Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National Institute of Dental and Craniofacial
Research (NIDCR), (http://www.nidcr.nih.gov)
National Cancer Institute (NCI), (http://www.nci.nih.gov)
Office of Research on Women’s
Health (ORWH), (http://orwh.od.nih.gov/)
Title: Pathophysiology
of Bisphosphonates-associated Osteonecrosis of the Jaw (R03)
Announcement Type
New
Update: The following update relating to this announcement has been issued:
Notice: Applications submitted in response to this Funding Opportunity Announcement (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 four weeks prior to the grant submission date. See Section IV.
Program Announcement (PA) Number: PA-06-502
Release/Posted Date: July 31, 2006
Opening Date: September 1, 2006 (Earliest date an application may be
submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not
applicable
NOTE: On time submission requires that applications be successfully submitted
to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): Standard dates apply, please see
http://grants1.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates
apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply,
please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation
Date): Not Applicable
Expiration Date: July 2, 2009 (now September 8, 2009 per NOT-OD-07-093)
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
The National Institute of Dental and Craniofacial Research (NIDCR) and the National Cancer Institute (NCI) invite Small Research Grant (R03) applications for research projects focusing on basic and translational studies of osteonecrosis of the jaw (ONJ), an oral complication associated with bisphosphonate use. Projects should aim to identify and characterize the pathophysiological mechanisms that lead to impaired bone healing and the development of ONJ.
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. Submitting an Application Electronically 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
Purpose:
The purpose of this Funding
Opportunity Announcement (FOA) is to stimulate research to determine the pathophysiology
of ONJ, a morbid bone disorder that is associated with bisphosphonate use.
Bisphosphonates are prescribed to alleviate bone pain in certain cancer patients,
or to reduce bone loss in osteoporotic or osteopenic individuals. Recent reports
suggest that there is an association between the use of bisphosphonates and
ONJ in a subset of these patients. Whether bisphosphonates are causal to the
development of ONJ remains to be determined, and the physiological mechanisms
by which ONJ manifests in bisphosphonate users are unknown. Although there
is a knowledge base on the effects of bisphosphonates on bone quality and
strength, there is a gap in our understanding of how bisphosphonates may interfere
with bone healing and repair at the genetic, molecular, cellular and tissue
levels. Therefore, we seek to support basic and translational studies that
will address the knowledge gap and enhance our understanding of this clinical
entity related to bisphosphonate therapy. This knowledge could also serve
as the basis for the prediction, prevention, diagnosis, and treatment of this
condition.
Background:
The bisphosphonates are a
class of drugs that inhibit the activities and functions of osteoclasts (bone
resorbing cells) and perturb the differentiation of osteoblasts (bone forming
cells). Intravenous bisphosphonates are primarily used to treat bone erosion
and hypercalcemia associated with bone metastasis, Paget’s disease and multiple
myeloma. Oral bisphosphonates are used to prevent bone loss and are prescribed
for patients with osteoporosis or osteopenia. In 2003, the first report surfaced
in the literature that suggests an association of ONJ with bisphosphonate
use in a subset of patients. Since then, several other reports have come to
light strengthening this association. However, whether bisphosphonates are
causal to the development of ONJ remains to be determined. Most incidences
are related to intravenous bisphosphonate use in cancer patients, but several
cases are associated with oral bisphosphonates as well. Patients with ONJ
present with painful, exposed and necrotic bone, which may occur following
dental procedures or spontaneously, and involving predominantly the mandible.
These lesions are non-healing or slow to heal, and often complicated by osteomyelitis.
Therefore, this is a significant clinical problem of potentially broad health
impact, yet with complete lack of mechanistic studies.
Bisphosphonates have been in use for almost 30 years. During this time, this class of compounds has significantly expanded, with the newest compounds three orders of magnitude more potent than the original ones in in vitro antiresorption assays. Bisphosphonates are synthetic analogs of cellular inorganic pyrophosphates with a P-C-P backbone structure. The two variable sidechains on the central carbon atom confer the compound’s binding affinity to bone and antiresorptive properties, respectively. Therefore, progressive chemical modifications to these sidechains resulted in a series of compounds with increasing binding affinity to bone and antiresorptive potency. The first generation of bisphosphonates such as etidronate, tiludronate and clodronate was non-nitrogen containing. These compounds exert their action by being incorporated into osteoclasts and forming non-hydrolysable analogs of ATP, which then cause metabolic starvation and consequential apoptosis. The next generation of bisphosphonates was nitrogen-containing; some such as alendronate and pamidronate contain the primary amine moiety and others such as risedronate, zoledronate and ibandronate contain nitrogen as tertiary amines. These bisphosphonates inhibit the activity of the enzyme farnesyl diphosphate synthase of the mevalonate pathway, which in turn prevents proper post-translational modification of small GTPases cell signaling molecules in osteoclasts. In addition, evidence suggests that bisphosphonates also modulate osteoblast formation and differentiation, thereby indirectly perturbing the osteoclasts. Once incorporated into bone, bisphosphonates have long term bioavailability, some for many years. Therefore, the benefits as well as risks associated with bisphosphonate use could be prolonged.
