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 Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
(http://www.niams.nih.gov).
National Cancer Institute (NCI), (http://www.nci.nih.gov).
Title: Pathophysiology of
Bisphosphonates-associated Osteonecrosis of the Jaw (R01)
Announcement Type
New
Update: The following update relating to this announcement has been issued:
Program Announcement (PA) Number: PA-06-500
Catalog of Federal Domestic Assistance
Number(s)
93.121, 93.846, 93.395
Key Dates
Release Date: July 31, 2006
Letters of Intent Receipt Date(s): Not applicable
Application Submission
Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Peer Review Date(s): Standard
dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Council Review Date(s): Standard
dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Additional Information To Be Available Date (Url Activation
Date): Not applicable
Expiration Date for R01 Non-AIDS Applications: November 2, 2006
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
The National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Cancer Institute (NCI) invite Individual Research Project Grant (R01) 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(s) 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. Address to 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
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.
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 will use the Individual
Research Project Grant (R01) award mechanism.
As an applicant, you will be solely responsible for
planning, directing, and executing the proposed project.
This funding opportunity uses just-in-time concepts.
It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in each
year of $250,000 or less, use the modular budget format described in the PHS
398 application instructions. Otherwise follow the instructions for non-modular
research grant applications.
2. Funds Available
The participating ICs have not set aside funds for this FOA. The number of awards will be dependent on their scientific merit. Applicants may request up to five years of support. There is no cost limit for the R01 mechanism.
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 costs requested by consortium
participants are not included in the direct cost limitation, see NOT-OD-05-004.
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
Cost sharing is not required
The most current Grants Policy Statement can be found
at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing
3. Other-Special Eligibility Criteria
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
1. Address to Request Application
Information
The PHS 398 application instructions are available
at http://grants.nih.gov/grants/funding/phs398/phs398.html
in an interactive format. Applicants must use the currently approved version
of the PHS 398. 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
Applications must be prepared using the most current
PHS 398 research grant application instructions and forms. Applications must
have a D&B Data Universal Numbering System (DUNS) number as the universal
identifier when applying for Federal grants or cooperative agreements. The
D&B number can be obtained by calling (866) 705-5711 or through the web
site at http://www.dnb.com/us/. The D&B
number should be entered on line 11 of the face page of the PHS 398 form.
The title and number of this funding opportunity must
be typed on line 2 of the face page of the application form and the YES box
must be checked.
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
Letters of Intent Receipt Date(s): Not applicable
Application Submission
Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Peer Review Date(s): Standard dates apply, please
see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Council Review Date(s): Standard dates apply, please
see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
Earliest Anticipated Start Date(s): Standard dates
apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
for details
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
Applications must be prepared using the research grant
application forms found in the PHS 398 instructions for preparing a research
grant application. Submit a signed, typewritten original of the application,
including the checklist, and five signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express
or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS
service)
Personal deliveries of applications are no longer
permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).
3.C. Application Processing
Applications must be submitted on or before the application receipt/submission dates described
above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm.
Upon receipt applications will be evaluated for completeness
by CSR. Incomplete applications will not be reviewed.
The NIH will not accept any application in response
to this funding opportunity 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 a substantial revision
of an application already reviewed, but such application must include an Introduction
addressing the previous critique.
Information on the status of an application should
be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.
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 Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.
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 or competing continuation 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 or
competing continuation 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 NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.
6. Other Submission Requirements
Specific Instructions for Modular Grant applications.
Applications requesting up to $250,000 per year in
direct costs must be submitted in a modular budget format. 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. Section C of the research grant application instructions for the
PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html
includes step-by-step guidance for preparing modular budgets. Applicants must
use the currently approved version of the PHS 398. Additional information
on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.
Specific Instructions for Applications Requesting
$500,000 (direct costs) or More per Year.
Applicants requesting $500,000 or more in direct costs
for any year must carry out the following steps:
1) Contact the IC program staff at least 6 weeks before
submitting the application, i.e., as you are developing plans for the study;
2) Obtain agreement from the IC staff that the IC
will accept your application for consideration for award; and,
3) Include a cover letter with the application that
identifies the staff member and IC who agreed to accept assignment of the
application.
This policy applies to all investigator-initiated new (type 1), competing
continuation (type 2), competing supplement, or any amended or revised version
of these grant application types. Additional information on this policy is
available in the NIH Guide for Grants and Contracts, October 19, 2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.
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 (NIH
Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm
and 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, http://grants.nih.gov/grants/funding/2590/2590.htm).
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 submitted for this funding opportunity
will be assigned to the ICs on the basis of established PHS referral guidelines.
Appropriate scientific review groups convened in accordance
with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm)
will evaluate applications for scientific and technical merit.
As part of the initial merit review, all applications
will:
The following will be considered in making funding decisions:
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 the
Research Plan, Section E on Human Subjects in the PHS Form 398).
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 the Research Plan, Section
E on Human Subjects in the PHS Form 398).
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five
items described under Section F of the PHS Form 398 research grant application
instructions 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: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research. The priority score
should not be affected by the evaluation of the budget.
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/part_ii_5.htm#availofrr
and http://ott.od.nih.gov/policy/rt_guide_final.html). 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.
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 or her Summary Statement (written critique)
via the 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
(designated in item 12 on the Application Face Page). If a grantee is not
email enabled, a hard copy of the NoA will be mailed to the 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
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 (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.
Section VII. Agency Contacts
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
Telephone: (301) 594-0618
Fax: (301) 480-8319?
Email: ShumL@nidcr.nih.gov
William Sharrock, Ph.D.
Director, Bone Biology Program
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal
and Skin Diseases
One Democracy Plaza
6701 Democracy Boulevard, Suite 800,
MSC 4872
Bethesda, MD 20872-4872|
Voice: (301) 594-5055
Fax: (301) 480-4543
Email: sharrockw@mail.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
2. Peer Review Contacts:
Not applicable
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
Telephone: (301) 594-4808
FAX: (301) 480-3562
Email: daleym@mail.nih.gov
Melinda Nelson, Chief Grants Management
Officer
National Institute of Arthritis and Musculoskeletal
and Skin Diseases
One Democracy Plaza
6701 Democracy Boulevard, Suite 800
Bethesda, MD 20892-4872
Voice: (301) 594-3535
Fax: (301) 480-5450
Emai: nelsonm@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 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 new PHS Form 398; and updated roles and responsibilities
of NIH staff and the extramural community. The policy continues to require
for all NIH-defined Phase III clinical trials that: a) all applications or
proposals and/or protocols must provide a description of plans to conduct
analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic
groups, including subgroups if applicable; and b) investigators must report
annual accrual and progress in conducting analyses, as appropriate, by sex/gender
and/or racial/ethnic group differences.
Inclusion of Children as Participants in 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. 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, 93.846, 93.395) 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
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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