conditions, survive and grow in the presence of bile, and metabolize selective substrates (e.g., carbohydrate and protein utilization patterns). Molecular techniques are also available to examine strain identity and stability.
Mechanisms of Action:
Human studies have been undertaken with probiotic strains without an understanding of mechanism of action related to the specific strain and the mode of administration. Different strains of probiotic bacteria may work by distinctly different mechanisms. In some cases, animal models exist to provide substantiation of in vitro effects and determination of probiotic mechanism.
Previous research into the mechanisms associated with probiotics focused on the bacteriology of the gut and concentrated on intestinal colonization and probiotic-induced suppression of pathogen growth and/or invasion. This may be accomplished by probiotic secretion or production of acids, hydrogen peroxide, antimicrobial substances, and/or bacteriocins (proteins elaborated by probiotic organisms that have specific antimicrobial effects against sensitive species) antagonistic to pathogen growth; competition for nutrients required for growth of pathogens; or competitive inhibition of adhesion of pathogens. In addition, some strains may coaggregate, persist and multiply forming normal, balanced flora. Whether colonization is critical for probiotics to have their effect remains unresolved.
More recent research has turned toward understanding the role of probiotics and their secreted products in enhancing and modulating innate and adaptive immune responses in the host by other mechanisms. They may interact with epithelial and immune cells and alter signal transduction pathways in the presence or absence of pathogenic bacteria and cytokines. Oral administration of probiotics has been shown to result in altered immunity at distant mucosal sites, including the female genital tract, the respiratory tract, the skin, and the nasal passages.
Gastrointestinal Bacteriology:
The precise qualitative and quantitative monitoring of enteric population changes has not been well addressed but seems to be a central requirement for the study of gut flora manipulation. Accurate methods for monitoring bacterial changes are absolutely essential. The simple absence or presence of probiotic strains in vivo is not sufficient to demonstrate their roles. Current genetic techniques and molecular methods may discriminate closely related bacteria and determine the constituents of complex microbiota.
A polyphasic strategy may be necessary to achieve an accurate interpretation of the gastrointestinal tract bacteriology and to understand the impact of probiotics. Approaches are needed to identify and monitor specific pathogenic or etiological agents, to study the effects of dietary intervention on bacterial populations, to demonstrate diversity, to quantify the population(s), to examine the complexity and dynamics of diverse microbiota, and to discriminate probiotic strains from commensal organisms. In addition, approaches are needed to address probiotic colonization and survival in the gastrointestinal tract after termination of exogenous supplementation.
Objectives of this FOA
Research responsive to this FOA may include, but is not limited to, the following objectives:
See Section
VIII, Other Information - Required Federal Citations, for policies related
to this announcement.
Section
II. Award Information
1. Mechanism of Support
This funding
opportunity will use the NCCAM R21 (Exploratory/Developmental
Project) award mechanisms.
The R21 awards are exploratory/developmental research grants for support of pilot and feasibility research designed to provide investigators with an opportunity to produce preliminary data in support of a larger project that may be submitted in the future as a research project (R01) grant application. Two NCCAM R21 funding mechanisms (http://nccam.nih.gov/research/instructions/r21/index.htm) are available: (1) Basic and Preclinical Research on Complementary and Alternative Medicine and (2) NCCAM Exploratory/Developmental Grant for Clinical Studies. Applicants are advised to check the website for the most current (or succeeding) NCCAM R21 announcements and to abide by the application guidance and allowable project period length and direct cost limits.
As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Applicants are encouraged to direct inquiries regarding the appropriate mechanisms to use to scientific and research staff listed in the Section VII.1. Scientific/Research Contacts.
This FOA
uses just-in-time concepts. It also uses the modular budget formats (see the
Modular Applications and Awards section of the NIH
Grants Policy Statement. Specifically, if you are submitting an
application with direct costs in each year of $250,000 or less (excluding
consortium Facilities and Administrative [F&A] costs), use the PHS398
Modular Budget component provided in the SF424 (R&R) Application Package
and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular
Budget Component, of the Application Guide).
2. Funds Available
The total
amount awarded and the number of awards will depend upon the numbers, quality,
duration, and costs of the applications received. This funding opportunity will
use the NCCAM R21 award mechanisms. The NCCAM R21 award mechanisms limit the
amount of funds that can be requested.
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 IC(s) provide support for this program, awards
pursuant to this funding opportunity are contingent upon the availability of
funds and the receipt of a sufficient number of meritorious applications.