The pathophysiological mechanisms underlying ONJ are unknown although several cellular processes, when altered, have been implicated in contributing to the condition. For example, the resorptive power of osteoclasts is essential in bone remodeling. Although bisphosphonates inhibit bone loss, they can also inhibit normal physiological bone remodeling and turnover to the extent that local microdamage of bone architecture due to mechanical loading during chewing, or local bone defects due to tooth extraction, cannot be effectively repaired. Another possibility is that bisphosphonates, some of which demonstrate antiangiogenic properties, may cause avascular necrosis of the bone. Finally, the data trend indicates that not all bisphosphonate users will eventually develop ONJ, suggesting that genetic variations among individuals that govern skeletal homeostasis or the bioavailability of bisphosphonates may confer susceptibility or resistance to developing ONJ. Several risk factors for the development of ONJ have also been implicated. These include concomitant corticosteroid therapy and chemotherapy, dental procedures such as tooth extraction, and poor oral health. The exact incidence of bisphosphonate-associated ONJ is unknown but ranges from 0.03% to 10.5% in published reports. However, collectively, there is an extremely low incidence of ONJ for patients receiving bisphosphonate treatment for less than 12 months, suggesting that the cumulative effects of dose and time contribute to the development of this adverse event.
Currently, there are no effective treatments for ONJ. Patients may be treated non-invasively with antibiotics and chlorhexidine mouth rinses to limit the extent of the damage. Surgical intervention such as local debridement or radical resection of necrotic bone often exacerbates the condition. Discontinuation of bisphosphonate use is not an effective remedy as these compounds have long resident time in the bone.
Although a causal relationship between bisphosphonates and ONJ has not been established, and other risk and comorbid factors for ONJ exist, this is clearly a new and emerging medical and dental concern. There is an urgent need to fill a significant knowledge gap in characterizing the condition, identifying the root cause, and determining individual susceptibility for the prevention and intervention of bisphosphonate-associated ONJ.
Scope and Objectives:
This FOA encourages investigations
in the 1) characterization of the relationship between bisphosphonate use
and ONJ in animal models, 2) genetic, molecular and cellular basis of jaw-specific
impaired bone healing in the presence of bisphosphonates, 3) pharmacogenetics
of bisphosphonates underlying the development of ONJ, 4) contribution of other
pharmacological or bone active factors on the development of ONJ, and 5) cumulative
effects of dose, exposure and type of bisphosphonates on the development of
ONJ.
Human subject research, as well as the use of appropriate animal models, is acceptable. Examples of research topics that would fill the knowledge gap include but are not limited to:
Projects must focus on studying oral bone homeostasis, healing response or repair capacity in the presence or absence of bisphosphonates rather than on the broad effects of bisphosphonates on bone quality. Projects that examine the effects of bisphosphonates on skeletal biology will not be considered unless the experimental design includes analysis of oral bones. Projects may study the effects of bisphosphonates on other physiological processes such as angiogenesis but only within the context that perturbation of these processes may compromise oral bone homeostasis and healing. Projects that examine the pharmacology of bisphosphonates will be considered non-responsive unless the projects propose to test whether genetic variations alter the pharmacokinetics or pharmacodynamics of bisphosphonates. Epidemiological studies are non-responsive.
This FOA is intended to accelerate discoveries so that we can better predict who may benefit from bisphosphonate treatment without accompanying risk of ONJ, who may be prone to adverse events, and how to overcome bisphosphonate-associated ONJ. Knowledge gained from these studies may pave the way for personalized recommendations for bisphosphonate therapy, including guidance for patients on oral health care prior to and during bisphosphonate use and new strategies for the prevention and intervention of bisphosphonate-associated ONJ, while also managing bone cancer pain or osteoporotic bone loss.
The participating institutes use the R03 mechanism in this FOA to support pilot and developmental research that is likely to lead to a subsequent Individual Research Project Grant (R01) application from scientists who are in the early stages of establishing an independent research career. Only new investigators are eligible to apply.
See Section
VIII, Other Information - Required Federal Citations, for policies related
to this announcement.
Section II. Award Information
1. Mechanism(s) of Support
This Funding Opportunity Announcement (FOA) will use the NIH Small Research
Grant (R03) award mechanism. The applicant will be solely responsible for
planning, directing, and executing the proposed project.
This FOA uses “Just-in-Time” information concepts. It also uses the modular budget formats (see the “Modular Applications and Awards” section of the NIH Grants Policy Statement. All applications submitted in response to this FOA must use the modular budget format. 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).
Competing renewal (formerly “competing continuation”) applications will not be accepted for the R03 grant mechanism. Small grant support may not be used for thesis or dissertation research. Up to two resubmissions (formerly “revisions/amendments") of a previously reviewed small grant application may be submitted. See NOT-OD-05-046, April 29, 2005.
For specific information about the R03 programs, see: http://grants.nih.gov/grants/funding/r03.htm.
2. Funds Available
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 NIH Institutes and Centers (ICs) 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.
A project period of up to two years and a budget for direct costs of up to two $25,000 modules, or $50,000 per year, may be requested (i.e., a maximum of $100,000 over two years in four modules of $25,000 each). Commensurate Facilities and Administrative (F&A) costs are allowed.
F&A costs requested by consortium participants
are not included in the direct cost limitation. See NOT-OD-05-004,
November 2, 2004.
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 as the Project Director/Principal
Investigator (PD/PI) is invited to work with his/her 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. The participating
institutes limit the R03
eligibility to new investigators only. Individuals who have received NIH support
for previous research (e.g., R03, R21, or R01) are not eligible. Individuals
who have received only training or career development support from the NIH
(e.g., K08, K22, K23, K16, K12, F30, F32, and T32) are eligible.
2. Cost Sharing or Matching
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.
Projects must focus on studying oral bone homeostasis, healing response or repair capacity in the presence or absence of bisphosphonates rather than on the broad effects of bisphosphonates on bone quality. Projects that examine the effects of bisphosphonates on skeletal biology will not be considered unless the experimental design includes analysis of oral bones. Projects may study the effects of bisphosphonates on other physiological processes such as angiogenesis but only within the context that perturbation of these processes may compromise oral bone homeostasis and healing. Projects that examine the pharmacology of bisphosphonates will be considered non-responsive unless the projects propose to test whether genetic variations alter the pharmacokinetics or pharmacodynamics of bisphosphonates. Epidemiological studies are non-responsive.
Section IV. Application and Submission Information
To download an Application Package and SF424 (R&R) 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 NIH 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
Grants.gov
Customer Support
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email support@grants.gov
2) Organizational/Institutional Registration in the eRA Commons
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours M-F 7:00 a.m. – 8:00 p.m. Eastern Time
Email commons@od.nih.gov
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 four 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 301-435-0714, Email: GrantsInfo@nih.gov.
Telecommunications for the hearing impaired: TTY 301-451-0088.
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 “Frequently Asked Questions – Application Guide, 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 Modular Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s)
Form
Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R03 uses ONLY the PHS398 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 special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
3. Submission Dates and Times
See Section IV.3.A. for
details.
3.A. Submission, Review, and
Anticipated Start Dates
Opening Date: September 1, 2006 (Earliest date an application may be
submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not applicable
Application Submission/Receipt Date(s): Standard
dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates apply, please
see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please
see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
3.A.1. Letter of Intent
A letter of intent is not required for the funding
opportunity.
3.B. Submitting an Application Electronically 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.
Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.
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 that 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.
Pre-Award Costs are allowable. A grantee may, at its
own risk and without NIH prior approval, incur obligations and expenditures
to cover costs up to 90 days before the beginning date of the initial budget
period of a new award if such costs: are necessary to conduct the project
and would be allowable under the grant, if awarded, without NIH prior approval.
If specific expenditures would otherwise require prior approval, the grantee
must obtain NIH approval before incurring the cost. NIH prior approval is
required for any costs to be incurred more than 90 days before the beginning
date of the initial budget period of a new award.
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
The NIH requires the PD/PI to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Registration FAQs – Important Tips -- Electronic Submission of Grant Applications.”
Renewal (formerly “competing continuation” or “Type 2”) applications are not permitted.
All application instructions outlined in the SF424 (R&R) Application Guide (MS Word or PDF) are to be followed, with the following requirements for R03 applications:
Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.