Facilities and
Administrative (F&A) costs requested by consortium participants are not
included in the direct cost limitation. See NOT-OD-05-004, which was published in the NIH Guide.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
You may submit (an)
application(s) if your organization has any of the following characteristics:
1.B. Eligible Individuals
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 support.
2. Cost Sharing or
Matching
Not applicable. This program does not require
cost sharing as defined in the current NIH
Grants Policy Statement.
3. Other-Special
Eligibility Criteria
Applicants may submit more
than one application, provided each application is scientifically distinct. However, NCCAM R21 grants may not
be renewed. Competing continuation of projected developed under this grant
mechanism should be submitted through the R01 grant mechanism.
Section IV. Application and Submission Information
Registration and Instructions for Submission via Grants.gov
To download a SF424 (R&R) Application Package and
SF424 (R&R) SBIR/STTR Application Guide for completing the SF424 (R&R)
forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations
to make sure they are registered in the eRA Commons.
Several additional separate actions are required before an applicant
institution/organization can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Started.
2) Organizational/Institutional Registration in the eRA Commons
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.
Several of the steps of the
registration process could take 4 weeks or more. Therefore, applicants should
immediately check with their business official to determine whether their
institution is already registered in both Grants.gov and the Commons. The NIH
will accept electronic applications only from organizations that have completed
all necessary registrations.
1. Request Application Information
Applicants must download
the SF424 (R&R) application forms and SF424 (R&R) Application Guide for
this FOA through Grants.gov/Apply.
Note: Only the forms package directly attached to a specific FOA can be used.
You will not be able to use any other SF424 (R&R) forms (e.g., sample
forms, forms from another FOA), although some of the "Attachment"
files may be useable for more than one FOA.
For further assistance, contact GrantsInfo; Telephone:
301-710-0267, E-mail: [email protected].
Telecommunications for the hearing impaired: TTY 301-451-5936.
2. Content and Form of
Application Submission
Prepare all applications using the SF424 (R &R) application forms and
in accordance with the SF424 (R&R) Application
Guide (MS Word or PDF).
The SF424 (R&R) Application Guide is critical to submitting a
complete and accurate application to NIH. There are fields within the SF424
(R&R) application components that, although not marked as mandatory, are
required by NIH (e.g., the Credential log-in field of the Research &
Related Senior/Key Person Profile component must contain the PD/PI’s assigned
eRA Commons User ID). Agency-specific instructions for such fields are
clearly identified in the Application Guide. For additional information, see
Tips and Tools for Navigating Electronic Submission on the front page of Electronic
Submission of Grant Applications.
The SF424 (R &R) application is comprised of data arranged in
separate components. Some components are required, others are optional. The
forms package associated with this FOA in Grants.gov/APPLY will include
all applicable components, required and optional. A completed application in
response to this FOA will include the following components:
Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site
Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398
Modular Budget
Optional Components:
PHS398 Cover Letter File
R&R Subaward Budget Attachment(s)
Form
Note: While both budget components are included in the SF424 (R&R)
forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)
Foreign Organizations
Several special provisions apply to applications
submitted by foreign organizations:
Proposed
research should provide a unique research opportunity not available in the U.S.
3. Submission Dates and Times
See Section IV.3.A for
details.
3.A.
Submission, Review and Anticipated Start Dates
Opening Date: May 2, 2006 (earliest date
an application may be submitted to Grants.gov).
Letter
of Intent Receipt Date:
Application Submission
Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
3.A.1. Letter of Intent
A letter of intent is
not required for the funding opportunity.
3.B. Sending an
Application to the NIH
To submit an application
in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow
steps 1-4. Note: Applications must only be submitted electronically
PAPER APPLICATIONS WILL NOT BE ACCEPTED.
3.C.
Application Processing
Applications may be submitted on or after the
opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the
applicant institution/organization) on the application submission/receipt date(s). (See Section
IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the
application may be delayed in the review process or not reviewed.
Upon receipt,
applications will be transferred from Grants.gov to the NIH Electronic Research
Administration process for validation. Both the PD/PI and the SO for the
organization must verify the submission via Commons within 2 business days
of notification of the NIH validation.
Upon receipt,
applications will be evaluated for completeness by the Center for Scientific
Review, NIH. Incomplete applications will not be reviewed.
There will be
an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the
assignment of an application to a Scientific Review Group is also in the Commons.
The NIH will not accept any application in response to this
FOA that is essentially the same as one currently pending initial merit review
unless the applicant withdraws the pending application. The NIH will not accept
any application that is essentially the same as one already reviewed. This does
not preclude the submission of an application already reviewed with substantial
changes, but such application must include an Introduction addressing the
previous critique. Note such an application is considered a
"resubmission" for the SF424 (R&R).
4. Intergovernmental
Review
This initiative is not subject to intergovernmental
review.
5.
Funding Restrictions
All NIH awards are subject to the terms and
conditions, cost principles, and other considerations described in the NIH Grants
Policy Statement.
The incurrence of pre-award costs in anticipation of a competing or
non-competing award imposes no obligation on NIH either to make the award or to
increase the amount of the approved budget if an award is made for less than
the amount anticipated and is inadequate to cover the pre-award costs incurred.
NIH expects the grantee to be fully aware that pre-award costs result in
borrowing against future support and that such borrowing must not impair the
grantee's ability to accomplish the project objectives in the approved time
frame or in any way adversely affect the conduct of the project. See the NIH
Grants Policy Statement.
6. Other Submission Requirements
Investigators are advised to consult the URL (http://nccam.nih.gov/research/instructions/r21/index.htm)
for specific requirements and restrictions on appendices, as well as additional
information. NCCAM supports two types of R21 funding mechanisms (http://nccam.nih.gov/research/instructions/r21/index.htm):
(1) NCCAM Exploratory/Developmental Grant for Clinical Studies and (2) Basic
and Preclinical Research on Complementary and Alternative Medicine. The
application instructions differ between the two NCCAM R21 funding mechanisms. Applicants are advised to check the
website for the most current (or succeeding) NCCAM R21 announcements.
The applicant must follow the NCCAM Interim Applicant Guidance: Product Quality: Biologically Active Agents Used in Complementary and Alternative Medicine and Placebo Materials: http://grants.nih.gov/grants/guide/notice-files/NOT-AT-05-004.html. Instructions are provided on the type of information that should be included in the application, as well as the type of information that NCCAM may request after review but before grant award.
Applicants are encouraged to address safety characteristics of the investigational products in their applications, as appropriate. For safety, probiotics may be characterized (for example) with: (1) a determination of antibiotic resistance patterns and transmission of genetic elements to other intestinal and/or food borne microorganisms; (2) an assessment for possibly deleterious metabolic activities; (3) an assessment of side effects during human studies; (4) a test for toxin production (if the strain belongs to a species known to be a mammalian toxin producer); (5) a determination of hemolytic activity (if the strain belongs to a species with known hemolytic potential).
Federal regulations attempt to achieve a balance of the protection of individual children with the importance of allowing research needed to improve pediatric medicine by empowering institutional review boards to approve pediatric research: http://www.hhs.gov/ohrp/irb/irb_chapter6.htm#g4. Investigators studying children are strongly encouraged to consult their local Institutional Review Board regarding ethical guidelines for pediatric research and how it applies the federal risk and benefit categories. Applicants are encouraged to address benefit and risk in their application.
Although Phase III studies will not be considered in response to this FOA, modest-sized (about 40-160 participants) Phase II studies are allowed. Dose-ranging studies may be a component of or need to precede the Phase II studies. Applicants intending to conduct clinical trials should be aware of NCCAM's guidance on determining dose ranges: http://nccam.nih.gov/research/policies/guideonct.htm. Applicants are encouraged to provide justification for dose and dosage in their application.
NCCAM requires all clinical projects undergo review by the Office of Clinical and Regulatory Affairs (OCRA) for conformity with the NCCAM Terms of Awards for Clinical Trials: http://nccam.nih.gov/research/policies/terms-of-awards.htm. For additional points to consider when submitting a clinical study to NCCAM, the applicant is directed to: http://nccam.nih.gov/research/instructions/poc.htm.
It is the sole responsibility of the applicant to obtain all necessary clearances from the Food and Drug Administration (FDA) as required. Questions regarding Investigational New Drug (IND) applications should be addressed to the FDA. (For FDA contact, see Section VII. 1. Scientific/Research Contacts). The applicant should present a plan for IND submission, evidence that an IND application is in process or that the FDA has allowed an exemption.
Specific Instructions for Modular Grant applications
Applications
requesting direct costs in each year of $250,000 or less (excluding consortium
F&A costs), must be submitted in a modular budget format using the Modular
Budget Component provided in the SF424 (R&R) Application Package and
Instructions Guide (see specifically Section 5.4). The modular budget 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.