Note: While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
The participating institutes require that the Project Director/Principal Investigator (PD/PI) commit a minimum effort of 3 person months of a 12-month calender year appointment or a 2.25 person months of a 9-month academic year appointment to the R03 project. In addition, letters of support from the Institution (preferably from the Dean or Departmental Chair) are strongly encouraged. The letters should describe the nature of the PI's appointment and commitments to the PD/PI, such as laboratory and office space, technical assistance, or travel funds. R03 eligibility criteria described in this FOA are limited to this solicitation only and not applicable to other FOAs that also solicit for R03 applications. Investigators interested in this mechanism should consult the NIH-wide Parent R03 FOA at http://grants.nih.gov/grants/guide/pa-files/PA-06-180.html and eligibility defined by each institute and FOA.
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.
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
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a sharing
research resources plan 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 (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).
Only the review criteria described below will be considered
in the review process.
2. Review and Selection Process
Applications submitted for this funding opportunity
will be assigned to the ICs on the basis of established Public Health Service
(PHS) referral guidelines.
Appropriate scientific review groups convened in accordance
with the standard NIH peer review procedures (http://cms.csr.nih.gov/ResourcesforApplicants/)
will evaluate applications for scientific and technical merit.
As part of the initial merit review, all applications
will:
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:
The NIH R03 small grant is a mechanism for supporting discrete, well-defined projects that realistically can be completed in two years and that require limited levels of funding. Because the Research Plan component is restricted to 10 pages, a small grant application will not have the same level of detail or extensive discussion found in an R01 application. Accordingly, reviewers should evaluate the conceptual framework and general approach to the problem, placing less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or from investigator-generated data. Preliminary data are not required, particularly in applications proposing pilot or feasibility studies.
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 comments, 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. The scientific review group will address and consider each of these criteria in assigning the application's 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 scientific health 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 PD/PI 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 number of person
months listed for the effort of 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).
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 http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a sharing
research resources plan 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 will be
considered by Program staff of the funding organization when making recommendations
about funding applications. Program staff may negotiate modifications of the
data and resource sharing plans with the awardee before recommending funding
of an application. The final version of the data and resource sharing plans
negotiated by both will become a condition of the award of the grant. 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.”
Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations. For the R03 mechanism, the presence or adequacy of a plan should not enter into the scoring of the application.
3. Anticipated Announcement and Award Dates
Not applicable.
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/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.
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 Section IV.5., “Funding
Restrictions.”
2. Administrative and National
Policy Requirements
All NIH grant and cooperative agreement awards include
the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants
Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart
A: General and Part II:
Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions
for Specific Types of Grants, Grantees, and Activities.
3. Reporting
When multiple years are involved, awardees will be required to submit the
Non-Competing Grant
Progress Report (PHS 2590) annually 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:
Lillian Shum, Ph.D.
Director, Mineralized Tissue and Salivary Gland Physiology Program
Center for Integrative Biology and Infectious Diseases
National Institute of Dental and Craniofacial Research
45 Center Drive
Building 45, Room 4AN-18B
Bethesda, MD 20892-6402
Voice: (301) 594-0618
Fax: (301) 480-8319
Email: ShumL@nidcr.nih.gov
Roy Wu, Ph.D.
Chief, Clinical Grants & Contracts Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN Room 7009, MSC 7432
Bethesda, MD 20892-7432 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-8866
Fax: (301) 480-4663
E-mail: wur@ctep.nci.nih.gov
Lisa Begg, Dr.P.H., R.N.
Director of Research Programs
Office of Research on Women's Health
Office of the NIH Director
Voice: (301) 496-7853
Fax: (301) 402-1798
E-mail: beggl@od.nih.gov
2. Peer Review Contacts:
Lynn Mertens King, PhD
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
45 Center Drive, Rm 4AN 32F
Bethesda, MD 20892-6402
Voice: (301) 594-5006
Fax: (301) 480-8303
Email: Lynn.King@nih.gov
3. Financial or Grants Management Contacts:
Mary Daley, Chief Grants Management Officer
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN 44B
45 Center Drive
Bethesda, MD 20892-6402
Voice: (301) 594-4808
FAX: (301) 480-3562
Email: daleym@mail.nih.gov
Carol Perry
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda, MD 20892-7150
Voice: (301) 496-7205
Fax: (301) 496-8601
Email: perryc@mail.nih.gov
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 the 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). Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal 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) application; 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.
Standards for Privacy of Individually Identifiable Health
Information:
The Department of Health and Human Services (HHS) 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 HHS 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. For publications listed in the appendix and/or
Progress report, internet addresses (URLs) must be used for publicly
accessible on-line journal articles. Unless otherwise specified in this
solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for 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
(CFDA# 93.121, 93.395) 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 Part 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 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
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
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