Plan for Sharing
Research Data
The precise content of the data-sharing plan will vary,
depending on the data being collected and how the investigator is planning to
share the data. Applicants who are planning to share data may wish to describe
briefly the expected schedule for data sharing, the format of the final
dataset, the documentation to be provided, whether or not any analytic tools
also will be provided, whether or not a data-sharing agreement will be required
and, if so, a brief description of such an agreement (including the criteria
for deciding who can receive the data and whether or not any conditions will be
placed on their use), and the mode of data sharing (e.g., under their own
auspices by mailing a disk or posting data on their institutional or personal
website, through a data archive or enclave). Investigators choosing to share
under their own auspices may wish to enter into a data-sharing agreement.
References to data sharing may also be appropriate in other sections of the
application.
Applicants
requesting more than $500,000 in direct costs in any year of the proposed
research must include a plan for sharing research data in their application.
The funding organization will be responsible for monitoring the data sharing
policy (http://grants.nih.gov/grants/policy/data_sharing).
The reasonableness of the data sharing plan or the
rationale for not sharing research data may be assessed by the reviewers.
However, reviewers will not factor the proposed data sharing plan into the
determination of scientific merit or the priority score.
Sharing Research
Resources
NIH policy requires that grant awardee recipients make
unique research resources readily available for research purposes to qualified
individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.
The adequacy of the resources sharing plan and any
related data sharing plans will be considered by Program staff of the funding
organization when making recommendations about funding applications. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
Reporting.
Section
V. Application Review Information
1. Criteria
Only the review
criteria described below will be considered in the review process.
2. Review and Selection Process
Applications that
are complete will be evaluated for scientific and technical merit by an
appropriate review group convened by NCCAM in accordance with the review criteria stated below.
As part of the
initial merit review, all applications will:
The following will be considered in making funding decisions:
Additional considerations for award will include portfolio balance, diversity among institutions and individuals within institutions, product quality, and geographic diversity.
The goals of
NIH supported research are to advance our understanding of biological systems,
to improve the control of disease, and to enhance health. In their written
critiques, reviewers will be asked to comment on each of the following criteria
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 in assigning the overall score, weighting them as
appropriate for each application. Note that an 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 or clinical practice be advanced? What will be the effect
of these studies on the concepts, methods, technologies, treatments, services,
or preventative interventions that drive this field?
Approach: Are the conceptual or
clinical framework, design, methods, and analyses adequately developed, well
integrated, well reasoned, and appropriate to the aims of the project? Does the
applicant acknowledge potential problem areas and consider alternative tactics?
Innovation: Is the project original and
innovative? For example: Does the project challenge existing paradigms or
clinical practice; address an innovative hypothesis or critical barrier to
progress in the field? Does the project develop or employ novel concepts,
approaches, methodologies, tools, or technologies for this area?
Investigators: Are the investigators
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? Does the investigative team bring complementary and
integrated expertise to the project (if applicable)?
Environment: Does the scientific environment
in which the work will be done contribute to the probability of success? Do the
proposed studies benefit from unique features of the scientific environment, or
subject populations, or employ useful collaborative arrangements? Is there
evidence of institutional support?
2.A. Additional Review
Criteria:
In addition to the
above criteria, the following items will continue to be considered in the
determination of scientific merit and the priority score:
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 item 6 of the Research Plan component of the SF424 (R&R).
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 item 7 of the Research Plan component of the SF424
(R&R).
Care and Use of Vertebrate Animals in
Research: If vertebrate animals are to
be used in the project, the five items described under item 11 of the Research
Plan component of the SF424 (R&R) will be assessed.
Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.
2.B. Additional
Review Considerations
Budget
and Period of Support: The reasonableness of the proposed budget and the
appropriateness of the requested period of support in relation to the proposed
research may be assessed by the reviewers. Is the effort listed for the PD/PI
appropriate for the work proposed? Is each budget category realistic and
justified in terms of the aims and methods?
2.C. Sharing
Research Data
Data Sharing Plan: The reasonableness of the
data sharing plan or the rationale for not sharing research data may be assessed
by the reviewers. However, reviewers will not factor the proposed data sharing
plan into the determination of scientific merit or the priority score. The
funding organization will be responsible for monitoring the data sharing
policy. http://grants.nih.gov/grants/policy/data_sharing. NCCAM does not
require a data sharing plan for applications requesting less than $500,000.
2.D. Sharing
Research Resources
NIH policy requires that grant awardee recipients make
unique research resources readily available for research purposes to qualified
individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.
Program staff will be responsible for the
administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan and any related data sharing plans
will be considered by Program staff of the funding organization when making
recommendations about funding applications. The effectiveness of the resource
sharing will be evaluated as part of the administrative review of each Non-Competing Grant
Progress Report (PHS 2590), See Section VI.3.,
Reporting.
3. Anticipated Announcement and Award Dates
Standard review and start dates apply.
Section VI. Award Administration Information
1. Award Notices
After the peer review of the application is
completed, the PD/PI will be able to access his or her Summary Statement
(written critique) via the NIH eRA Commons.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant. For
details, applicants may refer to the NIH
Grants Policy Statement Part II: Terms
and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).
A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.
Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Also Section
IV.5. Funding Restrictions.
2.
Administrative and National Policy Requirements
In addition to the Terms and Conditions listed
below related to clinical research, applicants submitting clinical trial
applications in response to this announcement should also follow the NCCAM
Policy on Terms of Award for Clinical Trials: http://nccam.nih.gov/research/policies/terms-of-awards.htm.
All NIH grant and
cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice
of Award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions
of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm)
and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and
Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
3. Reporting
Awardees will be required to submit the PHS Non-Competing
Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm)
and financial statements as required in the NIH Grants Policy Statement.
We encourage your inquiries
concerning this funding opportunity 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:
1. Scientific/Research
Contacts:
Marguerite Klein
Division of Extramural Research, Training and Review
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 402-5860
FAX: (301) 480-3621
Email: [email protected]
Rebecca B. Costello, Ph.D., F.A.C.N.
Office of Dietary Supplements
National Institutes of Health
6100 Executive Blvd., Room 3B01, MSC 7517
Bethesda, Maryland 20892-7517
Telephone: (301) 435-2920
FAX: (301) 480-1845
Email: [email protected]
Direct questions about IND applications to the FDA:
Jennifer Ross, PhD
Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Vaccines Research and Review
Division of Vaccines and Related Products Applications
Phone: 301-827-3070
Fax: 301-827-3532
E mail: [email protected]
2. Peer Review Contacts:
Martin Goldrosen, PhD
Office of Scientific Review
National Center for Complementary and Alternative Medicine
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-2014
FAX: (301) 480-2419
Email: [email protected]
3.
Financial or Grants Management Contacts:
George Tucker, MBA
Grants Management Office
National Center for Complementary and Alternative Medicine
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-8853
FAX: (301) 480-2419
Email: [email protected]
Section VIII. Other Information
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving
live, vertebrate animals must comply with PHS Policy on Humane Care and Use of
Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf)
as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm),
and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm)
as applicable.
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). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for
Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
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 and 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 scientific merit or the priority score.
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 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 funding opportunity 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.
Sharing of Model Organisms:
NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding pursuant
to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the
application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.
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 (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 SF424 (R&R); 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 Clinical
Research:
The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.
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 (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 applications
for research involving human subjects and individuals designated as key personnel.
The policy is available 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 (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.
NIH Public Access Policy:
NIH-funded investigators are requested to submit to
the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov)
at PubMed Central (PMC) an electronic version of the author's final manuscript
upon acceptance for publication, resulting from research supported in whole or
in part with direct costs from NIH. The author's final manuscript is defined as
the final version accepted for journal publication, and includes all modifications
from the publishing peer review process.
NIH is requesting that authors submit manuscripts
resulting from 1) currently funded NIH research projects or 2) previously
supported NIH research projects if they are accepted for publication on or
after May 2, 2005. The NIH Public Access Policy applies to all research grant
and career development award mechanisms, cooperative agreements, contracts,
Institutional and Individual Ruth L. Kirschstein National Research Service
Awards, as well as NIH intramural research studies. The Policy applies to
peer-reviewed, original research publications that have been supported in whole
or in part with direct costs from NIH, but it does not apply to book chapters,
editorials, reviews, or conference proceedings. Publications resulting from
non-NIH-supported research projects should not be submitted.
For more information about the Policy or the
submission process please visit the NIH Public Access Policy Web site at http://PublicAccess.nih.gov/ and
view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).
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).
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 PA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.
Authority and Regulations:
This program is described in the Catalog of Federal Domestic
Assistance 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.
Loan Repayment Programs:
NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50% of their time (at least 20 hours per week based on a 40
hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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